Carrel name: journal-sciRep-cord Creating study carrel named journal-sciRep-cord Initializing database file: cache/cord-001823-v60vv99o.json key: cord-001823-v60vv99o authors: Shen, Mingwang; Xiao, Yanni; Rong, Libin title: Modeling the effect of comprehensive interventions on Ebola virus transmission date: 2015-10-30 journal: Sci Rep DOI: 10.1038/srep15818 sha: doc_id: 1823 cord_uid: v60vv99o file: cache/cord-001704-pdxm0iiw.json key: cord-001704-pdxm0iiw authors: Xiong, Siping; Tang, Qi; Liang, Xudong; Zhou, Tingting; Yang, Jin; Liu, Peng; Chen, Ya; Wang, Changjun; Feng, Zhenqing; Zhu, Jin title: A Novel Chimeric Anti-PA Neutralizing Antibody for Postexposure Prophylaxis and Treatment of Anthrax date: 2015-07-02 journal: Sci Rep DOI: 10.1038/srep11776 sha: doc_id: 1704 cord_uid: pdxm0iiw file: cache/cord-001712-a1sbdhhn.json key: cord-001712-a1sbdhhn authors: Xiaokaiti, Yilixiati; Wu, Haoming; Chen, Ya; Yang, Haopeng; Duan, Jianhui; Li, Xin; Pan, Yan; Tie, Lu; Zhang, Liangren; Li, Xuejun title: EGCG reverses human neutrophil elastase-induced migration in A549 cells by directly binding to HNE and by regulating α1-AT date: 2015-07-16 journal: Sci Rep DOI: 10.1038/srep11494 sha: doc_id: 1712 cord_uid: a1sbdhhn file: cache/cord-001675-9717nzr7.json key: cord-001675-9717nzr7 authors: Sugiyama, Michael G.; Armstrong, Susan M.; Wang, Changsen; Hwang, David; Leong-Poi, Howard; Advani, Andrew; Advani, Suzanne; Zhang, Haibo; Szaszi, Katalin; Tabuchi, Arata; Kuebler, Wolfgang M.; Van Slyke, Paul; Dumont, Dan J.; Lee, Warren L. title: The Tie2-agonist Vasculotide rescues mice from influenza virus infection date: 2015-06-05 journal: Sci Rep DOI: 10.1038/srep11030 sha: doc_id: 1675 cord_uid: 9717nzr7 file: cache/cord-001116-2yvyiiuy.json key: cord-001116-2yvyiiuy authors: Nikas, Jason B. title: Inflammation and Immune System Activation in Aging: A Mathematical Approach date: 2013-11-19 journal: Sci Rep DOI: 10.1038/srep03254 sha: doc_id: 1116 cord_uid: 2yvyiiuy file: cache/cord-001875-ulq1xqma.json key: cord-001875-ulq1xqma authors: Li, Jing; Rao, Yuhan; Sun, Qinglan; Wu, Xiaoxu; Jin, Jiao; Bi, Yuhai; Chen, Jin; Lei, Fumin; Liu, Qiyong; Duan, Ziyuan; Ma, Juncai; Gao, George F.; Liu, Di; Liu, Wenjun title: Identification of climate factors related to human infection with avian influenza A H7N9 and H5N1 viruses in China date: 2015-12-11 journal: Sci Rep DOI: 10.1038/srep18094 sha: doc_id: 1875 cord_uid: ulq1xqma file: cache/cord-001852-c79vwr6t.json key: cord-001852-c79vwr6t authors: Xiao, Qiuyan; Ren, Luo; Zheng, Shouyan; Wang, Lili; Xie, Xiaohong; Deng, Yu; Zhao, Yao; Zhao, Xiaodong; Luo, Zhengxiu; Fu, Zhou; Huang, Ailong; Liu, Enmei title: Prevalence and molecular characterizations of enterovirus D68 among children with acute respiratory infection in China between 2012 and 2014 date: 2015-11-16 journal: Sci Rep DOI: 10.1038/srep16639 sha: doc_id: 1852 cord_uid: c79vwr6t file: cache/cord-001862-a097byk5.json key: cord-001862-a097byk5 authors: Saisawang, Chonticha; Saitornuang, Sawanan; Sillapee, Pornpan; Ubol, Sukathida; Smith, Duncan R.; Ketterman, Albert J. title: Chikungunya nsP2 protease is not a papain-like cysteine protease and the catalytic dyad cysteine is interchangeable with a proximal serine date: 2015-11-24 journal: Sci Rep DOI: 10.1038/srep17125 sha: doc_id: 1862 cord_uid: a097byk5 file: cache/cord-001829-rwnbxmt4.json key: cord-001829-rwnbxmt4 authors: Lu, Yi-Fan; Mauger, David M.; Goldstein, David B.; Urban, Thomas J.; Weeks, Kevin M.; Bradrick, Shelton S. title: IFNL3 mRNA structure is remodeled by a functional non-coding polymorphism associated with hepatitis C virus clearance date: 2015-11-04 journal: Sci Rep DOI: 10.1038/srep16037 sha: doc_id: 1829 cord_uid: rwnbxmt4 file: cache/cord-002312-jyk7f8hz.json key: cord-002312-jyk7f8hz authors: Branton, W. G.; Lu, J. Q.; Surette, M. G.; Holt, R. A.; Lind, J.; Laman, J. D.; Power, C. title: Brain microbiota disruption within inflammatory demyelinating lesions in multiple sclerosis date: 2016-11-28 journal: Sci Rep DOI: 10.1038/srep37344 sha: doc_id: 2312 cord_uid: jyk7f8hz file: cache/cord-002673-5a1rfi6k.json key: cord-002673-5a1rfi6k authors: Knibb, Wayne; Luu, Giang; Premachandra, H. K. A.; Lu, Ming-Wei; Nguyen, Nguyen Hong title: Regional genetic diversity for NNV grouper viruses across the Indo-Asian region – implications for selecting virus resistance in farmed groupers date: 2017-09-06 journal: Sci Rep DOI: 10.1038/s41598-017-11263-4 sha: doc_id: 2673 cord_uid: 5a1rfi6k file: cache/cord-002110-pbb247lp.json key: cord-002110-pbb247lp authors: Chen, Chin-Pei; Lin, Meng-Han; Chan, Ya-Ting; Chen, Li-Chyong; Ma, Che; Fischer, Wolfgang B. title: Membrane protein assembly: two cytoplasmic phosphorylated serine sites of Vpu from HIV-1 affect oligomerization date: 2016-06-29 journal: Sci Rep DOI: 10.1038/srep28866 sha: doc_id: 2110 cord_uid: pbb247lp file: cache/cord-002081-vi6rth9o.json key: cord-002081-vi6rth9o authors: Zhang, Chao; Yao, Yao; Zhu, Juan-Li; Zhang, Si-Nong; Zhang, Shan-Shan; Wei, Hua; Hui, Wen-Li; Cui, Ya-Li title: Establishment and application of a real-time loop-mediated isothermal amplification system for the detection of CYP2C19 polymorphisms date: 2016-06-01 journal: Sci Rep DOI: 10.1038/srep26533 sha: doc_id: 2081 cord_uid: vi6rth9o file: cache/cord-001522-82plcxv9.json key: cord-001522-82plcxv9 authors: Xu, Zhiwei; Hu, Wenbiao; Zhang, Yewu; Wang, Xiaofeng; Zhou, Maigeng; Su, Hong; Huang, Cunrui; Tong, Shilu; Guo, Qing title: Exploration of diarrhoea seasonality and its drivers in China date: 2015-02-04 journal: Sci Rep DOI: 10.1038/srep08241 sha: doc_id: 1522 cord_uid: 82plcxv9 file: cache/cord-001858-nmi39n6h.json key: cord-001858-nmi39n6h authors: Petriccione, Milena; Mastrobuoni, Francesco; Zampella, Luigi; Scortichini, Marco title: Reference gene selection for normalization of RT-qPCR gene expression data from Actinidia deliciosa leaves infected with Pseudomonas syringae pv. actinidiae date: 2015-11-19 journal: Sci Rep DOI: 10.1038/srep16961 sha: doc_id: 1858 cord_uid: nmi39n6h file: cache/cord-001901-2s6hpakk.json key: cord-001901-2s6hpakk authors: Kwok, Hoi-Hin; Poon, Po-Ying; Fok, Siu-Ping; Ying-Kit Yue, Patrick; Mak, Nai-Ki; Chan, Michael Chi-Wai; Peiris, Joseph Sriyal Malik; Wong, Ricky Ngok-Shun title: Anti-inflammatory effects of indirubin derivatives on influenza A virus-infected human pulmonary microvascular endothelial cells date: 2016-01-06 journal: Sci Rep DOI: 10.1038/srep18941 sha: doc_id: 1901 cord_uid: 2s6hpakk file: cache/cord-002072-qbh728ec.json key: cord-002072-qbh728ec authors: Bi, Yuhai; Liu, Jingyuan; Xiong, Haofeng; Zhang, Yue; Liu, Di; Liu, Yingxia; Gao, George F.; Wang, Beibei title: A new reassortment of influenza A (H7N9) virus causing human infection in Beijing, 2014 date: 2016-05-27 journal: Sci Rep DOI: 10.1038/srep26624 sha: doc_id: 2072 cord_uid: qbh728ec file: cache/cord-002490-kw8psrmz.json key: cord-002490-kw8psrmz authors: Beniac, Daniel R.; Booth, Timothy F. title: Structure of the Ebola virus glycoprotein spike within the virion envelope at 11 Å resolution date: 2017-04-11 journal: Sci Rep DOI: 10.1038/srep46374 sha: doc_id: 2490 cord_uid: kw8psrmz file: cache/cord-002758-d86hnox1.json key: cord-002758-d86hnox1 authors: Opuu, Vaitea; Silvert, Martin; Simonson, Thomas title: Computational design of fully overlapping coding schemes for protein pairs and triplets date: 2017-11-20 journal: Sci Rep DOI: 10.1038/s41598-017-16221-8 sha: doc_id: 2758 cord_uid: d86hnox1 file: cache/cord-002369-shk4n8f6.json key: cord-002369-shk4n8f6 authors: Fahmy, Ahmed M.; Labonté, Patrick title: The autophagy elongation complex (ATG5-12/16L1) positively regulates HCV replication and is required for wild-type membranous web formation date: 2017-01-09 journal: Sci Rep DOI: 10.1038/srep40351 sha: doc_id: 2369 cord_uid: shk4n8f6 file: cache/cord-002373-rueg4gsj.json key: cord-002373-rueg4gsj authors: Huang, Ao; Li, Weiwei; Shi, Shuo; Yao, Tianming title: Quantitative Fluorescence Quenching on Antibody-conjugated Graphene Oxide as a Platform for Protein Sensing date: 2017-01-13 journal: Sci Rep DOI: 10.1038/srep40772 sha: doc_id: 2373 cord_uid: rueg4gsj file: cache/cord-002111-mmpijsqb.json key: cord-002111-mmpijsqb authors: Philp, Lisa K.; Day, Tanya K.; Butler, Miriam S.; Laven-Law, Geraldine; Jindal, Shalini; Hickey, Theresa E.; Scher, Howard I.; Butler, Lisa M.; Tilley, Wayne D. title: Small Glutamine-Rich Tetratricopeptide Repeat-Containing Protein Alpha (SGTA) Ablation Limits Offspring Viability and Growth in Mice date: 2016-06-30 journal: Sci Rep DOI: 10.1038/srep28950 sha: doc_id: 2111 cord_uid: mmpijsqb file: cache/cord-002258-o9azey3m.json key: cord-002258-o9azey3m authors: Chan, Louisa L. Y.; Bui, Christine T. H.; Mok, Chris K. P.; Ng, Mandy M. T.; Nicholls, John M.; Peiris, J. S. Malik; Chan, Michael C. W.; Chan, Renee W. Y. title: Evaluation of the human adaptation of influenza A/H7N9 virus in PB2 protein using human and swine respiratory tract explant cultures date: 2016-10-14 journal: Sci Rep DOI: 10.1038/srep35401 sha: doc_id: 2258 cord_uid: o9azey3m file: cache/cord-002290-wvo22jx2.json key: cord-002290-wvo22jx2 authors: Liu, Cheng; He, Tao; Rong, Yanxiao; Du, Fengjiao; Ma, Dongxing; Wei, Yujie; Mei, Zhiqin; Wang, Yuling; Wang, Haibin; Zhu, Yuehua; Zhang, Zongde; Zheng, Li; Wu, Xueqiong; Liu, Huiliang; Ding, Wenjun title: Association of Mannose-binding Lectin Polymorphisms with Tuberculosis Susceptibility among Chinese date: 2016-11-04 journal: Sci Rep DOI: 10.1038/srep36488 sha: doc_id: 2290 cord_uid: wvo22jx2 file: cache/cord-002408-bbtslrrt.json key: cord-002408-bbtslrrt authors: Almogy, Gal; Stone, Lewi; Bernevig, B. Andrei; Wolf, Dana G.; Dorozko, Marina; Moses, Allon E.; Nir-Paz, Ran title: Analysis of Influenza and RSV dynamics in the community using a ‘Local Transmission Zone’ approach date: 2017-02-09 journal: Sci Rep DOI: 10.1038/srep42012 sha: doc_id: 2408 cord_uid: bbtslrrt file: cache/cord-003055-88q36g00.json key: cord-003055-88q36g00 authors: Imai, Kenji; Kotani, Tomomi; Tsuda, Hiroyuki; Nakano, Tomoko; Ushida, Takafumi; Iwase, Akira; Nagai, Taku; Toyokuni, Shinya; Suzumura, Akio; Kikkawa, Fumitaka title: Administration of molecular hydrogen during pregnancy improves behavioral abnormalities of offspring in a maternal immune activation model date: 2018-06-15 journal: Sci Rep DOI: 10.1038/s41598-018-27626-4 sha: doc_id: 3055 cord_uid: 88q36g00 file: cache/cord-002720-lrkscs71.json key: cord-002720-lrkscs71 authors: Kurosaki, Yohei; Martins, Danyelly Bruneska Gondim; Kimura, Mayuko; Catena, Andriu dos Santos; Borba, Maria Amélia Carlos Souto Maior; Mattos, Sandra da Silva; Abe, Haruka; Yoshikawa, Rokusuke; de Lima Filho, José Luiz; Yasuda, Jiro title: Development and evaluation of a rapid molecular diagnostic test for Zika virus infection by reverse transcription loop-mediated isothermal amplification date: 2017-10-18 journal: Sci Rep DOI: 10.1038/s41598-017-13836-9 sha: doc_id: 2720 cord_uid: lrkscs71 file: cache/cord-002782-mena480g.json key: cord-002782-mena480g authors: Chen, Jiajia; Wu, Jie; Hao, Shaorui; Yang, Meifang; Lu, Xiaoqing; Chen, Xiaoxiao; Li, Lanjuan title: Long term outcomes in survivors of epidemic Influenza A (H7N9) virus infection date: 2017-12-08 journal: Sci Rep DOI: 10.1038/s41598-017-17497-6 sha: doc_id: 2782 cord_uid: mena480g file: cache/cord-002644-yzan95du.json key: cord-002644-yzan95du authors: Ren, Rongrong; Wu, Shuxian; Cai, Jialin; Yang, Yuqin; Ren, Xiaonan; Feng, Yanling; Chen, Lixiang; Qin, Boyin; Xu, Chunhua; Yang, Hua; Song, Zhigang; Tian, Di; Hu, Yunwen; Zhou, Xiaohui; Meng, Guangxun title: The H7N9 influenza A virus infection results in lethal inflammation in the mammalian host via the NLRP3-caspase-1 inflammasome date: 2017-08-08 journal: Sci Rep DOI: 10.1038/s41598-017-07384-5 sha: doc_id: 2644 cord_uid: yzan95du file: cache/cord-001963-4wjvykx7.json key: cord-001963-4wjvykx7 authors: Liu, Chia-Lin; Hung, Hui-Chen; Lo, Shou-Chen; Chiang, Ching-Hui; Chen, I-Jung; Hsu, John T.-A.; Hou, Ming-Hon title: Using mutagenesis to explore conserved residues in the RNA-binding groove of influenza A virus nucleoprotein for antiviral drug development date: 2016-02-26 journal: Sci Rep DOI: 10.1038/srep21662 sha: doc_id: 1963 cord_uid: 4wjvykx7 file: cache/cord-002932-5e7xrd1y.json key: cord-002932-5e7xrd1y authors: Watanabe, Tokiko; Iwatsuki-Horimoto, Kiyoko; Kiso, Maki; Nakajima, Noriko; Takahashi, Kenta; Jose da Silva Lopes, Tiago; Ito, Mutsumi; Fukuyama, Satoshi; Hasegawa, Hideki; Kawaoka, Yoshihiro title: Experimental infection of Cynomolgus Macaques with highly pathogenic H5N1 influenza virus through the aerosol route date: 2018-03-19 journal: Sci Rep DOI: 10.1038/s41598-018-23022-0 sha: doc_id: 2932 cord_uid: 5e7xrd1y file: cache/cord-002844-jv42o789.json key: cord-002844-jv42o789 authors: Marcos-Villar, Laura; Díaz-Colunga, Juan; Sandoval, Juan; Zamarreño, Noelia; Landeras-Bueno, Sara; Esteller, Manel; Falcón, Ana; Nieto, Amelia title: Epigenetic control of influenza virus: role of H3K79 methylation in interferon-induced antiviral response date: 2018-01-19 journal: Sci Rep DOI: 10.1038/s41598-018-19370-6 sha: doc_id: 2844 cord_uid: jv42o789 file: cache/cord-002177-yyfgl9x5.json key: cord-002177-yyfgl9x5 authors: Guo, Jinyue; Li, Fei; Qian, Shaoju; Bi, Dingren; He, Qigai; Jin, Hui; Luo, Rui; Li, Shaowen; Meng, Xianrong; Li, Zili title: TGEV infection up-regulates FcRn expression via activation of NF-κB signaling date: 2016-08-24 journal: Sci Rep DOI: 10.1038/srep32154 sha: doc_id: 2177 cord_uid: yyfgl9x5 file: cache/cord-002320-m99amd4y.json key: cord-002320-m99amd4y authors: Mathur, Kalika; Anand, Abhishek; Dubey, Sunil Kumar; Sanan-Mishra, Neeti; Bhatnagar, Raj K.; Sunil, Sujatha title: Analysis of chikungunya virus proteins reveals that non-structural proteins nsP2 and nsP3 exhibit RNA interference (RNAi) suppressor activity date: 2016-11-30 journal: Sci Rep DOI: 10.1038/srep38065 sha: doc_id: 2320 cord_uid: m99amd4y file: cache/cord-002474-2l31d7ew.json key: cord-002474-2l31d7ew authors: Lv, Yang; Hu, Guangyao; Wang, Chunyang; Yuan, Wenjie; Wei, Shanshan; Gao, Jiaoqi; Wang, Boyuan; Song, Fangchao title: Actual measurement, hygrothermal response experiment and growth prediction analysis of microbial contamination of central air conditioning system in Dalian, China date: 2017-04-03 journal: Sci Rep DOI: 10.1038/srep44190 sha: doc_id: 2474 cord_uid: 2l31d7ew file: cache/cord-004181-exbs3tz7.json key: cord-004181-exbs3tz7 authors: Pumchan, Ansaya; Krobthong, Sucheewin; Roytrakul, Sittiruk; Sawatdichaikul, Orathai; Kondo, Hidehiro; Hirono, Ikuo; Areechon, Nontawith; Unajak, Sasimanas title: Novel Chimeric Multiepitope Vaccine for Streptococcosis Disease in Nile Tilapia (Oreochromis niloticus Linn.) date: 2020-01-17 journal: Sci Rep DOI: 10.1038/s41598-019-57283-0 sha: doc_id: 4181 cord_uid: exbs3tz7 file: cache/cord-003490-swlkjtyo.json key: cord-003490-swlkjtyo authors: Arzt, Jonathan; Branan, Matthew A.; Delgado, Amy H.; Yadav, Shankar; Moreno-Torres, Karla I.; Tildesley, Michael J.; Stenfeldt, Carolina title: Quantitative impacts of incubation phase transmission of foot-and-mouth disease virus date: 2019-02-25 journal: Sci Rep DOI: 10.1038/s41598-019-39029-0 sha: doc_id: 3490 cord_uid: swlkjtyo file: cache/cord-002411-iiw878w8.json key: cord-002411-iiw878w8 authors: Ding, Xibing; Jin, Shuqing; Tong, Yao; Jiang, Xi; Chen, Zhixia; Mei, Shuya; Zhang, Liming; Billiar, Timothy R.; Li, Quan title: TLR4 signaling induces TLR3 up-regulation in alveolar macrophages during acute lung injury date: 2017-02-15 journal: Sci Rep DOI: 10.1038/srep34278 sha: doc_id: 2411 cord_uid: iiw878w8 file: cache/cord-002874-9rxv6fy9.json key: cord-002874-9rxv6fy9 authors: Welch, David; Buonanno, Manuela; Grilj, Veljko; Shuryak, Igor; Crickmore, Connor; Bigelow, Alan W.; Randers-Pehrson, Gerhard; Johnson, Gary W.; Brenner, David J. title: Far-UVC light: A new tool to control the spread of airborne-mediated microbial diseases date: 2018-02-09 journal: Sci Rep DOI: 10.1038/s41598-018-21058-w sha: doc_id: 2874 cord_uid: 9rxv6fy9 file: cache/cord-002019-wtnf340p.json key: cord-002019-wtnf340p authors: Chen, Xiaojuan; Tu, Chongzhi; Qin, Tao; Zhu, Liqi; Yin, Yinyan; Yang, Qian title: Retinoic acid facilitates inactivated transmissible gastroenteritis virus induction of CD8(+) T-cell migration to the porcine gut date: 2016-04-15 journal: Sci Rep DOI: 10.1038/srep24152 sha: doc_id: 2019 cord_uid: wtnf340p file: cache/cord-002659-566uoozj.json key: cord-002659-566uoozj authors: Fujimoto, Yousuke; Hasegawa, Shunji; Matsushige, Takeshi; Wakiguchi, Hiroyuki; Nakamura, Tamaki; Hasegawa, Hideki; Nakajima, Noriko; Ainai, Akira; Oga, Atsunori; Itoh, Hiroshi; Shirabe, Komei; Toda, Shoichi; Atsuta, Ryo; Morishima, Tsuneo; Ohga, Shouichi title: Pulmonary inflammation and cytokine dynamics of bronchoalveolar lavage fluid from a mouse model of bronchial asthma during A(H1N1)pdm09 influenza infection date: 2017-08-22 journal: Sci Rep DOI: 10.1038/s41598-017-08030-w sha: doc_id: 2659 cord_uid: 566uoozj file: cache/cord-003148-o7y3wygc.json key: cord-003148-o7y3wygc authors: Shirvani, Edris; Paldurai, Anandan; Manoharan, Vinoth K.; Varghese, Berin P.; Samal, Siba K. title: A Recombinant Newcastle Disease Virus (NDV) Expressing S Protein of Infectious Bronchitis Virus (IBV) Protects Chickens against IBV and NDV date: 2018-08-10 journal: Sci Rep DOI: 10.1038/s41598-018-30356-2 sha: doc_id: 3148 cord_uid: o7y3wygc file: cache/cord-001915-b9dk07tk.json key: cord-001915-b9dk07tk authors: Liang, Xun; Sun, Leqiang; Yu, Teng; Pan, Yongfei; Wang, Dongdong; Hu, Xueying; Fu, Zhenfang; He, Qigai; Cao, Gang title: A CRISPR/Cas9 and Cre/Lox system-based express vaccine development strategy against re-emerging Pseudorabies virus date: 2016-01-18 journal: Sci Rep DOI: 10.1038/srep19176 sha: doc_id: 1915 cord_uid: b9dk07tk file: cache/cord-002013-rb9xdzro.json key: cord-002013-rb9xdzro authors: Zheng, Xuexing; Wong, Gary; Zhao, Yongkun; Wang, Hualei; He, Shihua; Bi, Yuhai; Chen, Weijin; Jin, Hongli; Gai, Weiwei; Chu, Di; Cao, Zengguo; Wang, Chong; Fan, Quanshui; Chi, Hang; Gao, Yuwei; Wang, Tiecheng; Feng, Na; Yan, Feihu; Huang, Geng; Zheng, Ying; Li, Nan; Li, Yuetao; Qian, Jun; Zou, Yong; Kobinger, Gary; Gao, George Fu; Qiu, Xiangguo; Yang, Songtao; Xia, Xianzhu title: Treatment with hyperimmune equine immunoglobulin or immunoglobulin fragments completely protects rodents from Ebola virus infection date: 2016-04-12 journal: Sci Rep DOI: 10.1038/srep24179 sha: doc_id: 2013 cord_uid: rb9xdzro file: cache/cord-002244-5h6monh3.json key: cord-002244-5h6monh3 authors: Lee, Seung Hoon; Park, Jin-Sil; Byun, Jae-Kyung; Jhun, JooYeon; Jung, KyungAh; Seo, Hyeon-Beom; Moon, Young-Mee; Kim, Ho-Youn; Park, Sung-Hwan; Cho, Mi-La title: PTEN ameliorates autoimmune arthritis through down-regulating STAT3 activation with reciprocal balance of Th17 and Tregs date: 2016-10-06 journal: Sci Rep DOI: 10.1038/srep34617 sha: doc_id: 2244 cord_uid: 5h6monh3 file: cache/cord-002843-dvfmpm54.json key: cord-002843-dvfmpm54 authors: Ai, Hannan; Ai, Yuncan; Meng, Fanmei title: GenomeLandscaper: Landscape analysis of genome-fingerprints maps assessing chromosome architecture date: 2018-01-18 journal: Sci Rep DOI: 10.1038/s41598-018-19366-2 sha: doc_id: 2843 cord_uid: dvfmpm54 file: cache/cord-003004-iif2lnez.json key: cord-003004-iif2lnez authors: Linster, Martin; Do, Lien Anh Ha; Minh, Ngo Ngoc Quang; Chen, Yihui; Zhe, Zhu; Tuan, Tran Anh; Tuan, Ha Manh; Su, Yvonne C. F.; van Doorn, H. Rogier; Moorthy, Mahesh; Smith, Gavin J. D. title: Clinical and Molecular Epidemiology of Human Parainfluenza Viruses 1–4 in Children from Viet Nam date: 2018-05-01 journal: Sci Rep DOI: 10.1038/s41598-018-24767-4 sha: doc_id: 3004 cord_uid: iif2lnez file: cache/cord-003166-k3jxvzfi.json key: cord-003166-k3jxvzfi authors: Noh, Ji Yeong; Jeong, Dae Gwin; Yoon, Sun-Woo; Kim, Ji Hyung; Choi, Yong Gun; Kang, Shien-Young; Kim, Hye Kwon title: Isolation and characterization of novel bat paramyxovirus B16-40 potentially belonging to the proposed genus Shaanvirus date: 2018-08-22 journal: Sci Rep DOI: 10.1038/s41598-018-30319-7 sha: doc_id: 3166 cord_uid: k3jxvzfi file: cache/cord-003623-n01rgqyv.json key: cord-003623-n01rgqyv authors: Schuh, Amy J.; Amman, Brian R.; Sealy, Tara S.; Flietstra, Timothy D.; Guito, Jonathan C.; Nichol, Stuart T.; Towner, Jonathan S. title: Comparative analysis of serologic cross-reactivity using convalescent sera from filovirus-experimentally infected fruit bats date: 2019-04-30 journal: Sci Rep DOI: 10.1038/s41598-019-43156-z sha: doc_id: 3623 cord_uid: n01rgqyv file: cache/cord-002389-k86hzbbx.json key: cord-002389-k86hzbbx authors: Fan, Hanlu; Du, Xiaohong; Zhang, Jingyuan; Zheng, Han; Lu, Xiaohui; Wu, Qihui; Li, Haifeng; Wang, Han; Shi, Yi; Gao, George; Zhou, Zhuan; Tan, Dun-Xian; Li, Xiangdong title: Selective inhibition of Ebola entry with selective estrogen receptor modulators by disrupting the endolysosomal calcium date: 2017-01-24 journal: Sci Rep DOI: 10.1038/srep41226 sha: doc_id: 2389 cord_uid: k86hzbbx file: cache/cord-003505-qr6ukfti.json key: cord-003505-qr6ukfti authors: Tabraue-Chávez, Mavys; Luque-González, María Angélica; Marín-Romero, Antonio; Sánchez-Martín, Rosario María; Escobedo-Araque, Pablo; Pernagallo, Salvatore; Díaz-Mochón, Juan José title: A colorimetric strategy based on dynamic chemistry for direct detection of Trypanosomatid species date: 2019-03-06 journal: Sci Rep DOI: 10.1038/s41598-019-39946-0 sha: doc_id: 3505 cord_uid: qr6ukfti file: cache/cord-004150-ybikajhh.json key: cord-004150-ybikajhh authors: Nyarko, Prince B.; Tarr, Sarah J.; Aniweh, Yaw; Stewart, Lindsay B.; Conway, David J.; Awandare, Gordon A. title: Investigating a Plasmodium falciparum erythrocyte invasion phenotype switch at the whole transcriptome level date: 2020-01-14 journal: Sci Rep DOI: 10.1038/s41598-019-56386-y sha: doc_id: 4150 cord_uid: ybikajhh file: cache/cord-001868-utsvsja0.json key: cord-001868-utsvsja0 authors: Uematsu, Takayuki; Iizasa, Ei’ichi; Kobayashi, Noritada; Yoshida, Hiroki; Hara, Hiromitsu title: Loss of CARD9-mediated innate activation attenuates severe influenza pneumonia without compromising host viral immunity date: 2015-12-02 journal: Sci Rep DOI: 10.1038/srep17577 sha: doc_id: 1868 cord_uid: utsvsja0 file: cache/cord-002956-e5ihpe4i.json key: cord-002956-e5ihpe4i authors: Chang, Ya-Chun; Huang, Kuo-Tung; Chen, Yu-Mu; Wang, Chin-Chou; Wang, Yi-Hsi; Tseng, Chia-Cheng; Lin, Meng-Chih; Fang, Wen-Feng title: Ventilator Dependence Risk Score for the Prediction of Prolonged Mechanical Ventilation in Patients Who Survive Sepsis/Septic Shock with Respiratory Failure date: 2018-04-04 journal: Sci Rep DOI: 10.1038/s41598-018-24028-4 sha: doc_id: 2956 cord_uid: e5ihpe4i file: cache/cord-003387-82573enr.json key: cord-003387-82573enr authors: Nam, Gyu-Hwi; Mishra, Anshuman; Gim, Jeong-An; Lee, Hee-Eun; Jo, Ara; Yoon, Dahye; Kim, Ahran; Kim, Woo-Jin; Ahn, Kung; Kim, Do-Hyung; Kim, Suhkmann; Cha, Hee-Jae; Choi, Yung Hyun; Park, Chan-Il; Kim, Heui-Soo title: Gene expression profiles alteration after infection of virus, bacteria, and parasite in the Olive flounder (Paralichthys olivaceus) date: 2018-12-24 journal: Sci Rep DOI: 10.1038/s41598-018-36342-y sha: doc_id: 3387 cord_uid: 82573enr file: cache/cord-004062-yxx3xxio.json key: cord-004062-yxx3xxio authors: Lee, Ing-Kit; Yang, Zih-Syuan; Ng, Hwee-Yeong; Li, Lung-Chih; Huang, Wen-Chi; Chen, Yi-Chun; Tsai, Ching-Yen; Lee, Chien-Te title: Impaired production of immune mediators in dengue virus type 2-infected mononuclear cells of adults with end stage renal disease date: 2019-12-24 journal: Sci Rep DOI: 10.1038/s41598-019-56381-3 sha: doc_id: 4062 cord_uid: yxx3xxio file: cache/cord-003504-wjab4y0g.json key: cord-003504-wjab4y0g authors: Copland, Alastair; Sparrow, Adam; Hart, Peter; Diogo, Gil Reynolds; Paul, Mathew; Azuma, Miyuki; Reljic, Rajko title: Bacillus Calmette-Guérin Induces PD-L1 Expression on Antigen-Presenting Cells via Autocrine and Paracrine Interleukin-STAT3 Circuits date: 2019-03-06 journal: Sci Rep DOI: 10.1038/s41598-019-40145-0 sha: doc_id: 3504 cord_uid: wjab4y0g file: cache/cord-004016-iaktm72a.json key: cord-004016-iaktm72a authors: Soto-Quintero, Albanelly; Guarrotxena, Nekane; García, Olga; Quijada-Garrido, Isabel title: Curcumin to Promote the Synthesis of Silver NPs and their Self-Assembly with a Thermoresponsive Polymer in Core-Shell Nanohybrids date: 2019-12-03 journal: Sci Rep DOI: 10.1038/s41598-019-54752-4 sha: doc_id: 4016 cord_uid: iaktm72a file: cache/cord-003196-fdb6az0v.json key: cord-003196-fdb6az0v authors: Casalino-Matsuda, S. Marina; Wang, Naizhen; Ruhoff, Peder T.; Matsuda, Hiroaki; Nlend, Marie C.; Nair, Aisha; Szleifer, Igal; Beitel, Greg J.; Sznajder, Jacob I.; Sporn, Peter H. S. title: Hypercapnia Alters Expression of Immune Response, Nucleosome Assembly and Lipid Metabolism Genes in Differentiated Human Bronchial Epithelial Cells date: 2018-09-10 journal: Sci Rep DOI: 10.1038/s41598-018-32008-x sha: doc_id: 3196 cord_uid: fdb6az0v file: cache/cord-004006-tfp2idq2.json key: cord-004006-tfp2idq2 authors: Hale, Alison C.; Sánchez-Vizcaíno, Fernando; Rowlingson, Barry; Radford, Alan D.; Giorgi, Emanuele; O’Brien, Sarah J.; Diggle, Peter J. title: A real-time spatio-temporal syndromic surveillance system with application to small companion animals date: 2019-11-28 journal: Sci Rep DOI: 10.1038/s41598-019-53352-6 sha: doc_id: 4006 cord_uid: tfp2idq2 file: cache/cord-004060-nxw5k9y1.json key: cord-004060-nxw5k9y1 authors: Zhang, Yewu; Wang, Xiaofeng; Li, Yanfei; Ma, Jiaqi title: Spatiotemporal Analysis of Influenza in China, 2005–2018 date: 2019-12-23 journal: Sci Rep DOI: 10.1038/s41598-019-56104-8 sha: doc_id: 4060 cord_uid: nxw5k9y1 file: cache/cord-004378-g1rxygef.json key: cord-004378-g1rxygef authors: Leinisch, Fabian; Mariotti, Michele; Andersen, Sofie Hagel; Lindemose, Søren; Hägglund, Per; Møllegaard, Niels Erik; Davies, Michael J. title: UV oxidation of cyclic AMP receptor protein, a global bacterial gene regulator, decreases DNA binding and cleaves DNA at specific sites date: 2020-02-20 journal: Sci Rep DOI: 10.1038/s41598-020-59855-x sha: doc_id: 4378 cord_uid: g1rxygef file: cache/cord-004419-81w7apdk.json key: cord-004419-81w7apdk authors: Course, Christopher; Chakraborty, Mallinath title: Management of Respiratory Distress Syndrome in Preterm Infants In Wales: A Full Audit Cycle of a Quality Improvement Project date: 2020-02-26 journal: Sci Rep DOI: 10.1038/s41598-020-60091-6 sha: doc_id: 4419 cord_uid: 81w7apdk file: cache/cord-002802-594mmlk8.json key: cord-002802-594mmlk8 authors: Zhang, Yun; Wei, Ying; Liu, Kang; Huang, Mengjiao; Li, Ran; Wang, Yang; Liu, Qiliang; Zheng, Jing; Xue, Chunyi; Cao, Yongchang title: Recombinant influenza H9N2 virus with a substitution of H3 hemagglutinin transmembrane domain showed enhanced immunogenicity in mice and chicken date: 2017-12-20 journal: Sci Rep DOI: 10.1038/s41598-017-18054-x sha: doc_id: 2802 cord_uid: 594mmlk8 file: cache/cord-004069-nuep8nim.json key: cord-004069-nuep8nim authors: DeWald, Lisa Evans; Johnson, Joshua C.; Gerhardt, Dawn M.; Torzewski, Lisa M.; Postnikova, Elena; Honko, Anna N.; Janosko, Krisztina; Huzella, Louis; Dowling, William E.; Eakin, Ann E.; Osborn, Blaire L.; Gahagen, Janet; Tang, Liang; Green, Carol E.; Mirsalis, Jon C.; Holbrook, Michael R.; Jahrling, Peter B.; Dyall, Julie; Hensley, Lisa E. title: In Vivo Activity of Amodiaquine against Ebola Virus Infection date: 2019-12-27 journal: Sci Rep DOI: 10.1038/s41598-019-56481-0 sha: doc_id: 4069 cord_uid: nuep8nim file: cache/cord-004170-ri5qsarz.json key: cord-004170-ri5qsarz authors: Yashima, Nozomi; Ito, Takashi; Kajiyama, Kenji; Maeda, Hiroyuki; Kakihana, Yasuyuki; Maruyama, Ikuro title: Leukocyte-derived extracellular DNA contributes to abnormal pressure elevation in the extracorporeal circulation circuit date: 2020-01-16 journal: Sci Rep DOI: 10.1038/s41598-019-57173-5 sha: doc_id: 4170 cord_uid: ri5qsarz file: cache/cord-002045-m44fic4g.json key: cord-002045-m44fic4g authors: Horie, Masayuki; Kobayashi, Yuki; Honda, Tomoyuki; Fujino, Kan; Akasaka, Takumi; Kohl, Claudia; Wibbelt, Gudrun; Mühldorfer, Kristin; Kurth, Andreas; Müller, Marcel A.; Corman, Victor M.; Gillich, Nadine; Suzuki, Yoshiyuki; Schwemmle, Martin; Tomonaga, Keizo title: An RNA-dependent RNA polymerase gene in bat genomes derived from an ancient negative-strand RNA virus date: 2016-05-13 journal: Sci Rep DOI: 10.1038/srep25873 sha: doc_id: 2045 cord_uid: m44fic4g file: cache/cord-003667-u1xa44nw.json key: cord-003667-u1xa44nw authors: Rodriguez, Sergio E.; Cross, Robert W.; Fenton, Karla A.; Bente, Dennis A.; Mire, Chad E.; Geisbert, Thomas W. title: Vesicular Stomatitis Virus-Based Vaccine Protects Mice against Crimean-Congo Hemorrhagic Fever date: 2019-05-23 journal: Sci Rep DOI: 10.1038/s41598-019-44210-6 sha: doc_id: 3667 cord_uid: u1xa44nw file: cache/cord-004292-6lnxb0px.json key: cord-004292-6lnxb0px authors: Lyu, Hongming; John, Mathews; Burkland, David; Greet, Brian; Post, Allison; Babakhani, Aydin; Razavi, Mehdi title: Synchronized Biventricular Heart Pacing in a Closed-chest Porcine Model based on Wirelessly Powered Leadless Pacemakers date: 2020-02-07 journal: Sci Rep DOI: 10.1038/s41598-020-59017-z sha: doc_id: 4292 cord_uid: 6lnxb0px file: cache/cord-003558-7lvqpz21.json key: cord-003558-7lvqpz21 authors: Davies, Patrick; Yasin, Samra; Gates, Simon; Bird, David; Silvestre, Catarina title: Clinical Scenarios of the Application of Electrical Impedance Tomography in Paediatric Intensive Care date: 2019-03-29 journal: Sci Rep DOI: 10.1038/s41598-019-41774-1 sha: doc_id: 3558 cord_uid: 7lvqpz21 file: cache/cord-002929-oqe3gjcs.json key: cord-002929-oqe3gjcs authors: Strano, Emanuele; Viana, Matheus P.; Sorichetta, Alessandro; Tatem, Andrew J. title: Mapping road network communities for guiding disease surveillance and control strategies date: 2018-03-16 journal: Sci Rep DOI: 10.1038/s41598-018-22969-4 sha: doc_id: 2929 cord_uid: oqe3gjcs file: cache/cord-003444-dmpoy0b1.json key: cord-003444-dmpoy0b1 authors: Rowe, John C.; Attia, Zayed; Kim, Eunsoo; Cormet-Boyaka, Estelle; Boyaka, Prosper N. title: A Novel Supplementation Approach to Enhance Host Response to Sublingual Vaccination date: 2019-01-24 journal: Sci Rep DOI: 10.1038/s41598-018-36370-8 sha: doc_id: 3444 cord_uid: dmpoy0b1 file: cache/cord-004379-91a7sgir.json key: cord-004379-91a7sgir authors: Han, Nayoung; Oh, Jung Mi; Kim, In-Wha title: Assessment of adverse events related to anti-influenza neuraminidase inhibitors using the FDA adverse event reporting system and online patient reviews date: 2020-02-20 journal: Sci Rep DOI: 10.1038/s41598-020-60068-5 sha: doc_id: 4379 cord_uid: 91a7sgir file: cache/cord-003011-vclnb0eh.json key: cord-003011-vclnb0eh authors: de Almeida, Carlos Podalirio Borges; Ziegelmann, Patrícia Klarmann; Couban, Rachel; Wang, Li; Busse, Jason Walter; Silva, Denise Rossato title: Predictors of In-Hospital Mortality among Patients with Pulmonary Tuberculosis: A Systematic Review and Meta-analysis date: 2018-05-08 journal: Sci Rep DOI: 10.1038/s41598-018-25409-5 sha: doc_id: 3011 cord_uid: vclnb0eh file: cache/cord-004222-z4butywi.json key: cord-004222-z4butywi authors: Joyce, Collin; Burton, Dennis R.; Briney, Bryan title: Comparisons of the antibody repertoires of a humanized rodent and humans by high throughput sequencing date: 2020-01-24 journal: Sci Rep DOI: 10.1038/s41598-020-57764-7 sha: doc_id: 4222 cord_uid: z4butywi file: cache/cord-004310-hl7fa4af.json key: cord-004310-hl7fa4af authors: Matsuishi, Yujiro; Sakuramoto, Hideaki; Hoshino, Haruhiko; Shimojo, Nobutake; Enomoto, Yuki; Mathis, Bryan J.; Hiramatsu, Yuji; Inoue, Yoshiaki title: Down Syndrome Reduces the Sedative Effect of Midazolam in Pediatric Cardiovascular Surgical Patients date: 2020-02-10 journal: Sci Rep DOI: 10.1038/s41598-020-58283-1 sha: doc_id: 4310 cord_uid: hl7fa4af file: cache/cord-004385-xna32qve.json key: cord-004385-xna32qve authors: Zhou, Yuqing; Fu, Xiaofang; Liu, Xiaoxiao; Huang, Chenyang; Tian, Guo; Ding, Cheng; Wu, Jie; Lan, Lei; Yang, Shigui title: Use of corticosteroids in influenza-associated acute respiratory distress syndrome and severe pneumonia: a systemic review and meta-analysis date: 2020-02-20 journal: Sci Rep DOI: 10.1038/s41598-020-59732-7 sha: doc_id: 4385 cord_uid: xna32qve file: cache/cord-010140-nl1j2s56.json key: cord-010140-nl1j2s56 authors: Nagaoka, Hikaru; Kanoi, Bernard N.; Ntege, Edward H.; Aoki, Masamitsu; Fukushima, Akihisa; Tsuboi, Takafumi; Takashima, Eizo title: Antibodies against a short region of PfRipr inhibit Plasmodium falciparum merozoite invasion and PfRipr interaction with Rh5 and SEMA7A date: 2020-04-20 journal: Sci Rep DOI: 10.1038/s41598-020-63611-6 sha: doc_id: 10140 cord_uid: nl1j2s56 file: cache/cord-002842-4evbeijx.json key: cord-002842-4evbeijx authors: Pandey, Rajan Kumar; Bhatt, Tarun Kumar; Prajapati, Vijay Kumar title: Novel Immunoinformatics Approaches to Design Multi-epitope Subunit Vaccine for Malaria by Investigating Anopheles Salivary Protein date: 2018-01-18 journal: Sci Rep DOI: 10.1038/s41598-018-19456-1 sha: doc_id: 2842 cord_uid: 4evbeijx file: cache/cord-002791-tqchfdmy.json key: cord-002791-tqchfdmy authors: Mikel, Pavel; Vasickova, Petra; Kralik, Petr title: One-plasmid double-expression His-tag system for rapid production and easy purification of MS2 phage-like particles date: 2017-12-13 journal: Sci Rep DOI: 10.1038/s41598-017-17951-5 sha: doc_id: 2791 cord_uid: tqchfdmy file: cache/cord-005507-equnyib7.json key: cord-005507-equnyib7 authors: Kamath, Kathy; Reifert, Jack; Johnston, Timothy; Gable, Cameron; Pantazes, Robert J.; Rivera, Hilda N.; McAuliffe, Isabel; Handali, Sukwan; Daugherty, Patrick S. title: Antibody epitope repertoire analysis enables rapid antigen discovery and multiplex serology date: 2020-03-24 journal: Sci Rep DOI: 10.1038/s41598-020-62256-9 sha: doc_id: 5507 cord_uid: equnyib7 file: cache/cord-009691-gkynxdz3.json key: cord-009691-gkynxdz3 authors: Rizzato, Cosmeri; Torres, Javier; Obazee, Ofure; Camorlinga-Ponce, Margarita; Trujillo, Esperanza; Stein, Angelika; Mendez-Tenorio, Alfonso; Bravo, Maria Mercedes; Canzian, Federico; Kato, Ikuko title: Variations in cag pathogenicity island genes of Helicobacter pylori from Latin American groups may influence neoplastic progression to gastric cancer date: 2020-04-16 journal: Sci Rep DOI: 10.1038/s41598-020-63463-0 sha: doc_id: 9691 cord_uid: gkynxdz3 file: cache/cord-004156-79peyzc9.json key: cord-004156-79peyzc9 authors: Lee, Shwu-Maan; Hickey, John M.; Miura, Kazutoyo; Joshi, Sangeeta B.; Volkin, David B.; King, C. Richter; Plieskatt, Jordan L. title: A C-terminal Pfs48/45 malaria transmission-blocking vaccine candidate produced in the baculovirus expression system date: 2020-01-15 journal: Sci Rep DOI: 10.1038/s41598-019-57384-w sha: doc_id: 4156 cord_uid: 79peyzc9 file: cache/cord-004342-9uok77wb.json key: cord-004342-9uok77wb authors: Lin, Chun-Yu; Lu, Cheng-Hui; Lee, Hsiu-An; See, Lai-Chu; Wu, Meng-Yu; Han, Yi; Tseng, Chi-Nan; Su, I-Li; Li, Han-Yan; Tsai, Feng-Chun title: Elderly versus non-elderly patients undergoing surgery for left-sided native valve infective endocarditis: A 10-year institutional experience date: 2020-02-14 journal: Sci Rep DOI: 10.1038/s41598-020-59657-1 sha: doc_id: 4342 cord_uid: 9uok77wb file: cache/cord-010675-acdfvjm5.json key: cord-010675-acdfvjm5 authors: Vila-Vicent, Susana; Gozalbo-Rovira, Roberto; Rubio-Del-Campo, Antonio; Santiso-Bellón, Cristina; Navarro-Lleó, Noemí; Muñoz, Carlos; Buesa, Javier; Rodríguez-Díaz, Jesús title: Sero-epidemiological study of the rotavirus VP8* protein from different P genotypes in Valencia, Spain date: 2020-05-08 journal: Sci Rep DOI: 10.1038/s41598-020-64767-x sha: doc_id: 10675 cord_uid: acdfvjm5 file: cache/cord-013977-xb0r2axf.json key: cord-013977-xb0r2axf authors: Heng, Kevin; Althaus, Christian L. title: The approximately universal shapes of epidemic curves in the Susceptible-Exposed-Infectious-Recovered (SEIR) model date: 2020-11-09 journal: Sci Rep DOI: 10.1038/s41598-020-76563-8 sha: doc_id: 13977 cord_uid: xb0r2axf file: cache/cord-004280-c470nlie.json key: cord-004280-c470nlie authors: Coleman, Kristen K.; Sigler, William V. title: Airborne Influenza A Virus Exposure in an Elementary School date: 2020-02-05 journal: Sci Rep DOI: 10.1038/s41598-020-58588-1 sha: doc_id: 4280 cord_uid: c470nlie file: cache/cord-004140-ujzrqzv3.json key: cord-004140-ujzrqzv3 authors: Lu, Xiaying; Wang, Juan; Chen, Xiaohuan; Jiang, Yong; Pan, Zhixing K. title: Rolipram Protects Mice from Gram-negative Bacterium Escherichia coli-induced Inflammation and Septic Shock date: 2020-01-13 journal: Sci Rep DOI: 10.1038/s41598-019-56899-6 sha: doc_id: 4140 cord_uid: ujzrqzv3 file: cache/cord-004416-qw6tusd2.json key: cord-004416-qw6tusd2 authors: Krishna, Smriti M.; Omer, Safraz Mohamed; Li, Jiaze; Morton, Susan K.; Jose, Roby J.; Golledge, Jonathan title: Development of a two-stage limb ischemia model to better simulate human peripheral artery disease date: 2020-02-26 journal: Sci Rep DOI: 10.1038/s41598-020-60352-4 sha: doc_id: 4416 cord_uid: qw6tusd2 file: cache/cord-004418-08dljap3.json key: cord-004418-08dljap3 authors: Young, Ginger; Bohning, Kelly J.; Zahralban-Steele, Melissa; Hather, Greg; Tadepalli, Sambasivarao; Mickey, Kristen; Godin, C. Steven; Sanisetty, Srisowmya; Sonnberg, Stephanie; Patel, Hetal K.; Dean, Hansi J. title: Complete Protection in Macaques Conferred by Purified Inactivated Zika Vaccine: Defining a Correlate of Protection date: 2020-02-26 journal: Sci Rep DOI: 10.1038/s41598-020-60415-6 sha: doc_id: 4418 cord_uid: 08dljap3 file: cache/cord-011892-b9zlig0r.json key: cord-011892-b9zlig0r authors: Mukherjee, Shradha title: Quiescent stem cell marker genes in glioma gene networks are sufficient to distinguish between normal and glioblastoma (GBM) samples date: 2020-07-02 journal: Sci Rep DOI: 10.1038/s41598-020-67753-5 sha: doc_id: 11892 cord_uid: b9zlig0r file: cache/cord-009690-kbwz7xop.json key: cord-009690-kbwz7xop authors: Toubanaki, Dimitra K.; Margaroni, Maritsa; Prapas, Athanasios; Karagouni, Evdokia title: Development of a Nanoparticle-based Lateral Flow Strip Biosensor for Visual Detection of Whole Nervous Necrosis Virus Particles date: 2020-04-16 journal: Sci Rep DOI: 10.1038/s41598-020-63553-z sha: doc_id: 9690 cord_uid: kbwz7xop file: cache/cord-010328-uxpedpz8.json key: cord-010328-uxpedpz8 authors: Ciencewicki, Jonathan M.; Schouest, Katherine R.; Gierman, Todd M.; Vandeberg, Peter J.; Gooch, Barry D. title: Plasma Donors in the Southwestern United States Positively Contribute to the Diverse Therapeutic Antibody Profile of Immune Globulin Products date: 2020-04-22 journal: Sci Rep DOI: 10.1038/s41598-020-63794-y sha: doc_id: 10328 cord_uid: uxpedpz8 file: cache/cord-012742-lpk6r54i.json key: cord-012742-lpk6r54i authors: Ferreira-Ramos, Ana Sofia; Sulzenbacher, Gerlind; Canard, Bruno; Coutard, Bruno title: Snapshots of ADP-ribose bound to Getah virus macro domain reveal an intriguing choreography date: 2020-09-02 journal: Sci Rep DOI: 10.1038/s41598-020-70870-w sha: doc_id: 12742 cord_uid: lpk6r54i file: cache/cord-034746-uxhpufnv.json key: cord-034746-uxhpufnv authors: Nusshag, Christian; Stütz, Alisa; Hägele, Stefan; Speer, Claudius; Kälble, Florian; Eckert, Christoph; Brenner, Thorsten; Weigand, Markus A.; Morath, Christian; Reiser, Jochen; Zeier, Martin; Krautkrämer, Ellen title: Glomerular filtration barrier dysfunction in a self-limiting, RNA virus-induced glomerulopathy resembles findings in idiopathic nephrotic syndromes date: 2020-11-05 journal: Sci Rep DOI: 10.1038/s41598-020-76050-0 sha: doc_id: 34746 cord_uid: uxhpufnv file: cache/cord-031937-qhlatg84.json key: cord-031937-qhlatg84 authors: Verma, Anukriti; Sharda, Shivani; Rathi, Bhawna; Somvanshi, Pallavi; Pandey, Bimlesh Dhar title: Elucidating potential molecular signatures through host-microbe interactions for reactive arthritis and inflammatory bowel disease using combinatorial approach date: 2020-09-15 journal: Sci Rep DOI: 10.1038/s41598-020-71674-8 sha: doc_id: 31937 cord_uid: qhlatg84 file: cache/cord-010640-s1oqphvn.json key: cord-010640-s1oqphvn authors: Baral, Prabin; Pavadai, Elumalai; Gerstman, Bernard S.; Chapagain, Prem P. title: In-silico identification of the vaccine candidate epitopes against the Lassa virus hemorrhagic fever date: 2020-05-06 journal: Sci Rep DOI: 10.1038/s41598-020-63640-1 sha: doc_id: 10640 cord_uid: s1oqphvn file: cache/cord-007851-v6h1yro7.json key: cord-007851-v6h1yro7 authors: Han, Ki-Cheol; Park, Daechan; Ju, Shinyeong; Lee, Young Eun; Heo, Sun-Hee; Kim, Young-Ae; Lee, Ji Eun; Lee, Yuna; Park, Kyong Hwa; Park, Se-Ho; Lee, Hee Jin; Lee, Cheolju; Jang, Mihue title: Streamlined selection of cancer antigens for vaccine development through integrative multi-omics and high-content cell imaging date: 2020-04-03 journal: Sci Rep DOI: 10.1038/s41598-020-62244-z sha: doc_id: 7851 cord_uid: v6h1yro7 file: cache/cord-259378-5g2y68i2.json key: cord-259378-5g2y68i2 authors: Cheng, Chao-Min title: Small-volume point-of-care analytical methods date: 2020-08-27 journal: Sci Rep DOI: 10.1038/s41598-020-70903-4 sha: doc_id: 259378 cord_uid: 5g2y68i2 file: cache/cord-255511-nk3iyg07.json key: cord-255511-nk3iyg07 authors: Chin, Wei Chien Benny; Bouffanais, Roland title: Spatial super-spreaders and super-susceptibles in human movement networks date: 2020-10-29 journal: Sci Rep DOI: 10.1038/s41598-020-75697-z sha: doc_id: 255511 cord_uid: nk3iyg07 file: cache/cord-258678-0atfsivf.json key: cord-258678-0atfsivf authors: Liu, Hong Yan; Gao, Xiaohu title: A Universal Protein Tag for Delivery of SiRNA-Aptamer Chimeras date: 2013-11-07 journal: Sci Rep DOI: 10.1038/srep03129 sha: doc_id: 258678 cord_uid: 0atfsivf file: cache/cord-272092-ko9y5m2s.json key: cord-272092-ko9y5m2s authors: Scalabrin, Matteo; Frasson, Ilaria; Ruggiero, Emanuela; Perrone, Rosalba; Tosoni, Elena; Lago, Sara; Tassinari, Martina; Palù, Giorgio; Richter, Sara N. title: The cellular protein hnRNP A2/B1 enhances HIV-1 transcription by unfolding LTR promoter G-quadruplexes date: 2017-03-24 journal: Sci Rep DOI: 10.1038/srep45244 sha: doc_id: 272092 cord_uid: ko9y5m2s file: cache/cord-030295-jlhht2l9.json key: cord-030295-jlhht2l9 authors: Cruz-Flores, Roberto; Mai, Hung N.; Kanrar, Siddhartha; Aranguren Caro, Luis Fernando; Dhar, Arun K. title: Genome reconstruction of white spot syndrome virus (WSSV) from archival Davidson’s-fixed paraffin embedded shrimp (Penaeus vannamei) tissue date: 2020-08-10 journal: Sci Rep DOI: 10.1038/s41598-020-70435-x sha: doc_id: 30295 cord_uid: jlhht2l9 file: cache/cord-254090-x8tnweih.json key: cord-254090-x8tnweih authors: Yang, Szu-Chi; Lin, Huan-Chun; Liu, Tzu-Ming; Lu, Jen-Tang; Hung, Wan-Ting; Huang, Yu-Ru; Tsai, Yi-Chun; Kao, Chuan-Liang; Chen, Shih-Yuan; Sun, Chi-Kuang title: Efficient Structure Resonance Energy Transfer from Microwaves to Confined Acoustic Vibrations in Viruses date: 2015-12-09 journal: Sci Rep DOI: 10.1038/srep18030 sha: doc_id: 254090 cord_uid: x8tnweih file: cache/cord-254653-4ffuivil.json key: cord-254653-4ffuivil authors: Cinelli, Matteo; Quattrociocchi, Walter; Galeazzi, Alessandro; Valensise, Carlo Michele; Brugnoli, Emanuele; Schmidt, Ana Lucia; Zola, Paola; Zollo, Fabiana; Scala, Antonio title: The COVID-19 social media infodemic date: 2020-10-06 journal: Sci Rep DOI: 10.1038/s41598-020-73510-5 sha: doc_id: 254653 cord_uid: 4ffuivil file: cache/cord-259794-6qoksn00.json key: cord-259794-6qoksn00 authors: Shi, Da; Shi, Hongyan; Sun, Dongbo; Chen, Jianfei; Zhang, Xin; Wang, Xiaobo; Zhang, Jialin; Ji, Zhaoyang; Liu, Jianbo; Cao, Liyan; Zhu, Xiangdong; Yuan, Jing; Dong, Hui; Wang, Xin; Chang, Tiecheng; Liu, Ye; Feng, Li title: Nucleocapsid Interacts with NPM1 and Protects it from Proteolytic Cleavage, Enhancing Cell Survival, and is Involved in PEDV Growth date: 2017-01-03 journal: Sci Rep DOI: 10.1038/srep39700 sha: doc_id: 259794 cord_uid: 6qoksn00 file: cache/cord-263627-8ufjh70o.json key: cord-263627-8ufjh70o authors: Liang, Li-Lin; Tseng, Ching-Hung; Ho, Hsiu J.; Wu, Chun-Ying title: Covid-19 mortality is negatively associated with test number and government effectiveness date: 2020-07-24 journal: Sci Rep DOI: 10.1038/s41598-020-68862-x sha: doc_id: 263627 cord_uid: 8ufjh70o file: cache/cord-265211-a7whyds8.json key: cord-265211-a7whyds8 authors: Hussein, Hosni A. M.; Akula, Shaw M. title: miRNA-36 inhibits KSHV, EBV, HSV-2 infection of cells via stifling expression of interferon induced transmembrane protein 1 (IFITM1) date: 2017-12-21 journal: Sci Rep DOI: 10.1038/s41598-017-18225-w sha: doc_id: 265211 cord_uid: a7whyds8 file: cache/cord-260834-v254de8k.json key: cord-260834-v254de8k authors: Lim, Chia Chiu; Woo, Patrick C. Y.; Lim, Theam Soon title: Development of a Phage Display Panning Strategy Utilizing Crude Antigens: Isolation of MERS-CoV Nucleoprotein human antibodies date: 2019-04-15 journal: Sci Rep DOI: 10.1038/s41598-019-42628-6 sha: doc_id: 260834 cord_uid: v254de8k file: cache/cord-263088-zj14ro5j.json key: cord-263088-zj14ro5j authors: DiPaola, Joshua D.; Yindee, Marnoch; Plotnik, Joshua M. title: Investigating the use of sensory information to detect and track prey by the Sunda pangolin (Manis javanica) with conservation in mind date: 2020-06-17 journal: Sci Rep DOI: 10.1038/s41598-020-65898-x sha: doc_id: 263088 cord_uid: zj14ro5j file: cache/cord-255586-wshvvgxg.json key: cord-255586-wshvvgxg authors: He, Shengyang; Zhou, Kefu; Hu, Mengyun; Liu, Chun; Xie, Lihua; Sun, Shenghua; Sun, Wenwu; Chen, Liangkai title: Clinical characteristics of “re-positive” discharged COVID-19 pneumonia patients in Wuhan, China date: 2020-10-15 journal: Sci Rep DOI: 10.1038/s41598-020-74284-6 sha: doc_id: 255586 cord_uid: wshvvgxg file: cache/cord-259416-gvzp2h5g.json key: cord-259416-gvzp2h5g authors: Ling, Shenglong; Zhang, Chengwei; Wang, Wei; Cai, Xiaoying; Yu, Lu; Wu, Fangming; Zhang, Longhua; Tian, Changlin title: Combined approaches of EPR and NMR illustrate only one transmembrane helix in the human IFITM3 date: 2016-04-05 journal: Sci Rep DOI: 10.1038/srep24029 sha: doc_id: 259416 cord_uid: gvzp2h5g file: cache/cord-265891-jmpterrj.json key: cord-265891-jmpterrj authors: Eilersen, Andreas; Sneppen, Kim title: Cost–benefit of limited isolation and testing in COVID-19 mitigation date: 2020-10-29 journal: Sci Rep DOI: 10.1038/s41598-020-75640-2 sha: doc_id: 265891 cord_uid: jmpterrj file: cache/cord-269756-tid8a464.json key: cord-269756-tid8a464 authors: Basso, Luis G. M.; Vicente, Eduardo F.; Crusca Jr., Edson; Cilli, Eduardo M.; Costa-Filho, Antonio J. title: SARS-CoV fusion peptides induce membrane surface ordering and curvature date: 2016-11-28 journal: Sci Rep DOI: 10.1038/srep37131 sha: doc_id: 269756 cord_uid: tid8a464 file: cache/cord-271328-zdf5ji4k.json key: cord-271328-zdf5ji4k authors: Gu, Hongjing; Xie, Zhengde; Li, Tieling; Zhang, Shaogeng; Lai, Chengcai; Zhu, Ping; Wang, Keyu; Han, Lina; Duan, Yueqiang; Zhao, Zhongpeng; Yang, Xiaolan; Xing, Li; Zhang, Peirui; Wang, Zhouhai; Li, Ruisheng; Yu, Jane J.; Wang, Xiliang; Yang, Penghui title: Angiotensin-converting enzyme 2 inhibits lung injury induced by respiratory syncytial virus date: 2016-01-27 journal: Sci Rep DOI: 10.1038/srep19840 sha: doc_id: 271328 cord_uid: zdf5ji4k file: cache/cord-271602-f14wccj3.json key: cord-271602-f14wccj3 authors: Kim, Hyun Cheol; Kim, Soontae; Kim, Byeong-Uk; Jin, Chun-Sil; Hong, Songyou; Park, Rokjin; Son, Seok-Woo; Bae, Changhan; Bae, MinAh; Song, Chang-Keun; Stein, Ariel title: Recent increase of surface particulate matter concentrations in the Seoul Metropolitan Area, Korea date: 2017-07-05 journal: Sci Rep DOI: 10.1038/s41598-017-05092-8 sha: doc_id: 271602 cord_uid: f14wccj3 file: cache/cord-269270-i2odcsx7.json key: cord-269270-i2odcsx7 authors: Sahlol, Ahmed T.; Yousri, Dalia; Ewees, Ahmed A.; Al-qaness, Mohammed A. A.; Damasevicius, Robertas; Elaziz, Mohamed Abd title: COVID-19 image classification using deep features and fractional-order marine predators algorithm date: 2020-09-21 journal: Sci Rep DOI: 10.1038/s41598-020-71294-2 sha: doc_id: 269270 cord_uid: i2odcsx7 file: cache/cord-277816-ncdy9qgb.json key: cord-277816-ncdy9qgb authors: Wang, Ji-gan; Cui, Hai-rong; Tang, Hua-bo; Deng, Xiu-li title: Gastrointestinal symptoms and fecal nucleic acid testing of children with 2019 coronavirus disease: a systematic review and meta-analysis date: 2020-10-20 journal: Sci Rep DOI: 10.1038/s41598-020-74913-0 sha: doc_id: 277816 cord_uid: ncdy9qgb file: cache/cord-280334-7b7rvr25.json key: cord-280334-7b7rvr25 authors: Abrantes, Joana; Droillard, Clément; Lopes, Ana M.; Lemaitre, Evelyne; Lucas, Pierrick; Blanchard, Yannick; Marchandeau, Stéphane; Esteves, Pedro J.; Le Gall-Reculé, Ghislaine title: Recombination at the emergence of the pathogenic rabbit haemorrhagic disease virus Lagovirus europaeus/GI.2 date: 2020-09-02 journal: Sci Rep DOI: 10.1038/s41598-020-71303-4 sha: doc_id: 280334 cord_uid: 7b7rvr25 file: cache/cord-281536-8y7yxcp4.json key: cord-281536-8y7yxcp4 authors: Lim, Hocheol; Baek, Ayoung; Kim, Jongwan; Kim, Min Sung; Liu, Jiaxin; Nam, Ky-Youb; Yoon, JeongHyeok; No, Kyoung Tai title: Hot spot profiles of SARS-CoV-2 and human ACE2 receptor protein protein interaction obtained by density functional tight binding fragment molecular orbital method date: 2020-10-08 journal: Sci Rep DOI: 10.1038/s41598-020-73820-8 sha: doc_id: 281536 cord_uid: 8y7yxcp4 file: cache/cord-273283-gb0m6fue.json key: cord-273283-gb0m6fue authors: Altschul, David J.; Unda, Santiago R.; Benton, Joshua; de la Garza Ramos, Rafael; Cezayirli, Phillip; Mehler, Mark; Eskandar, Emad N. title: A novel severity score to predict inpatient mortality in COVID-19 patients date: 2020-10-07 journal: Sci Rep DOI: 10.1038/s41598-020-73962-9 sha: doc_id: 273283 cord_uid: gb0m6fue file: cache/cord-276997-hbovh7s9.json key: cord-276997-hbovh7s9 authors: Alsved, Malin; Widell, Anders; Dahlin, Henrik; Karlson, Sara; Medstrand, Patrik; Löndahl, Jakob title: Aerosolization and recovery of viable murine norovirus in an experimental setup date: 2020-09-29 journal: Sci Rep DOI: 10.1038/s41598-020-72932-5 sha: doc_id: 276997 cord_uid: hbovh7s9 file: cache/cord-268414-7fcc5i7i.json key: cord-268414-7fcc5i7i authors: Hassani, Abdelkader; Azarian, Mohammad Mahdi Sabaghpour; Ibrahim, Wisam Nabeel; Hussain, Siti Aslina title: Preparation, characterization and therapeutic properties of gum arabic-stabilized gallic acid nanoparticles date: 2020-10-20 journal: Sci Rep DOI: 10.1038/s41598-020-71175-8 sha: doc_id: 268414 cord_uid: 7fcc5i7i file: cache/cord-272576-ez731lif.json key: cord-272576-ez731lif authors: Wada, Yoshiko; Wada, Kennosuke; Iwasaki, Yuki; Kanaya, Shigehiko; Ikemura, Toshimichi title: Directional and reoccurring sequence change in zoonotic RNA virus genomes visualized by time-series word count date: 2016-11-03 journal: Sci Rep DOI: 10.1038/srep36197 sha: doc_id: 272576 cord_uid: ez731lif file: cache/cord-272623-j5gpww9q.json key: cord-272623-j5gpww9q authors: Sun, Wei; Shi, Zhencai; Gao, Fuqiang; Wang, Bailiang; Li, Zirong title: The pathogenesis of multifocal osteonecrosis date: 2016-07-11 journal: Sci Rep DOI: 10.1038/srep29576 sha: doc_id: 272623 cord_uid: j5gpww9q file: cache/cord-283583-pwlbrxn3.json key: cord-283583-pwlbrxn3 authors: Zhang, Xiao-Ai; Lu, Qing-Bin; Wo, Ying; Zhao, Jin; Huang, Dou-Dou; Guo, Chen-Tao; Xu, Hong-Mei; Liu, En-Mei; Liu, Wei; Cao, Wu-Chun title: Prevalence and genetic characteristics of Saffold cardiovirus in China from 2009 to 2012 date: 2015-01-09 journal: Sci Rep DOI: 10.1038/srep07704 sha: doc_id: 283583 cord_uid: pwlbrxn3 file: cache/cord-284374-sqxlnk9e.json key: cord-284374-sqxlnk9e authors: Park, Jiyeon; Yoo, Seung Yeon; Ko, Jae-Hoon; Lee, Sangmin M.; Chung, Yoon Joo; Lee, Jong-Hwan; Peck, Kyong Ran; Min, Jeong Jin title: Infection Prevention Measures for Surgical Procedures during a Middle East Respiratory Syndrome Outbreak in a Tertiary Care Hospital in South Korea date: 2020-01-15 journal: Sci Rep DOI: 10.1038/s41598-019-57216-x sha: doc_id: 284374 cord_uid: sqxlnk9e file: cache/cord-276444-jidvkij5.json key: cord-276444-jidvkij5 authors: Robitaille, Alexa C.; Caron, Elise; Zucchini, Nicolas; Mukawera, Espérance; Adam, Damien; Mariani, Mélissa K.; Gélinas, Anaïs; Fortin, Audray; Brochiero, Emmanuelle; Grandvaux, Nathalie title: DUSP1 regulates apoptosis and cell migration, but not the JIP1-protected cytokine response, during Respiratory Syncytial Virus and Sendai Virus infection date: 2017-12-12 journal: Sci Rep DOI: 10.1038/s41598-017-17689-0 sha: doc_id: 276444 cord_uid: jidvkij5 file: cache/cord-284429-d7qxfo6d.json key: cord-284429-d7qxfo6d authors: Trezza, Alfonso; Iovinelli, Daniele; Santucci, Annalisa; Prischi, Filippo; Spiga, Ottavia title: An integrated drug repurposing strategy for the rapid identification of potential SARS-CoV-2 viral inhibitors date: 2020-08-17 journal: Sci Rep DOI: 10.1038/s41598-020-70863-9 sha: doc_id: 284429 cord_uid: d7qxfo6d file: cache/cord-279598-xzionafe.json key: cord-279598-xzionafe authors: Chang, Chia-Yu; Cheng, Ivan-Chen; Chang, Yen-Chen; Tsai, Pei-Shiue; Lai, Seiu-Yu; Huang, Yu-Liang; Jeng, Chian-Ren; Pang, Victor Fei; Chang, Hui-Wen title: Identification of Neutralizing Monoclonal Antibodies Targeting Novel Conformational Epitopes of the Porcine Epidemic Diarrhoea Virus Spike Protein date: 2019-02-21 journal: Sci Rep DOI: 10.1038/s41598-019-39844-5 sha: doc_id: 279598 cord_uid: xzionafe file: cache/cord-284582-xwedgllw.json key: cord-284582-xwedgllw authors: Korabecna, M.; Zinkova, A.; Brynychova, I.; Chylikova, B.; Prikryl, P.; Sedova, L.; Neuzil, P.; Seda, O. title: Cell-free DNA in plasma as an essential immune system regulator date: 2020-10-15 journal: Sci Rep DOI: 10.1038/s41598-020-74288-2 sha: doc_id: 284582 cord_uid: xwedgllw file: cache/cord-286559-y8z0pwgn.json key: cord-286559-y8z0pwgn authors: Ding, Nai-Zheng; Xu, Dong-Shuai; Sun, Yuan-Yuan; He, Hong-Bin; He, Cheng-Qiang title: A permanent host shift of rabies virus from Chiroptera to Carnivora associated with recombination date: 2017-03-21 journal: Sci Rep DOI: 10.1038/s41598-017-00395-2 sha: doc_id: 286559 cord_uid: y8z0pwgn file: cache/cord-287708-0qvwjejv.json key: cord-287708-0qvwjejv authors: Gera, Tamás; Nagy, Eszter; Smausz, Tamás; Budai, Judit; Ajtai, Tibor; Kun-Szabó, Fruzsina; Homik, Zsolt; Kopniczky, Judit; Bozóki, Zoltán; Szabó-Révész, Piroska; Ambrus, Rita; Hopp, Béla title: Application of pulsed laser ablation (PLA) for the size reduction of non-steroidal anti-inflammatory drugs (NSAIDs) date: 2020-09-25 journal: Sci Rep DOI: 10.1038/s41598-020-72865-z sha: doc_id: 287708 cord_uid: 0qvwjejv file: cache/cord-294220-ewp1m8jp.json key: cord-294220-ewp1m8jp authors: Churchward, Colin P.; Al-Kinani, Ali A.; Abdelkader, Hamdy; Swinden, Julian; Siwoku, Opeoluwa; Varnakulasingam, Thinuba; Alany, Raid G.; Snyder, Lori A. S. title: Monocaprin eye drop formulation to combat antibiotic resistant gonococcal blindness date: 2020-07-21 journal: Sci Rep DOI: 10.1038/s41598-020-68722-8 sha: doc_id: 294220 cord_uid: ewp1m8jp file: cache/cord-288721-3bv3aak6.json key: cord-288721-3bv3aak6 authors: Schneider, Annika; Kurz, Sandra; Manske, Katrin; Janas, Marianne; Heikenwälder, Mathias; Misgeld, Thomas; Aichler, Michaela; Weissmann, Sebastian Felix; Zischka, Hans; Knolle, Percy; Wohlleber, Dirk title: Single organelle analysis to characterize mitochondrial function and crosstalk during viral infection date: 2019-06-11 journal: Sci Rep DOI: 10.1038/s41598-019-44922-9 sha: doc_id: 288721 cord_uid: 3bv3aak6 file: cache/cord-288761-fyvr0tc1.json key: cord-288761-fyvr0tc1 authors: Santiago, César; Mudgal, Gaurav; Reguera, Juan; Recacha, Rosario; Albrecht, Sébastien; Enjuanes, Luis; Casasnovas, José M. title: Allosteric inhibition of aminopeptidase N functions related to tumor growth and virus infection date: 2017-04-10 journal: Sci Rep DOI: 10.1038/srep46045 sha: doc_id: 288761 cord_uid: fyvr0tc1 file: cache/cord-289932-dsysiefx.json key: cord-289932-dsysiefx authors: Király, Kornél; Kozsurek, Márk; Lukácsi, Erika; Barta, Benjamin; Alpár, Alán; Balázsa, Tamás; Fekete, Csaba; Szabon, Judit; Helyes, Zsuzsanna; Bölcskei, Kata; Tékus, Valéria; Tóth, Zsuzsanna E.; Pap, Károly; Gerber, Gábor; Puskár, Zita title: Glial cell type-specific changes in spinal dipeptidyl peptidase 4 expression and effects of its inhibitors in inflammatory and neuropatic pain date: 2018-02-22 journal: Sci Rep DOI: 10.1038/s41598-018-21799-8 sha: doc_id: 289932 cord_uid: dsysiefx file: cache/cord-288731-x2cwyvb7.json key: cord-288731-x2cwyvb7 authors: Puenpa, Jiratchaya; Suwannakarn, Kamol; Chansaenroj, Jira; Nilyanimit, Pornjarim; Yorsaeng, Ritthideach; Auphimai, Chompoonut; Kitphati, Rungrueng; Mungaomklang, Anek; Kongklieng, Amornmas; Chirathaworn, Chintana; Wanlapakorn, Nasamon; Poovorawan, Yong title: Molecular epidemiology of the first wave of severe acute respiratory syndrome coronavirus 2 infection in Thailand in 2020 date: 2020-10-06 journal: Sci Rep DOI: 10.1038/s41598-020-73554-7 sha: doc_id: 288731 cord_uid: x2cwyvb7 file: cache/cord-293747-ds8rhbkv.json key: cord-293747-ds8rhbkv authors: Lani, Rafidah; Hassandarvish, Pouya; Chiam, Chun Wei; Moghaddam, Ehsan; Chu, Justin Jang Hann; Rausalu, Kai; Merits, Andres; Higgs, Stephen; Vanlandingham, Dana; Abu Bakar, Sazaly; Zandi, Keivan title: Antiviral activity of silymarin against chikungunya virus date: 2015-06-16 journal: Sci Rep DOI: 10.1038/srep11421 sha: doc_id: 293747 cord_uid: ds8rhbkv file: cache/cord-286413-a7wue2e3.json key: cord-286413-a7wue2e3 authors: Cohen, Isaac V.; Makunts, Tigran; Moumedjian, Talar; Issa, Masara A.; Abagyan, Ruben title: Cardiac adverse events associated with chloroquine and hydroxychloroquine exposure in 20 years of drug safety surveillance reports date: 2020-11-05 journal: Sci Rep DOI: 10.1038/s41598-020-76258-0 sha: doc_id: 286413 cord_uid: a7wue2e3 file: cache/cord-288451-npefpo3t.json key: cord-288451-npefpo3t authors: Yinda, Claude Kwe; Zeller, Mark; Conceição-Neto, Nádia; Maes, Piet; Deboutte, Ward; Beller, Leen; Heylen, Elisabeth; Ghogomu, Stephen Mbigha; Van Ranst, Marc; Matthijnssens, Jelle title: Novel highly divergent reassortant bat rotaviruses in Cameroon, without evidence of zoonosis date: 2016-09-26 journal: Sci Rep DOI: 10.1038/srep34209 sha: doc_id: 288451 cord_uid: npefpo3t file: cache/cord-296867-6o4scan1.json key: cord-296867-6o4scan1 authors: Hisada, Shohei; Murayama, Taichi; Tsubouchi, Kota; Fujita, Sumio; Yada, Shuntaro; Wakamiya, Shoko; Aramaki, Eiji title: Surveillance of early stage COVID-19 clusters using search query logs and mobile device-based location information date: 2020-10-29 journal: Sci Rep DOI: 10.1038/s41598-020-75771-6 sha: doc_id: 296867 cord_uid: 6o4scan1 file: cache/cord-293372-saqoft9p.json key: cord-293372-saqoft9p authors: Heffner, Kelley; Hizal, Deniz Baycin; Majewska, Natalia I.; Kumar, Swetha; Dhara, Venkata Gayatri; Zhu, Jie; Bowen, Michael; Hatton, Diane; Yerganian, George; Yerganian, Athena; O’Meally, Robert; Cole, Robert; Betenbaugh, Michael title: Expanded Chinese hamster organ and cell line proteomics profiling reveals tissue-specific functionalities date: 2020-09-28 journal: Sci Rep DOI: 10.1038/s41598-020-72959-8 sha: doc_id: 293372 cord_uid: saqoft9p file: cache/cord-293505-1t3hg4wi.json key: cord-293505-1t3hg4wi authors: Bernard-Stoecklin, Sibylle; Nikolay, Birgit; Assiri, Abdullah; Bin Saeed, Abdul Aziz; Ben Embarek, Peter Karim; El Bushra, Hassan; Ki, Moran; Malik, Mamunur Rahman; Fontanet, Arnaud; Cauchemez, Simon; Van Kerkhove, Maria D. title: Comparative Analysis of Eleven Healthcare-Associated Outbreaks of Middle East Respiratory Syndrome Coronavirus (Mers-Cov) from 2015 to 2017 date: 2019-05-14 journal: Sci Rep DOI: 10.1038/s41598-019-43586-9 sha: doc_id: 293505 cord_uid: 1t3hg4wi file: cache/cord-299605-j1ewxk4q.json key: cord-299605-j1ewxk4q authors: Lin, Jing-wen; Sodenkamp, Jan; Cunningham, Deirdre; Deroost, Katrien; Tshitenge, Tshibuayi Christine; McLaughlin, Sarah; Lamb, Tracey J.; Spencer-Dene, Bradley; Hosking, Caroline; Ramesar, Jai; Janse, Chris J.; Graham, Christine; O’Garra, Anne; Langhorne, Jean title: Signatures of malaria-associated pathology revealed by high-resolution whole-blood transcriptomics in a rodent model of malaria date: 2017-02-03 journal: Sci Rep DOI: 10.1038/srep41722 sha: doc_id: 299605 cord_uid: j1ewxk4q file: cache/cord-306517-tls0849i.json key: cord-306517-tls0849i authors: Leidenberger, S.; Schröder, Ch.; Zani, L.; Auste, A.; Pinette, M.; Ambagala, A.; Nikolin, V.; de Smit, H.; Beer, M.; Blome, S. title: Virulence of current German PEDV strains in suckling pigs and investigation of protective effects of maternally derived antibodies date: 2017-09-07 journal: Sci Rep DOI: 10.1038/s41598-017-11160-w sha: doc_id: 306517 cord_uid: tls0849i file: cache/cord-301016-9t7v7ipt.json key: cord-301016-9t7v7ipt authors: Forni, Diego; Filippi, Giulia; Cagliani, Rachele; De Gioia, Luca; Pozzoli, Uberto; Al-Daghri, Nasser; Clerici, Mario; Sironi, Manuela title: The heptad repeat region is a major selection target in MERS-CoV and related coronaviruses date: 2015-09-25 journal: Sci Rep DOI: 10.1038/srep14480 sha: doc_id: 301016 cord_uid: 9t7v7ipt file: cache/cord-304040-64obh7i3.json key: cord-304040-64obh7i3 authors: Sande, Charles J.; Mutunga, Martin; Muteti, Jacqueline; Berkley, James A.; Nokes, D. James; Njunge, James title: Untargeted analysis of the airway proteomes of children with respiratory infections using mass spectrometry based proteomics date: 2018-09-14 journal: Sci Rep DOI: 10.1038/s41598-018-32072-3 sha: doc_id: 304040 cord_uid: 64obh7i3 file: cache/cord-296562-3h2oqb9k.json key: cord-296562-3h2oqb9k authors: Guillén, Lucía; Padilla, Sergio; Fernández, Marta; Agulló, Vanesa; García, José Alberto; Telenti, Guillermo; García-Abellán, Javier; Botella, Ángela; Gutiérrez, Félix; Masiá, Mar title: Preemptive interleukin-6 blockade in patients with COVID-19 date: 2020-10-08 journal: Sci Rep DOI: 10.1038/s41598-020-74001-3 sha: doc_id: 296562 cord_uid: 3h2oqb9k file: cache/cord-302080-fegcf1fu.json key: cord-302080-fegcf1fu authors: Oliveira-de-Souza, Deivide; Vinhaes, Caian L.; Arriaga, María B.; Kumar, Nathella Pavan; Queiroz, Artur T. L.; Fukutani, Kiyoshi F.; Babu, Subash; Andrade, Bruno B. title: Aging increases the systemic molecular degree of inflammatory perturbation in patients with tuberculosis date: 2020-07-09 journal: Sci Rep DOI: 10.1038/s41598-020-68255-0 sha: doc_id: 302080 cord_uid: fegcf1fu file: cache/cord-302459-grs2x26l.json key: cord-302459-grs2x26l authors: Matin, Farhana; Jeet, Varinder; Moya, Leire; Selth, Luke A.; Chambers, Suzanne; Clements, Judith A.; Batra, Jyotsna title: A Plasma Biomarker Panel of Four MicroRNAs for the Diagnosis of Prostate Cancer date: 2018-04-27 journal: Sci Rep DOI: 10.1038/s41598-018-24424-w sha: doc_id: 302459 cord_uid: grs2x26l file: cache/cord-303601-o8uk6if2.json key: cord-303601-o8uk6if2 authors: Tsay, Calvin; Lejarza, Fernando; Stadtherr, Mark A.; Baldea, Michael title: Modeling, state estimation, and optimal control for the US COVID-19 outbreak date: 2020-07-01 journal: Sci Rep DOI: 10.1038/s41598-020-67459-8 sha: doc_id: 303601 cord_uid: o8uk6if2 file: cache/cord-305132-jspxlk1a.json key: cord-305132-jspxlk1a authors: Homma, Takujiro; Ishibashi, Daisuke; Nakagaki, Takehiro; Fuse, Takayuki; Sano, Kazunori; Satoh, Katsuya; Atarashi, Ryuichiro; Nishida, Noriyuki title: Persistent prion infection disturbs the function of Oct-1, resulting in the down-regulation of murine interferon regulatory factor-3 date: 2014-08-08 journal: Sci Rep DOI: 10.1038/srep06006 sha: doc_id: 305132 cord_uid: jspxlk1a file: cache/cord-305473-w30hsr4m.json key: cord-305473-w30hsr4m authors: Jiang, Lili; Lee, Vernon Jian Ming; Cui, Lin; Lin, Raymond; Tan, Chyi Lin; Tan, Linda Wei Lin; Lim, Wei-yen; Leo, Yee-Sin; Low, Louie; Hibberd, Martin; Chen, Mark I-Cheng title: Detection of viral respiratory pathogens in mild and severe acute respiratory infections in Singapore date: 2017-02-20 journal: Sci Rep DOI: 10.1038/srep42963 sha: doc_id: 305473 cord_uid: w30hsr4m file: cache/cord-308302-5yns1hg9.json key: cord-308302-5yns1hg9 authors: Wu, Gang; Zhou, Shuchang; Wang, Yujin; Lv, Wenzhi; Wang, Shili; Wang, Ting; Li, Xiaoming title: A prediction model of outcome of SARS-CoV-2 pneumonia based on laboratory findings date: 2020-08-20 journal: Sci Rep DOI: 10.1038/s41598-020-71114-7 sha: doc_id: 308302 cord_uid: 5yns1hg9 file: cache/cord-309127-kxivgxbg.json key: cord-309127-kxivgxbg authors: Haverkamp, Ann-Kathrin; Lehmbecker, Annika; Spitzbarth, Ingo; Widagdo, Widagdo; Haagmans, Bart L.; Segalés, Joaquim; Vergara-Alert, Julia; Bensaid, Albert; van den Brand, Judith M. A.; Osterhaus, Albert D. M. E.; Baumgärtner, Wolfgang title: Experimental infection of dromedaries with Middle East respiratory syndrome-Coronavirus is accompanied by massive ciliary loss and depletion of the cell surface receptor dipeptidyl peptidase 4 date: 2018-06-27 journal: Sci Rep DOI: 10.1038/s41598-018-28109-2 sha: doc_id: 309127 cord_uid: kxivgxbg file: cache/cord-313126-7hrjzapj.json key: cord-313126-7hrjzapj authors: Chen, Fangzhou; Knutson, Todd P.; Rossow, Stephanie; Saif, Linda J.; Marthaler, Douglas G. title: Decline of transmissible gastroenteritis virus and its complex evolutionary relationship with porcine respiratory coronavirus in the United States date: 2019-03-08 journal: Sci Rep DOI: 10.1038/s41598-019-40564-z sha: doc_id: 313126 cord_uid: 7hrjzapj file: cache/cord-308687-wrzzb9cy.json key: cord-308687-wrzzb9cy authors: Brunner, Jesse L. title: Pooled samples and eDNA-based detection can facilitate the “clean trade” of aquatic animals date: 2020-06-24 journal: Sci Rep DOI: 10.1038/s41598-020-66280-7 sha: doc_id: 308687 cord_uid: wrzzb9cy file: cache/cord-312777-5925lvue.json key: cord-312777-5925lvue authors: Pan, Feng; Zheng, Chuansheng; Ye, Tianhe; Li, Lingli; Liu, Dehan; Li, Lin; Hesketh, Richard L.; Yang, Lian title: Different computed tomography patterns of Coronavirus Disease 2019 (COVID-19) between survivors and non-survivors date: 2020-07-09 journal: Sci Rep DOI: 10.1038/s41598-020-68057-4 sha: doc_id: 312777 cord_uid: 5925lvue file: cache/cord-316930-0s7k9guq.json key: cord-316930-0s7k9guq authors: Caldas, Lucio Ayres; Carneiro, Fabiana Avila; Higa, Luiza Mendonça; Monteiro, Fábio Luiz; da Silva, Gustavo Peixoto; da Costa, Luciana Jesus; Durigon, Edison Luiz; Tanuri, Amilcar; de Souza, Wanderley title: Ultrastructural analysis of SARS-CoV-2 interactions with the host cell via high resolution scanning electron microscopy date: 2020-09-30 journal: Sci Rep DOI: 10.1038/s41598-020-73162-5 sha: doc_id: 316930 cord_uid: 0s7k9guq file: cache/cord-305031-9ze0097w.json key: cord-305031-9ze0097w authors: Büchel, Beda; Spanninger, Thomas; Corman, Francesco title: Empirical dynamics of railway delay propagation identified during the large-scale Rastatt disruption date: 2020-10-29 journal: Sci Rep DOI: 10.1038/s41598-020-75538-z sha: doc_id: 305031 cord_uid: 9ze0097w file: cache/cord-314753-xflhxb13.json key: cord-314753-xflhxb13 authors: Manso, Carmen F.; Bibby, David F.; Mbisa, Jean L. title: Efficient and unbiased metagenomic recovery of RNA virus genomes from human plasma samples date: 2017-06-23 journal: Sci Rep DOI: 10.1038/s41598-017-02239-5 sha: doc_id: 314753 cord_uid: xflhxb13 file: cache/cord-315415-3aotsb2g.json key: cord-315415-3aotsb2g authors: Dong, Jianbo; Huang, Betty; Wang, Bo; Titong, Allison; Gallolu Kankanamalage, Sachith; Jia, Zhejun; Wright, Meredith; Parthasarathy, Pannaga; Liu, Yue title: Development of humanized tri-specific nanobodies with potent neutralization for SARS-CoV-2 date: 2020-10-20 journal: Sci Rep DOI: 10.1038/s41598-020-74761-y sha: doc_id: 315415 cord_uid: 3aotsb2g file: cache/cord-318187-c59c9vi3.json key: cord-318187-c59c9vi3 authors: Basu, Saikat; Holbrook, Landon T.; Kudlaty, Kathryn; Fasanmade, Olulade; Wu, Jihong; Burke, Alyssa; Langworthy, Benjamin W.; Farzal, Zainab; Mamdani, Mohammed; Bennett, William D.; Fine, Jason P.; Senior, Brent A.; Zanation, Adam M.; Ebert, Charles S.; Kimple, Adam J.; Thorp, Brian D.; Frank-Ito, Dennis O.; Garcia, Guilherme J. M.; Kimbell, Julia S. title: Numerical evaluation of spray position for improved nasal drug delivery date: 2020-06-29 journal: Sci Rep DOI: 10.1038/s41598-020-66716-0 sha: doc_id: 318187 cord_uid: c59c9vi3 file: cache/cord-317579-ige2h4pd.json key: cord-317579-ige2h4pd authors: Nie, Lei; Hou, Mengjuan; Wang, Tianwen; Sun, Meng; Hou, Ruixia title: Nanostructured selenium-doped biphasic calcium phosphate with in situ incorporation of silver for antibacterial applications date: 2020-08-13 journal: Sci Rep DOI: 10.1038/s41598-020-70776-7 sha: doc_id: 317579 cord_uid: ige2h4pd file: cache/cord-318587-ewvnkdr2.json key: cord-318587-ewvnkdr2 authors: Steeds, Kimberley; Hall, Yper; Slack, Gillian S.; Longet, Stephanie; Strecker, Thomas; Fehling, Sarah Katharina; Wright, Edward; Bore, Joseph Akoi; Koundouno, Fara Raymond; Konde, Mandy Kader; Hewson, Roger; Hiscox, Julian A.; Pollakis, Georgios; Carroll, Miles W. title: Pseudotyping of VSV with Ebola virus glycoprotein is superior to HIV-1 for the assessment of neutralising antibodies date: 2020-08-31 journal: Sci Rep DOI: 10.1038/s41598-020-71225-1 sha: doc_id: 318587 cord_uid: ewvnkdr2 file: cache/cord-316983-h4mtpcyc.json key: cord-316983-h4mtpcyc authors: Mathé-Hubert, Hugo; Colinet, Dominique; Deleury, Emeline; Belghazi, Maya; Ravallec, Marc; Poulain, Julie; Dossat, Carole; Poirié, Marylène; Gatti, Jean-Luc title: Comparative venomics of Psyttalia lounsburyi and P. concolor, two olive fruit fly parasitoids: a hypothetical role for a GH1 β-glucosidase date: 2016-10-25 journal: Sci Rep DOI: 10.1038/srep35873 sha: doc_id: 316983 cord_uid: h4mtpcyc file: cache/cord-276185-ysspkbj7.json key: cord-276185-ysspkbj7 authors: Milewska, Aleksandra; Kindler, Eveline; Vkovski, Philip; Zeglen, Slawomir; Ochman, Marek; Thiel, Volker; Rajfur, Zenon; Pyrc, Krzysztof title: APOBEC3-mediated restriction of RNA virus replication date: 2018-04-13 journal: Sci Rep DOI: 10.1038/s41598-018-24448-2 sha: doc_id: 276185 cord_uid: ysspkbj7 file: cache/cord-320709-2pnqpljt.json key: cord-320709-2pnqpljt authors: Munster, Vincent J.; Adney, Danielle R.; van Doremalen, Neeltje; Brown, Vienna R.; Miazgowicz, Kerri L.; Milne-Price, Shauna; Bushmaker, Trenton; Rosenke, Rebecca; Scott, Dana; Hawkinson, Ann; de Wit, Emmie; Schountz, Tony; Bowen, Richard A. title: Replication and shedding of MERS-CoV in Jamaican fruit bats (Artibeus jamaicensis) date: 2016-02-22 journal: Sci Rep DOI: 10.1038/srep21878 sha: doc_id: 320709 cord_uid: 2pnqpljt file: cache/cord-317813-sisfxdso.json key: cord-317813-sisfxdso authors: Banskar, Sunil; Bhute, Shrikant S.; Suryavanshi, Mangesh V.; Punekar, Sachin; Shouche, Yogesh S. title: Microbiome analysis reveals the abundance of bacterial pathogens in Rousettus leschenaultii guano date: 2016-11-15 journal: Sci Rep DOI: 10.1038/srep36948 sha: doc_id: 317813 cord_uid: sisfxdso file: cache/cord-318314-oxlv847d.json key: cord-318314-oxlv847d authors: O’Boyle, Nicky; Berry, Catherine C.; Davies, Robert L. title: Differentiated ovine tracheal epithelial cells support the colonisation of pathogenic and non-pathogenic strains of Mannheimia haemolytica date: 2020-09-11 journal: Sci Rep DOI: 10.1038/s41598-020-71604-8 sha: doc_id: 318314 cord_uid: oxlv847d file: cache/cord-325405-cu4nx891.json key: cord-325405-cu4nx891 authors: Luo, Lingfei; Gu, Yiqin; Wang, Xiaoguang; Zhang, Yinghua; Zhan, Longwen; Liu, Jiqian; Yan, Hongjing; Liu, Yun; Zhen, Shanshan; Chen, Xiuhua; Tong, Rui; Song, Chiping; He, Yingying title: Epidemiological and clinical differences between sexes and pathogens in a three-year surveillance of acute infectious gastroenteritis in Shanghai date: 2019-07-10 journal: Sci Rep DOI: 10.1038/s41598-019-46480-6 sha: doc_id: 325405 cord_uid: cu4nx891 file: cache/cord-319118-47ovbto5.json key: cord-319118-47ovbto5 authors: Yu, Xiaojuan; Zhang, Senyan; Jiang, Liwei; Cui, Ye; Li, Dongxia; Wang, Dongli; Wang, Nianshuang; Fu, Lili; Shi, Xuanlin; Li, Ziqiang; Zhang, Linqi; Wang, Xinquan title: Structural basis for the neutralization of MERS-CoV by a human monoclonal antibody MERS-27 date: 2015-08-18 journal: Sci Rep DOI: 10.1038/srep13133 sha: doc_id: 319118 cord_uid: 47ovbto5 file: cache/cord-315483-l6dm82pp.json key: cord-315483-l6dm82pp authors: Santhakumar, Diwakar; Rohaim, Mohammed Abdel Mohsen Shahaat; Hussein, Hussein A.; Hawes, Pippa; Ferreira, Helena Lage; Behboudi, Shahriar; Iqbal, Munir; Nair, Venugopal; Arns, Clarice W.; Munir, Muhammad title: Chicken Interferon-induced Protein with Tetratricopeptide Repeats 5 Antagonizes Replication of RNA Viruses date: 2018-05-01 journal: Sci Rep DOI: 10.1038/s41598-018-24905-y sha: doc_id: 315483 cord_uid: l6dm82pp file: cache/cord-321667-jkzxjk54.json key: cord-321667-jkzxjk54 authors: Papineau, Amber; Berhane, Yohannes; Wylie, Todd N.; Wylie, Kristine M.; Sharpe, Samuel; Lung, Oliver title: Genome Organization of Canada Goose Coronavirus, A Novel Species Identified in a Mass Die-off of Canada Geese date: 2019-04-11 journal: Sci Rep DOI: 10.1038/s41598-019-42355-y sha: doc_id: 321667 cord_uid: jkzxjk54 file: cache/cord-315781-dejh8q22.json key: cord-315781-dejh8q22 authors: Konishi, Tomokazu title: Re-evaluation of the evolution of influenza H1 viruses using direct PCA date: 2019-12-17 journal: Sci Rep DOI: 10.1038/s41598-019-55254-z sha: doc_id: 315781 cord_uid: dejh8q22 file: cache/cord-323087-3cxyogor.json key: cord-323087-3cxyogor authors: Widagdo, W.; Begeman, Lineke; Schipper, Debby; Run, Peter R. van; Cunningham, Andrew A.; Kley, Nils; Reusken, Chantal B.; Haagmans, Bart L.; van den Brand, Judith M. A. title: Tissue Distribution of the MERS-Coronavirus Receptor in Bats date: 2017-04-26 journal: Sci Rep DOI: 10.1038/s41598-017-01290-6 sha: doc_id: 323087 cord_uid: 3cxyogor file: cache/cord-324696-htx0ul4o.json key: cord-324696-htx0ul4o authors: Chothe, Shubhada K.; Bhushan, Gitanjali; Nissly, Ruth H.; Yeh, Yin-Ting; Brown, Justin; Turner, Gregory; Fisher, Jenny; Sewall, Brent J.; Reeder, DeeAnn M.; Terrones, Mauricio; Jayarao, Bhushan M.; Kuchipudi, Suresh V. title: Avian and human influenza virus compatible sialic acid receptors in little brown bats date: 2017-04-06 journal: Sci Rep DOI: 10.1038/s41598-017-00793-6 sha: doc_id: 324696 cord_uid: htx0ul4o file: cache/cord-322486-qwl7nzkr.json key: cord-322486-qwl7nzkr authors: Omori, Ryosuke; Matsuyama, Ryota; Nakata, Yukihiko title: The age distribution of mortality from novel coronavirus disease (COVID-19) suggests no large difference of susceptibility by age date: 2020-10-06 journal: Sci Rep DOI: 10.1038/s41598-020-73777-8 sha: doc_id: 322486 cord_uid: qwl7nzkr file: cache/cord-327405-xgtqfwyn.json key: cord-327405-xgtqfwyn authors: Liu, Bing; Han, Junyan; Cheng, Xiaohuan; Yu, Long; Zhang, Li; Wang, Wei; Ni, Lan; Wei, Chaojie; Huang, Yafei; Cheng, Zhenshun title: Reduced numbers of T cells and B cells correlates with persistent SARS-CoV-2 presence in non-severe COVID-19 patients date: 2020-10-19 journal: Sci Rep DOI: 10.1038/s41598-020-73955-8 sha: doc_id: 327405 cord_uid: xgtqfwyn file: cache/cord-326868-3az13h1h.json key: cord-326868-3az13h1h authors: Schiller, Bastian; Kleinert, Tobias; Teige-Mocigemba, Sarah; Klauer, Karl Christoph; Heinrichs, Markus title: Temporal dynamics of resting EEG networks are associated with prosociality date: 2020-08-03 journal: Sci Rep DOI: 10.1038/s41598-020-69999-5 sha: doc_id: 326868 cord_uid: 3az13h1h file: cache/cord-325657-s2vdazq0.json key: cord-325657-s2vdazq0 authors: Huang, Yan-Jang S.; Vanlandingham, Dana L.; Bilyeu, Ashley N.; Sharp, Haelea M.; Hettenbach, Susan M.; Higgs, Stephen title: SARS-CoV-2 failure to infect or replicate in mosquitoes: an extreme challenge date: 2020-07-17 journal: Sci Rep DOI: 10.1038/s41598-020-68882-7 sha: doc_id: 325657 cord_uid: s2vdazq0 file: cache/cord-329155-ddpfox68.json key: cord-329155-ddpfox68 authors: Mindikoglu, Ayse L.; Abdulsada, Mustafa M.; Jain, Antrix; Jalal, Prasun K.; Devaraj, Sridevi; Wilhelm, Zoe R.; Opekun, Antone R.; Jung, Sung Yun title: Intermittent fasting from dawn to sunset for four consecutive weeks induces anticancer serum proteome response and improves metabolic syndrome date: 2020-10-27 journal: Sci Rep DOI: 10.1038/s41598-020-73767-w sha: doc_id: 329155 cord_uid: ddpfox68 file: cache/cord-329766-9bwdb6o2.json key: cord-329766-9bwdb6o2 authors: Liu, Xiaofan; Zhou, Hong; Zhou, Yilu; Wu, Xiaojun; Zhao, Yang; Lu, Yang; Tan, Weijun; Yuan, Mingli; Ding, Xuhong; Zou, Jinjing; Li, Ruiyun; Liu, Hailing; Ewing, Rob M.; Hu, Yi; Nie, Hanxiang; Wang, Yihua title: Temporal radiographic changes in COVID-19 patients: relationship to disease severity and viral clearance date: 2020-06-24 journal: Sci Rep DOI: 10.1038/s41598-020-66895-w sha: doc_id: 329766 cord_uid: 9bwdb6o2 file: cache/cord-331475-mmcu18c8.json key: cord-331475-mmcu18c8 authors: Sahu, Amit Ranjan; Wani, Sajad Ahmad; Saxena, Shikha; Rajak, Kaushal Kishor; Chaudhary, Dheeraj; Sahoo, Aditya Prasad; Khanduri, Alok; Pandey, Aruna; Mondal, Piyali; Malla, Waseem Akram; Khan, Raja Ishaq Nabi; Tiwari, Ashok Kumar; Mishra, Bina; Muthuchelvan, D.; Mishra, Bishnu Prasad; Singh, Raj Kumar; Gandham, Ravi Kumar title: Selection and validation of suitable reference genes for qPCR gene expression analysis in goats and sheep under Peste des petits ruminants virus (PPRV), lineage IV infection date: 2018-10-29 journal: Sci Rep DOI: 10.1038/s41598-018-34236-7 sha: doc_id: 331475 cord_uid: mmcu18c8 file: cache/cord-331775-iaxkfszq.json key: cord-331775-iaxkfszq authors: Nachman, Dean; Constantini, Keren; Poris, Gal; Wagnert-Avraham, Linn; Gertz, S. David; Littman, Romi; Kabakov, Eli; Eisenkraft, Arik; Gepner, Yftach title: Wireless, non-invasive, wearable device for continuous remote monitoring of hemodynamic parameters in a swine model of controlled hemorrhagic shock date: 2020-10-19 journal: Sci Rep DOI: 10.1038/s41598-020-74686-6 sha: doc_id: 331775 cord_uid: iaxkfszq file: cache/cord-329424-hmsidrc7.json key: cord-329424-hmsidrc7 authors: Grunwell, Jocelyn R.; Stephenson, Susan T.; Mohammad, Ahmad F.; Jones, Kaitlin; Mason, Carrie; Opolka, Cydney; Fitzpatrick, Anne M. title: Differential type I interferon response and primary airway neutrophil extracellular trap release in children with acute respiratory distress syndrome date: 2020-11-04 journal: Sci Rep DOI: 10.1038/s41598-020-76122-1 sha: doc_id: 329424 cord_uid: hmsidrc7 file: cache/cord-335055-gzuug3p5.json key: cord-335055-gzuug3p5 authors: Kwiyolecha, Elizabeth; Groendahl, Britta; Okamo, Bernard; Kayange, Neema; Manyama, Festo; Kidenya, Benson R.; Mahamba, Dina C.; Msanga, Delfina R.; Gehring, Stephan; Majigo, Mtebe; Mshana, Stephen E.; Mirambo, Mariam M. title: Patterns of viral pathogens causing upper respiratory tract infections among symptomatic children in Mwanza, Tanzania date: 2020-10-28 journal: Sci Rep DOI: 10.1038/s41598-020-74555-2 sha: doc_id: 335055 cord_uid: gzuug3p5 file: cache/cord-333067-3zan82yf.json key: cord-333067-3zan82yf authors: Counoupas, Claudio; Pinto, Rachel; Nagalingam, Gayathri; Britton, Warwick J.; Petrovsky, Nikolai; Triccas, James A. title: Delta inulin-based adjuvants promote the generation of polyfunctional CD4(+) T cell responses and protection against Mycobacterium tuberculosis infection date: 2017-08-17 journal: Sci Rep DOI: 10.1038/s41598-017-09119-y sha: doc_id: 333067 cord_uid: 3zan82yf file: cache/cord-331148-40gvay7i.json key: cord-331148-40gvay7i authors: Hsieh, Yu-Chia; Tsao, Kuo-Chien; Huang, Ching-Tai; Chang, Kuang-Yi; Huang, Yhu-Chering; Gong, Yu-Nong title: Clinical characteristics of patients with laboratory-confirmed influenza A(H1N1)pdm09 during the 2013/2014 and 2015/2016 clade 6B/6B.1/6B.2-predominant outbreaks date: 2018-10-23 journal: Sci Rep DOI: 10.1038/s41598-018-34077-4 sha: doc_id: 331148 cord_uid: 40gvay7i file: cache/cord-334228-n69iewmx.json key: cord-334228-n69iewmx authors: Li, Chunmei; Teng, Xin; Qi, Yifei; Tang, Bo; Shi, Hailing; Ma, Xiaomin; Lai, Luhua title: Conformational Flexibility of a Short Loop near the Active Site of the SARS-3CLpro is Essential to Maintain Catalytic Activity date: 2016-02-16 journal: Sci Rep DOI: 10.1038/srep20918 sha: doc_id: 334228 cord_uid: n69iewmx file: cache/cord-335576-b34nc3ay.json key: cord-335576-b34nc3ay authors: Tsai, Andrew; Diawara, Oumou; Nahass, Ronald G.; Brunetti, Luigi title: Impact of tocilizumab administration on mortality in severe COVID-19 date: 2020-11-05 journal: Sci Rep DOI: 10.1038/s41598-020-76187-y sha: doc_id: 335576 cord_uid: b34nc3ay file: cache/cord-330562-dabjcvno.json key: cord-330562-dabjcvno authors: Poli, Piero; Boaga, Jacopo; Molinari, Irene; Cascone, Valeria; Boschi, Lapo title: The 2020 coronavirus lockdown and seismic monitoring of anthropic activities in Northern Italy date: 2020-06-10 journal: Sci Rep DOI: 10.1038/s41598-020-66368-0 sha: doc_id: 330562 cord_uid: dabjcvno file: cache/cord-330057-3vucm0s1.json key: cord-330057-3vucm0s1 authors: Franzo, Giovanni; Tucciarone, Claudia Maria; Moreno, Ana; Legnardi, Matteo; Massi, Paola; Tosi, Giovanni; Trogu, Tiziana; Ceruti, Raffaella; Pesente, Patrizia; Ortali, Giovanni; Gavazzi, Luigi; Cecchinato, Mattia title: Phylodynamic analysis and evaluation of the balance between anthropic and environmental factors affecting IBV spreading among Italian poultry farms date: 2020-04-29 journal: Sci Rep DOI: 10.1038/s41598-020-64477-4 sha: doc_id: 330057 cord_uid: 3vucm0s1 file: cache/cord-338041-gl65i3s0.json key: cord-338041-gl65i3s0 authors: Tang, Qin; Song, Yulong; Shi, Mijuan; Cheng, Yingyin; Zhang, Wanting; Xia, Xiao-Qin title: Inferring the hosts of coronavirus using dual statistical models based on nucleotide composition date: 2015-11-26 journal: Sci Rep DOI: 10.1038/srep17155 sha: doc_id: 338041 cord_uid: gl65i3s0 file: cache/cord-336493-ggo9wsrm.json key: cord-336493-ggo9wsrm authors: Huang, Stephen S. H.; Lin, Zhen; Banner, David; León, Alberto J.; Paquette, Stéphane G.; Rubin, Barry; Rubino, Salvatore; Guan, Yi; Kelvin, David J.; Kelvin, Alyson A. title: Immunity toward H1N1 influenza hemagglutinin of historical and contemporary strains suggests protection and vaccine failure date: 2013-04-23 journal: Sci Rep DOI: 10.1038/srep01698 sha: doc_id: 336493 cord_uid: ggo9wsrm file: cache/cord-336901-q6kgzuob.json key: cord-336901-q6kgzuob authors: Choi, Jeongan; Kang, Miran; Jung, Jae Hee title: Integrated micro-optofluidic platform for real-time detection of airborne microorganisms date: 2015-11-02 journal: Sci Rep DOI: 10.1038/srep15983 sha: doc_id: 336901 cord_uid: q6kgzuob file: cache/cord-340105-471x03f9.json key: cord-340105-471x03f9 authors: Kim, Sung-Il; Song, Jong Tae; Jeong, Jin-Yong; Seo, Hak Soo title: Niclosamide inhibits leaf blight caused by Xanthomonas oryzae in rice date: 2016-02-16 journal: Sci Rep DOI: 10.1038/srep21209 sha: doc_id: 340105 cord_uid: 471x03f9 file: cache/cord-338588-rc1h4drd.json key: cord-338588-rc1h4drd authors: Li, Xuanyi; Sigworth, Elizabeth A.; Wu, Adrianne H.; Behrens, Jess; Etemad, Shervin A.; Nagpal, Seema; Go, Ronald S.; Wuichet, Kristin; Chen, Eddy J.; Rubinstein, Samuel M.; Venepalli, Neeta K.; Tillman, Benjamin F.; Cowan, Andrew J.; Schoen, Martin W.; Malty, Andrew; Greer, John P.; Fernandes, Hermina D.; Seifter, Ari; Chen, Qingxia; Chowdhery, Rozina A.; Mohan, Sanjay R.; Dewdney, Summer B.; Osterman, Travis; Ambinder, Edward P.; Buchbinder, Elizabeth I.; Schwartz, Candice; Abraham, Ivy; Rioth, Matthew J.; Singh, Naina; Sharma, Sanjai; Gibson, Michael K.; Yang, Peter C.; Warner, Jeremy L. title: Seven decades of chemotherapy clinical trials: a pan-cancer social network analysis date: 2020-10-16 journal: Sci Rep DOI: 10.1038/s41598-020-73466-6 sha: doc_id: 338588 cord_uid: rc1h4drd file: cache/cord-338142-acqiyqwz.json key: cord-338142-acqiyqwz authors: Jeong, Hye Jin; Min, Sein; Chae, Heelim; Kim, Sarah; Lee, Gunwoo; Namgoong, Sung Keon; Jeong, Keunhong title: Signal amplification by reversible exchange for COVID-19 antiviral drug candidates date: 2020-08-31 journal: Sci Rep DOI: 10.1038/s41598-020-71282-6 sha: doc_id: 338142 cord_uid: acqiyqwz file: cache/cord-342289-zpstb7h9.json key: cord-342289-zpstb7h9 authors: Cui, Tingting; Theuns, Sebastiaan; Desmarets, Lowiese M. B.; Xie, Jiexiong; De Gryse, Gaëtan M. A.; Yang, Bo; Van den Broeck, Wim; Nauwynck, Hans J. title: Establishment of porcine enterocyte/myofibroblast co-cultures for the growth of porcine rota- and coronaviruses date: 2018-10-12 journal: Sci Rep DOI: 10.1038/s41598-018-33305-1 sha: doc_id: 342289 cord_uid: zpstb7h9 file: cache/cord-339973-kj56zi59.json key: cord-339973-kj56zi59 authors: Coleman, Kristen K.; Nguyen, Tham T.; Yadana, Su; Hansen-Estruch, Christophe; Lindsley, William G.; Gray, Gregory C. title: Bioaerosol Sampling for Respiratory Viruses in Singapore’s Mass Rapid Transit Network date: 2018-11-30 journal: Sci Rep DOI: 10.1038/s41598-018-35896-1 sha: doc_id: 339973 cord_uid: kj56zi59 file: cache/cord-343302-g9vcchrh.json key: cord-343302-g9vcchrh authors: Agrawal, Anurodh Shankar; Ying, Tianlei; Tao, Xinrong; Garron, Tania; Algaissi, Abdullah; Wang, Yanping; Wang, Lili; Peng, Bi-Hung; Jiang, Shibo; Dimitrov, Dimiter S.; Tseng, Chien-Te K. title: Passive Transfer of A Germline-like Neutralizing Human Monoclonal Antibody Protects Transgenic Mice Against Lethal Middle East Respiratory Syndrome Coronavirus Infection date: 2016-08-19 journal: Sci Rep DOI: 10.1038/srep31629 sha: doc_id: 343302 cord_uid: g9vcchrh file: cache/cord-344421-rmnck42f.json key: cord-344421-rmnck42f authors: Theuns, Sebastiaan; Vanmechelen, Bert; Bernaert, Quinten; Deboutte, Ward; Vandenhole, Marilou; Beller, Leen; Matthijnssens, Jelle; Maes, Piet; Nauwynck, Hans J. title: Nanopore sequencing as a revolutionary diagnostic tool for porcine viral enteric disease complexes identifies porcine kobuvirus as an important enteric virus date: 2018-06-29 journal: Sci Rep DOI: 10.1038/s41598-018-28180-9 sha: doc_id: 344421 cord_uid: rmnck42f file: cache/cord-342122-certy2v8.json key: cord-342122-certy2v8 authors: Ruscitti, Piero; Di Benedetto, Paola; Berardicurti, Onorina; Panzera, Noemi; Grazia, Nicolò; Lizzi, Anna Rita; Cipriani, Paola; Shoenfeld, Yehuda; Giacomelli, Roberto title: Pro-inflammatory properties of H-ferritin on human macrophages, ex vivo and in vitro observations date: 2020-07-22 journal: Sci Rep DOI: 10.1038/s41598-020-69031-w sha: doc_id: 342122 cord_uid: certy2v8 file: cache/cord-343528-5283jsnu.json key: cord-343528-5283jsnu authors: Zhang, Zhao; Shen, Libing; Gu, Xun title: Evolutionary Dynamics of MERS-CoV: Potential Recombination, Positive Selection and Transmission date: 2016-05-04 journal: Sci Rep DOI: 10.1038/srep25049 sha: doc_id: 343528 cord_uid: 5283jsnu file: cache/cord-350468-32qin4ak.json key: cord-350468-32qin4ak authors: Song, Cong-Ying; Xu, Jia; He, Jian-Qin; Lu, Yuan-Qiang title: Immune dysfunction following COVID-19, especially in severe patients date: 2020-09-28 journal: Sci Rep DOI: 10.1038/s41598-020-72718-9 sha: doc_id: 350468 cord_uid: 32qin4ak file: cache/cord-344344-q32b742a.json key: cord-344344-q32b742a authors: Sato, Shintaro; Matsumoto, Naomi; Hisaie, Kota; Uematsu, Satoshi title: Alcohol abrogates human norovirus infectivity in a pH-dependent manner date: 2020-09-28 journal: Sci Rep DOI: 10.1038/s41598-020-72609-z sha: doc_id: 344344 cord_uid: q32b742a file: cache/cord-351295-4toxlskr.json key: cord-351295-4toxlskr authors: Lanave, Gianvito; Capozza, Paolo; Diakoudi, Georgia; Catella, Cristiana; Catucci, Leonardo; Ghergo, Paola; Stasi, Fabio; Barrs, Vanessa; Beatty, Julia; Decaro, Nicola; Buonavoglia, Canio; Martella, Vito; Camero, Michele title: Identification of hepadnavirus in the sera of cats date: 2019-07-23 journal: Sci Rep DOI: 10.1038/s41598-019-47175-8 sha: doc_id: 351295 cord_uid: 4toxlskr file: cache/cord-344871-486sk4wc.json key: cord-344871-486sk4wc authors: Wu, Jianping; Mok, Chee-Keng; Chow, Vincent Tak Kwong; Yuan, Y. Adam; Tan, Yee-Joo title: Biochemical and structural characterization of the interface mediating interaction between the influenza A virus non-structural protein-1 and a monoclonal antibody date: 2016-09-16 journal: Sci Rep DOI: 10.1038/srep33382 sha: doc_id: 344871 cord_uid: 486sk4wc file: cache/cord-345359-okmkgsbr.json key: cord-345359-okmkgsbr authors: Ohno, Marumi; Sekiya, Toshiki; Nomura, Naoki; Daito, Taku ji; Shingai, Masashi; Kida, Hiroshi title: Influenza virus infection affects insulin signaling, fatty acid-metabolizing enzyme expressions, and the tricarboxylic acid cycle in mice date: 2020-07-02 journal: Sci Rep DOI: 10.1038/s41598-020-67879-6 sha: doc_id: 345359 cord_uid: okmkgsbr file: cache/cord-342676-ykog278j.json key: cord-342676-ykog278j authors: Stewart, H.; Bingham, R.J.; White, S. J.; Dykeman, E. C.; Zothner, C.; Tuplin, A. K.; Stockley, P. G.; Twarock, R.; Harris, M. title: Identification of novel RNA secondary structures within the hepatitis C virus genome reveals a cooperative involvement in genome packaging date: 2016-03-14 journal: Sci Rep DOI: 10.1038/srep22952 sha: doc_id: 342676 cord_uid: ykog278j file: cache/cord-344953-gtg12hiu.json key: cord-344953-gtg12hiu authors: Prather, Randall S.; Wells, Kevin D.; Whitworth, Kristin M.; Kerrigan, Maureen A.; Samuel, Melissa S.; Mileham, Alan; Popescu, Luca N.; Rowland, Raymond R. R. title: Knockout of maternal CD163 protects fetuses from infection with porcine reproductive and respiratory syndrome virus (PRRSV) date: 2017-10-17 journal: Sci Rep DOI: 10.1038/s41598-017-13794-2 sha: doc_id: 344953 cord_uid: gtg12hiu file: cache/cord-342782-xty16m8w.json key: cord-342782-xty16m8w authors: Marrugal-Lorenzo, José A.; Serna-Gallego, Ana; Berastegui-Cabrera, Judith; Pachón, Jerónimo; Sánchez-Céspedes, Javier title: Repositioning salicylanilide anthelmintic drugs to treat adenovirus infections date: 2019-01-09 journal: Sci Rep DOI: 10.1038/s41598-018-37290-3 sha: doc_id: 342782 cord_uid: xty16m8w file: cache/cord-350255-tthttyl3.json key: cord-350255-tthttyl3 authors: Poirier, Canelle; Luo, Wei; Majumder, Maimuna S.; Liu, Dianbo; Mandl, Kenneth D.; Mooring, Todd A.; Santillana, Mauricio title: The role of environmental factors on transmission rates of the COVID-19 outbreak: an initial assessment in two spatial scales date: 2020-10-12 journal: Sci Rep DOI: 10.1038/s41598-020-74089-7 sha: doc_id: 350255 cord_uid: tthttyl3 file: cache/cord-352020-9wxwktck.json key: cord-352020-9wxwktck authors: Zhang, Baoshan; Chao, Cara W.; Tsybovsky, Yaroslav; Abiona, Olubukola M.; Hutchinson, Geoffrey B.; Moliva, Juan I.; Olia, Adam S.; Pegu, Amarendra; Phung, Emily; Stewart-Jones, Guillaume B. E.; Verardi, Raffaello; Wang, Lingshu; Wang, Shuishu; Werner, Anne; Yang, Eun Sung; Yap, Christina; Zhou, Tongqing; Mascola, John R.; Sullivan, Nancy J.; Graham, Barney S.; Corbett, Kizzmekia S.; Kwong, Peter D. title: A platform incorporating trimeric antigens into self-assembling nanoparticles reveals SARS-CoV-2-spike nanoparticles to elicit substantially higher neutralizing responses than spike alone date: 2020-10-23 journal: Sci Rep DOI: 10.1038/s41598-020-74949-2 sha: doc_id: 352020 cord_uid: 9wxwktck file: cache/cord-340781-z348xbn0.json key: cord-340781-z348xbn0 authors: Namvar, Ali; Bolhassani, Azam; Javadi, Gholamreza; Noormohammadi, Zahra title: In silico/In vivo analysis of high-risk papillomavirus L1 and L2 conserved sequences for development of cross-subtype prophylactic vaccine date: 2019-10-23 journal: Sci Rep DOI: 10.1038/s41598-019-51679-8 sha: doc_id: 340781 cord_uid: z348xbn0 file: cache/cord-350957-10wcqgaq.json key: cord-350957-10wcqgaq authors: Shen, Zu T.; Sigalov, Alexander B. title: SARS Coronavirus Fusion Peptide-Derived Sequence Suppresses Collagen-Induced Arthritis in DBA/1J Mice date: 2016-06-28 journal: Sci Rep DOI: 10.1038/srep28672 sha: doc_id: 350957 cord_uid: 10wcqgaq file: cache/cord-351659-ujbxsus4.json key: cord-351659-ujbxsus4 authors: Jiang, Xiandeng; Chang, Le; Shi, Yanlin title: A retrospective analysis of the dynamic transmission routes of the COVID-19 in mainland China date: 2020-08-19 journal: Sci Rep DOI: 10.1038/s41598-020-71023-9 sha: doc_id: 351659 cord_uid: ujbxsus4 file: cache/cord-348515-bqqyly23.json key: cord-348515-bqqyly23 authors: Zhao, Suhui; Wan, Chengsong; Ke, Changwen; Seto, Jason; Dehghan, Shoaleh; Zou, Lirong; Zhou, Jie; Cheng, Zetao; Jing, Shuping; Zeng, Zhiwei; Zhang, Jing; Wan, Xuan; Wu, Xianbo; Zhao, Wei; Zhu, Li; Seto, Donald; Zhang, Qiwei title: Re-emergent Human Adenovirus Genome Type 7d Caused an Acute Respiratory Disease Outbreak in Southern China After a Twenty-one Year Absence date: 2014-12-08 journal: Sci Rep DOI: 10.1038/srep07365 sha: doc_id: 348515 cord_uid: bqqyly23 file: cache/cord-356027-ckdx56j1.json key: cord-356027-ckdx56j1 authors: Zheng, Shou-Yan; Xiao, Qiu-Yan; Xie, Xiao-Hong; Deng, Yu; Ren, Luo; Tian, Dai-Yin; Luo, Zheng-Xiu; Luo, Jian; Fu, Zhou; Huang, Ai-Long; Liu, En-Mei title: Association between secondary thrombocytosis and viral respiratory tract infections in children date: 2016-03-11 journal: Sci Rep DOI: 10.1038/srep22964 sha: doc_id: 356027 cord_uid: ckdx56j1 file: cache/cord-352061-x6tt9kx5.json key: cord-352061-x6tt9kx5 authors: Kiyota, Yasuhiro; Muramatsu, Hiroyasu; Sato, Yuiko; Kobayashi, Tami; Miyamoto, Kana; Iwamoto, Takuji; Matsumoto, Morio; Nakamura, Masaya; Tateno, Hiroki; Sato, Kazuki; Miyamoto, Takeshi title: Smoking cessation increases levels of osteocalcin and uncarboxylated osteocalcin in human sera date: 2020-10-08 journal: Sci Rep DOI: 10.1038/s41598-020-73789-4 sha: doc_id: 352061 cord_uid: x6tt9kx5 file: cache/cord-355179-wmfwl2bh.json key: cord-355179-wmfwl2bh authors: Jung, Eunhye; Nam, Sangwoo; Oh, Hyeryeon; Jun, Sangmi; Ro, Hyun-Joo; Kim, Baek; Kim, Meehyein; Go, Yun Young title: Neutralization of Acidic Intracellular Vesicles by Niclosamide Inhibits Multiple Steps of the Dengue Virus Life Cycle In Vitro date: 2019-06-18 journal: Sci Rep DOI: 10.1038/s41598-019-45095-1 sha: doc_id: 355179 cord_uid: wmfwl2bh file: cache/cord-346483-jc0xklzk.json key: cord-346483-jc0xklzk authors: Chen, Jun; Wu, Lianlian; Zhang, Jun; Zhang, Liang; Gong, Dexin; Zhao, Yilin; Chen, Qiuxiang; Huang, Shulan; Yang, Ming; Yang, Xiao; Hu, Shan; Wang, Yonggui; Hu, Xiao; Zheng, Biqing; Zhang, Kuo; Wu, Huiling; Dong, Zehua; Xu, Youming; Zhu, Yijie; Chen, Xi; Zhang, Mengjiao; Yu, Lilei; Cheng, Fan; Yu, Honggang title: Deep learning-based model for detecting 2019 novel coronavirus pneumonia on high-resolution computed tomography date: 2020-11-05 journal: Sci Rep DOI: 10.1038/s41598-020-76282-0 sha: doc_id: 346483 cord_uid: jc0xklzk Reading metadata file and updating bibliogrpahics === updating bibliographic database Building study carrel named journal-sciRep-cord === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 32145 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 32458 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 33320 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 33296 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 33811 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 34276 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 34637 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 34543 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 35425 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 36176 Aborted $FILE2BIB "$FILE" > "$OUTPUT" parallel: Warning: No more processes: Decreasing number of running jobs to 95. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 95. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === id: cord-001852-c79vwr6t author: Xiao, Qiuyan title: Prevalence and molecular characterizations of enterovirus D68 among children with acute respiratory infection in China between 2012 and 2014 date: 2015-11-16 pages: extension: .txt txt: ./txt/cord-001852-c79vwr6t.txt cache: ./cache/cord-001852-c79vwr6t.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-001852-c79vwr6t.txt' === file2bib.sh === id: cord-001522-82plcxv9 author: Xu, Zhiwei title: Exploration of diarrhoea seasonality and its drivers in China date: 2015-02-04 pages: extension: .txt txt: ./txt/cord-001522-82plcxv9.txt cache: ./cache/cord-001522-82plcxv9.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-001522-82plcxv9.txt' === file2bib.sh === id: cord-002072-qbh728ec author: Bi, Yuhai title: A new reassortment of influenza A (H7N9) virus causing human infection in Beijing, 2014 date: 2016-05-27 pages: extension: .txt txt: ./txt/cord-002072-qbh728ec.txt cache: ./cache/cord-002072-qbh728ec.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-002072-qbh728ec.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 35171 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 36631 Aborted $FILE2BIB "$FILE" > "$OUTPUT" parallel: Warning: No more processes: Decreasing number of running jobs to 95. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === id: cord-002081-vi6rth9o author: Zhang, Chao title: Establishment and application of a real-time loop-mediated isothermal amplification system for the detection of CYP2C19 polymorphisms date: 2016-06-01 pages: extension: .txt txt: ./txt/cord-002081-vi6rth9o.txt cache: ./cache/cord-002081-vi6rth9o.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-002081-vi6rth9o.txt' === file2bib.sh === id: cord-001823-v60vv99o author: Shen, Mingwang title: Modeling the effect of comprehensive interventions on Ebola virus transmission date: 2015-10-30 pages: extension: .txt txt: ./txt/cord-001823-v60vv99o.txt cache: ./cache/cord-001823-v60vv99o.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-001823-v60vv99o.txt' === file2bib.sh === id: cord-001862-a097byk5 author: Saisawang, Chonticha title: Chikungunya nsP2 protease is not a papain-like cysteine protease and the catalytic dyad cysteine is interchangeable with a proximal serine date: 2015-11-24 pages: extension: .txt txt: ./txt/cord-001862-a097byk5.txt cache: ./cache/cord-001862-a097byk5.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-001862-a097byk5.txt' === file2bib.sh === id: cord-002373-rueg4gsj author: Huang, Ao title: Quantitative Fluorescence Quenching on Antibody-conjugated Graphene Oxide as a Platform for Protein Sensing date: 2017-01-13 pages: extension: .txt txt: ./txt/cord-002373-rueg4gsj.txt cache: ./cache/cord-002373-rueg4gsj.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-002373-rueg4gsj.txt' === file2bib.sh === id: cord-002290-wvo22jx2 author: Liu, Cheng title: Association of Mannose-binding Lectin Polymorphisms with Tuberculosis Susceptibility among Chinese date: 2016-11-04 pages: extension: .txt txt: ./txt/cord-002290-wvo22jx2.txt cache: ./cache/cord-002290-wvo22jx2.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-002290-wvo22jx2.txt' === file2bib.sh === id: cord-001704-pdxm0iiw author: Xiong, Siping title: A Novel Chimeric Anti-PA Neutralizing Antibody for Postexposure Prophylaxis and Treatment of Anthrax date: 2015-07-02 pages: extension: .txt txt: ./txt/cord-001704-pdxm0iiw.txt cache: ./cache/cord-001704-pdxm0iiw.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-001704-pdxm0iiw.txt' === file2bib.sh === id: cord-001116-2yvyiiuy author: Nikas, Jason B. title: Inflammation and Immune System Activation in Aging: A Mathematical Approach date: 2013-11-19 pages: extension: .txt txt: ./txt/cord-001116-2yvyiiuy.txt cache: ./cache/cord-001116-2yvyiiuy.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-001116-2yvyiiuy.txt' === file2bib.sh === id: cord-001875-ulq1xqma author: Li, Jing title: Identification of climate factors related to human infection with avian influenza A H7N9 and H5N1 viruses in China date: 2015-12-11 pages: extension: .txt txt: ./txt/cord-001875-ulq1xqma.txt cache: ./cache/cord-001875-ulq1xqma.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-001875-ulq1xqma.txt' parallel: Warning: No more processes: Decreasing number of running jobs to 95. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 94. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === id: cord-001858-nmi39n6h author: Petriccione, Milena title: Reference gene selection for normalization of RT-qPCR gene expression data from Actinidia deliciosa leaves infected with Pseudomonas syringae pv. actinidiae date: 2015-11-19 pages: extension: .txt txt: ./txt/cord-001858-nmi39n6h.txt cache: ./cache/cord-001858-nmi39n6h.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-001858-nmi39n6h.txt' === file2bib.sh === id: cord-001901-2s6hpakk author: Kwok, Hoi-Hin title: Anti-inflammatory effects of indirubin derivatives on influenza A virus-infected human pulmonary microvascular endothelial cells date: 2016-01-06 pages: extension: .txt txt: ./txt/cord-001901-2s6hpakk.txt cache: ./cache/cord-001901-2s6hpakk.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-001901-2s6hpakk.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 36618 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 37139 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-002782-mena480g author: Chen, Jiajia title: Long term outcomes in survivors of epidemic Influenza A (H7N9) virus infection date: 2017-12-08 pages: extension: .txt txt: ./txt/cord-002782-mena480g.txt cache: ./cache/cord-002782-mena480g.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-002782-mena480g.txt' === file2bib.sh === id: cord-001712-a1sbdhhn author: Xiaokaiti, Yilixiati title: EGCG reverses human neutrophil elastase-induced migration in A549 cells by directly binding to HNE and by regulating α1-AT date: 2015-07-16 pages: extension: .txt txt: ./txt/cord-001712-a1sbdhhn.txt cache: ./cache/cord-001712-a1sbdhhn.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-001712-a1sbdhhn.txt' === file2bib.sh === id: cord-001675-9717nzr7 author: Sugiyama, Michael G. title: The Tie2-agonist Vasculotide rescues mice from influenza virus infection date: 2015-06-05 pages: extension: .txt txt: ./txt/cord-001675-9717nzr7.txt cache: ./cache/cord-001675-9717nzr7.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-001675-9717nzr7.txt' === file2bib.sh === id: cord-002312-jyk7f8hz author: Branton, W. G. title: Brain microbiota disruption within inflammatory demyelinating lesions in multiple sclerosis date: 2016-11-28 pages: extension: .txt txt: ./txt/cord-002312-jyk7f8hz.txt cache: ./cache/cord-002312-jyk7f8hz.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-002312-jyk7f8hz.txt' === file2bib.sh === id: cord-002490-kw8psrmz author: Beniac, Daniel R. title: Structure of the Ebola virus glycoprotein spike within the virion envelope at 11 Å resolution date: 2017-04-11 pages: extension: .txt txt: ./txt/cord-002490-kw8psrmz.txt cache: ./cache/cord-002490-kw8psrmz.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-002490-kw8psrmz.txt' === file2bib.sh === id: cord-002258-o9azey3m author: Chan, Louisa L. Y. title: Evaluation of the human adaptation of influenza A/H7N9 virus in PB2 protein using human and swine respiratory tract explant cultures date: 2016-10-14 pages: extension: .txt txt: ./txt/cord-002258-o9azey3m.txt cache: ./cache/cord-002258-o9azey3m.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-002258-o9azey3m.txt' /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes === file2bib.sh === id: cord-002720-lrkscs71 author: Kurosaki, Yohei title: Development and evaluation of a rapid molecular diagnostic test for Zika virus infection by reverse transcription loop-mediated isothermal amplification date: 2017-10-18 pages: extension: .txt txt: ./txt/cord-002720-lrkscs71.txt cache: ./cache/cord-002720-lrkscs71.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-002720-lrkscs71.txt' parallel: Warning: No more processes: Decreasing number of running jobs to 94. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === id: cord-002110-pbb247lp author: Chen, Chin-Pei title: Membrane protein assembly: two cytoplasmic phosphorylated serine sites of Vpu from HIV-1 affect oligomerization date: 2016-06-29 pages: extension: .txt txt: ./txt/cord-002110-pbb247lp.txt cache: ./cache/cord-002110-pbb247lp.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-002110-pbb247lp.txt' === file2bib.sh === id: cord-001963-4wjvykx7 author: Liu, Chia-Lin title: Using mutagenesis to explore conserved residues in the RNA-binding groove of influenza A virus nucleoprotein for antiviral drug development date: 2016-02-26 pages: extension: .txt txt: ./txt/cord-001963-4wjvykx7.txt cache: ./cache/cord-001963-4wjvykx7.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 8 resourceName b'cord-001963-4wjvykx7.txt' === file2bib.sh === id: cord-002874-9rxv6fy9 author: Welch, David title: Far-UVC light: A new tool to control the spread of airborne-mediated microbial diseases date: 2018-02-09 pages: extension: .txt txt: ./txt/cord-002874-9rxv6fy9.txt cache: ./cache/cord-002874-9rxv6fy9.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 12 resourceName b'cord-002874-9rxv6fy9.txt' === file2bib.sh === id: cord-002673-5a1rfi6k author: Knibb, Wayne title: Regional genetic diversity for NNV grouper viruses across the Indo-Asian region – implications for selecting virus resistance in farmed groupers date: 2017-09-06 pages: extension: .txt txt: ./txt/cord-002673-5a1rfi6k.txt cache: ./cache/cord-002673-5a1rfi6k.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-002673-5a1rfi6k.txt' === file2bib.sh === id: cord-002758-d86hnox1 author: Opuu, Vaitea title: Computational design of fully overlapping coding schemes for protein pairs and triplets date: 2017-11-20 pages: extension: .txt txt: ./txt/cord-002758-d86hnox1.txt cache: ./cache/cord-002758-d86hnox1.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-002758-d86hnox1.txt' === file2bib.sh === id: cord-002932-5e7xrd1y author: Watanabe, Tokiko title: Experimental infection of Cynomolgus Macaques with highly pathogenic H5N1 influenza virus through the aerosol route date: 2018-03-19 pages: extension: .txt txt: ./txt/cord-002932-5e7xrd1y.txt cache: ./cache/cord-002932-5e7xrd1y.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-002932-5e7xrd1y.txt' === file2bib.sh === id: cord-002474-2l31d7ew author: Lv, Yang title: Actual measurement, hygrothermal response experiment and growth prediction analysis of microbial contamination of central air conditioning system in Dalian, China date: 2017-04-03 pages: extension: .txt txt: ./txt/cord-002474-2l31d7ew.txt cache: ./cache/cord-002474-2l31d7ew.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-002474-2l31d7ew.txt' === file2bib.sh === id: cord-002177-yyfgl9x5 author: Guo, Jinyue title: TGEV infection up-regulates FcRn expression via activation of NF-κB signaling date: 2016-08-24 pages: extension: .txt txt: ./txt/cord-002177-yyfgl9x5.txt cache: ./cache/cord-002177-yyfgl9x5.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-002177-yyfgl9x5.txt' === file2bib.sh === id: cord-004419-81w7apdk author: Course, Christopher title: Management of Respiratory Distress Syndrome in Preterm Infants In Wales: A Full Audit Cycle of a Quality Improvement Project date: 2020-02-26 pages: extension: .txt txt: ./txt/cord-004419-81w7apdk.txt cache: ./cache/cord-004419-81w7apdk.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-004419-81w7apdk.txt' === file2bib.sh === id: cord-001829-rwnbxmt4 author: Lu, Yi-Fan title: IFNL3 mRNA structure is remodeled by a functional non-coding polymorphism associated with hepatitis C virus clearance date: 2015-11-04 pages: extension: .txt txt: ./txt/cord-001829-rwnbxmt4.txt cache: ./cache/cord-001829-rwnbxmt4.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-001829-rwnbxmt4.txt' === file2bib.sh === id: cord-002111-mmpijsqb author: Philp, Lisa K. title: Small Glutamine-Rich Tetratricopeptide Repeat-Containing Protein Alpha (SGTA) Ablation Limits Offspring Viability and Growth in Mice date: 2016-06-30 pages: extension: .txt txt: ./txt/cord-002111-mmpijsqb.txt cache: ./cache/cord-002111-mmpijsqb.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-002111-mmpijsqb.txt' === file2bib.sh === id: cord-003055-88q36g00 author: Imai, Kenji title: Administration of molecular hydrogen during pregnancy improves behavioral abnormalities of offspring in a maternal immune activation model date: 2018-06-15 pages: extension: .txt txt: ./txt/cord-003055-88q36g00.txt cache: ./cache/cord-003055-88q36g00.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-003055-88q36g00.txt' === file2bib.sh === id: cord-002644-yzan95du author: Ren, Rongrong title: The H7N9 influenza A virus infection results in lethal inflammation in the mammalian host via the NLRP3-caspase-1 inflammasome date: 2017-08-08 pages: extension: .txt txt: ./txt/cord-002644-yzan95du.txt cache: ./cache/cord-002644-yzan95du.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-002644-yzan95du.txt' === file2bib.sh === id: cord-002844-jv42o789 author: Marcos-Villar, Laura title: Epigenetic control of influenza virus: role of H3K79 methylation in interferon-induced antiviral response date: 2018-01-19 pages: extension: .txt txt: ./txt/cord-002844-jv42o789.txt cache: ./cache/cord-002844-jv42o789.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-002844-jv42o789.txt' === file2bib.sh === id: cord-002320-m99amd4y author: Mathur, Kalika title: Analysis of chikungunya virus proteins reveals that non-structural proteins nsP2 and nsP3 exhibit RNA interference (RNAi) suppressor activity date: 2016-11-30 pages: extension: .txt txt: ./txt/cord-002320-m99amd4y.txt cache: ./cache/cord-002320-m99amd4y.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 37 resourceName b'cord-002320-m99amd4y.txt' === file2bib.sh === id: cord-003004-iif2lnez author: Linster, Martin title: Clinical and Molecular Epidemiology of Human Parainfluenza Viruses 1–4 in Children from Viet Nam date: 2018-05-01 pages: extension: .txt txt: ./txt/cord-003004-iif2lnez.txt cache: ./cache/cord-003004-iif2lnez.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-003004-iif2lnez.txt' === file2bib.sh === id: cord-004379-91a7sgir author: Han, Nayoung title: Assessment of adverse events related to anti-influenza neuraminidase inhibitors using the FDA adverse event reporting system and online patient reviews date: 2020-02-20 pages: extension: .txt txt: ./txt/cord-004379-91a7sgir.txt cache: ./cache/cord-004379-91a7sgir.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-004379-91a7sgir.txt' === file2bib.sh === id: cord-002369-shk4n8f6 author: Fahmy, Ahmed M. title: The autophagy elongation complex (ATG5-12/16L1) positively regulates HCV replication and is required for wild-type membranous web formation date: 2017-01-09 pages: extension: .txt txt: ./txt/cord-002369-shk4n8f6.txt cache: ./cache/cord-002369-shk4n8f6.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-002369-shk4n8f6.txt' === file2bib.sh === id: cord-002408-bbtslrrt author: Almogy, Gal title: Analysis of Influenza and RSV dynamics in the community using a ‘Local Transmission Zone’ approach date: 2017-02-09 pages: extension: .txt txt: ./txt/cord-002408-bbtslrrt.txt cache: ./cache/cord-002408-bbtslrrt.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-002408-bbtslrrt.txt' === file2bib.sh === id: cord-003166-k3jxvzfi author: Noh, Ji Yeong title: Isolation and characterization of novel bat paramyxovirus B16-40 potentially belonging to the proposed genus Shaanvirus date: 2018-08-22 pages: extension: .txt txt: ./txt/cord-003166-k3jxvzfi.txt cache: ./cache/cord-003166-k3jxvzfi.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-003166-k3jxvzfi.txt' /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes === file2bib.sh === id: cord-004181-exbs3tz7 author: Pumchan, Ansaya title: Novel Chimeric Multiepitope Vaccine for Streptococcosis Disease in Nile Tilapia (Oreochromis niloticus Linn.) date: 2020-01-17 pages: extension: .txt txt: ./txt/cord-004181-exbs3tz7.txt cache: ./cache/cord-004181-exbs3tz7.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-004181-exbs3tz7.txt' === file2bib.sh === id: cord-004062-yxx3xxio author: Lee, Ing-Kit title: Impaired production of immune mediators in dengue virus type 2-infected mononuclear cells of adults with end stage renal disease date: 2019-12-24 pages: extension: .txt txt: ./txt/cord-004062-yxx3xxio.txt cache: ./cache/cord-004062-yxx3xxio.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-004062-yxx3xxio.txt' === file2bib.sh === id: cord-004292-6lnxb0px author: Lyu, Hongming title: Synchronized Biventricular Heart Pacing in a Closed-chest Porcine Model based on Wirelessly Powered Leadless Pacemakers date: 2020-02-07 pages: extension: .txt txt: ./txt/cord-004292-6lnxb0px.txt cache: ./cache/cord-004292-6lnxb0px.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-004292-6lnxb0px.txt' === file2bib.sh === id: cord-003558-7lvqpz21 author: Davies, Patrick title: Clinical Scenarios of the Application of Electrical Impedance Tomography in Paediatric Intensive Care date: 2019-03-29 pages: extension: .txt txt: ./txt/cord-003558-7lvqpz21.txt cache: ./cache/cord-003558-7lvqpz21.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-003558-7lvqpz21.txt' === file2bib.sh === id: cord-002659-566uoozj author: Fujimoto, Yousuke title: Pulmonary inflammation and cytokine dynamics of bronchoalveolar lavage fluid from a mouse model of bronchial asthma during A(H1N1)pdm09 influenza infection date: 2017-08-22 pages: extension: .txt txt: ./txt/cord-002659-566uoozj.txt cache: ./cache/cord-002659-566uoozj.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-002659-566uoozj.txt' === file2bib.sh === id: cord-002244-5h6monh3 author: Lee, Seung Hoon title: PTEN ameliorates autoimmune arthritis through down-regulating STAT3 activation with reciprocal balance of Th17 and Tregs date: 2016-10-06 pages: extension: .txt txt: ./txt/cord-002244-5h6monh3.txt cache: ./cache/cord-002244-5h6monh3.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-002244-5h6monh3.txt' === file2bib.sh === id: cord-001915-b9dk07tk author: Liang, Xun title: A CRISPR/Cas9 and Cre/Lox system-based express vaccine development strategy against re-emerging Pseudorabies virus date: 2016-01-18 pages: extension: .txt txt: ./txt/cord-001915-b9dk07tk.txt cache: ./cache/cord-001915-b9dk07tk.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-001915-b9dk07tk.txt' === file2bib.sh === id: cord-002956-e5ihpe4i author: Chang, Ya-Chun title: Ventilator Dependence Risk Score for the Prediction of Prolonged Mechanical Ventilation in Patients Who Survive Sepsis/Septic Shock with Respiratory Failure date: 2018-04-04 pages: extension: .txt txt: ./txt/cord-002956-e5ihpe4i.txt cache: ./cache/cord-002956-e5ihpe4i.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-002956-e5ihpe4i.txt' === file2bib.sh === id: cord-004310-hl7fa4af author: Matsuishi, Yujiro title: Down Syndrome Reduces the Sedative Effect of Midazolam in Pediatric Cardiovascular Surgical Patients date: 2020-02-10 pages: extension: .txt txt: ./txt/cord-004310-hl7fa4af.txt cache: ./cache/cord-004310-hl7fa4af.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-004310-hl7fa4af.txt' === file2bib.sh === id: cord-002389-k86hzbbx author: Fan, Hanlu title: Selective inhibition of Ebola entry with selective estrogen receptor modulators by disrupting the endolysosomal calcium date: 2017-01-24 pages: extension: .txt txt: ./txt/cord-002389-k86hzbbx.txt cache: ./cache/cord-002389-k86hzbbx.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-002389-k86hzbbx.txt' === file2bib.sh === id: cord-004069-nuep8nim author: DeWald, Lisa Evans title: In Vivo Activity of Amodiaquine against Ebola Virus Infection date: 2019-12-27 pages: extension: .txt txt: ./txt/cord-004069-nuep8nim.txt cache: ./cache/cord-004069-nuep8nim.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-004069-nuep8nim.txt' === file2bib.sh === id: cord-002802-594mmlk8 author: Zhang, Yun title: Recombinant influenza H9N2 virus with a substitution of H3 hemagglutinin transmembrane domain showed enhanced immunogenicity in mice and chicken date: 2017-12-20 pages: extension: .txt txt: ./txt/cord-002802-594mmlk8.txt cache: ./cache/cord-002802-594mmlk8.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-002802-594mmlk8.txt' === file2bib.sh === id: cord-002045-m44fic4g author: Horie, Masayuki title: An RNA-dependent RNA polymerase gene in bat genomes derived from an ancient negative-strand RNA virus date: 2016-05-13 pages: extension: .txt txt: ./txt/cord-002045-m44fic4g.txt cache: ./cache/cord-002045-m44fic4g.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-002045-m44fic4g.txt' /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes === file2bib.sh === id: cord-001868-utsvsja0 author: Uematsu, Takayuki title: Loss of CARD9-mediated innate activation attenuates severe influenza pneumonia without compromising host viral immunity date: 2015-12-02 pages: extension: .txt txt: ./txt/cord-001868-utsvsja0.txt cache: ./cache/cord-001868-utsvsja0.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-001868-utsvsja0.txt' === file2bib.sh === id: cord-003504-wjab4y0g author: Copland, Alastair title: Bacillus Calmette-Guérin Induces PD-L1 Expression on Antigen-Presenting Cells via Autocrine and Paracrine Interleukin-STAT3 Circuits date: 2019-03-06 pages: extension: .txt txt: ./txt/cord-003504-wjab4y0g.txt cache: ./cache/cord-003504-wjab4y0g.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-003504-wjab4y0g.txt' === file2bib.sh === id: cord-002013-rb9xdzro author: Zheng, Xuexing title: Treatment with hyperimmune equine immunoglobulin or immunoglobulin fragments completely protects rodents from Ebola virus infection date: 2016-04-12 pages: extension: .txt txt: ./txt/cord-002013-rb9xdzro.txt cache: ./cache/cord-002013-rb9xdzro.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-002013-rb9xdzro.txt' === file2bib.sh === id: cord-004170-ri5qsarz author: Yashima, Nozomi title: Leukocyte-derived extracellular DNA contributes to abnormal pressure elevation in the extracorporeal circulation circuit date: 2020-01-16 pages: extension: .txt txt: ./txt/cord-004170-ri5qsarz.txt cache: ./cache/cord-004170-ri5qsarz.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-004170-ri5qsarz.txt' /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable === file2bib.sh === id: cord-003490-swlkjtyo author: Arzt, Jonathan title: Quantitative impacts of incubation phase transmission of foot-and-mouth disease virus date: 2019-02-25 pages: extension: .txt txt: ./txt/cord-003490-swlkjtyo.txt cache: ./cache/cord-003490-swlkjtyo.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-003490-swlkjtyo.txt' === file2bib.sh === id: cord-003623-n01rgqyv author: Schuh, Amy J. title: Comparative analysis of serologic cross-reactivity using convalescent sera from filovirus-experimentally infected fruit bats date: 2019-04-30 pages: extension: .txt txt: ./txt/cord-003623-n01rgqyv.txt cache: ./cache/cord-003623-n01rgqyv.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-003623-n01rgqyv.txt' === file2bib.sh === id: cord-004150-ybikajhh author: Nyarko, Prince B. title: Investigating a Plasmodium falciparum erythrocyte invasion phenotype switch at the whole transcriptome level date: 2020-01-14 pages: extension: .txt txt: ./txt/cord-004150-ybikajhh.txt cache: ./cache/cord-004150-ybikajhh.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-004150-ybikajhh.txt' === file2bib.sh === id: cord-003505-qr6ukfti author: Tabraue-Chávez, Mavys title: A colorimetric strategy based on dynamic chemistry for direct detection of Trypanosomatid species date: 2019-03-06 pages: extension: .txt txt: ./txt/cord-003505-qr6ukfti.txt cache: ./cache/cord-003505-qr6ukfti.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-003505-qr6ukfti.txt' === file2bib.sh === id: cord-004222-z4butywi author: Joyce, Collin title: Comparisons of the antibody repertoires of a humanized rodent and humans by high throughput sequencing date: 2020-01-24 pages: extension: .txt txt: ./txt/cord-004222-z4butywi.txt cache: ./cache/cord-004222-z4butywi.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-004222-z4butywi.txt' === file2bib.sh === id: cord-003387-82573enr author: Nam, Gyu-Hwi title: Gene expression profiles alteration after infection of virus, bacteria, and parasite in the Olive flounder (Paralichthys olivaceus) date: 2018-12-24 pages: extension: .txt txt: ./txt/cord-003387-82573enr.txt cache: ./cache/cord-003387-82573enr.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-003387-82573enr.txt' === file2bib.sh === id: cord-004060-nxw5k9y1 author: Zhang, Yewu title: Spatiotemporal Analysis of Influenza in China, 2005–2018 date: 2019-12-23 pages: extension: .txt txt: ./txt/cord-004060-nxw5k9y1.txt cache: ./cache/cord-004060-nxw5k9y1.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-004060-nxw5k9y1.txt' === file2bib.sh === id: cord-004385-xna32qve author: Zhou, Yuqing title: Use of corticosteroids in influenza-associated acute respiratory distress syndrome and severe pneumonia: a systemic review and meta-analysis date: 2020-02-20 pages: extension: .txt txt: ./txt/cord-004385-xna32qve.txt cache: ./cache/cord-004385-xna32qve.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-004385-xna32qve.txt' === file2bib.sh === id: cord-002411-iiw878w8 author: Ding, Xibing title: TLR4 signaling induces TLR3 up-regulation in alveolar macrophages during acute lung injury date: 2017-02-15 pages: extension: .txt txt: ./txt/cord-002411-iiw878w8.txt cache: ./cache/cord-002411-iiw878w8.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-002411-iiw878w8.txt' === file2bib.sh === id: cord-002019-wtnf340p author: Chen, Xiaojuan title: Retinoic acid facilitates inactivated transmissible gastroenteritis virus induction of CD8(+) T-cell migration to the porcine gut date: 2016-04-15 pages: extension: .txt txt: ./txt/cord-002019-wtnf340p.txt cache: ./cache/cord-002019-wtnf340p.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-002019-wtnf340p.txt' === file2bib.sh === id: cord-003196-fdb6az0v author: Casalino-Matsuda, S. Marina title: Hypercapnia Alters Expression of Immune Response, Nucleosome Assembly and Lipid Metabolism Genes in Differentiated Human Bronchial Epithelial Cells date: 2018-09-10 pages: extension: .txt txt: ./txt/cord-003196-fdb6az0v.txt cache: ./cache/cord-003196-fdb6az0v.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-003196-fdb6az0v.txt' === file2bib.sh === id: cord-010675-acdfvjm5 author: Vila-Vicent, Susana title: Sero-epidemiological study of the rotavirus VP8* protein from different P genotypes in Valencia, Spain date: 2020-05-08 pages: extension: .txt txt: ./txt/cord-010675-acdfvjm5.txt cache: ./cache/cord-010675-acdfvjm5.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-010675-acdfvjm5.txt' === file2bib.sh === id: cord-004016-iaktm72a author: Soto-Quintero, Albanelly title: Curcumin to Promote the Synthesis of Silver NPs and their Self-Assembly with a Thermoresponsive Polymer in Core-Shell Nanohybrids date: 2019-12-03 pages: extension: .txt txt: ./txt/cord-004016-iaktm72a.txt cache: ./cache/cord-004016-iaktm72a.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-004016-iaktm72a.txt' === file2bib.sh === id: cord-004378-g1rxygef author: Leinisch, Fabian title: UV oxidation of cyclic AMP receptor protein, a global bacterial gene regulator, decreases DNA binding and cleaves DNA at specific sites date: 2020-02-20 pages: extension: .txt txt: ./txt/cord-004378-g1rxygef.txt cache: ./cache/cord-004378-g1rxygef.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-004378-g1rxygef.txt' === file2bib.sh === id: cord-034746-uxhpufnv author: Nusshag, Christian title: Glomerular filtration barrier dysfunction in a self-limiting, RNA virus-induced glomerulopathy resembles findings in idiopathic nephrotic syndromes date: 2020-11-05 pages: extension: .txt txt: ./txt/cord-034746-uxhpufnv.txt cache: ./cache/cord-034746-uxhpufnv.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-034746-uxhpufnv.txt' === file2bib.sh === id: cord-002843-dvfmpm54 author: Ai, Hannan title: GenomeLandscaper: Landscape analysis of genome-fingerprints maps assessing chromosome architecture date: 2018-01-18 pages: extension: .txt txt: ./txt/cord-002843-dvfmpm54.txt cache: ./cache/cord-002843-dvfmpm54.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-002843-dvfmpm54.txt' === file2bib.sh === id: cord-004280-c470nlie author: Coleman, Kristen K. title: Airborne Influenza A Virus Exposure in an Elementary School date: 2020-02-05 pages: extension: .txt txt: ./txt/cord-004280-c470nlie.txt cache: ./cache/cord-004280-c470nlie.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-004280-c470nlie.txt' === file2bib.sh === id: cord-009691-gkynxdz3 author: Rizzato, Cosmeri title: Variations in cag pathogenicity island genes of Helicobacter pylori from Latin American groups may influence neoplastic progression to gastric cancer date: 2020-04-16 pages: extension: .txt txt: ./txt/cord-009691-gkynxdz3.txt cache: ./cache/cord-009691-gkynxdz3.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-009691-gkynxdz3.txt' === file2bib.sh === id: cord-005507-equnyib7 author: Kamath, Kathy title: Antibody epitope repertoire analysis enables rapid antigen discovery and multiplex serology date: 2020-03-24 pages: extension: .txt txt: ./txt/cord-005507-equnyib7.txt cache: ./cache/cord-005507-equnyib7.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-005507-equnyib7.txt' === file2bib.sh === id: cord-012742-lpk6r54i author: Ferreira-Ramos, Ana Sofia title: Snapshots of ADP-ribose bound to Getah virus macro domain reveal an intriguing choreography date: 2020-09-02 pages: extension: .txt txt: ./txt/cord-012742-lpk6r54i.txt cache: ./cache/cord-012742-lpk6r54i.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-012742-lpk6r54i.txt' === file2bib.sh === id: cord-003148-o7y3wygc author: Shirvani, Edris title: A Recombinant Newcastle Disease Virus (NDV) Expressing S Protein of Infectious Bronchitis Virus (IBV) Protects Chickens against IBV and NDV date: 2018-08-10 pages: extension: .txt txt: ./txt/cord-003148-o7y3wygc.txt cache: ./cache/cord-003148-o7y3wygc.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-003148-o7y3wygc.txt' === file2bib.sh === id: cord-011892-b9zlig0r author: Mukherjee, Shradha title: Quiescent stem cell marker genes in glioma gene networks are sufficient to distinguish between normal and glioblastoma (GBM) samples date: 2020-07-02 pages: extension: .txt txt: ./txt/cord-011892-b9zlig0r.txt cache: ./cache/cord-011892-b9zlig0r.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-011892-b9zlig0r.txt' === file2bib.sh === id: cord-004418-08dljap3 author: Young, Ginger title: Complete Protection in Macaques Conferred by Purified Inactivated Zika Vaccine: Defining a Correlate of Protection date: 2020-02-26 pages: extension: .txt txt: ./txt/cord-004418-08dljap3.txt cache: ./cache/cord-004418-08dljap3.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-004418-08dljap3.txt' === file2bib.sh === id: cord-259378-5g2y68i2 author: Cheng, Chao-Min title: Small-volume point-of-care analytical methods date: 2020-08-27 pages: extension: .txt txt: ./txt/cord-259378-5g2y68i2.txt cache: ./cache/cord-259378-5g2y68i2.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-259378-5g2y68i2.txt' parallel: Warning: No more processes: Decreasing number of running jobs to 95. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 93. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 95. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 94. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 92. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 93. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 46580 Aborted $FILE2BIB "$FILE" > "$OUTPUT" parallel: Warning: No more processes: Decreasing number of running jobs to 94. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 94. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === id: cord-031937-qhlatg84 author: Verma, Anukriti title: Elucidating potential molecular signatures through host-microbe interactions for reactive arthritis and inflammatory bowel disease using combinatorial approach date: 2020-09-15 pages: extension: .txt txt: ./txt/cord-031937-qhlatg84.txt cache: ./cache/cord-031937-qhlatg84.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-031937-qhlatg84.txt' /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable /data-disk/reader-compute/reader-cord/bin/cordent2carrel.sh: fork: retry: No child processes === file2bib.sh === id: cord-009690-kbwz7xop author: Toubanaki, Dimitra K. title: Development of a Nanoparticle-based Lateral Flow Strip Biosensor for Visual Detection of Whole Nervous Necrosis Virus Particles date: 2020-04-16 pages: extension: .txt txt: ./txt/cord-009690-kbwz7xop.txt cache: ./cache/cord-009690-kbwz7xop.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-009690-kbwz7xop.txt' /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes === file2bib.sh === id: cord-010640-s1oqphvn author: Baral, Prabin title: In-silico identification of the vaccine candidate epitopes against the Lassa virus hemorrhagic fever date: 2020-05-06 pages: extension: .txt txt: ./txt/cord-010640-s1oqphvn.txt cache: ./cache/cord-010640-s1oqphvn.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-010640-s1oqphvn.txt' parallel: Warning: No more processes: Decreasing number of running jobs to 94. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 92. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 46895 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 47429 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 48244 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 48281 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 48428 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 48645 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 48885 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 48983 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 49417 Aborted $FILE2BIB "$FILE" > "$OUTPUT" parallel: Warning: No more processes: Decreasing number of running jobs to 93. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 93. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 91. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === id: cord-258678-0atfsivf author: Liu, Hong Yan title: A Universal Protein Tag for Delivery of SiRNA-Aptamer Chimeras date: 2013-11-07 pages: extension: .txt txt: ./txt/cord-258678-0atfsivf.txt cache: ./cache/cord-258678-0atfsivf.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-258678-0atfsivf.txt' === file2bib.sh === id: cord-272092-ko9y5m2s author: Scalabrin, Matteo title: The cellular protein hnRNP A2/B1 enhances HIV-1 transcription by unfolding LTR promoter G-quadruplexes date: 2017-03-24 pages: extension: .txt txt: ./txt/cord-272092-ko9y5m2s.txt cache: ./cache/cord-272092-ko9y5m2s.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-272092-ko9y5m2s.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 49947 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 50912 Aborted $FILE2BIB "$FILE" > "$OUTPUT" /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 50383 Aborted $FILE2BIB "$FILE" > "$OUTPUT" parallel: Warning: No more processes: Decreasing number of running jobs to 92. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 50253 Aborted $FILE2BIB "$FILE" > "$OUTPUT" /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes === file2bib.sh === id: cord-007851-v6h1yro7 author: Han, Ki-Cheol title: Streamlined selection of cancer antigens for vaccine development through integrative multi-omics and high-content cell imaging date: 2020-04-03 pages: extension: .txt txt: ./txt/cord-007851-v6h1yro7.txt cache: ./cache/cord-007851-v6h1yro7.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-007851-v6h1yro7.txt' /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: Resource temporarily unavailable /data-disk/reader-compute/reader-cord/bin/cordpos2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordpos2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordwrd2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: Resource temporarily unavailable === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 50443 Aborted $FILE2BIB "$FILE" > "$OUTPUT" /data-disk/reader-compute/reader-cord/bin/cordpos2carrel.sh: fork: retry: No child processes === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 50135 Aborted $FILE2BIB "$FILE" > "$OUTPUT" /data-disk/reader-compute/reader-cord/bin/cordwrd2carrel.sh: fork: retry: No child processes === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 53084 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 52169 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 52058 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-263627-8ufjh70o author: Liang, Li-Lin title: Covid-19 mortality is negatively associated with test number and government effectiveness date: 2020-07-24 pages: extension: .txt txt: ./txt/cord-263627-8ufjh70o.txt cache: ./cache/cord-263627-8ufjh70o.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-263627-8ufjh70o.txt' === file2bib.sh === id: cord-030295-jlhht2l9 author: Cruz-Flores, Roberto title: Genome reconstruction of white spot syndrome virus (WSSV) from archival Davidson’s-fixed paraffin embedded shrimp (Penaeus vannamei) tissue date: 2020-08-10 pages: extension: .txt txt: ./txt/cord-030295-jlhht2l9.txt cache: ./cache/cord-030295-jlhht2l9.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-030295-jlhht2l9.txt' /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 51611 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 51834 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 52909 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 51877 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-254090-x8tnweih author: Yang, Szu-Chi title: Efficient Structure Resonance Energy Transfer from Microwaves to Confined Acoustic Vibrations in Viruses date: 2015-12-09 pages: extension: .txt txt: ./txt/cord-254090-x8tnweih.txt cache: ./cache/cord-254090-x8tnweih.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-254090-x8tnweih.txt' === file2bib.sh === id: cord-259416-gvzp2h5g author: Ling, Shenglong title: Combined approaches of EPR and NMR illustrate only one transmembrane helix in the human IFITM3 date: 2016-04-05 pages: extension: .txt txt: ./txt/cord-259416-gvzp2h5g.txt cache: ./cache/cord-259416-gvzp2h5g.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-259416-gvzp2h5g.txt' === file2bib.sh === id: cord-265211-a7whyds8 author: Hussein, Hosni A. M. title: miRNA-36 inhibits KSHV, EBV, HSV-2 infection of cells via stifling expression of interferon induced transmembrane protein 1 (IFITM1) date: 2017-12-21 pages: extension: .txt txt: ./txt/cord-265211-a7whyds8.txt cache: ./cache/cord-265211-a7whyds8.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-265211-a7whyds8.txt' === file2bib.sh === id: cord-255586-wshvvgxg author: He, Shengyang title: Clinical characteristics of “re-positive” discharged COVID-19 pneumonia patients in Wuhan, China date: 2020-10-15 pages: extension: .txt txt: ./txt/cord-255586-wshvvgxg.txt cache: ./cache/cord-255586-wshvvgxg.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-255586-wshvvgxg.txt' /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: Resource temporarily unavailable /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes === file2bib.sh === id: cord-271602-f14wccj3 author: Kim, Hyun Cheol title: Recent increase of surface particulate matter concentrations in the Seoul Metropolitan Area, Korea date: 2017-07-05 pages: extension: .txt txt: ./txt/cord-271602-f14wccj3.txt cache: ./cache/cord-271602-f14wccj3.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-271602-f14wccj3.txt' === file2bib.sh === id: cord-265891-jmpterrj author: Eilersen, Andreas title: Cost–benefit of limited isolation and testing in COVID-19 mitigation date: 2020-10-29 pages: extension: .txt txt: ./txt/cord-265891-jmpterrj.txt cache: ./cache/cord-265891-jmpterrj.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-265891-jmpterrj.txt' === file2bib.sh === id: cord-271328-zdf5ji4k author: Gu, Hongjing title: Angiotensin-converting enzyme 2 inhibits lung injury induced by respiratory syncytial virus date: 2016-01-27 pages: extension: .txt txt: ./txt/cord-271328-zdf5ji4k.txt cache: ./cache/cord-271328-zdf5ji4k.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-271328-zdf5ji4k.txt' === file2bib.sh === id: cord-255511-nk3iyg07 author: Chin, Wei Chien Benny title: Spatial super-spreaders and super-susceptibles in human movement networks date: 2020-10-29 pages: extension: .txt txt: ./txt/cord-255511-nk3iyg07.txt cache: ./cache/cord-255511-nk3iyg07.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-255511-nk3iyg07.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 53921 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 55408 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 54871 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === /data-disk/reader-compute/reader-cord/bin/file2bib.sh: fork: retry: No child processes OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 56629 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 55202 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 54301 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 56202 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 56152 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 55642 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 56167 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 56259 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 56145 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 56277 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 56004 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === /data-disk/reader-compute/reader-cord/bin/file2bib.sh: fork: retry: No child processes id: cord-254653-4ffuivil author: Cinelli, Matteo title: The COVID-19 social media infodemic date: 2020-10-06 pages: extension: .txt txt: ./txt/cord-254653-4ffuivil.txt cache: ./cache/cord-254653-4ffuivil.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-254653-4ffuivil.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 57035 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 55014 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 56778 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 56781 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-277816-ncdy9qgb author: Wang, Ji-gan title: Gastrointestinal symptoms and fecal nucleic acid testing of children with 2019 coronavirus disease: a systematic review and meta-analysis date: 2020-10-20 pages: extension: .txt txt: ./txt/cord-277816-ncdy9qgb.txt cache: ./cache/cord-277816-ncdy9qgb.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-277816-ncdy9qgb.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 57677 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-283583-pwlbrxn3 author: Zhang, Xiao-Ai title: Prevalence and genetic characteristics of Saffold cardiovirus in China from 2009 to 2012 date: 2015-01-09 pages: extension: .txt txt: ./txt/cord-283583-pwlbrxn3.txt cache: ./cache/cord-283583-pwlbrxn3.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-283583-pwlbrxn3.txt' === file2bib.sh === id: cord-263088-zj14ro5j author: DiPaola, Joshua D. title: Investigating the use of sensory information to detect and track prey by the Sunda pangolin (Manis javanica) with conservation in mind date: 2020-06-17 pages: extension: .txt txt: ./txt/cord-263088-zj14ro5j.txt cache: ./cache/cord-263088-zj14ro5j.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-263088-zj14ro5j.txt' === file2bib.sh === id: cord-284374-sqxlnk9e author: Park, Jiyeon title: Infection Prevention Measures for Surgical Procedures during a Middle East Respiratory Syndrome Outbreak in a Tertiary Care Hospital in South Korea date: 2020-01-15 pages: extension: .txt txt: ./txt/cord-284374-sqxlnk9e.txt cache: ./cache/cord-284374-sqxlnk9e.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-284374-sqxlnk9e.txt' === file2bib.sh === id: cord-284582-xwedgllw author: Korabecna, M. title: Cell-free DNA in plasma as an essential immune system regulator date: 2020-10-15 pages: extension: .txt txt: ./txt/cord-284582-xwedgllw.txt cache: ./cache/cord-284582-xwedgllw.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-284582-xwedgllw.txt' === file2bib.sh === id: cord-259794-6qoksn00 author: Shi, Da title: Nucleocapsid Interacts with NPM1 and Protects it from Proteolytic Cleavage, Enhancing Cell Survival, and is Involved in PEDV Growth date: 2017-01-03 pages: extension: .txt txt: ./txt/cord-259794-6qoksn00.txt cache: ./cache/cord-259794-6qoksn00.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-259794-6qoksn00.txt' === file2bib.sh === id: cord-286413-a7wue2e3 author: Cohen, Isaac V. title: Cardiac adverse events associated with chloroquine and hydroxychloroquine exposure in 20 years of drug safety surveillance reports date: 2020-11-05 pages: extension: .txt txt: ./txt/cord-286413-a7wue2e3.txt cache: ./cache/cord-286413-a7wue2e3.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-286413-a7wue2e3.txt' === file2bib.sh === id: cord-281536-8y7yxcp4 author: Lim, Hocheol title: Hot spot profiles of SARS-CoV-2 and human ACE2 receptor protein protein interaction obtained by density functional tight binding fragment molecular orbital method date: 2020-10-08 pages: extension: .txt txt: ./txt/cord-281536-8y7yxcp4.txt cache: ./cache/cord-281536-8y7yxcp4.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-281536-8y7yxcp4.txt' === file2bib.sh === id: cord-296867-6o4scan1 author: Hisada, Shohei title: Surveillance of early stage COVID-19 clusters using search query logs and mobile device-based location information date: 2020-10-29 pages: extension: .txt txt: ./txt/cord-296867-6o4scan1.txt cache: ./cache/cord-296867-6o4scan1.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-296867-6o4scan1.txt' === file2bib.sh === id: cord-260834-v254de8k author: Lim, Chia Chiu title: Development of a Phage Display Panning Strategy Utilizing Crude Antigens: Isolation of MERS-CoV Nucleoprotein human antibodies date: 2019-04-15 pages: extension: .txt txt: ./txt/cord-260834-v254de8k.txt cache: ./cache/cord-260834-v254de8k.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-260834-v254de8k.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 58927 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-308302-5yns1hg9 author: Wu, Gang title: A prediction model of outcome of SARS-CoV-2 pneumonia based on laboratory findings date: 2020-08-20 pages: extension: .txt txt: ./txt/cord-308302-5yns1hg9.txt cache: ./cache/cord-308302-5yns1hg9.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-308302-5yns1hg9.txt' === file2bib.sh === id: cord-276997-hbovh7s9 author: Alsved, Malin title: Aerosolization and recovery of viable murine norovirus in an experimental setup date: 2020-09-29 pages: extension: .txt txt: ./txt/cord-276997-hbovh7s9.txt cache: ./cache/cord-276997-hbovh7s9.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-276997-hbovh7s9.txt' === file2bib.sh === id: cord-305132-jspxlk1a author: Homma, Takujiro title: Persistent prion infection disturbs the function of Oct-1, resulting in the down-regulation of murine interferon regulatory factor-3 date: 2014-08-08 pages: extension: .txt txt: ./txt/cord-305132-jspxlk1a.txt cache: ./cache/cord-305132-jspxlk1a.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-305132-jspxlk1a.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 60473 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 59819 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-288761-fyvr0tc1 author: Santiago, César title: Allosteric inhibition of aminopeptidase N functions related to tumor growth and virus infection date: 2017-04-10 pages: extension: .txt txt: ./txt/cord-288761-fyvr0tc1.txt cache: ./cache/cord-288761-fyvr0tc1.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-288761-fyvr0tc1.txt' === file2bib.sh === id: cord-293372-saqoft9p author: Heffner, Kelley title: Expanded Chinese hamster organ and cell line proteomics profiling reveals tissue-specific functionalities date: 2020-09-28 pages: extension: .txt txt: ./txt/cord-293372-saqoft9p.txt cache: ./cache/cord-293372-saqoft9p.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-293372-saqoft9p.txt' === file2bib.sh === id: cord-296562-3h2oqb9k author: Guillén, Lucía title: Preemptive interleukin-6 blockade in patients with COVID-19 date: 2020-10-08 pages: extension: .txt txt: ./txt/cord-296562-3h2oqb9k.txt cache: ./cache/cord-296562-3h2oqb9k.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-296562-3h2oqb9k.txt' === file2bib.sh === id: cord-268414-7fcc5i7i author: Hassani, Abdelkader title: Preparation, characterization and therapeutic properties of gum arabic-stabilized gallic acid nanoparticles date: 2020-10-20 pages: extension: .txt txt: ./txt/cord-268414-7fcc5i7i.txt cache: ./cache/cord-268414-7fcc5i7i.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-268414-7fcc5i7i.txt' === file2bib.sh === id: cord-288721-3bv3aak6 author: Schneider, Annika title: Single organelle analysis to characterize mitochondrial function and crosstalk during viral infection date: 2019-06-11 pages: extension: .txt txt: ./txt/cord-288721-3bv3aak6.txt cache: ./cache/cord-288721-3bv3aak6.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-288721-3bv3aak6.txt' === file2bib.sh === id: cord-331148-40gvay7i author: Hsieh, Yu-Chia title: Clinical characteristics of patients with laboratory-confirmed influenza A(H1N1)pdm09 during the 2013/2014 and 2015/2016 clade 6B/6B.1/6B.2-predominant outbreaks date: 2018-10-23 pages: extension: .txt txt: ./txt/cord-331148-40gvay7i.txt cache: ./cache/cord-331148-40gvay7i.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-331148-40gvay7i.txt' === file2bib.sh === id: cord-335576-b34nc3ay author: Tsai, Andrew title: Impact of tocilizumab administration on mortality in severe COVID-19 date: 2020-11-05 pages: extension: .txt txt: ./txt/cord-335576-b34nc3ay.txt cache: ./cache/cord-335576-b34nc3ay.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-335576-b34nc3ay.txt' === file2bib.sh === id: cord-299605-j1ewxk4q author: Lin, Jing-wen title: Signatures of malaria-associated pathology revealed by high-resolution whole-blood transcriptomics in a rodent model of malaria date: 2017-02-03 pages: extension: .txt txt: ./txt/cord-299605-j1ewxk4q.txt cache: ./cache/cord-299605-j1ewxk4q.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-299605-j1ewxk4q.txt' === file2bib.sh === id: cord-350468-32qin4ak author: Song, Cong-Ying title: Immune dysfunction following COVID-19, especially in severe patients date: 2020-09-28 pages: extension: .txt txt: ./txt/cord-350468-32qin4ak.txt cache: ./cache/cord-350468-32qin4ak.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-350468-32qin4ak.txt' === file2bib.sh === id: cord-325405-cu4nx891 author: Luo, Lingfei title: Epidemiological and clinical differences between sexes and pathogens in a three-year surveillance of acute infectious gastroenteritis in Shanghai date: 2019-07-10 pages: extension: .txt txt: ./txt/cord-325405-cu4nx891.txt cache: ./cache/cord-325405-cu4nx891.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-325405-cu4nx891.txt' === file2bib.sh === id: cord-327405-xgtqfwyn author: Liu, Bing title: Reduced numbers of T cells and B cells correlates with persistent SARS-CoV-2 presence in non-severe COVID-19 patients date: 2020-10-19 pages: extension: .txt txt: ./txt/cord-327405-xgtqfwyn.txt cache: ./cache/cord-327405-xgtqfwyn.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-327405-xgtqfwyn.txt' === file2bib.sh === id: cord-318587-ewvnkdr2 author: Steeds, Kimberley title: Pseudotyping of VSV with Ebola virus glycoprotein is superior to HIV-1 for the assessment of neutralising antibodies date: 2020-08-31 pages: extension: .txt txt: ./txt/cord-318587-ewvnkdr2.txt cache: ./cache/cord-318587-ewvnkdr2.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-318587-ewvnkdr2.txt' === file2bib.sh === id: cord-351295-4toxlskr author: Lanave, Gianvito title: Identification of hepadnavirus in the sera of cats date: 2019-07-23 pages: extension: .txt txt: ./txt/cord-351295-4toxlskr.txt cache: ./cache/cord-351295-4toxlskr.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-351295-4toxlskr.txt' === file2bib.sh === id: cord-335055-gzuug3p5 author: Kwiyolecha, Elizabeth title: Patterns of viral pathogens causing upper respiratory tract infections among symptomatic children in Mwanza, Tanzania date: 2020-10-28 pages: extension: .txt txt: ./txt/cord-335055-gzuug3p5.txt cache: ./cache/cord-335055-gzuug3p5.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-335055-gzuug3p5.txt' === file2bib.sh === id: cord-303601-o8uk6if2 author: Tsay, Calvin title: Modeling, state estimation, and optimal control for the US COVID-19 outbreak date: 2020-07-01 pages: extension: .txt txt: ./txt/cord-303601-o8uk6if2.txt cache: ./cache/cord-303601-o8uk6if2.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-303601-o8uk6if2.txt' === file2bib.sh === /data-disk/reader-compute/reader-cord/bin/file2bib.sh: fork: retry: No child processes id: cord-313126-7hrjzapj author: Chen, Fangzhou title: Decline of transmissible gastroenteritis virus and its complex evolutionary relationship with porcine respiratory coronavirus in the United States date: 2019-03-08 pages: extension: .txt txt: ./txt/cord-313126-7hrjzapj.txt cache: ./cache/cord-313126-7hrjzapj.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-313126-7hrjzapj.txt' === file2bib.sh === id: cord-315781-dejh8q22 author: Konishi, Tomokazu title: Re-evaluation of the evolution of influenza H1 viruses using direct PCA date: 2019-12-17 pages: extension: .txt txt: ./txt/cord-315781-dejh8q22.txt cache: ./cache/cord-315781-dejh8q22.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-315781-dejh8q22.txt' === file2bib.sh === id: cord-309127-kxivgxbg author: Haverkamp, Ann-Kathrin title: Experimental infection of dromedaries with Middle East respiratory syndrome-Coronavirus is accompanied by massive ciliary loss and depletion of the cell surface receptor dipeptidyl peptidase 4 date: 2018-06-27 pages: extension: .txt txt: ./txt/cord-309127-kxivgxbg.txt cache: ./cache/cord-309127-kxivgxbg.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-309127-kxivgxbg.txt' === file2bib.sh === id: cord-276185-ysspkbj7 author: Milewska, Aleksandra title: APOBEC3-mediated restriction of RNA virus replication date: 2018-04-13 pages: extension: .txt txt: ./txt/cord-276185-ysspkbj7.txt cache: ./cache/cord-276185-ysspkbj7.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-276185-ysspkbj7.txt' === file2bib.sh === id: cord-319118-47ovbto5 author: Yu, Xiaojuan title: Structural basis for the neutralization of MERS-CoV by a human monoclonal antibody MERS-27 date: 2015-08-18 pages: extension: .txt txt: ./txt/cord-319118-47ovbto5.txt cache: ./cache/cord-319118-47ovbto5.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-319118-47ovbto5.txt' === file2bib.sh === id: cord-324696-htx0ul4o author: Chothe, Shubhada K. title: Avian and human influenza virus compatible sialic acid receptors in little brown bats date: 2017-04-06 pages: extension: .txt txt: ./txt/cord-324696-htx0ul4o.txt cache: ./cache/cord-324696-htx0ul4o.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-324696-htx0ul4o.txt' === file2bib.sh === id: cord-308687-wrzzb9cy author: Brunner, Jesse L. title: Pooled samples and eDNA-based detection can facilitate the “clean trade” of aquatic animals date: 2020-06-24 pages: extension: .txt txt: ./txt/cord-308687-wrzzb9cy.txt cache: ./cache/cord-308687-wrzzb9cy.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-308687-wrzzb9cy.txt' === file2bib.sh === id: cord-344953-gtg12hiu author: Prather, Randall S. title: Knockout of maternal CD163 protects fetuses from infection with porcine reproductive and respiratory syndrome virus (PRRSV) date: 2017-10-17 pages: extension: .txt txt: ./txt/cord-344953-gtg12hiu.txt cache: ./cache/cord-344953-gtg12hiu.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-344953-gtg12hiu.txt' === file2bib.sh === id: cord-317813-sisfxdso author: Banskar, Sunil title: Microbiome analysis reveals the abundance of bacterial pathogens in Rousettus leschenaultii guano date: 2016-11-15 pages: extension: .txt txt: ./txt/cord-317813-sisfxdso.txt cache: ./cache/cord-317813-sisfxdso.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-317813-sisfxdso.txt' === file2bib.sh === id: cord-331475-mmcu18c8 author: Sahu, Amit Ranjan title: Selection and validation of suitable reference genes for qPCR gene expression analysis in goats and sheep under Peste des petits ruminants virus (PPRV), lineage IV infection date: 2018-10-29 pages: extension: .txt txt: ./txt/cord-331475-mmcu18c8.txt cache: ./cache/cord-331475-mmcu18c8.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-331475-mmcu18c8.txt' === file2bib.sh === id: cord-329424-hmsidrc7 author: Grunwell, Jocelyn R. title: Differential type I interferon response and primary airway neutrophil extracellular trap release in children with acute respiratory distress syndrome date: 2020-11-04 pages: extension: .txt txt: ./txt/cord-329424-hmsidrc7.txt cache: ./cache/cord-329424-hmsidrc7.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-329424-hmsidrc7.txt' === file2bib.sh === id: cord-326868-3az13h1h author: Schiller, Bastian title: Temporal dynamics of resting EEG networks are associated with prosociality date: 2020-08-03 pages: extension: .txt txt: ./txt/cord-326868-3az13h1h.txt cache: ./cache/cord-326868-3az13h1h.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-326868-3az13h1h.txt' === file2bib.sh === id: cord-318314-oxlv847d author: O’Boyle, Nicky title: Differentiated ovine tracheal epithelial cells support the colonisation of pathogenic and non-pathogenic strains of Mannheimia haemolytica date: 2020-09-11 pages: extension: .txt txt: ./txt/cord-318314-oxlv847d.txt cache: ./cache/cord-318314-oxlv847d.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-318314-oxlv847d.txt' === file2bib.sh === id: cord-339973-kj56zi59 author: Coleman, Kristen K. title: Bioaerosol Sampling for Respiratory Viruses in Singapore’s Mass Rapid Transit Network date: 2018-11-30 pages: extension: .txt txt: ./txt/cord-339973-kj56zi59.txt cache: ./cache/cord-339973-kj56zi59.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-339973-kj56zi59.txt' === file2bib.sh === id: cord-315415-3aotsb2g author: Dong, Jianbo title: Development of humanized tri-specific nanobodies with potent neutralization for SARS-CoV-2 date: 2020-10-20 pages: extension: .txt txt: ./txt/cord-315415-3aotsb2g.txt cache: ./cache/cord-315415-3aotsb2g.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-315415-3aotsb2g.txt' === file2bib.sh === id: cord-342122-certy2v8 author: Ruscitti, Piero title: Pro-inflammatory properties of H-ferritin on human macrophages, ex vivo and in vitro observations date: 2020-07-22 pages: extension: .txt txt: ./txt/cord-342122-certy2v8.txt cache: ./cache/cord-342122-certy2v8.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-342122-certy2v8.txt' === file2bib.sh === id: cord-322486-qwl7nzkr author: Omori, Ryosuke title: The age distribution of mortality from novel coronavirus disease (COVID-19) suggests no large difference of susceptibility by age date: 2020-10-06 pages: extension: .txt txt: ./txt/cord-322486-qwl7nzkr.txt cache: ./cache/cord-322486-qwl7nzkr.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-322486-qwl7nzkr.txt' === file2bib.sh === id: cord-269756-tid8a464 author: Basso, Luis G. M. title: SARS-CoV fusion peptides induce membrane surface ordering and curvature date: 2016-11-28 pages: extension: .txt txt: ./txt/cord-269756-tid8a464.txt cache: ./cache/cord-269756-tid8a464.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-269756-tid8a464.txt' === file2bib.sh === id: cord-350255-tthttyl3 author: Poirier, Canelle title: The role of environmental factors on transmission rates of the COVID-19 outbreak: an initial assessment in two spatial scales date: 2020-10-12 pages: extension: .txt txt: ./txt/cord-350255-tthttyl3.txt cache: ./cache/cord-350255-tthttyl3.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-350255-tthttyl3.txt' === file2bib.sh === id: cord-317579-ige2h4pd author: Nie, Lei title: Nanostructured selenium-doped biphasic calcium phosphate with in situ incorporation of silver for antibacterial applications date: 2020-08-13 pages: extension: .txt txt: ./txt/cord-317579-ige2h4pd.txt cache: ./cache/cord-317579-ige2h4pd.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-317579-ige2h4pd.txt' === file2bib.sh === id: cord-330057-3vucm0s1 author: Franzo, Giovanni title: Phylodynamic analysis and evaluation of the balance between anthropic and environmental factors affecting IBV spreading among Italian poultry farms date: 2020-04-29 pages: extension: .txt txt: ./txt/cord-330057-3vucm0s1.txt cache: ./cache/cord-330057-3vucm0s1.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-330057-3vucm0s1.txt' === file2bib.sh === /data-disk/reader-compute/reader-cord/bin/file2bib.sh: fork: retry: No child processes id: cord-314753-xflhxb13 author: Manso, Carmen F. title: Efficient and unbiased metagenomic recovery of RNA virus genomes from human plasma samples date: 2017-06-23 pages: extension: .txt txt: ./txt/cord-314753-xflhxb13.txt cache: ./cache/cord-314753-xflhxb13.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-314753-xflhxb13.txt' === file2bib.sh === id: cord-334228-n69iewmx author: Li, Chunmei title: Conformational Flexibility of a Short Loop near the Active Site of the SARS-3CLpro is Essential to Maintain Catalytic Activity date: 2016-02-16 pages: extension: .txt txt: ./txt/cord-334228-n69iewmx.txt cache: ./cache/cord-334228-n69iewmx.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-334228-n69iewmx.txt' === file2bib.sh === id: cord-352020-9wxwktck author: Zhang, Baoshan title: A platform incorporating trimeric antigens into self-assembling nanoparticles reveals SARS-CoV-2-spike nanoparticles to elicit substantially higher neutralizing responses than spike alone date: 2020-10-23 pages: extension: .txt txt: ./txt/cord-352020-9wxwktck.txt cache: ./cache/cord-352020-9wxwktck.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-352020-9wxwktck.txt' === file2bib.sh === id: cord-351659-ujbxsus4 author: Jiang, Xiandeng title: A retrospective analysis of the dynamic transmission routes of the COVID-19 in mainland China date: 2020-08-19 pages: extension: .txt txt: ./txt/cord-351659-ujbxsus4.txt cache: ./cache/cord-351659-ujbxsus4.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-351659-ujbxsus4.txt' === file2bib.sh === id: cord-340105-471x03f9 author: Kim, Sung-Il title: Niclosamide inhibits leaf blight caused by Xanthomonas oryzae in rice date: 2016-02-16 pages: extension: .txt txt: ./txt/cord-340105-471x03f9.txt cache: ./cache/cord-340105-471x03f9.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-340105-471x03f9.txt' === file2bib.sh === id: cord-318187-c59c9vi3 author: Basu, Saikat title: Numerical evaluation of spray position for improved nasal drug delivery date: 2020-06-29 pages: extension: .txt txt: ./txt/cord-318187-c59c9vi3.txt cache: ./cache/cord-318187-c59c9vi3.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-318187-c59c9vi3.txt' === file2bib.sh === id: cord-356027-ckdx56j1 author: Zheng, Shou-Yan title: Association between secondary thrombocytosis and viral respiratory tract infections in children date: 2016-03-11 pages: extension: .txt txt: ./txt/cord-356027-ckdx56j1.txt cache: ./cache/cord-356027-ckdx56j1.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-356027-ckdx56j1.txt' === file2bib.sh === id: cord-342782-xty16m8w author: Marrugal-Lorenzo, José A. title: Repositioning salicylanilide anthelmintic drugs to treat adenovirus infections date: 2019-01-09 pages: extension: .txt txt: ./txt/cord-342782-xty16m8w.txt cache: ./cache/cord-342782-xty16m8w.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-342782-xty16m8w.txt' === file2bib.sh === id: cord-305031-9ze0097w author: Büchel, Beda title: Empirical dynamics of railway delay propagation identified during the large-scale Rastatt disruption date: 2020-10-29 pages: extension: .txt txt: ./txt/cord-305031-9ze0097w.txt cache: ./cache/cord-305031-9ze0097w.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-305031-9ze0097w.txt' === file2bib.sh === id: cord-302459-grs2x26l author: Matin, Farhana title: A Plasma Biomarker Panel of Four MicroRNAs for the Diagnosis of Prostate Cancer date: 2018-04-27 pages: extension: .txt txt: ./txt/cord-302459-grs2x26l.txt cache: ./cache/cord-302459-grs2x26l.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-302459-grs2x26l.txt' === file2bib.sh === id: cord-350957-10wcqgaq author: Shen, Zu T. title: SARS Coronavirus Fusion Peptide-Derived Sequence Suppresses Collagen-Induced Arthritis in DBA/1J Mice date: 2016-06-28 pages: extension: .txt txt: ./txt/cord-350957-10wcqgaq.txt cache: ./cache/cord-350957-10wcqgaq.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-350957-10wcqgaq.txt' === file2bib.sh === id: cord-329155-ddpfox68 author: Mindikoglu, Ayse L. title: Intermittent fasting from dawn to sunset for four consecutive weeks induces anticancer serum proteome response and improves metabolic syndrome date: 2020-10-27 pages: extension: .txt txt: ./txt/cord-329155-ddpfox68.txt cache: ./cache/cord-329155-ddpfox68.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-329155-ddpfox68.txt' === file2bib.sh === id: cord-344871-486sk4wc author: Wu, Jianping title: Biochemical and structural characterization of the interface mediating interaction between the influenza A virus non-structural protein-1 and a monoclonal antibody date: 2016-09-16 pages: extension: .txt txt: ./txt/cord-344871-486sk4wc.txt cache: ./cache/cord-344871-486sk4wc.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-344871-486sk4wc.txt' === file2bib.sh === id: cord-342676-ykog278j author: Stewart, H. title: Identification of novel RNA secondary structures within the hepatitis C virus genome reveals a cooperative involvement in genome packaging date: 2016-03-14 pages: extension: .txt txt: ./txt/cord-342676-ykog278j.txt cache: ./cache/cord-342676-ykog278j.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-342676-ykog278j.txt' === file2bib.sh === id: cord-340781-z348xbn0 author: Namvar, Ali title: In silico/In vivo analysis of high-risk papillomavirus L1 and L2 conserved sequences for development of cross-subtype prophylactic vaccine date: 2019-10-23 pages: extension: .txt txt: ./txt/cord-340781-z348xbn0.txt cache: ./cache/cord-340781-z348xbn0.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-340781-z348xbn0.txt' === file2bib.sh === id: cord-342289-zpstb7h9 author: Cui, Tingting title: Establishment of porcine enterocyte/myofibroblast co-cultures for the growth of porcine rota- and coronaviruses date: 2018-10-12 pages: extension: .txt txt: ./txt/cord-342289-zpstb7h9.txt cache: ./cache/cord-342289-zpstb7h9.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-342289-zpstb7h9.txt' === file2bib.sh === id: cord-345359-okmkgsbr author: Ohno, Marumi title: Influenza virus infection affects insulin signaling, fatty acid-metabolizing enzyme expressions, and the tricarboxylic acid cycle in mice date: 2020-07-02 pages: extension: .txt txt: ./txt/cord-345359-okmkgsbr.txt cache: ./cache/cord-345359-okmkgsbr.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-345359-okmkgsbr.txt' === file2bib.sh === id: cord-348515-bqqyly23 author: Zhao, Suhui title: Re-emergent Human Adenovirus Genome Type 7d Caused an Acute Respiratory Disease Outbreak in Southern China After a Twenty-one Year Absence date: 2014-12-08 pages: extension: .txt txt: ./txt/cord-348515-bqqyly23.txt cache: ./cache/cord-348515-bqqyly23.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-348515-bqqyly23.txt' Que is empty; done journal-sciRep-cord === reduce.pl bib === id = cord-001675-9717nzr7 author = Sugiyama, Michael G. title = The Tie2-agonist Vasculotide rescues mice from influenza virus infection date = 2015-06-05 pages = extension = .txt mime = text/plain words = 4824 sentences = 260 flesch = 47 summary = Here we demonstrate that the Tie2-agonist tetrameric peptide Vasculotide improves survival in murine models of severe influenza, even if administered as late as 72 hours after infection; the benefit was observed using three strains of the virus and two strains of mice. While the drug had no effect on human lung endothelial proliferation (Supplemental Figure 8) , it significantly attenuated lung endothelial apoptosis in vitro in response to influenza virus, as assessed by cleavage of caspase-3 (Supplemental Figure 7c ); we observed a similar reduction in cleaved caspase-3 in lungs from infected mice who received Vasculotide (Supplemental Figure 7d ). First, these data strongly implicate failure of the lung endothelial barrier as the cause of death in murine models of severe influenza, as Vasculotide conferred a significant survival benefit against multiple strains of the virus in two strains of mice. cache = ./cache/cord-001675-9717nzr7.txt txt = ./txt/cord-001675-9717nzr7.txt === reduce.pl bib === id = cord-001823-v60vv99o author = Shen, Mingwang title = Modeling the effect of comprehensive interventions on Ebola virus transmission date = 2015-10-30 pages = extension = .txt mime = text/plain words = 5364 sentences = 303 flesch = 56 summary = By fitting the model to reported cumulative cases and deaths in Guinea, Sierra Leone and Liberia until March 22, 2015, we estimate the basic reproduction number in these countries as 1.2552, 1.6093 and 1.7994, respectively. The objective of this paper is to assess the effect of all possible intervention strategies (isolation, media impact, safe burial, and vaccination) on controlling the spread of Ebola virus in Guinea, Sierra Leone, Liberia. Using the model, we evaluate the potential effect of increasing the fraction of latent individuals prior to symptoms onset, shortening the duration between symptoms onset and isolation, improving media coverage, following restrict burial procedures, and administrating timely vaccine on the epidemic of Ebola infection. If the effectiveness of isolation increases to 80%, i.e., the relative transmissibility  of isolated individuals decreases to 20% (magenta lines in Fig. 5 ), then about 35%, 65%, 60% of pre-symptomatic patients need to be detected in Guinea, Sierra Leone and Liberia to control the disease. cache = ./cache/cord-001823-v60vv99o.txt txt = ./txt/cord-001823-v60vv99o.txt === reduce.pl bib === id = cord-001712-a1sbdhhn author = Xiaokaiti, Yilixiati title = EGCG reverses human neutrophil elastase-induced migration in A549 cells by directly binding to HNE and by regulating α1-AT date = 2015-07-16 pages = extension = .txt mime = text/plain words = 5801 sentences = 333 flesch = 51 summary = title: EGCG reverses human neutrophil elastase-induced migration in A549 cells by directly binding to HNE and by regulating α1-AT The mechanism underlying this effect may include two processes: EGCG directly binds to neutrophil elastase and inhibits its enzymatic activity; EGCG enhances the expression of α1-antitrypsin by regulating the PI3K/AKT pathway. In this study, we demonstrated additional contributions of inflammation to the progression of lung cancer metastasis and a novel molecular target of EGCG, human neutrophil elastase, which induces lung cancer cell migration. 14 demonstrated that the natural polyphenol product curcumin inhibits tumor proliferation induced by neutrophil elastase via the upregulation of AAT in lung cancer. These results indicated that treatment with EGCG at a concentration between 10 and 20 μ M induces a substantial anti-migratory effect without affecting the proliferation of A549 cells exposed to neutrophil elastase. Our results showed that the neutrophil elastase-induced decrease in IRS-1 expression was significantly inhibited by EGCG in A549 cells. cache = ./cache/cord-001712-a1sbdhhn.txt txt = ./txt/cord-001712-a1sbdhhn.txt === reduce.pl bib === id = cord-001875-ulq1xqma author = Li, Jing title = Identification of climate factors related to human infection with avian influenza A H7N9 and H5N1 viruses in China date = 2015-12-11 pages = extension = .txt mime = text/plain words = 4008 sentences = 175 flesch = 50 summary = Our results represent the first step in determining the effects of climate factors on two different virus infections in China and provide warning guidelines for the future when provinces fall into the risky windows. Previously, data have indicated that environmental factors affect the prevalence of H5N1 and H7N9, with the infection and spread of the two viruses being closely correlated with bird habitats, migration, and local climate factors (e.g., temperature and relative humidity) 17 . We collected the H5N1 and H7N9 influenza data reported on the Chinese mainland from The climate dataset contained the air temperature, ground surface temperature, relative humidity, wind speed, and atmospheric pressure of all meteorological stations in the reported provinces at the reported dates for each record. Environmental factors influencing the spread of the highly pathogenic avian influenza H5N1 virus in wild birds in cache = ./cache/cord-001875-ulq1xqma.txt txt = ./txt/cord-001875-ulq1xqma.txt === reduce.pl bib === id = cord-001852-c79vwr6t author = Xiao, Qiuyan title = Prevalence and molecular characterizations of enterovirus D68 among children with acute respiratory infection in China between 2012 and 2014 date = 2015-11-16 pages = extension = .txt mime = text/plain words = 3562 sentences = 197 flesch = 56 summary = In conclusion, our results found that a history of recurrent wheezing may be a risk factor for the detection of EV-D68 and viral-induced asthma exacerbation may be a clinical feature of EV-D68 infection. In a previous hospital-based viral surveillance study of RTI cases in Chongqing, China, from 2009 to 2012, the detection rate of EV-D68 was 0.4% (7/1565) 11 . In our study, most children infected with EV-D68 had a history of recurrent wheezing or asthma and a diagnosis of acute asthma exacerbation. Our study found that a history of recurrent wheezing or asthma may be a risk factor for the detection of EV-D68 and viral-induced acute asthma exacerbation may be a clinical feature of EV-D68 infection in Chongqing area. A history of recurrent wheezing or asthma appeared to be a risk factor for the detection of EV-D68 and viral-induced acute asthma exacerbation might be a clinical feature of EV-D68 infection. cache = ./cache/cord-001852-c79vwr6t.txt txt = ./txt/cord-001852-c79vwr6t.txt === reduce.pl bib === id = cord-001116-2yvyiiuy author = Nikas, Jason B. title = Inflammation and Immune System Activation in Aging: A Mathematical Approach date = 2013-11-19 pages = extension = .txt mime = text/plain words = 4534 sentences = 199 flesch = 49 summary = Since those functions are associated with the hippocampus, I analyzed the global gene expression data from post-mortem hippocampal tissue of 25 old (age ≥ 60 yrs) and 15 young (age ≤ 45 yrs) cognitively intact human subjects. Having employed three different and independent methods of statistical significance, namely, ROC curve analysis, fold change, and P-value, I was able to identify 36 genes that were the most significant in terms of differential expression. The seven genes [C4A (C4B), ADORA3, MS4A7, BCL6, CD44, C3AR1, and HLA-DRB1], which are the constituent input variables of the model (F 1 super variable), and all of which are -in terms of function -inflammation or immune system activation genes (Table 1) , were all found to be over-expressed in the old subjects compared with the young subjects (Table 1) . cache = ./cache/cord-001116-2yvyiiuy.txt txt = ./txt/cord-001116-2yvyiiuy.txt === reduce.pl bib === id = cord-001829-rwnbxmt4 author = Lu, Yi-Fan title = IFNL3 mRNA structure is remodeled by a functional non-coding polymorphism associated with hepatitis C virus clearance date = 2015-11-04 pages = extension = .txt mime = text/plain words = 7156 sentences = 384 flesch = 48 summary = Genome-wide association studies performed on diverse patient populations have identified polymorphisms near the interferon-λ 3 (IFNL3; formerly IL28B) gene that predict the efficacy of interferon-based therapy for chronic infection. The differential effects on mRNA versus protein levels strongly suggest that the IFNL3 3′ UTR regulates gene expression by repressing the efficiency of mRNA translation rather than mRNA abundance in HeLa cells. We used polysome profiling to examine whether the variant IFNL3 reporter mRNAs were differentially associated with translating ribosomes in stable HeLa cell lines. Although rs4803217 is not independently associated with patient phenotypes in the cohort we analyzed, this SNP occurs in the 3′ UTR of IFNL3 and showed clear functional effects on reporter gene expression, suggesting a role for this variant in control of HCV infection. cache = ./cache/cord-001829-rwnbxmt4.txt txt = ./txt/cord-001829-rwnbxmt4.txt === reduce.pl bib === id = cord-001704-pdxm0iiw author = Xiong, Siping title = A Novel Chimeric Anti-PA Neutralizing Antibody for Postexposure Prophylaxis and Treatment of Anthrax date = 2015-07-02 pages = extension = .txt mime = text/plain words = 4546 sentences = 269 flesch = 55 summary = hmPA6 injection before or after LeTx administration protected all rats from developing anthrax (Fig. 6C) . In the present study, we developed four murine mAbs that could well neutralize LeTx in vitro, and one clone was selected to form a human/mouse chimeric antibody known as hmPA6. In the in vivo test in the present study, irrespective of whether LF was injected before or after hmPA6, the antibody protected the rats from death provided that it was administered before or simultaneously with PA. In summary, we reported a human/murine chimeric IgG, namely, hmPA6, which can specifically identify PA with high affinity, neutralize LeTx, and protect macrophages and F344 rats from anthrax-related death. In vitro and in vivo characterization of anthrax anti-protective antigen and anti-lethal factor monoclonal antibodies after passive transfer in a mouse lethal toxin challenge model to define correlates of immunity An anthrax lethal factor-neutralizing monoclonal antibody protects rats before and after challenge with anthrax toxin cache = ./cache/cord-001704-pdxm0iiw.txt txt = ./txt/cord-001704-pdxm0iiw.txt === reduce.pl bib === id = cord-001862-a097byk5 author = Saisawang, Chonticha title = Chikungunya nsP2 protease is not a papain-like cysteine protease and the catalytic dyad cysteine is interchangeable with a proximal serine date = 2015-11-24 pages = extension = .txt mime = text/plain words = 4515 sentences = 226 flesch = 50 summary = The proteolytic activity of nsP2 has been characterized in other alphaviruses, such as Sindbis virus (SINV), Semliki forest virus (SFV) and Venezuelan Equine Encephalitis virus (VEEV), as a papain-like cysteine protease with a cysteine-histidine catalytic dyad in the active site 11, 12, [16] [17] [18] [19] . Although the dyad residues have been identified previously in other alphavirus nsP2 proteins; in SINV, SFV and VEEV 11, 12, [16] [17] [18] , the CHIKV nsP2 protease active site has not been experimentally characterized. In performing this study a structural comparison showed that CHIKV nsP2 protease is not papain-like, and we have found what appears to be a unique feature of CHIKV nsP2 protease, in which the cysteine dyad residue can be catalytically replaced by a vicinal serine. In our study the protease inhibitors leupeptin and E-64 showed little to no effect on wild type, Cys478Ala and Ser482Ala enzyme activities for all 3 substrates (Table 2) . cache = ./cache/cord-001862-a097byk5.txt txt = ./txt/cord-001862-a097byk5.txt === reduce.pl bib === id = cord-002673-5a1rfi6k author = Knibb, Wayne title = Regional genetic diversity for NNV grouper viruses across the Indo-Asian region – implications for selecting virus resistance in farmed groupers date = 2017-09-06 pages = extension = .txt mime = text/plain words = 6692 sentences = 298 flesch = 48 summary = This study uses statistical approaches and assessment of "characteristic attributes" (i.e. nucleotide positions that discriminate among strains) to assess whether published and new NNV RNA2 cds sequences show genetic differentiation over geography, host species and years. Within the red spotted grouper nervous necrosis virus (RGNNV) strain, to which all Asian grouper NNV belong, however, no one so far has reported evidence of genetic subgrouping by region, species or year in a formal statistical manner, especially when we restrict hosts just to Asian grouper. The goal of this report was to collate the most comprehensive data set to date on NNV RNA2 sequences for warm water Asian marine finfish, whether published and/or lodged in Genbank over the last 20 years, including some sequence data produced by our group for Vietnamese and Taiwanese grouper, to statistically test the data for evidence of NNV strain variation that associates with geography, host species and year and also to determine whether there are "characteristic attributes" that indicate regional (or host, year) specific differences among the strains. cache = ./cache/cord-002673-5a1rfi6k.txt txt = ./txt/cord-002673-5a1rfi6k.txt === reduce.pl bib === id = cord-002312-jyk7f8hz author = Branton, W. G. title = Brain microbiota disruption within inflammatory demyelinating lesions in multiple sclerosis date = 2016-11-28 pages = extension = .txt mime = text/plain words = 4611 sentences = 231 flesch = 41 summary = Massively parallel (deep) sequencing (RNAseq) of total RNA permitted analysis of all RNA sequences in MS (n = 6) and nonMS (n = 6) white matter samples, revealing that bacterial RNA (ribosomal and non-ribosomal) sequences were detected in all nonMS and MS brain specimens, including MS patients with relapsing-remitting disease (receiving disease modifying therapy) (RR-MS, n = 3) and progressive (untreated) MS (P-MS; n = 3) ( Fig. 2A) . The current study shows the presence of bacterial RNA and DNA sequences and proteins in human brain which are disrupted in conjunction with inflammatory demyelination in patients with MS. The present studies revealed the ratio of bacterium-encoded 16s rDNA to rRNA in matched brain samples to be ~1:2 in both white matter (and cortex, data not shown) with bacterial numbers of 1200-1400 genomes/cm 3 suggesting both bacterial burden and replication were low compared to active pathogenic infections in other tissues. cache = ./cache/cord-002312-jyk7f8hz.txt txt = ./txt/cord-002312-jyk7f8hz.txt === reduce.pl bib === id = cord-002110-pbb247lp author = Chen, Chin-Pei title = Membrane protein assembly: two cytoplasmic phosphorylated serine sites of Vpu from HIV-1 affect oligomerization date = 2016-06-29 pages = extension = .txt mime = text/plain words = 5987 sentences = 327 flesch = 60 summary = title: Membrane protein assembly: two cytoplasmic phosphorylated serine sites of Vpu from HIV-1 affect oligomerization Coarse-grained molecular dynamic simulations with models of wild-type and mutant Vpu in a hydrated lipid bilayer supported the experimental data in demonstrating that, in addition to a previously known role in downregulation of host factors, the phosphorylation sites of Vpu also modulate oligomerization. Coarse grained molecular dynamics (CGMD) simulations of Vpu proteins embedded in a planar lipid bilayer model were chosen to evaluate the oligomeric assembly under likely in vivo conditions such as an abundance of Vpu proteins in a large lipid patch and simulated over a long time period. The dynamics data was plotted as area of the peak of the higher oligomer (A P1 ), divided by the total area of A P1 and the peak area of the dimer (A P2 ), A P1 /(A P1 + A P2 ), over time for Vpu-WT with a double logarithmic growth curve (Fig. 4b , black and Table 2 ). Three-dimensional structure of the channel-forming trans-membrane domain of virus protein "u" (Vpu) from HIV-1 cache = ./cache/cord-002110-pbb247lp.txt txt = ./txt/cord-002110-pbb247lp.txt === reduce.pl bib === id = cord-001858-nmi39n6h author = Petriccione, Milena title = Reference gene selection for normalization of RT-qPCR gene expression data from Actinidia deliciosa leaves infected with Pseudomonas syringae pv. actinidiae date = 2015-11-19 pages = extension = .txt mime = text/plain words = 5567 sentences = 286 flesch = 50 summary = title: Reference gene selection for normalization of RT-qPCR gene expression data from Actinidia deliciosa leaves infected with Pseudomonas syringae pv. Primer sequence (5′-3′) BestKeeper and the deltaCt method) were used to evaluate the stability of expression of selected RGs. The analyses were performed for three comparison groups considering both low-and high-dose bacterial inocula in the leaves and their combined dataset. In kiwifruit leaves with a high dose of bacterial inoculum, BestKeeper revealed that only the expression of TUB overcame the stability threshold; CYP and GAPDH were considered to be the most stable genes, with SD values of 0.50 and 0.61, respectively (Table 3 ). The expression of three genes encoding the reactive oxygen species (ROS) scavenging enzymes ascorbate peroxidase (APX), superoxide dismutase (SOD) and catalase (CAT), induced during the systemic infection of kiwifruit leaves with PSA, were chosen to further validate the reliability of the selected RGs for the normalization of RT-qPCR data. cache = ./cache/cord-001858-nmi39n6h.txt txt = ./txt/cord-001858-nmi39n6h.txt === reduce.pl bib === id = cord-001522-82plcxv9 author = Xu, Zhiwei title = Exploration of diarrhoea seasonality and its drivers in China date = 2015-02-04 pages = extension = .txt mime = text/plain words = 3337 sentences = 161 flesch = 47 summary = In this study, we reviewed the data on ''other infectious diarrhoea'' in China from 2005-2012 obtained from CISDCP, aiming to characterize the seasonality of diarrhoea in China and identify its potential drivers, as well as explore potential opportunities for future diarrhoea control and prevention. In terms of the amplitude distribution by age and region (seasonal amplitude refers to the relative fluctuation of diarrhoea within a certain period of time, and it provides pivotal information on the possibility of diarrhoea outbreaks), we found that adults (.515 years) had much greater diarrhoea amplitudes than children (,15 years) (Figure 4 ), but the amplitude in persons .520 years declined progressively with increasing age, reaching its valley in elderly .585 years (Figure 4) , and this decreasing trend was remarkably consistent across years ( Figure S4 (supplementary material)). Demographic, economic, geographic and climate information in all 31 provinces from 2005 to 2012, including population, per capita gross regional product (PGRP), latitude, longitude, monthly average mean temperature, monthly average relative humidity, and monthly average rainfall, were collected from China Statistical Yearbook 27 to identify the putative drivers of diarrhoea seasonality. cache = ./cache/cord-001522-82plcxv9.txt txt = ./txt/cord-001522-82plcxv9.txt === reduce.pl bib === id = cord-002081-vi6rth9o author = Zhang, Chao title = Establishment and application of a real-time loop-mediated isothermal amplification system for the detection of CYP2C19 polymorphisms date = 2016-06-01 pages = extension = .txt mime = text/plain words = 3387 sentences = 211 flesch = 49 summary = In this work, a rapid one-step SNP detection method, real-time loop-mediated isothermal amplification (RT-LAMP), was first applied for CYP2C19 polymorphisms testing. The optimized method was established with specifically designed primers for target amplification by real-time detection in approximately 30 min under isothermal conditions. The successful establishment of an inexpensive, rapid and real-time LAMP protocol for CYP2C19*2 and CYP2C19*3 detection is significant for the extension of this technique for genotyping other SNPs. Our results suggest applications for this RT-LAMP assay system for both basic research and clinical diagnosis in pharmacogenomics. In this study, the successful establishment of an inexpensive, rapid and real-time LAMP protocol for CYP2C19 SNP genotyping expanded the scope of application of this technique to human gene mutation detection. In summary, as a rapid, feasible and cost-efficient point-of-care (POC) SNP detection method, we demonstrated that RT-LAMP could quantitatively detect human genomic DNA with high specificity and sensitivity in a single step. cache = ./cache/cord-002081-vi6rth9o.txt txt = ./txt/cord-002081-vi6rth9o.txt === reduce.pl bib === id = cord-001901-2s6hpakk author = Kwok, Hoi-Hin title = Anti-inflammatory effects of indirubin derivatives on influenza A virus-infected human pulmonary microvascular endothelial cells date = 2016-01-06 pages = extension = .txt mime = text/plain words = 3922 sentences = 254 flesch = 44 summary = title: Anti-inflammatory effects of indirubin derivatives on influenza A virus-infected human pulmonary microvascular endothelial cells In this report, we examined the potential immunomodulatory effects of two indirubin derivatives, indirubin-3′-(2,3-dihydroxypropyl)-oximether (E804) and indirubin-3′-oxime (E231), on IAV (H9N2) infected-human pulmonary microvascular endothelial cells (HPMECs). Using specific inhibitors or small-interfering RNA, we confirmed that indirubin derivatives can suppress H9N2-induced cytokines production through MAPKs and STAT3 signaling pathways. To detect the activity of individual MAPKs after treatment with IAV and indirubin derivatives, the non-radioactive In vitro protein kinase assay kit from Cell Signaling Technology was used. In this study, we found that the infection of influenza A virus subtype A/Quali/Hong Kong/G1/97 (H9N2) on HPMECs induced excessive production of various pro-inflammatory cytokines and chemokines, including IP-10 ( In this report, we demonstrated that indirubin derivatives, particularly E804 is a potent immunomodulatory compound for IAV-infection in vitro by inhibiting intracellular signaling pathways in pulmonary endothelial cells. cache = ./cache/cord-001901-2s6hpakk.txt txt = ./txt/cord-001901-2s6hpakk.txt === reduce.pl bib === id = cord-002758-d86hnox1 author = Opuu, Vaitea title = Computational design of fully overlapping coding schemes for protein pairs and triplets date = 2017-11-20 pages = extension = .txt mime = text/plain words = 5501 sentences = 303 flesch = 64 summary = We have examined the possibility to encode an arbitrary pair of protein domains as a dual gene, with the shorter coding sequence completely embedded in the longer one. An example of a designed overlapping gene was produced recently, where each DNA strand coded for a simplified but functional aminoacyl-tRNA synthetase "Urzyme" [13] [14] [15] [16] , with the two enzymes being homologous to the two modern synthetase classes. Considering all three reading frames, we found that over 16% of the (X, Y) pairs have homologous pairs (X′, Y′) that can be encoded in a fully overlapping manner, with a level of X/X′ and Y/Y′ homology corresponding to Blast E-values of 10 −10 or less and a match length of at least 85% of the total sequence length. Given the level of success and the generality of our algorithm, we also designed 200 triple genes, with three proteins encoded by the same DNA segment using both strands and three different reading frames. cache = ./cache/cord-002758-d86hnox1.txt txt = ./txt/cord-002758-d86hnox1.txt === reduce.pl bib === id = cord-002373-rueg4gsj author = Huang, Ao title = Quantitative Fluorescence Quenching on Antibody-conjugated Graphene Oxide as a Platform for Protein Sensing date = 2017-01-13 pages = extension = .txt mime = text/plain words = 3674 sentences = 203 flesch = 54 summary = Then, analyte IgG proteins in increasing concentrations were added to a set of buffer solutions containing antibody-conjugated GO. As the number density of the binding sites was limited on the modified GO, more adsorbed analyte IgG proteins resulted in a stronger fluorescence signal from free IgG-FITCs in the solutions. Therefore, there is a positive and quantitative correlation between the analyte IgG concentration and the fluorescence intensity of free IgG-FITCs. According to this principle, our assay relies on the effectiveness of GO as an energy acceptor to provide efficient fluorescence quenching. The experiment was repeated 4 times, and the average of the results was plotted in Fig. 4(a) , from which we can see the assay's fluorescence signal increased readily with the increasing analyte IgG concentration. We established an immunosensor platform based on quantitative fluorescence quenching between fluorescein-labelled antigens and antibody-conjugated GO nanosheets, a process controlled quantitatively by the concentration of analyte proteins. cache = ./cache/cord-002373-rueg4gsj.txt txt = ./txt/cord-002373-rueg4gsj.txt === reduce.pl bib === id = cord-002111-mmpijsqb author = Philp, Lisa K. title = Small Glutamine-Rich Tetratricopeptide Repeat-Containing Protein Alpha (SGTA) Ablation Limits Offspring Viability and Growth in Mice date = 2016-06-30 pages = extension = .txt mime = text/plain words = 7064 sentences = 399 flesch = 53 summary = title: Small Glutamine-Rich Tetratricopeptide Repeat-Containing Protein Alpha (SGTA) Ablation Limits Offspring Viability and Growth in Mice Small glutamine-rich tetratricopeptide repeat-containing protein α (SGTA) has been implicated as a co-chaperone and regulator of androgen and growth hormone receptor (AR, GHR) signalling. As some, but not all, androgen-regulated organs displayed potential signs of hyperandrogenisation during development in Sgta +/− and Sgta −/− mutants, we measured Ar mRNA expression in androgen-regulated tissues, the brain, and the prostate and testis in males, and the mammary and ovary in females (Fig. 4C) . However, the relative weights of vital and sex organs, adipose tissue, muscle and bone were not affected by a genotype* age interaction, suggesting that Sgta-null mice are not any more vulnerable to age-related stress than WT. Small glutamine-rich tetratricopeptide repeat-containing protein (SGT) interacts with the ubiquitin-dependent endocytosis (UbE) motif of the growth hormone receptor cache = ./cache/cord-002111-mmpijsqb.txt txt = ./txt/cord-002111-mmpijsqb.txt === reduce.pl bib === id = cord-002072-qbh728ec author = Bi, Yuhai title = A new reassortment of influenza A (H7N9) virus causing human infection in Beijing, 2014 date = 2016-05-27 pages = extension = .txt mime = text/plain words = 3096 sentences = 170 flesch = 48 summary = Genetic and phylogenetic analyses revealed that the virus belonged to a novel genotype, which probably emerged and further reassorted with other H9 or H7 viruses in poultry before transmitting to humans. The IFN-induced transmembrane protein-3 (IFITM3) C/C genotype was reported to be associated with severe clinical outcomes, as reflected by a higher viral load, more rapid progression to ARDS, higher cytokine/chemokine levels, and an increased mortality rate after H7N9 infection 22 . Although this was a severe H7N9-infected case with cytokine storm-like appearances and multiple organ failure, the patient was eventually cured after combination therapy with antivirals, mechanical ventilation, supportive nutrition and symptomatic treatment. Clinical, virological and immunological features from patients infected with re-emergent avian-origin human H7N9 influenza disease of varying severity in Guangdong province Cytokine and chemokine levels in patients infected with the novel avian influenza A (H7N9) virus in China cache = ./cache/cord-002072-qbh728ec.txt txt = ./txt/cord-002072-qbh728ec.txt === reduce.pl bib === id = cord-002490-kw8psrmz author = Beniac, Daniel R. title = Structure of the Ebola virus glycoprotein spike within the virion envelope at 11 Å resolution date = 2017-04-11 pages = extension = .txt mime = text/plain words = 4053 sentences = 184 flesch = 53 summary = We present the structure of the surface Ebola virus (EBOV) trimeric glycoprotein (GP) spike at 11 Å resolution, in situ within the viral plasma membrane of purified virus particles. In addition, 29,976 images were selected for reference-free analysis of the half-diameter of EBOV to investigate the spatial distribution of the GP spikes, as well as the periodicity and symmetrical relationships between GP and the matrix protein VP40 in the envelope, and the underlying nucleocapsid layer (Figs 1c and S3) . The spike structure of Beniac et al imaged within the virus-like particles was somehow clipped, since this should have included the mucin-like domains: in addition, tomography was combined with single-particle analysis, which may have distorted the results 4 . The structure that we report here is based entirely on the well-accepted method of single-particle analysis using projection matching, and is broadly similar to that published of expressed GP in virus-like particles using tomography 28, 29 : there are noticeable differences in shape and size of the spike, as well as in resolution (Fig. 4) . cache = ./cache/cord-002490-kw8psrmz.txt txt = ./txt/cord-002490-kw8psrmz.txt === reduce.pl bib === id = cord-002290-wvo22jx2 author = Liu, Cheng title = Association of Mannose-binding Lectin Polymorphisms with Tuberculosis Susceptibility among Chinese date = 2016-11-04 pages = extension = .txt mime = text/plain words = 3772 sentences = 201 flesch = 48 summary = In this study four functional single-nucleotide polymorphisms (SNPs, H/L, X/Y, P/Q and A/B) across the MBL2 gene were genotyped by direct DNA sequencing of PCR products in a case-control population of Chinese Han origin, consisting of 1,020 patients with pulmonary TB and 1,020 controls. In 1,020 controls, this distribution was 723 (70.9%), 234 (22.9%) and 63 (6.2%), respectively (OR = 1.56, 95% CI 1.29-1.90, P = 1.4 × 10 −6 , with adjustment for age and gender; simulation number = 10,000,000; Table 2 ), implicating that the individuals bearing medium or low expression haplotype pairs had an increased risk of TB and that the MBL deficiency might play a potential role in susceptibility to TB. In this study, we investigated all of the four functional SNPs in the MBL2 gene, individually or in haplotype or haplotype pairs, in a large case-control population of Chinese Han origin, totally consisting of 1,020 patients with TB and 1,020 controls. cache = ./cache/cord-002290-wvo22jx2.txt txt = ./txt/cord-002290-wvo22jx2.txt === reduce.pl bib === id = cord-002369-shk4n8f6 author = Fahmy, Ahmed M. title = The autophagy elongation complex (ATG5-12/16L1) positively regulates HCV replication and is required for wild-type membranous web formation date = 2017-01-09 pages = extension = .txt mime = text/plain words = 6131 sentences = 355 flesch = 50 summary = The expression of HCV proteins results in the induction of a major rearrangement of host cell membranes, thus leading to the formation of a complex membranous compartment termed the membranous web (MW), which favors viral RNA replication and assembly 3, 4 . To determine whether LC3 or the ATG5-12 conjugate modulates HCV RNA replication, we analyzed the effects of silencing these autophagy genes on viral RNA replication in Huh7 cells stably expressing the JFH1 subgenomic replicon (SGR). Because silencing of LC3 expression led to a clear inhibition of HCV RNA translation after electroporation of the viral RNA but did not significantly affect replication in JFH1-SGR cells, we sought to compare the effect of siRNA treatment before and after infection with HCVcc JFH1 (Fig. 3C) . The autophagy elongation complex proteins (ATG5-12 and ATG16L1) were also detected in the purified MW from NS4B HA replicon cells, but not in the control extract, thus indicating that the elongation complex is indeed present at the HCV replication site. cache = ./cache/cord-002369-shk4n8f6.txt txt = ./txt/cord-002369-shk4n8f6.txt === reduce.pl bib === id = cord-002720-lrkscs71 author = Kurosaki, Yohei title = Development and evaluation of a rapid molecular diagnostic test for Zika virus infection by reverse transcription loop-mediated isothermal amplification date = 2017-10-18 pages = extension = .txt mime = text/plain words = 4950 sentences = 251 flesch = 55 summary = title: Development and evaluation of a rapid molecular diagnostic test for Zika virus infection by reverse transcription loop-mediated isothermal amplification The assay detected viral RNA at 14.5 TCID(50)/mL in virus-spiked serum or urine samples within 15 min, although it was slightly less sensitive than reference real time RT-PCR assay. We then evaluated the utility of this assay as a molecular diagnostic test using 90 plasma or serum samples and 99 urine samples collected from 120 suspected cases of arbovirus infection in the states of Paraíba and Pernambuco, Brazil in 2016. Therefore, it is difficult to detect ZIKV in blood samples from patients after the acute phase of infection, even with sensitive molecular diagnostic methods, such as reverse transcription-polymerase chain reaction (RT-PCR) 14, 18, 19 . These results suggested that the RT-LAMP assay could be used as a rapid, sensitive diagnostic test for ZIKV, the Tp value (i.e., less than 15 min) can be used as an indicator of the number of RNA copies in each reaction. cache = ./cache/cord-002720-lrkscs71.txt txt = ./txt/cord-002720-lrkscs71.txt === reduce.pl bib === id = cord-002782-mena480g author = Chen, Jiajia title = Long term outcomes in survivors of epidemic Influenza A (H7N9) virus infection date = 2017-12-08 pages = extension = .txt mime = text/plain words = 3021 sentences = 179 flesch = 55 summary = Our findings suggest that pulmonary function and imaging findings improved during the first 6 months especially for those with ARDS, however long-term lung disability and psychological impairment in H7N9 survivors persisted at 2 years after discharge from the hospital. In survivors of H5N1 virus infection, radiologic abnormalities including ground-glass opacities with a reticular pattern remained evident at the 12-month follow-up visit 10 . A study of the long-term outcomes of survivors with ARDS reported a mild restrictive pattern on lung-function testing, with a mild-to-moderate reduction in carbon monoxide diffusion capacity at 3 months; The median DLCO improved by 9% of the predicted value from 3 to 12 months 13 . A meta-analysis showed that recovery in the HRQoL of ARDS survivors occurred during the first 6 months after discharge 20 , but no significant improvement was evident at the 2-year follow-up in our study. Follow-up study on pulmonary function and lung radiographic changes in rehabilitating severe acute respiratory syndrome patients after discharge cache = ./cache/cord-002782-mena480g.txt txt = ./txt/cord-002782-mena480g.txt === reduce.pl bib === id = cord-003055-88q36g00 author = Imai, Kenji title = Administration of molecular hydrogen during pregnancy improves behavioral abnormalities of offspring in a maternal immune activation model date = 2018-06-15 pages = extension = .txt mime = text/plain words = 6212 sentences = 313 flesch = 41 summary = The aim of the present study was to investigate long-term outcomes of the offspring in a lipopolysaccharide (LPS)-induced maternal immune activation (MIA) model and the effect of maternal molecular hydrogen (H(2)) administration. We have previously demonstrated in the MIA mouse model that maternal administration of H(2) attenuates oxidative damage and neuroinflammation, including induced pro-inflammatory cytokines and microglial activation, in the fetal brain. Since MIA has been considered to be a cause of behavioral abnormalities in offspring, including ASD/ Schizophrenia-like behavior, we subsequently evaluated the effect of LPS and maternal administration of HW on short-term memory, sociability, social novelty, and sensorimotor gating. Based on those findings, we subsequently performed Nissl staining and evaluated the number of neurons in the amygdala, cerebral cortex, and hippocampus to investigate the brain regions related to the results of the behavioral deficits induced by LPS exposure. cache = ./cache/cord-003055-88q36g00.txt txt = ./txt/cord-003055-88q36g00.txt === reduce.pl bib === id = cord-002644-yzan95du author = Ren, Rongrong title = The H7N9 influenza A virus infection results in lethal inflammation in the mammalian host via the NLRP3-caspase-1 inflammasome date = 2017-08-08 pages = extension = .txt mime = text/plain words = 5599 sentences = 371 flesch = 58 summary = Thus, our study reveals that the NLRP3 inflammasome is deleterious for the host during H7N9 infection in mice, which is due to an overwhelming inflammatory response via caspase-1 activation and associated IL-1 signal. To note, the production of above mentioned cytokines and chemokines from Nlrp3 −/− mice showed a similar pattern as that from Casp1/11 −/− mice (Fig. 5b) , indicating that deficiency of NLRP3 inflammasome genes reduced the secretion of several critical proinflammatory mediators in the lung of mice upon H7N9 IAV challenge. Pathology analysis showed that there were inflammatory responses in the infected lungs of all strains of mice, both at 3 d.p.i and at 7 d.p.i; and the pulmonary inflammations at 7 d.p.i. were more severe than that at 3 d.p.i.; moreover, the pulmonary inflammations of the WT mice were stronger than Casp1/11 −/− , Asc −/− and Nlrp3 −/− mice (Figs 3 and 7) . cache = ./cache/cord-002644-yzan95du.txt txt = ./txt/cord-002644-yzan95du.txt === reduce.pl bib === id = cord-001963-4wjvykx7 author = Liu, Chia-Lin title = Using mutagenesis to explore conserved residues in the RNA-binding groove of influenza A virus nucleoprotein for antiviral drug development date = 2016-02-26 pages = extension = .txt mime = text/plain words = 5457 sentences = 304 flesch = 56 summary = title: Using mutagenesis to explore conserved residues in the RNA-binding groove of influenza A virus nucleoprotein for antiviral drug development By interrupting the stacking interaction between Y148 and an RNA base, we identified an influenza virus NP inhibitor, (E, E)-1,7-bis(4-hydroxy-3-methoxyphenyl) -1,6-heptadiene-3,5-dione; this inhibitor reduced the NP's RNA-binding affinity and hindered viral replication. As shown in Fig. 7A , upon H7 treatment at 15μM, the M1 viral RNA synthesis in the influenza virus-infected cells was reduced by 75% at T2. NP is the most abundant RNA-binding viral protein in influenza virus-infected cells and is responsible for recognizing RNA and forming a filamentous nucleocapsid 24 . Using fluorescence titration and an SPR assay of the NPs, we identified one potential natural compound, curcumin (H7), that targets Y148 of influenza virus NP and potently interferes with its RNA-binding activity. cache = ./cache/cord-001963-4wjvykx7.txt txt = ./txt/cord-001963-4wjvykx7.txt === reduce.pl bib === id = cord-002258-o9azey3m author = Chan, Louisa L. Y. title = Evaluation of the human adaptation of influenza A/H7N9 virus in PB2 protein using human and swine respiratory tract explant cultures date = 2016-10-14 pages = extension = .txt mime = text/plain words = 5656 sentences = 278 flesch = 52 summary = In this study, we evaluated the role of amino acid substitution PB2-627K or compensatory changes at PB2-591K and PB2-701N, on the tropism and replication competence of H7N9 viruses for human and swine respiratory tracts using ex vivo organ explant cultures. There were very limited influenza antigen positive cells in the rgPB2-K627E + Q591K and rgPB2-K627E + D701N inoculated ex vivo culture of human bronchus (Fig. 2C ) while more infected cells were shown in these mutant viruses infected lung tissues (Fig. 2D ). In this study, we evaluated the effects of PB2-E627K mutation as well as two mammalian adaptation markers, PB2-Q591K and D701N on H7N9 virus replication competence in ex vivo cultures of human and swine respiratory tracts and in vitro cultures of human primary ATI and PMφ . Tropism and innate host responses of a novel avian influenza A H7N9 virus: an analysis of ex-vivo and in-vitro cultures of the human respiratory tract cache = ./cache/cord-002258-o9azey3m.txt txt = ./txt/cord-002258-o9azey3m.txt === reduce.pl bib === id = cord-002932-5e7xrd1y author = Watanabe, Tokiko title = Experimental infection of Cynomolgus Macaques with highly pathogenic H5N1 influenza virus through the aerosol route date = 2018-03-19 pages = extension = .txt mime = text/plain words = 4497 sentences = 212 flesch = 44 summary = In the ferret model, these studies demonstrated that the inoculation of animals with highly pathogenic avian influenza H5N1 virus via the aerosol route led to higher nasal wash virus titers, earlier onset of clinical signs, and/or a broader spectrum of disease compared with infection via intranasal inoculation despite no difference in lethality [9] [10] [11] . On day 3 post-infection, VN3040 virus was recovered from nasal swabs of two and three animals in the conventional and aerosol method groups, respectively, and the mean virus titers were comparable between the two groups. Cynomolgus macaques were inoculated with 4 ml of a 10 7 PFU/ml solution of the highly pathogenic H5N1 avian influenza virus A/Vietnam/ UT3040/2004 strain (VN3040) through the aerosol route by using the ultrasonic nebulizer NE-U17 (defined as "the aerosol method group"). In contrast, VN3040 replicated well in the right-and left-lower lung lobes of the infected animals in the conventional method group [the virus mean titers were 3.51 and 4.75 log 10 (PFU/g), respectively]. cache = ./cache/cord-002932-5e7xrd1y.txt txt = ./txt/cord-002932-5e7xrd1y.txt === reduce.pl bib === id = cord-002844-jv42o789 author = Marcos-Villar, Laura title = Epigenetic control of influenza virus: role of H3K79 methylation in interferon-induced antiviral response date = 2018-01-19 pages = extension = .txt mime = text/plain words = 6091 sentences = 308 flesch = 43 summary = These results indicate that epigenetic modifications induced by influenza virus infection mainly target the histone component of host cell chromatin, with H3K79 residue methylation the most frequently modified. Dot1L inhibition caused an increase in viral replication, higher in cells infected with the natural isolates, which suggests a general role of H3K79 methylation in control of the influenza virus life cycle. At 8 h, we found a weak increase on IFNβ, IFN-stimulated gene 56 (ISG56) and interferon-induced protein Mx1 (Mx1) RNA levels after IFNαβ addition or influenza virus infection, and Dot1L inhibitor treatment did not significantly decreased their accumulation (Fig. 6B,C) . Given the role of H3K79 methylation in the control of IFN signaling, we analyzed the effect of Dot1L inhibitor on influenza virus replication in cells with normal or deficient IFN responses. Since H3K79 methylation does not affect influenza virus replication in cells with impaired IFN signaling, we analyzed the effect of Dot1L inhibitor in subsequent stages of viral infection. cache = ./cache/cord-002844-jv42o789.txt txt = ./txt/cord-002844-jv42o789.txt === reduce.pl bib === id = cord-004181-exbs3tz7 author = Pumchan, Ansaya title = Novel Chimeric Multiepitope Vaccine for Streptococcosis Disease in Nile Tilapia (Oreochromis niloticus Linn.) date = 2020-01-17 pages = extension = .txt mime = text/plain words = 5769 sentences = 291 flesch = 42 summary = The efficacy of the chimeric multiepitope construct as a recombinant protein vaccine and DNA vaccine was evaluated in Nile tilapia, followed by S. The epitopes of immunogenic proteins were predicted by the BCPREDS server based on B cell epitopes to be used in chimeric multiepitope vaccine construction. In this study, not only immunogenic proteins from the immunoproteomics analysis were used but also other subunit vaccine candidates were subjected to epitope prediction and combined to produce a chimeric multiepitope vaccine. The recombinant chimeric multiepitope protein vaccination showed that 45F2 and 42E2 produced cumulative mortality rates of 30.00 ± 10.00% and 26.67 ± 5.77%, respectively, which were significantly lower than those of the negative control group, at 70% (P < 0.05) (Fig. 6A) . agalactiae serotype Ia and III demonstrated that fish vaccinated with recombinant protein vaccine 42E2 and 45F2 showed cross-reactivity to whole cell lysate of S. cache = ./cache/cord-004181-exbs3tz7.txt txt = ./txt/cord-004181-exbs3tz7.txt === reduce.pl bib === id = cord-002177-yyfgl9x5 author = Guo, Jinyue title = TGEV infection up-regulates FcRn expression via activation of NF-κB signaling date = 2016-08-24 pages = extension = .txt mime = text/plain words = 5211 sentences = 315 flesch = 52 summary = Furthermore, treatment of TGEV-infected IPEC-J2 cells with the NF-κB-specific inhibitor BAY 11-7082 resulted in down-regulation of pFcRn expression. We identified four NF-κB transcription factor binding sites in the promoter region of this gene using luciferase reporter system, chromatin immunoprecipitation, electromobility shift assay, and supershift analysis. In the present study, we investigated how TGEV infection activated the NF-κ B pathway in vitro and up-regulated pFcRn expression in IPEC-J2 cells. Furthermore, pFcRn expression induced by TGEV infection was strongly reduced by the NF-κ B-specific inhibitor BAY 11-7082 in IPEC-J2 cells (Fig. 3) . Transient transfection of the pFcRn promoter luciferase reporter plasmids revealed that pFcRn-luc-(1-3) plasmids resulted in increased promoter activity in the presence of TGEV infection (Fig. 4B) , further demonstrating that TGEV up-regulates pFcRn expression in IPEC-J2 cells. In summary, TGEV infection up-regulates pFcRn expression in IPEC-J2 cells, and activates the NF-κ B signaling pathway. cache = ./cache/cord-002177-yyfgl9x5.txt txt = ./txt/cord-002177-yyfgl9x5.txt === reduce.pl bib === id = cord-002408-bbtslrrt author = Almogy, Gal title = Analysis of Influenza and RSV dynamics in the community using a ‘Local Transmission Zone’ approach date = 2017-02-09 pages = extension = .txt mime = text/plain words = 5450 sentences = 246 flesch = 54 summary = We demonstrate that this urban area is not a single, perfectly mixed ecology, but is in fact comprised of a set of more basic, relatively independent pathogen transmission units, which we term here Local Transmission Zones, LTZs. By identifying these LTZs, and using the dynamic pathogen-content information contained within them, we are able to differentiate between disease-causes at the individual patient level often with near-perfect predictive accuracy. To investigate the possibility of LTZs in a large regional area, we analyze clinical data from a healthcare medical center in the city of Jerusalem, containing the clinical test results for Influenza virus and Respiratory Syncytial Virus (RSV) from patients presenting with ILI symptoms. Our analysis finds that while Influenza and RSV incidences tend to overlap and show more or less equal number of cases over the whole region, individual LTZs show a far more homogeneous disease content at most given times, with some being dominated by RSV while others by Influenza. cache = ./cache/cord-002408-bbtslrrt.txt txt = ./txt/cord-002408-bbtslrrt.txt === reduce.pl bib === id = cord-002320-m99amd4y author = Mathur, Kalika title = Analysis of chikungunya virus proteins reveals that non-structural proteins nsP2 and nsP3 exhibit RNA interference (RNAi) suppressor activity date = 2016-11-30 pages = extension = .txt mime = text/plain words = 5671 sentences = 338 flesch = 56 summary = Systematic analysis of all CHIKV proteins using a Sf21 RNAi sensor cell line based assay revealed that non-structural proteins nsP2 and nsP3 exhibited RNAi suppressor activity. Using cell lysate of the transfected cell expressing nsP2 and nsP3, we evaluated their ability to bind double stranded RNA by using [γ 32P] labeled shRNA of GFP and running the bound complex in a 6% polyacrylamide gel (Fig. 3e) . Having confirmed that both nsP2 and nsP3 exhibit RNAi suppressor activities, efforts were taken to characterise the proteins better and to identify those specific domains that were and NS4B (dengue virus) were taken as positive controls and empty vector was used as negative control. Taken together, the current study has identified CHIKV proteins nsP2 and nsP3 to exhibit RNAi suppressor activity in the in-vitro system that was further demonstrated in its natural hosts, namely, an Aedes and mammalian cell line. cache = ./cache/cord-002320-m99amd4y.txt txt = ./txt/cord-002320-m99amd4y.txt === reduce.pl bib === id = cord-002474-2l31d7ew author = Lv, Yang title = Actual measurement, hygrothermal response experiment and growth prediction analysis of microbial contamination of central air conditioning system in Dalian, China date = 2017-04-03 pages = extension = .txt mime = text/plain words = 4938 sentences = 270 flesch = 51 summary = title: Actual measurement, hygrothermal response experiment and growth prediction analysis of microbial contamination of central air conditioning system in Dalian, China Based on the data of Cladosporium in hygrothermal response experiment, this paper used the logistic equation and the Gompertz equation to fit the growth predictive model of Cladosporium genera in different temperature and relative humidity conditions, and the square root model was fitted based on the two environmental factors. Besides, according to the tested microbial density and the identified genome sequence of collected microorganisms, the hygrothermal response experiment of dominant fungal was detected, and the fitting analysis was carried out based on the prediction model, followed by a series of statistical analysis. The unit A showed the obvious microbial contamination status, though all components and airborne microorganism meet the Hygienic specification of central air conditioning ventilation system in public buildings of China 22 . cache = ./cache/cord-002474-2l31d7ew.txt txt = ./txt/cord-002474-2l31d7ew.txt === reduce.pl bib === id = cord-003490-swlkjtyo author = Arzt, Jonathan title = Quantitative impacts of incubation phase transmission of foot-and-mouth disease virus date = 2019-02-25 pages = extension = .txt mime = text/plain words = 7446 sentences = 327 flesch = 39 summary = The current investigation applied a Bayesian modeling approach to a unique experimental transmission study to estimate the occurrence of transmission of foot-and-mouth disease (FMD) during the incubation phase amongst group-housed pigs. This current study focused on investigating the concept of θ and ω for direct contact transmission of a virulent strain of foot-and-mouth disease virus (FMDV) amongst juvenile domestic pigs, and examining the impact of pre-clinical transmission on simulated outbreak size and severity within a US swine production system assuming either optimal or suboptimal response conditions. The most noteworthy findings from this approach were the substantial changes in the modeled estimates of the duration of latency and subclinical infectiousness (ω) when defining the onset of infectiousness by either the occurrence of clinical signs of FMD in donor pigs or by any detection of FMDV RNA in OPF. cache = ./cache/cord-003490-swlkjtyo.txt txt = ./txt/cord-003490-swlkjtyo.txt === reduce.pl bib === id = cord-002411-iiw878w8 author = Ding, Xibing title = TLR4 signaling induces TLR3 up-regulation in alveolar macrophages during acute lung injury date = 2017-02-15 pages = extension = .txt mime = text/plain words = 6653 sentences = 431 flesch = 57 summary = The enhanced TLR3 up-regulation in AMΦ augmented the expression of cytokines and chemokines in response to sequential challenges with LPS and Poly I:C, a TLR3 ligand, which was physiologically associated with amplified AMΦ-induced PMN migration into lung alveoli. To address the effect of LPS/TLR4-mediated activation of TLR3 in AMΦ on inflammatory cytokines, we assessed TNF-α and IL-6 in the serum and BALF, as well as the chemokines MIP-2 and MCP-1 in the BALF, following sequential intratracheal challenges with LPS and Poly I:C. This cross talk between TLR4 and TLR3 in AMΦ resulted in the amplification of cytokine (IL-6, TNF-α ) and chemokine (MIP-2, MCP-1) expression in response to LPS and Poly I:C, which activate TLR4 and TLR3, respectively, and subsequently led to enhanced PMN sequestration into the lung, which was found to be correlated with ALI based on the assessment of alveolar-capillary permeability and histological sections of lung tissue. cache = ./cache/cord-002411-iiw878w8.txt txt = ./txt/cord-002411-iiw878w8.txt === reduce.pl bib === id = cord-002874-9rxv6fy9 author = Welch, David title = Far-UVC light: A new tool to control the spread of airborne-mediated microbial diseases date = 2018-02-09 pages = extension = .txt mime = text/plain words = 3266 sentences = 166 flesch = 47 summary = Here we applied this approach to test the efficacy of the 222-nm far-UVC light to inactivate influenza A virus (H1N1) carried by aerosols in a benchtop aerosol UV irradiation chamber, which generated aerosol droplets of sizes similar to those generated by human coughing and breathing. If these results are confirmed in other scenarios, it follows that the use of overhead low-level far-UVC light in public locations may represent a safe and efficient methodology for limiting the transmission and spread of airborne-mediated microbial diseases such as influenza and tuberculosis. In conclusion, we have shown for the first time that very low doses of far-UVC light efficiently inactivate airborne viruses carried by aerosols. If these results are confirmed in other scenarios, it follows that the use of overhead very low level far-UVC light in public locations may represent a safe and efficient methodology for limiting the transmission and spread of airborne-mediated microbial diseases. cache = ./cache/cord-002874-9rxv6fy9.txt txt = ./txt/cord-002874-9rxv6fy9.txt === reduce.pl bib === id = cord-002019-wtnf340p author = Chen, Xiaojuan title = Retinoic acid facilitates inactivated transmissible gastroenteritis virus induction of CD8(+) T-cell migration to the porcine gut date = 2016-04-15 pages = extension = .txt mime = text/plain words = 7236 sentences = 354 flesch = 49 summary = We demonstrated that elevated numbers of gut-homing CD8(+) T cells (which express α4β7 and CCR9 molecules) were presented in porcine inguinal lymph nodes and were recruited to the small intestine by RA. Taken together, the cell migration assay results revealed a strong chemotactic response in T cells when activated by RA-activated DCs. These data demonstrated that RA-pretreated BMDCs could activate T cells to express high functional levels of the gut-homing receptor CCR9, as well as to migrate towards the porcine chemokine CCL25. In agreement with the migration of gut-homing CD8 + cells, our observations showed that after RA plus TGEV s.c. treatment, many CD3 + T cells were recruited to the intestinal villi and lamina propria, and these data also showed that RA-assisted antigen s.c. can establish a stronger and faster cellular immune response to defend against foreign pathogens 40 . cache = ./cache/cord-002019-wtnf340p.txt txt = ./txt/cord-002019-wtnf340p.txt === reduce.pl bib === id = cord-002659-566uoozj author = Fujimoto, Yousuke title = Pulmonary inflammation and cytokine dynamics of bronchoalveolar lavage fluid from a mouse model of bronchial asthma during A(H1N1)pdm09 influenza infection date = 2017-08-22 pages = extension = .txt mime = text/plain words = 4768 sentences = 275 flesch = 57 summary = Cytokine levels and virus titres in bronchoalveolar lavage fluid from mice with and without asthma after A(H1N1)pdm09 or seasonal H1N1 infection were examined. Virus titres in asthma/A(H1N1)pdm09 mice were highest at 3 days post-infection, and decreased by 7 days post-infection, although the levels at this time point were still higher than that in any other group. In the present study, we investigated the sequential changes in intra-tracheal cytokine production, viral loads, and pulmonary inflammation in a mouse model of bronchial asthma during the first 7 days after A(H1N1)pdm09 or seasonal H1N1 influenza infection. In contrast, the levels in control mice increased to 161.4 pg/mL by 3 days post-seasonal virus infection, which were similar to those in asthma/A(H1N1)pdm09 mice (p = 1.00), and these levels were maintained until 7 days post-infection. The notable findings in the present study were the early peak in both IL-6 and TNF-α levels, the high inflammatory cell infiltration in BAL fluids, and the severe pulmonary inflammation at 3 days post-infection in asthmatic/A(H1N1)pdm09 mice. cache = ./cache/cord-002659-566uoozj.txt txt = ./txt/cord-002659-566uoozj.txt === reduce.pl bib === id = cord-002244-5h6monh3 author = Lee, Seung Hoon title = PTEN ameliorates autoimmune arthritis through down-regulating STAT3 activation with reciprocal balance of Th17 and Tregs date = 2016-10-06 pages = extension = .txt mime = text/plain words = 4148 sentences = 279 flesch = 49 summary = Immunohistochemical analysis revealed that injection with PTEN overexpression vector significantly suppressed the expression of proinflammatory cytokines and osteoclastogenesis related factor such as RANKL and TRAP in joints compared to CIA mice treated with mock vector (Fig. 1D,E) . However, the differentiation of Treg cell was promoted in CIA induced mice injected with PTEN overexpression vector ( Fig. 2A) . However, the number of CD4 + p-Foxp3 + T cells in the spleen tissues of CIA induced mice was significantly upregulated compared to that in the spleen tissues of mice treated with mock vector based on immunofluorescence confocal microscopy ( Fig. 2C,D) . (A,B) Relative mRNA levels of PTEN and factors such as IL-17, RORγ t, and Foxp3 involved in the differentiation of Th17 and Treg in splenic CD4 + T cells, splenocytes, and draining lymph nodes from CIA induced WT or p53 −/− mice were assessed by real-time PCR. cache = ./cache/cord-002244-5h6monh3.txt txt = ./txt/cord-002244-5h6monh3.txt === reduce.pl bib === id = cord-002013-rb9xdzro author = Zheng, Xuexing title = Treatment with hyperimmune equine immunoglobulin or immunoglobulin fragments completely protects rodents from Ebola virus infection date = 2016-04-12 pages = extension = .txt mime = text/plain words = 6027 sentences = 286 flesch = 56 summary = To investigate whether EBOV infections can be controlled by virus neutralization alone, and to prevent the possible induction of serum sickness in humans that would be administered antisera, the post-exposure efficacy of F(ab′ ) 2 (immunoglobulin treated with pepsin to remove the Fc regions of the antibody) were also investigated side-by-side with equine antisera in all experiments as a potential alternate treatment. Three horses were immunized intramuscularly (IM) with 7 injections of eVLP over 11 weeks and the hyperimmune sera were collected from each animal at specified timepoints ( Fig. 1A) to determine the serum titers by neutralization assay against a recombinant HIV-1 virus pseudotyped with EBOV GP. The observation that administering F(ab′ ) 2 at 1 dpi is more efficacious than when the same treatment was given at 30 minutes post-exposure (Fig. 5A ) was also observed in past studies with therapeutic EBOV GP-specific monoclonal antibodies 25, 26 , and suggests that virus neutralization may play a bigger role in protection at a later timepoint after EBOV challenge. cache = ./cache/cord-002013-rb9xdzro.txt txt = ./txt/cord-002013-rb9xdzro.txt === reduce.pl bib === id = cord-003166-k3jxvzfi author = Noh, Ji Yeong title = Isolation and characterization of novel bat paramyxovirus B16-40 potentially belonging to the proposed genus Shaanvirus date = 2018-08-22 pages = extension = .txt mime = text/plain words = 4670 sentences = 244 flesch = 51 summary = Even though the HN amino acids sequences were similar to those from viruses in the proposed genera Shaanvirus, it was also related to that of Sendai virus and human parainfluenza virus 1, which belong to a different genus, Respirovirus showing (Table 1) . In addition, among three pooled sera (two mouse sera each) against human parainfluenza virus 1 (KBPV-VR-44), one pooled serum was cross-reactive to the bat paramyxovirus B16-40 with 40 as the end-point titer for the fluorescent signal ( Table 2 , Fig. 4 ). Notably, even though the HN amino acids sequences were similar to those from viruses in the proposed genera Shaanvirus, it was also related to that of Sendai virus and human parainfluenza virus 1, which belong to a different genus, Respirovirus (Table 1) . In fact, in this study, when mouse antisera were made and tested against bat paramyxovirus B16-40 and human parainfluenza virus 1 (KBPV-VR-44), the two viruses were partially cross-reactive to each other in an indirect immunofluorescence assay. cache = ./cache/cord-003166-k3jxvzfi.txt txt = ./txt/cord-003166-k3jxvzfi.txt === reduce.pl bib === id = cord-003004-iif2lnez author = Linster, Martin title = Clinical and Molecular Epidemiology of Human Parainfluenza Viruses 1–4 in Children from Viet Nam date = 2018-05-01 pages = extension = .txt mime = text/plain words = 4121 sentences = 223 flesch = 49 summary = The present study describes species-specific clinical presentation, the genetic variability and HPIV circulation in Viet Nam. The outcome of RSV infection in hospitalized children under 2 years of age presenting with acute lower respiratory infection (ALRI) in Ho Chi Minh City was described previously 17 . Samples were sourced from two previous acute respiratory infection (ARI) cohorts among in-and outpatients, that were conducted at Children's Hospital 1 and 2 in Ho Chi Minh City, Viet Nam during years 2009 and 2010. For sequencing, HPIV-positive samples were further amplified in a hemi-nested PCR approach with newly designed species-specific primers targeting overlapping regions of the viral genome (Table S2) . In this study, the median age and gender distribution of infected children and frequency of clinical presentation (fever, cough, sore throat, runny nose and nasal congestion) as well as vital signs (pulse and respiratory rate) and duration of illness at presentation were similar between HPIV species (p > 0.05). cache = ./cache/cord-003004-iif2lnez.txt txt = ./txt/cord-003004-iif2lnez.txt === reduce.pl bib === id = cord-002843-dvfmpm54 author = Ai, Hannan title = GenomeLandscaper: Landscape analysis of genome-fingerprints maps assessing chromosome architecture date = 2018-01-18 pages = extension = .txt mime = text/plain words = 6824 sentences = 382 flesch = 55 summary = We create a geometric analysis method (called GenomeLandscaper) to conduct landscape analysis of genome-fingerprints maps (GFM), trace large-scale repetitive regions, and assess their impacts on the global architectures of assembled chromosomes. Specifically, we delete a 1.30-Mbp (from 9,999,936 bp to 11,299,986 bp) target segment (Supplementary Dataset 1) from the prior-cleaned GRCh38p1.chrY, as guided by the turning-changed long sharp straight line on the 2D-trajectory map (X-Length) of the GGFM (Fig. 4a ). We conclude that the 1.30-Mbp target segment (Supplementary Dataset 1) does locate in the centromeric and pericentromeric region of GRCh38p1.chrY (and throughout GRCh38p10.chrY) (Figs 3, 4 and 5), which encourages us to trace its sub-constituents that contributed to the observed turning-changed long sharp straight line on the GGFM (Figs 3 and 4 ). cache = ./cache/cord-002843-dvfmpm54.txt txt = ./txt/cord-002843-dvfmpm54.txt === reduce.pl bib === id = cord-003623-n01rgqyv author = Schuh, Amy J. title = Comparative analysis of serologic cross-reactivity using convalescent sera from filovirus-experimentally infected fruit bats date = 2019-04-30 pages = extension = .txt mime = text/plain words = 6363 sentences = 277 flesch = 37 summary = To evaluate the ability of our system comprising seven filovirus-specific indirect ELISAs to predict the filovirus species most antigenically similar to the species responsible for past infection, we tested seven Marburg virus convalescent serum 35 or whole blood 36 samples collected from experimentally inoculated ERBs. Five of these samples www.nature.com/scientificreports www.nature.com/scientificreports/ were collected four weeks post primary Marburg virus inoculation 35, 36 , while two of the samples were collected at 23 and 27 weeks post primary inoculation following a "natural" boost (i.e., Marburg virus-specific antibody levels waned in these bats and then increased following contact with infectious cagemates) 36 . Although significant levels of serological IgG cross-reactivity were observed between the prime-boost filovirus-specific antisera and some of the filovirus antigens, when the overall covariance of the seven-individual indirect ELISAs in the system were considered, we were able to predict the filovirus species responsible for past infection 100% of the time using as little as 25 μL of sera (each serum was tested against each antigen in duplicate). cache = ./cache/cord-003623-n01rgqyv.txt txt = ./txt/cord-003623-n01rgqyv.txt === reduce.pl bib === id = cord-003148-o7y3wygc author = Shirvani, Edris title = A Recombinant Newcastle Disease Virus (NDV) Expressing S Protein of Infectious Bronchitis Virus (IBV) Protects Chickens against IBV and NDV date = 2018-08-10 pages = extension = .txt mime = text/plain words = 8668 sentences = 423 flesch = 55 summary = However, the results of the inoculation of the tracheal swab samples into 10-day-old embrynated chicken eggs showed that 14 out of 15 (93.3%) chickens vaccinated with rNDV expressing codon optimized S protein of IBV and 0 out of 5 (0%) of non-infected chickens were shedding virus in trachea, respectively, whereas 15 out of 15 (100%) of chickens of all other groups were shedding virus in the trachea (data not shown). To evaluate the effect of the route of inoculation of virulent IB challenge virus on the outcomes of the protective efficacy of rNDV expressing codon optimized S protein of IBV, SPF chicks were immunized at 1-day-old age. The protective efficacy of rNDV expressing codon optimized S gene of IBV was determined by challenging the immunized chickens with 10 4 EID 50 virulent IBV strain Mass-41 by the intraocular route at 3 week post-immunization. cache = ./cache/cord-003148-o7y3wygc.txt txt = ./txt/cord-003148-o7y3wygc.txt === reduce.pl bib === id = cord-004150-ybikajhh author = Nyarko, Prince B. title = Investigating a Plasmodium falciparum erythrocyte invasion phenotype switch at the whole transcriptome level date = 2020-01-14 pages = extension = .txt mime = text/plain words = 6221 sentences = 323 flesch = 39 summary = The genes with most markedly increased expression included members of the erythrocyte binding antigens (EBA), reticulocyte binding homologues (RH), surface associated interspersed proteins (SURFIN), exported protein family 1 (EPF1) and Plasmodium Helical Interspersed Sub-Telomeric (PHIST) gene families. The data indicate changes in expression of a repertoire of genes not previously associated with erythrocyte invasion phenotypes, suggesting the possibility that moving suspension culture may also select for other traits. Additionally, a large number of virulence associated genes, including members of the surface-associated interspersed protein (SURFIN) family, exported protein family 1 (EPF1), ring exported protein 1 (REX1) and interspersed repeat antigen (FIRA); all of which are exported into host erythrocytes, were significantly expressed at higher levels in SP parasites relative to BL (Fig. 2) . A comparison of the levels of differential expression of the eba and rh gene between ST and SP parasites in the current RNA sequencing study and our previous RT-qPCR analysis shows a strong positive correlation of results from the two studies ( Supplementary Fig. 12 ). cache = ./cache/cord-004150-ybikajhh.txt txt = ./txt/cord-004150-ybikajhh.txt === reduce.pl bib === id = cord-001915-b9dk07tk author = Liang, Xun title = A CRISPR/Cas9 and Cre/Lox system-based express vaccine development strategy against re-emerging Pseudorabies virus date = 2016-01-18 pages = extension = .txt mime = text/plain words = 3914 sentences = 236 flesch = 49 summary = title: A CRISPR/Cas9 and Cre/Lox system-based express vaccine development strategy against re-emerging Pseudorabies virus Here we present an express vaccine development strategy based on CRISPR/Cas9 and Cre/Lox system against re-emerging Pseudorabies virus, which caused the recent devastating swine pseudorabies outbreak in China. To establish an express vaccine development strategy, two highly efficient gene edit systems, CRISPR/Cas9 and Cre/Lox system were employed. Eight hours post transfection, cells were then infected with PRV HNX with different MOI (multiplicity of infection) and incubated until recombinant virus expressing red and/or green fluorescence were observed (Fig. 3b) . As shown in Fig. 4a , the Cre recombinase gene transfected HEK293T cells were infected with PRV-HNX-TK − /gE − GFP + mCherry + recombinant PRV with various MOI (0.1, 1, and 10). Here, our animal experiments in mouse and piglets validated the protective effect of this gene editing technologies based new vaccine candidate, demonstrating its potential in controlling the current pseudorabies outbreak in the swine industry. cache = ./cache/cord-001915-b9dk07tk.txt txt = ./txt/cord-001915-b9dk07tk.txt === reduce.pl bib === id = cord-002389-k86hzbbx author = Fan, Hanlu title = Selective inhibition of Ebola entry with selective estrogen receptor modulators by disrupting the endolysosomal calcium date = 2017-01-24 pages = extension = .txt mime = text/plain words = 5147 sentences = 274 flesch = 49 summary = As all stages of Ebola entry (binding to and internalization from the cell surface, as well as trafficking to and fusion with the limiting membrane of endolysosome) are mediated by trimeric GP spikes arrayed around the Ebola particles 29, 30 , so the pseudovirion model with Ebola GP can simulate the stages of wild-type Ebola entry, and several groups have studied the Ebola entry mechanism and screened the anti-Ebola entry drugs with Ebola pseudovirion model 3, 6, 31, 32 . To determine whether endolysosomal calcium is involved in the mechanism of Ebola entry inhibition, we treated HepG2 cell line with a high-affinity Rhod-dextran to chelate intraluminal calcium, and infected the cells with Ebola, WSN, or VSV pseudovirions. cache = ./cache/cord-002389-k86hzbbx.txt txt = ./txt/cord-002389-k86hzbbx.txt === reduce.pl bib === id = cord-004016-iaktm72a author = Soto-Quintero, Albanelly title = Curcumin to Promote the Synthesis of Silver NPs and their Self-Assembly with a Thermoresponsive Polymer in Core-Shell Nanohybrids date = 2019-12-03 pages = extension = .txt mime = text/plain words = 6440 sentences = 364 flesch = 52 summary = The Ag@cur-P(MEO 2 MA) core-doped shell hybrid NPs were prepared by free radical precipitation polymerization (FRPP) of the stimuli-responsive MEO 2 MA monomer in the presence of TEGDMA (crosslinking agent), using curcumin-decorated Ag@cur NPs as seeds (Fig. 1) . However, the dual key-role of curcumin, as reducing agent and growth-polymerization promoter in this specific synthesis, required additional investigation to understand and optimize the chemical variables (solubility, concentration and reaction temperature) in order to achieve homogeneous, monodisperse and mononuclear Ag@cur-P(MEO 2 MA) core-shell nanohybrids. The presence of hydrophobic curcumin nearby the metallic surface led to precipitation-polymerization of P(MEO 2 MA) around the AgNPs previously formed (Fig. 1B,C) ; and the resulting Ag@cur-P(MEO 2 MA) nanoparticles were born negatively charged due to the persulfate groups from the APS initiator, which promotes their colloidal stability. cache = ./cache/cord-004016-iaktm72a.txt txt = ./txt/cord-004016-iaktm72a.txt === reduce.pl bib === id = cord-002956-e5ihpe4i author = Chang, Ya-Chun title = Ventilator Dependence Risk Score for the Prediction of Prolonged Mechanical Ventilation in Patients Who Survive Sepsis/Septic Shock with Respiratory Failure date = 2018-04-04 pages = extension = .txt mime = text/plain words = 4666 sentences = 272 flesch = 46 summary = title: Ventilator Dependence Risk Score for the Prediction of Prolonged Mechanical Ventilation in Patients Who Survive Sepsis/Septic Shock with Respiratory Failure A total of 379 patients with sepsis or septic shock and acute respiratory failure requiring mechanical ventilation were admitted to the medical intensive care unit in the Kaohsiung Chang Gung Memorial Hospital from August 2013 to October 2015. We also tested and found that SOFA PaO 2 /FiO 2 subscore and GCS subscore on admission day 7 could help predict ventilator dependence on sepsis and septic shock patients with significant difference in univariate analysis ( Table 5 ). Ventilator dependence risk score, including a history of stroke and data from day 7 (thrombocytopenia, acidosis, and the higher fraction of inspired oxygen), can be applied to predict prolonged mechanical ventilation in patients who survive sepsis and septic shock. cache = ./cache/cord-002956-e5ihpe4i.txt txt = ./txt/cord-002956-e5ihpe4i.txt === reduce.pl bib === id = cord-003504-wjab4y0g author = Copland, Alastair title = Bacillus Calmette-Guérin Induces PD-L1 Expression on Antigen-Presenting Cells via Autocrine and Paracrine Interleukin-STAT3 Circuits date = 2019-03-06 pages = extension = .txt mime = text/plain words = 4856 sentences = 238 flesch = 47 summary = Finally, an in vivo immunisation model showed that BCG vaccination under PD-L1 blockade could enhance antigen-specific memory CD4 T-cell responses. Here, we show for the first time that BCG can induce the up-regulation of PD-L1 on both macrophages and dendritic cells (DCs) via autocrine/paracrine secretion of STAT3-activating cytokines, chiefly IL-6 and IL-10. Upon infection with BCG, both APC types expressed high levels of PD-L1 compared to the unstimulated control at 24 h and 48 h (p < 0.0001), and a dose trend was observed for increasing MOI in macrophages at 48 h. To confirm that STAT3 was mediating the up-regulation of PD-L1 expression by BCG, cells were then pre-treated with Stattic or a vehicle control for 2 hours before infection with a low dose of bacteria (Fig. 5C) . BCG vaccine mediated reduction in the MHC-II expression of macrophages and dendritic cells is reversed by activation of Toll-like receptors 7 and 9 cache = ./cache/cord-003504-wjab4y0g.txt txt = ./txt/cord-003504-wjab4y0g.txt === reduce.pl bib === id = cord-004378-g1rxygef author = Leinisch, Fabian title = UV oxidation of cyclic AMP receptor protein, a global bacterial gene regulator, decreases DNA binding and cleaves DNA at specific sites date = 2020-02-20 pages = extension = .txt mime = text/plain words = 5840 sentences = 325 flesch = 55 summary = In this study we show that exposure of isolated dimeric CRP-cAMP to UV modifies specific Met, Trp, Tyr, and Pro side-chains, induces inter-protein Tyr63-Tyr41 cross-links, and decreases DNA binding via oxidation of Met114/Pro110 residues in close proximity at the CRP dimer interface. The modifications at the CRP dimer interface, and the site-specific DNA strand cleavage are proposed to occur via oxidation of two species Met residues (Met114 and Met189, respectively) to reactive persulfoxides that damage neighbouring amino acids and DNA bases. Panel B: Material balance for Trp and Tyr residues determined by UPLC analysis with direct fluorescence detection on acid-hydrolysed UV-exposed CRP-cAMP complex. UPLC analysis of native and oxidized CRP showed that UV exposure of CRP resulted in significant modification (relative to controls) to Trp, Tyr, Ser, Met and Arg residues (Fig. 3A) . Q-TOF MS analysis of cAMP-CRP-DNA complexes exposed to UV light showed a similar pattern of damage, but higher extents of Met modification (7.6%; Fig. 3C ). cache = ./cache/cord-004378-g1rxygef.txt txt = ./txt/cord-004378-g1rxygef.txt === reduce.pl bib === id = cord-004062-yxx3xxio author = Lee, Ing-Kit title = Impaired production of immune mediators in dengue virus type 2-infected mononuclear cells of adults with end stage renal disease date = 2019-12-24 pages = extension = .txt mime = text/plain words = 3744 sentences = 191 flesch = 47 summary = We performed an in vitro study to evaluate the sequential immunological reactions and viral load in dengue virus type 2-infected mononuclear cells of patients with ESRD (n = 34) and in healthy controls (n = 30). The concentrations of interleukins (IL)-1 receptor antagonist (Ra), IL-2, IL-6, IL-8, IL-10, IL-12p40, granulocyte-macrophage colony-stimulating factor (GM-CSF), monocyte chemotactic protein-1 (MCP-1), macrophage inflammatory protein-1b (MIP-1b), vascular endothelial growth factor (VEGF), tumor necrosis factor (TNF)-α and viral load cycle threshold (Ct) were measured in the dengue virus type 2-infected mononuclear cells at 6 h, 24 h, 48 h, and 72 h post-infection. In the present study, eleven immune mediators and viral load Ct values were measured in DENV2-infected mononuclear cells of adults with ESRD, and in healthy participants. Our results have been somewhat inconsistent with the reported overwhelming immune activation that is associated with dengue disease severity 5, 7 ; however, our findings clearly reflect the impairment of immune responses in vitro study of DENV2-infected mononuclear cells in ESRD patients. cache = ./cache/cord-004062-yxx3xxio.txt txt = ./txt/cord-004062-yxx3xxio.txt === reduce.pl bib === id = cord-004060-nxw5k9y1 author = Zhang, Yewu title = Spatiotemporal Analysis of Influenza in China, 2005–2018 date = 2019-12-23 pages = extension = .txt mime = text/plain words = 5547 sentences = 301 flesch = 47 summary = After adjusting for other covariates, a spatially unstructured random effect term (v i ), a spatially structured conditional autoregression term (υ i ), a first-order random walk-correlated time variable (γ 1j ), and an interaction term for time and place (δ ij ) in the multivariate adjusted spatiotemporal model, the flu vaccines (per million doses), flu surveillance protocols, rate of influenza A (H1N1)pdm09, latitude and longitude still remain statistically significant. Based on the incidence data of influenza gained from the Chinese Notifiable Infectious Disease Reporting System, we used the Bayesian spatiotemporal model in this study to assess the space-time patterns of the influenza epidemic at the prefecture level in mainland China from 2005 to 2018 and explored several factors that may be associated with the changing spatial and temporal patterns in the influenza incidence risk. cache = ./cache/cord-004060-nxw5k9y1.txt txt = ./txt/cord-004060-nxw5k9y1.txt === reduce.pl bib === id = cord-003505-qr6ukfti author = Tabraue-Chávez, Mavys title = A colorimetric strategy based on dynamic chemistry for direct detection of Trypanosomatid species date = 2019-03-06 pages = extension = .txt mime = text/plain words = 5655 sentences = 331 flesch = 50 summary = In this work, we have developed a novel colorimetric molecular assay that integrates nucleic acid analysis by dynamic chemistry (ChemNAT) with reverse dot-blot hybridization in an array format for a rapid and easy discrimination of Leishmania major and Trypanosoma cruzi. Once the abasic PNA probes hybridize with target sequences, the SMART-C-Biotin dynamic incorporation takes place, enabling the unequivocal identification of the parasite present in the amplicon sample, because of the unique colorimetric pattern that each Trypanosomatid amplicon generates. DNA amplicon products were denatured and then together with the dynamic chemistry reaction reagents added directly into the internal column of the Spin-Tube that supports the nylon membrane for the color-development assay (Fig. 4) . 20 ng of human gDNA were used as PCR template for its amplification with the set of primers described in our study and neither colorimetric signals nor bands were detected using the Spin-Tube and capillary electrophoresis analysis respectively (Fig. 5 , column 2: 2A and 2B), hence probing the specificity when human gDNA is present. cache = ./cache/cord-003505-qr6ukfti.txt txt = ./txt/cord-003505-qr6ukfti.txt === reduce.pl bib === id = cord-003387-82573enr author = Nam, Gyu-Hwi title = Gene expression profiles alteration after infection of virus, bacteria, and parasite in the Olive flounder (Paralichthys olivaceus) date = 2018-12-24 pages = extension = .txt mime = text/plain words = 5177 sentences = 279 flesch = 43 summary = title: Gene expression profiles alteration after infection of virus, bacteria, and parasite in the Olive flounder (Paralichthys olivaceus) In this study, we carried out transcriptome analysis using the olive flounder gill tissues after infection of three types of pathogens (Virus; Viral hemorrhagic septicemia virus, Bacteria; Streptococcus parauberis, and Parasite; Miamiensis avidus), respectively. Our goals are to provide plenty of genomic knowledge about olive flounder transcripts for further research and report genes, which were changed in their expression after specific pathogen infection. To profile gene expression after infection of three pathogens (VHSV, Streptococcus parauberis, and Miamiensis avidus), transcriptome analysis was conducted using gill tissues of olive flounders, respectively. In this study, we understood the relation between three types of pathogen infection and differential gene expression in the olive flounder genome through transcriptome analysis, respectively. cDNA microarray analysis of viral hemorrhagic septicemia infected olive flounder, Paralichthys olivaceus: immune gene expression at different water temperature cache = ./cache/cord-003387-82573enr.txt txt = ./txt/cord-003387-82573enr.txt === reduce.pl bib === id = cord-001868-utsvsja0 author = Uematsu, Takayuki title = Loss of CARD9-mediated innate activation attenuates severe influenza pneumonia without compromising host viral immunity date = 2015-12-02 pages = extension = .txt mime = text/plain words = 4974 sentences = 284 flesch = 53 summary = In this study, we focused on CARD9, a signaling adaptor known to regulate innate immune activation through multiple innate sensor proteins, and investigated its role in anti-IFV defense and lung pathogenesis in a mouse model recapitulating severe influenza pneumonia with ARDS. Our results showed that the CARD9 pathway was involved in fatal influenza pneumonia mediated by inflammatory cytokine/chemokine production, whereas it was dispensable for type-I interferon production as well as the development of anti-viral acquired immunity. adapted IFV A/PR/8/34 strain (PR8) shows similar lung pathology to human ARDS 10-12 , we intratracheally infected wild-type (WT: C57BL/6) and Card9 -/mice with a lethal dose (10 4 PFU/mouse) of PR8 to determine whether CARD9-mediated innate immune responses contributed to severe influenza pneumonia. However, no reduction in cytokine/chemokine levels was evident on day 8, indicating that a CARD9-mediated innate response controls cytokine/chemokine production at an early time point after IFV infection and influences subsequent inflammatory cell recruitment and lung pathology at a later time point. cache = ./cache/cord-001868-utsvsja0.txt txt = ./txt/cord-001868-utsvsja0.txt === reduce.pl bib === id = cord-003196-fdb6az0v author = Casalino-Matsuda, S. Marina title = Hypercapnia Alters Expression of Immune Response, Nucleosome Assembly and Lipid Metabolism Genes in Differentiated Human Bronchial Epithelial Cells date = 2018-09-10 pages = extension = .txt mime = text/plain words = 4652 sentences = 252 flesch = 37 summary = title: Hypercapnia Alters Expression of Immune Response, Nucleosome Assembly and Lipid Metabolism Genes in Differentiated Human Bronchial Epithelial Cells These changes in gene expression indicate the potential for hypercapnia to impact bronchial epithelial cell function in ways that may contribute to poor clinical outcomes in patients with severe acute or advanced chronic lung diseases. Major clusters from hypercapnia-downregulated genes are linked to immune response, nucleosome assembly, cell differentiation, oxidation reduction, and ion and lipid transport (Fig. 2) . In addition, the suppressive effect of elevated CO 2 on immune gene expression in the airway epithelium, along with similar effects on immune cells, suggest a reason why severe COPD and other lung disease associated with hypercapnia all carry a high risk of pulmonary infection. Thus, CO 2 -induced alterations in airway epithelial gene expression may underlie the increase in mortality associated with hypercapnia in advanced COPD, as well as community-acquired pneumonia 9 , adenoviral lung infections 10 and cystic fibrosis 11 . cache = ./cache/cord-003196-fdb6az0v.txt txt = ./txt/cord-003196-fdb6az0v.txt === reduce.pl bib === === reduce.pl bib === id = cord-004419-81w7apdk author = Course, Christopher title = Management of Respiratory Distress Syndrome in Preterm Infants In Wales: A Full Audit Cycle of a Quality Improvement Project date = 2020-02-26 pages = extension = .txt mime = text/plain words = 2600 sentences = 132 flesch = 47 summary = Little variation was seen between level two and three units, although gestational age was a significant independent variable for several practices, including delayed cord clamping, stabilisation with intubation, early enteral feeding and caffeine administration. Prospective, anonymised audits of the management of RDS in all preterm infants born at <34 weeks gestational age and cared for in a participating neonatal unit in Wales were undertaken. This represented the best-practice document for the management of RDS in infants born at <34 weeks gestational age, concentrating on areas which were supported by Grade A evidence (http://www.gradeworkinggroup.org/). The audit proforma was based upon the recommendations in the European Consensus Guideline on the Management of RDS in Preterm Infants 2013, and concentrated on management areas which were supported by Grade A evidence 9 . The 2013 edition of the European consensus guideline recommended a change in practice towards stabilising preterm infants on non-invasive respiratory support at delivery rather than elective intubation 9 . cache = ./cache/cord-004419-81w7apdk.txt txt = ./txt/cord-004419-81w7apdk.txt === reduce.pl bib === id = cord-004069-nuep8nim author = DeWald, Lisa Evans title = In Vivo Activity of Amodiaquine against Ebola Virus Infection date = 2019-12-27 pages = extension = .txt mime = text/plain words = 5707 sentences = 288 flesch = 53 summary = A pharmacokinetic (PK) study in rhesus macaques (2 groups of 2 males and 2 females) was performed to monitor plasma concentrations of AQ (Fig. 1a ) and the active metabolite DEAQ (Fig. 1b) . samples from infected animals collected on days 0, 3, 5, and 7 postexposure and on day of necropsy (days 6, 7 or 8) were analyzed for determination of plasma levels of AQ and its metabolite DEAQ. Animals that were treated on days 0, 1 and 2 (Group 2, Fig. 7a ), had plasma DEAQ levels ranging from 0 to 205 ng/ml on days 3, 5, 7 and 8 postexposure. www.nature.com/scientificreports www.nature.com/scientificreports/ The goal of the study was to treat animals with AQ using a similar dosing strategy as for human patients, with a target blood concentration range of the parent compound AQ of 29.2 ± 10.9 ng/mL 12 . cache = ./cache/cord-004069-nuep8nim.txt txt = ./txt/cord-004069-nuep8nim.txt === reduce.pl bib === id = cord-004170-ri5qsarz author = Yashima, Nozomi title = Leukocyte-derived extracellular DNA contributes to abnormal pressure elevation in the extracorporeal circulation circuit date = 2020-01-16 pages = extension = .txt mime = text/plain words = 3584 sentences = 234 flesch = 44 summary = title: Leukocyte-derived extracellular DNA contributes to abnormal pressure elevation in the extracorporeal circulation circuit Abnormal in-circuit elevation in pressure was associated with deposition of extracellular DNA on the outlet surface of the filter. In-circuit pressure was elevated at the oxygenator if heparin was administered in whole blood that was stored for 7 days (Fig. S1B) . Then, we examined whether leukocyte stimulation results in elevation of in-circuit pressure since previous studies have suggested that stimulated leukocytes are prone to releasing DNA into the extracellular space 13 . Our study showed that leukocyte-derived extracellular DNA induced an elevation of in-circuit pressure. Our study suggested that extracellular DNA from disrupted leukocytes contributed to elevation of in-circuit pressure. In conclusion, our study shows that leukocyte-derived extracellular DNA contributes to abnormal in-circuit elevation of pressure in an ex vivo circuit. cache = ./cache/cord-004170-ri5qsarz.txt txt = ./txt/cord-004170-ri5qsarz.txt === reduce.pl bib === === reduce.pl bib === id = cord-002802-594mmlk8 author = Zhang, Yun title = Recombinant influenza H9N2 virus with a substitution of H3 hemagglutinin transmembrane domain showed enhanced immunogenicity in mice and chicken date = 2017-12-20 pages = extension = .txt mime = text/plain words = 4269 sentences = 246 flesch = 47 summary = Further, the recombinant TM-replaced H9N2-TM virus could provide better inter-clade protection in both mice and chickens against H9N2, suggesting that the H3-TM-replacement could be considered as a strategy to develop efficient subtype-specific H9N2 influenza vaccines. However, the biological characteristics, such as virus growth, ratio of trimer, thermal stability, acidic resistance and fusion activity were altered, suggesting an important role of the TM domain in viral replication and pathogenicity. Taken together, the increased thermal and acidic resistances of the recombinant H9N2-TM virus suggest that the substitution in the transmembrane (TM) domain can affect the stability of the HA, therefore alters viral biological characteristics. To explore whether the increased HA trimers and increased thermal and acidic resistances could result in better immune responses thus providing better protection in mice, we first vaccinated six-week-old mice with inactivated recombinant H9N2-WT and H9N2-TM viruses twice to check antibody responses. cache = ./cache/cord-002802-594mmlk8.txt txt = ./txt/cord-002802-594mmlk8.txt === reduce.pl bib === id = cord-002045-m44fic4g author = Horie, Masayuki title = An RNA-dependent RNA polymerase gene in bat genomes derived from an ancient negative-strand RNA virus date = 2016-05-13 pages = extension = .txt mime = text/plain words = 4805 sentences = 312 flesch = 59 summary = Endogenous bornavirus-like L (EBLL) elements are inheritable sequences derived from ancient bornavirus L genes that encode a viral RNA-dependent RNA polymerase (RdRp) in many eukaryotic genomes. Furthermore, we showed that the EBLLs evolved under purifying selection and still possess functional motifs conserved among the Mononegavirales RdRps. These results strongly suggest that the EBLL elements encode functional proteins that may be RdRps. ORF screening for these elements in several mammalian species and found an EBLL element in the bat species Eptesicus fuscus (designated efEBLL-1; accession number ALEH01013293). Notably, this element (eEBLL-1) contains a 1,718-amino acid ORF that was conserved for more than 11.8 MY and included almost all of the sequence motifs essential for the enzymatic activity of a RNA virus RdRp. To the best of our knowledge, eEBLL-1 is the first example of an RNA virus-derived RdRp encoded by the mammalian genome. cache = ./cache/cord-002045-m44fic4g.txt txt = ./txt/cord-002045-m44fic4g.txt === reduce.pl bib === id = cord-003558-7lvqpz21 author = Davies, Patrick title = Clinical Scenarios of the Application of Electrical Impedance Tomography in Paediatric Intensive Care date = 2019-03-29 pages = extension = .txt mime = text/plain words = 4016 sentences = 240 flesch = 44 summary = We present the clinical use of EIT in six conditions: Asthma, Ventilation weaning and expansion recoil, Sequential Lobar Collapse, Targeted Physiotherapy, Pleural Effusion assessment, and PEEP optimisation. Electrical Impedance Tomography (EIT) is a radiation-free functional modality that enables bedside imaging and monitoring of lung function and expansion. It has been used in various clinical settings including acute respiratory distress syndrome (ARDS), establishing the best positive end expiratory pressure (PEEP) [8] [9] [10] [11] [12] , the response of the lungs to recruitment manoeuvres [12] [13] [14] [15] [16] and trying to minimize areas of collapse and hyperinflation 6, 17 . Clinical interest in this method has been driven by the need for bedside monitoring of the dynamics of the lungs and the effects of ventilatory manoeuvres, including changes in ventilator settings, suctioning, chest drains, positioning and physiotherapy. Clinical interest in this method has been driven by the need for bedside monitoring of the dynamics of the lungs and the effects of ventilatory manoeuvres, including changes in ventilator settings, suctioning, chest drains, positioning and physiotherapy. cache = ./cache/cord-003558-7lvqpz21.txt txt = ./txt/cord-003558-7lvqpz21.txt === reduce.pl bib === id = cord-004292-6lnxb0px author = Lyu, Hongming title = Synchronized Biventricular Heart Pacing in a Closed-chest Porcine Model based on Wirelessly Powered Leadless Pacemakers date = 2020-02-07 pages = extension = .txt mime = text/plain words = 3772 sentences = 233 flesch = 51 summary = With their flexible form factors, two pacemakers were implanted epicardially on the right and left ventricles of a porcine model and were inductively powered at 13.56 MHz and 40.68 MHz industrial, scientific, and medical (ISM) bands, respectively. The closed-chest pacing only requires the external source power of 0.3 W and 0.8 W at 13.56 MHz and 40.68 MHz, respectively, which leads to specific absorption rates (SARs) 2–3 orders of magnitude lower than the safety regulation limit. Not only is the need for intravascular leads eliminated, but synchronized and leadless pacing across different chambers becomes feasible, which offers the flexibility in customizing patient-specific CRTs. Prior studies have investigated wirelessly powered single-site cardiac pacing on rodent, rabbit and open-chest porcine models 4, 5, 21 . To demonstrate wireless CRT, two such pacemakers were epicardially implanted on the right ventricle (RV) and left ventricle (LV) in a porcine model for synchronized biventricular (BiV) pacing with controllable interventricular offsets. cache = ./cache/cord-004292-6lnxb0px.txt txt = ./txt/cord-004292-6lnxb0px.txt === reduce.pl bib === id = cord-004379-91a7sgir author = Han, Nayoung title = Assessment of adverse events related to anti-influenza neuraminidase inhibitors using the FDA adverse event reporting system and online patient reviews date = 2020-02-20 pages = extension = .txt mime = text/plain words = 3261 sentences = 190 flesch = 46 summary = The aim of this study was to evaluate age-related clinical manifestations of adverse events (AEs) related to NAIs. FAERS and WebMD data were downloaded. A disproportionality analysis showed that signals for vomiting and hallucinations were detected in younger patients given oseltamivir, while an abnormal hepatic function, cardiac failure, shock, and cardio-respiratory arrest were detected in older patients given peramivir. However, there is still concern regarding the adverse effects of NAIs. This study analyzed the age-related AEs associated with NAIs using data from FAERS and WebMD. Oseltamivir was the NAI most commonly showing AEs in the FAERS data, and the most common AEs for this drug were psychiatric and gastrointestinal disorders, similar to the findings of previous studies 8, [13] [14] [15] [16] . However, in the WebMD data, we could not detect signals by these disproportionality analyses due to the small number of AE cases, although psychiatric and gastrointestinal disorders were the most common AEs reported. cache = ./cache/cord-004379-91a7sgir.txt txt = ./txt/cord-004379-91a7sgir.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-004385-xna32qve author = Zhou, Yuqing title = Use of corticosteroids in influenza-associated acute respiratory distress syndrome and severe pneumonia: a systemic review and meta-analysis date = 2020-02-20 pages = extension = .txt mime = text/plain words = 4494 sentences = 234 flesch = 39 summary = title: Use of corticosteroids in influenza-associated acute respiratory distress syndrome and severe pneumonia: a systemic review and meta-analysis We obtained the following data: (a) characteristics of studies (design, setting, country, period, methodological details for quality assessment); (b) characteristics of participants (demographics, co-morbid illnesses, disease severity, numbers in each group, influenza virus type); (c) characteristics of interventions (type, dose, timing and duration of corticosteroid use); and (d) outcomes. Another study reporting the result of 62 patients with acute respiratory failure due to influenza showed no statistically significant difference between low dose and high dose corticosteroid therapy (8/19 versus 7/19, p > 0.05) 16 . The overall findings of this meta-analysis indicated that patients with pneumonia or acute respiratory distress syndrome who were administered corticosteroids had significantly higher mortality and incidence of nosocomial infection but the use of corticosteroids did not influence the length of hospital stay. cache = ./cache/cord-004385-xna32qve.txt txt = ./txt/cord-004385-xna32qve.txt === reduce.pl bib === id = cord-004222-z4butywi author = Joyce, Collin title = Comparisons of the antibody repertoires of a humanized rodent and humans by high throughput sequencing date = 2020-01-24 pages = extension = .txt mime = text/plain words = 3718 sentences = 187 flesch = 46 summary = We characterized the heavy chain and kappa light chain antibody repertoires of a model animal, the OmniRat, by high throughput antibody sequencing and made use of two novel datasets for comparison to human repertoires. Multiple differences were found in both the heavy and kappa chain repertoires between OmniRats and humans including gene segment usage, CDR3 length distributions, class switch recombination, somatic hypermutation levels and in features of V(D)J recombination. We individually separated total RNA from spleens and lymph nodes of three unimmunized OmniRats and PCR amplified the heavy and kappa chain antibody V gene segments. We started by making intra-animal comparisons, intra-species comparisons and inter-species comparisons of the immunoglobulin gene segment usage frequencies for each antibody repertoire by performing hierarchical clustering ( Fig. 1 ) and linear regression analysis (Figs. cache = ./cache/cord-004222-z4butywi.txt txt = ./txt/cord-004222-z4butywi.txt === reduce.pl bib === === reduce.pl bib === id = cord-004310-hl7fa4af author = Matsuishi, Yujiro title = Down Syndrome Reduces the Sedative Effect of Midazolam in Pediatric Cardiovascular Surgical Patients date = 2020-02-10 pages = extension = .txt mime = text/plain words = 3488 sentences = 187 flesch = 48 summary = We recorded patient information, including age, sex, surgical procedure, and daily severity data (including severity of organ dysfunction and sedative/muscle relaxant dosages) during PICU stays for five days after the end of muscle relaxant usage. We found that, overall, the amount of MDZ administered was increased in DS versus controls after ending muscle relaxants and observed the reduced sedative effect of MDZ for DS patients while DEX was not different as estimated by Bayesian inference modeling. To adjust these biases, we used multivariate www.nature.com/scientificreports www.nature.com/scientificreports/ analysis with respect to these factors but we also "double checked" our results by using the demographic data propensity score for DS patients as a covariate in Bayesian inference modeling. To conclude, we conducted a retrospective study based on validated evaluative tools that indicated a need for higher doses of MDZ with higher doses of compensating sedatives for the 5-day period immediately after muscle relaxant usage following pediatric heart surgery. cache = ./cache/cord-004310-hl7fa4af.txt txt = ./txt/cord-004310-hl7fa4af.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-005507-equnyib7 author = Kamath, Kathy title = Antibody epitope repertoire analysis enables rapid antigen discovery and multiplex serology date = 2020-03-24 pages = extension = .txt mime = text/plain words = 5189 sentences = 261 flesch = 38 summary = Given this, we developed serum epitope repertoire analysis (SERA), a method to rapidly discover conserved, pathogen-specific antigens and their epitopes, and applied it to develop an assay for Chagas disease caused by the protozoan parasite Trypanosoma cruzi. We applied serum epitope repertoire analysis (SERA) to discover shared, but highly specific immunogenic epitope motifs associated with Chagas disease caused by the protozoan parasite Trypanosoma cruzi, and thereby develop a serological assay. To identify antibody epitope motifs specific to Chagas disease, we applied the IMUNE motif discovery algorithm 15 (see Methods for parameters) to epitope repertoires from 28 Chagas specimens and 30 non-Chagas sera, yielding 331 candidate motifs (Supplementary Table S2 ). Using Chagas disease seropositive specimens, a panel of 31 peptide motifs was identified that exhibited 100% sensitivity (60/60) and 100% specificity (120/120) in independent validation sets. cache = ./cache/cord-005507-equnyib7.txt txt = ./txt/cord-005507-equnyib7.txt === reduce.pl bib === === reduce.pl bib === id = cord-009691-gkynxdz3 author = Rizzato, Cosmeri title = Variations in cag pathogenicity island genes of Helicobacter pylori from Latin American groups may influence neoplastic progression to gastric cancer date = 2020-04-16 pages = extension = .txt mime = text/plain words = 4504 sentences = 239 flesch = 47 summary = The present study revealed that several cagPAI genes from Latin American Western HP strains contains a number of non-synonymous variants in relatively high frequencies which could influence on the clinical outcome. When comparing the frequency of the 520 selected alleles between the isolates from subjects with gastritis and isolates from subjects with IM or GC we found statistically significant differences in allele distribution for three polymorphisms in cagA gene (Q/K427R, N467G and V1041T), three in cagC gene (V22I, V37I, I45V), one in the cagE gene (K981E), one in cagL gene (S10F), one in cagX gene (G11N), one in cagS (G146D), one in cagζ (S35A), three in cagδ (V353I, P406L, N407E) and one in cagβ (N125A) ( Table 2) . In a previous study conducted with amplicon sequencing by 454 for 84 Mexican and 11 Venezuelan samples we reported 10 non-synonymous SNPs with differential allelic distribution between gastritis and gastric cancer at conventional P-values between 0.01-0.05 28 . cache = ./cache/cord-009691-gkynxdz3.txt txt = ./txt/cord-009691-gkynxdz3.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-010675-acdfvjm5 author = Vila-Vicent, Susana title = Sero-epidemiological study of the rotavirus VP8* protein from different P genotypes in Valencia, Spain date = 2020-05-08 pages = extension = .txt mime = text/plain words = 4595 sentences = 272 flesch = 54 summary = The aims of the present work were to determine the prevalence and titer of serum antibodies against several rotavirus VP8* proteins from different P genotypes in children and adults in Valencia, Spain; and to determine the role of the secretor status (FUT2(G428A) polymorphism) in the antibody response. Significant differences in the antibody titers between secretors and non-secretors were found when the whole viral particles from the Wa rotavirus strain (G1P[8]) were used as the antigen. Sero-epidemiological studies are of importance to elucidate the different viral agents and genotypes that are circulating in a particular area, for this reason the main aim of this work was to determine the serum antibody prevalence and titer to a panel of VP8* proteins from different rotavirus genotypes (P [4] , P [6] , P [8] , P [9] , P [11] , P [14] and P [25] ) in children and adults. cache = ./cache/cord-010675-acdfvjm5.txt txt = ./txt/cord-010675-acdfvjm5.txt === reduce.pl bib === id = cord-004280-c470nlie author = Coleman, Kristen K. title = Airborne Influenza A Virus Exposure in an Elementary School date = 2020-02-05 pages = extension = .txt mime = text/plain words = 4118 sentences = 212 flesch = 46 summary = In this study, we evaluated the use of a bioaerosol sampling method to noninvasively detect and quantify airborne influenza A virus (IAV) densities in a public elementary school. Significantly different (p = 0.049) airborne IAV densities were detected between all three indoor locations (i.e., gymnasium, classroom, and corridor) and all positive samples were collected during the last two weeks of 66 , and a 20-30% relative humidity level; Descriptive of an average elementary school student in the USA weighing ~23-32 kg with an assumed tidal volume (V T ) of 7 mL per kg of body mass. Given the high airborne IAV densities detected in the school corridor, along with elevated student contact rates, it is plausible to conclude that the school corridor is a "hotspot" for influenza virus transmission. cache = ./cache/cord-004280-c470nlie.txt txt = ./txt/cord-004280-c470nlie.txt === reduce.pl bib === === reduce.pl bib === id = cord-011892-b9zlig0r author = Mukherjee, Shradha title = Quiescent stem cell marker genes in glioma gene networks are sufficient to distinguish between normal and glioblastoma (GBM) samples date = 2020-07-02 pages = extension = .txt mime = text/plain words = 6161 sentences = 421 flesch = 51 summary = In this work, two different network construction algorithms, Weighted correlation network analysis (WGCNA) and Multiscale Clustering of Geometric Network (MEGENA), were applied on publicly available glioma, control brain and stem cell gene expression RNA-seq datasets, to identify gene network regulatory modules associated with GBM. Characterization of HuAgeGBsplit_18 (WGCNA) and c1_HuAgeGBsplit_32/193 (MEGENA) modules showed significant enrichment of rodent quiescent stem cell marker genes (GSE70696_QNPbyTAP). Enrichment of proliferative and quiescent stem cell marker genes identified by differential gene expression analysis above, in WGCNA and MEGENA modules was determined using useListEnrichment R function 22, 23, 46 . showed that HuAgeGBsplit_18 WGCNA GBM module and its equivalent c1_HuAgeGBsplit_193/32 MEGENA GBM modules, were the only GBM modules significantly enriched with proliferative and quiescent stem cell marker genes (Fig. 4A,B) . A meta-analysis was performed on publicly available high-throughput gene expression datasets from human glioma samples, control human brains, normal stem cells and GBM cells in quiescent and proliferative states 18, [26] [27] [28] [29] [30] [31] [32] [33] [34] . cache = ./cache/cord-011892-b9zlig0r.txt txt = ./txt/cord-011892-b9zlig0r.txt === reduce.pl bib === === reduce.pl bib === id = cord-004418-08dljap3 author = Young, Ginger title = Complete Protection in Macaques Conferred by Purified Inactivated Zika Vaccine: Defining a Correlate of Protection date = 2020-02-26 pages = extension = .txt mime = text/plain words = 4619 sentences = 265 flesch = 53 summary = In this study we evaluated the antibody responses and efficacy of an aluminum hydroxide adjuvanted purified inactivated Zika vaccine (PIZV) against challenge with Zika virus (ZIKV) strain PRVABC59. As with neutralizing antibodies, all PIZV doses were immunogenic and no anti-Zika IgG was detected in the control group prior to ZIKV challenge. PIZV elicited a dose dependent neutralizing antibody immune response and an anti-Zika IgG response which correlated with a reduction in ZIKV vRNA post-challenge (Table 2 ). Vaccinating with a broad range of PIZV dose levels enabled us to correlate both neutralizing and anti-Zika IgG antibody titers to protection against ZIKV infection. A Zika RVP assay (Sonnberg et al., manuscript in preparation) was used to determine neutralizing antibody titers in serum following the administration of PIZV (study days 1, 29, 57, and 71), and 30 days post-ZIKV challenge (day 101). cache = ./cache/cord-004418-08dljap3.txt txt = ./txt/cord-004418-08dljap3.txt === reduce.pl bib === id = cord-009690-kbwz7xop author = Toubanaki, Dimitra K. title = Development of a Nanoparticle-based Lateral Flow Strip Biosensor for Visual Detection of Whole Nervous Necrosis Virus Particles date = 2020-04-16 pages = extension = .txt mime = text/plain words = 6767 sentences = 381 flesch = 47 summary = title: Development of a Nanoparticle-based Lateral Flow Strip Biosensor for Visual Detection of Whole Nervous Necrosis Virus Particles The principle of viral particles detection based on lateral flow biosensor with functionalized nanoparticles is presented in Fig. 1 . Nodavirus intact particles (virions), obtained either from SSN-1 cell culture supernatants or homogenized tissue samples, are directly applied on the LFB. The sample contains the nodavirus particles (virions) and is applied on the conjugation pad next to functionalized gold nanoparticles (Au) with polyclonal anti-nodavirus antibody. Application of that conjugate on the LFB resulted in a strong signal in the control zone, confirming the successful conjugation of anti-nodavirus antibody to Au nanoparticles (Fig. 2e) . To enable on site analysis of nodavirus, we developed and optimized a paper LFB based on gold nanoparticles for easy, specific and sensitive visual detection of nodavirus viral particles (virions) in biological samples. cache = ./cache/cord-009690-kbwz7xop.txt txt = ./txt/cord-009690-kbwz7xop.txt === reduce.pl bib === === reduce.pl bib === id = cord-034746-uxhpufnv author = Nusshag, Christian title = Glomerular filtration barrier dysfunction in a self-limiting, RNA virus-induced glomerulopathy resembles findings in idiopathic nephrotic syndromes date = 2020-11-05 pages = extension = .txt mime = text/plain words = 3642 sentences = 194 flesch = 36 summary = We therefore analyzed standard markers of glomerular proteinuria (e.g. immunoglobulin G [IgG]), urinary nephrin excretion (podocyte injury) and serum levels of the soluble urokinase plasminogen activator receptor (suPAR), a proposed pathomechanically involved molecule in INS, in PUUV-infected patients. On admission, patients suffering from hantavirus infection showed significantly increased urinary nephrin, IgG, α1-MG and serum suPAR levels compared to healthy controls (Fig. 3A ). Though, urinary biomarker levels decreased in both groups over time, patients with severe PCR showed significantly higher levels of nephrin, IgG, ACR and PCR during the first 48 h after admission ( Table 2 ). Our data show a strong association between urinary nephrin levels and the extent of (non-selective) glomerular proteinuria, suggesting that hantavirus infection causes a pronounced podocyte damage and subsequent impairment of the GFB. To date, one other study showed significantly elevated blood suPAR levels and their association with hantavirus disease severity but did not include nephrinuria and the extent of proteinuria in their analysis 19 . cache = ./cache/cord-034746-uxhpufnv.txt txt = ./txt/cord-034746-uxhpufnv.txt === reduce.pl bib === id = cord-031937-qhlatg84 author = Verma, Anukriti title = Elucidating potential molecular signatures through host-microbe interactions for reactive arthritis and inflammatory bowel disease using combinatorial approach date = 2020-09-15 pages = extension = .txt mime = text/plain words = 6760 sentences = 326 flesch = 31 summary = In-silico analysis involving text mining, metabolic network reconstruction, simulation, filtering, host-microbe interaction, docking and molecular mimicry studies results in robust drug target/s and biomarker/s for co-evolved IBD and ReA. The contributions of the microorganisms in the co-evolved IBD and ReA as part of the disease network was created through the interactive maps of the essential host interaction proteins (verified using literature survey) and the information processed through gene expression data analysis 64 . The pathways of the above host interacting proteins were found out using KEGG database that provides ontologies for proteins related to biological processes 67 www.nature.com/scientificreports/ Subsequently, the role of drugs or inhibitors used to suppress the effect of IBD and ReA such as indomethacin, prednisone, ciprofloxacin, sulfasalazine, azathioprine, methotrexate and hydroxychloroquine was scored in the disease network through their docking studies against the potential targets (both host as well microbial targets) as per published methodologies 68, 69 . cache = ./cache/cord-031937-qhlatg84.txt txt = ./txt/cord-031937-qhlatg84.txt === reduce.pl bib === id = cord-012742-lpk6r54i author = Ferreira-Ramos, Ana Sofia title = Snapshots of ADP-ribose bound to Getah virus macro domain reveal an intriguing choreography date = 2020-09-02 pages = extension = .txt mime = text/plain words = 5433 sentences = 259 flesch = 52 summary = Soaking experi-Scientific RepoRtS | (2020) 10:14422 | https://doi.org/10.1038/s41598-020-70870-w www.nature.com/scientificreports/ ments were performed with crystals of GETV macro domain co-crystallized with ADP-ribose by adding mother liquor supplemented with aspartic acid to the crystallization droplet followed by 2-3 h or overnight incubation at 20 °C. Finally, we obtained a last GETV macro domain/ADP-ribose complex by co-crystallizing the protein with 3 mM ADP-ribose and 3 mM aspartic acid and diffraction data were collected to 1.45 Å resolution. Lastly, co-crystallization of GETV macro domain with low concentrations of ADP-ribose and aspartic acid (3 mM each) led to a structure where the distal ribose is covalently attached to Cys34. In addition to the pose of ADP-ribose found in other structures of alphavirus macro domain, this work reveals original features such as the opening of the distal Scientific RepoRtS | (2020) 10:14422 | https://doi.org/10.1038/s41598-020-70870-w www.nature.com/scientificreports/ ribose, and its stabilization by Ser30, representing a peculiar GETV specific substitution in the catalytic loop. cache = ./cache/cord-012742-lpk6r54i.txt txt = ./txt/cord-012742-lpk6r54i.txt === reduce.pl bib === id = cord-010640-s1oqphvn author = Baral, Prabin title = In-silico identification of the vaccine candidate epitopes against the Lassa virus hemorrhagic fever date = 2020-05-06 pages = extension = .txt mime = text/plain words = 4835 sentences = 276 flesch = 51 summary = In an effort to discover new LASV vaccines, we employ several sequence-based computational prediction tools to identify LASV GP major histocompatibility complex (MHC) class I and II T-cell epitopes. In this study, we have identified and characterized T and B-cell epitopes for the LASV GP using different sequence and structure-based computational epitope prediction methods. MHC-I T-cell epitope prediction with the LASV GP sequence was performed using three different methods separately: ProPred-1, CTLPred, and NetCTL1.2, and the results are shown in Supplementary Table S1. MHC-II T-cell epitope prediction with the LASV GP sequence was performed using three different methods separately: ProPred, NetMHCII 2.3, and EpiTOP 3.0, and the results are shown in Supplementary Table S2 . Docking of the four consensus MHC-I epitopes (Table 1 ) was performed using Autodock Vina, which enabled the docking of epitopes obtained from the sequence-based MHC-1 T-cell prediction into the promising allele structures. cache = ./cache/cord-010640-s1oqphvn.txt txt = ./txt/cord-010640-s1oqphvn.txt === reduce.pl bib === id = cord-007851-v6h1yro7 author = Han, Ki-Cheol title = Streamlined selection of cancer antigens for vaccine development through integrative multi-omics and high-content cell imaging date = 2020-04-03 pages = extension = .txt mime = text/plain words = 4886 sentences = 260 flesch = 41 summary = We used a combined application of this method involving immune-specific signature analysis and HLA-associated peptidomics using samples from six patients with triple-negative breast cancer (TNBC) in order to select immunogenic HLA epitopes for in vitro testing. Integrated WTS data revealed a higher priority to select promising HLA-peptides via high-resolution bioinformatics analysis, showing immune-cell-specific signatures and TCR-repertoire diversity in tumors. We then found a positive correlation between TCR diversity, reflecting clonal composition, and the expression of MHC-class І molecules, suggesting that active tumor-antigen presentation promotes the generation of antigen-specific TILs. Additionally, immune-specific signature analysis can discriminate specific immune-cell types in each patient and thus enhance the efficiency of selective HLA-peptidomic approaches. In this study, the HLA-peptidomics approach combined with comprehensive analysis of immune-specific signatures and TCR repertories showed high selectivity to determine the immunogenic T-cell epitopes. Identification of potential vaccine epitopes coupled with immune-specific signature analysis, HLA-peptidomics, and single-cell-based immunogenicity testing offers a discriminative and powerful tool for cancer-vaccine development. cache = ./cache/cord-007851-v6h1yro7.txt txt = ./txt/cord-007851-v6h1yro7.txt === reduce.pl bib === id = cord-259378-5g2y68i2 author = Cheng, Chao-Min title = Small-volume point-of-care analytical methods date = 2020-08-27 pages = extension = .txt mime = text/plain words = 1556 sentences = 71 flesch = 38 summary = With recent technological advances in multiple research fields-such as materials science, micro-/nano-technology, cellular and molecular biology, and bioengineering-attention is shifting toward the development of new diagnostic tools that not only address needs for high sensitivity and specificity, but that fulfill economic, environmental, and rapid point-of-care (POC) needs, for groups and individuals with constrained resources and, possibly, limited training. This pump accepted commonly available silicone rubber tubing in a range of sizes, from 1.5 to 3 mm, and was capable of producing flow rates up to 1.6 mL/min 6 www.nature.com/scientificreports/ microfluidic technologies may be used for a variety of POC diagnostic applications (e.g., infectious diseases, COVID-19 diagnosis) because they are disposable, inexpensive, portable, and easy to use, especially when they are manufactured using low-cost materials such as paper (and other materials such as cotton or bamboo 7, 8 ). cache = ./cache/cord-259378-5g2y68i2.txt txt = ./txt/cord-259378-5g2y68i2.txt === reduce.pl bib === id = cord-255511-nk3iyg07 author = Chin, Wei Chien Benny title = Spatial super-spreaders and super-susceptibles in human movement networks date = 2020-10-29 pages = extension = .txt mime = text/plain words = 9067 sentences = 466 flesch = 54 summary = Here, we propose a quantitative and systematic framework to identify spatial super-spreaders and the novel concept of super-susceptibles, i.e. respectively, places most likely to contribute to disease spread or to people contracting it. We applied this analysis framework to the Singapore public transport flow network, and identified the SSP and SSS using the SUI and SPI indexes. This study uses a community detection method (MapEquation algorithm 60 ) to identify the zones from the flow network, instead of using the administrative spatial boundaries (i.e. the boundaries of planning areas and regions as defined by the Singapore Government in its Master Plan 2014 59 ) that were designed and selected for governance and political purposes. Figure 7 shows the local out-and in-degree (left column), the outgoing and incoming neighborhood zone-entropy (central column) and coreness-entropy (right column) of the weekday (first two rows) and weekend (bottom two rows) flow networks. cache = ./cache/cord-255511-nk3iyg07.txt txt = ./txt/cord-255511-nk3iyg07.txt === reduce.pl bib === id = cord-272092-ko9y5m2s author = Scalabrin, Matteo title = The cellular protein hnRNP A2/B1 enhances HIV-1 transcription by unfolding LTR promoter G-quadruplexes date = 2017-03-24 pages = extension = .txt mime = text/plain words = 4096 sentences = 246 flesch = 58 summary = title: The cellular protein hnRNP A2/B1 enhances HIV-1 transcription by unfolding LTR promoter G-quadruplexes Surface plasmon resonance confirmed G-quadruplex specificity over linear sequences and fluorescence resonance energy transfer analysis indicated that hnRNP A2/B1 is able to efficiently unfold the LTR G-quadruplexes. Our data highlight a tightly regulated control of transcription based on G-quadruplex folding/unfolding, which depends on interacting cellular proteins. Silencing of the LTR G4 folding/stabilizing protein nucleolin significantly increased promoter activity, indicating the inhibitory effect of nucleolin on LTR-driven transcription 22 . Our results showing decreased transcriptional activity upon depletion of hnRNP A2/B1 indicate a possible additional mechanism of inhibition of virus production mediated by increased G4 folding in the HIV-1 LTR promoter in the absence of hnRNP A2/B1. Nucleolin stabilizes G-quadruplex structures folded by the LTR promoter and silences HIV-1 viral transcription Protein hnRNP A1 and its derivative Up1 unfold quadruplex DNA in the human KRAS promoter: implications for transcription cache = ./cache/cord-272092-ko9y5m2s.txt txt = ./txt/cord-272092-ko9y5m2s.txt === reduce.pl bib === id = cord-258678-0atfsivf author = Liu, Hong Yan title = A Universal Protein Tag for Delivery of SiRNA-Aptamer Chimeras date = 2013-11-07 pages = extension = .txt mime = text/plain words = 4788 sentences = 282 flesch = 51 summary = Here, we report the development of a small and simple protein tag that complements the therapeutic and targeting functionalities of chimera with two functional domains: a dsRNA binding domain (dsRBD) for siRNA docking and a pH-dependent polyhistidine to disrupt endosomal membrane. Therefore, it is of critical importance to design a delivery system that is simple for potential regulatory approval and mass production, universal for all siRNAaptamer chimera, neutral and siRNA-binding specific to ensure aptamer targeting, and small to avoid major alteration of chimera's biodistribution profile. To assess their dsRNA binding activity, siRNA-aptamer chimera labeled with fluorophore FAM were incubated with the protein tags and probed with gel electrophoresis (1% agarose). To evaluate the targeting specificity of the aptamer block, PSMA-positive LNCaP cells and PSMA-negative PC3 cells were treated with complex of chimera and dsRBD-His 18 (chimera/protein tag molar ratio at 152, 100 nM chimera) in serum free medium for 2 hours, followed by incubation in complete medium for another 12 h. cache = ./cache/cord-258678-0atfsivf.txt txt = ./txt/cord-258678-0atfsivf.txt === reduce.pl bib === id = cord-030295-jlhht2l9 author = Cruz-Flores, Roberto title = Genome reconstruction of white spot syndrome virus (WSSV) from archival Davidson’s-fixed paraffin embedded shrimp (Penaeus vannamei) tissue date = 2020-08-10 pages = extension = .txt mime = text/plain words = 4004 sentences = 209 flesch = 49 summary = title: Genome reconstruction of white spot syndrome virus (WSSV) from archival Davidson's-fixed paraffin embedded shrimp (Penaeus vannamei) tissue In this study, the complete genome of white spot syndrome virus (WSSV) was reconstructed from ~ 2-year-old archived Davidson's-fixed paraffin-embedded (DFPE) shrimp tissue using Next Generation Sequencing (NGS). Archived Davidson's-fixed paraffin-embedded (DFPE) tissues in the Aquaculture Pathology Laboratory of The University of Arizona are an untapped invaluable resource for pathogen discovery, metagenomic and evolutionary studies to understand the origin, evolution and spread of shrimp pathogens worldwide. Our results confirm that NGS from DNA extracted from DFPE tissue is also a viable approach to detect know viral sequences. The ability to reconstruct DNA viral genomes as large as 300 kbp size from DFPE tissues shows the feasibility to generate baseline genetic data from archived tissue and determine how pathogens have evolved over time. cache = ./cache/cord-030295-jlhht2l9.txt txt = ./txt/cord-030295-jlhht2l9.txt === reduce.pl bib === id = cord-254090-x8tnweih author = Yang, Szu-Chi title = Efficient Structure Resonance Energy Transfer from Microwaves to Confined Acoustic Vibrations in Viruses date = 2015-12-09 pages = extension = .txt mime = text/plain words = 6073 sentences = 302 flesch = 53 summary = It is interesting to notice that the required threshold electric field magnitudes at the resonant frequency (86.9 V/m) to fracture H3N2 viruses as shown in Fig. 3 (c) are within the IEEE Microwave Safety Standard (106 V/m), indicating high SRET efficiency, even though the quality factor of the H3N2 virus is low. To further investigate the efficiency of this SRET effect from microwave to virus and the threshold effect, we further measured the inactivation ratio of H3N2 virus with different power densities at the resonant frequency ~8 GHz of the confined acoustic dipolar mode. Second, at the resonant frequency, we do observe H3N2 virus inactivation by illuminating 82 W/m 2 (lower than the IEEE safety standard in public space) 8 GHz microwaves on our viral solution, corresponding to an average 87 V/m electric field intensity inside the solution, confirming that our proposed simple model to estimate the field threshold (86.9 V/m) to structurally fracture the virus is quantitatively correct, especially combining the observed threshold effect as discussed above. cache = ./cache/cord-254090-x8tnweih.txt txt = ./txt/cord-254090-x8tnweih.txt === reduce.pl bib === id = cord-265211-a7whyds8 author = Hussein, Hosni A. M. title = miRNA-36 inhibits KSHV, EBV, HSV-2 infection of cells via stifling expression of interferon induced transmembrane protein 1 (IFITM1) date = 2017-12-21 pages = extension = .txt mime = text/plain words = 5486 sentences = 375 flesch = 55 summary = title: miRNA-36 inhibits KSHV, EBV, HSV-2 infection of cells via stifling expression of interferon induced transmembrane protein 1 (IFITM1) In this study, we show the ability of host cell novel miR-36 to specifically inhibit KSHV-induced expression of interferon induced transmembrane protein 1 (IFITM1) to limit virus infection of cells. Transfecting cells with miR-36 mimic specifically lowered IFITM1 expression and thereby significantly dampening KSHV infection. The doses of the mimic In panels 'C and D' , Student t test was performed to study the effect of HS and compare infection of cells with KSHV versus UV.KSHV on miR-36 expression at 5, 10, 15, and 30 min PI. Transfection of BJAB (Fig. 2C ) and HMVEC-d (Fig. 2D ) cells with miR-36 mimic significantly reduced KSHV infection of cells as monitored by the expression of ORF50 gene as early as 30 min PI. Interestingly, the effect of miR-36 mimic on KSHV infection of BJAB and HMVEC-d cells could be significantly reversed by co-transfecting cells with 10 nM of miR-36 inhibitor (Fig. 2E ). cache = ./cache/cord-265211-a7whyds8.txt txt = ./txt/cord-265211-a7whyds8.txt === reduce.pl bib === id = cord-263627-8ufjh70o author = Liang, Li-Lin title = Covid-19 mortality is negatively associated with test number and government effectiveness date = 2020-07-24 pages = extension = .txt mime = text/plain words = 2747 sentences = 164 flesch = 46 summary = Covid-19 mortality rate was negatively associated with Covid-19 test number per 100 people (RR = 0.92, P = 0.001), government effectiveness score (RR = 0.96, P = 0.017), and number of hospital beds (RR = 0.85, P < 0.001). Furthermore, the negative association between Covid-19 mortality and test number was stronger among low-income countries and countries with lower government effectiveness scores, younger populations and fewer hospital beds. In the multiple regression analysis, Covid-19 mortality rate was regressed on Covid-19 test number, case number, critical case rate, government effectiveness score, proportion of population aged 65 or older, number of beds, deaths attributable to communicable diseases, and transport infrastructure quality score. Figure 1e and 1f exhibits that the negative correlation between Covid-19 mortality rate and test number was significant for countries with moderate (r = -0.33, P = 0.021) and low (r = − 0.42, P = 0.002) government effectiveness scores, respectively. cache = ./cache/cord-263627-8ufjh70o.txt txt = ./txt/cord-263627-8ufjh70o.txt === reduce.pl bib === id = cord-259794-6qoksn00 author = Shi, Da title = Nucleocapsid Interacts with NPM1 and Protects it from Proteolytic Cleavage, Enhancing Cell Survival, and is Involved in PEDV Growth date = 2017-01-03 pages = extension = .txt mime = text/plain words = 7086 sentences = 400 flesch = 50 summary = Porcine epidemic diarrhea virus (PEDV) replicates in the cytoplasm of infected cells, but its nucleocapsid (N) protein localizes specifically to the nucleolus. The results suggest potential linkages among viral strategies for the regulation of cell survival activities, possibly through an interaction of N protein with NPM1 which prevents its proteolytic cleavage and enhances cell survival, thus ultimately promoting the replication of PEDV. In this study, to determine the intracellular distribution of N protein at the protein level, PEDV-infected Vero E6 cells were lysed, separated into nuclear and cytoplasmic fractions, and analyzed by western blotting. This study was based on different lines of evidence, reflecting both in vivo and in vitro situations, and demonstrated that PEDV N protein is able to associate with the major nucleolar protein NPM1 of Vero E6 cells (Fig. 2) ; we failed to detect an interaction with the fibrillarin or nucleolin (See Supplementary Fig. S2 ). cache = ./cache/cord-259794-6qoksn00.txt txt = ./txt/cord-259794-6qoksn00.txt === reduce.pl bib === id = cord-260834-v254de8k author = Lim, Chia Chiu title = Development of a Phage Display Panning Strategy Utilizing Crude Antigens: Isolation of MERS-CoV Nucleoprotein human antibodies date = 2019-04-15 pages = extension = .txt mime = text/plain words = 8295 sentences = 456 flesch = 52 summary = The phage ELISA was conducted to measure the performances and effects of different blocking agents on the binding of αUbi phages against crude rUbi. Out of the four samples, the combination of PTM buffer and lysate showed the highest signal (1.226) detected with anti-c-myc-HRP as shown in Fig. 4c . Lysate preblocking and phage preincubation effects towards αUbi and M13KO7 phages against rUbi. To further optimize the biopanning conditions against crude antigens, the 'Yin-Yang' (capture and eliminate) approach was designed to reduce non-specific binding by background phages. coli proteins in the crude fraction of rUbi with the actual concentration of rUbi being expected to be lower than the purified rUbi, the binding capability of αUbi is still unaffected as shown in phage ELISA assay upon affinity selection against crude rUbi. The blocking effect of PTM and E. cache = ./cache/cord-260834-v254de8k.txt txt = ./txt/cord-260834-v254de8k.txt === reduce.pl bib === id = cord-263088-zj14ro5j author = DiPaola, Joshua D. title = Investigating the use of sensory information to detect and track prey by the Sunda pangolin (Manis javanica) with conservation in mind date = 2020-06-17 pages = extension = .txt mime = text/plain words = 7515 sentences = 326 flesch = 52 summary = All trials across the 'olfactory' , 'visual' , and 'acoustic' conditions of phase I were pseudo-randomised within a session so that each session consisted of an equal number of trials of left and right correct choices (based on the side of the chamber in which a container was placed), no one side was baited with food more than three consecutive times in a row, and the first three trials for each session across all conditions were always tests rather than controls to avoid a frustration effect. Phase I control containers (i.e., opaque with solid lids) were used as the stimulus containers in the test trials for this condition as we wanted the subject to make olfactory decisions based on the trail scent without being influenced by the odor of the food inside the container. cache = ./cache/cord-263088-zj14ro5j.txt txt = ./txt/cord-263088-zj14ro5j.txt === reduce.pl bib === id = cord-259416-gvzp2h5g author = Ling, Shenglong title = Combined approaches of EPR and NMR illustrate only one transmembrane helix in the human IFITM3 date = 2016-04-05 pages = extension = .txt mime = text/plain words = 3975 sentences = 228 flesch = 50 summary = Systematic site-directed spin labeling (SDSL) and electron paramagnetic resonance (EPR) studies of IFITM3 in detergent micelles identified a single, long transmembrane helix in the C-terminus and an intramembrane segment in the N-terminal hydrophobic region. Systematic site scanning of spin labeling, EPR dynamic and accessibility analysis identified a C-terminal transmembrane α -helix and an N-terminal IFITM3 segment (composed of two short α -helices) lying on the surface of micelles. Collectively, the analysis of the accessibility parameter (Π O2 and Π NiEDDA ) and the immersion depth parameter (Φ ) derived from the power saturation experiments demonstrated that the IFITM3 protein contains a long transmembrane α -helix covering the residue sequence from A96 to A131 in the putative hydrophobic region. Therefore, the combined EPR and solution NMR studies clearly supported the type II transmembrane protein topology model for IFITM3, which is consistent with the previously proposed mechanism of its antiviral function. cache = ./cache/cord-259416-gvzp2h5g.txt txt = ./txt/cord-259416-gvzp2h5g.txt === reduce.pl bib === id = cord-271602-f14wccj3 author = Kim, Hyun Cheol title = Recent increase of surface particulate matter concentrations in the Seoul Metropolitan Area, Korea date = 2017-07-05 pages = extension = .txt mime = text/plain words = 3264 sentences = 170 flesch = 45 summary = A 12-year (2004–2015) regional air quality simulation was conducted over East Asia (27-km) and over South Korea (9-km) to assess the impact of meteorology under constant anthropogenic emissions. Simulated PM concentrations show a strong negative correlation (i.e. R = −0.86) with regional wind speed, implying that reduced regional ventilation is likely associated with more stagnant conditions that cause severe pollutant episodes in South Korea. We conclude that the current PM concentration trend in South Korea is a combination of long-term decline by emission control efforts and short-term fluctuation of regional wind speed interannual variability. Three factors, long-term trend by emission control, short-term variation by meteorology, and sporadic offsets by unexpected social or economic episodes, seem to be affecting PM concentrations in South Korea. In order to investigate the interannual variation of surface PM concentration in the SMA, we conducted a 12-year simulation using a regional air quality modeling system. cache = ./cache/cord-271602-f14wccj3.txt txt = ./txt/cord-271602-f14wccj3.txt === reduce.pl bib === id = cord-254653-4ffuivil author = Cinelli, Matteo title = The COVID-19 social media infodemic date = 2020-10-06 pages = extension = .txt mime = text/plain words = 5100 sentences = 289 flesch = 50 summary = We address the diffusion of information about the COVID-19 with a massive data analysis on Twitter, Instagram, YouTube, Reddit and Gab. We analyze engagement and interest in the COVID-19 topic and provide a differential assessment on the evolution of the discourse on a global scale for each platform and their users. We fit information spreading with epidemic models characterizing the basic reproduction number [Formula: see text] for each social media platform. Unlike previous works, we do not only focus on models that imply specific growth mechanisms, but also on phenomenological models that emphasize the reproducibility of empirical data 41 www.nature.com/scientificreports/ Most of the epidemiological models focus on the basic reproduction number R 0 , representing the expected number of new infectors directly generated by an infected individual for a given time period 42 . Furthermore, we model the spread of information using epidemic models and provide basic growth parameters for each social media platform. cache = ./cache/cord-254653-4ffuivil.txt txt = ./txt/cord-254653-4ffuivil.txt === reduce.pl bib === id = cord-255586-wshvvgxg author = He, Shengyang title = Clinical characteristics of “re-positive” discharged COVID-19 pneumonia patients in Wuhan, China date = 2020-10-15 pages = extension = .txt mime = text/plain words = 2920 sentences = 163 flesch = 45 summary = The demographic features, clinical symptoms, laboratory results, comorbidities, co-infections, treatments, illness severities and chest CT scan results of 267 patients were collected from 1st January to 15th February 2020. | (2020) 10:17365 | https://doi.org/10.1038/s41598-020-74284-6 www.nature.com/scientificreports/ disease progression, no differences were found, suggesting this group of COVID-19 patients could be difficult to detect by using standard clinical data. All raw clinical and laboratory results were collected from electronic medical records system of the Central Hospital of Wuhan, followed by a follow up visit up to 14 days (also known as the discharge quarantine) to test for a re-positive nucleic acid assay. Definition of "re-positive": when a confirmed COVID-19 patient is detected SARS-CoV-2 RNA positive during the 14 days post-discharge quarantine (random test timing). Since understanding of the mechanisms of SARS-CoV-2 infection is still lacking, a careful discharge protocol should be applied (e.g. negative results of the nucleic acid tests of respiratory pathogens for 3 consecutive times), and post-discharge quarantine should be strictly observed, especially for severe and critical COVID-19 patients. cache = ./cache/cord-255586-wshvvgxg.txt txt = ./txt/cord-255586-wshvvgxg.txt === reduce.pl bib === id = cord-271328-zdf5ji4k author = Gu, Hongjing title = Angiotensin-converting enzyme 2 inhibits lung injury induced by respiratory syncytial virus date = 2016-01-27 pages = extension = .txt mime = text/plain words = 3910 sentences = 196 flesch = 52 summary = In this paper, we report that angiotensin-converting enzyme-2 (ACE2) protected against severe lung injury induced by RSV infection in an experimental mouse model and in pediatric patients. To determine the role of ACE2 in RSV-induced lung injury, we first measured the levels of Ang II in the plasma of RSV-infected patients. Importantly, ACE2 protein levels were dramatically decreased in lung homogenates from mice infected with RSV BJ016 virus at 3 days post-infection (p < 0.01; Fig. 1d ). Our data suggest that RSV infection causes severe lung injury in an experimental mouse model and in patients, at least in part by modulating the RAS system via down-regulation of the ACE2-AT1R axis. Importantly, the levels of Ang II were elevated following down-regulation of ACE2, causing severe lung injury via AT1R during the process of RSV infection (Fig. 5d) . cache = ./cache/cord-271328-zdf5ji4k.txt txt = ./txt/cord-271328-zdf5ji4k.txt === reduce.pl bib === id = cord-269756-tid8a464 author = Basso, Luis G. M. title = SARS-CoV fusion peptides induce membrane surface ordering and curvature date = 2016-11-28 pages = extension = .txt mime = text/plain words = 12194 sentences = 532 flesch = 49 summary = Although membrane fusion promoted by class I viral glycoproteins, such as SARS-CoV Spike, human immunodeficiency virus (HIV) gp160 or influenza virus hemagglutinin (HA), has been broadly studied in recent years [16] [17] [18] [19] , many aspects of the molecular mechanism behind the virus-host cell membrane fusion remain unknown, including conformational changes of the lipid bilayers during peptide-membrane interactions. In the present study, we investigated the effects of two putative fusion peptides from SARS-CoV S glycoprotein, corresponding to residues 770-788 (SARS FP ) and 873-888 (SARS IFP ) 13, 15, 22, 23 , on the structural dynamics, physicochemical properties, and thermotropic phase behavior of lipid model membranes by differential scanning calorimetry (DSC), continuous wave (CW) and pulsed electron spin resonance (ESR) along with nonlinear least-squares (NLLS) spectral fitting 24 . cache = ./cache/cord-269756-tid8a464.txt txt = ./txt/cord-269756-tid8a464.txt === reduce.pl bib === id = cord-265891-jmpterrj author = Eilersen, Andreas title = Cost–benefit of limited isolation and testing in COVID-19 mitigation date = 2020-10-29 pages = extension = .txt mime = text/plain words = 3925 sentences = 233 flesch = 56 summary = Therefore, we will here implement a crude form of contact tracing where we (1) close the workplaces of people who are tested positive for the disease, (2) isolate their regular social contacts for a limited period, and (3) keep symptomatic individuals in quarantine until they recover. If 10% efficiency is possible, corresponding to detecting about a third of infectious cases, then peak height could be reduced by a factor of almost three with to a 60% drop, if the probability of infected people being tested is only 10% per day of illness. In Fig. 4 , we show two possible scenarios where testing and contact tracing is implemented after a 30-day lockdown with a 75% reduction of the work and social spheres. Using reasonable COVID-19 infection parameters we find that the 1STQ strategy can contribute to epidemic mitigation, in the sense that it can reduce the peak number of infected individuals by about a factor of two even with a realistic testing rate of 10% per day of illness. cache = ./cache/cord-265891-jmpterrj.txt txt = ./txt/cord-265891-jmpterrj.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-277816-ncdy9qgb author = Wang, Ji-gan title = Gastrointestinal symptoms and fecal nucleic acid testing of children with 2019 coronavirus disease: a systematic review and meta-analysis date = 2020-10-20 pages = extension = .txt mime = text/plain words = 3600 sentences = 202 flesch = 48 summary = title: Gastrointestinal symptoms and fecal nucleic acid testing of children with 2019 coronavirus disease: a systematic review and meta-analysis In order to understand the clinical manifestations and incidence of gastrointestinal symptoms of coronavirus disease (COVID-19) in children and discuss the importance of fecal nucleic acid testing.We retrospectively analyzed studies on gastrointestinal symptoms and fecal nucleic acid detection in pediatric COVID-19 patients from January 1, 2020 to August 10, 2020, including prospective clinical studies and case reports. Stata12.0 software was used for meta-analysis.The results showed that the most common gastrointestinal symptoms in children with COVID-19 were vomiting and diarrhea, with a total incidence of 17.7% (95% Cl 13.9–21.5%). At present, there is no relevant study on whether there is a difference in the positive rate of fecal nucleic acid testing in COVID-19 children with and without diarrhea. Clinical features of 33 cases in children infected with SARS-CoV-2 in Anhui Province, China: a multi-center retrospective cohort study. cache = ./cache/cord-277816-ncdy9qgb.txt txt = ./txt/cord-277816-ncdy9qgb.txt === reduce.pl bib === id = cord-276997-hbovh7s9 author = Alsved, Malin title = Aerosolization and recovery of viable murine norovirus in an experimental setup date = 2020-09-29 pages = extension = .txt mime = text/plain words = 6031 sentences = 297 flesch = 46 summary = However, the infectivity of airborne human noroviruses has not been possible to assess in real-world environments, nor in laboratory experiments, since there is no well-established cell culturing system for these viruses working at the low concentrations obtained in air samples 6 . SLAG: Sparging liquid aerosol generator; HEPA filter: high efficiency particulate air filter; nsRNA: negative sense RNA; psRNA: positive sense RNA; MNV: murine norovirus; qRT-PCR: quantitative reverse transcriptase polymerase chain reaction. Taken together, as compared to the atomizer, a smaller amount of SLAG aerosol is collected by the BioSampler (i.e., higher physical dilution), but these particles contain more MNV psRNA copies (lower viral dilution relative the physical dilution). The experimental setup described here highlights some difficulties in studies on aerosolized viruses: (1) the lack of standards in how to generate bioaerosol that results in significant differences in aerosol particle size and concentration, (2) the necessity to determine both physical and viral dilution factors, and (3) www.nature.com/scientificreports/ during airborne transport due to the low-solute solution and dilution in the setup. cache = ./cache/cord-276997-hbovh7s9.txt txt = ./txt/cord-276997-hbovh7s9.txt === reduce.pl bib === id = cord-281536-8y7yxcp4 author = Lim, Hocheol title = Hot spot profiles of SARS-CoV-2 and human ACE2 receptor protein protein interaction obtained by density functional tight binding fragment molecular orbital method date = 2020-10-08 pages = extension = .txt mime = text/plain words = 3527 sentences = 178 flesch = 55 summary = title: Hot spot profiles of SARS-CoV-2 and human ACE2 receptor protein protein interaction obtained by density functional tight binding fragment molecular orbital method In this work, to find common hot spot amino acids on the interfaces between the RBD domain and hACE2 of the three complexes, RBD-SARS-CoV-2/hACE2 (twelve experimental structural data), RBD-SARS-CoV-1/ hACE2 (four experimental structural data), and RBD-HCoV-NL63/hACE2 (one experimental structural data), we performed FMO-DFTB3/D/PCM calculations. Consequently, we summarized the FMO-DFTB3/D/PCM/3D-SPIEs results as interaction maps and found the hot spot regions in RBD-SARS-CoV-2 and hACE2 at a QM level. In order to narrow down the hot spot regions between hACE2 and RBD-SARS-CoV-1, we performed FMO calculations on four RBD-SARS-CoV-1/antibody complexes (Supplementary Table S14-S19). In order to find common hot spot amino acids in RBD-SARS-CoV-1 against hACE2 and SARS-CoV-1 antibodies, we illustrated the FMO results with a 3D-SPIEs-based map. cache = ./cache/cord-281536-8y7yxcp4.txt txt = ./txt/cord-281536-8y7yxcp4.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-283583-pwlbrxn3 author = Zhang, Xiao-Ai title = Prevalence and genetic characteristics of Saffold cardiovirus in China from 2009 to 2012 date = 2015-01-09 pages = extension = .txt mime = text/plain words = 3779 sentences = 207 flesch = 51 summary = A higher frequency of severe clinical outcome and nervous system manifestation were also observed in the SAFV-positive HFMD patients. A patient was considered to be infected with SAFV when positive detection was obtained in any type of the samples. Genetic characterization of SAFVs. A phylogenetic tree was constructed based on the VP1 nucleotide sequences of Saffold cardiovirus detected in clinical samples of 82 patients in the current study, and sequences downloaded from GenBank by maximum likelihood method using MEGA 6.0 (Figure 1) . Detection of SAFV in sera and CSFs. Additional 171 CSFs were collected from patients with HFMD-associated encephalitis, and six (3.5%) were found to be SAFV-positive using real-time RT-PCR, and five were further confirmed by nested RT-PCR targeting the 59-UTR. In our study, SAFVs were co-detected with other viruses in 14 (82.4%), 9 (75.0%), and 28 (32.6) specimens in ARTI, diarrhea and HFMD patients respectively. cache = ./cache/cord-283583-pwlbrxn3.txt txt = ./txt/cord-283583-pwlbrxn3.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-284374-sqxlnk9e author = Park, Jiyeon title = Infection Prevention Measures for Surgical Procedures during a Middle East Respiratory Syndrome Outbreak in a Tertiary Care Hospital in South Korea date = 2020-01-15 pages = extension = .txt mime = text/plain words = 4252 sentences = 208 flesch = 44 summary = title: Infection Prevention Measures for Surgical Procedures during a Middle East Respiratory Syndrome Outbreak in a Tertiary Care Hospital in South Korea Our experience with setting up a temporary negative-pressure operation room and our conservative approach for managing MERS-related patients can be referred in cases of future unexpected MERS outbreaks in non-endemic countries. Anesthesiologists were recommended to apply enhanced PPE (including PAPR from the middle of the outbreak) when managing all MERS-related patients because they were most directly exposed to the aerosol-producing high-risk procedures, such as endotracheal intubation and extubation. Almost all hospitals generally have positive-pressure operating rooms and they may experience an outbreak without facilities that are prepared for perioperative management of MERS patients, as our hospital did in 2015. First, although the previous guidelines recommended that asymptomatic MERS-exposed patients be managed as general patients undergoing surgery, we applied standard PPE to HCWs and we performed MERS-CoV PCR screening twice. cache = ./cache/cord-284374-sqxlnk9e.txt txt = ./txt/cord-284374-sqxlnk9e.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-268414-7fcc5i7i author = Hassani, Abdelkader title = Preparation, characterization and therapeutic properties of gum arabic-stabilized gallic acid nanoparticles date = 2020-10-20 pages = extension = .txt mime = text/plain words = 7105 sentences = 379 flesch = 47 summary = The formulated nanoparticles (GANPs) were characterized for physicochemical properties and size and were then evaluated for antioxidant and antihypertensive effects using various established in vitro assays, including 1,1-diphenyl-2-picrylhydrazyl (DPPH), nitric oxide scavenging (NO), β-carotene bleaching and angiotensin-converting enzyme (ACE) inhibitory assays. This study is the first to confirm the synergistic effects of gum arabic in the encapsulation of gallic acid by increasing the selectivity towards cancer cells and enhancing the antioxidant properties. According to the results, significant cytotoxicity was elicited among the HepG2, MCF7, MDA-MB231, and HT29 cell lines after treatment with IC 50 concentrations of free and nano encapsulated gallic acid as shown in Fig. 12 . The MDA-MB231 and HT29 cells had a lower fluorescence intensity of PI attributed to the lower toxicity of GA/C6NPs. www.nature.com/scientificreports/ The migration assay was carried out to assess the effect of GANPS and free GA with the IC 50 value of concentrations on MCF7, MDA-MB-231, HepG2, and HT29. cache = ./cache/cord-268414-7fcc5i7i.txt txt = ./txt/cord-268414-7fcc5i7i.txt === reduce.pl bib === id = cord-284582-xwedgllw author = Korabecna, M. title = Cell-free DNA in plasma as an essential immune system regulator date = 2020-10-15 pages = extension = .txt mime = text/plain words = 5714 sentences = 306 flesch = 46 summary = These expression profiles provide evidence that the presence of cfDNA and its clearance in plasma of healthy individuals regulate fundamental mechanisms of the inflammation process and tissue homeostasis. We used native human plasma samples obtained from healthy volunteers with no animal serum addition to the cultivation medium in order to avoid the presence of uncharacterized animal cfDNA and DNases in the experiments. We used the validation phase results to perform a direct comparison of signaling pathways activated in cells as a consequence of their treatment with NP or TP samples (Table 1a , b) using the database Reactome. The changes in expression profiles of selected validated genes were detectable after the decrease of cfDNA levels to 69.10% of its original native concentration as the result of endogenous DNAse I activity ( Supplementary Fig. 1 ). However, the cells treated with identical plasma samples with degraded cfDNA directly activate IIR with elevated production of mRNA for interleukin 8 at the transcriptomic level. cache = ./cache/cord-284582-xwedgllw.txt txt = ./txt/cord-284582-xwedgllw.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-288761-fyvr0tc1 author = Santiago, César title = Allosteric inhibition of aminopeptidase N functions related to tumor growth and virus infection date = 2017-04-10 pages = extension = .txt mime = text/plain words = 5859 sentences = 342 flesch = 58 summary = These structures identified three distinct APN conformations, based on active site accessibility, which we termed closed, intermediate and open forms (Fig. 1a) . The phenylalanine was located in the loop that connects α 26 and α 27 in the single domain IV ARM repeat of human and pig APN (Fig. 2a) ; it penetrated the active site groove in the closed conformation and locked the peptide, ready for hydrolysis. CoV binding to APN would lock the protein in its open conformation (Fig. 2b) , preventing the ectodomain movement probably necessary for peptide hydrolysis (Fig. 2a) . In flow cytometry, we determined the binding of an RBD-Fc fusion protein to cells that expressed pAPN or an active site mutant (pAPN-HH/AA), alone or with various drugs (Fig. 4a,b) . Disulfide bonds that lock the APN closed conformation or drugs that prevent opening of the ectodomain inhibited CoV protein binding and cell infection, whereas porcine CoV S proteins probably hinder APN transition to the closed form and peptide hydrolysis. cache = ./cache/cord-288761-fyvr0tc1.txt txt = ./txt/cord-288761-fyvr0tc1.txt === reduce.pl bib === id = cord-288721-3bv3aak6 author = Schneider, Annika title = Single organelle analysis to characterize mitochondrial function and crosstalk during viral infection date = 2019-06-11 pages = extension = .txt mime = text/plain words = 5604 sentences = 309 flesch = 39 summary = Thus, single-organelle and multi-parameter resolution allows to explore altered energy metabolism and antiviral defence by tagged mitochondria selectively in virus-infected cells and will be instrumental to identify viral immune escape and to develop and monitor novel mitochondrial-targeted therapies. When challenged with high concentrations of calcium (100 µM), mitochondria isolated from virus-infected livers are much more fragile shown by time-dependent loss of membrane potential and change of their morphology indicated by decrease in side-scatter (Fig. 2F ). Number of viable mitochondria detected per second by flow-cytometry declined after calcium challenge, consistent with loss of mitochondrial integrity, and did so much faster in samples from virus-infected livers (Fig. 2F ). In order to further evaluate mitochondrial functionality, we challenged mitochondria with Ca 2+ as stress test and performed time kinetic measurements of DilC 1 (5) fluorescence and side-scatter of mito-DsRed + and mito-DsRed − mitochondria isolated from Ad-CMV-mitoRL infected livers. cache = ./cache/cord-288721-3bv3aak6.txt txt = ./txt/cord-288721-3bv3aak6.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-286413-a7wue2e3 author = Cohen, Isaac V. title = Cardiac adverse events associated with chloroquine and hydroxychloroquine exposure in 20 years of drug safety surveillance reports date = 2020-11-05 pages = extension = .txt mime = text/plain words = 3609 sentences = 205 flesch = 48 summary = title: Cardiac adverse events associated with chloroquine and hydroxychloroquine exposure in 20 years of drug safety surveillance reports The cardiac AEs of these therapeutics are of increased concern since a subset of patients infected with COVID-19 present with cardiac injury, suggesting a relevant cardiovascular involvement in the pathophysiology of the disease 22 . The goal of this study is to reanalyze the extensive clinical data of CQ and HCQ cardiac AEs collected during the last 20 years to derive the strength of the associations and, more importantly, contributing risk factors. In our study we analyzed 702,274 FDA adverse event reports divided into CQ, HCQ and control cohorts to determine their association with cardiac AEs when taking into account other factors. The regression model was instrumental to exclude this aspirin association from the quantification of the direct cardiac side effects of CQ and HCQ, which remained significant after adjustment ( Generalizability of results to COVID-19 treatment with CQ and HCQ. cache = ./cache/cord-286413-a7wue2e3.txt txt = ./txt/cord-286413-a7wue2e3.txt === reduce.pl bib === id = cord-296867-6o4scan1 author = Hisada, Shohei title = Surveillance of early stage COVID-19 clusters using search query logs and mobile device-based location information date = 2020-10-29 pages = extension = .txt mime = text/plain words = 3803 sentences = 206 flesch = 59 summary = title: Surveillance of early stage COVID-19 clusters using search query logs and mobile device-based location information In contrast, we utilized web search query logs per user to detect WSSCI and gather their location histories to identify locations they visited or passed through, resulting in COVID-19 cluster detection. In the Kitami area (Fig. 3a) , the WSSCI has a maximum cross-correlation of 0.766, determined 2 days after the change in the number of new patients. This study attempted to detect early clusters by identifying people who suspected their own COVID-19 infection using web search query logs and by extracting their location information. We utilized web search query log data and location information provided by Yahoo Japan Corporation 17 as signals for syndromic surveillance. Syndromic surveillance using search query logs and user location information from smartphones against COVID-19 clusters in Japan cache = ./cache/cord-296867-6o4scan1.txt txt = ./txt/cord-296867-6o4scan1.txt === reduce.pl bib === === reduce.pl bib === id = cord-293372-saqoft9p author = Heffner, Kelley title = Expanded Chinese hamster organ and cell line proteomics profiling reveals tissue-specific functionalities date = 2020-09-28 pages = extension = .txt mime = text/plain words = 4862 sentences = 274 flesch = 45 summary = Quantitative proteomics data were obtained from two CHO cell lines (CHO-S and CHO DG44) and compared with seven Chinese hamster (Cricetulus griseus) tissues (brain, heart, kidney, liver, lung, ovary and spleen) by tandem mass tag (TMT) labeling followed by mass spectrometry, providing a comprehensive hamster tissue and cell line proteomics atlas. This study was undertaken to compare protein expression of various CHO cell lines and hamster tissues, resulting in the most comprehensive multi-tissue analysis of the Cricetulus griseus proteome (Fig. 1A) . Similar to the ovary and lung comparison, there are a greater number of proteins with higher expression in the heart tissue when compared to cell lines. These differences highlight the role of tissues in executing key organ functions which require a specific metabolic processes, such as transport and communication, in comparison to CHO cells, which are focused on replication and gene expression, characteristics useful for rapid growth and the production of biologics. cache = ./cache/cord-293372-saqoft9p.txt txt = ./txt/cord-293372-saqoft9p.txt === reduce.pl bib === id = cord-299605-j1ewxk4q author = Lin, Jing-wen title = Signatures of malaria-associated pathology revealed by high-resolution whole-blood transcriptomics in a rodent model of malaria date = 2017-02-03 pages = extension = .txt mime = text/plain words = 6667 sentences = 326 flesch = 49 summary = c. chabaudi, AS and CB, that differ in virulence in C57BL/6 mice, we performed high-resolution comparative whole-blood transcriptomic analysis throughout the acute phase of the blood-stage infection, and identified several transcriptomic signatures associated with severe malarial pathology before the onset of pathology or disease. Spearman's rank correlation coefficient (r s ) analysis of unfiltered transcripts normalised across the median of all samples, revealed high levels of similarity amongst naïve and 2, 4 dpi samples in both AS and CB infections (Fig. 2ai ,ii, r s ranging from 0.73 to 0.88), while from 6 dpi onwards the whole blood transcriptomes diverge significantly from the earlier time points (r s ranging from 0.08 to − 0.59 compared to naïve controls). Importantly, in 4 of the CB infected mice that had reached humane end points at 9 dpi, these 5 genes showed an even higher level of up-regulation compared to naïve controls (Fig. 3c) , indicating possible lung pathology in these 4 CB infected mice. cache = ./cache/cord-299605-j1ewxk4q.txt txt = ./txt/cord-299605-j1ewxk4q.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-296562-3h2oqb9k author = Guillén, Lucía title = Preemptive interleukin-6 blockade in patients with COVID-19 date = 2020-10-08 pages = extension = .txt mime = text/plain words = 4874 sentences = 246 flesch = 44 summary = In contrast to other respiratory viral infections like influenza, a major pathogenic mechanism implicated in severe clinical manifestations of COVID-19 is an aberrant host immune response resulting in an excessive cytokine and chemokine release known as "cytokine storm" or "cytokine release syndrome" 2,3 . In a sensitivity analysis including only the 55 patients with confirmed SARS-CoV-2 infection by RT-PCR, the significant variables in the adjusted multivariate model were a NLR > 2.55 (OR 5.26; 95% CI 1.02-25), higher Charlson comorbidity index (OR 1.56; 95% CI 1.04-2.34) per unit, and higher SOFA score (OR 5.05; 95% CI 1.10-23.24) (Supplementary Table 2 ). This biomarker reflects excessive inflammation and dysregulation of immune cells that play a central role in severity of disease in viral infections 23 , and has been associated with mortality in patients hospitalized with COVID-19 24 . www.nature.com/scientificreports/ four comorbidities are included in the Charlson index, and have been associated with higher disease severity in patients with COVID-19 31 . cache = ./cache/cord-296562-3h2oqb9k.txt txt = ./txt/cord-296562-3h2oqb9k.txt === reduce.pl bib === id = cord-302459-grs2x26l author = Matin, Farhana title = A Plasma Biomarker Panel of Four MicroRNAs for the Diagnosis of Prostate Cancer date = 2018-04-27 pages = extension = .txt mime = text/plain words = 8311 sentences = 413 flesch = 48 summary = In this study we profiled 372 cancer-associated miRNAs in plasma collected before (~60% patients) and after/during commencement of treatment (~40% patients), from age-matched prostate cancer patients and healthy controls, and observed elevated levels of 4 miRNAs miR-4289, miR-326, miR-152-3p and miR-98-5p, which were validated in an independent cohort. Analysis of published miRNA transcriptomic data from clinical samples in the TCGA dataset demonstrated low expression of miR-152-3p in tumour compared to adjacent non-malignant tissues (p = 0.001) (Wilcoxon test, p ≤ 0.05) (Fig. 4) Figure S3) . Similarly, other groups have assessed the diagnostic performance of plasma or serum miRNAs in patients with localised or metastatic prostate cancer, BPH and healthy controls, and in most instances the specificity and sensitivity of the miRNA biomarkers have outperformed the accuracy of the PSA test 23, 28, 29 . cache = ./cache/cord-302459-grs2x26l.txt txt = ./txt/cord-302459-grs2x26l.txt === reduce.pl bib === id = cord-303601-o8uk6if2 author = Tsay, Calvin title = Modeling, state estimation, and optimal control for the US COVID-19 outbreak date = 2020-07-01 pages = extension = .txt mime = text/plain words = 6180 sentences = 331 flesch = 49 summary = This includes modeling the dynamics of affected populations, estimating the model parameters and hidden states from data, and an optimal control strategy for sequencing social distancing and testing events such that the number of infections is minimized. Figure 2 shows the predicted values obtained by solving the parameter estimation problem and the historical data by country, retrieved by the Center for Systems Science and Engineering (CSSE) at Johns Hopkins University (https ://githu b.com/CSSEG ISand Data/COVID -19; accessed April 16, 2020). For the estimated parameter values as described previously, we simulate the results of implementing two different simplistic control policies: (i) continuing with strict social distancing, quarantining, and testing, policies that result from continuing to lower the asymptomatic ( α a ) and infected ( α i ) exposures shown in Fig. 2 ; and (ii) a relaxed policy with more lenient measures and reduced testing, in this case the values of α a and α i are increased to 0.2 and 0.02, respectively, while κ is decreased to 0.2. cache = ./cache/cord-303601-o8uk6if2.txt txt = ./txt/cord-303601-o8uk6if2.txt === reduce.pl bib === id = cord-308302-5yns1hg9 author = Wu, Gang title = A prediction model of outcome of SARS-CoV-2 pneumonia based on laboratory findings date = 2020-08-20 pages = extension = .txt mime = text/plain words = 2966 sentences = 202 flesch = 48 summary = We used machine learning for processing laboratory findings of 110 patients with SARS-CoV-2 pneumonia (including 51 non-survivors and 59 discharged patients). Thus it is feasible to establish an accurate prediction model of outcome of SARS-CoV-2 pneumonia based on laboratory findings. Laboratory tests for SARS-CoV-2 pneumonia included: blood routine test, serum biochemical (including glucose, renal and liver function, creatine kinase, lactate dehydrogenase, and electrolytes), coagulation profile, cytokine test, markers of myocardial injury, infection-related makers, and other enzymes. 68 discharged patients with SARS-CoV-2 pneumonia whose age and gender matched the non-survivors were selected (46 male, median age 66 years). A number of laboratory features were compared between non-survivors and discharged patients with SARS-CoV-2 pneumonia. With machine learning methods previously used in radiomics, a prediction model combining seven out of thirty-eight laboratory features was built for predicting the outcome of SARS-CoV-2 pneumonia. cache = ./cache/cord-308302-5yns1hg9.txt txt = ./txt/cord-308302-5yns1hg9.txt === reduce.pl bib === id = cord-305132-jspxlk1a author = Homma, Takujiro title = Persistent prion infection disturbs the function of Oct-1, resulting in the down-regulation of murine interferon regulatory factor-3 date = 2014-08-08 pages = extension = .txt mime = text/plain words = 3536 sentences = 248 flesch = 56 summary = In this study, we analyzed murine IRF-3 promoter activity in detail and its relationship to prion infection, and have shown that the octamer-binding transcription factor-1 (Oct-1) positively regulates murine IRF-3, and the expression levels of Oct-1 decreased in prion-infected cells. Furthermore, in the persistently other prion strain-infected cells by the mouse-adapted Gerstmann-Sträussler-Schenker syndrome (GSS) Fukuoka-1 strain (FK-N2a58), IRF-3 mRNA and the promoter activity were also significantly decreased (Supplementary Fig. S6a and S6b). PCR analysis revealed that the Oct-1 antibody precipitated the promoter region (nt -119 to -1) from N2a58 cells (Fig. 4a) , while the negative control (anti-rabbit IgG) did not exhibit the DNA binding activity. These results demonstrate that reduced IRF-3 promoter activity in prion-infected cells is accompanied by decreased levels of Oct-1. In summary, our results demonstrated that Oct-1 binds to the murine IRF-3 promoter region and increases the transcription level and IRF-3 expression is reduced by prion infection. cache = ./cache/cord-305132-jspxlk1a.txt txt = ./txt/cord-305132-jspxlk1a.txt === reduce.pl bib === id = cord-309127-kxivgxbg author = Haverkamp, Ann-Kathrin title = Experimental infection of dromedaries with Middle East respiratory syndrome-Coronavirus is accompanied by massive ciliary loss and depletion of the cell surface receptor dipeptidyl peptidase 4 date = 2018-06-27 pages = extension = .txt mime = text/plain words = 6524 sentences = 296 flesch = 38 summary = title: Experimental infection of dromedaries with Middle East respiratory syndrome-Coronavirus is accompanied by massive ciliary loss and depletion of the cell surface receptor dipeptidyl peptidase 4 In line with these observations, high amounts of MERS-CoV antigen were detected within the respiratory epithelium of the nasal turbinates of mock-vaccinated dromedaries at 4 dpi by immunohistochemistry in areas SciEntiFic REpORTS | (2018) 8:9778 | DOI:10.1038/s41598-018-28109-2 with most severe lesions ( Fig. 2A) . To finally elucidate the histogenesis of cells staining positive for MERS-CoV nucleocapsid antigen within the lamina propria of the nasal turbinates of mock-vaccinated dromedaries, additional double immunofluorescence labeling was performed. Since DPP4 was only detectable within the apical brush border of the surface epithelium and submucosal glands, but not on the surface of inflammatory cells within lamina propria and submucosa of the nasal turbinates by immunofluorescence, dromedary and human lymphoid tissue were stained for comparison and control. cache = ./cache/cord-309127-kxivgxbg.txt txt = ./txt/cord-309127-kxivgxbg.txt === reduce.pl bib === === reduce.pl bib === id = cord-308687-wrzzb9cy author = Brunner, Jesse L. title = Pooled samples and eDNA-based detection can facilitate the “clean trade” of aquatic animals date = 2020-06-24 pages = extension = .txt mime = text/plain words = 6488 sentences = 322 flesch = 46 summary = swabs) and eDNA samples collected from finite populations and discuss key assumptions and considerations for their use with a focus on detecting Batrachochytrium salamandrivorans, an emerging pathogen that threatens global salamander diversity. www.nature.com/scientificreports www.nature.com/scientificreports/ context of screening U.S. service members for syphilis, pooling samples to reduce the number of tests required to detect rare infections is common in numerous contexts 22 , including surveys for disease freedom. In this paper I therefore develop formulae for imperfect tests of pooled samples in closed populations and eDNA, discuss the key assumptions and considerations in their application, and illustrate how eDNA may be especially useful for detecting infections in the live animal trade. Pooling and batch-processing samples collected from individual animals (e.g., swabs) can reduce several fold the number of diagnostic tests (e.g., DNA extractions and PCR reactions) required to detect rare infections. cache = ./cache/cord-308687-wrzzb9cy.txt txt = ./txt/cord-308687-wrzzb9cy.txt === reduce.pl bib === === reduce.pl bib === id = cord-315415-3aotsb2g author = Dong, Jianbo title = Development of humanized tri-specific nanobodies with potent neutralization for SARS-CoV-2 date = 2020-10-20 pages = extension = .txt mime = text/plain words = 7194 sentences = 427 flesch = 57 summary = In this study we used computer-aided design to construct multi-specific VHH antibodies fused to human IgG1 Fc domains based on the epitope predictions for leading VHHs. The resulting tri-specific VHH-Fc antibodies show more potent S1 binding, S1/ACE2 blocking, and SARS-CoV-2 pseudovirus neutralization than the bi-specific VHH-Fcs or combination of individual monoclonal VHH-Fcs. Furthermore, protein stability analysis of the VHH-Fcs shows favorable developability features, which enable them to be quickly and successfully developed into therapeutics against COVID-19. (c) The binding of VHH-Fcs and ACE2 to Expi293 cells expressing SARS-CoV-2 S1 wild type (WT) or mutant proteins (del1-del5) were assessed by flow cytometry following FITC-conjugated secondary antibody treatment. Based on the binding and epitope binning data, we constructed 3D docking models that predicted the interactions between SARS-CoV-2 S1 RBD, ACE2 and lead VHH-Fcs (Fig. 2e) . Next, we tested whether the combination of individual VHHs binding to different S1 RBD epitopes into bi-specific antibody molecules would yield synergistic effects in SARS-CoV-2 binding and S/ACE2 blocking. cache = ./cache/cord-315415-3aotsb2g.txt txt = ./txt/cord-315415-3aotsb2g.txt === reduce.pl bib === id = cord-305031-9ze0097w author = Büchel, Beda title = Empirical dynamics of railway delay propagation identified during the large-scale Rastatt disruption date = 2020-10-29 pages = extension = .txt mime = text/plain words = 7695 sentences = 336 flesch = 47 summary = We cannot consider delay changes for freight traffic, as its volume was strongly affected by the Rastatt disruption; and more generally, freight traffic does not stop at stations thus having a ill-defined delay; and Scientific Reports | (2020) 10:18584 | https://doi.org/10.1038/s41598-020-75538-z www.nature.com/scientificreports/ despite its buffer times are typically large, its performance is often erratic. We now discuss how a state-of-the-art simulation model, OnTime, based on typical delay propagation theory 39 (the Methods section describes its assumptions and functioning, and its calibration for the test case) can partially replicate the degree by which the delay performance of passenger trains improved in the area of Basel, and decreased in the area of Schaffhausen. Newly designed statistical tests were applied to delay analysis in railway networks, performed at different percentile levels, over multiple time scales, and two specific factors (reduced entrance delay for passenger trains and rerouted freight trains). cache = ./cache/cord-305031-9ze0097w.txt txt = ./txt/cord-305031-9ze0097w.txt === reduce.pl bib === id = cord-313126-7hrjzapj author = Chen, Fangzhou title = Decline of transmissible gastroenteritis virus and its complex evolutionary relationship with porcine respiratory coronavirus in the United States date = 2019-03-08 pages = extension = .txt mime = text/plain words = 4467 sentences = 211 flesch = 44 summary = Nineteen complete TGEV genomes and a single strain of porcine respiratory coronavirus (PRCV) from the US were generated and compared to historical strains to investigate the evolution of these endemic coronaviruses. The "variant" genotype shared similar unique deletions and amino acid changes with the recent PRCV strain identified in this study, suggesting a recombination event occurred between the ''variant'' TGEV and PRCV. Complete genomic sequences, a key residue in the spike protein and deletions in nonstructural protein 3b of US strains of the virulent and attenuated coronaviruses, transmissible gastroenteritis virus and porcine respiratory coronavirus cache = ./cache/cord-313126-7hrjzapj.txt txt = ./txt/cord-313126-7hrjzapj.txt === reduce.pl bib === id = cord-318187-c59c9vi3 author = Basu, Saikat title = Numerical evaluation of spray position for improved nasal drug delivery date = 2020-06-29 pages = extension = .txt mime = text/plain words = 7843 sentences = 375 flesch = 44 summary = The protocol involves re-orienting the spray axis to harness inertial motion of particulates and has been developed using computational fluid dynamics simulations of respiratory airflow and droplet transport in medical imaging-based digital models. Of interest are nasal spray simulation studies on in silico models, re-constructed from medical imaging, to measure drug delivery along the nasal passages 9 , in the sinuses 10, 11 , and on the effects of surgical alterations of the anatomy on nasal airflow [12] [13] [14] [15] as well as on topical transport of drugs [16] [17] [18] [19] . The computational fluid dynamics (CFD) models of droplet transport and the in silico prediction of their deposition sites along the nasal airway walls have been compared with in vitro spray experiments in 3D-printed solid replicas of the same anatomic reconstructions. cache = ./cache/cord-318187-c59c9vi3.txt txt = ./txt/cord-318187-c59c9vi3.txt === reduce.pl bib === id = cord-317579-ige2h4pd author = Nie, Lei title = Nanostructured selenium-doped biphasic calcium phosphate with in situ incorporation of silver for antibacterial applications date = 2020-08-13 pages = extension = .txt mime = text/plain words = 6082 sentences = 354 flesch = 47 summary = The results confirmed that the SeO(3)(2−) was doped at the PO(4)(3−) position and silver nanoparticles were deposited on the surface of SeB-NPs. Next, Transmission Electron Microscopy (TEM) analysis displayed that the prepared (Ag)SeB-NPs had a needle-cluster-like morphology. At the same time, biphasic calcium phosphate nanoparticles (BCP-NPs) and selenium-doped hydroxyapatite nanoparticles (SeHA-NPs) were prepared for comparison (Electronic Supplementary Material). Compared with the control group, the doping selenium into BCP-NPs had slight influence on the antibacterial activity, and it had a slight inhibitory effect against bacteria of SeB-NPs after 12 h of culture. The stated objective of this study was to synthesis new-style biphasic calcium phosphate nanoparticles (BCP-NPs) with excellent cytocompatibility and antibacterial activity for further hard-tissue engineering applications. After the deposition of silver, cells cultured with all Ag SeB-NPs samples had similar proliferation profiles compared with SeB-NPs. Not only can the addition of selenium and silver improve the growth of the cells with BCP-NPs, but the antibacterial activity was acquired, which has potential for infection-resistant replacement materials 61, 62 . cache = ./cache/cord-317579-ige2h4pd.txt txt = ./txt/cord-317579-ige2h4pd.txt === reduce.pl bib === id = cord-318587-ewvnkdr2 author = Steeds, Kimberley title = Pseudotyping of VSV with Ebola virus glycoprotein is superior to HIV-1 for the assessment of neutralising antibodies date = 2020-08-31 pages = extension = .txt mime = text/plain words = 4973 sentences = 244 flesch = 46 summary = We evaluated the suitability of EBOV GP pseudotyped human immunodeficiency virus type 1 (HIV-1) and vesicular stomatitis virus (VSV) to measure the neutralising ability of plasma from EVD survivors, when compared to results from a live EBOV neutralisation assay. The aim of this study was to assess the suitability of EBOV GP pseudotyped HIV-1 and VSV systems to measure neutralisation by EVD survivor plasma, in comparison with results from a live EBOV neutralisation assay. To determine the optimal pseudotyped virus input to use in the HIV-and VSV-based assays, neutralisation of different amounts of the EBOV GP pseudotyped viruses by plasma from a Guinean EVD survivor donor or human anti-EBOV GP mAb KZ52 was assessed. When IC 50 values of EBOV GP pseudotyped HIV-1 neutralisation of the 30 EVD survivor and 10 negative plasma samples were compared with GMT values for the live EBOV neutralisation assay, a positive correlation (r s = 0.54) was determined using the nonparametric Spearman correlation coefficient (Fig. 5a) and this was statistically significant (p = 0.0004). cache = ./cache/cord-318587-ewvnkdr2.txt txt = ./txt/cord-318587-ewvnkdr2.txt === reduce.pl bib === === reduce.pl bib === id = cord-314753-xflhxb13 author = Manso, Carmen F. title = Efficient and unbiased metagenomic recovery of RNA virus genomes from human plasma samples date = 2017-06-23 pages = extension = .txt mime = text/plain words = 6333 sentences = 296 flesch = 48 summary = The percentage of reads mapping to RNA virus genomes in the rRNA-depleted BBV Panel samples was between 40 and 150-fold higher than in corresponding untreated controls. The depth plots in Fig. 3 again show unbiased and even coverages across both genomes, and the percentages of reads mapping to viral targets was again much higher in the rRNA-depleted sample than in the untreated comparator (61-fold and 85-fold for HCV and HPgV respectively). By depleting host-derived nucleic acids and making modifications to an existing library preparation protocol to account for ultra-low RNA input quantities, we have been able to reconstruct effectively full-length genomes of HCV, HEV and HIV from plasma samples with viral loads of 10 4 IU/ml (copies/ml for HIV) and substantial fractions of complete genomes at 10 3 IU/ml. Additionally, our system was able to recover viral sequences from a panel of diverse RNA viruses diluted in human plasma, with a broad correlation between the genomic coverage and depth metrics and approximate concentration. cache = ./cache/cord-314753-xflhxb13.txt txt = ./txt/cord-314753-xflhxb13.txt === reduce.pl bib === id = cord-276185-ysspkbj7 author = Milewska, Aleksandra title = APOBEC3-mediated restriction of RNA virus replication date = 2018-04-13 pages = extension = .txt mime = text/plain words = 5507 sentences = 317 flesch = 54 summary = In experiments in vitro, three human APOBEC3 proteins (A3C, A3F and A3H) inhibited HCoV-NL63 infection and limited production of progeny virus, but did not cause hypermutation of the coronaviral genome. Although the precise molecular mechanism of deaminase-dependent inhibition of coronavirus replication remains elusive, our results further our understanding of APOBEC-mediated restriction of RNA virus infections. HCoV-NL63 infection resulted in upregulation of expression of A3A, A3C, A3D and A3F and A3C, A3F and A3H all inhibited HCoV-NL63 replication, we tested whether this inhibition was the result of the catalytic activity of the APOBECs. Plasmids encoding variants of A3C, A3F and A3H with Glu → Gln substitutions in the catalytic site were prepared 31 and mRNAs encoding active or inactive proteins were transfected into LLC-Mk2 cells, which were infected with HCoV-NL63 and cultured prior to visualisation of viral proteins with specific antibodies. cache = ./cache/cord-276185-ysspkbj7.txt txt = ./txt/cord-276185-ysspkbj7.txt === reduce.pl bib === id = cord-317813-sisfxdso author = Banskar, Sunil title = Microbiome analysis reveals the abundance of bacterial pathogens in Rousettus leschenaultii guano date = 2016-11-15 pages = extension = .txt mime = text/plain words = 6582 sentences = 379 flesch = 48 summary = Applying in-depth bacterial community analysis using high-throughput 16 S rRNA gene sequencing, a high inter-individual variation was observed among the studied guano samples. Additionally, 16 S rRNA gene sequencing was performed using Ion Torrent PGM to identify the bacterial communities and screened for the presence of putative human pathogens. Sequence analysis of the cytochrome B (cytB) gene amplified from total extracted DNA of the guano pellets revealed that the collected fecal pellets were from a single bat species i.e. Rousettus leschenaultii, a predominant bat species reported from the Robber's cave 23 . Further, computation of core microbiome from Ion Torrent sequences of fresh guano revealed the presence of five bacterial phyla i.e. Proteobacteria, Tenericutes, Candidate division TM7, Firmicutes and Actinobacteria but in different proportions (Fig. 5, Supplementary Figure S7 ). Additionally, Ion Torrent sequencing of 16 S rRNA gene provided information about the general bacterial communities with specific emphasis on pathogens among the total communities present in bat guano. cache = ./cache/cord-317813-sisfxdso.txt txt = ./txt/cord-317813-sisfxdso.txt === reduce.pl bib === === reduce.pl bib === id = cord-318314-oxlv847d author = O’Boyle, Nicky title = Differentiated ovine tracheal epithelial cells support the colonisation of pathogenic and non-pathogenic strains of Mannheimia haemolytica date = 2020-09-11 pages = extension = .txt mime = text/plain words = 5482 sentences = 266 flesch = 39 summary = Comparison of single representative pathogenic and non-pathogenic ovine isolates over ten time-points by enumeration of tissue-associated bacteria, histology, immunofluorescence microscopy and scanning electron microscopy revealed temporal differences in adhesion, proliferation, bacterial cell physiology and host cell responses. Comparison of eight isolates of bovine and ovine origin at three key time-points (2 h, 48 h and 72 h), revealed that colonisation was not strictly pathogen or serotype specific, with isolates of serotype A1, A2, A6 and A12 being capable of colonising the cell layer regardless of host species or disease status of the host. haemolytica 11, 38 , coupled with a suggested role for the polysaccharide capsule (on which the serotyping classification is based) in cell adhesion 17 , indicates that isolates may be specifically adapted to colonising the airway tissues of discrete hosts. We assessed whether interactions with differentiated OTECs could reflect this species-specificity by analysing colonisation of pathogenic and non-pathogenic isolates of both bovine and ovine origin. cache = ./cache/cord-318314-oxlv847d.txt txt = ./txt/cord-318314-oxlv847d.txt === reduce.pl bib === id = cord-325405-cu4nx891 author = Luo, Lingfei title = Epidemiological and clinical differences between sexes and pathogens in a three-year surveillance of acute infectious gastroenteritis in Shanghai date = 2019-07-10 pages = extension = .txt mime = text/plain words = 4189 sentences = 191 flesch = 34 summary = Logistic regression analyses with sex stratification showed that abdominal pain, fever and ingestion of unsafe food at restaurants were independent factors more frequently associated with bacterial gastroenteritis irrespective of sex; red cell-positive fecal matter was associated with bacterial gastroenteritis with an odds ratio (OR) of 3.28 only in males; and white blood cell count was associated with bacterial gastroenteritis with an OR of 1.02 only in females. No significant differences in the age, percentage of local residents, frequency of vomiting, frequency of watery stools, frequency of diarrhea, duration of diarrhea, rate dehydration, heart rate, blood pressure, or rate of ingesting possible unsafe food variables was observed between the viral and bacterial gastroenteritis groups ( Independent factors differentially associated with pathogen by sex. Among males, univariate analyses showed that nausea, vomiting frequency, watery stools, abdominal pain, fever, ingesting unsafe food at restaurants, fecal leukocyte-positive, fecal red cell-positive and white blood cell count were potential independent factors that were differentially associated with viral and bacterial gastroenteritis. cache = ./cache/cord-325405-cu4nx891.txt txt = ./txt/cord-325405-cu4nx891.txt === reduce.pl bib === id = cord-319118-47ovbto5 author = Yu, Xiaojuan title = Structural basis for the neutralization of MERS-CoV by a human monoclonal antibody MERS-27 date = 2015-08-18 pages = extension = .txt mime = text/plain words = 4796 sentences = 254 flesch = 53 summary = We previously reported two human monoclonal antibodies that target the receptor binding domain (RBD) of the spike and exhibit strong neutralization activity against live and pesudotyped MERS-CoV infection. We found Trp535 as an anchor residue in the RBD for MERS-27 recognition, and its interaction with N-linked carbohydrates of DPP4 is important for the binding to DPP4 and for viral entry of MERS-CoV. In sum, results of viral entry, neutralization, and binding assays consistently indicated that Trp535 and Asp539 are critical for both MERS-CoV spike glycoprotein recognition by MERS-27 and binding with receptor DPP4. The interaction between Trp535 of RBD and the DPP4 carbohydrate is also important for receptor binding and viral entry of MERS-CoV. The receptor binding domain of the new Middle East respiratory syndrome coronavirus maps to a 231-residue region in the spike protein that efficiently elicits neutralizing antibodies A conformation-dependent neutralizing monoclonal antibody specifically targeting receptor-binding domain in Middle East respiratory syndrome coronavirus spike protein cache = ./cache/cord-319118-47ovbto5.txt txt = ./txt/cord-319118-47ovbto5.txt === reduce.pl bib === === reduce.pl bib === id = cord-315781-dejh8q22 author = Konishi, Tomokazu title = Re-evaluation of the evolution of influenza H1 viruses using direct PCA date = 2019-12-17 pages = extension = .txt mime = text/plain words = 4590 sentences = 308 flesch = 65 summary = It should be noted that avian viruses showed lower PC values and appeared around the centre of the PCA, while swine and human viruses exhibited extreme values (Figs. Thus, avian viruses had sequences that were similar to the average among samples at amino acids that were characteristic to the three groups of human and swine viruses: R, M, and U. Avian samples also showed characteristic motifs at other positions, which may appear in lower PCs. The relationships observed among the strains presented here are different from the classic ones 4, [8] [9] [10] [11] [12] in several elements. www.nature.com/scientificreports www.nature.com/scientificreports/ One of the major differences observed was the direct shift from avian to swine or human viruses. Drifts and spreading: the genomes of the R group of human viruses have been changing yearly (Figs. cache = ./cache/cord-315781-dejh8q22.txt txt = ./txt/cord-315781-dejh8q22.txt === reduce.pl bib === id = cord-324696-htx0ul4o author = Chothe, Shubhada K. title = Avian and human influenza virus compatible sialic acid receptors in little brown bats date = 2017-04-06 pages = extension = .txt mime = text/plain words = 3853 sentences = 212 flesch = 50 summary = This first ever study of IAV receptors in a bat species suggest that LBBs, a widely-distributed bat species in North America, could potentially be co-infected with avian and human IAVs, facilitating the emergence of zoonotic strains. To resolve this enigma, we investigated for the first time the distribution of SA receptors in little brown bats (LBBs) (Myotis lucifugus), a widely-distributed bat species in North America and their compatibility to support avian and human IAV binding. H5N2 virus binding pattern was in accordance with the relative abundance of SA α2,3-Gal receptors in tissues such that greater virus binding to the tracheal ( In addition to the virus binding assay using antibody-based detection, we also visualized virus binding using scanning electron microscopy (SEM) which also confirmed abundant binding of avian H5N2 virus (Fig. 5A ) and human H1N1 virus (Fig. 5B ) to LBB trachea (Fig. 5) . time, this study demonstrated that little brown bats (LBBs), a widely-distributed bat species in North America, co-express both avian and human type influenza receptors in their respiratory and gastrointestinal systems. cache = ./cache/cord-324696-htx0ul4o.txt txt = ./txt/cord-324696-htx0ul4o.txt === reduce.pl bib === === reduce.pl bib === id = cord-327405-xgtqfwyn author = Liu, Bing title = Reduced numbers of T cells and B cells correlates with persistent SARS-CoV-2 presence in non-severe COVID-19 patients date = 2020-10-19 pages = extension = .txt mime = text/plain words = 3725 sentences = 199 flesch = 52 summary = 37 non-severe patients with persistent SARS-CoV-2 presence that were transferred to Zhongnan hospital of Wuhan University were retrospectively recruited to the PP (persistently positive) group, which was further allocated to PPP group (n = 19) and PPN group (n = 18), according to their testing results after 7 days (N = negative). Finally, paired results of these lymphocyte subpopulations from 10 PPN patients demonstrated that the number of T cells and B cells significantly increased when the SARS-CoV-2 tests turned negative. These results indicated that non-severe COVID-19 patients (PA group) have already dysregulated immune system at disease onset, and those with persistent SARS-CoV-2 shedding could restore this abnormality to certain level. Together, these results indicated that the abnormalities in adaptive immune cells, but not symptoms and laboratory indicators, were associated with SARS-CoV-2 viral RNA detection in non-severe COVID-19 patients. cache = ./cache/cord-327405-xgtqfwyn.txt txt = ./txt/cord-327405-xgtqfwyn.txt === reduce.pl bib === id = cord-322486-qwl7nzkr author = Omori, Ryosuke title = The age distribution of mortality from novel coronavirus disease (COVID-19) suggests no large difference of susceptibility by age date = 2020-10-06 pages = extension = .txt mime = text/plain words = 4857 sentences = 247 flesch = 52 summary = We estimated the parameter which describes the age-dependency of susceptibility by fitting the model to reported data, including the effect of change in contact patterns during the epidemics of COVID-19, and the fraction of symptomatic infections. Our study revealed that if the mortality rate or the fraction of symptomatic infections among all COVID-19 cases does not depend on age, then unrealistically different age-dependencies of susceptibilities against COVID-19 infections between Italy, Japan, and Spain are required to explain the similar age distribution of mortality but different basic reproduction numbers (R(0)). Assuming that the age-dependency of mortality by COVID-19 is determined by only age-dependent susceptibility (model 1), i.e., the mortality rate does not depend on age, the exponent parameter, φ, describing the variation of susceptibility among age groups for each country, Italy, Japan, and Spain, was estimated as shown in Fig. 4 . cache = ./cache/cord-322486-qwl7nzkr.txt txt = ./txt/cord-322486-qwl7nzkr.txt === reduce.pl bib === id = cord-326868-3az13h1h author = Schiller, Bastian title = Temporal dynamics of resting EEG networks are associated with prosociality date = 2020-08-03 pages = extension = .txt mime = text/plain words = 5310 sentences = 278 flesch = 39 summary = The present study takes a neural trait approach, examining whether the temporal dynamics of resting EEG networks are associated with inter-individual differences in prosociality. In two experimental sessions, we collected 55 healthy males' resting EEG, their self-reported prosocial concern and values, and their incentivized prosocial behavior across different reward domains (money, time) and social contexts (collective, individual). On the basis of resting EEG networks' significance for non-social behavior, personality, and psychiatric conditions 20,31 , we expected that revealing an individual's tendency to engage these networks at rest would help explain inter-individual differences in prosociality and illuminate the potential psychological processes that underlie these differences. Correlative analyses revealed that participants with more transitions from microstate C to A were more prosocial [R(53) = 0.414, P = 0.002, Scientific RepoRtS | (2020) 10:13066 | https://doi.org/10.1038/s41598-020-69999-5 www.nature.com/scientificreports/ significant after Bonferroni-correction for multiple testing; prosocial concern: R s (53) = 0.261, P = 0.054; prosocial values: R s (53) = 0.366, P = 0.006; collective prosocial behavior: R s (53) = 0.081, P > 0.20; individual prosocial behavior: R s (53) = 0.261, P = 0.054, see Fig. 4 ]. cache = ./cache/cord-326868-3az13h1h.txt txt = ./txt/cord-326868-3az13h1h.txt === reduce.pl bib === === reduce.pl bib === id = cord-329155-ddpfox68 author = Mindikoglu, Ayse L. title = Intermittent fasting from dawn to sunset for four consecutive weeks induces anticancer serum proteome response and improves metabolic syndrome date = 2020-10-27 pages = extension = .txt mime = text/plain words = 8186 sentences = 379 flesch = 43 summary = Our results showed that 30-day intermittent fasting from dawn to sunset, the human activity phase, was associated with an anticancer serum proteome response and upregulated several key regulatory proteins that play a key role in tumor suppression, DNA repair, insulin signaling, glucose, and lipid metabolism, circadian clock, cytoskeletal remodeling, immune system, and cognitive function 15 . In accord with the findings of these murine and human studies 13,25 , we found a significant fold increase in the levels of specific tumor suppressor/anticancer proteins at the end of 4th week during 4-week intermittent fasting from dawn to sunset and/or 1 week after 4-week intermittent fasting from dawn to sunset, including CALR, CALU, INTS6, KIT, CROCC, PIGR, IGFBP4, and SEMA4B that are downregulated in several cancers resulting in cancer metastasis and poor prognosis (Table 2, Fig. 2 ). cache = ./cache/cord-329155-ddpfox68.txt txt = ./txt/cord-329155-ddpfox68.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-331475-mmcu18c8 author = Sahu, Amit Ranjan title = Selection and validation of suitable reference genes for qPCR gene expression analysis in goats and sheep under Peste des petits ruminants virus (PPRV), lineage IV infection date = 2018-10-29 pages = extension = .txt mime = text/plain words = 4735 sentences = 257 flesch = 49 summary = title: Selection and validation of suitable reference genes for qPCR gene expression analysis in goats and sheep under Peste des petits ruminants virus (PPRV), lineage IV infection In this study, we evaluated the expression stability of ten most commonly used reference genes (GAPDH, ACTB, HSP90, HMBS, 18S rRNA, B2M, POLR2A, HPRT1, ACAC, YWHAZ) in fourteen different Peste des petits ruminants virus (PPRV) infected tissues of goats and sheep. GAPDH (Glyceraldehyde-3-phosphate dehydrogenase), 18S rRNA (18S ribosomal RNA), B2M (β 2 microglobulin), HSP 90 (heat shock protein 90), ACAC-alpha (Acetyl coenzyme carboxylase alpha), HMBS (Hydroxymethylbilane synthase), YWHAZ (Tyrosine 3-monooxygenase activation protein zeta polypeptide), POLR2A (Polymerase 32 II (DNA directed) polypeptide A), ACTB (beta actin) and HPRT1 (Hypoxanthin Phosphoribosyl transferase 1) in fourteen different tissues obtained from healthy and PPRV infected goats and sheep to identify the best possible reference gene(s) for qRT-PCR normalization. cache = ./cache/cord-331475-mmcu18c8.txt txt = ./txt/cord-331475-mmcu18c8.txt === reduce.pl bib === === reduce.pl bib === id = cord-329424-hmsidrc7 author = Grunwell, Jocelyn R. title = Differential type I interferon response and primary airway neutrophil extracellular trap release in children with acute respiratory distress syndrome date = 2020-11-04 pages = extension = .txt mime = text/plain words = 4860 sentences = 274 flesch = 38 summary = title: Differential type I interferon response and primary airway neutrophil extracellular trap release in children with acute respiratory distress syndrome Since viral lower respiratory tract infections are a primary trigger for PARDS, we questioned whether differential ISG expression was associated with neutrophil responses in intubated children at risk or with PARDS. We hypothesized that children with PARDS would have a greater type I IFN response resulting in more neutrophil extracellular trap (NET) release. Our study assessed neutrophil activation, the differential expression of ISGs and activation of the STAT1 signaling pathway, and NETosis in the airways of intubated children with acute respiratory failure due to lower respiratory tract infections. While we detected higher type I IFN signaling and NET production in the airways of children with versus without PARDS, due to the clinical nature of our study, we are not able to attribute causation of neutrophil dysfunction to high ISG expression in study participants. cache = ./cache/cord-329424-hmsidrc7.txt txt = ./txt/cord-329424-hmsidrc7.txt === reduce.pl bib === id = cord-334228-n69iewmx author = Li, Chunmei title = Conformational Flexibility of a Short Loop near the Active Site of the SARS-3CLpro is Essential to Maintain Catalytic Activity date = 2016-02-16 pages = extension = .txt mime = text/plain words = 4643 sentences = 251 flesch = 59 summary = Like other known CoV-3CLpro structures, such as TGEV, hCoV-229E, hCoV-HKU1, and IBV 2-5 , SARS-3CLpro has a highly conserved three-dimensional structure, dimer interface, catalysis dyad, and substrate binding site, but an extremely low homology with cellular proteases. Ser139 and Phe140 are two key residues that not only contribute to interactions between the two protomers in the parent dimer but also maintain the correct conformation of the S1 subsite in the substrate-binding pocket. Other residue mutations, which are neither on the dimer interface nor key to catalysis, can also influence enzyme activity and dimer association-dissociation of SARS-3CLpro via long-range interactions 15, 16 . Our molecular dynamics simulations showed that Ser139-Leu141 maintains a stable 3 10 -helix conformation in the inactive monomer structure and a well-defined loop conformation in the active protomer of the dimer structure. Although SARS-3CLpro uses the dimer structure to maintain its enzyme activity, our study shows that the monomer can also be evolved into an active enzyme via mutations. cache = ./cache/cord-334228-n69iewmx.txt txt = ./txt/cord-334228-n69iewmx.txt === reduce.pl bib === id = cord-331148-40gvay7i author = Hsieh, Yu-Chia title = Clinical characteristics of patients with laboratory-confirmed influenza A(H1N1)pdm09 during the 2013/2014 and 2015/2016 clade 6B/6B.1/6B.2-predominant outbreaks date = 2018-10-23 pages = extension = .txt mime = text/plain words = 3185 sentences = 166 flesch = 43 summary = Independently, a retrospective cohort study (which enrolled 639 infected patients during the five seasons) was conducted at Chang Gung Memorial Hospital to explore the risk factors associated with influenza A(H1N1)pdm09-related complications. The results of the logistic regression analysis on the risk factors associated with influenza A(H1N1)pdm09-related complications and pneumonia are shown in Table 4 , and respiratory failure with mechanical ventilation and ARDS are also presented in Table 5 . In the univariate analysis, 6B/6B.1/6B.2 season, age (50-64 years), onset to presentation, underlying conditions, obesity, smoking, alcoholism, and antiviral therapy were significant risk factors of complications, pneumonia, mechanical ventilation, and ARDS (Tables 4 and 5 ). In the multivariate logistic regression analysis, 6B/6B.1/6B.2 season, age (50-64 years and ≥65 years), underlying conditions, and antiviral therapy were significant independent risk factors of complications, pneumonia, and mechanical ventilation (Tables 4 and 5). cache = ./cache/cord-331148-40gvay7i.txt txt = ./txt/cord-331148-40gvay7i.txt === reduce.pl bib === id = cord-335055-gzuug3p5 author = Kwiyolecha, Elizabeth title = Patterns of viral pathogens causing upper respiratory tract infections among symptomatic children in Mwanza, Tanzania date = 2020-10-28 pages = extension = .txt mime = text/plain words = 3311 sentences = 196 flesch = 45 summary = title: Patterns of viral pathogens causing upper respiratory tract infections among symptomatic children in Mwanza, Tanzania Therefore, there is a paramount need to establish information on the common etiologies of RTIs in Tanzania, the information that can stimulate further studies and possible control interventions including introduction of cheap and reliable methods to detect these pathogens in clinical settings. In addition due to increased use of antibiotic without a support of a diagnostic test in the treatment of URTI as observed in number of previous studies [11] [12] [13] , make the availability of epidemiological data on the patterns of etiology of URTI of paramount important. A cross sectional hospital based study involving 339 children aged 1-59 months presenting with RTI symptoms was conducted from October 2017 to February 2018 in the city of Mwanza, Tanzania. A previous study 33 , documented Rhinovirus to cause up to 25-85% of the upper respiratory tract infections. cache = ./cache/cord-335055-gzuug3p5.txt txt = ./txt/cord-335055-gzuug3p5.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-330057-3vucm0s1 author = Franzo, Giovanni title = Phylodynamic analysis and evaluation of the balance between anthropic and environmental factors affecting IBV spreading among Italian poultry farms date = 2020-04-29 pages = extension = .txt mime = text/plain words = 5537 sentences = 280 flesch = 40 summary = In the present study, 361 IBV QX (the most relevant field genotype in Italy) sequences were obtained between 2012 and 2016 from the two main Italian integrated poultry companies. Finally, the different viral population pattern observed in the two companies over the same time period supports the pivotal role of management and control strategies on IBV epidemiology. Almost identical results were obtained including a third "ghost" deme (i.e. an estimated deme for which no sequences were available, representative of other unsampled companies and farms) in the analysis or using the "traditional" coalescent approach. In the particular Italian QX scenario, the serially sampled (i.e. with known collection date) strains were used to infer the migration rate and history between the two integrated poultry companies (i.e. considered as different demes) over time. cache = ./cache/cord-330057-3vucm0s1.txt txt = ./txt/cord-330057-3vucm0s1.txt === reduce.pl bib === === reduce.pl bib === id = cord-342289-zpstb7h9 author = Cui, Tingting title = Establishment of porcine enterocyte/myofibroblast co-cultures for the growth of porcine rota- and coronaviruses date = 2018-10-12 pages = extension = .txt mime = text/plain words = 8364 sentences = 435 flesch = 49 summary = As subepithelial myofibroblasts secrete extracellular matrix and growth factors contributing to the attachment, proliferation and differentiation of epithelial cells, co-cultures of primary porcine enterocytes (ileocytes and colonocytes) with myofibroblasts were developed and evaluated for their susceptibility to enteric viruses. The differentiation status of porcine intestinal epithelial cells of 3 days old piglets and the co-cultured enterocytes were analyzed by scanning electron microscopy. To determine the percentage of rotavirus infected cells in primary porcine enterocytes, cells were fixed at different time points (0, 3, 6, 9, 12, 24 h) post inoculation with a low-passage archival RVA strain. Therefore, the susceptibility of primary porcine enterocytes co-cultured with myofibroblasts to four different genotypes of rotavirus A contained in fecal suspensions was tested by RT-qPCR (Fig. 7) . Although rotavirus was reported to have an exclusive tropism for small intestinal enterocytes 41 , rotavirus RVA/Pig-tc/BEL/RV277/1977/G1P [7] strain could infect both primary ileum and colon epithelial cells with a trypsin treatment. cache = ./cache/cord-342289-zpstb7h9.txt txt = ./txt/cord-342289-zpstb7h9.txt === reduce.pl bib === id = cord-339973-kj56zi59 author = Coleman, Kristen K. title = Bioaerosol Sampling for Respiratory Viruses in Singapore’s Mass Rapid Transit Network date = 2018-11-30 pages = extension = .txt mime = text/plain words = 4775 sentences = 228 flesch = 46 summary = Although baseline metagenomic maps created from these studies are said to be useful for mitigating bioterrorism and infectious disease outbreaks, most of them focus largely on mapping surface-borne bacterial DNA 17 and neglect to address the threat of weaponized or global catastrophic biological risk-level (GCBR-level) agents, both of which would likely be aerosolized or respiratory-borne RNA viruses 19 . Bioaerosol sampling in the field provides a noninvasive way to monitor and characterize the community of aerosolized respiratory viruses that regularly infect the public, as well as potentially detect or discover novel pathogens with pandemic potential, such as the influenza A(H7N9) virus. Although the air pump flow rate and sample collection times used in our study have been demonstrated to efficiently capture aerosolized influenza virus and RSV RNA [33] [34] [35] , it is possible that these parameters are not optimal for capturing the other respiratory virus DNA/RNA targeted in our study. cache = ./cache/cord-339973-kj56zi59.txt txt = ./txt/cord-339973-kj56zi59.txt === reduce.pl bib === === reduce.pl bib === id = cord-335576-b34nc3ay author = Tsai, Andrew title = Impact of tocilizumab administration on mortality in severe COVID-19 date = 2020-11-05 pages = extension = .txt mime = text/plain words = 2917 sentences = 180 flesch = 44 summary = Patients were stratified according to the receipt of tocilizumab for cytokine storm and matched to controls using propensity scores. The current analysis does not support the use of tocilizumab for the management of cytokine storm in patients with COVID-19. The objective of this analysis was to evaluate the clinical outcome of in-hospital mortality in patients with COVID-19 treated with tocilizumab in a single medical center. Subsequently, propensity score matching was performed to account for treatment strategy influenced by confounding by indication (the tendency of clinicians to prescribe tocilizumab in patients perceived to have cytokine storm and worsening trajectory). Currently Food and Drug Administration approved for use in the management of rheumatoid conditions and cytokine release storm-related to chimeric antigen receptor (CAR)-T cell therapy, tocilizumab has gained momentum as a potentially effective option in reducing IL-6 associated fevers and preventing clinical deterioration in COVID-19. cache = ./cache/cord-335576-b34nc3ay.txt txt = ./txt/cord-335576-b34nc3ay.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-340105-471x03f9 author = Kim, Sung-Il title = Niclosamide inhibits leaf blight caused by Xanthomonas oryzae in rice date = 2016-02-16 pages = extension = .txt mime = text/plain words = 5612 sentences = 333 flesch = 53 summary = First, to determine the minimum concentration of niclosamide that would block bacterial blight, we examined the niclosamide dosage effect on disease responses to the representative Xoo strain PXO99. These results clearly indicate that niclosamide blocks the development of rice leaf blight by directly inhibiting Xoo bacterial growth (Figs 2c and 3c) and/or by inducing defense-related gene expression (Fig. 6) . In conclusion, the results presented herein indicate that niclosamide protects rice plants from bacterial leaf blight by inhibiting Xoo growth, inducing SA accumulation, and/or by inducing the expression of defense-related gene pathways. To examine the systemic effect of niclosamide on Xoo-mediated leaf blight development, the fully expanded uppermost leaves of 80-day-old rice plants were inoculated with PXO99 by the leaf-clipping as described above. Plant growth-promoting rhizobacteria mediate induced systemic resistance in rice against bacterial leaf blight caused by Xanthomonas oryzae pv cache = ./cache/cord-340105-471x03f9.txt txt = ./txt/cord-340105-471x03f9.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-342122-certy2v8 author = Ruscitti, Piero title = Pro-inflammatory properties of H-ferritin on human macrophages, ex vivo and in vitro observations date = 2020-07-22 pages = extension = .txt mime = text/plain words = 4624 sentences = 236 flesch = 44 summary = In this work, we tested (1) FeH and FeL in bone marrow (BM) and sera in patients with macrophage activation syndrome (MAS); (2) pro-inflammatory effects of ferritin, FeL, and FeH on macrophages; (3) ability of FeH-stimulated macrophages to stimulate the proliferation of peripheral blood mononuclear cells (PBMCs); (4) production of mature IL-1β and IL-12p70 in extracellular compartments of FeH-stimulated macrophages. Finally, www.nature.com/scientificreports/ FeH-treated macrophages enhanced the proliferation of co-cultured PBMCs. Taking together all these results and considering that AOSD and MAS could be included in the so-called "hyperferritinaemic syndrome" 14 , our data could reinforce the hypothesis that higher levels of ferritin may not only be considered a consequence or an epiphenomenon of the inflammation, but it may actively play a role in pathogenic mechanisms of those diseases, thus enhancing the inflammatory burden. cache = ./cache/cord-342122-certy2v8.txt txt = ./txt/cord-342122-certy2v8.txt === reduce.pl bib === id = cord-350468-32qin4ak author = Song, Cong-Ying title = Immune dysfunction following COVID-19, especially in severe patients date = 2020-09-28 pages = extension = .txt mime = text/plain words = 2958 sentences = 177 flesch = 55 summary = Multivariate logistic regression analysis showed that CD4(+) cell count, neutrophil-to-lymphocyte ratio (NLR) and D-dimer were risk factors for severe cases. Afterward, the CD4 + cell count (P = 0.015), NLR (P = 0.032) and D-dimer (P = 0.016) were considered the independent risk factors of the severe COVID-19 cases (Table 3) www.nature.com/scientificreports/ To evaluate the predictive value of CT score, CPIS, and three independent risk factors, the ROC curve analysis was performed (Fig. 7) . In our study, we compared clinical characteristics between healthy people and COVID-19 patients, and then compared these features between severe and mild cases. Parameters including CD4 + T cell count, NLR, and D-dimer, CT score, and CPIS had quite great value for predicting disease severity, which could be considered in early warning of severe patients. Several studies have shown that severe SARS-CoV-2-infected patients have a higher NLR 11, 12 , an independent risk factor for mortality in COVID-19 patients 13 . cache = ./cache/cord-350468-32qin4ak.txt txt = ./txt/cord-350468-32qin4ak.txt === reduce.pl bib === === reduce.pl bib === id = cord-351295-4toxlskr author = Lanave, Gianvito title = Identification of hepadnavirus in the sera of cats date = 2019-07-23 pages = extension = .txt mime = text/plain words = 2665 sentences = 159 flesch = 48 summary = Also, in 7/10 animals with suspected hepatic disease, virus load was >10(4) genome copies per mL, i.e. above the threshold considered at risk of active hepatitis and liver damage for HBV. DCH DNA was detected in 31 (17.8%) out of 174 sera collected with a request for diagnosis of infectious diseases (collection A) and in 11 (5.1%) out of 216 sera submitted to the laboratory for pre-surgical evaluation or for suspected metabolic or neoplastic disease (collection B) that were used to generate a baseline. In this study we observed a marked and significantly higher prevalence (17.8%, 31/174) in the cohort of cats with suspected infectious diseases (collection A) with respect to a group of animals (collection B) used as baseline. Almost half of the sera positive for DCH (14/31, 45 .2%) of this cohort were collected from cats with retroviral infection (FIV and/or feline leukemia virus, FeLV). cache = ./cache/cord-351295-4toxlskr.txt txt = ./txt/cord-351295-4toxlskr.txt === reduce.pl bib === id = cord-345359-okmkgsbr author = Ohno, Marumi title = Influenza virus infection affects insulin signaling, fatty acid-metabolizing enzyme expressions, and the tricarboxylic acid cycle in mice date = 2020-07-02 pages = extension = .txt mime = text/plain words = 6474 sentences = 314 flesch = 45 summary = After infecting mice with intranasal applications of 500 plaque-forming units of A/Puerto Rico/8/34 (H1N1; PR8) virus, the serum levels of most intermediates in the tricarboxylic acid (TCA) cycle and related metabolic pathways were significantly reduced. www.nature.com/scientificreports/ investigated metabolic changes by determining the serum levels of metabolites, insulin sensitivity in the liver, glucose availability, and hepatic gene expressions in the early stages of symptom onset as well as the lethal phase of influenza in a mouse model. The results of this study indicate that influenza virus infection dysregulates glucose and fatty acid metabolism and decreases tricarboxylic acid (TCA) cycle activity, leading to enhanced degradation of adenosine triphosphate (ATP) and guanosine triphosphate (GTP). Metabolites that were present at reduced levels in the sera of PR8 virus-infected mice were mainly related to the TCA cycle, urea cycle, and amino acid metabolism, as indicated by the serum levels of metabolite in these pathways at 1, 3, and 6 dpi (Fig. 2) . cache = ./cache/cord-345359-okmkgsbr.txt txt = ./txt/cord-345359-okmkgsbr.txt === reduce.pl bib === id = cord-344871-486sk4wc author = Wu, Jianping title = Biochemical and structural characterization of the interface mediating interaction between the influenza A virus non-structural protein-1 and a monoclonal antibody date = 2016-09-16 pages = extension = .txt mime = text/plain words = 6992 sentences = 379 flesch = 58 summary = We have previously shown that a non-structural protein 1 (NS1)-binding monoclonal antibody, termed as 2H6, can significantly reduce influenza A virus (IAV) replication when expressed intracellularly. As comparative ELISA in this and previous studies 29 showed that residues N48 and T49 in NS1(RBD) are important for the interaction with mAb 2H6, they were defined as active residues involved in the binding interaction to generate a series of models of the NS1(RBD) and 2H6-Fab complex. Overall, the predicted model from cluster 2 is consistent with our comparative ELISA data and suggests that residues N48 and T49 are important for the binding between NS1(RBD) and 2H6-Fab because their side-chains could make hydrogen bonds with residues in the VH-CDR2 of the Fab. In addition, R44 of NS1(RBD) was distal from the antibody-antigen interface, which is consistent with the results from comparative ELISA ( Figure S1 ) showing that substitution of R44 of NS1(RBD) with K did not affect its interaction with mAb 2H6. cache = ./cache/cord-344871-486sk4wc.txt txt = ./txt/cord-344871-486sk4wc.txt === reduce.pl bib === id = cord-342676-ykog278j author = Stewart, H. title = Identification of novel RNA secondary structures within the hepatitis C virus genome reveals a cooperative involvement in genome packaging date = 2016-03-14 pages = extension = .txt mime = text/plain words = 6858 sentences = 338 flesch = 46 summary = To identify the regions of the viral genome involved in this process, we used SELEX (systematic evolution of ligands by exponential enrichment) to identify RNA aptamers which bind specifically to Core in vitro. Comparison of these aptamers to multiple HCV genomes revealed the presence of a conserved terminal loop motif within short RNA stem-loop structures. We wished to investigate the possibility that similar specific secondary structures are present within HCV RNAs destined for packaging, and whether their interactions with Core cooperatively drive the RNA encapsidation and nucleocapsid assembly processes. A mutant genome unable to form such structures displays impaired viral infectivity whilst RNA replication is unaffected, indicating these motifs may interact specifically with Core. Role of RNA structures in genome terminal sequences of the hepatitis C virus for replication and assembly cache = ./cache/cord-342676-ykog278j.txt txt = ./txt/cord-342676-ykog278j.txt === reduce.pl bib === id = cord-342782-xty16m8w author = Marrugal-Lorenzo, José A. title = Repositioning salicylanilide anthelmintic drugs to treat adenovirus infections date = 2019-01-09 pages = extension = .txt mime = text/plain words = 5099 sentences = 267 flesch = 47 summary = Data suggests that the studied salicylanilide anthelmintic drugs could be suitable for further clinical evaluation for the development of new antiviral drugs to treat infections by adenovirus in immunosuppressed patients and in immunocompetent individuals with community-acquired pneumonia. The three salicylanilide anthelmintic drugs showed a dose-dependent anti-HAdV activity against both HAdV5 and HAdV16, with 100% inhibition of plaques formation at 1.25, 5 and 2.5 μM for NIC, OXY and RAF, respectively ( Fig. 2a,b) . The CC 50 values for these molecules were in all cases significantly higher than the IC 50 concentrations required for inhibition in our antiviral activity and mechanistic assays for both 293β5 cells (Table 1 ) and A549 cells (22.9 ± 9.8 µM, 76.1 ± 14.4 µM and 80.6 ± 34.7 µM for NIC, OXY and RAF, respectively). The aim of this study was to evaluate the anti-HAdV activity of NIC, a salicylanilide anthelmintic drug of human use to set the basis for its further experimental and clinical development as a potential new treatment for HAdV infections. cache = ./cache/cord-342782-xty16m8w.txt txt = ./txt/cord-342782-xty16m8w.txt === reduce.pl bib === id = cord-344953-gtg12hiu author = Prather, Randall S. title = Knockout of maternal CD163 protects fetuses from infection with porcine reproductive and respiratory syndrome virus (PRRSV) date = 2017-10-17 pages = extension = .txt mime = text/plain words = 2628 sentences = 158 flesch = 55 summary = title: Knockout of maternal CD163 protects fetuses from infection with porcine reproductive and respiratory syndrome virus (PRRSV) After infection of the porcine dam at about 90 days of gestation, porcine reproductive and respiratory syndrome virus (PRRSV) crosses the placenta and begins to infect fetuses. In this study, CD163-positive fetuses, recovered between 109 days of gestation or 20 days after maternal infection, were completely protected from PRRSV in dams possessing a complete knockout of the CD163 receptor. The hypothesis to be tested was that the presence of the CD163 KO genotype of the dam would be sufficient to protect fetuses following maternal infection with PRRSV. PRRSV nucleic acid, measured at 7 dpi, showed a viremia level for Dam No. 139 of 5.5 log 10 templates per reaction, demonstrating the presence of a productive PRRSV infection. Gene-edited pigs are protected from porcine reproductive and respiratory syndrome virus cache = ./cache/cord-344953-gtg12hiu.txt txt = ./txt/cord-344953-gtg12hiu.txt === reduce.pl bib === id = cord-350255-tthttyl3 author = Poirier, Canelle title = The role of environmental factors on transmission rates of the COVID-19 outbreak: an initial assessment in two spatial scales date = 2020-10-12 pages = extension = .txt mime = text/plain words = 4288 sentences = 205 flesch = 47 summary = To disentangle if our reproductive number estimates could be explained by importation of cases from Wuhan, Hubei, alone; and if they could be interpreted as indicators of local transmission, we formulated a linear model with the local R proxy as the response variable, and human mobility as a predictor at the province level. In all steps of filtering at the province-level, and for both time periods, τ 1 and τ 2 , absolute humidity was not associated to R proxy , with P values ranging between 0.161 and 0.922 (Tables 9, 10 , 11, 12, 13, 14, 15) . For cities, for time-period τ 1 , and after the first step of filtering, absolute humidity appeared to be associate with R proxy with a p value equal to 0.004 (Supplementary Table S5 ). cache = ./cache/cord-350255-tthttyl3.txt txt = ./txt/cord-350255-tthttyl3.txt === reduce.pl bib === id = cord-340781-z348xbn0 author = Namvar, Ali title = In silico/In vivo analysis of high-risk papillomavirus L1 and L2 conserved sequences for development of cross-subtype prophylactic vaccine date = 2019-10-23 pages = extension = .txt mime = text/plain words = 6646 sentences = 357 flesch = 50 summary = Moreover, in vivo studies indicated that the combination of L1 and L2 DNA constructs without any adjuvant or delivery system induced effective immune responses, and protected mice against C3 tumor cells (the percentage of tumor-free mice: ~66.67%). The framework begins with conservancy analysis of all 13 high-risk HPV strains following with (1) B-cell epitope mapping, (2) T-cell epitope mapping (CD4 + and CD8 + ), (3) allergenicity assessment, (4) tap transport and proteasomal cleavage, (5) population coverage, (6) global and template-based docking and (7) data collection, analysis, and design of the L1 and L2 DNA constructs. In this study, for the first time, comprehensively integrated methods (using sequence-based tools in combination with flexible peptide-protein docking) were used to design highly immunogenic and protective vaccine candidates which were able to boost both humoral and cellular Table 12 . cache = ./cache/cord-340781-z348xbn0.txt txt = ./txt/cord-340781-z348xbn0.txt === reduce.pl bib === id = cord-352020-9wxwktck author = Zhang, Baoshan title = A platform incorporating trimeric antigens into self-assembling nanoparticles reveals SARS-CoV-2-spike nanoparticles to elicit substantially higher neutralizing responses than spike alone date = 2020-10-23 pages = extension = .txt mime = text/plain words = 4914 sentences = 266 flesch = 46 summary = To alleviate this issue, we developed a plug-and-play platform using the spontaneous isopeptide-bond formation of the SpyTag:SpyCatcher system to display trimeric antigens on self-assembling nanoparticles, including the 60-subunit Aquifex aeolicus lumazine synthase (LuS) and the 24-subunit Helicobacter pylori ferritin. The versatile platform described here thus allows for multivalent plug-and-play presentation on self-assembling nanoparticles of trimeric viral antigens, with SARS-CoV-2 spike-LuS nanoparticles inducing particularly potent neutralizing responses. To improve protein solubility and expression, we added glycans to the surface of the nanoparticles, designing a panel of LuS and ferritin constructs with SpyTag and SpyCatcher (Table 1 and Supplementary Table S1 ). To demonstrate the versatility of our SpyTag-displaying nanoparticles in immunogen development, we conjugated them to three viral antigens of vaccine interest, the DS2-preF stabilized RSV F 33 , a DS2-stabilized version of PIV3 F 34 , and the 2P-stabilized version of SARS-CoV-2 spike 24 . cache = ./cache/cord-352020-9wxwktck.txt txt = ./txt/cord-352020-9wxwktck.txt === reduce.pl bib === id = cord-350957-10wcqgaq author = Shen, Zu T. title = SARS Coronavirus Fusion Peptide-Derived Sequence Suppresses Collagen-Induced Arthritis in DBA/1J Mice date = 2016-06-28 pages = extension = .txt mime = text/plain words = 5609 sentences = 265 flesch = 48 summary = Recently, based on our model of immune signaling, the Signaling Chain HOmoOLigomerization (SCHOOL) model, we suggested specific molecular mechanisms used by different viruses such as severe acute respiratory syndrome coronavirus (SARS-CoV) to modulate the host immune response mediated by members of the family of multichain immune recognition receptors (MIRRs). Previously, we reported that incorporation of another immunomodulatory peptide, GF9, that employs the SCHOOL mechanisms of action and targets triggering receptor expressed on myeloid cells 1 (TREM-1), into synthetic HDL-like nanoparticles of spherical shape (sHDL) significantly reduces the effective therapeutic dosage of GF9 in animal models of sepsis, lung cancer, and RA 33, 34 . As expected from the anti-arthritic activities demonstrated in animal models of autoimmune arthritis for TCR CP 20,21,23 and HIV gp41 FP 18 , the SARS-CoV FP-derived peptide sequence MG11 significantly suppresses CIA in mice: the peptide at 25 mg/kg/day inhibits inflammation in CIA as assessed by clinical evaluation and scoring of the disease (Fig. 2) . cache = ./cache/cord-350957-10wcqgaq.txt txt = ./txt/cord-350957-10wcqgaq.txt === reduce.pl bib === id = cord-351659-ujbxsus4 author = Jiang, Xiandeng title = A retrospective analysis of the dynamic transmission routes of the COVID-19 in mainland China date = 2020-08-19 pages = extension = .txt mime = text/plain words = 4367 sentences = 252 flesch = 56 summary = We propose a time-varying sparse vector autoregressive (VAR) model to retrospectively analyze and visualize the dynamic transmission routes of this outbreak in mainland China over January 31–February 19, 2020. Our results demonstrate that the influential inter-location routes from Hubei have become unidentifiable since February 4, 2020, whereas the self-transmission in each provincial-level administrative region (location, hereafter) was accelerating over February 4–15, 2020. Implications of our results suggest that in addition to the origin of the outbreak, virus preventions are of crucial importance in locations with the largest migrant workers percentages (e.g., Jiangxi, Henan and Anhui) to controlling the spread of COVID-19. This enables the detection and visualization of time-varying inter-location and self-transmission routes of the COVID-19 on the daily basis. On the fifth day (February 4, 2020), no influential transmission routes were found from Hubei to directly affect other locations, and there were only three influential routes identified nationally, including Zhejiang-Shaanxi, www.nature.com/scientificreports/ Zhejiang-Jiangxi and Jiangxi-Shanghai. cache = ./cache/cord-351659-ujbxsus4.txt txt = ./txt/cord-351659-ujbxsus4.txt === reduce.pl bib === id = cord-348515-bqqyly23 author = Zhao, Suhui title = Re-emergent Human Adenovirus Genome Type 7d Caused an Acute Respiratory Disease Outbreak in Southern China After a Twenty-one Year Absence date = 2014-12-08 pages = extension = .txt mime = text/plain words = 6569 sentences = 323 flesch = 43 summary = Recombination analysis reveals this genome differs from the 1950s-era prototype and vaccine strains by a lateral gene transfer, substituting the coding region for the L1 52/55 kDa DNA packaging protein from HAdV-16. Recombination analysis reveals this genome differs from the 1950s-era prototype and vaccine strains by a lateral gene transfer, substituting the coding region for the L1 52/55 kDa DNA packaging protein from HAdV-16. Thorough characterization of these pathogens is evidenced by the availability of two genome sequences (JF800905 and JX625134), both of which are further identified as the HAdV-7d genome type in this report, and shown to be nearly identical to this report of an isolate from a 2011 ARD outbreak in Guangdong Province (strain DG01_2011) by comparative genomics and, in particular, in silico REA pattern analysis, as presented in Figure 2 . cache = ./cache/cord-348515-bqqyly23.txt txt = ./txt/cord-348515-bqqyly23.txt === reduce.pl bib === id = cord-356027-ckdx56j1 author = Zheng, Shou-Yan title = Association between secondary thrombocytosis and viral respiratory tract infections in children date = 2016-03-11 pages = extension = .txt mime = text/plain words = 3340 sentences = 194 flesch = 49 summary = Compared with the normal group, the detection rates of respiratory syncytial virus (RSV) and human rhinovirus (HRV) were significantly higher in the thrombocytosis group (P = 0.017 and 0.042, respectively). Multiplex nested polymerase chain reaction (PCR) was used to detect the following common respiratory viruses, as described previously [11] [12] [13] [14] [15] : RSV subtypes A and B (RSVA, RSVB); influenza virus (IFV) subtypes A, B and C (IFVA, IFVB, IFVC); human coronaviruses (HCoV); metapneumovirus (MPV); parainfluenza virus type 1 to 4 (PIV1-4); adenovirus (ADV); human bocavirus type 1 (HBoV1) and human rhinovirus (HRV) subtypes A and C (HRVA, HRVC). Compared with the normal group, the total detection rates of RSV and HRV were both significantly higher (P = 0.001 and 0.033, respectively) in the thrombocytosis group, and ADV and IFV were lower (P = 0.001 and 0.007, respectively). ST was especially common in patients with lower respiratory tract infections and occurred most frequently in the mild thrombocytosis group (500-699 × 10 9 /L). cache = ./cache/cord-356027-ckdx56j1.txt txt = ./txt/cord-356027-ckdx56j1.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === ===== Reducing email addresses cord-004006-tfp2idq2 cord-272576-ez731lif cord-294220-ewp1m8jp Creating transaction Updating adr table ===== Reducing keywords cord-001823-v60vv99o cord-001704-pdxm0iiw cord-001712-a1sbdhhn cord-001675-9717nzr7 cord-001829-rwnbxmt4 cord-001852-c79vwr6t cord-001116-2yvyiiuy cord-001862-a097byk5 cord-002312-jyk7f8hz cord-001875-ulq1xqma cord-002673-5a1rfi6k cord-002081-vi6rth9o cord-001858-nmi39n6h cord-002110-pbb247lp cord-002072-qbh728ec cord-001522-82plcxv9 cord-002490-kw8psrmz cord-001901-2s6hpakk cord-002758-d86hnox1 cord-002373-rueg4gsj cord-002111-mmpijsqb cord-002369-shk4n8f6 cord-003055-88q36g00 cord-002258-o9azey3m cord-002720-lrkscs71 cord-002408-bbtslrrt cord-002290-wvo22jx2 cord-002644-yzan95du cord-001963-4wjvykx7 cord-002844-jv42o789 cord-002474-2l31d7ew cord-002320-m99amd4y cord-004181-exbs3tz7 cord-002932-5e7xrd1y cord-002874-9rxv6fy9 cord-002411-iiw878w8 cord-002782-mena480g cord-003490-swlkjtyo cord-002177-yyfgl9x5 cord-002019-wtnf340p cord-002659-566uoozj cord-003148-o7y3wygc cord-003623-n01rgqyv cord-002244-5h6monh3 cord-002843-dvfmpm54 cord-003166-k3jxvzfi cord-002013-rb9xdzro cord-003004-iif2lnez cord-001915-b9dk07tk cord-002389-k86hzbbx cord-004150-ybikajhh cord-003505-qr6ukfti cord-003387-82573enr cord-002956-e5ihpe4i cord-001868-utsvsja0 cord-004062-yxx3xxio cord-003504-wjab4y0g cord-004016-iaktm72a cord-004060-nxw5k9y1 cord-004006-tfp2idq2 cord-004378-g1rxygef cord-003196-fdb6az0v cord-004170-ri5qsarz cord-002802-594mmlk8 cord-004419-81w7apdk cord-003667-u1xa44nw cord-004069-nuep8nim cord-004292-6lnxb0px cord-004379-91a7sgir cord-003558-7lvqpz21 cord-003444-dmpoy0b1 cord-002929-oqe3gjcs cord-004385-xna32qve cord-002045-m44fic4g cord-010140-nl1j2s56 cord-004310-hl7fa4af cord-002842-4evbeijx cord-004222-z4butywi cord-003011-vclnb0eh cord-005507-equnyib7 cord-002791-tqchfdmy cord-009691-gkynxdz3 cord-004342-9uok77wb cord-004156-79peyzc9 cord-013977-xb0r2axf cord-010675-acdfvjm5 cord-004280-c470nlie cord-004140-ujzrqzv3 cord-011892-b9zlig0r cord-004416-qw6tusd2 cord-004418-08dljap3 cord-009690-kbwz7xop cord-010328-uxpedpz8 cord-034746-uxhpufnv cord-012742-lpk6r54i cord-010640-s1oqphvn cord-007851-v6h1yro7 cord-255511-nk3iyg07 cord-259378-5g2y68i2 cord-258678-0atfsivf cord-272092-ko9y5m2s cord-030295-jlhht2l9 cord-254090-x8tnweih cord-265211-a7whyds8 cord-263627-8ufjh70o cord-259794-6qoksn00 cord-254653-4ffuivil cord-259416-gvzp2h5g cord-263088-zj14ro5j cord-260834-v254de8k cord-271602-f14wccj3 cord-271328-zdf5ji4k cord-255586-wshvvgxg cord-269756-tid8a464 cord-280334-7b7rvr25 cord-265891-jmpterrj cord-269270-i2odcsx7 cord-277816-ncdy9qgb cord-281536-8y7yxcp4 cord-276997-hbovh7s9 cord-273283-gb0m6fue cord-272576-ez731lif cord-283583-pwlbrxn3 cord-272623-j5gpww9q cord-268414-7fcc5i7i cord-276444-jidvkij5 cord-284374-sqxlnk9e cord-284429-d7qxfo6d cord-279598-xzionafe cord-287708-0qvwjejv cord-286559-y8z0pwgn cord-284582-xwedgllw cord-294220-ewp1m8jp cord-288721-3bv3aak6 cord-288761-fyvr0tc1 cord-288731-x2cwyvb7 cord-286413-a7wue2e3 cord-289932-dsysiefx cord-293747-ds8rhbkv cord-296867-6o4scan1 cord-288451-npefpo3t cord-293505-1t3hg4wi cord-293372-saqoft9p cord-306517-tls0849i cord-299605-j1ewxk4q cord-304040-64obh7i3 cord-301016-9t7v7ipt cord-305473-w30hsr4m cord-302080-fegcf1fu cord-296562-3h2oqb9k cord-302459-grs2x26l cord-308302-5yns1hg9 cord-303601-o8uk6if2 cord-305132-jspxlk1a cord-309127-kxivgxbg cord-313126-7hrjzapj cord-308687-wrzzb9cy cord-312777-5925lvue cord-316930-0s7k9guq cord-315415-3aotsb2g cord-314753-xflhxb13 cord-305031-9ze0097w cord-318187-c59c9vi3 cord-317579-ige2h4pd cord-318587-ewvnkdr2 cord-316983-h4mtpcyc cord-276185-ysspkbj7 cord-320709-2pnqpljt cord-317813-sisfxdso cord-318314-oxlv847d cord-319118-47ovbto5 cord-325405-cu4nx891 cord-315483-l6dm82pp cord-321667-jkzxjk54 cord-315781-dejh8q22 cord-323087-3cxyogor cord-324696-htx0ul4o cord-322486-qwl7nzkr cord-327405-xgtqfwyn cord-325657-s2vdazq0 cord-326868-3az13h1h cord-329155-ddpfox68 cord-329766-9bwdb6o2 cord-331475-mmcu18c8 cord-331775-iaxkfszq cord-335055-gzuug3p5 cord-329424-hmsidrc7 cord-333067-3zan82yf cord-331148-40gvay7i cord-334228-n69iewmx cord-330562-dabjcvno cord-336901-q6kgzuob cord-338041-gl65i3s0 cord-336493-ggo9wsrm cord-339973-kj56zi59 cord-340105-471x03f9 cord-338142-acqiyqwz cord-338588-rc1h4drd cord-342122-certy2v8 cord-342289-zpstb7h9 cord-350468-32qin4ak cord-343528-5283jsnu cord-344421-rmnck42f cord-351295-4toxlskr cord-344344-q32b742a cord-330057-3vucm0s1 cord-343302-g9vcchrh cord-335576-b34nc3ay cord-350255-tthttyl3 cord-350957-10wcqgaq cord-342676-ykog278j cord-351659-ujbxsus4 cord-348515-bqqyly23 cord-345359-okmkgsbr cord-344953-gtg12hiu cord-342782-xty16m8w cord-356027-ckdx56j1 cord-352020-9wxwktck cord-352061-x6tt9kx5 cord-344871-486sk4wc cord-355179-wmfwl2bh cord-346483-jc0xklzk cord-340781-z348xbn0 cord-031937-qhlatg84 Creating transaction Updating wrd table ===== Reducing urls cord-001704-pdxm0iiw cord-001712-a1sbdhhn cord-002673-5a1rfi6k cord-001829-rwnbxmt4 cord-002312-jyk7f8hz cord-002072-qbh728ec cord-002369-shk4n8f6 cord-002081-vi6rth9o cord-001522-82plcxv9 cord-002290-wvo22jx2 cord-002758-d86hnox1 cord-002644-yzan95du cord-002111-mmpijsqb cord-002782-mena480g cord-003055-88q36g00 cord-002844-jv42o789 cord-002932-5e7xrd1y cord-004181-exbs3tz7 cord-002720-lrkscs71 cord-003490-swlkjtyo cord-002659-566uoozj cord-003148-o7y3wygc cord-002843-dvfmpm54 cord-002874-9rxv6fy9 cord-002244-5h6monh3 cord-003623-n01rgqyv cord-003166-k3jxvzfi cord-003004-iif2lnez cord-001915-b9dk07tk cord-002389-k86hzbbx cord-004150-ybikajhh cord-003505-qr6ukfti cord-002956-e5ihpe4i cord-003387-82573enr cord-004062-yxx3xxio cord-003504-wjab4y0g cord-004060-nxw5k9y1 cord-004378-g1rxygef cord-004006-tfp2idq2 cord-004419-81w7apdk cord-004170-ri5qsarz cord-003196-fdb6az0v cord-004069-nuep8nim cord-002802-594mmlk8 cord-002045-m44fic4g cord-003667-u1xa44nw cord-003558-7lvqpz21 cord-004310-hl7fa4af cord-004292-6lnxb0px cord-004379-91a7sgir cord-003011-vclnb0eh cord-003444-dmpoy0b1 cord-004222-z4butywi cord-004385-xna32qve cord-010140-nl1j2s56 cord-002842-4evbeijx cord-002929-oqe3gjcs cord-005507-equnyib7 cord-002791-tqchfdmy cord-009691-gkynxdz3 cord-004156-79peyzc9 cord-010675-acdfvjm5 cord-004342-9uok77wb cord-013977-xb0r2axf cord-004280-c470nlie cord-004140-ujzrqzv3 cord-004416-qw6tusd2 cord-011892-b9zlig0r cord-004418-08dljap3 cord-009690-kbwz7xop cord-010328-uxpedpz8 cord-034746-uxhpufnv cord-012742-lpk6r54i cord-031937-qhlatg84 cord-010640-s1oqphvn cord-007851-v6h1yro7 cord-259378-5g2y68i2 cord-255511-nk3iyg07 cord-272092-ko9y5m2s cord-030295-jlhht2l9 cord-263627-8ufjh70o cord-265211-a7whyds8 cord-254653-4ffuivil cord-260834-v254de8k cord-263088-zj14ro5j cord-255586-wshvvgxg cord-265891-jmpterrj cord-271602-f14wccj3 cord-277816-ncdy9qgb cord-276997-hbovh7s9 cord-269270-i2odcsx7 cord-273283-gb0m6fue cord-272576-ez731lif cord-281536-8y7yxcp4 cord-272623-j5gpww9q cord-276444-jidvkij5 cord-268414-7fcc5i7i cord-284374-sqxlnk9e cord-284429-d7qxfo6d cord-283583-pwlbrxn3 cord-279598-xzionafe cord-287708-0qvwjejv cord-284582-xwedgllw cord-286559-y8z0pwgn cord-294220-ewp1m8jp cord-288721-3bv3aak6 cord-289932-dsysiefx cord-286413-a7wue2e3 cord-288731-x2cwyvb7 cord-288451-npefpo3t cord-296867-6o4scan1 cord-293372-saqoft9p cord-293505-1t3hg4wi cord-304040-64obh7i3 cord-306517-tls0849i cord-301016-9t7v7ipt cord-302080-fegcf1fu cord-305473-w30hsr4m cord-308302-5yns1hg9 cord-296562-3h2oqb9k cord-302459-grs2x26l cord-303601-o8uk6if2 cord-316930-0s7k9guq cord-313126-7hrjzapj cord-308687-wrzzb9cy cord-305132-jspxlk1a cord-312777-5925lvue cord-309127-kxivgxbg cord-315415-3aotsb2g cord-305031-9ze0097w cord-314753-xflhxb13 cord-318187-c59c9vi3 cord-318587-ewvnkdr2 cord-317579-ige2h4pd cord-316983-h4mtpcyc cord-276185-ysspkbj7 cord-317813-sisfxdso cord-318314-oxlv847d cord-315483-l6dm82pp cord-325405-cu4nx891 cord-321667-jkzxjk54 cord-315781-dejh8q22 cord-323087-3cxyogor cord-324696-htx0ul4o cord-326868-3az13h1h cord-327405-xgtqfwyn cord-325657-s2vdazq0 cord-331775-iaxkfszq cord-329424-hmsidrc7 cord-331475-mmcu18c8 cord-329766-9bwdb6o2 cord-335055-gzuug3p5 cord-322486-qwl7nzkr cord-333067-3zan82yf cord-331148-40gvay7i cord-335576-b34nc3ay cord-334228-n69iewmx cord-330562-dabjcvno cord-330057-3vucm0s1 cord-336901-q6kgzuob cord-329155-ddpfox68 cord-338041-gl65i3s0 cord-340105-471x03f9 cord-342289-zpstb7h9 cord-338588-rc1h4drd cord-339973-kj56zi59 cord-344421-rmnck42f cord-342122-certy2v8 cord-350468-32qin4ak cord-344871-486sk4wc cord-351295-4toxlskr cord-345359-okmkgsbr cord-344953-gtg12hiu cord-344344-q32b742a cord-350255-tthttyl3 cord-342782-xty16m8w cord-340781-z348xbn0 cord-343528-5283jsnu cord-350957-10wcqgaq cord-346483-jc0xklzk cord-352020-9wxwktck cord-352061-x6tt9kx5 cord-355179-wmfwl2bh cord-351659-ujbxsus4 cord-348515-bqqyly23 Creating transaction Updating url table ===== Reducing named entities cord-001704-pdxm0iiw cord-001712-a1sbdhhn cord-001875-ulq1xqma cord-001823-v60vv99o cord-001522-82plcxv9 cord-001829-rwnbxmt4 cord-001858-nmi39n6h cord-002673-5a1rfi6k cord-001862-a097byk5 cord-002490-kw8psrmz cord-002111-mmpijsqb cord-002072-qbh728ec cord-001901-2s6hpakk cord-002782-mena480g cord-002720-lrkscs71 cord-002373-rueg4gsj cord-002312-jyk7f8hz cord-002844-jv42o789 cord-002644-yzan95du cord-001963-4wjvykx7 cord-002369-shk4n8f6 cord-002290-wvo22jx2 cord-002258-o9azey3m cord-001675-9717nzr7 cord-002320-m99amd4y cord-001116-2yvyiiuy cord-002474-2l31d7ew cord-002177-yyfgl9x5 cord-004181-exbs3tz7 cord-002932-5e7xrd1y cord-002110-pbb247lp cord-002874-9rxv6fy9 cord-003490-swlkjtyo cord-001852-c79vwr6t cord-002411-iiw878w8 cord-002408-bbtslrrt cord-002758-d86hnox1 cord-002081-vi6rth9o cord-003055-88q36g00 cord-002019-wtnf340p cord-003148-o7y3wygc cord-003623-n01rgqyv cord-002843-dvfmpm54 cord-002244-5h6monh3 cord-002013-rb9xdzro cord-002659-566uoozj cord-003166-k3jxvzfi cord-003505-qr6ukfti cord-004150-ybikajhh cord-001915-b9dk07tk cord-003004-iif2lnez cord-002389-k86hzbbx cord-003387-82573enr cord-002956-e5ihpe4i cord-001868-utsvsja0 cord-004062-yxx3xxio cord-004060-nxw5k9y1 cord-004016-iaktm72a cord-004378-g1rxygef cord-004170-ri5qsarz cord-003504-wjab4y0g cord-004419-81w7apdk cord-004069-nuep8nim cord-002802-594mmlk8 cord-003667-u1xa44nw cord-002045-m44fic4g cord-004006-tfp2idq2 cord-003196-fdb6az0v cord-004292-6lnxb0px cord-003558-7lvqpz21 cord-004379-91a7sgir cord-003444-dmpoy0b1 cord-002929-oqe3gjcs cord-010140-nl1j2s56 cord-004310-hl7fa4af cord-004385-xna32qve cord-004222-z4butywi cord-002842-4evbeijx cord-003011-vclnb0eh cord-002791-tqchfdmy cord-005507-equnyib7 cord-004156-79peyzc9 cord-004342-9uok77wb cord-009691-gkynxdz3 cord-013977-xb0r2axf cord-010675-acdfvjm5 cord-004280-c470nlie cord-004140-ujzrqzv3 cord-004416-qw6tusd2 cord-011892-b9zlig0r cord-009690-kbwz7xop cord-010328-uxpedpz8 cord-004418-08dljap3 cord-034746-uxhpufnv cord-012742-lpk6r54i cord-010640-s1oqphvn cord-031937-qhlatg84 cord-259378-5g2y68i2 cord-007851-v6h1yro7 cord-255511-nk3iyg07 cord-272092-ko9y5m2s cord-258678-0atfsivf cord-030295-jlhht2l9 cord-263627-8ufjh70o cord-254090-x8tnweih cord-259794-6qoksn00 cord-265211-a7whyds8 cord-254653-4ffuivil cord-260834-v254de8k cord-263088-zj14ro5j cord-259416-gvzp2h5g cord-271602-f14wccj3 cord-255586-wshvvgxg cord-280334-7b7rvr25 cord-269756-tid8a464 cord-265891-jmpterrj cord-269270-i2odcsx7 cord-271328-zdf5ji4k cord-277816-ncdy9qgb cord-276997-hbovh7s9 cord-281536-8y7yxcp4 cord-273283-gb0m6fue cord-272576-ez731lif cord-283583-pwlbrxn3 cord-272623-j5gpww9q cord-268414-7fcc5i7i cord-284374-sqxlnk9e cord-284429-d7qxfo6d cord-276444-jidvkij5 cord-279598-xzionafe cord-287708-0qvwjejv cord-284582-xwedgllw cord-286559-y8z0pwgn cord-294220-ewp1m8jp cord-288721-3bv3aak6 cord-288761-fyvr0tc1 cord-288731-x2cwyvb7 cord-293747-ds8rhbkv cord-289932-dsysiefx cord-288451-npefpo3t cord-286413-a7wue2e3 cord-296867-6o4scan1 cord-293372-saqoft9p cord-293505-1t3hg4wi cord-299605-j1ewxk4q cord-306517-tls0849i cord-304040-64obh7i3 cord-301016-9t7v7ipt cord-305473-w30hsr4m cord-302080-fegcf1fu cord-296562-3h2oqb9k cord-302459-grs2x26l cord-308302-5yns1hg9 cord-303601-o8uk6if2 cord-309127-kxivgxbg cord-305132-jspxlk1a cord-313126-7hrjzapj cord-308687-wrzzb9cy cord-312777-5925lvue cord-316930-0s7k9guq cord-314753-xflhxb13 cord-315415-3aotsb2g cord-305031-9ze0097w cord-318187-c59c9vi3 cord-317579-ige2h4pd cord-318587-ewvnkdr2 cord-316983-h4mtpcyc cord-276185-ysspkbj7 cord-317813-sisfxdso cord-320709-2pnqpljt cord-325405-cu4nx891 cord-318314-oxlv847d cord-315483-l6dm82pp cord-321667-jkzxjk54 cord-315781-dejh8q22 cord-319118-47ovbto5 cord-323087-3cxyogor cord-322486-qwl7nzkr cord-324696-htx0ul4o cord-327405-xgtqfwyn cord-326868-3az13h1h cord-329155-ddpfox68 cord-325657-s2vdazq0 cord-329766-9bwdb6o2 cord-331775-iaxkfszq cord-331475-mmcu18c8 cord-335055-gzuug3p5 cord-333067-3zan82yf cord-334228-n69iewmx cord-331148-40gvay7i cord-335576-b34nc3ay cord-329424-hmsidrc7 cord-330562-dabjcvno cord-330057-3vucm0s1 cord-338041-gl65i3s0 cord-336493-ggo9wsrm cord-336901-q6kgzuob cord-340105-471x03f9 cord-338588-rc1h4drd cord-338142-acqiyqwz cord-342289-zpstb7h9 cord-339973-kj56zi59 cord-343302-g9vcchrh cord-344421-rmnck42f cord-342122-certy2v8 cord-343528-5283jsnu cord-350468-32qin4ak cord-344871-486sk4wc cord-345359-okmkgsbr cord-342676-ykog278j cord-342782-xty16m8w cord-344953-gtg12hiu cord-344344-q32b742a cord-351295-4toxlskr cord-340781-z348xbn0 cord-350255-tthttyl3 cord-350957-10wcqgaq cord-351659-ujbxsus4 cord-356027-ckdx56j1 cord-352061-x6tt9kx5 cord-346483-jc0xklzk cord-348515-bqqyly23 cord-355179-wmfwl2bh cord-352020-9wxwktck Creating transaction Updating ent table ===== Reducing parts of speech cord-001862-a097byk5 cord-001704-pdxm0iiw cord-001712-a1sbdhhn cord-001823-v60vv99o cord-001675-9717nzr7 cord-001116-2yvyiiuy cord-002312-jyk7f8hz cord-001875-ulq1xqma cord-002081-vi6rth9o cord-002110-pbb247lp cord-001522-82plcxv9 cord-002072-qbh728ec cord-002490-kw8psrmz cord-002673-5a1rfi6k cord-002373-rueg4gsj cord-001901-2s6hpakk cord-001858-nmi39n6h cord-002369-shk4n8f6 cord-002258-o9azey3m cord-002758-d86hnox1 cord-002290-wvo22jx2 cord-002782-mena480g cord-003055-88q36g00 cord-002720-lrkscs71 cord-002111-mmpijsqb cord-001852-c79vwr6t cord-002408-bbtslrrt cord-002644-yzan95du cord-001963-4wjvykx7 cord-002844-jv42o789 cord-001829-rwnbxmt4 cord-004181-exbs3tz7 cord-002932-5e7xrd1y cord-002474-2l31d7ew cord-002177-yyfgl9x5 cord-002320-m99amd4y cord-003490-swlkjtyo cord-002411-iiw878w8 cord-002874-9rxv6fy9 cord-002019-wtnf340p cord-003623-n01rgqyv cord-003148-o7y3wygc cord-002843-dvfmpm54 cord-002013-rb9xdzro cord-002659-566uoozj cord-002244-5h6monh3 cord-003166-k3jxvzfi cord-003004-iif2lnez cord-004150-ybikajhh cord-003505-qr6ukfti cord-003387-82573enr cord-002389-k86hzbbx cord-002956-e5ihpe4i cord-001915-b9dk07tk cord-001868-utsvsja0 cord-004062-yxx3xxio cord-004016-iaktm72a cord-003504-wjab4y0g cord-004060-nxw5k9y1 cord-004378-g1rxygef cord-003196-fdb6az0v cord-004170-ri5qsarz cord-004006-tfp2idq2 cord-004419-81w7apdk cord-004069-nuep8nim cord-002802-594mmlk8 cord-002045-m44fic4g cord-003667-u1xa44nw cord-004292-6lnxb0px cord-004379-91a7sgir cord-003558-7lvqpz21 cord-003444-dmpoy0b1 cord-002929-oqe3gjcs cord-004385-xna32qve cord-010140-nl1j2s56 cord-004222-z4butywi cord-004310-hl7fa4af cord-003011-vclnb0eh cord-002842-4evbeijx cord-002791-tqchfdmy cord-009691-gkynxdz3 cord-004342-9uok77wb cord-004156-79peyzc9 cord-013977-xb0r2axf cord-010675-acdfvjm5 cord-004280-c470nlie cord-005507-equnyib7 cord-004418-08dljap3 cord-034746-uxhpufnv cord-031937-qhlatg84 cord-011892-b9zlig0r cord-010328-uxpedpz8 cord-010640-s1oqphvn cord-004416-qw6tusd2 cord-012742-lpk6r54i cord-009690-kbwz7xop cord-007851-v6h1yro7 cord-259378-5g2y68i2 cord-255511-nk3iyg07 cord-004140-ujzrqzv3 cord-258678-0atfsivf cord-272092-ko9y5m2s cord-254090-x8tnweih cord-265211-a7whyds8 cord-030295-jlhht2l9 cord-263627-8ufjh70o cord-259794-6qoksn00 cord-254653-4ffuivil cord-260834-v254de8k cord-263088-zj14ro5j cord-259416-gvzp2h5g cord-271602-f14wccj3 cord-255586-wshvvgxg cord-271328-zdf5ji4k cord-269756-tid8a464 cord-265891-jmpterrj cord-280334-7b7rvr25 cord-269270-i2odcsx7 cord-277816-ncdy9qgb cord-273283-gb0m6fue cord-281536-8y7yxcp4 cord-276997-hbovh7s9 cord-272576-ez731lif cord-283583-pwlbrxn3 cord-272623-j5gpww9q cord-268414-7fcc5i7i cord-284374-sqxlnk9e cord-276444-jidvkij5 cord-284429-d7qxfo6d cord-287708-0qvwjejv cord-279598-xzionafe cord-286559-y8z0pwgn cord-284582-xwedgllw cord-294220-ewp1m8jp cord-288721-3bv3aak6 cord-288761-fyvr0tc1 cord-289932-dsysiefx cord-293747-ds8rhbkv cord-288731-x2cwyvb7 cord-286413-a7wue2e3 cord-288451-npefpo3t cord-293372-saqoft9p cord-296867-6o4scan1 cord-293505-1t3hg4wi cord-299605-j1ewxk4q cord-306517-tls0849i cord-304040-64obh7i3 cord-305473-w30hsr4m cord-301016-9t7v7ipt cord-302080-fegcf1fu cord-296562-3h2oqb9k cord-302459-grs2x26l cord-308302-5yns1hg9 cord-303601-o8uk6if2 cord-305132-jspxlk1a cord-309127-kxivgxbg cord-313126-7hrjzapj cord-308687-wrzzb9cy cord-312777-5925lvue cord-316930-0s7k9guq cord-315415-3aotsb2g cord-305031-9ze0097w cord-316983-h4mtpcyc cord-276185-ysspkbj7 cord-317579-ige2h4pd cord-318314-oxlv847d cord-318187-c59c9vi3 cord-318587-ewvnkdr2 cord-325405-cu4nx891 cord-320709-2pnqpljt cord-319118-47ovbto5 cord-321667-jkzxjk54 cord-315781-dejh8q22 cord-317813-sisfxdso cord-323087-3cxyogor cord-315483-l6dm82pp cord-322486-qwl7nzkr cord-314753-xflhxb13 cord-327405-xgtqfwyn cord-329155-ddpfox68 cord-331775-iaxkfszq cord-335055-gzuug3p5 cord-329766-9bwdb6o2 cord-329424-hmsidrc7 cord-331475-mmcu18c8 cord-331148-40gvay7i cord-334228-n69iewmx cord-335576-b34nc3ay cord-325657-s2vdazq0 cord-330562-dabjcvno cord-330057-3vucm0s1 cord-326868-3az13h1h cord-338041-gl65i3s0 cord-336493-ggo9wsrm cord-338588-rc1h4drd cord-333067-3zan82yf cord-340105-471x03f9 cord-338142-acqiyqwz cord-336901-q6kgzuob cord-342289-zpstb7h9 cord-342122-certy2v8 cord-344344-q32b742a cord-344421-rmnck42f cord-343528-5283jsnu cord-343302-g9vcchrh cord-350468-32qin4ak cord-342676-ykog278j cord-344871-486sk4wc cord-351295-4toxlskr cord-344953-gtg12hiu cord-350255-tthttyl3 cord-342782-xty16m8w cord-345359-okmkgsbr cord-352020-9wxwktck cord-356027-ckdx56j1 cord-350957-10wcqgaq cord-340781-z348xbn0 cord-352061-x6tt9kx5 cord-346483-jc0xklzk cord-324696-htx0ul4o cord-351659-ujbxsus4 cord-355179-wmfwl2bh cord-348515-bqqyly23 cord-339973-kj56zi59 Creating transaction Updating pos table Building ./etc/reader.txt cord-348515-bqqyly23 cord-002258-o9azey3m cord-342289-zpstb7h9 cord-355179-wmfwl2bh cord-352061-x6tt9kx5 cord-352020-9wxwktck number of items: 224 sum of words: 844,798 average size in words: 5,119 average readability score: 48 nouns: virus; cells; protein; infection; study; analysis; cell; patients; data; influenza; expression; time; disease; samples; mice; gene; viruses; proteins; results; model; control; number; °; group; antibody; studies; genes; levels; use; effect; activity; system; detection; acid; days; sequence; host; coronavirus; assay; sequences; genome; treatment; response; antibodies; groups; type; vaccine; role; sample; cases verbs: using; shown; including; based; performed; indicate; compare; induce; bind; associated; increased; following; identify; found; observed; infect; detected; reported; obtain; suggests; containing; determined; provide; described; expressed; reduces; given; demonstrated; collected; confirm; analyze; tested; considered; results; generated; caused; remained; makes; treated; assessed; evaluated; related; incubated; revealed; predict; lead; required; permitted; represent; measure adjectives: human; viral; different; specific; high; respiratory; clinical; non; positive; significant; higher; anti; immune; severe; similar; first; single; molecular; negative; low; acute; available; infectious; lower; bacterial; new; novel; infected; previous; large; multiple; several; inflammatory; important; total; present; small; free; like; potential; recombinant; dependent; possible; early; relative; porcine; current; common; antiviral; real adverbs: also; however; respectively; significantly; well; previously; therefore; highly; directly; even; first; together; approximately; furthermore; moreover; still; long; prior; additionally; otherwise; recently; interestingly; especially; statistically; finally; specifically; less; relatively; mainly; subsequently; next; likely; rather; hence; briefly; least; almost; similarly; alone; completely; much; currently; indeed; potentially; particularly; strongly; overnight; clearly; often; rapidly pronouns: we; our; it; their; its; they; i; you; his; them; your; us; one; itself; he; her; themselves; she; my; imagej; e804; hunovs; him; ifitm3; ifit5; me; y′; ours; ≤4; −; y148; tnf)-α; silico/; shrna#3; sgp; s230; ribosnitches; rh4; procaspase-1; oneself; oligod; mg; lysate/; kf442963; ints6p1; interleukin-15; inflammation/; in-/; illinois139/2006; il-12(p70 proper nouns: Fig; RNA; SARS; PCR; MERS; Table; China; C; Creative; Commons; Supplementary; S; www.nature.com/scientificreports/; CoV; T; COVID-19; CoV-2; PBS; RT; Ebola; USA; A; H7N9; S1; IBV; H1N1; IFN; DOI; RSV; PEDV; M; WT; II; Scientific; DNA; TGEV; F; East; ELISA; NPs; EBOV; B; mg; |; RBD; Sci; Rep; N; HCV; University keywords: rna; sars; covid-19; virus; patient; dna; cell; china; pcr; mers; protein; rsv; pedv; influenza; ifn; h7n9; ebola; east; tgev; mouse; model; gene; ebov; table; rbd; middle; mhc; lps; hcv; gfp; bat; zikv; vsv; vaccine; trial; tlr4; supplementary; study; strain; stat3; singapore; sample; rva; pten; plasmodium; plasma; pbs; particle; niclosamide; network one topic; one dimension: virus file(s): https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4626779/ titles(s): Modeling the effect of comprehensive interventions on Ebola virus transmission three topics; one dimension: virus; patients; mice file(s): https://doi.org/10.1038/srep37131, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6882870/, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7044206/ titles(s): SARS-CoV fusion peptides induce membrane surface ordering and curvature | A real-time spatio-temporal syndromic surveillance system with application to small companion animals | Development of a two-stage limb ischemia model to better simulate human peripheral artery disease five topics; three dimensions: protein virus using; cells infection virus; patients study covid; virus using 10; analysis using 10 file(s): https://doi.org/10.1038/srep37131, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4832189/, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6882870/, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5587679/, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5773709/ titles(s): SARS-CoV fusion peptides induce membrane surface ordering and curvature | Retinoic acid facilitates inactivated transmissible gastroenteritis virus induction of CD8(+) T-cell migration to the porcine gut | A real-time spatio-temporal syndromic surveillance system with application to small companion animals | Regional genetic diversity for NNV grouper viruses across the Indo-Asian region – implications for selecting virus resistance in farmed groupers | GenomeLandscaper: Landscape analysis of genome-fingerprints maps assessing chromosome architecture Type: cord title: journal-sciRep-cord date: 2021-05-30 time: 16:05 username: emorgan patron: Eric Morgan email: emorgan@nd.edu input: facet_journal:"Sci Rep" ==== make-pages.sh htm files ==== make-pages.sh complex files ==== make-pages.sh named enities ==== making bibliographics id: cord-280334-7b7rvr25 author: Abrantes, Joana title: Recombination at the emergence of the pathogenic rabbit haemorrhagic disease virus Lagovirus europaeus/GI.2 date: 2020-09-02 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Rabbit haemorrhagic disease is a viral disease that emerged in the 1980s and causes high mortality and morbidity in the European rabbit (Oryctolagus cuniculus). In 2010, a new genotype of the rabbit haemorrhagic disease virus emerged and replaced the former circulating Lagovirus europaeus/GI.1 strains. Several recombination events have been reported for the new genotype Lagovirus europaeus/GI.2, with pathogenic (variants GI.1a and GI.1b) and benign (genotype GI.4) strains that served as donors for the non-structural part while GI.2 composed the structural part; another recombination event has also been described at the p16/p23 junction involving GI.4 strains. In this study, we analysed new complete coding sequences of four benign GI.3 strains and four GI.2 strains. Phylogenetic and recombination detection analyses revealed that the first GI.2 strains, considered as non-recombinant, resulted from a recombination event between GI.3 and GI.2, with GI.3 as the major donor for the non-structural part and GI.2 for the structural part. Our results indicate that recombination contributed to the emergence, persistence and dissemination of GI.2 as a pathogenic form and that all described GI.2 strains so far are the product of recombination. This highlights the need to study full-genomic sequences of lagoviruses to understand their emergence and evolution. url: https://www.ncbi.nlm.nih.gov/pubmed/32879332/ doi: 10.1038/s41598-020-71303-4 id: cord-343302-g9vcchrh author: Agrawal, Anurodh Shankar title: Passive Transfer of A Germline-like Neutralizing Human Monoclonal Antibody Protects Transgenic Mice Against Lethal Middle East Respiratory Syndrome Coronavirus Infection date: 2016-08-19 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Middle East Respiratory Syndrome coronavirus (MERS-CoV) has repeatedly caused outbreaks in the Arabian Peninsula. To date, no approved medical countermeasures (MCM) are available to combat MERS-CoV infections. Several neutralizing human monoclonal antibodies (mAbs), including m336, a germline-like human mAb, have been chosen as promising MCM for MERS-CoV. However, their clinical development has been hindered by the lack of a robust animal model that recapitulate the morbidity and mortality of human infections. We assessed the prophylactic and therapeutic efficacy of m336 by using well-characterized transgenic mice shown to be highly sensitive to MERS-CoV infection and disease. We found that mice treated with m336 prior to or post lethal MERS-CoV challenging were fully protected, compared to control mice which sufferered from profound weight loss and uniform death within days after infection. Taken together, these results support further development of m336 and other human monoclonal antibodies as potential therapeutics for MERS-CoV infection. url: https://doi.org/10.1038/srep31629 doi: 10.1038/srep31629 id: cord-002843-dvfmpm54 author: Ai, Hannan title: GenomeLandscaper: Landscape analysis of genome-fingerprints maps assessing chromosome architecture date: 2018-01-18 words: 6824.0 sentences: 382.0 pages: flesch: 55.0 cache: ./cache/cord-002843-dvfmpm54.txt txt: ./txt/cord-002843-dvfmpm54.txt summary: We create a geometric analysis method (called GenomeLandscaper) to conduct landscape analysis of genome-fingerprints maps (GFM), trace large-scale repetitive regions, and assess their impacts on the global architectures of assembled chromosomes. Specifically, we delete a 1.30-Mbp (from 9,999,936 bp to 11,299,986 bp) target segment (Supplementary Dataset 1) from the prior-cleaned GRCh38p1.chrY, as guided by the turning-changed long sharp straight line on the 2D-trajectory map (X-Length) of the GGFM (Fig. 4a ). We conclude that the 1.30-Mbp target segment (Supplementary Dataset 1) does locate in the centromeric and pericentromeric region of GRCh38p1.chrY (and throughout GRCh38p10.chrY) (Figs 3, 4 and 5), which encourages us to trace its sub-constituents that contributed to the observed turning-changed long sharp straight line on the GGFM (Figs 3 and 4 ). abstract: Assessing correctness of an assembled chromosome architecture is a central challenge. We create a geometric analysis method (called GenomeLandscaper) to conduct landscape analysis of genome-fingerprints maps (GFM), trace large-scale repetitive regions, and assess their impacts on the global architectures of assembled chromosomes. We develop an alignment-free method for phylogenetics analysis. The human Y chromosomes (GRCh.chrY, HuRef.chrY and YH.chrY) are analysed as a proof-of-concept study. We construct a galaxy of genome-fingerprints maps (GGFM) for them, and a landscape compatibility among relatives is observed. But a long sharp straight line on the GGFM breaks such a landscape compatibility, distinguishing GRCh38p1.chrY (and throughout GRCh38p7.chrY) from GRCh37p13.chrY, HuRef.chrY and YH.chrY. We delete a 1.30-Mbp target segment to rescue the landscape compatibility, matching the antecedent GRCh37p13.chrY. We re-locate it into the modelled centromeric and pericentromeric region of GRCh38p10.chrY, matching a gap placeholder of GRCh37p13.chrY. We decompose it into sub-constituents (such as BACs, interspersed repeats, and tandem repeats) and trace their homologues by phylogenetics analysis. We elucidate that most examined tandem repeats are of reasonable quality, but the BAC-sized repeats, 173U1020C (176.46 Kbp) and 5U41068C (205.34 Kbp), are likely over-repeated. These results offer unique insights into the centromeric and pericentromeric regions of the human Y chromosomes. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5773709/ doi: 10.1038/s41598-018-19366-2 id: cord-002408-bbtslrrt author: Almogy, Gal title: Analysis of Influenza and RSV dynamics in the community using a ‘Local Transmission Zone’ approach date: 2017-02-09 words: 5450.0 sentences: 246.0 pages: flesch: 54.0 cache: ./cache/cord-002408-bbtslrrt.txt txt: ./txt/cord-002408-bbtslrrt.txt summary: We demonstrate that this urban area is not a single, perfectly mixed ecology, but is in fact comprised of a set of more basic, relatively independent pathogen transmission units, which we term here Local Transmission Zones, LTZs. By identifying these LTZs, and using the dynamic pathogen-content information contained within them, we are able to differentiate between disease-causes at the individual patient level often with near-perfect predictive accuracy. To investigate the possibility of LTZs in a large regional area, we analyze clinical data from a healthcare medical center in the city of Jerusalem, containing the clinical test results for Influenza virus and Respiratory Syncytial Virus (RSV) from patients presenting with ILI symptoms. Our analysis finds that while Influenza and RSV incidences tend to overlap and show more or less equal number of cases over the whole region, individual LTZs show a far more homogeneous disease content at most given times, with some being dominated by RSV while others by Influenza. abstract: Understanding the dynamics of pathogen spread within urban areas is critical for the effective prevention and containment of communicable diseases. At these relatively small geographic scales, short-distance interactions and tightly knit sub-networks dominate the dynamics of pathogen transmission; yet, the effective boundaries of these micro-scale groups are generally not known and often ignored. Using clinical test results from hospital admitted patients we analyze the spatio-temporal distribution of Influenza Like Illness (ILI) in the city of Jerusalem over a period of three winter seasons. We demonstrate that this urban area is not a single, perfectly mixed ecology, but is in fact comprised of a set of more basic, relatively independent pathogen transmission units, which we term here Local Transmission Zones, LTZs. By identifying these LTZs, and using the dynamic pathogen-content information contained within them, we are able to differentiate between disease-causes at the individual patient level often with near-perfect predictive accuracy. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5299452/ doi: 10.1038/srep42012 id: cord-276997-hbovh7s9 author: Alsved, Malin title: Aerosolization and recovery of viable murine norovirus in an experimental setup date: 2020-09-29 words: 6031.0 sentences: 297.0 pages: flesch: 46.0 cache: ./cache/cord-276997-hbovh7s9.txt txt: ./txt/cord-276997-hbovh7s9.txt summary: However, the infectivity of airborne human noroviruses has not been possible to assess in real-world environments, nor in laboratory experiments, since there is no well-established cell culturing system for these viruses working at the low concentrations obtained in air samples 6 . SLAG: Sparging liquid aerosol generator; HEPA filter: high efficiency particulate air filter; nsRNA: negative sense RNA; psRNA: positive sense RNA; MNV: murine norovirus; qRT-PCR: quantitative reverse transcriptase polymerase chain reaction. Taken together, as compared to the atomizer, a smaller amount of SLAG aerosol is collected by the BioSampler (i.e., higher physical dilution), but these particles contain more MNV psRNA copies (lower viral dilution relative the physical dilution). The experimental setup described here highlights some difficulties in studies on aerosolized viruses: (1) the lack of standards in how to generate bioaerosol that results in significant differences in aerosol particle size and concentration, (2) the necessity to determine both physical and viral dilution factors, and (3) www.nature.com/scientificreports/ during airborne transport due to the low-solute solution and dilution in the setup. abstract: Noroviruses are the major cause for viral acute gastroenteritis in the world. Despite the existing infection prevention strategies in hospitals, the disease continues to spread and causes extensive and numerous outbreaks. Hence, there is a need to investigate the possibility of airborne transmission of norovirus. In this study, we developed an experimental setup for studies on the infectivity of aerosolized murine norovirus (MNV), a model for the human norovirus. Two aerosol generation principles were evaluated: bubble bursting, a common natural aerosolization mechanism, and nebulization, a common aerosolization technique in laboratory studies. The aerosolization setup was characterized by physical and viral dilution factors, generated aerosol particle size distributions, and the viral infectivity after aerosolization. We found a lower physical dilution factor when using the nebulization generator than with the bubble bursting generator. The viral dilution factor of the system was higher than the physical dilution; however, when comparing the physical and viral dilution factors, bubble bursting generation was more efficient. The infectivity per virus was similar using either generation principle, suggesting that the generation itself had a minor impact on MNV infectivity and that instead, the effect of drying in air could be a major reason for infectivity losses. url: https://doi.org/10.1038/s41598-020-72932-5 doi: 10.1038/s41598-020-72932-5 id: cord-273283-gb0m6fue author: Altschul, David J. title: A novel severity score to predict inpatient mortality in COVID-19 patients date: 2020-10-07 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: COVID-19 is commonly mild and self-limiting, but in a considerable portion of patients the disease is severe and fatal. Determining which patients are at high risk of severe illness or mortality is essential for appropriate clinical decision making. We propose a novel severity score specifically for COVID-19 to help predict disease severity and mortality. 4711 patients with confirmed SARS-CoV-2 infection were included. We derived a risk model using the first half of the cohort (n = 2355 patients) by logistic regression and bootstrapping methods. The discriminative power of the risk model was assessed by calculating the area under the receiver operating characteristic curves (AUC). The severity score was validated in a second half of 2356 patients. Mortality incidence was 26.4% in the derivation cohort and 22.4% in the validation cohort. A COVID-19 severity score ranging from 0 to 10, consisting of age, oxygen saturation, mean arterial pressure, blood urea nitrogen, C-Reactive protein, and the international normalized ratio was developed. A ROC curve analysis was performed in the derivation cohort achieved an AUC of 0.824 (95% CI 0.814–0.851) and an AUC of 0.798 (95% CI 0.789–0.818) in the validation cohort. Furthermore, based on the risk categorization the probability of mortality was 11.8%, 39% and 78% for patient with low (0–3), moderate (4–6) and high (7–10) COVID-19 severity score. This developed and validated novel COVID-19 severity score will aid physicians in predicting mortality during surge periods. url: https://www.ncbi.nlm.nih.gov/pubmed/33028914/ doi: 10.1038/s41598-020-73962-9 id: cord-003490-swlkjtyo author: Arzt, Jonathan title: Quantitative impacts of incubation phase transmission of foot-and-mouth disease virus date: 2019-02-25 words: 7446.0 sentences: 327.0 pages: flesch: 39.0 cache: ./cache/cord-003490-swlkjtyo.txt txt: ./txt/cord-003490-swlkjtyo.txt summary: The current investigation applied a Bayesian modeling approach to a unique experimental transmission study to estimate the occurrence of transmission of foot-and-mouth disease (FMD) during the incubation phase amongst group-housed pigs. This current study focused on investigating the concept of θ and ω for direct contact transmission of a virulent strain of foot-and-mouth disease virus (FMDV) amongst juvenile domestic pigs, and examining the impact of pre-clinical transmission on simulated outbreak size and severity within a US swine production system assuming either optimal or suboptimal response conditions. The most noteworthy findings from this approach were the substantial changes in the modeled estimates of the duration of latency and subclinical infectiousness (ω) when defining the onset of infectiousness by either the occurrence of clinical signs of FMD in donor pigs or by any detection of FMDV RNA in OPF. abstract: The current investigation applied a Bayesian modeling approach to a unique experimental transmission study to estimate the occurrence of transmission of foot-and-mouth disease (FMD) during the incubation phase amongst group-housed pigs. The primary outcome was that transmission occurred approximately one day prior to development of visible signs of disease (posterior median 21 hours, 95% CI: 1.1–45.0). Updated disease state durations were incorporated into a simulation model to examine the importance of addressing preclinical transmission in the face of robust response measures. Simulation of FMD outbreaks in the US pig production sector demonstrated that including a preclinical infectious period of one day would result in a 40% increase in the median number of farms affected (166 additional farms and 664,912 pigs euthanized) compared to the scenario of no preclinical transmission, assuming suboptimal outbreak response. These findings emphasize the importance of considering transmission of FMD during the incubation phase in modeling and response planning. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6389902/ doi: 10.1038/s41598-019-39029-0 id: cord-317813-sisfxdso author: Banskar, Sunil title: Microbiome analysis reveals the abundance of bacterial pathogens in Rousettus leschenaultii guano date: 2016-11-15 words: 6582.0 sentences: 379.0 pages: flesch: 48.0 cache: ./cache/cord-317813-sisfxdso.txt txt: ./txt/cord-317813-sisfxdso.txt summary: Applying in-depth bacterial community analysis using high-throughput 16 S rRNA gene sequencing, a high inter-individual variation was observed among the studied guano samples. Additionally, 16 S rRNA gene sequencing was performed using Ion Torrent PGM to identify the bacterial communities and screened for the presence of putative human pathogens. Sequence analysis of the cytochrome B (cytB) gene amplified from total extracted DNA of the guano pellets revealed that the collected fecal pellets were from a single bat species i.e. Rousettus leschenaultii, a predominant bat species reported from the Robber''s cave 23 . Further, computation of core microbiome from Ion Torrent sequences of fresh guano revealed the presence of five bacterial phyla i.e. Proteobacteria, Tenericutes, Candidate division TM7, Firmicutes and Actinobacteria but in different proportions (Fig. 5, Supplementary Figure S7 ). Additionally, Ion Torrent sequencing of 16 S rRNA gene provided information about the general bacterial communities with specific emphasis on pathogens among the total communities present in bat guano. abstract: Bats are crucial for proper functioning of an ecosystem. They provide various important services to ecosystem and environment. While, bats are well-known carrier of pathogenic viruses, their possible role as a potential carrier of pathogenic bacteria is under-explored. Here, using culture-based approach, employing multiple bacteriological media, over thousand bacteria were cultivated and identified from Rousettus leschenaultii (a frugivorous bat species), the majority of which were from the family Enterobacteriaceae and putative pathogens. Next, pathogenic potential of most frequently cultivated component of microbiome i.e. Escherichia coli was assessed to identify its known pathotypes which revealed the presence of virulent factors in many cultivated E. coli isolates. Applying in-depth bacterial community analysis using high-throughput 16 S rRNA gene sequencing, a high inter-individual variation was observed among the studied guano samples. Interestingly, a higher diversity of bacterial communities was observed in decaying guano representative. The search against human pathogenic bacteria database at 97% identity, a small proportion of sequences were found associated to well-known human pathogens. The present study thus indicates that this bat species may carry potential bacterial pathogens and advice to study the effect of these pathogens on bats itself and the probable mode of transmission to humans and other animals. url: https://www.ncbi.nlm.nih.gov/pubmed/27845426/ doi: 10.1038/srep36948 id: cord-010640-s1oqphvn author: Baral, Prabin title: In-silico identification of the vaccine candidate epitopes against the Lassa virus hemorrhagic fever date: 2020-05-06 words: 4835.0 sentences: 276.0 pages: flesch: 51.0 cache: ./cache/cord-010640-s1oqphvn.txt txt: ./txt/cord-010640-s1oqphvn.txt summary: In an effort to discover new LASV vaccines, we employ several sequence-based computational prediction tools to identify LASV GP major histocompatibility complex (MHC) class I and II T-cell epitopes. In this study, we have identified and characterized T and B-cell epitopes for the LASV GP using different sequence and structure-based computational epitope prediction methods. MHC-I T-cell epitope prediction with the LASV GP sequence was performed using three different methods separately: ProPred-1, CTLPred, and NetCTL1.2, and the results are shown in Supplementary Table S1. MHC-II T-cell epitope prediction with the LASV GP sequence was performed using three different methods separately: ProPred, NetMHCII 2.3, and EpiTOP 3.0, and the results are shown in Supplementary Table S2 . Docking of the four consensus MHC-I epitopes (Table 1 ) was performed using Autodock Vina, which enabled the docking of epitopes obtained from the sequence-based MHC-1 T-cell prediction into the promising allele structures. abstract: Lassa virus (LASV), a member of the Arenaviridae, is an ambisense RNA virus that causes severe hemorrhagic fever with a high fatality rate in humans in West and Central Africa. Currently, no FDA approved drugs or vaccines are available for the treatment of LASV fever. The LASV glycoprotein complex (GP) is a promising target for vaccine or drug development. It is situated on the virion envelope and plays key roles in LASV growth, cell tropism, host range, and pathogenicity. In an effort to discover new LASV vaccines, we employ several sequence-based computational prediction tools to identify LASV GP major histocompatibility complex (MHC) class I and II T-cell epitopes. In addition, many sequence- and structure-based computational prediction tools were used to identify LASV GP B-cell epitopes. The predicted T- and B-cell epitopes were further filtered based on the consensus approach that resulted in the identification of thirty new epitopes that have not been previously tested experimentally. Epitope-allele complexes were obtained for selected strongly binding alleles to the MHC-I T-cell epitopes using molecular docking and the complexes were relaxed with molecular dynamics simulations to investigate the interaction and dynamics of the epitope-allele complexes. These predictions provide guidance to the experimental investigations and validation of the epitopes with the potential for stimulating T-cell responses and B-cell antibodies against LASV and allow the design and development of LASV vaccines. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7203123/ doi: 10.1038/s41598-020-63640-1 id: cord-269756-tid8a464 author: Basso, Luis G. M. title: SARS-CoV fusion peptides induce membrane surface ordering and curvature date: 2016-11-28 words: 12194.0 sentences: 532.0 pages: flesch: 49.0 cache: ./cache/cord-269756-tid8a464.txt txt: ./txt/cord-269756-tid8a464.txt summary: Although membrane fusion promoted by class I viral glycoproteins, such as SARS-CoV Spike, human immunodeficiency virus (HIV) gp160 or influenza virus hemagglutinin (HA), has been broadly studied in recent years [16] [17] [18] [19] , many aspects of the molecular mechanism behind the virus-host cell membrane fusion remain unknown, including conformational changes of the lipid bilayers during peptide-membrane interactions. In the present study, we investigated the effects of two putative fusion peptides from SARS-CoV S glycoprotein, corresponding to residues 770-788 (SARS FP ) and 873-888 (SARS IFP ) 13, 15, 22, 23 , on the structural dynamics, physicochemical properties, and thermotropic phase behavior of lipid model membranes by differential scanning calorimetry (DSC), continuous wave (CW) and pulsed electron spin resonance (ESR) along with nonlinear least-squares (NLLS) spectral fitting 24 . abstract: Viral membrane fusion is an orchestrated process triggered by membrane-anchored viral fusion glycoproteins. The S2 subunit of the spike glycoprotein from severe acute respiratory syndrome (SARS) coronavirus (CoV) contains internal domains called fusion peptides (FP) that play essential roles in virus entry. Although membrane fusion has been broadly studied, there are still major gaps in the molecular details of lipid rearrangements in the bilayer during fusion peptide-membrane interactions. Here we employed differential scanning calorimetry (DSC) and electron spin resonance (ESR) to gather information on the membrane fusion mechanism promoted by two putative SARS FPs. DSC data showed the peptides strongly perturb the structural integrity of anionic vesicles and support the hypothesis that the peptides generate opposing curvature stresses on phosphatidylethanolamine membranes. ESR showed that both FPs increase lipid packing and head group ordering as well as reduce the intramembrane water content for anionic membranes. Therefore, bending moment in the bilayer could be generated, promoting negative curvature. The significance of the ordering effect, membrane dehydration, changes in the curvature properties and the possible role of negatively charged phospholipids in helping to overcome the high kinetic barrier involved in the different stages of the SARS-CoV-mediated membrane fusion are discussed. url: https://doi.org/10.1038/srep37131 doi: 10.1038/srep37131 id: cord-318187-c59c9vi3 author: Basu, Saikat title: Numerical evaluation of spray position for improved nasal drug delivery date: 2020-06-29 words: 7843.0 sentences: 375.0 pages: flesch: 44.0 cache: ./cache/cord-318187-c59c9vi3.txt txt: ./txt/cord-318187-c59c9vi3.txt summary: The protocol involves re-orienting the spray axis to harness inertial motion of particulates and has been developed using computational fluid dynamics simulations of respiratory airflow and droplet transport in medical imaging-based digital models. Of interest are nasal spray simulation studies on in silico models, re-constructed from medical imaging, to measure drug delivery along the nasal passages 9 , in the sinuses 10, 11 , and on the effects of surgical alterations of the anatomy on nasal airflow [12] [13] [14] [15] as well as on topical transport of drugs [16] [17] [18] [19] . The computational fluid dynamics (CFD) models of droplet transport and the in silico prediction of their deposition sites along the nasal airway walls have been compared with in vitro spray experiments in 3D-printed solid replicas of the same anatomic reconstructions. abstract: Topical intra-nasal sprays are amongst the most commonly prescribed therapeutic options for sinonasal diseases in humans. However, inconsistency and ambiguity in instructions show a lack of definitive knowledge on best spray use techniques. In this study, we have identified a new usage strategy for nasal sprays available over-the-counter, that registers an average 8-fold improvement in topical delivery of drugs at diseased sites, when compared to prevalent spray techniques. The protocol involves re-orienting the spray axis to harness inertial motion of particulates and has been developed using computational fluid dynamics simulations of respiratory airflow and droplet transport in medical imaging-based digital models. Simulated dose in representative models is validated through in vitro spray measurements in 3D-printed anatomic replicas using the gamma scintigraphy technique. This work breaks new ground in proposing an alternative user-friendly strategy that can significantly enhance topical delivery inside human nose. While these findings can eventually translate into personalized spray usage instructions and hence merit a change in nasal standard-of-care, this study also demonstrates how relatively simple engineering analysis tools can revolutionize everyday healthcare. Finally, with respiratory mucosa as the initial coronavirus infection site, our findings are relevant to intra-nasal vaccines that are in-development, to mitigate the COVID-19 pandemic. url: https://www.ncbi.nlm.nih.gov/pubmed/32601278/ doi: 10.1038/s41598-020-66716-0 id: cord-002490-kw8psrmz author: Beniac, Daniel R. title: Structure of the Ebola virus glycoprotein spike within the virion envelope at 11 Å resolution date: 2017-04-11 words: 4053.0 sentences: 184.0 pages: flesch: 53.0 cache: ./cache/cord-002490-kw8psrmz.txt txt: ./txt/cord-002490-kw8psrmz.txt summary: We present the structure of the surface Ebola virus (EBOV) trimeric glycoprotein (GP) spike at 11 Å resolution, in situ within the viral plasma membrane of purified virus particles. In addition, 29,976 images were selected for reference-free analysis of the half-diameter of EBOV to investigate the spatial distribution of the GP spikes, as well as the periodicity and symmetrical relationships between GP and the matrix protein VP40 in the envelope, and the underlying nucleocapsid layer (Figs 1c and S3) . The spike structure of Beniac et al imaged within the virus-like particles was somehow clipped, since this should have included the mucin-like domains: in addition, tomography was combined with single-particle analysis, which may have distorted the results 4 . The structure that we report here is based entirely on the well-accepted method of single-particle analysis using projection matching, and is broadly similar to that published of expressed GP in virus-like particles using tomography 28, 29 : there are noticeable differences in shape and size of the spike, as well as in resolution (Fig. 4) . abstract: We present the structure of the surface Ebola virus (EBOV) trimeric glycoprotein (GP) spike at 11 Å resolution, in situ within the viral plasma membrane of purified virus particles. GP functions in cellular attachment, endosomal entry, and membrane fusion to initiate infection, and is a key therapeutic target. Nevertheless, only about half of the GP molecule has yet been solved to atomic resolution, excluding the mucin-like and transmembrane domains, and some of the glycans. Fitting of the atomic resolution X-ray data from expressed, truncated deletion constructs within our 11 Å structure of the entire molecule demonstrates the relationship between the GP1-GP2 domains, the mucin-like and transmembrane domains, and the bilaminar lipid envelope. We show that the mucin-like domain covers the glycan cap and partially occludes the receptor binding sites prior to proteolytic cleavage. Our structure is also consistent with key antibody neutralisation sites on GP being accessible prior to proteolysis. Based on the findings of us and others, GP-mediated binding may create an angle of 18 degrees between the planes of viral and endosomal membranes. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5387728/ doi: 10.1038/srep46374 id: cord-293505-1t3hg4wi author: Bernard-Stoecklin, Sibylle title: Comparative Analysis of Eleven Healthcare-Associated Outbreaks of Middle East Respiratory Syndrome Coronavirus (Mers-Cov) from 2015 to 2017 date: 2019-05-14 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Since its emergence in 2012, 2,260 cases and 803 deaths due to Middle East respiratory syndrome coronavirus (MERS-CoV) have been reported to the World Health Organization. Most cases were due to transmission in healthcare settings, sometimes causing large outbreaks. We analyzed epidemiologic and clinical data of laboratory-confirmed MERS-CoV cases from eleven healthcare-associated outbreaks in the Kingdom of Saudi Arabia and the Republic of Korea between 2015–2017. We quantified key epidemiological differences between outbreaks. Twenty-five percent (n = 105/422) of MERS cases who acquired infection in a hospital setting were healthcare personnel. In multivariate analyses, age ≥65 (OR 4.8, 95%CI: 2.6–8.7) and the presence of underlying comorbidities (OR: 2.7, 95% CI: 1.3–5.7) were associated with increased mortality whereas working as healthcare personnel was protective (OR 0.07, 95% CI: 0.01–0.34). At the start of these outbreaks, the reproduction number ranged from 1.0 to 5.7; it dropped below 1 within 2 to 6 weeks. This study provides a comprehensive characterization of MERS HCA-outbreaks. Our results highlight heterogeneities in the epidemiological profile of healthcare-associated outbreaks. The limitations of our study stress the urgent need for standardized data collection for high-threat respiratory pathogens, such as MERS-CoV. url: https://www.ncbi.nlm.nih.gov/pubmed/31089148/ doi: 10.1038/s41598-019-43586-9 id: cord-002072-qbh728ec author: Bi, Yuhai title: A new reassortment of influenza A (H7N9) virus causing human infection in Beijing, 2014 date: 2016-05-27 words: 3096.0 sentences: 170.0 pages: flesch: 48.0 cache: ./cache/cord-002072-qbh728ec.txt txt: ./txt/cord-002072-qbh728ec.txt summary: Genetic and phylogenetic analyses revealed that the virus belonged to a novel genotype, which probably emerged and further reassorted with other H9 or H7 viruses in poultry before transmitting to humans. The IFN-induced transmembrane protein-3 (IFITM3) C/C genotype was reported to be associated with severe clinical outcomes, as reflected by a higher viral load, more rapid progression to ARDS, higher cytokine/chemokine levels, and an increased mortality rate after H7N9 infection 22 . Although this was a severe H7N9-infected case with cytokine storm-like appearances and multiple organ failure, the patient was eventually cured after combination therapy with antivirals, mechanical ventilation, supportive nutrition and symptomatic treatment. Clinical, virological and immunological features from patients infected with re-emergent avian-origin human H7N9 influenza disease of varying severity in Guangdong province Cytokine and chemokine levels in patients infected with the novel avian influenza A (H7N9) virus in China abstract: A 73-year-old man was confirmed to have an influenza A (H7N9) virus infection, and the causative agent A/Beijing/02/2014(H7N9) virus was isolated. Genetic and phylogenetic analyses revealed that the virus belonged to a novel genotype, which probably emerged and further reassorted with other H9 or H7 viruses in poultry before transmitting to humans. This virus caused a severe infection with high levels of cytokines and neutralizing antibodies. Eventually, the patient was cured after serially combined treatments. Taken together, our findings indicated that this novel genotype of the human H7N9 virus did not evolve directly from the first Beijing isolate A/Beijing/01/2013(H7N9), suggesting that the H7N9 virus has not obtained the ability for human-to-human transmissibility and the virus only evolves in poultry and then infects human by direct contact. Hence, the major measures to prevent human H7N9 virus infection are still to control and standardize the live poultry trade. Early antiviral treatment with combination therapies, including mechanical ventilation, nutrition support and symptomatic treatment, are effective for H7N9 infection. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4882526/ doi: 10.1038/srep26624 id: cord-002312-jyk7f8hz author: Branton, W. G. title: Brain microbiota disruption within inflammatory demyelinating lesions in multiple sclerosis date: 2016-11-28 words: 4611.0 sentences: 231.0 pages: flesch: 41.0 cache: ./cache/cord-002312-jyk7f8hz.txt txt: ./txt/cord-002312-jyk7f8hz.txt summary: Massively parallel (deep) sequencing (RNAseq) of total RNA permitted analysis of all RNA sequences in MS (n = 6) and nonMS (n = 6) white matter samples, revealing that bacterial RNA (ribosomal and non-ribosomal) sequences were detected in all nonMS and MS brain specimens, including MS patients with relapsing-remitting disease (receiving disease modifying therapy) (RR-MS, n = 3) and progressive (untreated) MS (P-MS; n = 3) ( Fig. 2A) . The current study shows the presence of bacterial RNA and DNA sequences and proteins in human brain which are disrupted in conjunction with inflammatory demyelination in patients with MS. The present studies revealed the ratio of bacterium-encoded 16s rDNA to rRNA in matched brain samples to be ~1:2 in both white matter (and cortex, data not shown) with bacterial numbers of 1200-1400 genomes/cm 3 suggesting both bacterial burden and replication were low compared to active pathogenic infections in other tissues. abstract: Microbial communities reside in healthy tissues but are often disrupted during disease. Bacterial genomes and proteins are detected in brains from humans, nonhuman primates, rodents and other species in the absence of neurological disease. We investigated the composition and abundance of microbiota in frozen and fixed autopsied brain samples from patients with multiple sclerosis (MS) and age- and sex-matched nonMS patients as controls, using neuropathological, molecular and bioinformatics tools. 16s rRNA sequencing revealed Proteobacteria to be the dominant phylum with restricted diversity in cerebral white matter (WM) from MS compared to nonMS patients. Both clinical groups displayed 1,200–1,400 bacterial genomes/cm(3) and low bacterial rRNA:rDNA ratios in WM. RNAseq analyses showed a predominance of Proteobacteria in progressive MS patients’ WM, associated with increased inflammatory gene expression, relative to a broader range of bacterial phyla in relapsing-remitting MS patients’ WM. Although bacterial peptidoglycan (PGN) and RNA polymerase beta subunit immunoreactivities were observed in all patients, PGN immunodetection was correlated with demyelination and neuroinflammation in MS brains. Principal component analysis revealed that demyelination, PGN and inflammatory gene expression accounted for 86% of the observed variance. Thus, inflammatory demyelination is linked to an organ-specific dysbiosis in MS that could contribute to underlying disease mechanisms. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5125007/ doi: 10.1038/srep37344 id: cord-308687-wrzzb9cy author: Brunner, Jesse L. title: Pooled samples and eDNA-based detection can facilitate the “clean trade” of aquatic animals date: 2020-06-24 words: 6488.0 sentences: 322.0 pages: flesch: 46.0 cache: ./cache/cord-308687-wrzzb9cy.txt txt: ./txt/cord-308687-wrzzb9cy.txt summary: swabs) and eDNA samples collected from finite populations and discuss key assumptions and considerations for their use with a focus on detecting Batrachochytrium salamandrivorans, an emerging pathogen that threatens global salamander diversity. www.nature.com/scientificreports www.nature.com/scientificreports/ context of screening U.S. service members for syphilis, pooling samples to reduce the number of tests required to detect rare infections is common in numerous contexts 22 , including surveys for disease freedom. In this paper I therefore develop formulae for imperfect tests of pooled samples in closed populations and eDNA, discuss the key assumptions and considerations in their application, and illustrate how eDNA may be especially useful for detecting infections in the live animal trade. Pooling and batch-processing samples collected from individual animals (e.g., swabs) can reduce several fold the number of diagnostic tests (e.g., DNA extractions and PCR reactions) required to detect rare infections. abstract: The regional and international trade of live animals facilitates the movement, spillover, and emergence of zoonotic and epizootic pathogens around the world. Detecting pathogens in trade is critical for preventing their continued movement and introduction, but screening a sufficient fraction to ensure rare infections are detected is simply infeasible for many taxa and settings because of the vast numbers of animals involved—hundreds of millions of live animals are imported into the U.S.A. alone every year. Batch processing pools of individual samples or using environmental DNA (eDNA)—the genetic material shed into an organism’s environment—collected from whole consignments of animals may substantially reduce the time and cost associated with pathogen surveillance. Both approaches, however, lack a framework with which to determine sampling requirements and interpret results. Here I present formulae for pooled individual samples (e.g,. swabs) and eDNA samples collected from finite populations and discuss key assumptions and considerations for their use with a focus on detecting Batrachochytrium salamandrivorans, an emerging pathogen that threatens global salamander diversity. While empirical validation is key, these formulae illustrate the potential for eDNA-based detection in particular to reduce sample sizes and help bring clean trade into reach for a greater number of taxa, places, and contexts. url: https://www.ncbi.nlm.nih.gov/pubmed/32581260/ doi: 10.1038/s41598-020-66280-7 id: cord-305031-9ze0097w author: Büchel, Beda title: Empirical dynamics of railway delay propagation identified during the large-scale Rastatt disruption date: 2020-10-29 words: 7695.0 sentences: 336.0 pages: flesch: 47.0 cache: ./cache/cord-305031-9ze0097w.txt txt: ./txt/cord-305031-9ze0097w.txt summary: We cannot consider delay changes for freight traffic, as its volume was strongly affected by the Rastatt disruption; and more generally, freight traffic does not stop at stations thus having a ill-defined delay; and Scientific Reports | (2020) 10:18584 | https://doi.org/10.1038/s41598-020-75538-z www.nature.com/scientificreports/ despite its buffer times are typically large, its performance is often erratic. We now discuss how a state-of-the-art simulation model, OnTime, based on typical delay propagation theory 39 (the Methods section describes its assumptions and functioning, and its calibration for the test case) can partially replicate the degree by which the delay performance of passenger trains improved in the area of Basel, and decreased in the area of Schaffhausen. Newly designed statistical tests were applied to delay analysis in railway networks, performed at different percentile levels, over multiple time scales, and two specific factors (reduced entrance delay for passenger trains and rerouted freight trains). abstract: Transport networks are becoming increasingly large and interconnected. This interconnectivity is a key enabler of accessibility; on the other hand, it results in vulnerability, i.e. reduced performance, in case any specific part is subject to disruptions. We analyse how railway systems are vulnerable to delay, and how delays propagate in railway networks, studying real-life delay propagation phenomena on empirical data, determining real-life impact and delay propagation for the uncommon case of railway disruptions. We take a unique approach by looking at the same system, in two different operating conditions, to disentangle processes and dynamics that are normally present and co-occurring in railway operations. We exploit the unique chance to observe a systematic change in railway operations conditions, without a correspondent system change of infrastructure or timetable, coming from the occurrence of the large-scale disruption at Rastatt, Germany, in 2017. We define new statistical methods able to detect weak signals in the noisy dataset of recorded punctuality for passenger traffic in Switzerland, in the disrupted and undisrupted state, along a period of 1 year. We determine how delay propagation changed, and quantify the heterogeneous, large-scale cascading effects of the Rastatt disruption towards the Swiss network, hundreds of kilometers away. Operational measures of transport performance (i.e. punctuality and delays), while globally being very decreased, had a statistically relevant positive increase (though very geographically heterogeneous) on the Swiss passenger traffic during the disruption period. We identify two factors for this: (1) the reduced delay propagation at an international scale; and (2) to a minor extent, rerouted railway freight traffic; which show to combine linearly in the observed outcomes. url: https://www.ncbi.nlm.nih.gov/pubmed/33122669/ doi: 10.1038/s41598-020-75538-z id: cord-316930-0s7k9guq author: Caldas, Lucio Ayres title: Ultrastructural analysis of SARS-CoV-2 interactions with the host cell via high resolution scanning electron microscopy date: 2020-09-30 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: SARS-CoV-2 is the cause of the ongoing COVID-19 pandemic. Here, we investigated the interaction of this new coronavirus with Vero cells using high resolution scanning electron microscopy. Surface morphology, the interior of infected cells and the distribution of viral particles in both environments were observed 2 and 48 h after infection. We showed areas of viral processing, details of vacuole contents, and viral interactions with the cell surface. Intercellular connections were also approached, and viral particles were adhered to these extensions suggesting direct cell-to-cell transmission of SARS-CoV-2. url: https://www.ncbi.nlm.nih.gov/pubmed/32999356/ doi: 10.1038/s41598-020-73162-5 id: cord-003196-fdb6az0v author: Casalino-Matsuda, S. Marina title: Hypercapnia Alters Expression of Immune Response, Nucleosome Assembly and Lipid Metabolism Genes in Differentiated Human Bronchial Epithelial Cells date: 2018-09-10 words: 4652.0 sentences: 252.0 pages: flesch: 37.0 cache: ./cache/cord-003196-fdb6az0v.txt txt: ./txt/cord-003196-fdb6az0v.txt summary: title: Hypercapnia Alters Expression of Immune Response, Nucleosome Assembly and Lipid Metabolism Genes in Differentiated Human Bronchial Epithelial Cells These changes in gene expression indicate the potential for hypercapnia to impact bronchial epithelial cell function in ways that may contribute to poor clinical outcomes in patients with severe acute or advanced chronic lung diseases. Major clusters from hypercapnia-downregulated genes are linked to immune response, nucleosome assembly, cell differentiation, oxidation reduction, and ion and lipid transport (Fig. 2) . In addition, the suppressive effect of elevated CO 2 on immune gene expression in the airway epithelium, along with similar effects on immune cells, suggest a reason why severe COPD and other lung disease associated with hypercapnia all carry a high risk of pulmonary infection. Thus, CO 2 -induced alterations in airway epithelial gene expression may underlie the increase in mortality associated with hypercapnia in advanced COPD, as well as community-acquired pneumonia 9 , adenoviral lung infections 10 and cystic fibrosis 11 . abstract: Hypercapnia, the elevation of CO(2) in blood and tissues, commonly occurs in severe acute and chronic respiratory diseases, and is associated with increased risk of mortality. Recent studies have shown that hypercapnia adversely affects innate immunity, host defense, lung edema clearance and cell proliferation. Airway epithelial dysfunction is a feature of advanced lung disease, but the effect of hypercapnia on airway epithelium is unknown. Thus, in the current study we examined the effect of normoxic hypercapnia (20% CO(2) for 24 h) vs normocapnia (5% CO(2)), on global gene expression in differentiated normal human airway epithelial cells. Gene expression was assessed on Affymetrix microarrays, and subjected to gene ontology analysis for biological process and cluster-network representation. We found that hypercapnia downregulated the expression of 183 genes and upregulated 126. Among these, major gene clusters linked to immune responses and nucleosome assembly were largely downregulated, while lipid metabolism genes were largely upregulated. The overwhelming majority of these genes were not previously known to be regulated by CO(2). These changes in gene expression indicate the potential for hypercapnia to impact bronchial epithelial cell function in ways that may contribute to poor clinical outcomes in patients with severe acute or advanced chronic lung diseases. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6131151/ doi: 10.1038/s41598-018-32008-x id: cord-002258-o9azey3m author: Chan, Louisa L. Y. title: Evaluation of the human adaptation of influenza A/H7N9 virus in PB2 protein using human and swine respiratory tract explant cultures date: 2016-10-14 words: 5656.0 sentences: 278.0 pages: flesch: 52.0 cache: ./cache/cord-002258-o9azey3m.txt txt: ./txt/cord-002258-o9azey3m.txt summary: In this study, we evaluated the role of amino acid substitution PB2-627K or compensatory changes at PB2-591K and PB2-701N, on the tropism and replication competence of H7N9 viruses for human and swine respiratory tracts using ex vivo organ explant cultures. There were very limited influenza antigen positive cells in the rgPB2-K627E + Q591K and rgPB2-K627E + D701N inoculated ex vivo culture of human bronchus (Fig. 2C ) while more infected cells were shown in these mutant viruses infected lung tissues (Fig. 2D ). In this study, we evaluated the effects of PB2-E627K mutation as well as two mammalian adaptation markers, PB2-Q591K and D701N on H7N9 virus replication competence in ex vivo cultures of human and swine respiratory tracts and in vitro cultures of human primary ATI and PMφ . Tropism and innate host responses of a novel avian influenza A H7N9 virus: an analysis of ex-vivo and in-vitro cultures of the human respiratory tract abstract: Novel avian H7N9 virus emerged in China in 2013 resulting in a case fatality rate of around 39% and continues to pose zoonotic and pandemic risk. Amino acid substitutions in PB2 protein were shown to influence the pathogenicity and transmissibility of H7N9 following experimental infection of ferrets and mice. In this study, we evaluated the role of amino acid substitution PB2-627K or compensatory changes at PB2-591K and PB2-701N, on the tropism and replication competence of H7N9 viruses for human and swine respiratory tracts using ex vivo organ explant cultures. Recombinant viruses of A/Shanghai/2/2013 (rgH7N9) and its mutants with PB2-K627E, PB2-K627E + Q591K and PB2-K627E + D701N were generated by plasmid-based reverse genetics. PB2-E627K was essential for efficient replication of rgH7N9 in ex vivo cultures of human and swine respiratory tracts. Mutant rgPB2-K627E + D701N replicated better than rgPB2-K627E in human lung but not as well as rgH7N9 virus. The rgPB2-K627E mutant failed to replicate in human type I-like pneumocytes (ATI) and peripheral blood monocyte-derived macrophages (PMϕ) at 37 °C while the compensatory mutant rgPB2-K627E + Q591K and rgPB2-K627E + D701N had partly restored replication competence in PMϕ. Our results demonstrate that PB2-E627K was important for efficient replication of influenza H7N9 in both human and swine respiratory tracts. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5064379/ doi: 10.1038/srep35401 id: cord-279598-xzionafe author: Chang, Chia-Yu title: Identification of Neutralizing Monoclonal Antibodies Targeting Novel Conformational Epitopes of the Porcine Epidemic Diarrhoea Virus Spike Protein date: 2019-02-21 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Since 2010, newly identified variants of porcine epidemic diarrhoea virus (PEDV) have caused high mortality in neonatal piglets which has devastated the swine industry. The spike (S) glycoprotein of PEDV contains multiple neutralizing epitopes and is a major target for PEDV neutralization and vaccine development. To understand the antigenicity of the new PEDV variant, we characterized the neutralizing epitopes of a new genotype 2b PEDV isolate from Taiwan, PEDV Pintung 52 (PEDV-PT), by the generation of neutralizing monoclonal antibodies (NmAbs). Two NmAbs, P4B-1, and E10E-1–10 that recognized the ectodomain of the full-length recombinant PEDV S protein and exhibited neutralizing ability against the PEDV-PT virus were selected. Recombinant truncated S proteins were used to identify the target sequences for the NmAbs and P4B-1 was shown to recognize the C-terminus of CO-26K equivalent epitope (COE) at amino acids (a.a.) 575–639 of the PEDV S. Interestingly, E10E-1–10 could recognize a novel neutralizing epitope at a.a. 435–485 within the S1(A) domain of the PEDV S protein, whose importance and function are yet to be determined. Moreover, both NmAbs could not bind to linearized S proteins, indicating that only conformational epitopes are recognized. This data could improve our understanding of the antigenic structures of the PEDV S protein and facilitate future development of novel epitope-based vaccines. url: https://doi.org/10.1038/s41598-019-39844-5 doi: 10.1038/s41598-019-39844-5 id: cord-002956-e5ihpe4i author: Chang, Ya-Chun title: Ventilator Dependence Risk Score for the Prediction of Prolonged Mechanical Ventilation in Patients Who Survive Sepsis/Septic Shock with Respiratory Failure date: 2018-04-04 words: 4666.0 sentences: 272.0 pages: flesch: 46.0 cache: ./cache/cord-002956-e5ihpe4i.txt txt: ./txt/cord-002956-e5ihpe4i.txt summary: title: Ventilator Dependence Risk Score for the Prediction of Prolonged Mechanical Ventilation in Patients Who Survive Sepsis/Septic Shock with Respiratory Failure A total of 379 patients with sepsis or septic shock and acute respiratory failure requiring mechanical ventilation were admitted to the medical intensive care unit in the Kaohsiung Chang Gung Memorial Hospital from August 2013 to October 2015. We also tested and found that SOFA PaO 2 /FiO 2 subscore and GCS subscore on admission day 7 could help predict ventilator dependence on sepsis and septic shock patients with significant difference in univariate analysis ( Table 5 ). Ventilator dependence risk score, including a history of stroke and data from day 7 (thrombocytopenia, acidosis, and the higher fraction of inspired oxygen), can be applied to predict prolonged mechanical ventilation in patients who survive sepsis and septic shock. abstract: We intended to develop a scoring system to predict mechanical ventilator dependence in patients who survive sepsis/septic shock with respiratory failure. This study evaluated 251 adult patients in medical intensive care units (ICUs) between August 2013 to October 2015, who had survived for over 21 days and received aggressive treatment. The risk factors for ventilator dependence were determined. We then constructed a ventilator dependence (VD) risk score using the identified risk factors. The ventilator dependence risk score was calculated as the sum of the following four variables after being adjusted by proportion to the beta coefficient. We assigned a history of previous stroke, a score of one point, platelet count less than 150,000/μL a score of one point, pH value less than 7.35 a score of two points, and the fraction of inspired oxygen on admission day 7 over 39% as two points. The area under the curve in the derivation group was 0.725 (p < 0.001). We then applied the VD risk score for validation on 175 patients. The area under the curve in the validation group was 0.658 (p = 0.001). VD risk score could be applied to predict prolonged mechanical ventilation in patients who survive sepsis/septic shock. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5884833/ doi: 10.1038/s41598-018-24028-4 id: cord-002110-pbb247lp author: Chen, Chin-Pei title: Membrane protein assembly: two cytoplasmic phosphorylated serine sites of Vpu from HIV-1 affect oligomerization date: 2016-06-29 words: 5987.0 sentences: 327.0 pages: flesch: 60.0 cache: ./cache/cord-002110-pbb247lp.txt txt: ./txt/cord-002110-pbb247lp.txt summary: title: Membrane protein assembly: two cytoplasmic phosphorylated serine sites of Vpu from HIV-1 affect oligomerization Coarse-grained molecular dynamic simulations with models of wild-type and mutant Vpu in a hydrated lipid bilayer supported the experimental data in demonstrating that, in addition to a previously known role in downregulation of host factors, the phosphorylation sites of Vpu also modulate oligomerization. Coarse grained molecular dynamics (CGMD) simulations of Vpu proteins embedded in a planar lipid bilayer model were chosen to evaluate the oligomeric assembly under likely in vivo conditions such as an abundance of Vpu proteins in a large lipid patch and simulated over a long time period. The dynamics data was plotted as area of the peak of the higher oligomer (A P1 ), divided by the total area of A P1 and the peak area of the dimer (A P2 ), A P1 /(A P1 + A P2 ), over time for Vpu-WT with a double logarithmic growth curve (Fig. 4b , black and Table 2 ). Three-dimensional structure of the channel-forming trans-membrane domain of virus protein "u" (Vpu) from HIV-1 abstract: Viral protein U (Vpu) encoded by human immunodeficiency virus type 1 (HIV-1) is a short integral membrane protein which is known to self-assemble within the lipid membrane and associate with host factors during the HIV-1 infectivity cycle. In this study, full-length Vpu (M group) from clone NL4-3 was over-expressed in human cells and purified in an oligomeric state. Various single and double mutations were constructed on its phosphorylation sites to mimic different degrees of phosphorylation. Size exclusion chromatography of wild-type Vpu and mutants indicated that the smallest assembly unit of Vpu was a dimer and over time Vpu formed higher oligomers. The rate of oligomerization increased when (i) the degree of phosphorylation at serines 52 and 56 was decreased and (ii) when the ionic strength was increased indicating that the cytoplasmic domain of Vpu affects oligomerization. Coarse-grained molecular dynamic simulations with models of wild-type and mutant Vpu in a hydrated lipid bilayer supported the experimental data in demonstrating that, in addition to a previously known role in downregulation of host factors, the phosphorylation sites of Vpu also modulate oligomerization. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4926278/ doi: 10.1038/srep28866 id: cord-313126-7hrjzapj author: Chen, Fangzhou title: Decline of transmissible gastroenteritis virus and its complex evolutionary relationship with porcine respiratory coronavirus in the United States date: 2019-03-08 words: 4467.0 sentences: 211.0 pages: flesch: 44.0 cache: ./cache/cord-313126-7hrjzapj.txt txt: ./txt/cord-313126-7hrjzapj.txt summary: Nineteen complete TGEV genomes and a single strain of porcine respiratory coronavirus (PRCV) from the US were generated and compared to historical strains to investigate the evolution of these endemic coronaviruses. The "variant" genotype shared similar unique deletions and amino acid changes with the recent PRCV strain identified in this study, suggesting a recombination event occurred between the ''''variant'''' TGEV and PRCV. Complete genomic sequences, a key residue in the spike protein and deletions in nonstructural protein 3b of US strains of the virulent and attenuated coronaviruses, transmissible gastroenteritis virus and porcine respiratory coronavirus abstract: The epidemiology and genetic diversity of transmissible gastroenteritis virus (TGEV) in the United States (US) was investigated by testing clinical cases for TGEV by real time RT-PCR between January 2008 and November 2016. Prevalence of TGEV ranged between 3.8–6.8% and peaked during cold months until March 2013, in which prevalence decreased to < 0.1%. Nineteen complete TGEV genomes and a single strain of porcine respiratory coronavirus (PRCV) from the US were generated and compared to historical strains to investigate the evolution of these endemic coronaviruses. Sixteen of our TGEV strains share 8 unique deletions and 119 distinct amino acid changes, which might greatly affect the biological characteristics of the variant TGEV, and resulted in a “variant” genotype of TGEV. The “variant” genotype shared similar unique deletions and amino acid changes with the recent PRCV strain identified in this study, suggesting a recombination event occurred between the ‘‘variant’’ TGEV and PRCV. Moreover, the results indicate the “variant” genotype is the dominant genotype circulating in the US. Therefore, this study provides insight into the occurrence, origin, genetic characteristics, and evolution of TGEV and PRCV circulating in the US. url: https://www.ncbi.nlm.nih.gov/pubmed/30850666/ doi: 10.1038/s41598-019-40564-z id: cord-002782-mena480g author: Chen, Jiajia title: Long term outcomes in survivors of epidemic Influenza A (H7N9) virus infection date: 2017-12-08 words: 3021.0 sentences: 179.0 pages: flesch: 55.0 cache: ./cache/cord-002782-mena480g.txt txt: ./txt/cord-002782-mena480g.txt summary: Our findings suggest that pulmonary function and imaging findings improved during the first 6 months especially for those with ARDS, however long-term lung disability and psychological impairment in H7N9 survivors persisted at 2 years after discharge from the hospital. In survivors of H5N1 virus infection, radiologic abnormalities including ground-glass opacities with a reticular pattern remained evident at the 12-month follow-up visit 10 . A study of the long-term outcomes of survivors with ARDS reported a mild restrictive pattern on lung-function testing, with a mild-to-moderate reduction in carbon monoxide diffusion capacity at 3 months; The median DLCO improved by 9% of the predicted value from 3 to 12 months 13 . A meta-analysis showed that recovery in the HRQoL of ARDS survivors occurred during the first 6 months after discharge 20 , but no significant improvement was evident at the 2-year follow-up in our study. Follow-up study on pulmonary function and lung radiographic changes in rehabilitating severe acute respiratory syndrome patients after discharge abstract: Patients who survive influenza A (H7N9) virus infection are at risk of physical and psychological complications of lung injury and multi-organ dysfunction. However, there were no prospectively individualized assessments of physiological, functional and quality-of-life measures after hospital discharge. The current study aims to assess the main determinants of functional disability of these patients during the follow-up. Fifty-six influenza A (H7N9) survivors were investigated during the 2-year after discharge from the hospital. Results show interstitial change and fibrosis on pulmonary imaging remained 6 months after hospital discharge. Both ventilation and diffusion dysfunction improved, but restrictive and obstructive patterns on ventilation function test persisted throughout the follow-up period. For patients with acute respiratory distress syndrome lung functions improved faster during the first six months. Role-physical and Role-emotional domains in the 36-Item Short-Form Health Survey were worse than those of a sex- and age-matched general population group. The quality of life of survivors with ARDS was lower than those with no ARDS. Our findings suggest that pulmonary function and imaging findings improved during the first 6 months especially for those with ARDS, however long-term lung disability and psychological impairment in H7N9 survivors persisted at 2 years after discharge from the hospital. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5722861/ doi: 10.1038/s41598-017-17497-6 id: cord-346483-jc0xklzk author: Chen, Jun title: Deep learning-based model for detecting 2019 novel coronavirus pneumonia on high-resolution computed tomography date: 2020-11-05 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Computed tomography (CT) is the preferred imaging method for diagnosing 2019 novel coronavirus (COVID19) pneumonia. We aimed to construct a system based on deep learning for detecting COVID-19 pneumonia on high resolution CT. For model development and validation, 46,096 anonymous images from 106 admitted patients, including 51 patients of laboratory confirmed COVID-19 pneumonia and 55 control patients of other diseases in Renmin Hospital of Wuhan University were retrospectively collected. Twenty-seven prospective consecutive patients in Renmin Hospital of Wuhan University were collected to evaluate the efficiency of radiologists against 2019-CoV pneumonia with that of the model. An external test was conducted in Qianjiang Central Hospital to estimate the system’s robustness. The model achieved a per-patient accuracy of 95.24% and a per-image accuracy of 98.85% in internal retrospective dataset. For 27 internal prospective patients, the system achieved a comparable performance to that of expert radiologist. In external dataset, it achieved an accuracy of 96%. With the assistance of the model, the reading time of radiologists was greatly decreased by 65%. The deep learning model showed a comparable performance with expert radiologist, and greatly improved the efficiency of radiologists in clinical practice. url: https://www.ncbi.nlm.nih.gov/pubmed/33154542/ doi: 10.1038/s41598-020-76282-0 id: cord-002019-wtnf340p author: Chen, Xiaojuan title: Retinoic acid facilitates inactivated transmissible gastroenteritis virus induction of CD8(+) T-cell migration to the porcine gut date: 2016-04-15 words: 7236.0 sentences: 354.0 pages: flesch: 49.0 cache: ./cache/cord-002019-wtnf340p.txt txt: ./txt/cord-002019-wtnf340p.txt summary: We demonstrated that elevated numbers of gut-homing CD8(+) T cells (which express α4β7 and CCR9 molecules) were presented in porcine inguinal lymph nodes and were recruited to the small intestine by RA. Taken together, the cell migration assay results revealed a strong chemotactic response in T cells when activated by RA-activated DCs. These data demonstrated that RA-pretreated BMDCs could activate T cells to express high functional levels of the gut-homing receptor CCR9, as well as to migrate towards the porcine chemokine CCL25. In agreement with the migration of gut-homing CD8 + cells, our observations showed that after RA plus TGEV s.c. treatment, many CD3 + T cells were recruited to the intestinal villi and lamina propria, and these data also showed that RA-assisted antigen s.c. can establish a stronger and faster cellular immune response to defend against foreign pathogens 40 . abstract: The digestive tract is the entry site for transmissible gastroenteritis virus (TGEV). TGEV transmission can be prevented if local immunity is established with increased lymphocytes. The current parenteral mode of vaccination stimulates systemic immunity well, but it does not induce sufficient mucosal immunity. Retinoic acid (RA) plays an important role in the induction of cells that imprint gut-homing molecules. We examined whether RA assist parenteral vaccination of pigs could improve mucosal immunity. We demonstrated that elevated numbers of gut-homing CD8(+) T cells (which express α4β7 and CCR9 molecules) were presented in porcine inguinal lymph nodes and were recruited to the small intestine by RA. Intestinal mucosal immunity (IgA titre) and systemic immunity (serum IgG titre) were enhanced by RA. Therefore, we hypothesized that RA could induce DCs to form an immature mucosal phenotype and could recruit them to the small intestinal submucosa. Porcine T-cells expressed β7 integrin and CCR9 receptors and migrated to CCL25 by a mechanism that was dependent of activation by RA-pretreated DCs, rather than direct activation by RA. Together, our results provide powerful evidence that RA can assist whole inactivated TGEV (WI-TGEV) via subcutaneous (s.c.) immunization to generate intestinal immunity, and offer new vaccination strategies against TGEV. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4832189/ doi: 10.1038/srep24152 id: cord-259378-5g2y68i2 author: Cheng, Chao-Min title: Small-volume point-of-care analytical methods date: 2020-08-27 words: 1556.0 sentences: 71.0 pages: flesch: 38.0 cache: ./cache/cord-259378-5g2y68i2.txt txt: ./txt/cord-259378-5g2y68i2.txt summary: With recent technological advances in multiple research fields-such as materials science, micro-/nano-technology, cellular and molecular biology, and bioengineering-attention is shifting toward the development of new diagnostic tools that not only address needs for high sensitivity and specificity, but that fulfill economic, environmental, and rapid point-of-care (POC) needs, for groups and individuals with constrained resources and, possibly, limited training. This pump accepted commonly available silicone rubber tubing in a range of sizes, from 1.5 to 3 mm, and was capable of producing flow rates up to 1.6 mL/min 6 www.nature.com/scientificreports/ microfluidic technologies may be used for a variety of POC diagnostic applications (e.g., infectious diseases, COVID-19 diagnosis) because they are disposable, inexpensive, portable, and easy to use, especially when they are manufactured using low-cost materials such as paper (and other materials such as cotton or bamboo 7, 8 ). abstract: Detecting clinically relevant diagnostic biomarkers, suitable for point-of-care detection, may facilitate rapid treatment and prevention of disease. However, medical diagnosis for which there are limited quantities of testable tissue or fluid, require point-of-care technologies with superior sensitivity and specificity. The purpose of this Editorial is to provide an overview of the Collection’s content, comprising original research into fluidics-based diagnostic platforms—specifically those made of paper or other low-cost materials, that can suitably operate with tiny sample volumes from mL to nL. In particular, we will focus on the clinical applications of such research, with potential uses in a number of fields including combating the COVID-19 pandemic for instance. url: https://doi.org/10.1038/s41598-020-70903-4 doi: 10.1038/s41598-020-70903-4 id: cord-255511-nk3iyg07 author: Chin, Wei Chien Benny title: Spatial super-spreaders and super-susceptibles in human movement networks date: 2020-10-29 words: 9067.0 sentences: 466.0 pages: flesch: 54.0 cache: ./cache/cord-255511-nk3iyg07.txt txt: ./txt/cord-255511-nk3iyg07.txt summary: Here, we propose a quantitative and systematic framework to identify spatial super-spreaders and the novel concept of super-susceptibles, i.e. respectively, places most likely to contribute to disease spread or to people contracting it. We applied this analysis framework to the Singapore public transport flow network, and identified the SSP and SSS using the SUI and SPI indexes. This study uses a community detection method (MapEquation algorithm 60 ) to identify the zones from the flow network, instead of using the administrative spatial boundaries (i.e. the boundaries of planning areas and regions as defined by the Singapore Government in its Master Plan 2014 59 ) that were designed and selected for governance and political purposes. Figure 7 shows the local out-and in-degree (left column), the outgoing and incoming neighborhood zone-entropy (central column) and coreness-entropy (right column) of the weekday (first two rows) and weekend (bottom two rows) flow networks. abstract: As lockdowns and stay-at-home orders start to be lifted across the globe, governments are struggling to establish effective and practical guidelines to reopen their economies. In dense urban environments with people returning to work and public transportation resuming full capacity, enforcing strict social distancing measures will be extremely challenging, if not practically impossible. Governments are thus paying close attention to particular locations that may become the next cluster of disease spreading. Indeed, certain places, like some people, can be “super-spreaders”. Is a bustling train station in a central business district more or less susceptible and vulnerable as compared to teeming bus interchanges in the suburbs? Here, we propose a quantitative and systematic framework to identify spatial super-spreaders and the novel concept of super-susceptibles, i.e. respectively, places most likely to contribute to disease spread or to people contracting it. Our proposed data-analytic framework is based on the daily-aggregated ridership data of public transport in Singapore. By constructing the directed and weighted human movement networks and integrating human flow intensity with two neighborhood diversity metrics, we are able to pinpoint super-spreader and super-susceptible locations. Our results reveal that most super-spreaders are also super-susceptibles and that counterintuitively, busy peripheral bus interchanges are riskier places than crowded central train stations. Our analysis is based on data from Singapore, but can be readily adapted and extended for any other major urban center. It therefore serves as a useful framework for devising targeted and cost-effective preventive measures for urban planning and epidemiological preparedness. url: https://doi.org/10.1038/s41598-020-75697-z doi: 10.1038/s41598-020-75697-z id: cord-336901-q6kgzuob author: Choi, Jeongan title: Integrated micro-optofluidic platform for real-time detection of airborne microorganisms date: 2015-11-02 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: We demonstrate an integrated micro-optofluidic platform for real-time, continuous detection and quantification of airborne microorganisms. Measurements of the fluorescence and light scattering from single particles in a microfluidic channel are used to determine the total particle number concentration and the microorganism number concentration in real-time. The system performance is examined by evaluating standard particle measurements with various sample flow rates and the ratios of fluorescent to non-fluorescent particles. To apply this method to real-time detection of airborne microorganisms, airborne Escherichia coli, Bacillus subtilis, and Staphylococcus epidermidis cells were introduced into the micro-optofluidic platform via bioaerosol generation, and a liquid-type particle collection setup was used. We demonstrate successful discrimination of SYTO82-dyed fluorescent bacterial cells from other residue particles in a continuous and real-time manner. In comparison with traditional microscopy cell counting and colony culture methods, this micro-optofluidic platform is not only more accurate in terms of the detection efficiency for airborne microorganisms but it also provides additional information on the total particle number concentration. url: https://www.ncbi.nlm.nih.gov/pubmed/26522006/ doi: 10.1038/srep15983 id: cord-324696-htx0ul4o author: Chothe, Shubhada K. title: Avian and human influenza virus compatible sialic acid receptors in little brown bats date: 2017-04-06 words: 3853.0 sentences: 212.0 pages: flesch: 50.0 cache: ./cache/cord-324696-htx0ul4o.txt txt: ./txt/cord-324696-htx0ul4o.txt summary: This first ever study of IAV receptors in a bat species suggest that LBBs, a widely-distributed bat species in North America, could potentially be co-infected with avian and human IAVs, facilitating the emergence of zoonotic strains. To resolve this enigma, we investigated for the first time the distribution of SA receptors in little brown bats (LBBs) (Myotis lucifugus), a widely-distributed bat species in North America and their compatibility to support avian and human IAV binding. H5N2 virus binding pattern was in accordance with the relative abundance of SA α2,3-Gal receptors in tissues such that greater virus binding to the tracheal ( In addition to the virus binding assay using antibody-based detection, we also visualized virus binding using scanning electron microscopy (SEM) which also confirmed abundant binding of avian H5N2 virus (Fig. 5A ) and human H1N1 virus (Fig. 5B ) to LBB trachea (Fig. 5) . time, this study demonstrated that little brown bats (LBBs), a widely-distributed bat species in North America, co-express both avian and human type influenza receptors in their respiratory and gastrointestinal systems. abstract: Influenza A viruses (IAVs) continue to threaten animal and human health globally. Bats are asymptomatic reservoirs for many zoonotic viruses. Recent reports of two novel IAVs in fruit bats and serological evidence of avian influenza virus (AIV) H9 infection in frugivorous bats raise questions about the role of bats in IAV epidemiology. IAVs bind to sialic acid (SA) receptors on host cells, and it is widely believed that hosts expressing both SA α2,3-Gal and SA α2,6-Gal receptors could facilitate genetic reassortment of avian and human IAVs. We found abundant co-expression of both avian (SA α2,3-Gal) and human (SA α2,6-Gal) type SA receptors in little brown bats (LBBs) that were compatible with avian and human IAV binding. This first ever study of IAV receptors in a bat species suggest that LBBs, a widely-distributed bat species in North America, could potentially be co-infected with avian and human IAVs, facilitating the emergence of zoonotic strains. url: https://doi.org/10.1038/s41598-017-00793-6 doi: 10.1038/s41598-017-00793-6 id: cord-294220-ewp1m8jp author: Churchward, Colin P. title: Monocaprin eye drop formulation to combat antibiotic resistant gonococcal blindness date: 2020-07-21 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Neisseria gonorrhoeae bacteria are acknowledged as an urgent threat to human health because this species has developed resistances to all of the antibiotics used clinically to treat its infections. N. gonorrhoeae causes the sexually transmitted disease gonorrhoea, but also causes blindness when the bacteria infect the eyes. Infants are particularly susceptible, acquiring the infection from their mothers at birth. We have shown that the monoglyceride monocaprin rapidly kills N. gonorrhoeae and other bacterial species and is non-irritating in ocular assays. Here we show that the physical and chemical properties of monocaprin make it ideal for use in a thickened eye drop formulation to combat eye infections. Monocaprin-containing formulations were assessed using analytical techniques and for antimicrobial activity in vitro and in ex vivo infections. Monocaprin-containing formulations retained activity after three years and are non-irritating, unlike preparations of povidone iodine in our assays. A recommended formulation for further development and investigation is 0.25% monocaprin in 1% HPMC with 1% polysorbate 20. url: https://doi.org/10.1038/s41598-020-68722-8 doi: 10.1038/s41598-020-68722-8 id: cord-010328-uxpedpz8 author: Ciencewicki, Jonathan M. title: Plasma Donors in the Southwestern United States Positively Contribute to the Diverse Therapeutic Antibody Profile of Immune Globulin Products date: 2020-04-22 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Human-plasma-derived immune globulin (IG) is used in augmentation therapy to provide protective levels of antibodies to patients with primary immune deficiency diseases (PIDD) and for prophylaxis against infectious diseases. To maintain the breadth of antibodies necessary for clinical protection, it is important to understand regional patterns of antibody seroprevalence in source plasma from which IG products are manufactured. In this study, source plasma from donation centers in various locations of the Southwestern quarter of the United States was surveyed for antibody titers to hepatitis A virus (HAV), measles virus (MeV), and cytomegalovirus (CMV). A broad range of anti-HAV Ig plasma titers was observed among these centers, with some centers exhibiting 3–5 times the titers of the others. Minor to no differences were observed for levels of anti-MeV and anti-CMV, respectively. Importantly, elevated anti-HAV Ig titers were broadly observed across plasma units obtained from the centers exhibiting high titers, indicative of a potential regional phenomenon among donors as opposed to few donors with singularly high titers. Plasma from these high-titer centers conferred significantly greater neutralization against HAV in vitro. The outcomes of this study give a glimpse of the antibody diversity inherent in human plasma used to manufacture IG products.. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7176631/ doi: 10.1038/s41598-020-63794-y id: cord-254653-4ffuivil author: Cinelli, Matteo title: The COVID-19 social media infodemic date: 2020-10-06 words: 5100.0 sentences: 289.0 pages: flesch: 50.0 cache: ./cache/cord-254653-4ffuivil.txt txt: ./txt/cord-254653-4ffuivil.txt summary: We address the diffusion of information about the COVID-19 with a massive data analysis on Twitter, Instagram, YouTube, Reddit and Gab. We analyze engagement and interest in the COVID-19 topic and provide a differential assessment on the evolution of the discourse on a global scale for each platform and their users. We fit information spreading with epidemic models characterizing the basic reproduction number [Formula: see text] for each social media platform. Unlike previous works, we do not only focus on models that imply specific growth mechanisms, but also on phenomenological models that emphasize the reproducibility of empirical data 41 www.nature.com/scientificreports/ Most of the epidemiological models focus on the basic reproduction number R 0 , representing the expected number of new infectors directly generated by an infected individual for a given time period 42 . Furthermore, we model the spread of information using epidemic models and provide basic growth parameters for each social media platform. abstract: We address the diffusion of information about the COVID-19 with a massive data analysis on Twitter, Instagram, YouTube, Reddit and Gab. We analyze engagement and interest in the COVID-19 topic and provide a differential assessment on the evolution of the discourse on a global scale for each platform and their users. We fit information spreading with epidemic models characterizing the basic reproduction number [Formula: see text] for each social media platform. Moreover, we identify information spreading from questionable sources, finding different volumes of misinformation in each platform. However, information from both reliable and questionable sources do not present different spreading patterns. Finally, we provide platform-dependent numerical estimates of rumors’ amplification. url: https://www.ncbi.nlm.nih.gov/pubmed/33024152/ doi: 10.1038/s41598-020-73510-5 id: cord-286413-a7wue2e3 author: Cohen, Isaac V. title: Cardiac adverse events associated with chloroquine and hydroxychloroquine exposure in 20 years of drug safety surveillance reports date: 2020-11-05 words: 3609.0 sentences: 205.0 pages: flesch: 48.0 cache: ./cache/cord-286413-a7wue2e3.txt txt: ./txt/cord-286413-a7wue2e3.txt summary: title: Cardiac adverse events associated with chloroquine and hydroxychloroquine exposure in 20 years of drug safety surveillance reports The cardiac AEs of these therapeutics are of increased concern since a subset of patients infected with COVID-19 present with cardiac injury, suggesting a relevant cardiovascular involvement in the pathophysiology of the disease 22 . The goal of this study is to reanalyze the extensive clinical data of CQ and HCQ cardiac AEs collected during the last 20 years to derive the strength of the associations and, more importantly, contributing risk factors. In our study we analyzed 702,274 FDA adverse event reports divided into CQ, HCQ and control cohorts to determine their association with cardiac AEs when taking into account other factors. The regression model was instrumental to exclude this aspirin association from the quantification of the direct cardiac side effects of CQ and HCQ, which remained significant after adjustment ( Generalizability of results to COVID-19 treatment with CQ and HCQ. abstract: Chloroquine (CQ) and hydroxychloroquine (HCQ) are on the World Health Organization’s List of Essential Medications for treating non-resistant malaria, rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). In addition, both drugs are currently used off-label in hospitals worldwide and in numerous clinical trials for the treatment of SARS-CoV-2 infection. However, CQ and HCQ use has been associated with cardiac side effects, which is of concern due to the higher risk of COVID-19 complications in patients with heart related disorders, and increased mortality associated with COVID-19 cardiac complications. In this study we analyzed over thirteen million adverse event reports form the United States Food and Drug Administration Adverse Event Reporting System to confirm and quantify the association of cardiac side effects of CQ and HCQ. Additionally, we identified several confounding factors, including male sex, NSAID coadministration, advanced age, and prior diagnoses contributing to drug related cardiotoxicity. These findings may help guide therapeutic decision making and ethical trial design for COVID-19 treatment. url: https://doi.org/10.1038/s41598-020-76258-0 doi: 10.1038/s41598-020-76258-0 id: cord-004280-c470nlie author: Coleman, Kristen K. title: Airborne Influenza A Virus Exposure in an Elementary School date: 2020-02-05 words: 4118.0 sentences: 212.0 pages: flesch: 46.0 cache: ./cache/cord-004280-c470nlie.txt txt: ./txt/cord-004280-c470nlie.txt summary: In this study, we evaluated the use of a bioaerosol sampling method to noninvasively detect and quantify airborne influenza A virus (IAV) densities in a public elementary school. Significantly different (p = 0.049) airborne IAV densities were detected between all three indoor locations (i.e., gymnasium, classroom, and corridor) and all positive samples were collected during the last two weeks of 66 , and a 20-30% relative humidity level; Descriptive of an average elementary school student in the USA weighing ~23-32 kg with an assumed tidal volume (V T ) of 7 mL per kg of body mass. Given the high airborne IAV densities detected in the school corridor, along with elevated student contact rates, it is plausible to conclude that the school corridor is a "hotspot" for influenza virus transmission. abstract: Influenza contributes significantly to childhood morbidity and mortality. Given the magnitude of the school-aged child population, a sizeable proportion of influenza virus transmission events are expected to occur within school settings. However, influenza virus activity in schools is not well-understood, likely due to our limited ability to accurately monitor for respiratory viruses without disrupting the school environment. In this study, we evaluated the use of a bioaerosol sampling method to noninvasively detect and quantify airborne influenza A virus (IAV) densities in a public elementary school. Air samples were collected from multiple locations in the school, two days per week, throughout an eight-week sampling period during influenza season. Real-time RT-PCR targeting the IAV M gene revealed detectable IAV on five occasions in densities ranging from 2.0 × 10(−1) to 1.9 × 10(4). No significant differences in IAV densities were related to student presence/absence. The majority of IAV-associated particles were ≤4 μm in diameter, and theoretical calculations indicate infectious thresholds after minutes of exposure. Our study represents the first identification and quantification of airborne influenza virus in an elementary school, and the results suggest that airborne IAV has the potential to circulate in schools during influenza season, in large enough doses known to cause infection. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7002614/ doi: 10.1038/s41598-020-58588-1 id: cord-339973-kj56zi59 author: Coleman, Kristen K. title: Bioaerosol Sampling for Respiratory Viruses in Singapore’s Mass Rapid Transit Network date: 2018-11-30 words: 4775.0 sentences: 228.0 pages: flesch: 46.0 cache: ./cache/cord-339973-kj56zi59.txt txt: ./txt/cord-339973-kj56zi59.txt summary: Although baseline metagenomic maps created from these studies are said to be useful for mitigating bioterrorism and infectious disease outbreaks, most of them focus largely on mapping surface-borne bacterial DNA 17 and neglect to address the threat of weaponized or global catastrophic biological risk-level (GCBR-level) agents, both of which would likely be aerosolized or respiratory-borne RNA viruses 19 . Bioaerosol sampling in the field provides a noninvasive way to monitor and characterize the community of aerosolized respiratory viruses that regularly infect the public, as well as potentially detect or discover novel pathogens with pandemic potential, such as the influenza A(H7N9) virus. Although the air pump flow rate and sample collection times used in our study have been demonstrated to efficiently capture aerosolized influenza virus and RSV RNA [33] [34] [35] , it is possible that these parameters are not optimal for capturing the other respiratory virus DNA/RNA targeted in our study. abstract: As a leading global city with a high population density, Singapore is at risk for the introduction of novel biological threats. This risk has been recently reinforced by human epidemics in Singapore of SARS coronavirus, 2009 pandemic H1N1 influenza A virus, and enterovirus 71. Other major threats to Singapore include MERS-coronavirus and various avian and swine influenza viruses. The ability to quickly identify and robustly track such threats to initiate an early emergency response remains a significant challenge. In an effort to enhance respiratory virus surveillance in Singapore, our team conducted a pilot study employing a noninvasive bioaerosol sampling method to detect respiratory viruses in Singapore’s Mass Rapid Transit (MRT) network. Over a period of 52 weeks, 89 aerosol samples were collected during peak MRT ridership hours. Nine (10%) tested positive for adenovirus, four (4.5%) tested positive for respiratory syncytial virus type A, and one (1%) tested positive for influenza A virus using real-time RT-PCR/PCR. To our knowledge, this is the first time molecular evidence for any infectious respiratory agent has been collected from Singapore’s MRT. Our pilot study data support the possibility of employing bioaerosol samplers in crowded public spaces to noninvasively monitor for respiratory viruses circulating in communities. url: https://doi.org/10.1038/s41598-018-35896-1 doi: 10.1038/s41598-018-35896-1 id: cord-003504-wjab4y0g author: Copland, Alastair title: Bacillus Calmette-Guérin Induces PD-L1 Expression on Antigen-Presenting Cells via Autocrine and Paracrine Interleukin-STAT3 Circuits date: 2019-03-06 words: 4856.0 sentences: 238.0 pages: flesch: 47.0 cache: ./cache/cord-003504-wjab4y0g.txt txt: ./txt/cord-003504-wjab4y0g.txt summary: Finally, an in vivo immunisation model showed that BCG vaccination under PD-L1 blockade could enhance antigen-specific memory CD4 T-cell responses. Here, we show for the first time that BCG can induce the up-regulation of PD-L1 on both macrophages and dendritic cells (DCs) via autocrine/paracrine secretion of STAT3-activating cytokines, chiefly IL-6 and IL-10. Upon infection with BCG, both APC types expressed high levels of PD-L1 compared to the unstimulated control at 24 h and 48 h (p < 0.0001), and a dose trend was observed for increasing MOI in macrophages at 48 h. To confirm that STAT3 was mediating the up-regulation of PD-L1 expression by BCG, cells were then pre-treated with Stattic or a vehicle control for 2 hours before infection with a low dose of bacteria (Fig. 5C) . BCG vaccine mediated reduction in the MHC-II expression of macrophages and dendritic cells is reversed by activation of Toll-like receptors 7 and 9 abstract: Bacillus Calmette-Guérin (BCG) is the only licensed vaccine for tuberculosis (TB), and is also used as an immunotherapy for bladder cancer and other malignancies due to its immunostimulatory properties. Mycobacteria spp., however, are well known for their numerous immune evasion mechanisms that limit the true potential of their therapeutic use. One such major mechanism is the induction of programmed death ligand-1 (PD-L1), which mitigates adaptive immune responses. Here, we sought to unravel the molecular pathways behind PD-L1 up-regulation on antigen-presenting cells (APCs) by BCG. We found that infection of APCs with BCG induced PD-L1 up-regulation, but that this did not depend on direct infection, suggesting a soluble mediator for this effect. BCG induced potent quantities of IL-6 and IL-10, and the downstream transcription factor STAT3 was hyper-phosphorylated. Intracellular analyses revealed that levels of PD-L1 molecules were associated with the STAT3 phosphorylation state, suggesting a causal link. Neutralisation of the IL-6 or IL-10 cytokine receptors dampened STAT3 phosphorylation and BCG-mediated up-regulation of PD-L1 on APCs. Pharmacological inhibition of STAT3 achieved the same effect, confirming an autocrine-paracrine cytokine loop as a mechanism for BCG-mediated up-regulation of PD-L1. Finally, an in vivo immunisation model showed that BCG vaccination under PD-L1 blockade could enhance antigen-specific memory CD4 T-cell responses. These novel findings could lead to refinement of BCG as both a vaccine for infectious disease and as a cancer immunotherapy. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6403281/ doi: 10.1038/s41598-019-40145-0 id: cord-333067-3zan82yf author: Counoupas, Claudio title: Delta inulin-based adjuvants promote the generation of polyfunctional CD4(+) T cell responses and protection against Mycobacterium tuberculosis infection date: 2017-08-17 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: There is an urgent need for the rational design of safe and effective vaccines to protect against chronic bacterial pathogens such as Mycobacterium tuberculosis. Advax™ is a novel adjuvant based on delta inulin microparticles that enhances immunity with a minimal inflammatory profile and has entered human trials to protect against viral pathogens. In this report we determined if Advax displays broad applicability against important human pathogens by assessing protective immunity against infection with M. tuberculosis. The fusion protein CysVac2, comprising the M. tuberculosis antigens Ag85B (Rv1886c) and CysD (Rv1285) formulated with Advax provided significant protection in the lungs of M. tuberculosis-infected mice. Protection was associated with the generation of CysVac2-specific multifunctional CD4(+) T cells (IFN-γ(+)TNF(+)IL-2(+)). Addition to Advax of the TLR9 agonist, CpG oligonucleotide (Advax(CpG)), improved both the immunogenicity and protective efficacy of CysVac2. Immunisation with CysVac2/Advax(CpG) resulted in heightened release of the chemoattractants, CXCL1, CCL3, and TNF, and rapid influx of monocytes and neutrophils to the site of vaccination, with pronounced early priming of CysVac2-specific CD4(+) T cells. As delta inulin adjuvants have shown an excellent safety and tolerability profile in humans, CysVac2/Advax(CpG) is a strong candidate for further preclinical evaluation for progression to human trials. url: https://www.ncbi.nlm.nih.gov/pubmed/28819247/ doi: 10.1038/s41598-017-09119-y id: cord-004419-81w7apdk author: Course, Christopher title: Management of Respiratory Distress Syndrome in Preterm Infants In Wales: A Full Audit Cycle of a Quality Improvement Project date: 2020-02-26 words: 2600.0 sentences: 132.0 pages: flesch: 47.0 cache: ./cache/cord-004419-81w7apdk.txt txt: ./txt/cord-004419-81w7apdk.txt summary: Little variation was seen between level two and three units, although gestational age was a significant independent variable for several practices, including delayed cord clamping, stabilisation with intubation, early enteral feeding and caffeine administration. Prospective, anonymised audits of the management of RDS in all preterm infants born at <34 weeks gestational age and cared for in a participating neonatal unit in Wales were undertaken. This represented the best-practice document for the management of RDS in infants born at <34 weeks gestational age, concentrating on areas which were supported by Grade A evidence (http://www.gradeworkinggroup.org/). The audit proforma was based upon the recommendations in the European Consensus Guideline on the Management of RDS in Preterm Infants 2013, and concentrated on management areas which were supported by Grade A evidence 9 . The 2013 edition of the European consensus guideline recommended a change in practice towards stabilising preterm infants on non-invasive respiratory support at delivery rather than elective intubation 9 . abstract: Respiratory Distress Syndrome (RDS) is the commonest diagnosis after premature birth. We aimed to audit clinical practices before and after introduction of a national guideline in Wales on RDS management. Anonymised, prospective data on all infants born at <34 weeks of gestation and cared for at one of the participating neonatal units in Wales were collected in two six-month time periods in 2015 and 2018. A national guideline was introduced in 2016 by the Wales Neonatal Network. Data collection included areas of antenatal management, delivery room stabilisation, invasive and non-invasive respiratory support, surfactant treatment and elements of supportive care. Univariate and multivariate methods were used to compare data between the two epochs. Comparing care before and after introduction of the national guideline, areas of significant improvement include use of targeted tidal volume ventilation, use of caffeine therapy, oxygen therapy post-surfactant and increasing early use of parenteral nutrition. Areas of poorer management included levels of positive end expiratory pressures and timing of introduction of enteral feeds. Little variation was seen between level two and three units, although gestational age was a significant independent variable for several practices, including delayed cord clamping, stabilisation with intubation, early enteral feeding and caffeine administration. A national guideline for management of RDS in Wales has significantly improved practice in several areas. However, despite a large volume of high-quality evidence and robust guidance, there remains a significant variation in some elements of best practice for RDS management. Further work should focus on education and training, especially for elements requiring cross-departmental work. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7044423/ doi: 10.1038/s41598-020-60091-6 id: cord-030295-jlhht2l9 author: Cruz-Flores, Roberto title: Genome reconstruction of white spot syndrome virus (WSSV) from archival Davidson’s-fixed paraffin embedded shrimp (Penaeus vannamei) tissue date: 2020-08-10 words: 4004.0 sentences: 209.0 pages: flesch: 49.0 cache: ./cache/cord-030295-jlhht2l9.txt txt: ./txt/cord-030295-jlhht2l9.txt summary: title: Genome reconstruction of white spot syndrome virus (WSSV) from archival Davidson''s-fixed paraffin embedded shrimp (Penaeus vannamei) tissue In this study, the complete genome of white spot syndrome virus (WSSV) was reconstructed from ~ 2-year-old archived Davidson''s-fixed paraffin-embedded (DFPE) shrimp tissue using Next Generation Sequencing (NGS). Archived Davidson''s-fixed paraffin-embedded (DFPE) tissues in the Aquaculture Pathology Laboratory of The University of Arizona are an untapped invaluable resource for pathogen discovery, metagenomic and evolutionary studies to understand the origin, evolution and spread of shrimp pathogens worldwide. Our results confirm that NGS from DNA extracted from DFPE tissue is also a viable approach to detect know viral sequences. The ability to reconstruct DNA viral genomes as large as 300 kbp size from DFPE tissues shows the feasibility to generate baseline genetic data from archived tissue and determine how pathogens have evolved over time. abstract: Formalin-fixed paraffin-embedded (FFPE) tissues are a priceless resource for diagnostic laboratories worldwide. However, DNA extracted from these tissues is often not optimal for most downstream molecular analysis due to fragmentation and chemical modification. In this study, the complete genome of white spot syndrome virus (WSSV) was reconstructed from ~ 2-year-old archived Davidson’s-fixed paraffin-embedded (DFPE) shrimp tissue using Next Generation Sequencing (NGS). A histological analysis was performed on archived DFPE shrimp tissue and a sample showing a high level of WSSV infection was selected for molecular analysis. The viral infection was further confirmed by molecular methods. DNA isolated from DFPE and fresh frozen (FF) tissues were sequenced by NGS. The complete genome reconstruction of WSSV (~ 305 kbp) was achieved from both DFPE and FF tissue. Single nucleotide polymorphisms, insertion and deletions were compared between the genomes. Thirty-eight mutations were identified in the WSSV genomes from the DFPE and FF that differed from the reference genome. This is the first study that has successfully sequenced the complete genome of a virus of over 300 kbp from archival DFPE tissue. These findings demonstrate that DFPE shrimp tissue represents an invaluable resource for prospective and retrospective studies, evolutionary studies and opens avenues for pathogen discovery. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7417530/ doi: 10.1038/s41598-020-70435-x id: cord-342289-zpstb7h9 author: Cui, Tingting title: Establishment of porcine enterocyte/myofibroblast co-cultures for the growth of porcine rota- and coronaviruses date: 2018-10-12 words: 8364.0 sentences: 435.0 pages: flesch: 49.0 cache: ./cache/cord-342289-zpstb7h9.txt txt: ./txt/cord-342289-zpstb7h9.txt summary: As subepithelial myofibroblasts secrete extracellular matrix and growth factors contributing to the attachment, proliferation and differentiation of epithelial cells, co-cultures of primary porcine enterocytes (ileocytes and colonocytes) with myofibroblasts were developed and evaluated for their susceptibility to enteric viruses. The differentiation status of porcine intestinal epithelial cells of 3 days old piglets and the co-cultured enterocytes were analyzed by scanning electron microscopy. To determine the percentage of rotavirus infected cells in primary porcine enterocytes, cells were fixed at different time points (0, 3, 6, 9, 12, 24 h) post inoculation with a low-passage archival RVA strain. Therefore, the susceptibility of primary porcine enterocytes co-cultured with myofibroblasts to four different genotypes of rotavirus A contained in fecal suspensions was tested by RT-qPCR (Fig. 7) . Although rotavirus was reported to have an exclusive tropism for small intestinal enterocytes 41 , rotavirus RVA/Pig-tc/BEL/RV277/1977/G1P [7] strain could infect both primary ileum and colon epithelial cells with a trypsin treatment. abstract: A stable culture of primary porcine enterocytes is necessary to study porcine enteric virus replication characteristics. Because the direct cultivation of primary porcine enterocytes is difficult, alternatives have to be considered. As subepithelial myofibroblasts secrete extracellular matrix and growth factors contributing to the attachment, proliferation and differentiation of epithelial cells, co-cultures of primary porcine enterocytes (ileocytes and colonocytes) with myofibroblasts were developed and evaluated for their susceptibility to enteric viruses. First, it was demonstrated that the co-cultured ileocytes and colonocytes were susceptible to an archival rotavirus strain RVA/pig-tc/BEL/RV277/1977/G1P[7] and different other rotavirus genotypes (fecal samples containing G5P[7], G5P[13], G9P[23], G4P[6]). Next, the TGEV Purdue strain infected both ileocytes and colonocytes whereas the Miller strain only infected ileocytes. Last, the PEDV CV777 Vero adapted and non-adapted (fecal suspension) strains could infect co-cultured ileocytes but not colonocytes. The infectivity of the CV777 Vero adapted strain was higher when the cells were cultured without fetal bovine serum and the CV777 fecal suspension only infected the ileocytes cultured without fetal bovine serum. In conclusion, a novel co-culture of porcine enterocytes with myofibroblasts was established, which can be used for the investigation of the replication of enteric viruses. url: https://www.ncbi.nlm.nih.gov/pubmed/30315177/ doi: 10.1038/s41598-018-33305-1 id: cord-003558-7lvqpz21 author: Davies, Patrick title: Clinical Scenarios of the Application of Electrical Impedance Tomography in Paediatric Intensive Care date: 2019-03-29 words: 4016.0 sentences: 240.0 pages: flesch: 44.0 cache: ./cache/cord-003558-7lvqpz21.txt txt: ./txt/cord-003558-7lvqpz21.txt summary: We present the clinical use of EIT in six conditions: Asthma, Ventilation weaning and expansion recoil, Sequential Lobar Collapse, Targeted Physiotherapy, Pleural Effusion assessment, and PEEP optimisation. Electrical Impedance Tomography (EIT) is a radiation-free functional modality that enables bedside imaging and monitoring of lung function and expansion. It has been used in various clinical settings including acute respiratory distress syndrome (ARDS), establishing the best positive end expiratory pressure (PEEP) [8] [9] [10] [11] [12] , the response of the lungs to recruitment manoeuvres [12] [13] [14] [15] [16] and trying to minimize areas of collapse and hyperinflation 6, 17 . Clinical interest in this method has been driven by the need for bedside monitoring of the dynamics of the lungs and the effects of ventilatory manoeuvres, including changes in ventilator settings, suctioning, chest drains, positioning and physiotherapy. Clinical interest in this method has been driven by the need for bedside monitoring of the dynamics of the lungs and the effects of ventilatory manoeuvres, including changes in ventilator settings, suctioning, chest drains, positioning and physiotherapy. abstract: EIT is a radiation-free functional modality that enables bedside imaging and monitoring of lung function and expansion. Clinical interest in this method has been driven by the need for bedside monitoring of the dynamics of the lungs and the effects of ventilatory manoeuvres, including changes in ventilator settings, suctioning, chest drains, positioning and physiotherapy. We aimed to describe the use of Electrical Impedance Tomography (EIT) as a clinical tool in a tertiary Paediatric Intensive Care unit. Children requiring intensive care with a variety of clinical conditions had an electrode belt with 16 electrodes wrapped around the chest, which sequentially applied a small alternating current from each electrode pair. The signal gives information on both real time, regional, global, and relative data. With the correct application, and understanding of the monitor, much clinical information can be gained, with potentially significant patient benefit. We present the clinical use of EIT in six conditions: Asthma, Ventilation weaning and expansion recoil, Sequential Lobar Collapse, Targeted Physiotherapy, Pleural Effusion assessment, and PEEP optimisation. Screenshots and analyses are offered displaying the pragmatic use of this technology. Electrical Impedance Tomography is a clinically useful tool on the Paediatric Intensive Care unit. It allows monitoring of a patient’s respiratory function in ways which are not possible through any other means. An understanding of respiratory physiology will allow use of this information to improve patient outcomes. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6441075/ doi: 10.1038/s41598-019-41774-1 id: cord-004069-nuep8nim author: DeWald, Lisa Evans title: In Vivo Activity of Amodiaquine against Ebola Virus Infection date: 2019-12-27 words: 5707.0 sentences: 288.0 pages: flesch: 53.0 cache: ./cache/cord-004069-nuep8nim.txt txt: ./txt/cord-004069-nuep8nim.txt summary: A pharmacokinetic (PK) study in rhesus macaques (2 groups of 2 males and 2 females) was performed to monitor plasma concentrations of AQ (Fig. 1a ) and the active metabolite DEAQ (Fig. 1b) . samples from infected animals collected on days 0, 3, 5, and 7 postexposure and on day of necropsy (days 6, 7 or 8) were analyzed for determination of plasma levels of AQ and its metabolite DEAQ. Animals that were treated on days 0, 1 and 2 (Group 2, Fig. 7a ), had plasma DEAQ levels ranging from 0 to 205 ng/ml on days 3, 5, 7 and 8 postexposure. www.nature.com/scientificreports www.nature.com/scientificreports/ The goal of the study was to treat animals with AQ using a similar dosing strategy as for human patients, with a target blood concentration range of the parent compound AQ of 29.2 ± 10.9 ng/mL 12 . abstract: During the Ebola virus disease (EVD) epidemic in Western Africa (2013‒2016), antimalarial treatment was administered to EVD patients due to the high coexisting malaria burden in accordance with World Health Organization guidelines. In an Ebola treatment center in Liberia, EVD patients receiving the combination antimalarial artesunate-amodiaquine had a lower risk of death compared to those treated with artemether-lumefantrine. As artemether and artesunate are derivatives of artemisinin, the beneficial anti-Ebola virus (EBOV) effect observed could possibly be attributed to the change from lumefantrine to amodiaquine. Amodiaquine is a widely used antimalarial in the countries that experience outbreaks of EVD and, therefore, holds promise as an approved drug that could be repurposed for treating EBOV infections. We investigated the potential anti-EBOV effect of amodiaquine in a well-characterized nonhuman primate model of EVD. Using a similar 3-day antimalarial dosing strategy as for human patients, plasma concentrations of amodiaquine in healthy animals were similar to those found in humans. However, the treatment regimen did not result in a survival benefit or decrease of disease signs in EBOV-infected animals. While amodiaquine on its own failed to demonstrate efficacy, we cannot exclude potential therapeutic value of amodiaquine when used in combination with artesunate or another antiviral. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6934550/ doi: 10.1038/s41598-019-56481-0 id: cord-263088-zj14ro5j author: DiPaola, Joshua D. title: Investigating the use of sensory information to detect and track prey by the Sunda pangolin (Manis javanica) with conservation in mind date: 2020-06-17 words: 7515.0 sentences: 326.0 pages: flesch: 52.0 cache: ./cache/cord-263088-zj14ro5j.txt txt: ./txt/cord-263088-zj14ro5j.txt summary: All trials across the ''olfactory'' , ''visual'' , and ''acoustic'' conditions of phase I were pseudo-randomised within a session so that each session consisted of an equal number of trials of left and right correct choices (based on the side of the chamber in which a container was placed), no one side was baited with food more than three consecutive times in a row, and the first three trials for each session across all conditions were always tests rather than controls to avoid a frustration effect. Phase I control containers (i.e., opaque with solid lids) were used as the stimulus containers in the test trials for this condition as we wanted the subject to make olfactory decisions based on the trail scent without being influenced by the odor of the food inside the container. abstract: Pangolins are of conservation concern as one of the most heavily poached, yet least understood mammals. The Sunda pangolin (Manis javanica) in particular is a critically endangered species. Here, we investigate the behaviour of these pangolins, for the first time, using a battery of cognitive tasks based on a manipulation of available sensory information. In an object-choice task in which only one of two containers was baited with food, the pangolins were able to find the food with olfactory information alone (N = 2), but not with visual or acoustic information alone (N = 1). The single subject tested on all three domains was further tested on how he used smell to find food by providing him with an opportunity to find it from a controlled distance or by using scent trails as a guide. The results suggest that our subject may have the capacity to exploit scent trails left by prey which can be tracked to a final source, though we found no evidence to suggest that he had the ability to initiate hunts based on distant prey odors. Despite the small sample size, this is the first controlled experiment to investigate pangolin foraging behaviour and cognition, which may have implications for the future protection of pangolin habitat based on the location of prey species. url: https://doi.org/10.1038/s41598-020-65898-x doi: 10.1038/s41598-020-65898-x id: cord-286559-y8z0pwgn author: Ding, Nai-Zheng title: A permanent host shift of rabies virus from Chiroptera to Carnivora associated with recombination date: 2017-03-21 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Bat virus host shifts can result in the spread of diseases with significant effects. The rabies virus (RABV) is able to infect almost all mammals and is therefore a useful model for the study of host shift mechanisms. Carnivore RABVs originated from two historical host shifts from bat viruses. To reveal the genetic pathways by which bat RABVs changed their host tropism from bats to carnivores, we investigated the second permanent bat-to-carnivore shift resulting in two carnivore variants, known as raccoon RABV (RRV) and south-central skunk RABV (SCSKV). We found that their glycoprotein (G) genes are the result of recombination between an American bat virus and a carnivore virus. This recombination allowed the bat RABV to acquire the head of the G-protein ectodomain of the carnivore virus. This region is involved in receptor recognition and binding, response to changes in the pH microenvironment, trimerization of G proteins, and cell-to-cell transmission during the viral infection. Therefore, this recombination event may have significantly improved the variant’s adaptability to carnivores, altering its host tropism and thus leading to large-scale epidemics in striped skunk and raccoon. url: https://doi.org/10.1038/s41598-017-00395-2 doi: 10.1038/s41598-017-00395-2 id: cord-002411-iiw878w8 author: Ding, Xibing title: TLR4 signaling induces TLR3 up-regulation in alveolar macrophages during acute lung injury date: 2017-02-15 words: 6653.0 sentences: 431.0 pages: flesch: 57.0 cache: ./cache/cord-002411-iiw878w8.txt txt: ./txt/cord-002411-iiw878w8.txt summary: The enhanced TLR3 up-regulation in AMΦ augmented the expression of cytokines and chemokines in response to sequential challenges with LPS and Poly I:C, a TLR3 ligand, which was physiologically associated with amplified AMΦ-induced PMN migration into lung alveoli. To address the effect of LPS/TLR4-mediated activation of TLR3 in AMΦ on inflammatory cytokines, we assessed TNF-α and IL-6 in the serum and BALF, as well as the chemokines MIP-2 and MCP-1 in the BALF, following sequential intratracheal challenges with LPS and Poly I:C. This cross talk between TLR4 and TLR3 in AMΦ resulted in the amplification of cytokine (IL-6, TNF-α ) and chemokine (MIP-2, MCP-1) expression in response to LPS and Poly I:C, which activate TLR4 and TLR3, respectively, and subsequently led to enhanced PMN sequestration into the lung, which was found to be correlated with ALI based on the assessment of alveolar-capillary permeability and histological sections of lung tissue. abstract: Acute lung injury is a life-threatening inflammatory response caused by severe infection. Toll-like receptors in alveolar macrophages (AMΦ) recognize the molecular constituents of pathogens and activate the host’s innate immune responses. Numerous studies have documented the importance of TLR-TLR cross talk, but few studies have specifically addressed the relationship between TLR4 and TLR3. We explored a novel mechanism of TLR3 up-regulation that is induced by LPS-TLR4 signaling in a dose- and time-dependent manner in AMΦ from C57BL/6 mice, while the LPS-induced TLR3 expression was significantly reduced in TLR4(−/−) and Myd88(−/−) mice and following pretreatment with a NF-κB inhibitor. The enhanced TLR3 up-regulation in AMΦ augmented the expression of cytokines and chemokines in response to sequential challenges with LPS and Poly I:C, a TLR3 ligand, which was physiologically associated with amplified AMΦ-induced PMN migration into lung alveoli. Our study demonstrates that the synergistic effect between TLR4 and TLR3 in macrophages is an important determinant in acute lung injury and, more importantly, that TLR3 up-regulation is dependent on TLR4-MyD88-NF-κB signaling. These results raise the possibility that bacterial infections can induce sensitivity to viral infections, which may have important implications for the therapeutic manipulation of the innate immune system. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5309825/ doi: 10.1038/srep34278 id: cord-315415-3aotsb2g author: Dong, Jianbo title: Development of humanized tri-specific nanobodies with potent neutralization for SARS-CoV-2 date: 2020-10-20 words: 7194.0 sentences: 427.0 pages: flesch: 57.0 cache: ./cache/cord-315415-3aotsb2g.txt txt: ./txt/cord-315415-3aotsb2g.txt summary: In this study we used computer-aided design to construct multi-specific VHH antibodies fused to human IgG1 Fc domains based on the epitope predictions for leading VHHs. The resulting tri-specific VHH-Fc antibodies show more potent S1 binding, S1/ACE2 blocking, and SARS-CoV-2 pseudovirus neutralization than the bi-specific VHH-Fcs or combination of individual monoclonal VHH-Fcs. Furthermore, protein stability analysis of the VHH-Fcs shows favorable developability features, which enable them to be quickly and successfully developed into therapeutics against COVID-19. (c) The binding of VHH-Fcs and ACE2 to Expi293 cells expressing SARS-CoV-2 S1 wild type (WT) or mutant proteins (del1-del5) were assessed by flow cytometry following FITC-conjugated secondary antibody treatment. Based on the binding and epitope binning data, we constructed 3D docking models that predicted the interactions between SARS-CoV-2 S1 RBD, ACE2 and lead VHH-Fcs (Fig. 2e) . Next, we tested whether the combination of individual VHHs binding to different S1 RBD epitopes into bi-specific antibody molecules would yield synergistic effects in SARS-CoV-2 binding and S/ACE2 blocking. abstract: SARS-CoV-2 is a newly emergent coronavirus, which has adversely impacted human health and has led to the COVID-19 pandemic. There is an unmet need to develop therapies against SARS-CoV-2 due to its severity and lack of treatment options. A promising approach to combat COVID-19 is through the neutralization of SARS-CoV-2 by therapeutic antibodies. Previously, we described a strategy to rapidly identify and generate llama nanobodies (VHH) from naïve and synthetic humanized VHH phage libraries that specifically bind the S1 SARS-CoV-2 spike protein, and block the interaction with the human ACE2 receptor. In this study we used computer-aided design to construct multi-specific VHH antibodies fused to human IgG1 Fc domains based on the epitope predictions for leading VHHs. The resulting tri-specific VHH-Fc antibodies show more potent S1 binding, S1/ACE2 blocking, and SARS-CoV-2 pseudovirus neutralization than the bi-specific VHH-Fcs or combination of individual monoclonal VHH-Fcs. Furthermore, protein stability analysis of the VHH-Fcs shows favorable developability features, which enable them to be quickly and successfully developed into therapeutics against COVID-19. url: https://www.ncbi.nlm.nih.gov/pubmed/33082473/ doi: 10.1038/s41598-020-74761-y id: cord-265891-jmpterrj author: Eilersen, Andreas title: Cost–benefit of limited isolation and testing in COVID-19 mitigation date: 2020-10-29 words: 3925.0 sentences: 233.0 pages: flesch: 56.0 cache: ./cache/cord-265891-jmpterrj.txt txt: ./txt/cord-265891-jmpterrj.txt summary: Therefore, we will here implement a crude form of contact tracing where we (1) close the workplaces of people who are tested positive for the disease, (2) isolate their regular social contacts for a limited period, and (3) keep symptomatic individuals in quarantine until they recover. If 10% efficiency is possible, corresponding to detecting about a third of infectious cases, then peak height could be reduced by a factor of almost three with to a 60% drop, if the probability of infected people being tested is only 10% per day of illness. In Fig. 4 , we show two possible scenarios where testing and contact tracing is implemented after a 30-day lockdown with a 75% reduction of the work and social spheres. Using reasonable COVID-19 infection parameters we find that the 1STQ strategy can contribute to epidemic mitigation, in the sense that it can reduce the peak number of infected individuals by about a factor of two even with a realistic testing rate of 10% per day of illness. abstract: The international community has been put in an unprecedented situation by the COVID-19 pandemic. Creating models to describe and quantify alternative mitigation strategies becomes increasingly urgent. In this study, we propose an agent-based model of disease transmission in a society divided into closely connected families, workplaces, and social groups. This allows us to discuss mitigation strategies, including targeted quarantine measures. We find that workplace and more diffuse social contacts are roughly equally important to disease spread, and that an effective lockdown must target both. We examine the cost–benefit of replacing a lockdown with tracing and quarantining contacts of the infected. Quarantine can contribute substantially to mitigation, even if it has short duration and is done within households. When reopening society, testing and quarantining is a strategy that is much cheaper in terms of lost workdays than a long lockdown. A targeted quarantine strategy is quite efficient with only 5 days of quarantine, and its effect increases when testing is more widespread. url: https://www.ncbi.nlm.nih.gov/pubmed/33122753/ doi: 10.1038/s41598-020-75640-2 id: cord-002369-shk4n8f6 author: Fahmy, Ahmed M. title: The autophagy elongation complex (ATG5-12/16L1) positively regulates HCV replication and is required for wild-type membranous web formation date: 2017-01-09 words: 6131.0 sentences: 355.0 pages: flesch: 50.0 cache: ./cache/cord-002369-shk4n8f6.txt txt: ./txt/cord-002369-shk4n8f6.txt summary: The expression of HCV proteins results in the induction of a major rearrangement of host cell membranes, thus leading to the formation of a complex membranous compartment termed the membranous web (MW), which favors viral RNA replication and assembly 3, 4 . To determine whether LC3 or the ATG5-12 conjugate modulates HCV RNA replication, we analyzed the effects of silencing these autophagy genes on viral RNA replication in Huh7 cells stably expressing the JFH1 subgenomic replicon (SGR). Because silencing of LC3 expression led to a clear inhibition of HCV RNA translation after electroporation of the viral RNA but did not significantly affect replication in JFH1-SGR cells, we sought to compare the effect of siRNA treatment before and after infection with HCVcc JFH1 (Fig. 3C) . The autophagy elongation complex proteins (ATG5-12 and ATG16L1) were also detected in the purified MW from NS4B HA replicon cells, but not in the control extract, thus indicating that the elongation complex is indeed present at the HCV replication site. abstract: Hepatitis C virus (HCV) infection induces intracellular membrane rearrangements, thus forming a membranous web (MW) in which HCV replication and assembly occur. The HCV-induced MW is primarily composed of double membrane vesicles (DMVs) transfused by multi-membrane vesicles. The autophagy machinery has been proposed to participate in the formation of such vesicles. However, no clear evidence has been found linking autophagy to the formation of these DMVs. In this study, we evaluated the role of the autophagy elongation complex (ATG5-12/16L1) in HCV replication and MW formation. Using a dominant negative form of ATG12 and an siRNA approach, we demonstrated that the ATG5-12 conjugate, but not LC3-II formation, is crucial for efficient viral replication. Furthermore, purification of HCV MW revealed the presence of ATG5-12 and ATG16L1 along with HCV nonstructural proteins. Interestingly, LC3 was not recruited along with the elongation complex to the site of viral replication. Finally, inhibition of the elongation complex, but not LC3, greatly impaired the formation of the wild-type MW phenotype. To our knowledge, this study provides the first evidence of the involvement of autophagy proteins in the formation of wild-type MWs. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5220323/ doi: 10.1038/srep40351 id: cord-002389-k86hzbbx author: Fan, Hanlu title: Selective inhibition of Ebola entry with selective estrogen receptor modulators by disrupting the endolysosomal calcium date: 2017-01-24 words: 5147.0 sentences: 274.0 pages: flesch: 49.0 cache: ./cache/cord-002389-k86hzbbx.txt txt: ./txt/cord-002389-k86hzbbx.txt summary: As all stages of Ebola entry (binding to and internalization from the cell surface, as well as trafficking to and fusion with the limiting membrane of endolysosome) are mediated by trimeric GP spikes arrayed around the Ebola particles 29, 30 , so the pseudovirion model with Ebola GP can simulate the stages of wild-type Ebola entry, and several groups have studied the Ebola entry mechanism and screened the anti-Ebola entry drugs with Ebola pseudovirion model 3, 6, 31, 32 . To determine whether endolysosomal calcium is involved in the mechanism of Ebola entry inhibition, we treated HepG2 cell line with a high-affinity Rhod-dextran to chelate intraluminal calcium, and infected the cells with Ebola, WSN, or VSV pseudovirions. abstract: The Ebola crisis occurred in West-Africa highlights the urgency for its clinical treatments. Currently, no Food and Drug Administration (FDA)-approved therapeutics are available. Several FDA-approved drugs, including selective estrogen receptor modulators (SERMs), possess selective anti-Ebola activities. However, the inhibitory mechanisms of these drugs remain elusive. By analyzing the structures of SERMs and their incidental biological activity (cholesterol accumulation), we hypothesized that this incidental biological activity induced by SERMs could be a plausible mechanism as to their inhibitory effects on Ebola infection. Herein, we demonstrated that the same dosages of SERMs which induced cholesterol accumulation also inhibited Ebola infection. SERMs reduced the cellular sphingosine and subsequently caused endolysosomal calcium accumulation, which in turn led to blocking the Ebola entry. Our study clarified the specific anti-Ebola mechanism of SERMs, even the cationic amphiphilic drugs (CADs), this mechanism led to the endolysosomal calcium as a critical target for development of anti-Ebola drugs. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5259750/ doi: 10.1038/srep41226 id: cord-012742-lpk6r54i author: Ferreira-Ramos, Ana Sofia title: Snapshots of ADP-ribose bound to Getah virus macro domain reveal an intriguing choreography date: 2020-09-02 words: 5433.0 sentences: 259.0 pages: flesch: 52.0 cache: ./cache/cord-012742-lpk6r54i.txt txt: ./txt/cord-012742-lpk6r54i.txt summary: Soaking experi-Scientific RepoRtS | (2020) 10:14422 | https://doi.org/10.1038/s41598-020-70870-w www.nature.com/scientificreports/ ments were performed with crystals of GETV macro domain co-crystallized with ADP-ribose by adding mother liquor supplemented with aspartic acid to the crystallization droplet followed by 2-3 h or overnight incubation at 20 °C. Finally, we obtained a last GETV macro domain/ADP-ribose complex by co-crystallizing the protein with 3 mM ADP-ribose and 3 mM aspartic acid and diffraction data were collected to 1.45 Å resolution. Lastly, co-crystallization of GETV macro domain with low concentrations of ADP-ribose and aspartic acid (3 mM each) led to a structure where the distal ribose is covalently attached to Cys34. In addition to the pose of ADP-ribose found in other structures of alphavirus macro domain, this work reveals original features such as the opening of the distal Scientific RepoRtS | (2020) 10:14422 | https://doi.org/10.1038/s41598-020-70870-w www.nature.com/scientificreports/ ribose, and its stabilization by Ser30, representing a peculiar GETV specific substitution in the catalytic loop. abstract: Alphaviruses are (re-)emerging arboviruses of public health concern. The nsP3 gene product is one of the key players during viral replication. NsP3 comprises three domains: a macro domain, a zinc-binding domain and a hypervariable region. The macro domain is essential at both early and late stages of the replication cycle through ADP-ribose (ADPr) binding and de-ADP-ribosylation of host proteins. However, both its specific role and the precise molecular mechanism of de-ADP-ribosylation across specific viral families remains to be elucidated. Here we investigate by X-ray crystallography the mechanism of ADPr reactivity in the active site of Getah virus macro domain, which displays a peculiar substitution of one of the conserved residues in the catalytic loop. ADPr adopts distinct poses including a covalent bond between the C′′1 of the ADPr and a conserved Togaviridae-specific cysteine. These different poses observed for ADPr may represent snapshots of the de-ADP-ribosylation mechanism, highlighting residues to be further characterised. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7468284/ doi: 10.1038/s41598-020-70870-w id: cord-301016-9t7v7ipt author: Forni, Diego title: The heptad repeat region is a major selection target in MERS-CoV and related coronaviruses date: 2015-09-25 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Middle East respiratory syndrome coronavirus (MERS-CoV) originated in bats and spread to humans via zoonotic transmission from camels. We analyzed the evolution of the spike (S) gene in betacoronaviruses (betaCoVs) isolated from different mammals, in bat coronavirus populations, as well as in MERS-CoV strains from the current outbreak. Results indicated several positively selected sites located in the region comprising the two heptad repeats (HR1 and HR2) and their linker. Two sites (R652 and V1060) were positively selected in the betaCoVs phylogeny and correspond to mutations associated with expanded host range in other coronaviruses. During the most recent evolution of MERS-CoV, adaptive mutations in the HR1 (Q/R/H1020) arose in camels or in a previous host and spread to humans. We determined that different residues at position 1020 establish distinct inter- and intra-helical interactions and affect the stability of the six-helix bundle formed by the HRs. A similar effect on stability was observed for a nearby mutation (T1015N) that increases MERS-CoV infection efficiency in vitro. Data herein indicate that the heptad repeat region was a major target of adaptive evolution in MERS-CoV-related viruses; these results are relevant for the design of fusion inhibitor peptides with antiviral function. url: https://doi.org/10.1038/srep14480 doi: 10.1038/srep14480 id: cord-330057-3vucm0s1 author: Franzo, Giovanni title: Phylodynamic analysis and evaluation of the balance between anthropic and environmental factors affecting IBV spreading among Italian poultry farms date: 2020-04-29 words: 5537.0 sentences: 280.0 pages: flesch: 40.0 cache: ./cache/cord-330057-3vucm0s1.txt txt: ./txt/cord-330057-3vucm0s1.txt summary: In the present study, 361 IBV QX (the most relevant field genotype in Italy) sequences were obtained between 2012 and 2016 from the two main Italian integrated poultry companies. Finally, the different viral population pattern observed in the two companies over the same time period supports the pivotal role of management and control strategies on IBV epidemiology. Almost identical results were obtained including a third "ghost" deme (i.e. an estimated deme for which no sequences were available, representative of other unsampled companies and farms) in the analysis or using the "traditional" coalescent approach. In the particular Italian QX scenario, the serially sampled (i.e. with known collection date) strains were used to infer the migration rate and history between the two integrated poultry companies (i.e. considered as different demes) over time. abstract: Infectious bronchitis virus (IBV) control is mainly based on wide vaccine administration. Although effective, its efficacy is not absolute, the viral circulation is not prevented and some side effects cannot be denied. Despite this, the determinants of IBV epidemiology and the factors affecting its circulation are still largely unknown and poorly investigated. In the present study, 361 IBV QX (the most relevant field genotype in Italy) sequences were obtained between 2012 and 2016 from the two main Italian integrated poultry companies. Several biostatistical and bioinformatics approaches were used to reconstruct the history of the QX genotype in Italy and to assess the effect of different environmental, climatic and social factors on its spreading patterns. Moreover, two structured coalescent models were considered in order to investigate if an actual compartmentalization occurs between the two integrated poultry companies and the role of a third “ghost” deme, representative of minor industrial poultry companies and the rural sector. The obtained results suggest that the integration of the poultry companies is an effective barrier against IBV spreading, since the strains sampled from the two companies formed two essentially-independent clades. Remarkably, the only exceptions were represented by farms located in the high densely populated poultry area of Northern Italy. The inclusion of a third deme in the model revealed the likely role of other poultry companies and rural farms (particularly concentrated in Northern Italy) as sources of strain introduction into one of the major poultry companies, whose farms are mainly located in the high densely populated poultry area of Northern Italy. Accordingly, when the effect of different environmental and urban parameters on IBV geographic spreading was investigated, no factor seems to contribute to IBV dispersal velocity, being poultry population density the only exception. Finally, the different viral population pattern observed in the two companies over the same time period supports the pivotal role of management and control strategies on IBV epidemiology. Overall, the present study results stress the crucial relevance of human action rather than environmental factors, highlighting the direct benefits that could derive from improved management and organization of the poultry sector on a larger scale. url: https://doi.org/10.1038/s41598-020-64477-4 doi: 10.1038/s41598-020-64477-4 id: cord-002659-566uoozj author: Fujimoto, Yousuke title: Pulmonary inflammation and cytokine dynamics of bronchoalveolar lavage fluid from a mouse model of bronchial asthma during A(H1N1)pdm09 influenza infection date: 2017-08-22 words: 4768.0 sentences: 275.0 pages: flesch: 57.0 cache: ./cache/cord-002659-566uoozj.txt txt: ./txt/cord-002659-566uoozj.txt summary: Cytokine levels and virus titres in bronchoalveolar lavage fluid from mice with and without asthma after A(H1N1)pdm09 or seasonal H1N1 infection were examined. Virus titres in asthma/A(H1N1)pdm09 mice were highest at 3 days post-infection, and decreased by 7 days post-infection, although the levels at this time point were still higher than that in any other group. In the present study, we investigated the sequential changes in intra-tracheal cytokine production, viral loads, and pulmonary inflammation in a mouse model of bronchial asthma during the first 7 days after A(H1N1)pdm09 or seasonal H1N1 influenza infection. In contrast, the levels in control mice increased to 161.4 pg/mL by 3 days post-seasonal virus infection, which were similar to those in asthma/A(H1N1)pdm09 mice (p = 1.00), and these levels were maintained until 7 days post-infection. The notable findings in the present study were the early peak in both IL-6 and TNF-α levels, the high inflammatory cell infiltration in BAL fluids, and the severe pulmonary inflammation at 3 days post-infection in asthmatic/A(H1N1)pdm09 mice. abstract: Asthmatic patients present more rapid progression of respiratory distress after A(H1N1)pdm09 influenza infection than after seasonal infection. Here, we sought to clarify the pathophysiology of early deterioration in asthmatic patients after A(H1N1)pdm09 infection. Cytokine levels and virus titres in bronchoalveolar lavage fluid from mice with and without asthma after A(H1N1)pdm09 or seasonal H1N1 infection were examined. In asthma/A(H1N1)pdm09 mice, IL-6 and TNF-α levels peaked at 3 days post-infection and were higher than those in all other groups. IFN-γ levels in asthma/A(H1N1)pdm09 mice at 3 days post-infection were higher than in all other mice at any time point, whereas at 7 days post-infection, the levels were lowest in asthma/A(H1N1)pdm09 mice. Virus titres in asthma/A(H1N1)pdm09 mice were highest at 3 days post-infection, and decreased by 7 days post-infection, although the levels at this time point were still higher than that in any other group. Histopathological examination showed more inflammatory cell infiltration and lung tissue destruction in the asthma/A(H1N1)pdm09 group than in any other group. The distinct cytokine profiles in A(H1N1)pdm09-infected asthmatic mice indicated excessive inflammation and virus replication within a few days after infection. Thus, bronchial asthma could be a more exacerbating factor for pandemic influenza infection than for seasonal influenza infection. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5567326/ doi: 10.1038/s41598-017-08030-w id: cord-287708-0qvwjejv author: Gera, Tamás title: Application of pulsed laser ablation (PLA) for the size reduction of non-steroidal anti-inflammatory drugs (NSAIDs) date: 2020-09-25 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: We studied the application of pulsed laser ablation (PLA) for particle size reduction in non-steroidal anti-inflammatory drugs (NSAIDs). Grinding of the poorly water-soluble NSAID crystallites can considerably increase their solubility and bioavailability, thereby the necessary doses can be reduced significantly. We used tablets of ibuprofen, niflumic acid and meloxicam as targets. Nanosecond laser pulses were applied at various wavelengths (KrF excimer laser, λ = 248 nm, FWHM = 18 ns and Nd:YAG laser, λ(1) = 532 nm/λ(2) = 1064 nm, FWHM = 6 ns) and at various fluences. FTIR and Raman spectra showed that the chemical compositions of the drugs had not changed during ablation at 532 nm and 1064 nm laser wavelengths. The size distribution of the ablated products was established using two types of particle size analyzers (SMPS and OPC) having complementary measuring ranges. The mean size of the drug crystallites decreased from the initial 30–80 µm to the submicron to nanometer range. For a better understanding of the ablation mechanism we made several investigations (SEM, Ellipsometry, Fast photography) and some model calculations. We have established that PLA offers a chemical-free and simple method for the size reduction of poorly water-soluble drugs and a possible new way for pharmaceutical drug preformulation for nasal administration. url: https://doi.org/10.1038/s41598-020-72865-z doi: 10.1038/s41598-020-72865-z id: cord-329424-hmsidrc7 author: Grunwell, Jocelyn R. title: Differential type I interferon response and primary airway neutrophil extracellular trap release in children with acute respiratory distress syndrome date: 2020-11-04 words: 4860.0 sentences: 274.0 pages: flesch: 38.0 cache: ./cache/cord-329424-hmsidrc7.txt txt: ./txt/cord-329424-hmsidrc7.txt summary: title: Differential type I interferon response and primary airway neutrophil extracellular trap release in children with acute respiratory distress syndrome Since viral lower respiratory tract infections are a primary trigger for PARDS, we questioned whether differential ISG expression was associated with neutrophil responses in intubated children at risk or with PARDS. We hypothesized that children with PARDS would have a greater type I IFN response resulting in more neutrophil extracellular trap (NET) release. Our study assessed neutrophil activation, the differential expression of ISGs and activation of the STAT1 signaling pathway, and NETosis in the airways of intubated children with acute respiratory failure due to lower respiratory tract infections. While we detected higher type I IFN signaling and NET production in the airways of children with versus without PARDS, due to the clinical nature of our study, we are not able to attribute causation of neutrophil dysfunction to high ISG expression in study participants. abstract: Acute respiratory distress syndrome (ARDS) is a heterogeneous condition characterized by the recruitment of large numbers of neutrophils into the lungs. Neutrophils isolated from the blood of adults with ARDS have elevated expression of interferon (IFN) stimulated genes (ISGs) associated with decreased capacity of neutrophils to kill Staphylococcus aureus and worse clinical outcomes. Neutrophil extracellular traps (NETs) are elevated in adults with ARDS. Whether pediatric ARDS (PARDS) is similarly associated with altered neutrophil expression of ISGs and neutrophil extracellular trap release is not known. Tracheal aspirate fluid and cells were collected within 72 h from seventy-seven intubated children. Primary airway neutrophils were analyzed for differential ISG expression by PCR, STAT1 phosphorylation and markers of degranulation and activation by flow cytometry. Airway fluid was analyzed for the release of NETs by myeloperoxidase-DNA complexes using an ELISA. Higher STAT1 phosphorylation, markers of neutrophil degranulation, activation and NET release were found in children with versus without PARDS. Higher NETs were detected in the airways of children with ventilator-free days less than 20 days. Increased airway cell IFN signaling, neutrophil activation, and NET production is associated with PARDS. Higher levels of airway NETs are associated with fewer ventilator-free days. url: https://www.ncbi.nlm.nih.gov/pubmed/33149247/ doi: 10.1038/s41598-020-76122-1 id: cord-271328-zdf5ji4k author: Gu, Hongjing title: Angiotensin-converting enzyme 2 inhibits lung injury induced by respiratory syncytial virus date: 2016-01-27 words: 3910.0 sentences: 196.0 pages: flesch: 52.0 cache: ./cache/cord-271328-zdf5ji4k.txt txt: ./txt/cord-271328-zdf5ji4k.txt summary: In this paper, we report that angiotensin-converting enzyme-2 (ACE2) protected against severe lung injury induced by RSV infection in an experimental mouse model and in pediatric patients. To determine the role of ACE2 in RSV-induced lung injury, we first measured the levels of Ang II in the plasma of RSV-infected patients. Importantly, ACE2 protein levels were dramatically decreased in lung homogenates from mice infected with RSV BJ016 virus at 3 days post-infection (p < 0.01; Fig. 1d ). Our data suggest that RSV infection causes severe lung injury in an experimental mouse model and in patients, at least in part by modulating the RAS system via down-regulation of the ACE2-AT1R axis. Importantly, the levels of Ang II were elevated following down-regulation of ACE2, causing severe lung injury via AT1R during the process of RSV infection (Fig. 5d) . abstract: Respiratory syncytial virus (RSV) infection is a major cause of severe lower respiratory illness in infants and young children, but the underlying mechanisms responsible for viral pathogenesis have not been fully elucidated. To date, no drugs or vaccines have been employed to improve clinical outcomes for RSV-infected patients. In this paper, we report that angiotensin-converting enzyme-2 (ACE2) protected against severe lung injury induced by RSV infection in an experimental mouse model and in pediatric patients. Moreover, ACE2 deficiency aggravated RSV-associated disease pathogenesis, mainly by its action on the angiotensin II type 1 receptor (AT1R). Furthermore, administration of a recombinant ACE2 protein alleviated the severity of RSV-induced lung injury. These findings demonstrate that ACE2 plays a critical role in preventing RSV-induced lung injury, and suggest that ACE2 is a promising potential therapeutic target in the management of RSV-induced lung disease. url: https://www.ncbi.nlm.nih.gov/pubmed/26813885/ doi: 10.1038/srep19840 id: cord-296562-3h2oqb9k author: Guillén, Lucía title: Preemptive interleukin-6 blockade in patients with COVID-19 date: 2020-10-08 words: 4874.0 sentences: 246.0 pages: flesch: 44.0 cache: ./cache/cord-296562-3h2oqb9k.txt txt: ./txt/cord-296562-3h2oqb9k.txt summary: In contrast to other respiratory viral infections like influenza, a major pathogenic mechanism implicated in severe clinical manifestations of COVID-19 is an aberrant host immune response resulting in an excessive cytokine and chemokine release known as "cytokine storm" or "cytokine release syndrome" 2,3 . In a sensitivity analysis including only the 55 patients with confirmed SARS-CoV-2 infection by RT-PCR, the significant variables in the adjusted multivariate model were a NLR > 2.55 (OR 5.26; 95% CI 1.02-25), higher Charlson comorbidity index (OR 1.56; 95% CI 1.04-2.34) per unit, and higher SOFA score (OR 5.05; 95% CI 1.10-23.24) (Supplementary Table 2 ). This biomarker reflects excessive inflammation and dysregulation of immune cells that play a central role in severity of disease in viral infections 23 , and has been associated with mortality in patients hospitalized with COVID-19 24 . www.nature.com/scientificreports/ four comorbidities are included in the Charlson index, and have been associated with higher disease severity in patients with COVID-19 31 . abstract: Excessive interleukin-6 signaling is a key factor contributing to the cytokine release syndrome implicated in clinical manifestations of COVID-19. Preliminary results suggest that tocilizumab, a humanized monoclonal anti-interleukin-6 receptor antibody, may be beneficial in severely ill patients, but no data are available on earlier stages of disease. An anticipated blockade of interleukin-6 might hypothetically prevent the catastrophic consequences of the overt cytokine storm. We evaluated early-given tocilizumab in patients hospitalized with COVID-19, and identified outcome predictors. Consecutive patients with initial Sequential-Organ-Failure-Assessment (SOFA) score < 3 fulfilling pre-defined criteria were treated with tocilizumab. Serial plasma biomarkers and nasopharyngeal swabs were collected. Of 193 patients admitted with COVID-19, 64 met the inclusion criteria. After tocilizumab, 49 (76.6%) had an early favorable response. Adjusted predictors of response were gender, SOFA score, neutrophil/lymphocyte ratio, Charlson comorbidity index and systolic blood pressure. At week-4, 56.1% of responders and 30% of non-responders had cleared the SARS-CoV-2 from nasopharynx. Temporal profiles of interleukin-6, C-reactive protein, neutrophil/lymphocyte ratio, NT-ProBNP, D-dimer, and cardiac-troponin-I differed according to tocilizumab response and discriminated final in-hospital outcome. No deaths or disease recurrences were observed. Preemptive therapy with tocilizumab was safe and associated with favorable outcomes in most patients. Biological and clinical markers predicted outcomes. url: https://doi.org/10.1038/s41598-020-74001-3 doi: 10.1038/s41598-020-74001-3 id: cord-002177-yyfgl9x5 author: Guo, Jinyue title: TGEV infection up-regulates FcRn expression via activation of NF-κB signaling date: 2016-08-24 words: 5211.0 sentences: 315.0 pages: flesch: 52.0 cache: ./cache/cord-002177-yyfgl9x5.txt txt: ./txt/cord-002177-yyfgl9x5.txt summary: Furthermore, treatment of TGEV-infected IPEC-J2 cells with the NF-κB-specific inhibitor BAY 11-7082 resulted in down-regulation of pFcRn expression. We identified four NF-κB transcription factor binding sites in the promoter region of this gene using luciferase reporter system, chromatin immunoprecipitation, electromobility shift assay, and supershift analysis. In the present study, we investigated how TGEV infection activated the NF-κ B pathway in vitro and up-regulated pFcRn expression in IPEC-J2 cells. Furthermore, pFcRn expression induced by TGEV infection was strongly reduced by the NF-κ B-specific inhibitor BAY 11-7082 in IPEC-J2 cells (Fig. 3) . Transient transfection of the pFcRn promoter luciferase reporter plasmids revealed that pFcRn-luc-(1-3) plasmids resulted in increased promoter activity in the presence of TGEV infection (Fig. 4B) , further demonstrating that TGEV up-regulates pFcRn expression in IPEC-J2 cells. In summary, TGEV infection up-regulates pFcRn expression in IPEC-J2 cells, and activates the NF-κ B signaling pathway. abstract: It has been well characterized that the neonatal Fc receptor (FcRn) transports maternal IgG to a fetus or newborn and protects IgG from degradation. We previously reported that FcRn is expressed in a model of normal porcine intestinal epithelial cells (IPEC-J2). Transmissible gastroenteritis is an acute enteric disease of swine that is caused by transmissible gastroenteritis virus (TGEV). How porcine FcRn (pFcRn) expression is regulated by pathogenic infection remains unknown. Our research shows that IPEC-J2 cells infected with TGEV had up-regulated pFcRn expression. In addition, the NF-κB signaling pathway was activated in IPEC-J2 cells by TGEV infection. Furthermore, treatment of TGEV-infected IPEC-J2 cells with the NF-κB-specific inhibitor BAY 11-7082 resulted in down-regulation of pFcRn expression. Transient transfection of pFcRn promoter luciferase report plasmids with overexpression of NF-κB p65 transcription factor enhanced the activation of the luciferase report plasmids. We identified four NF-κB transcription factor binding sites in the promoter region of this gene using luciferase reporter system, chromatin immunoprecipitation, electromobility shift assay, and supershift analysis. Together, the data provide the first evidence that TGEV infection up-regulates pFcRn expression via activation of NF-κB signaling. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4995372/ doi: 10.1038/srep32154 id: cord-004006-tfp2idq2 author: Hale, Alison C. title: A real-time spatio-temporal syndromic surveillance system with application to small companion animals date: 2019-11-28 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Lack of disease surveillance in small companion animals worldwide has contributed to a deficit in our ability to detect and respond to outbreaks. In this paper we describe the first real-time syndromic surveillance system that conducts integrated spatio-temporal analysis of data from a national network of veterinary premises for the early detection of disease outbreaks in small animals. We illustrate the system’s performance using data relating to gastrointestinal disease in dogs and cats. The data consist of approximately one million electronic health records for dogs and cats, collected from 458 UK veterinary premises between March 2014 and 2016. For this illustration, the system predicts the relative reporting rate of gastrointestinal disease amongst all presentations, and updates its predictions as new data accrue. The system was able to detect simulated outbreaks of varying spatial geometry, extent and severity. The system is flexible: it generates outcomes that are easily interpretable; the user can set their own outbreak detection thresholds. The system provides the foundation for prompt detection and control of health threats in companion animals. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6882870/ doi: 10.1038/s41598-019-53352-6 id: cord-007851-v6h1yro7 author: Han, Ki-Cheol title: Streamlined selection of cancer antigens for vaccine development through integrative multi-omics and high-content cell imaging date: 2020-04-03 words: 4886.0 sentences: 260.0 pages: flesch: 41.0 cache: ./cache/cord-007851-v6h1yro7.txt txt: ./txt/cord-007851-v6h1yro7.txt summary: We used a combined application of this method involving immune-specific signature analysis and HLA-associated peptidomics using samples from six patients with triple-negative breast cancer (TNBC) in order to select immunogenic HLA epitopes for in vitro testing. Integrated WTS data revealed a higher priority to select promising HLA-peptides via high-resolution bioinformatics analysis, showing immune-cell-specific signatures and TCR-repertoire diversity in tumors. We then found a positive correlation between TCR diversity, reflecting clonal composition, and the expression of MHC-class І molecules, suggesting that active tumor-antigen presentation promotes the generation of antigen-specific TILs. Additionally, immune-specific signature analysis can discriminate specific immune-cell types in each patient and thus enhance the efficiency of selective HLA-peptidomic approaches. In this study, the HLA-peptidomics approach combined with comprehensive analysis of immune-specific signatures and TCR repertories showed high selectivity to determine the immunogenic T-cell epitopes. Identification of potential vaccine epitopes coupled with immune-specific signature analysis, HLA-peptidomics, and single-cell-based immunogenicity testing offers a discriminative and powerful tool for cancer-vaccine development. abstract: Identification of tumor antigens that induce cytotoxic T lymphocytes (CTLs) is crucial for cancer-vaccine development. Despite their predictive ability, current algorithmic approaches and human leukocyte antigen (HLA)-peptidomic analysis allow limited selectivity. Here, we optimized a method to rapidly screen and identify highly immunogenic epitopes that trigger CTL responses. We used a combined application of this method involving immune-specific signature analysis and HLA-associated peptidomics using samples from six patients with triple-negative breast cancer (TNBC) in order to select immunogenic HLA epitopes for in vitro testing. Additionally, we applied high-throughput imaging at the single-cell level in order to confirm the immunoreactivity of the selected peptides. The results indicated that this method enabled identification of promising CTL peptides capable of inducing antitumor immunity. This platform combining high-resolution computational analysis, HLA-peptidomics, and high-throughput immunogenicity testing allowed rapid and robust identification of highly immunogenic epitopes and represents a powerful technique for cancer-vaccine development. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7125174/ doi: 10.1038/s41598-020-62244-z id: cord-004379-91a7sgir author: Han, Nayoung title: Assessment of adverse events related to anti-influenza neuraminidase inhibitors using the FDA adverse event reporting system and online patient reviews date: 2020-02-20 words: 3261.0 sentences: 190.0 pages: flesch: 46.0 cache: ./cache/cord-004379-91a7sgir.txt txt: ./txt/cord-004379-91a7sgir.txt summary: The aim of this study was to evaluate age-related clinical manifestations of adverse events (AEs) related to NAIs. FAERS and WebMD data were downloaded. A disproportionality analysis showed that signals for vomiting and hallucinations were detected in younger patients given oseltamivir, while an abnormal hepatic function, cardiac failure, shock, and cardio-respiratory arrest were detected in older patients given peramivir. However, there is still concern regarding the adverse effects of NAIs. This study analyzed the age-related AEs associated with NAIs using data from FAERS and WebMD. Oseltamivir was the NAI most commonly showing AEs in the FAERS data, and the most common AEs for this drug were psychiatric and gastrointestinal disorders, similar to the findings of previous studies 8, [13] [14] [15] [16] . However, in the WebMD data, we could not detect signals by these disproportionality analyses due to the small number of AE cases, although psychiatric and gastrointestinal disorders were the most common AEs reported. abstract: The recommended antiviral drugs available for the treatment and prevention of influenza are neuraminidase inhibitors (NAIs). The aim of this study was to evaluate age-related clinical manifestations of adverse events (AEs) related to NAIs. FAERS and WebMD data were downloaded. The available NAIs selected for the analysis were oseltamivir, peramivir, zanamivir, and laninamivir. Disproportionality was analyzed using the proportional reporting ratio (PRR), the reporting odds ratio (ROR), and the information component (IC) methods. In total, 16729 AEs from 4598 patients and 575 AEs from 440 patients in the FAERS and WebMD, respectively, were included in the analysis. In the FAERS, AEs were more common among those who were younger (<19 years) for zanamivir, while for those who were older (>65 years) for peramivir. A disproportionality analysis showed that signals for vomiting and hallucinations were detected in younger patients given oseltamivir, while an abnormal hepatic function, cardiac failure, shock, and cardio-respiratory arrest were detected in older patients given peramivir. Psychiatric disorders were most common in younger and older patients, while gastrointestinal disorders were most common in adult given oseltamivir in the WebMD. Adverse symptoms related to NAIs varied and depended on the drugs used and the age of the patient. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7033147/ doi: 10.1038/s41598-020-60068-5 id: cord-268414-7fcc5i7i author: Hassani, Abdelkader title: Preparation, characterization and therapeutic properties of gum arabic-stabilized gallic acid nanoparticles date: 2020-10-20 words: 7105.0 sentences: 379.0 pages: flesch: 47.0 cache: ./cache/cord-268414-7fcc5i7i.txt txt: ./txt/cord-268414-7fcc5i7i.txt summary: The formulated nanoparticles (GANPs) were characterized for physicochemical properties and size and were then evaluated for antioxidant and antihypertensive effects using various established in vitro assays, including 1,1-diphenyl-2-picrylhydrazyl (DPPH), nitric oxide scavenging (NO), β-carotene bleaching and angiotensin-converting enzyme (ACE) inhibitory assays. This study is the first to confirm the synergistic effects of gum arabic in the encapsulation of gallic acid by increasing the selectivity towards cancer cells and enhancing the antioxidant properties. According to the results, significant cytotoxicity was elicited among the HepG2, MCF7, MDA-MB231, and HT29 cell lines after treatment with IC 50 concentrations of free and nano encapsulated gallic acid as shown in Fig. 12 . The MDA-MB231 and HT29 cells had a lower fluorescence intensity of PI attributed to the lower toxicity of GA/C6NPs. www.nature.com/scientificreports/ The migration assay was carried out to assess the effect of GANPS and free GA with the IC 50 value of concentrations on MCF7, MDA-MB-231, HepG2, and HT29. abstract: Gallic acid (GA) is a natural phenolic compound with therapeutic effects that are often challenged by its rapid metabolism and clearance. Therefore, GA was encapsulated using gum arabic into nanoparticles to increase its bioavailability. The formulated nanoparticles (GANPs) were characterized for physicochemical properties and size and were then evaluated for antioxidant and antihypertensive effects using various established in vitro assays, including 1,1-diphenyl-2-picrylhydrazyl (DPPH), nitric oxide scavenging (NO), β-carotene bleaching and angiotensin-converting enzyme (ACE) inhibitory assays. The GANPs were further evaluated for the in vitro cytotoxicity, cell uptake and cell migration in four types of human cancer cell lines including (MCF-7, MDA-MB231) breast adenocarcinoma, HepG2 hepatocellular cancer, HT-29 colorectal adenocarcinoma, and MCF-10A breast epithelial cell lines. The GANPs demonstrated potent antioxidant effects and have shown promising anti-cancer properties in a dose-dependent manner with a predilection toward HepG2 and MCF7 cancer cells. The uptake of GANPs was successful in the majority of cancer cells with a propensity to accumulate in the nuclear region of the cells. The HepG2 and MCF7 cancer cells also had a significantly higher percentage of apoptosis and were more sensitive to gallic acid nanoparticle treatment in the cell migration assay. This study is the first to confirm the synergistic effects of gum arabic in the encapsulation of gallic acid by increasing the selectivity towards cancer cells and enhancing the antioxidant properties. The formulated nanoparticles also had remarkably low toxicity in normal cells. Based on these findings, GANPs may have promising therapeutic applications towards the development of more effective treatments with a probable targeting precision in cancer cells. url: https://www.ncbi.nlm.nih.gov/pubmed/33082415/ doi: 10.1038/s41598-020-71175-8 id: cord-309127-kxivgxbg author: Haverkamp, Ann-Kathrin title: Experimental infection of dromedaries with Middle East respiratory syndrome-Coronavirus is accompanied by massive ciliary loss and depletion of the cell surface receptor dipeptidyl peptidase 4 date: 2018-06-27 words: 6524.0 sentences: 296.0 pages: flesch: 38.0 cache: ./cache/cord-309127-kxivgxbg.txt txt: ./txt/cord-309127-kxivgxbg.txt summary: title: Experimental infection of dromedaries with Middle East respiratory syndrome-Coronavirus is accompanied by massive ciliary loss and depletion of the cell surface receptor dipeptidyl peptidase 4 In line with these observations, high amounts of MERS-CoV antigen were detected within the respiratory epithelium of the nasal turbinates of mock-vaccinated dromedaries at 4 dpi by immunohistochemistry in areas SciEntiFic REpORTS | (2018) 8:9778 | DOI:10.1038/s41598-018-28109-2 with most severe lesions ( Fig. 2A) . To finally elucidate the histogenesis of cells staining positive for MERS-CoV nucleocapsid antigen within the lamina propria of the nasal turbinates of mock-vaccinated dromedaries, additional double immunofluorescence labeling was performed. Since DPP4 was only detectable within the apical brush border of the surface epithelium and submucosal glands, but not on the surface of inflammatory cells within lamina propria and submucosa of the nasal turbinates by immunofluorescence, dromedary and human lymphoid tissue were stained for comparison and control. abstract: Middle East respiratory syndrome (MERS) represents an important respiratory disease accompanied by lethal outcome in one-third of human patients. Recent data indicate that dromedaries represent an important source of infection, although information regarding viral cell tropism and pathogenesis is sparse. In the current study, tissues of eight dromedaries receiving inoculation of MERS-Coronavirus (MERS-CoV) after recombinant Modified-Vaccinia-Virus-Ankara (MVA-S)-vaccination (n = 4), MVA-vaccination (mock vaccination, n = 2) and PBS application (mock vaccination, n = 2), respectively, were investigated. Tissues were analyzed by histology, immunohistochemistry, immunofluorescence, and scanning electron microscopy. MERS-CoV infection in mock-vaccinated dromedaries revealed high numbers of MERS-CoV-nucleocapsid positive cells, T cells, and macrophages within nasal turbinates and trachea at day four post infection. Double immunolabeling demonstrated cytokeratin (CK) 18 expressing epithelial cells to be the prevailing target cell of MERS-CoV, while CK5/6 and CK14 expressing cells did not co-localize with virus. In addition, virus was occasionally detected in macrophages. The acute disease was further accompanied by ciliary loss along with a lack of dipeptidyl peptidase 4 (DPP4), known to mediate virus entry. DPP4 was mainly expressed by human lymphocytes and dromedary monocytes, but overall the expression level was lower in dromedaries. The present study underlines significant species-specific manifestations of MERS and highlights ciliary loss as an important finding in dromedaries. The obtained results promote a better understanding of coronavirus infections, which pose major health challenges. url: https://doi.org/10.1038/s41598-018-28109-2 doi: 10.1038/s41598-018-28109-2 id: cord-255586-wshvvgxg author: He, Shengyang title: Clinical characteristics of “re-positive” discharged COVID-19 pneumonia patients in Wuhan, China date: 2020-10-15 words: 2920.0 sentences: 163.0 pages: flesch: 45.0 cache: ./cache/cord-255586-wshvvgxg.txt txt: ./txt/cord-255586-wshvvgxg.txt summary: The demographic features, clinical symptoms, laboratory results, comorbidities, co-infections, treatments, illness severities and chest CT scan results of 267 patients were collected from 1st January to 15th February 2020. | (2020) 10:17365 | https://doi.org/10.1038/s41598-020-74284-6 www.nature.com/scientificreports/ disease progression, no differences were found, suggesting this group of COVID-19 patients could be difficult to detect by using standard clinical data. All raw clinical and laboratory results were collected from electronic medical records system of the Central Hospital of Wuhan, followed by a follow up visit up to 14 days (also known as the discharge quarantine) to test for a re-positive nucleic acid assay. Definition of "re-positive": when a confirmed COVID-19 patient is detected SARS-CoV-2 RNA positive during the 14 days post-discharge quarantine (random test timing). Since understanding of the mechanisms of SARS-CoV-2 infection is still lacking, a careful discharge protocol should be applied (e.g. negative results of the nucleic acid tests of respiratory pathogens for 3 consecutive times), and post-discharge quarantine should be strictly observed, especially for severe and critical COVID-19 patients. abstract: To analyze the clinical characteristics of re-positive discharged COVID-19 patients and find distinguishing markers. The demographic features, clinical symptoms, laboratory results, comorbidities, co-infections, treatments, illness severities and chest CT scan results of 267 patients were collected from 1st January to 15th February 2020. COVID-19 was diagnosed by RT-PCR. Clinical symptoms and nucleic acid test results were collected during the 14 days post-hospitalization quarantine. 30 out of 267 COVID-19 patients were detected re-positive during the post-hospitalization quarantine. Re-positive patients could not be distinguished by demographic features, clinical symptoms, laboratory results, comorbidities, co-infections, treatments, chest CT scan results or subsequent clinical symptoms. However, re-positive rate was found to be correlated to illness severity, according the Acute Physiology and Chronic Health Evaluation II (APACHE II) severity-of-disease classification system, and the confusion, urea, respiratory rate and blood pressure (CURB-65) score. Common clinical characteristics were not able to distinguish re-positive patients. However, severe and critical cases classified high according APACHE II and CURB-65 scores, were more likely to become re-positive after discharge. url: https://doi.org/10.1038/s41598-020-74284-6 doi: 10.1038/s41598-020-74284-6 id: cord-293372-saqoft9p author: Heffner, Kelley title: Expanded Chinese hamster organ and cell line proteomics profiling reveals tissue-specific functionalities date: 2020-09-28 words: 4862.0 sentences: 274.0 pages: flesch: 45.0 cache: ./cache/cord-293372-saqoft9p.txt txt: ./txt/cord-293372-saqoft9p.txt summary: Quantitative proteomics data were obtained from two CHO cell lines (CHO-S and CHO DG44) and compared with seven Chinese hamster (Cricetulus griseus) tissues (brain, heart, kidney, liver, lung, ovary and spleen) by tandem mass tag (TMT) labeling followed by mass spectrometry, providing a comprehensive hamster tissue and cell line proteomics atlas. This study was undertaken to compare protein expression of various CHO cell lines and hamster tissues, resulting in the most comprehensive multi-tissue analysis of the Cricetulus griseus proteome (Fig. 1A) . Similar to the ovary and lung comparison, there are a greater number of proteins with higher expression in the heart tissue when compared to cell lines. These differences highlight the role of tissues in executing key organ functions which require a specific metabolic processes, such as transport and communication, in comparison to CHO cells, which are focused on replication and gene expression, characteristics useful for rapid growth and the production of biologics. abstract: Chinese hamster ovary (CHO) cells are the predominant production vehicle for biotherapeutics. Quantitative proteomics data were obtained from two CHO cell lines (CHO-S and CHO DG44) and compared with seven Chinese hamster (Cricetulus griseus) tissues (brain, heart, kidney, liver, lung, ovary and spleen) by tandem mass tag (TMT) labeling followed by mass spectrometry, providing a comprehensive hamster tissue and cell line proteomics atlas. Of the 8470 unique proteins identified, high similarity was observed between CHO-S and CHO DG44 and included increases in proteins involved in DNA replication, cell cycle, RNA processing, and chromosome processing. Alternatively, gene ontology and pathway analysis in tissues indicated increased protein intensities related to important tissue functionalities. Proteins enriched in the brain included those involved in acidic amino acid metabolism, Golgi apparatus, and ion and phospholipid transport. The lung showed enrichment in proteins involved in BCAA catabolism, ROS metabolism, vesicle trafficking, and lipid synthesis while the ovary exhibited enrichments in extracellular matrix and adhesion proteins. The heart proteome included vasoconstriction, complement activation, and lipoprotein metabolism enrichments. These detailed comparisons of CHO cell lines and hamster tissues will enhance understanding of the relationship between proteins and tissue function and pinpoint potential pathways of biotechnological relevance for future cell engineering. url: https://www.ncbi.nlm.nih.gov/pubmed/32985598/ doi: 10.1038/s41598-020-72959-8 id: cord-013977-xb0r2axf author: Heng, Kevin title: The approximately universal shapes of epidemic curves in the Susceptible-Exposed-Infectious-Recovered (SEIR) model date: 2020-11-09 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Compartmental transmission models have become an invaluable tool to study the dynamics of infectious diseases. The Susceptible-Infectious-Recovered (SIR) model is known to have an exact semi-analytical solution. In the current study, the approach of Harko et al. (Appl. Math. Comput. 236:184–194, 2014) is generalised to obtain an approximate semi-analytical solution of the Susceptible-Exposed-Infectious-Recovered (SEIR) model. The SEIR model curves have nearly the same shapes as the SIR ones, but with a stretch factor applied to them across time that is related to the ratio of the incubation to infectious periods. This finding implies an approximate characteristic timescale, scaled by this stretch factor, that is universal to all SEIR models, which only depends on the basic reproduction number and initial fraction of the population that is infectious. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7653910/ doi: 10.1038/s41598-020-76563-8 id: cord-296867-6o4scan1 author: Hisada, Shohei title: Surveillance of early stage COVID-19 clusters using search query logs and mobile device-based location information date: 2020-10-29 words: 3803.0 sentences: 206.0 pages: flesch: 59.0 cache: ./cache/cord-296867-6o4scan1.txt txt: ./txt/cord-296867-6o4scan1.txt summary: title: Surveillance of early stage COVID-19 clusters using search query logs and mobile device-based location information In contrast, we utilized web search query logs per user to detect WSSCI and gather their location histories to identify locations they visited or passed through, resulting in COVID-19 cluster detection. In the Kitami area (Fig. 3a) , the WSSCI has a maximum cross-correlation of 0.766, determined 2 days after the change in the number of new patients. This study attempted to detect early clusters by identifying people who suspected their own COVID-19 infection using web search query logs and by extracting their location information. We utilized web search query log data and location information provided by Yahoo Japan Corporation 17 as signals for syndromic surveillance. Syndromic surveillance using search query logs and user location information from smartphones against COVID-19 clusters in Japan abstract: Two clusters of the coronavirus disease 2019 (COVID-19) were confirmed in Hokkaido, Japan, in February 2020. To identify these clusters, this study employed web search query logs of multiple devices and user location information from location-aware mobile devices. We anonymously identified users who used a web search engine (i.e., Yahoo! JAPAN) to search for COVID-19 or its symptoms. We regarded them as web searchers who were suspicious of their own COVID-19 infection (WSSCI). We extracted the location of WSSCI via a mobile operating system application and compared the spatio-temporal distribution of WSSCI with the actual location of the two known clusters. In the early stage of cluster development, we confirmed several WSSCI. Our approach was accurate in this stage and became biased after a public announcement of the cluster development. When other cluster-related resources, such as detailed population statistics, are not available, the proposed metric can capture hints of emerging clusters. url: https://www.ncbi.nlm.nih.gov/pubmed/33122686/ doi: 10.1038/s41598-020-75771-6 id: cord-305132-jspxlk1a author: Homma, Takujiro title: Persistent prion infection disturbs the function of Oct-1, resulting in the down-regulation of murine interferon regulatory factor-3 date: 2014-08-08 words: 3536.0 sentences: 248.0 pages: flesch: 56.0 cache: ./cache/cord-305132-jspxlk1a.txt txt: ./txt/cord-305132-jspxlk1a.txt summary: In this study, we analyzed murine IRF-3 promoter activity in detail and its relationship to prion infection, and have shown that the octamer-binding transcription factor-1 (Oct-1) positively regulates murine IRF-3, and the expression levels of Oct-1 decreased in prion-infected cells. Furthermore, in the persistently other prion strain-infected cells by the mouse-adapted Gerstmann-Sträussler-Schenker syndrome (GSS) Fukuoka-1 strain (FK-N2a58), IRF-3 mRNA and the promoter activity were also significantly decreased (Supplementary Fig. S6a and S6b). PCR analysis revealed that the Oct-1 antibody precipitated the promoter region (nt -119 to -1) from N2a58 cells (Fig. 4a) , while the negative control (anti-rabbit IgG) did not exhibit the DNA binding activity. These results demonstrate that reduced IRF-3 promoter activity in prion-infected cells is accompanied by decreased levels of Oct-1. In summary, our results demonstrated that Oct-1 binds to the murine IRF-3 promoter region and increases the transcription level and IRF-3 expression is reduced by prion infection. abstract: As a prompt response against invasion of various viruses, interferon regulatory factor-3 (IRF-3) is initially phosphorylated to become activated and upregulates mainly Type I Interferons (IFN-I) in most cell types. We previously reported that IRF-3-dependent host innate immune responses partially interfere in infection of prions. Here, we found that stable infection of prion suppressed IRF-3 gene-expression. The decreased promoter activity of IRF-3 was significantly restored along with treatment of anti-prion drugs in the prion-infected cells, suggesting that infection of prion directly influence the regulation of IRF-3 transcription. We further investigated promoter activity of 5′- flanking region of murine IRF-3 using a luciferase reporter system and found that the nucleotides -119 to -1 were indispensable for the promoter activity. Within this region, mutations in the Oct-1 binding site significantly reduced the promoter activity and chromatin immunoprecipitation (ChIP) assay revealed that Oct-1 indeed binds to the region. In addition, overexpression of Oct-1 increased the promoter activity of IRF-3. Intriguingly, Oct-1 protein was significantly reduced in prion-infected cells and mice brains compared with uninfected groups. Taken together, we concluded that prion infection could interfere in the function of Oct-1, resulting in the down-regulation of IRF-3. url: https://www.ncbi.nlm.nih.gov/pubmed/25103253/ doi: 10.1038/srep06006 id: cord-002045-m44fic4g author: Horie, Masayuki title: An RNA-dependent RNA polymerase gene in bat genomes derived from an ancient negative-strand RNA virus date: 2016-05-13 words: 4805.0 sentences: 312.0 pages: flesch: 59.0 cache: ./cache/cord-002045-m44fic4g.txt txt: ./txt/cord-002045-m44fic4g.txt summary: Endogenous bornavirus-like L (EBLL) elements are inheritable sequences derived from ancient bornavirus L genes that encode a viral RNA-dependent RNA polymerase (RdRp) in many eukaryotic genomes. Furthermore, we showed that the EBLLs evolved under purifying selection and still possess functional motifs conserved among the Mononegavirales RdRps. These results strongly suggest that the EBLL elements encode functional proteins that may be RdRps. ORF screening for these elements in several mammalian species and found an EBLL element in the bat species Eptesicus fuscus (designated efEBLL-1; accession number ALEH01013293). Notably, this element (eEBLL-1) contains a 1,718-amino acid ORF that was conserved for more than 11.8 MY and included almost all of the sequence motifs essential for the enzymatic activity of a RNA virus RdRp. To the best of our knowledge, eEBLL-1 is the first example of an RNA virus-derived RdRp encoded by the mammalian genome. abstract: Endogenous bornavirus-like L (EBLL) elements are inheritable sequences derived from ancient bornavirus L genes that encode a viral RNA-dependent RNA polymerase (RdRp) in many eukaryotic genomes. Here, we demonstrate that bats of the genus Eptesicus have preserved for more than 11.8 million years an EBLL element named eEBLL-1, which has an intact open reading frame of 1,718 codons. The eEBLL-1 coding sequence revealed that functional motifs essential for mononegaviral RdRp activity are well conserved in the EBLL-1 genes. Genetic analyses showed that natural selection operated on eEBLL-1 during the evolution of Eptesicus. Notably, we detected efficient transcription of eEBLL-1 in tissues from Eptesicus bats. To the best of our knowledge, this study is the first report showing that the eukaryotic genome has gained a riboviral polymerase gene from an ancient virus that has the potential to encode a functional RdRp. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4865735/ doi: 10.1038/srep25873 id: cord-331148-40gvay7i author: Hsieh, Yu-Chia title: Clinical characteristics of patients with laboratory-confirmed influenza A(H1N1)pdm09 during the 2013/2014 and 2015/2016 clade 6B/6B.1/6B.2-predominant outbreaks date: 2018-10-23 words: 3185.0 sentences: 166.0 pages: flesch: 43.0 cache: ./cache/cord-331148-40gvay7i.txt txt: ./txt/cord-331148-40gvay7i.txt summary: Independently, a retrospective cohort study (which enrolled 639 infected patients during the five seasons) was conducted at Chang Gung Memorial Hospital to explore the risk factors associated with influenza A(H1N1)pdm09-related complications. The results of the logistic regression analysis on the risk factors associated with influenza A(H1N1)pdm09-related complications and pneumonia are shown in Table 4 , and respiratory failure with mechanical ventilation and ARDS are also presented in Table 5 . In the univariate analysis, 6B/6B.1/6B.2 season, age (50-64 years), onset to presentation, underlying conditions, obesity, smoking, alcoholism, and antiviral therapy were significant risk factors of complications, pneumonia, mechanical ventilation, and ARDS (Tables 4 and 5 ). In the multivariate logistic regression analysis, 6B/6B.1/6B.2 season, age (50-64 years and ≥65 years), underlying conditions, and antiviral therapy were significant independent risk factors of complications, pneumonia, and mechanical ventilation (Tables 4 and 5). abstract: A novel pandemic influenza A(H1N1)pdm09 virus emerged in 2009 globally, and it continues to circulate in humans. The National Influenza Surveillance Network in Taiwan identified five A(H1N1)pdm09-predominant seasons, representing the 2009/2010, 2010/2011, 2012/2013, 2013/2014, and 2015/2016 outbreaks from 2009 to 2016. Independently, a retrospective cohort study (which enrolled 639 infected patients during the five seasons) was conducted at Chang Gung Memorial Hospital to explore the risk factors associated with influenza A(H1N1)pdm09-related complications. A phylogenetic analysis of hemagglutinin (HA) sequences showed that the circulating A(H1N1)pdm09 virus belonged to clades 1, 2, and 8 in 2009/2010; clades 3, 4, 5, and 7 in 2010/2011; clades 7 and 6C in 2012/2013; clades 6B in 2013/2014; and 6B/6B.1/6B.2 in 2015/2016. Compared to individuals infected in non-6B/6B.1/6B.2 seasons (2009/2010, 2010/2011, and 2012/2013), those infected in 6B/6B.1/6B.2 seasons (2013/2014 and 2015/2016) were at higher risk for influenza-related complications (adjusted odds ratio [aOR]: 1.6, 95% confidence interval [CI]: 1.0–2.8), pneumonia (aOR: 1.78, 95% CI: 1.04–3.04), mechanical ventilation (aOR: 2.6, 95% CI: 1.2–5.6), and acute respiratory distress syndrome (aOR: 5.5, 95% CI: 1.9–15.9). For the increased severity of infection during the influenza A(H1N1)pdm09 clade 6B/6B.1/6B.2 seasons, aspects related to the antigenic change of A(H1N1)pdm09 virus, immune response of the host, and environmental factors required further investigation. url: https://doi.org/10.1038/s41598-018-34077-4 doi: 10.1038/s41598-018-34077-4 id: cord-002373-rueg4gsj author: Huang, Ao title: Quantitative Fluorescence Quenching on Antibody-conjugated Graphene Oxide as a Platform for Protein Sensing date: 2017-01-13 words: 3674.0 sentences: 203.0 pages: flesch: 54.0 cache: ./cache/cord-002373-rueg4gsj.txt txt: ./txt/cord-002373-rueg4gsj.txt summary: Then, analyte IgG proteins in increasing concentrations were added to a set of buffer solutions containing antibody-conjugated GO. As the number density of the binding sites was limited on the modified GO, more adsorbed analyte IgG proteins resulted in a stronger fluorescence signal from free IgG-FITCs in the solutions. Therefore, there is a positive and quantitative correlation between the analyte IgG concentration and the fluorescence intensity of free IgG-FITCs. According to this principle, our assay relies on the effectiveness of GO as an energy acceptor to provide efficient fluorescence quenching. The experiment was repeated 4 times, and the average of the results was plotted in Fig. 4(a) , from which we can see the assay''s fluorescence signal increased readily with the increasing analyte IgG concentration. We established an immunosensor platform based on quantitative fluorescence quenching between fluorescein-labelled antigens and antibody-conjugated GO nanosheets, a process controlled quantitatively by the concentration of analyte proteins. abstract: We created an immunosensing platform for the detection of proteins in a buffer solution. Our sensing platform relies on graphene oxide (GO) nanosheets conjugated with antibodies to provide quantitative binding sites for analyte proteins. When analyte proteins and standard fluorescein-labelled proteins are competing for the binding sites, the assay exhibits quantitative fluorescence quenching by GO for the fluorescein-labelled proteins as determined by the analyte protein concentration. Because of this mechanism, measured fluorescence intensity from unquenched fluorescein-labelled protein was shown to increase with an increasing analyte protein concentration. As an alternative to the conventional enzyme-linked immunosorbent assay (ELISA), our method does not require an enzyme-linked second antibody for protein recognition and the enzyme for optical signal measurement. Thus, it is beneficial with its low cost and fewer systematic errors caused by the series of antigen-antibody recognition steps in ELISA. Immune globulin G (IgG) was introduced as a model protein to test our method and our results showed that the limit of detection for IgG was 4.67 pmol mL(−1) in the buffer solution. This sensing mechanism could be developed into a promising biosensor for the detection of proteins, which would broaden the spectrum of GO applications in both analytical biochemistry and clinical diagnosis. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5233999/ doi: 10.1038/srep40772 id: cord-336493-ggo9wsrm author: Huang, Stephen S. H. title: Immunity toward H1N1 influenza hemagglutinin of historical and contemporary strains suggests protection and vaccine failure date: 2013-04-23 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Evolution of H1N1 influenza A outbreaks of the past 100 years is interesting and significantly complex and details of H1N1 genetic drift remains unknown. Here we investigated the clinical characteristics and immune cross-reactivity of significant historical H1N1 strains. We infected ferrets with H1N1 strains from 1943, 1947, 1977, 1986, 1999, and 2009 and showed each produced a unique clinical signature. We found significant cross-reactivity between viruses with similar HA sequences. Interestingly, A/FortMonmouth/1/1947 antisera cross-reacted with A/USSR/90/1977 virus, thought to be a 1947 resurfaced virus. Importantly, our immunological data that didn't show cross-reactivity can be extrapolated to failure of past H1N1 influenza vaccines, ie. 1947, 1986 and 2009. Together, our results help to elucidate H1N1 immuno-genetic alterations that occurred in the past 100 years and immune responses caused by H1N1 evolution. This work will facilitate development of future influenza therapeutics and prophylactics such as influenza vaccines. url: https://doi.org/10.1038/srep01698 doi: 10.1038/srep01698 id: cord-325657-s2vdazq0 author: Huang, Yan-Jang S. title: SARS-CoV-2 failure to infect or replicate in mosquitoes: an extreme challenge date: 2020-07-17 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: This research addresses public speculation that SARS-CoV-2 might be transmitted by mosquitoes. The World Health Organization has stated “To date there has been no information nor evidence to suggest that the new coronavirus could be transmitted by mosquitoes”. Here we provide the first experimental data to investigate the capacity of SARS-CoV-2 to infect and be transmitted by mosquitoes. Three widely distributed species of mosquito; Aedes aegypti, Ae. albopictus and Culex quinquefasciatus, representing the two most significant genera of arbovirus vectors that infect people, were tested. We demonstrate that even under extreme conditions, SARS-CoV-2 virus is unable to replicate in these mosquitoes and therefore cannot be transmitted to people even in the unlikely event that a mosquito fed upon a viremic host. url: https://doi.org/10.1038/s41598-020-68882-7 doi: 10.1038/s41598-020-68882-7 id: cord-265211-a7whyds8 author: Hussein, Hosni A. M. title: miRNA-36 inhibits KSHV, EBV, HSV-2 infection of cells via stifling expression of interferon induced transmembrane protein 1 (IFITM1) date: 2017-12-21 words: 5486.0 sentences: 375.0 pages: flesch: 55.0 cache: ./cache/cord-265211-a7whyds8.txt txt: ./txt/cord-265211-a7whyds8.txt summary: title: miRNA-36 inhibits KSHV, EBV, HSV-2 infection of cells via stifling expression of interferon induced transmembrane protein 1 (IFITM1) In this study, we show the ability of host cell novel miR-36 to specifically inhibit KSHV-induced expression of interferon induced transmembrane protein 1 (IFITM1) to limit virus infection of cells. Transfecting cells with miR-36 mimic specifically lowered IFITM1 expression and thereby significantly dampening KSHV infection. The doses of the mimic In panels ''C and D'' , Student t test was performed to study the effect of HS and compare infection of cells with KSHV versus UV.KSHV on miR-36 expression at 5, 10, 15, and 30 min PI. Transfection of BJAB (Fig. 2C ) and HMVEC-d (Fig. 2D ) cells with miR-36 mimic significantly reduced KSHV infection of cells as monitored by the expression of ORF50 gene as early as 30 min PI. Interestingly, the effect of miR-36 mimic on KSHV infection of BJAB and HMVEC-d cells could be significantly reversed by co-transfecting cells with 10 nM of miR-36 inhibitor (Fig. 2E ). abstract: Kaposi’s sarcoma-associated herpesvirus (KSHV) is etiologically associated with all forms of Kaposi’s sarcoma worldwide. Little is currently known about the role of microRNAs (miRNAs) in KSHV entry. We recently demonstrated that KSHV induces a plethora of host cell miRNAs during the early stages of infection. In this study, we show the ability of host cell novel miR-36 to specifically inhibit KSHV-induced expression of interferon induced transmembrane protein 1 (IFITM1) to limit virus infection of cells. Transfecting cells with miR-36 mimic specifically lowered IFITM1 expression and thereby significantly dampening KSHV infection. In contrast, inhibition of miR-36 using miR-36 inhibitor had the direct opposite effect on KSHV infection of cells, allowing enhanced viral infection of cells. The effect of miR-36 on KSHV infection of cells was at a post-binding stage of virus entry. The highlight of this work was in deciphering a common theme in the ability of miR-36 to regulate infection of closely related DNA viruses: KSHV, Epstein-Barr virus (EBV), and herpes simplexvirus-2 (HSV-2). Taken together, we report for the first time the ability of host cell miRNA to regulate internalization of KSHV, EBV, and HSV-2 in hematopoietic and endothelial cells. url: https://doi.org/10.1038/s41598-017-18225-w doi: 10.1038/s41598-017-18225-w id: cord-003055-88q36g00 author: Imai, Kenji title: Administration of molecular hydrogen during pregnancy improves behavioral abnormalities of offspring in a maternal immune activation model date: 2018-06-15 words: 6212.0 sentences: 313.0 pages: flesch: 41.0 cache: ./cache/cord-003055-88q36g00.txt txt: ./txt/cord-003055-88q36g00.txt summary: The aim of the present study was to investigate long-term outcomes of the offspring in a lipopolysaccharide (LPS)-induced maternal immune activation (MIA) model and the effect of maternal molecular hydrogen (H(2)) administration. We have previously demonstrated in the MIA mouse model that maternal administration of H(2) attenuates oxidative damage and neuroinflammation, including induced pro-inflammatory cytokines and microglial activation, in the fetal brain. Since MIA has been considered to be a cause of behavioral abnormalities in offspring, including ASD/ Schizophrenia-like behavior, we subsequently evaluated the effect of LPS and maternal administration of HW on short-term memory, sociability, social novelty, and sensorimotor gating. Based on those findings, we subsequently performed Nissl staining and evaluated the number of neurons in the amygdala, cerebral cortex, and hippocampus to investigate the brain regions related to the results of the behavioral deficits induced by LPS exposure. abstract: The aim of the present study was to investigate long-term outcomes of the offspring in a lipopolysaccharide (LPS)-induced maternal immune activation (MIA) model and the effect of maternal molecular hydrogen (H(2)) administration. We have previously demonstrated in the MIA mouse model that maternal administration of H(2) attenuates oxidative damage and neuroinflammation, including induced pro-inflammatory cytokines and microglial activation, in the fetal brain. Short-term memory, sociability and social novelty, and sensorimotor gating were evaluated using the Y-maze, three-chamber, and prepulse inhibition (PPI) tests, respectively, at postnatal 3 or 4 weeks. The number of neurons and oligodendrocytes was also analyzed at postnatal 5 weeks by immunohistochemical analysis. Offspring of the LPS-exposed dams showed deficits in short-term memory and social interaction, following neuronal and oligodendrocytic loss in the amygdala and cortex. Maternal H(2) administration markedly attenuated these LPS-induced abnormalities. Moreover, we evaluated the effect of H(2) on LPS-induced astrocytic activation, both in vivo and in vitro. The number of activated astrocytes with hypertrophic morphology was increased in LPS-exposed offspring, but decreased in the offspring of H(2)-administered dams. In primary cultured astrocytes, LPS-induced pro-inflammatory cytokines were attenuated by H(2) administration. Overall, these findings indicate that maternal H(2) administration exerts neuroprotective effects and ameliorates MIA-induced neurodevelopmental deficits of offspring later in life. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6003913/ doi: 10.1038/s41598-018-27626-4 id: cord-338142-acqiyqwz author: Jeong, Hye Jin title: Signal amplification by reversible exchange for COVID-19 antiviral drug candidates date: 2020-08-31 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Several drug candidates have been proposed and tested as the latest clinical treatment for coronavirus pneumonia (COVID-19). Chloroquine, hydroxychloroquine, ritonavir/lopinavir, and favipiravir are under trials for the treatment of this disease. The hyperpolarization technique has the ability to further provide a better understanding of the roles of these drugs at the molecular scale and in different applications in the field of nuclear magnetic resonance/magnetic resonance imaging. This technique may provide new opportunities in diagnosis and research of COVID-19. Signal amplification by reversible exchange-based hyperpolarization studies on large-sized drug candidates were carried out. We observed hyperpolarized proton signals from whole structures, due to the unprecedented long-distance polarization transfer by para-hydrogen. We also found that the optimal magnetic field for the maximum polarization transfer yield was dependent on the molecular structure. We can expect further research on the hyperpolarization of other important large molecules, isotope labeling, as well as polarization transfer on nuclei with a long spin relaxation time. A clinical perspective of these features on drug molecules can broaden the application of hyperpolarization techniques for therapeutic studies. url: https://doi.org/10.1038/s41598-020-71282-6 doi: 10.1038/s41598-020-71282-6 id: cord-305473-w30hsr4m author: Jiang, Lili title: Detection of viral respiratory pathogens in mild and severe acute respiratory infections in Singapore date: 2017-02-20 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: To investigate the performance of laboratory methods and clinical case definitions in detecting the viral pathogens for acute respiratory infections (ARIs) from a prospective community cohort and hospital inpatients, nasopharyngeal swabs from cohort members reporting ARIs (community-ARI) and inpatients admitted with ARIs (inpatient-ARI) were tested by Singleplex Real Time-Polymerase Chain Reaction (SRT-PCR), multiplex RT-PCR (MRT-PCR) and pathogen-chip system (PathChip) between April 2012 and December 2013. Community-ARI and inpatient-ARI was also combined with mild and severe cases of influenza from a historical prospective study as mild-ARI and severe-ARI respectively to evaluate the performance of clinical case definitions. We analysed 130 community-ARI and 140 inpatient-ARI episodes (5 inpatient-ARI excluded because multiple pathogens were detected), involving 138 and 207 samples respectively. Detection by PCR declined with days post-onset for influenza virus; decrease was faster for community-ARI than for inpatient-ARI. No such patterns were observed for non-influenza respiratory virus infections. PathChip added substantially to viruses detected for community-ARI only. Clinical case definitions discriminated influenza from other mild-ARI but performed poorly for severe-ARI and for older participants. Rational strategies for diagnosis and surveillance of influenza and other respiratory virus must acknowledge the differences between ARIs presenting in community and hospital settings. url: https://doi.org/10.1038/srep42963 doi: 10.1038/srep42963 id: cord-351659-ujbxsus4 author: Jiang, Xiandeng title: A retrospective analysis of the dynamic transmission routes of the COVID-19 in mainland China date: 2020-08-19 words: 4367.0 sentences: 252.0 pages: flesch: 56.0 cache: ./cache/cord-351659-ujbxsus4.txt txt: ./txt/cord-351659-ujbxsus4.txt summary: We propose a time-varying sparse vector autoregressive (VAR) model to retrospectively analyze and visualize the dynamic transmission routes of this outbreak in mainland China over January 31–February 19, 2020. Our results demonstrate that the influential inter-location routes from Hubei have become unidentifiable since February 4, 2020, whereas the self-transmission in each provincial-level administrative region (location, hereafter) was accelerating over February 4–15, 2020. Implications of our results suggest that in addition to the origin of the outbreak, virus preventions are of crucial importance in locations with the largest migrant workers percentages (e.g., Jiangxi, Henan and Anhui) to controlling the spread of COVID-19. This enables the detection and visualization of time-varying inter-location and self-transmission routes of the COVID-19 on the daily basis. On the fifth day (February 4, 2020), no influential transmission routes were found from Hubei to directly affect other locations, and there were only three influential routes identified nationally, including Zhejiang-Shaanxi, www.nature.com/scientificreports/ Zhejiang-Jiangxi and Jiangxi-Shanghai. abstract: The fourth outbreak of the Coronaviruses, known as the COVID-19, has occurred in Wuhan city of Hubei province in China in December 2019. We propose a time-varying sparse vector autoregressive (VAR) model to retrospectively analyze and visualize the dynamic transmission routes of this outbreak in mainland China over January 31–February 19, 2020. Our results demonstrate that the influential inter-location routes from Hubei have become unidentifiable since February 4, 2020, whereas the self-transmission in each provincial-level administrative region (location, hereafter) was accelerating over February 4–15, 2020. From February 16, 2020, all routes became less detectable, and no influential transmissions could be identified on February 18 and 19, 2020. Such evidence supports the effectiveness of government interventions, including the travel restrictions in Hubei. Implications of our results suggest that in addition to the origin of the outbreak, virus preventions are of crucial importance in locations with the largest migrant workers percentages (e.g., Jiangxi, Henan and Anhui) to controlling the spread of COVID-19. url: https://doi.org/10.1038/s41598-020-71023-9 doi: 10.1038/s41598-020-71023-9 id: cord-004222-z4butywi author: Joyce, Collin title: Comparisons of the antibody repertoires of a humanized rodent and humans by high throughput sequencing date: 2020-01-24 words: 3718.0 sentences: 187.0 pages: flesch: 46.0 cache: ./cache/cord-004222-z4butywi.txt txt: ./txt/cord-004222-z4butywi.txt summary: We characterized the heavy chain and kappa light chain antibody repertoires of a model animal, the OmniRat, by high throughput antibody sequencing and made use of two novel datasets for comparison to human repertoires. Multiple differences were found in both the heavy and kappa chain repertoires between OmniRats and humans including gene segment usage, CDR3 length distributions, class switch recombination, somatic hypermutation levels and in features of V(D)J recombination. We individually separated total RNA from spleens and lymph nodes of three unimmunized OmniRats and PCR amplified the heavy and kappa chain antibody V gene segments. We started by making intra-animal comparisons, intra-species comparisons and inter-species comparisons of the immunoglobulin gene segment usage frequencies for each antibody repertoire by performing hierarchical clustering ( Fig. 1 ) and linear regression analysis (Figs. abstract: The humanization of animal model immune systems by genetic engineering has shown great promise for antibody discovery, tolerance studies and for the evaluation of vaccines. Assessment of the baseline antibody repertoires of unimmunized model animals will be useful as a benchmark for future immunization experiments. We characterized the heavy chain and kappa light chain antibody repertoires of a model animal, the OmniRat, by high throughput antibody sequencing and made use of two novel datasets for comparison to human repertoires. Intra-animal and inter-animal repertoire comparisons reveal a high level of conservation in antibody diversity between the lymph node and spleen and between members of the species. Multiple differences were found in both the heavy and kappa chain repertoires between OmniRats and humans including gene segment usage, CDR3 length distributions, class switch recombination, somatic hypermutation levels and in features of V(D)J recombination. The Inference and Generation of Repertoires (IGoR) software tool was used to model recombination in VH regions which allowed for the quantification of some of these differences. Diversity estimates of the OmniRat heavy chain repertoires almost reached that of humans, around two orders of magnitude less. Despite variation between the species repertoires, a high frequency of OmniRat clonotypes were also found in the human repertoire. These data give insights into the development and selection of humanized animal antibodies and provide actionable information for use in vaccine studies. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6981180/ doi: 10.1038/s41598-020-57764-7 id: cord-355179-wmfwl2bh author: Jung, Eunhye title: Neutralization of Acidic Intracellular Vesicles by Niclosamide Inhibits Multiple Steps of the Dengue Virus Life Cycle In Vitro date: 2019-06-18 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Dengue fever is one of the most important mosquito-borne viral infections in large parts of tropical and subtropical countries and is a significant public health concern and socioeconomic burden. There is an urgent need to develop antivirals that can effectively reduce dengue virus (DENV) replication and decrease viral load. Niclosamide, an antiparasitic drug approved for human use, has been recently identified as an effective antiviral agent against a number of pH-dependent viruses, including flaviviruses. Here, we reveal that neutralization of low-pH intracellular compartments by niclosamide affects multiple steps of the DENV infectious cycle. Specifically, niclosamide-induced endosomal neutralization not only prevents viral RNA replication but also affects the maturation of DENV particles, rendering them non-infectious. We found that niclosamide-induced endosomal neutralization prevented E glycoprotein conformational changes on the virion surface of flaviviruses, resulting in the release of non-infectious immature virus particles with uncleaved pr peptide from host cells. Collectively, our findings support the potential application of niclosamide as an antiviral agent against flavivirus infection and highlight a previously uncharacterized mechanism of action of the drug. url: https://www.ncbi.nlm.nih.gov/pubmed/31213630/ doi: 10.1038/s41598-019-45095-1 id: cord-005507-equnyib7 author: Kamath, Kathy title: Antibody epitope repertoire analysis enables rapid antigen discovery and multiplex serology date: 2020-03-24 words: 5189.0 sentences: 261.0 pages: flesch: 38.0 cache: ./cache/cord-005507-equnyib7.txt txt: ./txt/cord-005507-equnyib7.txt summary: Given this, we developed serum epitope repertoire analysis (SERA), a method to rapidly discover conserved, pathogen-specific antigens and their epitopes, and applied it to develop an assay for Chagas disease caused by the protozoan parasite Trypanosoma cruzi. We applied serum epitope repertoire analysis (SERA) to discover shared, but highly specific immunogenic epitope motifs associated with Chagas disease caused by the protozoan parasite Trypanosoma cruzi, and thereby develop a serological assay. To identify antibody epitope motifs specific to Chagas disease, we applied the IMUNE motif discovery algorithm 15 (see Methods for parameters) to epitope repertoires from 28 Chagas specimens and 30 non-Chagas sera, yielding 331 candidate motifs (Supplementary Table S2 ). Using Chagas disease seropositive specimens, a panel of 31 peptide motifs was identified that exhibited 100% sensitivity (60/60) and 100% specificity (120/120) in independent validation sets. abstract: The detection of pathogen-specific antibodies remains a cornerstone of clinical diagnostics. Yet, many test exhibit undesirable performance or are completely lacking. Given this, we developed serum epitope repertoire analysis (SERA), a method to rapidly discover conserved, pathogen-specific antigens and their epitopes, and applied it to develop an assay for Chagas disease caused by the protozoan parasite Trypanosoma cruzi. Antibody binding peptide motifs were identified from 28 Chagas repertoires using a bacterial display random 12-mer peptide library and next-generation sequencing (NGS). Thirty-three motifs were selected and mapped to candidate Chagas antigens. In a blinded validation set (n = 72), 30/30 Chagas were positive, 30/30 non-Chagas were negative, and 1/12 Leishmania sp. was positive. After unblinding, a Leishmania cross-reactive epitope was identified and removed from the panel. The Chagas assay exhibited 100% sensitivity (30/30) and specificity (90/90) in a second blinded validation set including individuals with other parasitic infections. Amongst additional epitope repertoires with unknown Chagas serostatus, assay specificity was 99.8% (998/1000). Thus, the Chagas assay achieved a combined sensitivity and specificity equivalent or superior to diagnostic algorithms that rely on three separate tests to achieve high specificity. NGS-based serology via SERA provides an effective approach to discover antigenic epitopes and develop high performance multiplex serological assays. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7093460/ doi: 10.1038/s41598-020-62256-9 id: cord-271602-f14wccj3 author: Kim, Hyun Cheol title: Recent increase of surface particulate matter concentrations in the Seoul Metropolitan Area, Korea date: 2017-07-05 words: 3264.0 sentences: 170.0 pages: flesch: 45.0 cache: ./cache/cord-271602-f14wccj3.txt txt: ./txt/cord-271602-f14wccj3.txt summary: A 12-year (2004–2015) regional air quality simulation was conducted over East Asia (27-km) and over South Korea (9-km) to assess the impact of meteorology under constant anthropogenic emissions. Simulated PM concentrations show a strong negative correlation (i.e. R = −0.86) with regional wind speed, implying that reduced regional ventilation is likely associated with more stagnant conditions that cause severe pollutant episodes in South Korea. We conclude that the current PM concentration trend in South Korea is a combination of long-term decline by emission control efforts and short-term fluctuation of regional wind speed interannual variability. Three factors, long-term trend by emission control, short-term variation by meteorology, and sporadic offsets by unexpected social or economic episodes, seem to be affecting PM concentrations in South Korea. In order to investigate the interannual variation of surface PM concentration in the SMA, we conducted a 12-year simulation using a regional air quality modeling system. abstract: Recent changes of surface particulate matter (PM) concentration in the Seoul Metropolitan Area (SMA), South Korea, are puzzling. The long-term trend of surface PM concentration in the SMA declined in the 2000s, but since 2012 its concentrations have tended to incline, which is coincident with frequent severe hazes in South Korea. This increase puts the Korean government’s emission reduction efforts in jeopardy. This study reports that interannual variation of surface PM concentration in South Korea is closely linked with the interannual variations of wind speed. A 12-year (2004–2015) regional air quality simulation was conducted over East Asia (27-km) and over South Korea (9-km) to assess the impact of meteorology under constant anthropogenic emissions. Simulated PM concentrations show a strong negative correlation (i.e. R = −0.86) with regional wind speed, implying that reduced regional ventilation is likely associated with more stagnant conditions that cause severe pollutant episodes in South Korea. We conclude that the current PM concentration trend in South Korea is a combination of long-term decline by emission control efforts and short-term fluctuation of regional wind speed interannual variability. When the meteorology-driven variations are removed, PM concentrations in South Korea have declined continuously even after 2012. url: https://doi.org/10.1038/s41598-017-05092-8 doi: 10.1038/s41598-017-05092-8 id: cord-340105-471x03f9 author: Kim, Sung-Il title: Niclosamide inhibits leaf blight caused by Xanthomonas oryzae in rice date: 2016-02-16 words: 5612.0 sentences: 333.0 pages: flesch: 53.0 cache: ./cache/cord-340105-471x03f9.txt txt: ./txt/cord-340105-471x03f9.txt summary: First, to determine the minimum concentration of niclosamide that would block bacterial blight, we examined the niclosamide dosage effect on disease responses to the representative Xoo strain PXO99. These results clearly indicate that niclosamide blocks the development of rice leaf blight by directly inhibiting Xoo bacterial growth (Figs 2c and 3c) and/or by inducing defense-related gene expression (Fig. 6) . In conclusion, the results presented herein indicate that niclosamide protects rice plants from bacterial leaf blight by inhibiting Xoo growth, inducing SA accumulation, and/or by inducing the expression of defense-related gene pathways. To examine the systemic effect of niclosamide on Xoo-mediated leaf blight development, the fully expanded uppermost leaves of 80-day-old rice plants were inoculated with PXO99 by the leaf-clipping as described above. Plant growth-promoting rhizobacteria mediate induced systemic resistance in rice against bacterial leaf blight caused by Xanthomonas oryzae pv abstract: Rice leaf blight, which is caused by the bacterial pathogen Xanthomonas oryzae pv. oryzae (Xoo), results in huge losses in grain yield. Here, we show that Xoo-induced rice leaf blight is effectively controlled by niclosamide, an oral antihelminthic drug and molluscicide, which also functions as an anti-tumor agent. Niclosamide directly inhibited the growth of the three Xoo strains PXO99, 10208 and K3a. Niclosamide moved long distances from the site of local application to distant rice tissues. Niclosamide also increased the levels of salicylate and induced the expression of defense-related genes such as OsPR1 and OsWRKY45, which suppressed Xoo-induced leaf wilting. Niclosamide had no detrimental effects on vegetative/reproductive growth and yield. These combined results indicate that niclosamide can be used to block bacterial leaf blight in rice with no negative side effects. url: https://doi.org/10.1038/srep21209 doi: 10.1038/srep21209 id: cord-289932-dsysiefx author: Király, Kornél title: Glial cell type-specific changes in spinal dipeptidyl peptidase 4 expression and effects of its inhibitors in inflammatory and neuropatic pain date: 2018-02-22 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Altered pain sensations such as hyperalgesia and allodynia are characteristic features of various pain states, and remain difficult to treat. We have shown previously that spinal application of dipeptidyl peptidase 4 (DPP4) inhibitors induces strong antihyperalgesic effect during inflammatory pain. In this study we observed low level of DPP4 mRNA in the rat spinal dorsal horn in physiological conditions, which did not change significantly either in carrageenan-induced inflammatory or partial nerve ligation-generated neuropathic states. In naïve animals, microglia and astrocytes expressed DPP4 protein with one and two orders of magnitude higher than neurons, respectively. DPP4 significantly increased in astrocytes during inflammation and in microglia in neuropathy. Intrathecal application of two DPP4 inhibitors tripeptide isoleucin-prolin-isoleucin (IPI) and the antidiabetic drug vildagliptin resulted in robust opioid-dependent antihyperalgesic effect during inflammation, and milder but significant opioid-independent antihyperalgesic action in the neuropathic model. The opioid-mediated antihyperalgesic effect of IPI was exclusively related to mu-opioid receptors, while vildagliptin affected mainly delta-receptor activity, although mu- and kappa-receptors were also involved. None of the inhibitors influenced allodynia. Our results suggest pathology and glia-type specific changes of DPP4 activity in the spinal cord, which contribute to the development and maintenance of hyperalgesia and interact with endogenous opioid systems. url: https://doi.org/10.1038/s41598-018-21799-8 doi: 10.1038/s41598-018-21799-8 id: cord-352061-x6tt9kx5 author: Kiyota, Yasuhiro title: Smoking cessation increases levels of osteocalcin and uncarboxylated osteocalcin in human sera date: 2020-10-08 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Smoking is thought to be a risk factor for osteoporosis development; however, the consequences of stopping smoking for bone homeostasis remain unknown. Here we conducted two separate human studies and show that bone mineral density was significantly lower in smokers than in non-smokers. The first was an observational study of pre- and post-menopausal healthy female smokers and non-smokers; the second included 139 current smokers determined to stop smoking. In the second study, levels of bone formation markers such as osteocalcin and uncarboxylated osteocalcin significantly increased after successful smoking cessation, as verified by significantly reduced levels of serum cotinine, a nicotine metabolite. Moreover, nicotine administration to mice reduced bone mineral density and significantly increased the number of osteoclasts in bone. Reduced bone mass phenotypes seen in nicotine-treated mice were significantly increased following nicotine withdrawal, an outcome accompanied by significantly reduced serum levels of tartrate-resistant acid phosphatase, a bone resorption marker. Taken together, our findings suggest that bone homeostasis is perturbed but can be rescued by smoking cessation. url: https://doi.org/10.1038/s41598-020-73789-4 doi: 10.1038/s41598-020-73789-4 id: cord-002673-5a1rfi6k author: Knibb, Wayne title: Regional genetic diversity for NNV grouper viruses across the Indo-Asian region – implications for selecting virus resistance in farmed groupers date: 2017-09-06 words: 6692.0 sentences: 298.0 pages: flesch: 48.0 cache: ./cache/cord-002673-5a1rfi6k.txt txt: ./txt/cord-002673-5a1rfi6k.txt summary: This study uses statistical approaches and assessment of "characteristic attributes" (i.e. nucleotide positions that discriminate among strains) to assess whether published and new NNV RNA2 cds sequences show genetic differentiation over geography, host species and years. Within the red spotted grouper nervous necrosis virus (RGNNV) strain, to which all Asian grouper NNV belong, however, no one so far has reported evidence of genetic subgrouping by region, species or year in a formal statistical manner, especially when we restrict hosts just to Asian grouper. The goal of this report was to collate the most comprehensive data set to date on NNV RNA2 sequences for warm water Asian marine finfish, whether published and/or lodged in Genbank over the last 20 years, including some sequence data produced by our group for Vietnamese and Taiwanese grouper, to statistically test the data for evidence of NNV strain variation that associates with geography, host species and year and also to determine whether there are "characteristic attributes" that indicate regional (or host, year) specific differences among the strains. abstract: Grouper aquaculture around Asia is impacted by the nervous necrosis virus (NNV) and, in response, host resistance to this infection is being considered as a trait for selection. However efficient selection may be confounded if there are different genetic strains of NNV within and between regions and over years. This study uses statistical approaches and assessment of “characteristic attributes” (i.e. nucleotide positions that discriminate among strains) to assess whether published and new NNV RNA2 cds sequences show genetic differentiation over geography, host species and years. Rather clear evidence was found for regional strains of NNV. Interestingly, most of the geographic defining “characteristic attributes” were in codon position three, and not translated into differences for the protein capsid (i.e. they were synonymous variations), suggesting that while NNV strains were geographically isolated and had diverged in different regions for RNA sequences, selection had largely conserved the protein sequences among regions. The apparent selection constraint on the capsid protein may mitigate the risk that despite geographic subdivision, NNV strain variability will confound genetic selection for host resistance. The existence of regional Asian NNV strains may suggest that hatcheries are at risk from NNV not only from imported material but also from endemic reservoirs. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5587679/ doi: 10.1038/s41598-017-11263-4 id: cord-315781-dejh8q22 author: Konishi, Tomokazu title: Re-evaluation of the evolution of influenza H1 viruses using direct PCA date: 2019-12-17 words: 4590.0 sentences: 308.0 pages: flesch: 65.0 cache: ./cache/cord-315781-dejh8q22.txt txt: ./txt/cord-315781-dejh8q22.txt summary: It should be noted that avian viruses showed lower PC values and appeared around the centre of the PCA, while swine and human viruses exhibited extreme values (Figs. Thus, avian viruses had sequences that were similar to the average among samples at amino acids that were characteristic to the three groups of human and swine viruses: R, M, and U. Avian samples also showed characteristic motifs at other positions, which may appear in lower PCs. The relationships observed among the strains presented here are different from the classic ones 4, [8] [9] [10] [11] [12] in several elements. www.nature.com/scientificreports www.nature.com/scientificreports/ One of the major differences observed was the direct shift from avian to swine or human viruses. Drifts and spreading: the genomes of the R group of human viruses have been changing yearly (Figs. abstract: The history of influenza H1 virus was re-evaluated by applying a new methodology to sequencing data; this objective method enables comparisons among viral types. The approach led to the segregation of all segments of swine and human viruses into three distinct groups: two of them included the pandemic 1977 and 2009 human viruses, and the remaining group may be new in humans. These three groups might have originated from avian viruses and drifted out independently. Genome shifts occurred occasionally among swine viruses; however, distances between avian and swine/human viruses negated the existence of direct shifts from avian viruses. In humans, only one or two viruses appeared each year, which suggests the presence of competition among viruses that migrated freely. All segments drifted continuously under certain rules and constant velocity. Viruses that had caused an outbreak did not appear again over subsequent decades, which may mean populations had become immune to such viruses. In contrast, the viruses in livestock were rather conserved and maintained unique strains in small, separate areas. Such collections of swine strains included human segments, which could become an epidemic in the future. url: https://doi.org/10.1038/s41598-019-55254-z doi: 10.1038/s41598-019-55254-z id: cord-284582-xwedgllw author: Korabecna, M. title: Cell-free DNA in plasma as an essential immune system regulator date: 2020-10-15 words: 5714.0 sentences: 306.0 pages: flesch: 46.0 cache: ./cache/cord-284582-xwedgllw.txt txt: ./txt/cord-284582-xwedgllw.txt summary: These expression profiles provide evidence that the presence of cfDNA and its clearance in plasma of healthy individuals regulate fundamental mechanisms of the inflammation process and tissue homeostasis. We used native human plasma samples obtained from healthy volunteers with no animal serum addition to the cultivation medium in order to avoid the presence of uncharacterized animal cfDNA and DNases in the experiments. We used the validation phase results to perform a direct comparison of signaling pathways activated in cells as a consequence of their treatment with NP or TP samples (Table 1a , b) using the database Reactome. The changes in expression profiles of selected validated genes were detectable after the decrease of cfDNA levels to 69.10% of its original native concentration as the result of endogenous DNAse I activity ( Supplementary Fig. 1 ). However, the cells treated with identical plasma samples with degraded cfDNA directly activate IIR with elevated production of mRNA for interleukin 8 at the transcriptomic level. abstract: The cell-free DNA (cfDNA) is always present in plasma, and it is biomarker of growing interest in prenatal diagnostics as well as in oncology and transplantology for therapy efficiency monitoring. But does this cfDNA have a physiological role? Here we show that cfDNA presence and clearance in plasma of healthy individuals plays an indispensable role in immune system regulation. We exposed THP1 cells to healthy individuals’ plasma with (NP) and without (TP) cfDNA. In cells treated with NP, we found elevated expression of genes whose products maintain immune system homeostasis. Exposure of cells to TP triggered an innate immune response (IIR), documented particularly by elevated expression of pro-inflammatory interleukin 8. The results of mass spectrometry showed a higher abundance of proteins associated with IIR activation due to the regulation of complement cascade in cells cultivated with TP. These expression profiles provide evidence that the presence of cfDNA and its clearance in plasma of healthy individuals regulate fundamental mechanisms of the inflammation process and tissue homeostasis. The detailed understanding how neutrophil extracellular traps and their naturally occurring degradation products affect the performance of immune system is of crucial interest for future medical applications. url: https://doi.org/10.1038/s41598-020-74288-2 doi: 10.1038/s41598-020-74288-2 id: cord-004416-qw6tusd2 author: Krishna, Smriti M. title: Development of a two-stage limb ischemia model to better simulate human peripheral artery disease date: 2020-02-26 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Peripheral arterial disease (PAD) develops due to the narrowing or blockage of arteries supplying blood to the lower limbs. Surgical and endovascular interventions are the main treatments for advanced PAD but alternative and adjunctive medical therapies are needed. Currently the main preclinical experimental model employed in PAD research is based on induction of acute hind limb ischemia (HLI) by a 1-stage procedure. Since there are concerns regarding the ability to translate findings from this animal model to patients, we aimed to develop a novel clinically relevant animal model of PAD. HLI was induced in male Apolipoprotein E (ApoE(−/−)) deficient mice by a 2-stage procedure of initial gradual femoral artery occlusion by ameroid constrictors for 14 days and subsequent excision of the femoral artery. This 2-stage HLI model was compared to the classical 1-stage HLI model and sham controls. Ischemia severity was assessed using Laser Doppler Perfusion Imaging (LDPI). Ambulatory ability was assessed using an open field test, a treadmill test and using established scoring scales. Molecular markers of angiogenesis and shear stress were assessed within gastrocnemius muscle tissue samples using quantitative polymerase chain reaction. HLI was more severe in mice receiving the 2-stage compared to the 1-stage ischemia induction procedure as assessed by LDPI (p = 0.014), and reflected in a higher ischemic score (p = 0.004) and lower average distance travelled on a treadmill test (p = 0.045). Mice undergoing the 2-stage HLI also had lower expression of angiogenesis markers (vascular endothelial growth factor, p = 0.004; vascular endothelial growth factor- receptor 2, p = 0.008) and shear stress response mechano-transducer transient receptor potential vanilloid 4 (p = 0.041) within gastrocnemius muscle samples, compared to animals having the 1-stage HLI procedure. Mice subjected to the 2-stage HLI receiving an exercise program showed significantly greater improvement in their ambulatory ability on a treadmill test than a sedentary control group. This study describes a novel model of HLI which leads to more severe and sustained ischemia than the conventionally used model. Exercise therapy, which has established efficacy in PAD patients, was also effective in this new model. This new model maybe useful in the evaluation of potential novel PAD therapies. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7044206/ doi: 10.1038/s41598-020-60352-4 id: cord-002720-lrkscs71 author: Kurosaki, Yohei title: Development and evaluation of a rapid molecular diagnostic test for Zika virus infection by reverse transcription loop-mediated isothermal amplification date: 2017-10-18 words: 4950.0 sentences: 251.0 pages: flesch: 55.0 cache: ./cache/cord-002720-lrkscs71.txt txt: ./txt/cord-002720-lrkscs71.txt summary: title: Development and evaluation of a rapid molecular diagnostic test for Zika virus infection by reverse transcription loop-mediated isothermal amplification The assay detected viral RNA at 14.5 TCID(50)/mL in virus-spiked serum or urine samples within 15 min, although it was slightly less sensitive than reference real time RT-PCR assay. We then evaluated the utility of this assay as a molecular diagnostic test using 90 plasma or serum samples and 99 urine samples collected from 120 suspected cases of arbovirus infection in the states of Paraíba and Pernambuco, Brazil in 2016. Therefore, it is difficult to detect ZIKV in blood samples from patients after the acute phase of infection, even with sensitive molecular diagnostic methods, such as reverse transcription-polymerase chain reaction (RT-PCR) 14, 18, 19 . These results suggested that the RT-LAMP assay could be used as a rapid, sensitive diagnostic test for ZIKV, the Tp value (i.e., less than 15 min) can be used as an indicator of the number of RNA copies in each reaction. abstract: The recent outbreak of Zika virus (ZIKV) disease caused an enormous number of infections in Central and South America, and the unusual increase in the number of infants born with microcephaly associated with ZIKV infection aroused global concern. Here, we developed a reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay using a portable device for the detection of ZIKV. The assay specifically detected ZIKV strains of both Asian and African genotypes without cross-reactivity with other arboviruses, including Dengue and Chikungunya viruses. The assay detected viral RNA at 14.5 TCID(50)/mL in virus-spiked serum or urine samples within 15 min, although it was slightly less sensitive than reference real time RT-PCR assay. We then evaluated the utility of this assay as a molecular diagnostic test using 90 plasma or serum samples and 99 urine samples collected from 120 suspected cases of arbovirus infection in the states of Paraíba and Pernambuco, Brazil in 2016. The results of this assay were consistent with those of the reference RT-PCR test. This portable RT-LAMP assay was highly specific for ZIKV, and enable rapid diagnosis of the virus infection. Our results provide new insights into ZIKV molecular diagnostics and may improve preparedness for future outbreaks. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5647432/ doi: 10.1038/s41598-017-13836-9 id: cord-335055-gzuug3p5 author: Kwiyolecha, Elizabeth title: Patterns of viral pathogens causing upper respiratory tract infections among symptomatic children in Mwanza, Tanzania date: 2020-10-28 words: 3311.0 sentences: 196.0 pages: flesch: 45.0 cache: ./cache/cord-335055-gzuug3p5.txt txt: ./txt/cord-335055-gzuug3p5.txt summary: title: Patterns of viral pathogens causing upper respiratory tract infections among symptomatic children in Mwanza, Tanzania Therefore, there is a paramount need to establish information on the common etiologies of RTIs in Tanzania, the information that can stimulate further studies and possible control interventions including introduction of cheap and reliable methods to detect these pathogens in clinical settings. In addition due to increased use of antibiotic without a support of a diagnostic test in the treatment of URTI as observed in number of previous studies [11] [12] [13] , make the availability of epidemiological data on the patterns of etiology of URTI of paramount important. A cross sectional hospital based study involving 339 children aged 1-59 months presenting with RTI symptoms was conducted from October 2017 to February 2018 in the city of Mwanza, Tanzania. A previous study 33 , documented Rhinovirus to cause up to 25-85% of the upper respiratory tract infections. abstract: Upper-respiratory tract infections (URTI) are the leading causes of childhood morbidities. This study investigated etiologies and patterns of URTI among children in Mwanza, Tanzania. A cross-sectional study involving 339 children was conducted between October-2017 and February-2018. Children with features suggestive of URTI such as nasal congestion, dry cough, painful swallowing and nasal discharge with/without fever were enrolled. Pathogens were detected from nasopharyngeal and ear-swabs by multiplex-PCR and culture respectively. Full blood count and C-reactive protein analysis were also done. The median age was 16 (IQR: 8–34) months. Majority (82.3%) had fever and nasal-congestion (65.5%). Rhinitis (55.9%) was the commonest diagnosis followed by pharyngitis (19.5%). Viruses were isolated in 46% of children, the commonest being Rhinoviruses (23.9%). Nineteen percent of children had more than 2 viruses; Rhinovirus and Enterovirus being the commonest combination. The commonest bacteria isolated from ears were Staphylococcus aureus and Pseudomonas aeruginosa. Children with viral pathogens had significantly right shift of lymphocytes (73%—sensitivity). Majority (257/339) of children were symptoms free on eighth day. Viruses are the commonest cause of URTI with Rhinitis being the common diagnosis. Rapid diagnostic assays for URTI pathogens are urgently needed in low-income countries to reduce unnecessary antibiotic prescriptions which is associated with antibiotic resistance. url: https://doi.org/10.1038/s41598-020-74555-2 doi: 10.1038/s41598-020-74555-2 id: cord-001901-2s6hpakk author: Kwok, Hoi-Hin title: Anti-inflammatory effects of indirubin derivatives on influenza A virus-infected human pulmonary microvascular endothelial cells date: 2016-01-06 words: 3922.0 sentences: 254.0 pages: flesch: 44.0 cache: ./cache/cord-001901-2s6hpakk.txt txt: ./txt/cord-001901-2s6hpakk.txt summary: title: Anti-inflammatory effects of indirubin derivatives on influenza A virus-infected human pulmonary microvascular endothelial cells In this report, we examined the potential immunomodulatory effects of two indirubin derivatives, indirubin-3′-(2,3-dihydroxypropyl)-oximether (E804) and indirubin-3′-oxime (E231), on IAV (H9N2) infected-human pulmonary microvascular endothelial cells (HPMECs). Using specific inhibitors or small-interfering RNA, we confirmed that indirubin derivatives can suppress H9N2-induced cytokines production through MAPKs and STAT3 signaling pathways. To detect the activity of individual MAPKs after treatment with IAV and indirubin derivatives, the non-radioactive In vitro protein kinase assay kit from Cell Signaling Technology was used. In this study, we found that the infection of influenza A virus subtype A/Quali/Hong Kong/G1/97 (H9N2) on HPMECs induced excessive production of various pro-inflammatory cytokines and chemokines, including IP-10 ( In this report, we demonstrated that indirubin derivatives, particularly E804 is a potent immunomodulatory compound for IAV-infection in vitro by inhibiting intracellular signaling pathways in pulmonary endothelial cells. abstract: Influenza A virus (IAV) poses global threats to human health. Acute respiratory distress syndrome and multi-organ dysfunction are major complications in patients with severe influenza infection. This may be explained by the recent studies which highlighted the role of the pulmonary endothelium as the center of innate immune cells recruitment and excessive pro-inflammatory cytokines production. In this report, we examined the potential immunomodulatory effects of two indirubin derivatives, indirubin-3′-(2,3-dihydroxypropyl)-oximether (E804) and indirubin-3′-oxime (E231), on IAV (H9N2) infected-human pulmonary microvascular endothelial cells (HPMECs). Infection of H9N2 on HPMECs induced a high level of chemokines and cytokines production including IP-10, RANTES, IL-6, IFN-β and IFN-γ1. Post-treatment of E804 or E231 could significantly suppress the production of these cytokines. H9N2 infection rapidly triggered the activation of innate immunity through phosphorylation of signaling molecules including mitogen-activated protein kinases (MAPKs) and signal transducer and activator of transcription (STAT) proteins. Using specific inhibitors or small-interfering RNA, we confirmed that indirubin derivatives can suppress H9N2-induced cytokines production through MAPKs and STAT3 signaling pathways. These results underscore the immunomodulatory effects of indirubin derivatives on pulmonary endothelium and its therapeutic potential on IAV-infection. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4702174/ doi: 10.1038/srep18941 id: cord-351295-4toxlskr author: Lanave, Gianvito title: Identification of hepadnavirus in the sera of cats date: 2019-07-23 words: 2665.0 sentences: 159.0 pages: flesch: 48.0 cache: ./cache/cord-351295-4toxlskr.txt txt: ./txt/cord-351295-4toxlskr.txt summary: Also, in 7/10 animals with suspected hepatic disease, virus load was >10(4) genome copies per mL, i.e. above the threshold considered at risk of active hepatitis and liver damage for HBV. DCH DNA was detected in 31 (17.8%) out of 174 sera collected with a request for diagnosis of infectious diseases (collection A) and in 11 (5.1%) out of 216 sera submitted to the laboratory for pre-surgical evaluation or for suspected metabolic or neoplastic disease (collection B) that were used to generate a baseline. In this study we observed a marked and significantly higher prevalence (17.8%, 31/174) in the cohort of cats with suspected infectious diseases (collection A) with respect to a group of animals (collection B) used as baseline. Almost half of the sera positive for DCH (14/31, 45 .2%) of this cohort were collected from cats with retroviral infection (FIV and/or feline leukemia virus, FeLV). abstract: Hepadnaviruses infect several animal species. The prototype species, human hepatitis B virus (HBV), increases the risk of liver diseases and may cause cirrhosis and hepatocellular carcinoma. Recently a novel hepadnavirus, similar to HBV, has been identified through transcriptomics studies in a domestic cat with large cell lymphoma in Australia. Herewith, a collection of 390 feline serum samples was screened for hepadnavirus. Overall, the virus was identified in 10.8% of the sera with a significantly higher prevalence (17.8%) in the sera of animals with a clinical suspect of infectious disease. Upon genome sequencing, the virus was closely related (97.0% nt identity) to the prototype Australian feline virus Sydney 2016. The mean and median values of hepadnavirus in the feline sera were 1.3 × 10(6) and 2.1 × 10(4) genome copies per mL (range 3.3 × 10(0)–2.5 × 10(7) genome copies per mL). For a subset of hepadnavirus-positive samples, information on the hemato-chemical parameters was available and in 10/20 animals a profile suggestive of liver damage was present. Also, in 7/10 animals with suspected hepatic disease, virus load was >10(4) genome copies per mL, i.e. above the threshold considered at risk of active hepatitis and liver damage for HBV. url: https://www.ncbi.nlm.nih.gov/pubmed/31337847/ doi: 10.1038/s41598-019-47175-8 id: cord-293747-ds8rhbkv author: Lani, Rafidah title: Antiviral activity of silymarin against chikungunya virus date: 2015-06-16 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The mosquito-borne chikungunya virus (CHIKV) causes chikungunya fever, with clinical presentations such as severe back and small joint pain, and debilitating arthritis associated with crippling pains that persist for weeks and even years. Although there are several studies to evaluate the efficacy of drugs against CHIKV, the treatment for chikungunya fever is mainly symptom-based and no effective licensed vaccine or antiviral are available. Here, we investigated the antiviral activity of three types of flavonoids against CHIKV in vitro replication. Three compounds: silymarin, quercetin and kaempferol were evaluated for their in vitro antiviral activities against CHIKV using a CHIKV replicon cell line and clinical isolate of CHIKV of Central/East African genotype. A cytopathic effect inhibition assay was used to determine their activities on CHIKV viral replication and quantitative reverse transcription PCR was used to calculate virus yield. Antiviral activity of effective compound was further investigated by evaluation of CHIKV protein expression using western blotting for CHIKV nsP1, nsP3, and E2E1 proteins. Briefly, silymarin exhibited significant antiviral activity against CHIKV, reducing both CHIKV replication efficiency and down-regulating production of viral proteins involved in replication. This study may have important consequence for broaden the chance of getting the effective antiviral for CHIKV infection. url: https://doi.org/10.1038/srep11421 doi: 10.1038/srep11421 id: cord-004062-yxx3xxio author: Lee, Ing-Kit title: Impaired production of immune mediators in dengue virus type 2-infected mononuclear cells of adults with end stage renal disease date: 2019-12-24 words: 3744.0 sentences: 191.0 pages: flesch: 47.0 cache: ./cache/cord-004062-yxx3xxio.txt txt: ./txt/cord-004062-yxx3xxio.txt summary: We performed an in vitro study to evaluate the sequential immunological reactions and viral load in dengue virus type 2-infected mononuclear cells of patients with ESRD (n = 34) and in healthy controls (n = 30). The concentrations of interleukins (IL)-1 receptor antagonist (Ra), IL-2, IL-6, IL-8, IL-10, IL-12p40, granulocyte-macrophage colony-stimulating factor (GM-CSF), monocyte chemotactic protein-1 (MCP-1), macrophage inflammatory protein-1b (MIP-1b), vascular endothelial growth factor (VEGF), tumor necrosis factor (TNF)-α and viral load cycle threshold (Ct) were measured in the dengue virus type 2-infected mononuclear cells at 6 h, 24 h, 48 h, and 72 h post-infection. In the present study, eleven immune mediators and viral load Ct values were measured in DENV2-infected mononuclear cells of adults with ESRD, and in healthy participants. Our results have been somewhat inconsistent with the reported overwhelming immune activation that is associated with dengue disease severity 5, 7 ; however, our findings clearly reflect the impairment of immune responses in vitro study of DENV2-infected mononuclear cells in ESRD patients. abstract: Chronic kidney disease is an epidemiologically identified risk factor for development of severe dengue in dengue-affected patients. However, available data on the immune pathogenesis in end stage renal disease (ESRD) patients affected by dengue is insufficient. We performed an in vitro study to evaluate the sequential immunological reactions and viral load in dengue virus type 2-infected mononuclear cells of patients with ESRD (n = 34) and in healthy controls (n = 30). The concentrations of interleukins (IL)-1 receptor antagonist (Ra), IL-2, IL-6, IL-8, IL-10, IL-12p40, granulocyte-macrophage colony-stimulating factor (GM-CSF), monocyte chemotactic protein-1 (MCP-1), macrophage inflammatory protein-1b (MIP-1b), vascular endothelial growth factor (VEGF), tumor necrosis factor (TNF)-α and viral load cycle threshold (Ct) were measured in the dengue virus type 2-infected mononuclear cells at 6 h, 24 h, 48 h, and 72 h post-infection. We found in the ESRD group significantly higher GM-CSF and IL-2 levels at 6 h post-infection. However, IL-8, IL-10, IL-12p40, TNF-α, MCP-1, and MIP-1b levels were found significantly lower than in the control group. At 24 h, 48 h, and 72 h post-infection, significantly lower levels of IL-1Ra, IL-6, IL-8, IL-10, IL-12p40, TNF-α, MCP-1, and MIP-1b were detected in ESRD group. Concentration of VEGF at 24 h and 48 h, and of GM-CSF at 48 h and 72 h were also found to be lower in ESRD group than in control group. Compared with controls, the viral load Ct values were significantly lower in ESRD group at 6 h and 24 h post-infection No significant difference in viral load Ct values between two groups was found at 48 h and 72 h post-infection. Our study discloses that the expression of immune mediators of dengue-infected mononuclear cells is impaired in ESRD patients. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6930266/ doi: 10.1038/s41598-019-56381-3 id: cord-002244-5h6monh3 author: Lee, Seung Hoon title: PTEN ameliorates autoimmune arthritis through down-regulating STAT3 activation with reciprocal balance of Th17 and Tregs date: 2016-10-06 words: 4148.0 sentences: 279.0 pages: flesch: 49.0 cache: ./cache/cord-002244-5h6monh3.txt txt: ./txt/cord-002244-5h6monh3.txt summary: Immunohistochemical analysis revealed that injection with PTEN overexpression vector significantly suppressed the expression of proinflammatory cytokines and osteoclastogenesis related factor such as RANKL and TRAP in joints compared to CIA mice treated with mock vector (Fig. 1D,E) . However, the differentiation of Treg cell was promoted in CIA induced mice injected with PTEN overexpression vector ( Fig. 2A) . However, the number of CD4 + p-Foxp3 + T cells in the spleen tissues of CIA induced mice was significantly upregulated compared to that in the spleen tissues of mice treated with mock vector based on immunofluorescence confocal microscopy ( Fig. 2C,D) . (A,B) Relative mRNA levels of PTEN and factors such as IL-17, RORγ t, and Foxp3 involved in the differentiation of Th17 and Treg in splenic CD4 + T cells, splenocytes, and draining lymph nodes from CIA induced WT or p53 −/− mice were assessed by real-time PCR. abstract: PTEN is a tyrosine phosphatase with significant function in inhibiting STAT3 activation. Recently, inactivation of STAT3 has been demonstrated as a therapeutic candidate for autoimmune arthritis. The expression of PTEN controlled by p53 regulates autoimmune arthritis through modulating the balance between Th17 and Treg. We hypothesized that PTEN regulated by p53 might reduce CIA severity and inflammatory response via inhibiting STAT3 activation. Our results revealed that PTEN could ameliorate experimental autoimmune arthritis by reducing STAT3 activity and Th17 differentiation. Systemic infusion of PTEN overexpression downregulated CIA severity. In addition, PTEN overexpression decreased the activation of T cells and modulated reciprocal differentiation of Th17 and Treg cells. We observed that PTEN expression downregulated by p53 deficiency induced the activation of STAT3. Loss of p53 exacerbated autoimmune arthritis and dysregulated the population of Th17 and Treg. These data suggest that induction of STAT3-modulatory activity of PTEN may be a therapeutic target for rheumatoid arthritis therapy. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5052580/ doi: 10.1038/srep34617 id: cord-004156-79peyzc9 author: Lee, Shwu-Maan title: A C-terminal Pfs48/45 malaria transmission-blocking vaccine candidate produced in the baculovirus expression system date: 2020-01-15 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The Plasmodium falciparum gametocyte surface protein, Pfs48/45, is a potential target for malaria transmission-blocking vaccines. However, due to its size and complexity, expression of the full-length protein has been difficult, leading to focus on the C-terminal six cysteine domain (6C) with the use of fusion proteins to facilitate expression and folding. In this study, we utilized the baculovirus system to evaluate the expression of three Pfs48/45 proteins including the full-length protein, the 6C domain fragment and the 6C domain mutant to prevent glycosylation. Expression of the recombinant Pfs48/45 proteins was conducted in super Sf9 cells combined with the use of tunicamycin to prevent N-glycosylation. The proteins were then evaluated as immunogens in mice to demonstrate the induction of functionally active polyclonal antibody responses as measured in the standard membrane feeding assay (SMFA). Only the 6C protein was found to exhibit significant transmission-reducing activity. Further characterization of the biologically active 6C protein demonstrated it was homogeneous in terms of size, charge, conformation, absence of glycosylation, and containing proper disulfide bond pairings. This study presents an alternative expression system, without the need of a fusion protein partner, for the Pfs48/45 6C protein fragment including further evaluation as a potential transmission-blocking vaccine candidate. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6962329/ doi: 10.1038/s41598-019-57384-w id: cord-306517-tls0849i author: Leidenberger, S. title: Virulence of current German PEDV strains in suckling pigs and investigation of protective effects of maternally derived antibodies date: 2017-09-07 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Porcine epidemic diarrhea (PED) has caused tremendous losses to the United States pig industry since 2013. From 2014, outbreaks were also reported from Central Europe. To characterize the Central European PEDV strains regarding their virulence in suckling piglets, and to assess the protective effect of maternally derived antibodies (MDA), four trial groups were randomly assigned, each consisting of two pregnant sows and their litter. To induce MDA in a subset of piglets, two sows received a cell culture-adapted PEDV strain, and another two sows were inoculated with field material from German PED outbreaks. Four sows stayed naïve. Subsequently, all piglets were inoculated with the corresponding PEDV strains at an age of 3 to 6 days, and virus shedding, clinical signs and occurrence of specific antibodies were assessed. Piglets without MDA showed a morbidity of 100% and low lethality, while almost all MDA-positive piglets stayed clinically healthy and showed considerably lower virus shedding. Taken together, the Central European PEDV strains showed rather low virulence under experimental conditions, and pre-inoculation of sows led to a solid protection of their offspring. The latter is the prerequisite for a sow vaccination concept that could help to prevent PED induced losses in the piglet sector. url: https://www.ncbi.nlm.nih.gov/pubmed/28883628/ doi: 10.1038/s41598-017-11160-w id: cord-004378-g1rxygef author: Leinisch, Fabian title: UV oxidation of cyclic AMP receptor protein, a global bacterial gene regulator, decreases DNA binding and cleaves DNA at specific sites date: 2020-02-20 words: 5840.0 sentences: 325.0 pages: flesch: 55.0 cache: ./cache/cord-004378-g1rxygef.txt txt: ./txt/cord-004378-g1rxygef.txt summary: In this study we show that exposure of isolated dimeric CRP-cAMP to UV modifies specific Met, Trp, Tyr, and Pro side-chains, induces inter-protein Tyr63-Tyr41 cross-links, and decreases DNA binding via oxidation of Met114/Pro110 residues in close proximity at the CRP dimer interface. The modifications at the CRP dimer interface, and the site-specific DNA strand cleavage are proposed to occur via oxidation of two species Met residues (Met114 and Met189, respectively) to reactive persulfoxides that damage neighbouring amino acids and DNA bases. Panel B: Material balance for Trp and Tyr residues determined by UPLC analysis with direct fluorescence detection on acid-hydrolysed UV-exposed CRP-cAMP complex. UPLC analysis of native and oxidized CRP showed that UV exposure of CRP resulted in significant modification (relative to controls) to Trp, Tyr, Ser, Met and Arg residues (Fig. 3A) . Q-TOF MS analysis of cAMP-CRP-DNA complexes exposed to UV light showed a similar pattern of damage, but higher extents of Met modification (7.6%; Fig. 3C ). abstract: UV light is a widely-employed, and environmentally-sensitive bactericide but its mechanism of action is not fully defined. Proteins are major chromophores and targets for damage due to their abundance, but the role of proteins in inducing damage to bound DNA, and the effects on DNA-protein interactions is less well characterized. In E. coli (and other Gram-negative bacteria) the cyclic AMP receptor protein (CRP/CAP) regulates more than 500 genes. In this study we show that exposure of isolated dimeric CRP-cAMP to UV modifies specific Met, Trp, Tyr, and Pro side-chains, induces inter-protein Tyr63-Tyr41 cross-links, and decreases DNA binding via oxidation of Met114/Pro110 residues in close proximity at the CRP dimer interface. UV exposure also modifies DNA-bound cAMP-CRP, with this resulting in DNA cleavage at specific G/C residues within the sequence bound to CRP, but not at other G/C sites. Oxidation also increases CRP dissociation from DNA. The modifications at the CRP dimer interface, and the site-specific DNA strand cleavage are proposed to occur via oxidation of two species Met residues (Met114 and Met189, respectively) to reactive persulfoxides that damage neighbouring amino acids and DNA bases. These data suggest that modification to CRP, and bound DNA, contributes to UV sensitivity. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7033146/ doi: 10.1038/s41598-020-59855-x id: cord-334228-n69iewmx author: Li, Chunmei title: Conformational Flexibility of a Short Loop near the Active Site of the SARS-3CLpro is Essential to Maintain Catalytic Activity date: 2016-02-16 words: 4643.0 sentences: 251.0 pages: flesch: 59.0 cache: ./cache/cord-334228-n69iewmx.txt txt: ./txt/cord-334228-n69iewmx.txt summary: Like other known CoV-3CLpro structures, such as TGEV, hCoV-229E, hCoV-HKU1, and IBV 2-5 , SARS-3CLpro has a highly conserved three-dimensional structure, dimer interface, catalysis dyad, and substrate binding site, but an extremely low homology with cellular proteases. Ser139 and Phe140 are two key residues that not only contribute to interactions between the two protomers in the parent dimer but also maintain the correct conformation of the S1 subsite in the substrate-binding pocket. Other residue mutations, which are neither on the dimer interface nor key to catalysis, can also influence enzyme activity and dimer association-dissociation of SARS-3CLpro via long-range interactions 15, 16 . Our molecular dynamics simulations showed that Ser139-Leu141 maintains a stable 3 10 -helix conformation in the inactive monomer structure and a well-defined loop conformation in the active protomer of the dimer structure. Although SARS-3CLpro uses the dimer structure to maintain its enzyme activity, our study shows that the monomer can also be evolved into an active enzyme via mutations. abstract: The SARS 3C-like proteinase (SARS-3CLpro), which is the main proteinase of the SARS coronavirus, is essential to the virus life cycle. This enzyme has been shown to be active as a dimer in which only one protomer is active. However, it remains unknown how the dimer structure maintains an active monomer conformation. It has been observed that the Ser139-Leu141 loop forms a short 3(10)-helix that disrupts the catalytic machinery in the inactive monomer structure. We have tried to disrupt this helical conformation by mutating L141 to T in the stable inactive monomer G11A/R298A/Q299A. The resulting tetra-mutant G11A/L141T/R298A/Q299A is indeed enzymatically active as a monomer. Molecular dynamics simulations revealed that the L141T mutation disrupts the 3(10)-helix and helps to stabilize the active conformation. The coil-3(10)-helix conformational transition of the Ser139-Leu141 loop serves as an enzyme activity switch. Our study therefore indicates that the dimer structure can stabilize the active conformation but is not a required structure in the evolution of the active enzyme, which can also arise through simple mutations. url: https://www.ncbi.nlm.nih.gov/pubmed/26879383/ doi: 10.1038/srep20918 id: cord-001875-ulq1xqma author: Li, Jing title: Identification of climate factors related to human infection with avian influenza A H7N9 and H5N1 viruses in China date: 2015-12-11 words: 4008.0 sentences: 175.0 pages: flesch: 50.0 cache: ./cache/cord-001875-ulq1xqma.txt txt: ./txt/cord-001875-ulq1xqma.txt summary: Our results represent the first step in determining the effects of climate factors on two different virus infections in China and provide warning guidelines for the future when provinces fall into the risky windows. Previously, data have indicated that environmental factors affect the prevalence of H5N1 and H7N9, with the infection and spread of the two viruses being closely correlated with bird habitats, migration, and local climate factors (e.g., temperature and relative humidity) 17 . We collected the H5N1 and H7N9 influenza data reported on the Chinese mainland from The climate dataset contained the air temperature, ground surface temperature, relative humidity, wind speed, and atmospheric pressure of all meteorological stations in the reported provinces at the reported dates for each record. Environmental factors influencing the spread of the highly pathogenic avian influenza H5N1 virus in wild birds in abstract: Human influenza infections display a strongly seasonal pattern. However, whether H7N9 and H5N1 infections correlate with climate factors has not been examined. Here, we analyzed 350 cases of H7N9 infection and 47 cases of H5N1 infection. The spatial characteristics of these cases revealed that H5N1 infections mainly occurred in the South, Middle, and Northwest of China, while the occurrence of H7N9 was concentrated in coastal areas of East and South of China. Aside from spatial-temporal characteristics, the most adaptive meteorological conditions for the occurrence of human infections by these two viral subtypes were different. We found that H7N9 infections correlate with climate factors, especially temperature (TEM) and relative humidity (RHU), while H5N1 infections correlate with TEM and atmospheric pressure (PRS). Hence, we propose a risky window (TEM 4–14 °C and RHU 65–95%) for H7N9 infection and (TEM 2–22 °C and PRS 980-1025 kPa) for H5N1 infection. Our results represent the first step in determining the effects of climate factors on two different virus infections in China and provide warning guidelines for the future when provinces fall into the risky windows. These findings revealed integrated predictive meteorological factors rooted in statistic data that enable the establishment of preventive actions and precautionary measures against future outbreaks. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4676028/ doi: 10.1038/srep18094 id: cord-338588-rc1h4drd author: Li, Xuanyi title: Seven decades of chemotherapy clinical trials: a pan-cancer social network analysis date: 2020-10-16 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Clinical trials establish the standard of cancer care, yet the evolution and characteristics of the social dynamics between the people conducting this work remain understudied. We performed a social network analysis of authors publishing chemotherapy-based prospective trials from 1946 to 2018 to understand how social influences, including the role of gender, have influenced the growth and development of this network, which has expanded exponentially from fewer than 50 authors in 1946 to 29,197 in 2018. While 99.4% of authors were directly or indirectly connected by 2018, our results indicate a tendency to predominantly connect with others in the same or similar fields, as well as an increasing disparity in author impact and number of connections. Scale-free effects were evident, with small numbers of individuals having disproportionate impact. Women were under-represented and likelier to have lower impact, shorter productive periods (P < 0.001 for both comparisons), less centrality, and a greater proportion of co-authors in their same subspecialty. The past 30 years were characterized by a trend towards increased authorship by women, with new author parity anticipated in 2032. The network of cancer clinical trialists is best characterized as strategic or mixed-motive, with cooperative and competitive elements influencing its appearance. Network effects such as low centrality, which may limit access to high-profile individuals, likely contribute to the observed disparities. url: https://www.ncbi.nlm.nih.gov/pubmed/33067482/ doi: 10.1038/s41598-020-73466-6 id: cord-263627-8ufjh70o author: Liang, Li-Lin title: Covid-19 mortality is negatively associated with test number and government effectiveness date: 2020-07-24 words: 2747.0 sentences: 164.0 pages: flesch: 46.0 cache: ./cache/cord-263627-8ufjh70o.txt txt: ./txt/cord-263627-8ufjh70o.txt summary: Covid-19 mortality rate was negatively associated with Covid-19 test number per 100 people (RR = 0.92, P = 0.001), government effectiveness score (RR = 0.96, P = 0.017), and number of hospital beds (RR = 0.85, P < 0.001). Furthermore, the negative association between Covid-19 mortality and test number was stronger among low-income countries and countries with lower government effectiveness scores, younger populations and fewer hospital beds. In the multiple regression analysis, Covid-19 mortality rate was regressed on Covid-19 test number, case number, critical case rate, government effectiveness score, proportion of population aged 65 or older, number of beds, deaths attributable to communicable diseases, and transport infrastructure quality score. Figure 1e and 1f exhibits that the negative correlation between Covid-19 mortality rate and test number was significant for countries with moderate (r = -0.33, P = 0.021) and low (r = − 0.42, P = 0.002) government effectiveness scores, respectively. abstract: A question central to the Covid-19 pandemic is why the Covid-19 mortality rate varies so greatly across countries. This study aims to investigate factors associated with cross-country variation in Covid-19 mortality. Covid-19 mortality rate was calculated as number of deaths per 100 Covid-19 cases. To identify factors associated with Covid-19 mortality rate, linear regressions were applied to a cross-sectional dataset comprising 169 countries. We retrieved data from the Worldometer website, the Worldwide Governance Indicators, World Development Indicators, and Logistics Performance Indicators databases. Covid-19 mortality rate was negatively associated with Covid-19 test number per 100 people (RR = 0.92, P = 0.001), government effectiveness score (RR = 0.96, P = 0.017), and number of hospital beds (RR = 0.85, P < 0.001). Covid-19 mortality rate was positively associated with proportion of population aged 65 or older (RR = 1.12, P < 0.001) and transport infrastructure quality score (RR = 1.08, P = 0.002). Furthermore, the negative association between Covid-19 mortality and test number was stronger among low-income countries and countries with lower government effectiveness scores, younger populations and fewer hospital beds. Predicted mortality rates were highly associated with observed mortality rates (r = 0.77; P < 0.001). Increasing Covid-19 testing, improving government effectiveness and increasing hospital beds may have the potential to attenuate Covid-19 mortality. url: https://www.ncbi.nlm.nih.gov/pubmed/32709854/ doi: 10.1038/s41598-020-68862-x id: cord-001915-b9dk07tk author: Liang, Xun title: A CRISPR/Cas9 and Cre/Lox system-based express vaccine development strategy against re-emerging Pseudorabies virus date: 2016-01-18 words: 3914.0 sentences: 236.0 pages: flesch: 49.0 cache: ./cache/cord-001915-b9dk07tk.txt txt: ./txt/cord-001915-b9dk07tk.txt summary: title: A CRISPR/Cas9 and Cre/Lox system-based express vaccine development strategy against re-emerging Pseudorabies virus Here we present an express vaccine development strategy based on CRISPR/Cas9 and Cre/Lox system against re-emerging Pseudorabies virus, which caused the recent devastating swine pseudorabies outbreak in China. To establish an express vaccine development strategy, two highly efficient gene edit systems, CRISPR/Cas9 and Cre/Lox system were employed. Eight hours post transfection, cells were then infected with PRV HNX with different MOI (multiplicity of infection) and incubated until recombinant virus expressing red and/or green fluorescence were observed (Fig. 3b) . As shown in Fig. 4a , the Cre recombinase gene transfected HEK293T cells were infected with PRV-HNX-TK − /gE − GFP + mCherry + recombinant PRV with various MOI (0.1, 1, and 10). Here, our animal experiments in mouse and piglets validated the protective effect of this gene editing technologies based new vaccine candidate, demonstrating its potential in controlling the current pseudorabies outbreak in the swine industry. abstract: Virus evolves rapidly to escape vaccine-induced immunity, posing a desperate demand for efficient vaccine development biotechnologies. Here we present an express vaccine development strategy based on CRISPR/Cas9 and Cre/Lox system against re-emerging Pseudorabies virus, which caused the recent devastating swine pseudorabies outbreak in China. By CRISPR/Cas9 system, the virulent genes of the newly isolated strain were simultaneously substituted by marker genes, which were subsequently excised using Cre/Lox system for vaccine safety concern. Notably, single cell FACS technology was applied to further promote virus purification efficiency. The combination of these state-of-art technologies greatly accelerated vaccine development. Finally, vaccination and challenge experiments proved this vaccine candidate’s protective efficacy in pigs and the promise to control current pseudorabies outbreak. This is, to our knowledge, the first successful vaccine development based on gene edit technologies, demonstrating these technologies leap from laboratory to industry. It may pave the way for future express antiviral vaccine development. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4726036/ doi: 10.1038/srep19176 id: cord-260834-v254de8k author: Lim, Chia Chiu title: Development of a Phage Display Panning Strategy Utilizing Crude Antigens: Isolation of MERS-CoV Nucleoprotein human antibodies date: 2019-04-15 words: 8295.0 sentences: 456.0 pages: flesch: 52.0 cache: ./cache/cord-260834-v254de8k.txt txt: ./txt/cord-260834-v254de8k.txt summary: The phage ELISA was conducted to measure the performances and effects of different blocking agents on the binding of αUbi phages against crude rUbi. Out of the four samples, the combination of PTM buffer and lysate showed the highest signal (1.226) detected with anti-c-myc-HRP as shown in Fig. 4c . Lysate preblocking and phage preincubation effects towards αUbi and M13KO7 phages against rUbi. To further optimize the biopanning conditions against crude antigens, the ''Yin-Yang'' (capture and eliminate) approach was designed to reduce non-specific binding by background phages. coli proteins in the crude fraction of rUbi with the actual concentration of rUbi being expected to be lower than the purified rUbi, the binding capability of αUbi is still unaffected as shown in phage ELISA assay upon affinity selection against crude rUbi. The blocking effect of PTM and E. abstract: Antibody phage display has been pivotal in the quest to generate human monoclonal antibodies for biomedical and research applications. Target antigen preparation is a main bottleneck associated with the panning process. This includes production complexity, downstream purification, quality and yield. In many instances, purified antigens are preferred for panning but this may not be possible for certain difficult target antigens. Here, we describe an improved procedure of affinity selection against crude or non-purified antigen by saturation of non-binders with blocking agents to promote positive binder enrichment termed as Yin-Yang panning. A naïve human scFv library with kappa light chain repertoire with a library size of 10(9) was developed. The improved Yin-Yang biopanning process was able to enrich monoclonal antibodies specific to the MERS-CoV nucleoprotein. Three unique monoclonal antibodies were isolated in the process. The Yin-Yang biopanning method highlights the possibility of utilizing crude antigens for the isolation of monoclonal antibodies by phage display. url: https://www.ncbi.nlm.nih.gov/pubmed/30988390/ doi: 10.1038/s41598-019-42628-6 id: cord-281536-8y7yxcp4 author: Lim, Hocheol title: Hot spot profiles of SARS-CoV-2 and human ACE2 receptor protein protein interaction obtained by density functional tight binding fragment molecular orbital method date: 2020-10-08 words: 3527.0 sentences: 178.0 pages: flesch: 55.0 cache: ./cache/cord-281536-8y7yxcp4.txt txt: ./txt/cord-281536-8y7yxcp4.txt summary: title: Hot spot profiles of SARS-CoV-2 and human ACE2 receptor protein protein interaction obtained by density functional tight binding fragment molecular orbital method In this work, to find common hot spot amino acids on the interfaces between the RBD domain and hACE2 of the three complexes, RBD-SARS-CoV-2/hACE2 (twelve experimental structural data), RBD-SARS-CoV-1/ hACE2 (four experimental structural data), and RBD-HCoV-NL63/hACE2 (one experimental structural data), we performed FMO-DFTB3/D/PCM calculations. Consequently, we summarized the FMO-DFTB3/D/PCM/3D-SPIEs results as interaction maps and found the hot spot regions in RBD-SARS-CoV-2 and hACE2 at a QM level. In order to narrow down the hot spot regions between hACE2 and RBD-SARS-CoV-1, we performed FMO calculations on four RBD-SARS-CoV-1/antibody complexes (Supplementary Table S14-S19). In order to find common hot spot amino acids in RBD-SARS-CoV-1 against hACE2 and SARS-CoV-1 antibodies, we illustrated the FMO results with a 3D-SPIEs-based map. abstract: The prevalence of a novel β-coronavirus (SARS-CoV-2) was declared as a public health emergency of international concern on 30 January 2020 and a global pandemic on 11 March 2020 by WHO. The spike glycoprotein of SARS-CoV-2 is regarded as a key target for the development of vaccines and therapeutic antibodies. In order to develop anti-viral therapeutics for SARS-CoV-2, it is crucial to find amino acid pairs that strongly attract each other at the interface of the spike glycoprotein and the human angiotensin-converting enzyme 2 (hACE2) complex. In order to find hot spot residues, the strongly attracting amino acid pairs at the protein–protein interaction (PPI) interface, we introduce a reliable inter-residue interaction energy calculation method, FMO-DFTB3/D/PCM/3D-SPIEs. In addition to the SARS-CoV-2 spike glycoprotein/hACE2 complex, the hot spot residues of SARS-CoV-1 spike glycoprotein/hACE2 complex, SARS-CoV-1 spike glycoprotein/antibody complex, and HCoV-NL63 spike glycoprotein/hACE2 complex were obtained using the same FMO method. Following this, a 3D-SPIEs-based interaction map was constructed with hot spot residues for the hACE2/SARS-CoV-1 spike glycoprotein, hACE2/HCoV-NL63 spike glycoprotein, and hACE2/SARS-CoV-2 spike glycoprotein complexes. Finally, the three 3D-SPIEs-based interaction maps were combined and analyzed to find the consensus hot spots among the three complexes. As a result of the analysis, two hot spots were identified between hACE2 and the three spike proteins. In particular, E37, K353, G354, and D355 of the hACE2 receptor strongly interact with the spike proteins of coronaviruses. The 3D-SPIEs-based map would provide valuable information to develop anti-viral therapeutics that inhibit PPIs between the spike protein of SARS-CoV-2 and hACE2. url: https://www.ncbi.nlm.nih.gov/pubmed/33033344/ doi: 10.1038/s41598-020-73820-8 id: cord-004342-9uok77wb author: Lin, Chun-Yu title: Elderly versus non-elderly patients undergoing surgery for left-sided native valve infective endocarditis: A 10-year institutional experience date: 2020-02-14 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: This retrospective study aimed to clarify the short- and mid-term outcomes of elderly patients who underwent surgery to treat left-sided native valve infective endocarditis (LSNIE). Between July 2005 and September 2015, 179 patients underwent surgical treatment for active LSNIE at a single institution. Patients were classified into two groups: ≥65 years (elderly group) and <65 years (non-elderly group). Clinical features, surgical information, postoperative complications, and three-year survival rates were compared. The average ages were 74.2 ± 6.4 and 45.2 ± 12.6 years in the elderly and non-elderly groups, respectively. The elderly group had a higher predicted mortality rate and a lower incidence of preoperative septic emboli-related complications. Echocardiographic assessments of infected valves were generally homogenous between the groups. The elderly patients had a higher in-hospital mortality rate than the non-elderly patients (26.3% vs. 5.7%, P = 0.001). For patients who survived to discharge, the three-year cumulative survival rates were 75.0% ± 8.2% and 81.2% ± 3.4% in the elderly and non-elderly groups, respectively (P = 0.484). In conclusion, elderly patients are at a higher risk of in-hospital mortality after surgery for LSNIE. However, once elderly patients are stabilized by surgical treatment and survive to discharge, the mid-term outcomes are promising. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7021775/ doi: 10.1038/s41598-020-59657-1 id: cord-299605-j1ewxk4q author: Lin, Jing-wen title: Signatures of malaria-associated pathology revealed by high-resolution whole-blood transcriptomics in a rodent model of malaria date: 2017-02-03 words: 6667.0 sentences: 326.0 pages: flesch: 49.0 cache: ./cache/cord-299605-j1ewxk4q.txt txt: ./txt/cord-299605-j1ewxk4q.txt summary: c. chabaudi, AS and CB, that differ in virulence in C57BL/6 mice, we performed high-resolution comparative whole-blood transcriptomic analysis throughout the acute phase of the blood-stage infection, and identified several transcriptomic signatures associated with severe malarial pathology before the onset of pathology or disease. Spearman''s rank correlation coefficient (r s ) analysis of unfiltered transcripts normalised across the median of all samples, revealed high levels of similarity amongst naïve and 2, 4 dpi samples in both AS and CB infections (Fig. 2ai ,ii, r s ranging from 0.73 to 0.88), while from 6 dpi onwards the whole blood transcriptomes diverge significantly from the earlier time points (r s ranging from 0.08 to − 0.59 compared to naïve controls). Importantly, in 4 of the CB infected mice that had reached humane end points at 9 dpi, these 5 genes showed an even higher level of up-regulation compared to naïve controls (Fig. 3c) , indicating possible lung pathology in these 4 CB infected mice. abstract: The influence of parasite genetic factors on immune responses and development of severe pathology of malaria is largely unknown. In this study, we performed genome-wide transcriptomic profiling of mouse whole blood during blood-stage infections of two strains of the rodent malaria parasite Plasmodium chabaudi that differ in virulence. We identified several transcriptomic signatures associated with the virulent infection, including signatures for platelet aggregation, stronger and prolonged anemia and lung inflammation. The first two signatures were detected prior to pathology. The anemia signature indicated deregulation of host erythropoiesis, and the lung inflammation signature was linked to increased neutrophil infiltration, more cell death and greater parasite sequestration in the lungs. This comparative whole-blood transcriptomics profiling of virulent and avirulent malaria shows the validity of this approach to inform severity of the infection and provide insight into pathogenic mechanisms. url: https://www.ncbi.nlm.nih.gov/pubmed/28155887/ doi: 10.1038/srep41722 id: cord-259416-gvzp2h5g author: Ling, Shenglong title: Combined approaches of EPR and NMR illustrate only one transmembrane helix in the human IFITM3 date: 2016-04-05 words: 3975.0 sentences: 228.0 pages: flesch: 50.0 cache: ./cache/cord-259416-gvzp2h5g.txt txt: ./txt/cord-259416-gvzp2h5g.txt summary: Systematic site-directed spin labeling (SDSL) and electron paramagnetic resonance (EPR) studies of IFITM3 in detergent micelles identified a single, long transmembrane helix in the C-terminus and an intramembrane segment in the N-terminal hydrophobic region. Systematic site scanning of spin labeling, EPR dynamic and accessibility analysis identified a C-terminal transmembrane α -helix and an N-terminal IFITM3 segment (composed of two short α -helices) lying on the surface of micelles. Collectively, the analysis of the accessibility parameter (Π O2 and Π NiEDDA ) and the immersion depth parameter (Φ ) derived from the power saturation experiments demonstrated that the IFITM3 protein contains a long transmembrane α -helix covering the residue sequence from A96 to A131 in the putative hydrophobic region. Therefore, the combined EPR and solution NMR studies clearly supported the type II transmembrane protein topology model for IFITM3, which is consistent with the previously proposed mechanism of its antiviral function. abstract: Interferon-inducible transmembrane protein IFITM3 was known to restrict the entry of a wide spectrum of viruses to the cytosol of the host. The mechanism used by the protein to restrict viral entry is unclear given the unavailability of the membrane topology and structures of the IFITM family proteins. Systematic site-directed spin labeling (SDSL) and electron paramagnetic resonance (EPR) studies of IFITM3 in detergent micelles identified a single, long transmembrane helix in the C-terminus and an intramembrane segment in the N-terminal hydrophobic region. Solution NMR studies of the same sample verified the secondary structure distribution and demonstrated two rigid regions interacting with the micellar surface. The resulting membrane topology of IFITM3 supports the mechanism of an enhanced restricted membrane hemi-fusion. url: https://www.ncbi.nlm.nih.gov/pubmed/27046158/ doi: 10.1038/srep24029 id: cord-003004-iif2lnez author: Linster, Martin title: Clinical and Molecular Epidemiology of Human Parainfluenza Viruses 1–4 in Children from Viet Nam date: 2018-05-01 words: 4121.0 sentences: 223.0 pages: flesch: 49.0 cache: ./cache/cord-003004-iif2lnez.txt txt: ./txt/cord-003004-iif2lnez.txt summary: The present study describes species-specific clinical presentation, the genetic variability and HPIV circulation in Viet Nam. The outcome of RSV infection in hospitalized children under 2 years of age presenting with acute lower respiratory infection (ALRI) in Ho Chi Minh City was described previously 17 . Samples were sourced from two previous acute respiratory infection (ARI) cohorts among in-and outpatients, that were conducted at Children''s Hospital 1 and 2 in Ho Chi Minh City, Viet Nam during years 2009 and 2010. For sequencing, HPIV-positive samples were further amplified in a hemi-nested PCR approach with newly designed species-specific primers targeting overlapping regions of the viral genome (Table S2) . In this study, the median age and gender distribution of infected children and frequency of clinical presentation (fever, cough, sore throat, runny nose and nasal congestion) as well as vital signs (pulse and respiratory rate) and duration of illness at presentation were similar between HPIV species (p > 0.05). abstract: HPIVs are serologically and genetically grouped into four species that account for up to 10% of all hospitalizations due to acute respiratory infection in children under the age of five. Genetic and epidemiological data for the four HPIVs derived from two pediatric cohorts in Viet Nam are presented. Respiratory samples were screened for HPIV1–4 by real-time PCR. Demographic and clinical data of patients infected with different HPIV were compared. We used a hemi-nested PCR approach to generate viral genome sequences from HPIV-positive samples and conducted a comprehensive phylogenetic analysis. In total, 170 samples tested positive for HPIV. HPIV3 was most commonly detected in our cohort and 80 co-detections of HPIV with other respiratory viruses were found. Phylogenetic analyses suggest local endemic circulation as well as punctuated introductions of new HPIV lineages. Viral gene flow analysis revealed that Viet Nam is a net importer of viral genetic diversity. Epidemiological analyses imply similar disease severity for all HPIV species. HPIV sequences from Viet Nam formed local clusters and were interspersed with sequences from diverse geographic regions. Combined, this new knowledge will help to investigate global HPIV circulation patterns in more detail and ultimately define more suitable vaccine strains. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5931535/ doi: 10.1038/s41598-018-24767-4 id: cord-327405-xgtqfwyn author: Liu, Bing title: Reduced numbers of T cells and B cells correlates with persistent SARS-CoV-2 presence in non-severe COVID-19 patients date: 2020-10-19 words: 3725.0 sentences: 199.0 pages: flesch: 52.0 cache: ./cache/cord-327405-xgtqfwyn.txt txt: ./txt/cord-327405-xgtqfwyn.txt summary: 37 non-severe patients with persistent SARS-CoV-2 presence that were transferred to Zhongnan hospital of Wuhan University were retrospectively recruited to the PP (persistently positive) group, which was further allocated to PPP group (n = 19) and PPN group (n = 18), according to their testing results after 7 days (N = negative). Finally, paired results of these lymphocyte subpopulations from 10 PPN patients demonstrated that the number of T cells and B cells significantly increased when the SARS-CoV-2 tests turned negative. These results indicated that non-severe COVID-19 patients (PA group) have already dysregulated immune system at disease onset, and those with persistent SARS-CoV-2 shedding could restore this abnormality to certain level. Together, these results indicated that the abnormalities in adaptive immune cells, but not symptoms and laboratory indicators, were associated with SARS-CoV-2 viral RNA detection in non-severe COVID-19 patients. abstract: COVID-19 has been widely spreading. We aimed to examine adaptive immune cells in non-severe patients with persistent SARS-CoV-2 shedding. 37 non-severe patients with persistent SARS-CoV-2 presence that were transferred to Zhongnan hospital of Wuhan University were retrospectively recruited to the PP (persistently positive) group, which was further allocated to PPP group (n = 19) and PPN group (n = 18), according to their testing results after 7 days (N = negative). Epidemiological, demographic, clinical and laboratory data were collected and analyzed. Data from age- and sex-matched non-severe patients at disease onset (PA [positive on admission] patients, n = 37), and lymphocyte subpopulation measurements from matched 54 healthy subjects were extracted for comparison (HC). Compared with PA patients, PP patients had much improved laboratory findings. The absolute numbers of CD3(+) T cells, CD4(+) T cells, and NK cells were significantly higher in PP group than that in PA group, and were comparable to that in healthy controls. PPP subgroup had markedly reduced B cells and T cells compared to PPN group and healthy subjects. Finally, paired results of these lymphocyte subpopulations from 10 PPN patients demonstrated that the number of T cells and B cells significantly increased when the SARS-CoV-2 tests turned negative. Persistent SARS-CoV-2 presence in non-severe COVID-19 patients is associated with reduced numbers of adaptive immune cells. Monitoring lymphocyte subpopulations could be clinically meaningful in identifying fully recovered COVID-19 patients. url: https://doi.org/10.1038/s41598-020-73955-8 doi: 10.1038/s41598-020-73955-8 id: cord-002290-wvo22jx2 author: Liu, Cheng title: Association of Mannose-binding Lectin Polymorphisms with Tuberculosis Susceptibility among Chinese date: 2016-11-04 words: 3772.0 sentences: 201.0 pages: flesch: 48.0 cache: ./cache/cord-002290-wvo22jx2.txt txt: ./txt/cord-002290-wvo22jx2.txt summary: In this study four functional single-nucleotide polymorphisms (SNPs, H/L, X/Y, P/Q and A/B) across the MBL2 gene were genotyped by direct DNA sequencing of PCR products in a case-control population of Chinese Han origin, consisting of 1,020 patients with pulmonary TB and 1,020 controls. In 1,020 controls, this distribution was 723 (70.9%), 234 (22.9%) and 63 (6.2%), respectively (OR = 1.56, 95% CI 1.29-1.90, P = 1.4 × 10 −6 , with adjustment for age and gender; simulation number = 10,000,000; Table 2 ), implicating that the individuals bearing medium or low expression haplotype pairs had an increased risk of TB and that the MBL deficiency might play a potential role in susceptibility to TB. In this study, we investigated all of the four functional SNPs in the MBL2 gene, individually or in haplotype or haplotype pairs, in a large case-control population of Chinese Han origin, totally consisting of 1,020 patients with TB and 1,020 controls. abstract: Tuberculosis (TB) is caused by infection of Mycobacterium tuberculosis. Host genetic variability is an important determinant of the risk of developing TB in humans. Although the association between MBL2 polymorphisms and TB has been studied in various populations, the results are controversial. In this study four functional single-nucleotide polymorphisms (SNPs, H/L, X/Y, P/Q and A/B) across the MBL2 gene were genotyped by direct DNA sequencing of PCR products in a case-control population of Chinese Han origin, consisting of 1,020 patients with pulmonary TB and 1,020 controls. We found that individuals carrying variant allele at A/B (namely BB or AB genotypes) was associated with increased susceptibility to TB (odds ratios [OR] = 1.57, 95% confidence interval [CI] 1.30–1.91, P = 1.3 × 10(−6)). Additionally, LYPB haplotype showed a significant association with increased risk of TB (OR = 1.54, 95% CI 1.27–1.87, P = 4.2 × 10(−6); global haplotype association P = 3.5 × 10(−5)). Furthermore, individuals bearing low- or medium- MBL expression haplotype pairs had an increased risk of TB (OR = 1.56, 95% CI 1.29–1.90, P = 1.4 × 10(−6)). Thus, the reduced expression of functional MBL secondary to having MBL2 variants may partially mediate the increased susceptibility to TB risk. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5095599/ doi: 10.1038/srep36488 id: cord-001963-4wjvykx7 author: Liu, Chia-Lin title: Using mutagenesis to explore conserved residues in the RNA-binding groove of influenza A virus nucleoprotein for antiviral drug development date: 2016-02-26 words: 5457.0 sentences: 304.0 pages: flesch: 56.0 cache: ./cache/cord-001963-4wjvykx7.txt txt: ./txt/cord-001963-4wjvykx7.txt summary: title: Using mutagenesis to explore conserved residues in the RNA-binding groove of influenza A virus nucleoprotein for antiviral drug development By interrupting the stacking interaction between Y148 and an RNA base, we identified an influenza virus NP inhibitor, (E, E)-1,7-bis(4-hydroxy-3-methoxyphenyl) -1,6-heptadiene-3,5-dione; this inhibitor reduced the NP''s RNA-binding affinity and hindered viral replication. As shown in Fig. 7A , upon H7 treatment at 15μM, the M1 viral RNA synthesis in the influenza virus-infected cells was reduced by 75% at T2. NP is the most abundant RNA-binding viral protein in influenza virus-infected cells and is responsible for recognizing RNA and forming a filamentous nucleocapsid 24 . Using fluorescence titration and an SPR assay of the NPs, we identified one potential natural compound, curcumin (H7), that targets Y148 of influenza virus NP and potently interferes with its RNA-binding activity. abstract: Nucleoprotein (NP) is the most abundant type of RNA-binding viral protein in influenza A virus–infected cells and is necessary for viral RNA transcription and replication. Recent studies demonstrated that influenza NP is a valid target for antiviral drug development. The surface of the groove, covered with numerous conserved residues between the head and body domains of influenza A NP, plays a crucial role in RNA binding. To explore the mechanism by which NP binds RNA, we performed a series of site-directed mutagenesis in the RNA-binding groove, followed by surface plasmon resonance (SPR), to characterize the interactions between RNA and NP. Furthermore, a role of Y148 in NP stability and NP-RNA binding was evaluated. The aromatic residue of Y148 was found to stack with a nucleotide base. By interrupting the stacking interaction between Y148 and an RNA base, we identified an influenza virus NP inhibitor, (E, E)-1,7-bis(4-hydroxy-3-methoxyphenyl) -1,6-heptadiene-3,5-dione; this inhibitor reduced the NP’s RNA-binding affinity and hindered viral replication. Our findings will be useful for the development of new drugs that disrupt the interaction between RNA and viral NP in the influenza virus. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4768256/ doi: 10.1038/srep21662 id: cord-258678-0atfsivf author: Liu, Hong Yan title: A Universal Protein Tag for Delivery of SiRNA-Aptamer Chimeras date: 2013-11-07 words: 4788.0 sentences: 282.0 pages: flesch: 51.0 cache: ./cache/cord-258678-0atfsivf.txt txt: ./txt/cord-258678-0atfsivf.txt summary: Here, we report the development of a small and simple protein tag that complements the therapeutic and targeting functionalities of chimera with two functional domains: a dsRNA binding domain (dsRBD) for siRNA docking and a pH-dependent polyhistidine to disrupt endosomal membrane. Therefore, it is of critical importance to design a delivery system that is simple for potential regulatory approval and mass production, universal for all siRNAaptamer chimera, neutral and siRNA-binding specific to ensure aptamer targeting, and small to avoid major alteration of chimera''s biodistribution profile. To assess their dsRNA binding activity, siRNA-aptamer chimera labeled with fluorophore FAM were incubated with the protein tags and probed with gel electrophoresis (1% agarose). To evaluate the targeting specificity of the aptamer block, PSMA-positive LNCaP cells and PSMA-negative PC3 cells were treated with complex of chimera and dsRBD-His 18 (chimera/protein tag molar ratio at 152, 100 nM chimera) in serum free medium for 2 hours, followed by incubation in complete medium for another 12 h. abstract: siRNA-aptamer chimeras have emerged as one of the most promising approaches for targeted delivery of siRNA due to the modularity of their diblock RNA structure, relatively lower cost over other targeted delivery approaches, and, most importantly, the outstanding potential for clinical translation. However, additional challenges must be addressed for efficient RNA interference (RNAi), in particular, endosomal escape. Currently, vast majority of siRNA delivery vehicles are based on cationic materials, which form complexes with negatively charged siRNA. Unfortunately, these approaches complicate the formulations again by forming large complexes with heterogeneous sizes, unfavorable surface charges, colloidal instability, and poor targeting ligand orientation. Here, we report the development of a small and simple protein tag that complements the therapeutic and targeting functionalities of chimera with two functional domains: a dsRNA binding domain (dsRBD) for siRNA docking and a pH-dependent polyhistidine to disrupt endosomal membrane. The protein selectively tags along the siRNA block of individual chimera, rendering the overall size of the complex small, desirable for deep tissue penetration, and the aptamer block accessible for target recognition. More interestingly, we found that extending the c-terminal polyhistidine segment in the protein tag to 18 amino acids completely abolishes the RNA binding function of dsRBD. url: https://www.ncbi.nlm.nih.gov/pubmed/24196104/ doi: 10.1038/srep03129 id: cord-329766-9bwdb6o2 author: Liu, Xiaofan title: Temporal radiographic changes in COVID-19 patients: relationship to disease severity and viral clearance date: 2020-06-24 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: COVID-19 is “public enemy number one” and has placed an enormous burden on health authorities across the world. Given the wide clinical spectrum of COVID-19, understanding the factors that can predict disease severity will be essential since this will help frontline clinical staff to stratify patients with increased confidence. To investigate the diagnostic value of the temporal radiographic changes, and the relationship to disease severity and viral clearance in COVID-19 patients. In this retrospective cohort study, we included 99 patients admitted to the Renmin Hospital of Wuhan University, with laboratory confirmed moderate or severe COVID-19. Temporal radiographic changes and viral clearance were explored using appropriate statistical methods. Radiographic features from HRCT scans included ground-glass opacity, consolidation, air bronchogram, nodular opacities and pleural effusion. The HRCT scores (peak) during disease course in COVID-19 patients with severe pneumonia (median: 24.5) were higher compared to those with pneumonia (median: 10) (p = 3.56 × 10 (−12)), with more frequency of consolidation (p = 0.025) and air bronchogram (p = 7.50 × 10(−6)). The median values of days when the peak HRCT scores were reached in pneumonia or severe pneumonia patients were 12 vs. 14, respectively (p = 0.048). Log-rank test and Spearman’s Rank-Order correlation suggested temporal radiographic changes as a valuable predictor for viral clearance. In addition, follow up CT scans from 11 pneumonia patients showed full recovery. Given the values of HRCT scores for both disease severity and viral clearance, a standardised HRCT score system for COVID-19 is highly demanded. url: https://www.ncbi.nlm.nih.gov/pubmed/32581324/ doi: 10.1038/s41598-020-66895-w id: cord-004140-ujzrqzv3 author: Lu, Xiaying title: Rolipram Protects Mice from Gram-negative Bacterium Escherichia coli-induced Inflammation and Septic Shock date: 2020-01-13 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Sepsis is typically triggered by an overwhelming systemic inflammatory response to pathogens, and may lead to severe organ dysfunction and/or death. Sepsis consequently has a high mortality rate and a high rate of complications for survivors, despite modern medical advances. Therefore, drug identification and validation for the treatment of sepsis is of the utmost importance. As a selective phosphodiesterase-4 inhibitor, rolipram also exhibits the abilities of inhibiting multiple pro-inflammatory cytokines production in macrophages and toxin-induced inflammation in mice. However, this drug has never been studied as a sepsis treatment method. We found that rolipram significantly improves survival in mice challenged with gram-negative bacterium E. coli, CLP, or E. coli derived lipopolysaccharide. We have also found that rolipram inhibits organ damage, pro-inflammatory cytokine production, and intracellular migration of early-stage inflammatory elements. Our results also show that rolipram increases anti-inflammatory cytokine production. The protective effects of rolipram on septic mice may result from inhibition of the MAP kinase and NF-κB signaling pathways. Rolipram may therefore be a potential novel sepsis treatment, one that would bypass the time-consuming and costly drug-discovery process. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6957694/ doi: 10.1038/s41598-019-56899-6 id: cord-001829-rwnbxmt4 author: Lu, Yi-Fan title: IFNL3 mRNA structure is remodeled by a functional non-coding polymorphism associated with hepatitis C virus clearance date: 2015-11-04 words: 7156.0 sentences: 384.0 pages: flesch: 48.0 cache: ./cache/cord-001829-rwnbxmt4.txt txt: ./txt/cord-001829-rwnbxmt4.txt summary: Genome-wide association studies performed on diverse patient populations have identified polymorphisms near the interferon-λ 3 (IFNL3; formerly IL28B) gene that predict the efficacy of interferon-based therapy for chronic infection. The differential effects on mRNA versus protein levels strongly suggest that the IFNL3 3′ UTR regulates gene expression by repressing the efficiency of mRNA translation rather than mRNA abundance in HeLa cells. We used polysome profiling to examine whether the variant IFNL3 reporter mRNAs were differentially associated with translating ribosomes in stable HeLa cell lines. Although rs4803217 is not independently associated with patient phenotypes in the cohort we analyzed, this SNP occurs in the 3′ UTR of IFNL3 and showed clear functional effects on reporter gene expression, suggesting a role for this variant in control of HCV infection. abstract: Polymorphisms near the interferon lambda 3 (IFNL3) gene strongly predict clearance of hepatitis C virus (HCV) infection. We analyzed a variant (rs4803217 G/T) located within the IFNL3 mRNA 3′ untranslated region (UTR); the G allele (protective allele) is associated with elevated therapeutic HCV clearance. We show that the IFNL3 3′ UTR represses mRNA translation and the rs4803217 allele modulates the extent of translational regulation. We analyzed the structures of IFNL3 variant mRNAs at nucleotide resolution by SHAPE-MaP. The rs4803217 G allele mRNA forms well-defined 3′ UTR structure while the T allele mRNA is more dynamic. The observed differences between alleles are among the largest possible RNA structural alterations that can be induced by a single nucleotide change and transform the UTR from a single well-defined conformation to one with multiple dynamic interconverting structures. These data illustrate that non-coding genetic variants can have significant functional effects by impacting RNA structure. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4631997/ doi: 10.1038/srep16037 id: cord-325405-cu4nx891 author: Luo, Lingfei title: Epidemiological and clinical differences between sexes and pathogens in a three-year surveillance of acute infectious gastroenteritis in Shanghai date: 2019-07-10 words: 4189.0 sentences: 191.0 pages: flesch: 34.0 cache: ./cache/cord-325405-cu4nx891.txt txt: ./txt/cord-325405-cu4nx891.txt summary: Logistic regression analyses with sex stratification showed that abdominal pain, fever and ingestion of unsafe food at restaurants were independent factors more frequently associated with bacterial gastroenteritis irrespective of sex; red cell-positive fecal matter was associated with bacterial gastroenteritis with an odds ratio (OR) of 3.28 only in males; and white blood cell count was associated with bacterial gastroenteritis with an OR of 1.02 only in females. No significant differences in the age, percentage of local residents, frequency of vomiting, frequency of watery stools, frequency of diarrhea, duration of diarrhea, rate dehydration, heart rate, blood pressure, or rate of ingesting possible unsafe food variables was observed between the viral and bacterial gastroenteritis groups ( Independent factors differentially associated with pathogen by sex. Among males, univariate analyses showed that nausea, vomiting frequency, watery stools, abdominal pain, fever, ingesting unsafe food at restaurants, fecal leukocyte-positive, fecal red cell-positive and white blood cell count were potential independent factors that were differentially associated with viral and bacterial gastroenteritis. abstract: Acute infectious gastroenteritis cases in Shanghai, reported over three years, were analyzed. Pathogens were identified in 1031 patients; of these, 725 and 306 were bacterial and viral cases, respectively. Vibrio parahemolyticus and Salmonella were the dominant bacteria, and Caliciviridae and Reoviridae were the dominant viral families in the local area. The acute gastroenteritis epidemic peaks appeared in August and January, which represented the active peak periods of bacteria and viruses, respectively. Logistic regression analyses with sex stratification showed that abdominal pain, fever and ingestion of unsafe food at restaurants were independent factors more frequently associated with bacterial gastroenteritis irrespective of sex; red cell-positive fecal matter was associated with bacterial gastroenteritis with an odds ratio (OR) of 3.28 only in males; and white blood cell count was associated with bacterial gastroenteritis with an OR of 1.02 only in females. Pathogen stratification showed that age, vomiting and red cell-positive fecal matter were associated with males with ORs of 0.99, 0.61 and 1.71, respectively, in bacterial gastroenteritis; and the migrant ratio was higher in males with an OR of 2.29 only in viral gastroenteritis. In conclusion, although bacterial and viral gastroenteritis shared many features, epidemiological and clinical factors differed between sexes and pathogens. url: https://www.ncbi.nlm.nih.gov/pubmed/31292502/ doi: 10.1038/s41598-019-46480-6 id: cord-002474-2l31d7ew author: Lv, Yang title: Actual measurement, hygrothermal response experiment and growth prediction analysis of microbial contamination of central air conditioning system in Dalian, China date: 2017-04-03 words: 4938.0 sentences: 270.0 pages: flesch: 51.0 cache: ./cache/cord-002474-2l31d7ew.txt txt: ./txt/cord-002474-2l31d7ew.txt summary: title: Actual measurement, hygrothermal response experiment and growth prediction analysis of microbial contamination of central air conditioning system in Dalian, China Based on the data of Cladosporium in hygrothermal response experiment, this paper used the logistic equation and the Gompertz equation to fit the growth predictive model of Cladosporium genera in different temperature and relative humidity conditions, and the square root model was fitted based on the two environmental factors. Besides, according to the tested microbial density and the identified genome sequence of collected microorganisms, the hygrothermal response experiment of dominant fungal was detected, and the fitting analysis was carried out based on the prediction model, followed by a series of statistical analysis. The unit A showed the obvious microbial contamination status, though all components and airborne microorganism meet the Hygienic specification of central air conditioning ventilation system in public buildings of China 22 . abstract: The microbial contamination of central air conditioning system is one of the important factors that affect the indoor air quality. Actual measurement and analysis were carried out on microbial contamination in central air conditioning system at a venue in Dalian, China. Illumina miseq method was used and three fungal samples of two units were analysed by high throughput sequencing. Results showed that the predominant fungus in air conditioning unit A and B were Candida spp. and Cladosporium spp., and two fungus were further used in the hygrothermal response experiment. Based on the data of Cladosporium in hygrothermal response experiment, this paper used the logistic equation and the Gompertz equation to fit the growth predictive model of Cladosporium genera in different temperature and relative humidity conditions, and the square root model was fitted based on the two environmental factors. In addition, the models were carried on the analysis to verify the accuracy and feasibility of the established model equation. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5377260/ doi: 10.1038/srep44190 id: cord-004292-6lnxb0px author: Lyu, Hongming title: Synchronized Biventricular Heart Pacing in a Closed-chest Porcine Model based on Wirelessly Powered Leadless Pacemakers date: 2020-02-07 words: 3772.0 sentences: 233.0 pages: flesch: 51.0 cache: ./cache/cord-004292-6lnxb0px.txt txt: ./txt/cord-004292-6lnxb0px.txt summary: With their flexible form factors, two pacemakers were implanted epicardially on the right and left ventricles of a porcine model and were inductively powered at 13.56 MHz and 40.68 MHz industrial, scientific, and medical (ISM) bands, respectively. The closed-chest pacing only requires the external source power of 0.3 W and 0.8 W at 13.56 MHz and 40.68 MHz, respectively, which leads to specific absorption rates (SARs) 2–3 orders of magnitude lower than the safety regulation limit. Not only is the need for intravascular leads eliminated, but synchronized and leadless pacing across different chambers becomes feasible, which offers the flexibility in customizing patient-specific CRTs. Prior studies have investigated wirelessly powered single-site cardiac pacing on rodent, rabbit and open-chest porcine models 4, 5, 21 . To demonstrate wireless CRT, two such pacemakers were epicardially implanted on the right ventricle (RV) and left ventricle (LV) in a porcine model for synchronized biventricular (BiV) pacing with controllable interventricular offsets. abstract: About 30% of patients with impaired cardiac function have ventricular dyssynchrony and seek cardiac resynchronization therapy (CRT). In this study, we demonstrate synchronized biventricular (BiV) pacing in a leadless fashion by implementing miniaturized and wirelessly powered pacemakers. With their flexible form factors, two pacemakers were implanted epicardially on the right and left ventricles of a porcine model and were inductively powered at 13.56 MHz and 40.68 MHz industrial, scientific, and medical (ISM) bands, respectively. The power consumption of these pacemakers is reduced to µW-level by a novel integrated circuit design, which considerably extends the maximum operating distance. Leadless BiV pacing is demonstrated for the first time in both open-chest and closed-chest porcine settings. The clinical outcomes associated with different interventricular delays are verified through electrophysiologic and hemodynamic responses. The closed-chest pacing only requires the external source power of 0.3 W and 0.8 W at 13.56 MHz and 40.68 MHz, respectively, which leads to specific absorption rates (SARs) 2–3 orders of magnitude lower than the safety regulation limit. This work serves as a basis for future wirelessly powered leadless pacemakers that address various cardiac resynchronization challenges. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7005712/ doi: 10.1038/s41598-020-59017-z id: cord-314753-xflhxb13 author: Manso, Carmen F. title: Efficient and unbiased metagenomic recovery of RNA virus genomes from human plasma samples date: 2017-06-23 words: 6333.0 sentences: 296.0 pages: flesch: 48.0 cache: ./cache/cord-314753-xflhxb13.txt txt: ./txt/cord-314753-xflhxb13.txt summary: The percentage of reads mapping to RNA virus genomes in the rRNA-depleted BBV Panel samples was between 40 and 150-fold higher than in corresponding untreated controls. The depth plots in Fig. 3 again show unbiased and even coverages across both genomes, and the percentages of reads mapping to viral targets was again much higher in the rRNA-depleted sample than in the untreated comparator (61-fold and 85-fold for HCV and HPgV respectively). By depleting host-derived nucleic acids and making modifications to an existing library preparation protocol to account for ultra-low RNA input quantities, we have been able to reconstruct effectively full-length genomes of HCV, HEV and HIV from plasma samples with viral loads of 10 4 IU/ml (copies/ml for HIV) and substantial fractions of complete genomes at 10 3 IU/ml. Additionally, our system was able to recover viral sequences from a panel of diverse RNA viruses diluted in human plasma, with a broad correlation between the genomic coverage and depth metrics and approximate concentration. abstract: RNA viruses cause significant human pathology and are responsible for the majority of emerging zoonoses. Mainstream diagnostic assays are challenged by their intrinsic diversity, leading to false negatives and incomplete characterisation. New sequencing techniques are expanding our ability to agnostically interrogate nucleic acids within diverse sample types, but in the clinical setting are limited by overwhelming host material and ultra-low target frequency. Through selective host RNA depletion and compensatory protocol adjustments for ultra-low RNA inputs, we are able to detect three major blood-borne RNA viruses – HIV, HCV and HEV. We recovered complete genomes and up to 43% of the genome from samples with viral loads of 10(4) and 10(3) IU/ml respectively. Additionally, we demonstrated the utility of this method in detecting and characterising members of diverse RNA virus families within a human plasma background, some present at very low levels. By applying this method to a patient sample series, we have simultaneously determined the full genome of both a novel subtype of HCV genotype 6, and a co-infecting human pegivirus. This method builds upon earlier RNA metagenomic techniques and can play an important role in the surveillance and diagnostics of blood-borne viruses. url: https://www.ncbi.nlm.nih.gov/pubmed/28646219/ doi: 10.1038/s41598-017-02239-5 id: cord-002844-jv42o789 author: Marcos-Villar, Laura title: Epigenetic control of influenza virus: role of H3K79 methylation in interferon-induced antiviral response date: 2018-01-19 words: 6091.0 sentences: 308.0 pages: flesch: 43.0 cache: ./cache/cord-002844-jv42o789.txt txt: ./txt/cord-002844-jv42o789.txt summary: These results indicate that epigenetic modifications induced by influenza virus infection mainly target the histone component of host cell chromatin, with H3K79 residue methylation the most frequently modified. Dot1L inhibition caused an increase in viral replication, higher in cells infected with the natural isolates, which suggests a general role of H3K79 methylation in control of the influenza virus life cycle. At 8 h, we found a weak increase on IFNβ, IFN-stimulated gene 56 (ISG56) and interferon-induced protein Mx1 (Mx1) RNA levels after IFNαβ addition or influenza virus infection, and Dot1L inhibitor treatment did not significantly decreased their accumulation (Fig. 6B,C) . Given the role of H3K79 methylation in the control of IFN signaling, we analyzed the effect of Dot1L inhibitor on influenza virus replication in cells with normal or deficient IFN responses. Since H3K79 methylation does not affect influenza virus replication in cells with impaired IFN signaling, we analyzed the effect of Dot1L inhibitor in subsequent stages of viral infection. abstract: Influenza virus stablishes a network of virus-host functional interactions, which depends on chromatin dynamic and therefore on epigenetic modifications. Using an unbiased search, we analyzed the epigenetic changes at DNA methylation and post-translational histone modification levels induced by the infection. DNA methylation was unaltered, while we found a general decrease on histone acetylation, which correlates with transcriptional inactivation and may cooperate with the impairment of cellular transcription that causes influenza virus infection. A particular increase in H3K79 methylation was observed and the use of an inhibitor of the specific H3K79 methylase, Dot1L enzyme, or its silencing, increased influenza virus replication. The antiviral response was reduced in conditions of Dot1L downregulation, since decreased nuclear translocation of NF-kB complex, and IFN-β, Mx1 and ISG56 expression was detected. The data suggested a control of antiviral signaling by methylation of H3K79 and consequently, influenza virus replication was unaffected in IFN pathway-compromised, Dot1L-inhibited cells. H3K79 methylation also controlled replication of another potent interferon-inducing virus such as vesicular stomatitis virus, but did not modify amplification of respiratory syncytial virus that poorly induces interferon signaling. Epigenetic methylation of H3K79 might have an important role in controlling interferon-induced signaling against viral pathogens. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5775356/ doi: 10.1038/s41598-018-19370-6 id: cord-342782-xty16m8w author: Marrugal-Lorenzo, José A. title: Repositioning salicylanilide anthelmintic drugs to treat adenovirus infections date: 2019-01-09 words: 5099.0 sentences: 267.0 pages: flesch: 47.0 cache: ./cache/cord-342782-xty16m8w.txt txt: ./txt/cord-342782-xty16m8w.txt summary: Data suggests that the studied salicylanilide anthelmintic drugs could be suitable for further clinical evaluation for the development of new antiviral drugs to treat infections by adenovirus in immunosuppressed patients and in immunocompetent individuals with community-acquired pneumonia. The three salicylanilide anthelmintic drugs showed a dose-dependent anti-HAdV activity against both HAdV5 and HAdV16, with 100% inhibition of plaques formation at 1.25, 5 and 2.5 μM for NIC, OXY and RAF, respectively ( Fig. 2a,b) . The CC 50 values for these molecules were in all cases significantly higher than the IC 50 concentrations required for inhibition in our antiviral activity and mechanistic assays for both 293β5 cells (Table 1 ) and A549 cells (22.9 ± 9.8 µM, 76.1 ± 14.4 µM and 80.6 ± 34.7 µM for NIC, OXY and RAF, respectively). The aim of this study was to evaluate the anti-HAdV activity of NIC, a salicylanilide anthelmintic drug of human use to set the basis for its further experimental and clinical development as a potential new treatment for HAdV infections. abstract: The repositioning of drugs already approved by regulatory agencies for other indications is an emerging alternative for the development of new antimicrobial therapies. The repositioning process involves lower risks and costs than the de novo development of novel antimicrobial drugs. Currently, infections by adenovirus show a steady increment with a high clinical impact in immunosuppressed and immunocompetent patients. The lack of a safe and efficacious drug to treat these infections supports the search for new antiviral drugs. Here we evaluated the anti-adenovirus activity of niclosanide, oxyclozanide, and rafoxanide, three salicylanilide anthelmintic drugs. Also, we carried out the cytotoxicity evaluation and partial characterization of the mechanism of action of these drugs. The salicylanilide anthelmintic drugs showed significant anti-adenovirus activity at low micromolar concentrations with little cytotoxicity. Moreover, our mechanistic assays suggest differences in the way the drugs exert anti-adenovirus activity. Niclosamide and rafoxanide target transport of the HAdV particle from the endosome to the nuclear envelope, whilst oxyclozanide specifically targets adenovirus immediately early gene E1A transcription. Data suggests that the studied salicylanilide anthelmintic drugs could be suitable for further clinical evaluation for the development of new antiviral drugs to treat infections by adenovirus in immunosuppressed patients and in immunocompetent individuals with community-acquired pneumonia. url: https://www.ncbi.nlm.nih.gov/pubmed/30626902/ doi: 10.1038/s41598-018-37290-3 id: cord-002320-m99amd4y author: Mathur, Kalika title: Analysis of chikungunya virus proteins reveals that non-structural proteins nsP2 and nsP3 exhibit RNA interference (RNAi) suppressor activity date: 2016-11-30 words: 5671.0 sentences: 338.0 pages: flesch: 56.0 cache: ./cache/cord-002320-m99amd4y.txt txt: ./txt/cord-002320-m99amd4y.txt summary: Systematic analysis of all CHIKV proteins using a Sf21 RNAi sensor cell line based assay revealed that non-structural proteins nsP2 and nsP3 exhibited RNAi suppressor activity. Using cell lysate of the transfected cell expressing nsP2 and nsP3, we evaluated their ability to bind double stranded RNA by using [γ 32P] labeled shRNA of GFP and running the bound complex in a 6% polyacrylamide gel (Fig. 3e) . Having confirmed that both nsP2 and nsP3 exhibit RNAi suppressor activities, efforts were taken to characterise the proteins better and to identify those specific domains that were and NS4B (dengue virus) were taken as positive controls and empty vector was used as negative control. Taken together, the current study has identified CHIKV proteins nsP2 and nsP3 to exhibit RNAi suppressor activity in the in-vitro system that was further demonstrated in its natural hosts, namely, an Aedes and mammalian cell line. abstract: RNAi pathway is an antiviral defence mechanism employed by insects that result in degradation of viral RNA thereby curbing infection. Several viruses including flaviviruses encode viral suppressors of RNAi (VSRs) to counteract the antiviral RNAi pathway. Till date, no VSR has been reported in alphaviruses. The present study was undertaken to evaluate chikungunya virus (CHIKV) proteins for RNAi suppressor activity. We systematically analyzed all nine CHIKV proteins for RNAi suppressor activity using Sf21 RNAi sensor cell line based assay. Two non-structural proteins, namely, nsP2 and nsP3 were found to exhibit RNAi suppressor activity. We further validated the findings in natural hosts, namely in Aedes and in mammalian cell lines and further through EMSA and Agrobacterium infiltration in GFP silenced transgenic tobacco plants. Domains responsible for maximum RNAi suppressor activity were also identified within these proteins. RNA binding motifs in these domains were identified and their participation in RNAi suppression evaluated using site directed mutagenesis. Sequence alignment of these motifs across all species of known alphaviruses revealed conservation of these motifs emphasizing on a similar role of action in other species of alphaviruses as well. Further validation of RNAi suppressor activity of these proteins awaits establishment of specific virus infection models. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5128919/ doi: 10.1038/srep38065 id: cord-316983-h4mtpcyc author: Mathé-Hubert, Hugo title: Comparative venomics of Psyttalia lounsburyi and P. concolor, two olive fruit fly parasitoids: a hypothetical role for a GH1 β-glucosidase date: 2016-10-25 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Venom composition of parasitoid wasps attracts increasing interest – notably molecules ensuring parasitism success on arthropod pests – but its variation within and among taxa is not yet understood. We have identified here the main venom proteins of two braconid wasps, Psyttalia lounsburyi (two strains from South Africa and Kenya) and P. concolor, olive fruit fly parasitoids that differ in host range. Among the shared abundant proteins, we found a GH1 β-glucosidase and a family of leucine-rich repeat (LRR) proteins. Olive is extremely rich in glycoside compounds that are hydrolyzed by β-glucosidases into defensive toxic products in response to phytophagous insect attacks. Assuming that Psyttalia host larvae sequester ingested glycosides, the injected venom GH1 β-glucosidase could induce the release of toxic compounds, thus participating in parasitism success by weakening the host. Venom LRR proteins are similar to truncated Toll-like receptors and may possibly scavenge the host immunity. The abundance of one of these LRR proteins in the venom of only one of the two P. lounsburyi strains evidences intraspecific variation in venom composition. Altogether, venom intra- and inter-specific variation in Psyttalia spp. were much lower than previously reported in the Leptopilina genus (Figitidae), suggesting it might depend upon the parasitoid taxa. url: https://doi.org/10.1038/srep35873 doi: 10.1038/srep35873 id: cord-302459-grs2x26l author: Matin, Farhana title: A Plasma Biomarker Panel of Four MicroRNAs for the Diagnosis of Prostate Cancer date: 2018-04-27 words: 8311.0 sentences: 413.0 pages: flesch: 48.0 cache: ./cache/cord-302459-grs2x26l.txt txt: ./txt/cord-302459-grs2x26l.txt summary: In this study we profiled 372 cancer-associated miRNAs in plasma collected before (~60% patients) and after/during commencement of treatment (~40% patients), from age-matched prostate cancer patients and healthy controls, and observed elevated levels of 4 miRNAs miR-4289, miR-326, miR-152-3p and miR-98-5p, which were validated in an independent cohort. Analysis of published miRNA transcriptomic data from clinical samples in the TCGA dataset demonstrated low expression of miR-152-3p in tumour compared to adjacent non-malignant tissues (p = 0.001) (Wilcoxon test, p ≤ 0.05) (Fig. 4) Figure S3) . Similarly, other groups have assessed the diagnostic performance of plasma or serum miRNAs in patients with localised or metastatic prostate cancer, BPH and healthy controls, and in most instances the specificity and sensitivity of the miRNA biomarkers have outperformed the accuracy of the PSA test 23, 28, 29 . abstract: Prostate cancer is diagnosed in over 1 million men every year globally, yet current diagnostic modalities are inadequate for identification of significant cancer and more reliable early diagnostic biomarkers are necessary for improved clinical management of prostate cancer patients. MicroRNAs (miRNAs) modulate important cellular processes/pathways contributing to cancer and are stably present in body fluids. In this study we profiled 372 cancer-associated miRNAs in plasma collected before (~60% patients) and after/during commencement of treatment (~40% patients), from age-matched prostate cancer patients and healthy controls, and observed elevated levels of 4 miRNAs - miR-4289, miR-326, miR-152-3p and miR-98-5p, which were validated in an independent cohort. The miRNA panel was able to differentiate between prostate cancer patients and controls (AUC = 0.88). Analysis of published miRNA transcriptomic data from clinical samples demonstrated low expression of miR-152-3p in tumour compared to adjacent non-malignant tissues. Overexpression of miR-152-3p increased proliferation and migration of prostate cancer cells, suggesting a role for this miRNA in prostate cancer pathogenesis, a concept that was supported by pathway analysis of predicted miR-152-3p target genes. In summary, a four miRNA panel, including miR-152-3p which likely targets genes with key roles in prostate cancer pathogenesis, has the potential to improve early prostate cancer diagnosis. url: https://doi.org/10.1038/s41598-018-24424-w doi: 10.1038/s41598-018-24424-w id: cord-004310-hl7fa4af author: Matsuishi, Yujiro title: Down Syndrome Reduces the Sedative Effect of Midazolam in Pediatric Cardiovascular Surgical Patients date: 2020-02-10 words: 3488.0 sentences: 187.0 pages: flesch: 48.0 cache: ./cache/cord-004310-hl7fa4af.txt txt: ./txt/cord-004310-hl7fa4af.txt summary: We recorded patient information, including age, sex, surgical procedure, and daily severity data (including severity of organ dysfunction and sedative/muscle relaxant dosages) during PICU stays for five days after the end of muscle relaxant usage. We found that, overall, the amount of MDZ administered was increased in DS versus controls after ending muscle relaxants and observed the reduced sedative effect of MDZ for DS patients while DEX was not different as estimated by Bayesian inference modeling. To adjust these biases, we used multivariate www.nature.com/scientificreports www.nature.com/scientificreports/ analysis with respect to these factors but we also "double checked" our results by using the demographic data propensity score for DS patients as a covariate in Bayesian inference modeling. To conclude, we conducted a retrospective study based on validated evaluative tools that indicated a need for higher doses of MDZ with higher doses of compensating sedatives for the 5-day period immediately after muscle relaxant usage following pediatric heart surgery. abstract: Down syndrome (DS) is frequently comorbid with congenital heart disease and has recently been shown to reduce the sedative effect of benzodiazepine (BDZ)-class anesthesia but this effect in a clinical setting has not been studied. Therefore, this study compared midazolam sedation after heart surgery in DS and normal children. We retrospectively reviewed patient records in our pediatric intensive care unit (PICU) of pediatric cardiovascular operations between March 2015 and March 2018. We selected five days of continuous post-operative data just after termination of muscle relaxants. Midazolam sedation was estimated by Bayesian inference for generalized linear mixed models. We enrolled 104 patients (average age 26 weeks) of which 16 (15%) had DS. DS patients had a high probability of receiving a higher midazolam dosage and dexmedetomidine dosage over the study period (probability = 0.99, probability = 0.97) while depth of sedation was not different in DS patients (probability = 0.35). Multi regression modeling included severity scores and demographic data showed DS decreases midazolam sedation compared with controls (posterior OR = 1.32, 95% CrI = 1.01–1.75). In conclusion, midazolam dosages should be carefully adjusted as DS significantly decreases midazolam sedative effect in pediatric heart surgery patients. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7010829/ doi: 10.1038/s41598-020-58283-1 id: cord-002791-tqchfdmy author: Mikel, Pavel title: One-plasmid double-expression His-tag system for rapid production and easy purification of MS2 phage-like particles date: 2017-12-13 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: MS2 phage-like particles (MS2 PLP) are artificially constructed pseudo-viral particles derived from bacteriophage MS2. They are able to carry a specific single stranded RNA (ssRNA) sequence of choice inside their capsid, thus protecting it against the effects of ubiquitous nucleases. Such particles are able to mimic ssRNA viruses and, thus, may serve as the process control for molecular detection and quantification of such agents in several kinds of matrices, vaccines and vaccine candidates, drug delivery systems, and systems for the display of immunologically active peptides or nanomachines. Currently, there are several different in vivo plasmid-driven packaging systems for production of MS2 PLP. In order to combine all the advantages of the available systems and to upgrade and simplify the production and purification of MS2 PLP, a one-plasmid double-expression His-tag system was designed. The described system utilizes a unique fusion insertional mutation enabling purification of particles using His-tag affinity. Using this new production system, highly pure MS2 PLP can be quickly produced and purified by a fast performance liquid chromatography (FPLC) approach. The system can be easily adapted to produce other MS2 PLP with different properties. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5727534/ doi: 10.1038/s41598-017-17951-5 id: cord-276185-ysspkbj7 author: Milewska, Aleksandra title: APOBEC3-mediated restriction of RNA virus replication date: 2018-04-13 words: 5507.0 sentences: 317.0 pages: flesch: 54.0 cache: ./cache/cord-276185-ysspkbj7.txt txt: ./txt/cord-276185-ysspkbj7.txt summary: In experiments in vitro, three human APOBEC3 proteins (A3C, A3F and A3H) inhibited HCoV-NL63 infection and limited production of progeny virus, but did not cause hypermutation of the coronaviral genome. Although the precise molecular mechanism of deaminase-dependent inhibition of coronavirus replication remains elusive, our results further our understanding of APOBEC-mediated restriction of RNA virus infections. HCoV-NL63 infection resulted in upregulation of expression of A3A, A3C, A3D and A3F and A3C, A3F and A3H all inhibited HCoV-NL63 replication, we tested whether this inhibition was the result of the catalytic activity of the APOBECs. Plasmids encoding variants of A3C, A3F and A3H with Glu → Gln substitutions in the catalytic site were prepared 31 and mRNAs encoding active or inactive proteins were transfected into LLC-Mk2 cells, which were infected with HCoV-NL63 and cultured prior to visualisation of viral proteins with specific antibodies. abstract: APOBEC3 family members are cytidine deaminases with roles in intrinsic responses to infection by retroviruses and retrotransposons, and in the control of other DNA viruses, such as herpesviruses, parvoviruses and hepatitis B virus. Although effects of APOBEC3 members on viral DNA have been demonstrated, it is not known whether they edit RNA genomes through cytidine deamination. Here, we investigated APOBEC3-mediated restriction of Coronaviridae. In experiments in vitro, three human APOBEC3 proteins (A3C, A3F and A3H) inhibited HCoV-NL63 infection and limited production of progeny virus, but did not cause hypermutation of the coronaviral genome. APOBEC3-mediated restriction was partially dependent on enzyme activity, and was reduced by the use of enzymatically inactive APOBEC3. Moreover, APOBEC3 proteins bound to the coronaviral nucleoprotein, and this interaction also affected viral replication. Although the precise molecular mechanism of deaminase-dependent inhibition of coronavirus replication remains elusive, our results further our understanding of APOBEC-mediated restriction of RNA virus infections. url: https://www.ncbi.nlm.nih.gov/pubmed/29654310/ doi: 10.1038/s41598-018-24448-2 id: cord-329155-ddpfox68 author: Mindikoglu, Ayse L. title: Intermittent fasting from dawn to sunset for four consecutive weeks induces anticancer serum proteome response and improves metabolic syndrome date: 2020-10-27 words: 8186.0 sentences: 379.0 pages: flesch: 43.0 cache: ./cache/cord-329155-ddpfox68.txt txt: ./txt/cord-329155-ddpfox68.txt summary: Our results showed that 30-day intermittent fasting from dawn to sunset, the human activity phase, was associated with an anticancer serum proteome response and upregulated several key regulatory proteins that play a key role in tumor suppression, DNA repair, insulin signaling, glucose, and lipid metabolism, circadian clock, cytoskeletal remodeling, immune system, and cognitive function 15 . In accord with the findings of these murine and human studies 13,25 , we found a significant fold increase in the levels of specific tumor suppressor/anticancer proteins at the end of 4th week during 4-week intermittent fasting from dawn to sunset and/or 1 week after 4-week intermittent fasting from dawn to sunset, including CALR, CALU, INTS6, KIT, CROCC, PIGR, IGFBP4, and SEMA4B that are downregulated in several cancers resulting in cancer metastasis and poor prognosis (Table 2, Fig. 2 ). abstract: Metabolic syndrome is characterized by central obesity, insulin resistance, elevated blood pressure, and dyslipidemia. Metabolic syndrome is a significant risk factor for several common cancers (e.g., liver, colorectal, breast, pancreas). Pharmacologic treatments used for the components of the metabolic syndrome appear to be insufficient to control cancer development in subjects with metabolic syndrome. Murine models showed that cancer has the slowest progression when there is no food consumption during the daily activity phase. Intermittent fasting from dawn to sunset is a form of fasting practiced during human activity hours. To test the anticancer effect of intermittent fasting from dawn to sunset in metabolic syndrome, we conducted a pilot study in 14 subjects with metabolic syndrome who fasted (no eating or drinking) from dawn to sunset for more than 14 h daily for four consecutive weeks. We collected serum samples before 4-week intermittent fasting, at the end of 4th week during 4-week intermittent fasting and 1 week after 4-week intermittent fasting. We performed serum proteomic analysis using nano ultra-high performance liquid chromatography-tandem mass spectrometry. We found a significant fold increase in the levels of several tumor suppressor and DNA repair gene protein products (GP)s at the end of 4th week during 4-week intermittent fasting (CALU, INTS6, KIT, CROCC, PIGR), and 1 week after 4-week intermittent fasting (CALU, CALR, IGFBP4, SEMA4B) compared with the levels before 4-week intermittent fasting. We also found a significant reduction in the levels of tumor promoter GPs at the end of 4th week during 4-week intermittent fasting (POLK, CD109, CAMP, NIFK, SRGN), and 1 week after 4-week intermittent fasting (CAMP, PLAC1) compared with the levels before 4-week intermittent fasting. Fasting from dawn to sunset for four weeks also induced an anti-diabetes proteome response by upregulating the key regulatory proteins of insulin signaling at the end of 4th week during 4-week intermittent fasting (VPS8, POLRMT, IGFBP-5) and 1 week after 4-week intermittent fasting (PRKCSH), and an anti-aging proteome response by upregulating H2B histone proteins 1 week after 4-week intermittent fasting. Subjects had a significant reduction in body mass index, waist circumference, and improvement in blood pressure that co-occurred with the anticancer, anti-diabetes, and anti-aging serum proteome response. These findings suggest that intermittent fasting from dawn to sunset actively modulates the respective genes and can be an adjunct treatment in metabolic syndrome. Further studies are needed to test the intermittent fasting from dawn to sunset in the prevention and treatment of metabolic syndrome-induced cancers. url: https://www.ncbi.nlm.nih.gov/pubmed/33110154/ doi: 10.1038/s41598-020-73767-w id: cord-011892-b9zlig0r author: Mukherjee, Shradha title: Quiescent stem cell marker genes in glioma gene networks are sufficient to distinguish between normal and glioblastoma (GBM) samples date: 2020-07-02 words: 6161.0 sentences: 421.0 pages: flesch: 51.0 cache: ./cache/cord-011892-b9zlig0r.txt txt: ./txt/cord-011892-b9zlig0r.txt summary: In this work, two different network construction algorithms, Weighted correlation network analysis (WGCNA) and Multiscale Clustering of Geometric Network (MEGENA), were applied on publicly available glioma, control brain and stem cell gene expression RNA-seq datasets, to identify gene network regulatory modules associated with GBM. Characterization of HuAgeGBsplit_18 (WGCNA) and c1_HuAgeGBsplit_32/193 (MEGENA) modules showed significant enrichment of rodent quiescent stem cell marker genes (GSE70696_QNPbyTAP). Enrichment of proliferative and quiescent stem cell marker genes identified by differential gene expression analysis above, in WGCNA and MEGENA modules was determined using useListEnrichment R function 22, 23, 46 . showed that HuAgeGBsplit_18 WGCNA GBM module and its equivalent c1_HuAgeGBsplit_193/32 MEGENA GBM modules, were the only GBM modules significantly enriched with proliferative and quiescent stem cell marker genes (Fig. 4A,B) . A meta-analysis was performed on publicly available high-throughput gene expression datasets from human glioma samples, control human brains, normal stem cells and GBM cells in quiescent and proliferative states 18, [26] [27] [28] [29] [30] [31] [32] [33] [34] . abstract: Grade 4 glioma or GBM has poor prognosis and is the most aggressive grade of glioma. Accurate diagnosis and classification of tumor grade is a critical determinant for development of treatment pathway. Extensive genomic sequencing of gliomas, different cell types, brain tissue regions and advances in bioinformatics algorithms, have presented an opportunity to identify molecular markers that can complement existing histology and imaging methods used to diagnose and classify gliomas. ‘Cancer stem cell theory’ purports that a minor population of stem cells among the heterogeneous population of different cell types in the tumor, drive tumor growth and resistance to therapies. However, characterization of stem cell states in GBM and ability of stem cell state signature genes to serve as diagnostic or prognostic molecular markers are unknown. In this work, two different network construction algorithms, Weighted correlation network analysis (WGCNA) and Multiscale Clustering of Geometric Network (MEGENA), were applied on publicly available glioma, control brain and stem cell gene expression RNA-seq datasets, to identify gene network regulatory modules associated with GBM. Both gene network algorithms identified consensus or equivalent modules, HuAgeGBsplit_18 (WGCNA) and c1_HuAgeGBsplit_32/193 (MEGENA), significantly associated with GBM. Characterization of HuAgeGBsplit_18 (WGCNA) and c1_HuAgeGBsplit_32/193 (MEGENA) modules showed significant enrichment of rodent quiescent stem cell marker genes (GSE70696_QNPbyTAP). A logistic regression model built with eight of these quiescent stem cell marker genes (GSE70696_QNPbyTAP) was sufficient to distinguish between control and GBM samples. This study demonstrates that GBM associated gene regulatory modules are characterized by diagnostic quiescent stem cell marker genes, which may potentially be used clinically as diagnostic markers and therapeutic targets in GBM. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7363816/ doi: 10.1038/s41598-020-67753-5 id: cord-320709-2pnqpljt author: Munster, Vincent J. title: Replication and shedding of MERS-CoV in Jamaican fruit bats (Artibeus jamaicensis) date: 2016-02-22 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) highlights the zoonotic potential of Betacoronaviruses. Investigations into the origin of MERS-CoV have focused on two potential reservoirs: bats and camels. Here, we investigated the role of bats as a potential reservoir for MERS-CoV. In vitro, the MERS-CoV spike glycoprotein interacted with Jamaican fruit bat (Artibeus jamaicensis) dipeptidyl peptidase 4 (DPP4) receptor and MERS-CoV replicated efficiently in Jamaican fruit bat cells, suggesting there is no restriction at the receptor or cellular level for MERS-CoV. To shed light on the intrinsic host-virus relationship, we inoculated 10 Jamaican fruit bats with MERS-CoV. Although all bats showed evidence of infection, none of the bats showed clinical signs of disease. Virus shedding was detected in the respiratory and intestinal tract for up to 9 days. MERS-CoV replicated transiently in the respiratory and, to a lesser extent, the intestinal tracts and internal organs; with limited histopathological changes observed only in the lungs. Analysis of the innate gene expression in the lungs showed a moderate, transient induction of expression. Our results indicate that MERS-CoV maintains the ability to replicate in bats without clinical signs of disease, supporting the general hypothesis of bats as ancestral reservoirs for MERS-CoV. url: https://doi.org/10.1038/srep21878 doi: 10.1038/srep21878 id: cord-331775-iaxkfszq author: Nachman, Dean title: Wireless, non-invasive, wearable device for continuous remote monitoring of hemodynamic parameters in a swine model of controlled hemorrhagic shock date: 2020-10-19 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Accurate and continuous monitoring of critically ill patients is frequently achieved using invasive catheters, which is technically complex. Our purpose was to evaluate the validity and accuracy of a photoplethysmography (PPG)-based remote monitoring device compared to invasive methods of arterial line (AL) and Swan-Ganz (SG) catheters in a swine model of controlled hemorrhagic shock. Following a baseline phase, hemorrhagic shock was induced in 11 pigs by bleeding 35% of their blood volume, followed by a post-bleeding follow-up phase. Animals were monitored concomitantly by the PPG device, an AL and a SG catheter, for a median period of 447 min. Heart rate (HR), systolic and diastolic blood pressure (SBP and DBP, respectively), and cardiac output (CO) were recorded continuously. The complete data set consisted of 1312 paired observations. Correlations between the PPG-based technique and the invasive methods were significant (p < 0.001) during baseline, bleeding and follow-up phases for HR (r = 0.90–0.98), SBP (r = 0.90–0.94), DBP (r = 0.89–0.93), and CO (r = 0.76–0.90). Intraclass correlations for all phases combined were 0.96, 0.92, 0.93 and 0.87 for HR, SBP, DBP and CO, respectively. Correlations for changes in CO, SBP and DBP were significant (p < 0.001) and strong (r > 0.88), with concordance rates (determined by quadrant plots) of 86%, 66% and 68%, respectively. The novel PPG-based device was accurate and valid compared to existing invasive techniques and might be used for continuous monitoring in several clinical settings following further studies. url: https://doi.org/10.1038/s41598-020-74686-6 doi: 10.1038/s41598-020-74686-6 id: cord-010140-nl1j2s56 author: Nagaoka, Hikaru title: Antibodies against a short region of PfRipr inhibit Plasmodium falciparum merozoite invasion and PfRipr interaction with Rh5 and SEMA7A date: 2020-04-20 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Plasmodium falciparum merozoite invasion into erythrocytes is an essential step of the blood-stage cycle, survival of parasites, and malaria pathogenesis. P. falciparum merozoite Rh5 interacting protein (PfRipr) forms a complex with Rh5 and CyRPA in sequential molecular events leading to erythrocyte invasion. Recently we described PfRipr as a conserved protein that induces strain-transcending growth inhibitory antibodies in in vitro assays. However, being a large and complex protein of 1086 amino acids (aa) with 87 cysteine residues, PfRipr is difficult to express in conventional expression systems towards vaccine development. In this study we sought to identify the most potent region of PfRipr that could be developed to overcome difficulties related to protein expression, as well as to elucidate the invasion inhibitory mechanism of anti-PfRipr antibodies. Using the wheat germ cell-free system, Ecto- PfRipr and truncates of approximately 200 aa were expressed as soluble proteins. We demonstrate that antibodies against PfRipr truncate 5 (PfRipr_5: C(720)-D(934)), a region within the PfRipr C-terminal EGF-like domains, potently inhibit merozoite invasion. Furthermore, the antibodies strongly block PfRipr/Rh5 interaction, as well as that between PfRipr and its erythrocyte-surface receptor, SEMA7A. Taken together, PfRipr_5 is a potential candidate for further development as a blood-stage malaria vaccine. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7171142/ doi: 10.1038/s41598-020-63611-6 id: cord-003387-82573enr author: Nam, Gyu-Hwi title: Gene expression profiles alteration after infection of virus, bacteria, and parasite in the Olive flounder (Paralichthys olivaceus) date: 2018-12-24 words: 5177.0 sentences: 279.0 pages: flesch: 43.0 cache: ./cache/cord-003387-82573enr.txt txt: ./txt/cord-003387-82573enr.txt summary: title: Gene expression profiles alteration after infection of virus, bacteria, and parasite in the Olive flounder (Paralichthys olivaceus) In this study, we carried out transcriptome analysis using the olive flounder gill tissues after infection of three types of pathogens (Virus; Viral hemorrhagic septicemia virus, Bacteria; Streptococcus parauberis, and Parasite; Miamiensis avidus), respectively. Our goals are to provide plenty of genomic knowledge about olive flounder transcripts for further research and report genes, which were changed in their expression after specific pathogen infection. To profile gene expression after infection of three pathogens (VHSV, Streptococcus parauberis, and Miamiensis avidus), transcriptome analysis was conducted using gill tissues of olive flounders, respectively. In this study, we understood the relation between three types of pathogen infection and differential gene expression in the olive flounder genome through transcriptome analysis, respectively. cDNA microarray analysis of viral hemorrhagic septicemia infected olive flounder, Paralichthys olivaceus: immune gene expression at different water temperature abstract: Olive flounder (Paralichthys olivaceus) is one of economically valuable fish species in the East Asia. In comparison with its economic importance, available genomic information of the olive flounder is very limited. The mass mortality caused by variety of pathogens (virus, bacteria and parasites) is main problem in aquaculture industry, including in olive flounder culture. In this study, we carried out transcriptome analysis using the olive flounder gill tissues after infection of three types of pathogens (Virus; Viral hemorrhagic septicemia virus, Bacteria; Streptococcus parauberis, and Parasite; Miamiensis avidus), respectively. As a result, we identified total 12,415 differentially expressed genes (DEG) from viral infection, 1,754 from bacterial infection, and 795 from parasite infection, respectively. To investigate the effects of pathogenic infection on immune response, we analyzed Gene ontology (GO) enrichment analysis with DEGs and sorted immune-related GO terms per three pathogen groups. Especially, we verified various GO terms, and genes in these terms showed down-regulated expression pattern. In addition, we identified 67 common genes (10 up-regulated and 57 down-regulated) present in three pathogen infection groups. Our goals are to provide plenty of genomic knowledge about olive flounder transcripts for further research and report genes, which were changed in their expression after specific pathogen infection. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6305387/ doi: 10.1038/s41598-018-36342-y id: cord-340781-z348xbn0 author: Namvar, Ali title: In silico/In vivo analysis of high-risk papillomavirus L1 and L2 conserved sequences for development of cross-subtype prophylactic vaccine date: 2019-10-23 words: 6646.0 sentences: 357.0 pages: flesch: 50.0 cache: ./cache/cord-340781-z348xbn0.txt txt: ./txt/cord-340781-z348xbn0.txt summary: Moreover, in vivo studies indicated that the combination of L1 and L2 DNA constructs without any adjuvant or delivery system induced effective immune responses, and protected mice against C3 tumor cells (the percentage of tumor-free mice: ~66.67%). The framework begins with conservancy analysis of all 13 high-risk HPV strains following with (1) B-cell epitope mapping, (2) T-cell epitope mapping (CD4 + and CD8 + ), (3) allergenicity assessment, (4) tap transport and proteasomal cleavage, (5) population coverage, (6) global and template-based docking and (7) data collection, analysis, and design of the L1 and L2 DNA constructs. In this study, for the first time, comprehensively integrated methods (using sequence-based tools in combination with flexible peptide-protein docking) were used to design highly immunogenic and protective vaccine candidates which were able to boost both humoral and cellular Table 12 . abstract: Human papillomavirus (HPV) is the most common sexually transmitted infection in the world and the main cause of cervical cancer. Nowadays, the virus-like particles (VLPs) based on L1 proteins have been considered as the best candidate for vaccine development against HPV infections. Two commercial HPV (Gardasil and Cervarix) are available. These HPV VLP vaccines induce genotype-limited protection. The major impediments such as economic barriers especially gaps in financing obstructed the optimal delivery of vaccines in developing countries. Thus, many efforts are underway to develop the next generation of vaccines against other types of high-risk HPV. In this study, we developed DNA constructs (based on L1 and L2 genes) that were potentially immunogenic and highly conserved among the high-risk HPV types. The framework of analysis include (1) B-cell epitope mapping, (2) T-cell epitope mapping (i.e., CD4(+) and CD8(+) T cells), (3) allergenicity assessment, (4) tap transport and proteasomal cleavage, (5) population coverage, (6) global and template-based docking, and (7) data collection, analysis, and design of the L1 and L2 DNA constructs. Our data indicated the 8-epitope candidates for helper T-cell and CTL in L1 and L2 sequences. For the L1 and L2 constructs, combination of these peptides in a single universal vaccine could involve all world population by the rate of 95.55% and 96.33%, respectively. In vitro studies showed high expression rates of multiepitope L1 (~57.86%) and L2 (~68.42%) DNA constructs in HEK-293T cells. Moreover, in vivo studies indicated that the combination of L1 and L2 DNA constructs without any adjuvant or delivery system induced effective immune responses, and protected mice against C3 tumor cells (the percentage of tumor-free mice: ~66.67%). Thus, the designed L1 and L2 DNA constructs would represent promising applications for HPV vaccine development. url: https://www.ncbi.nlm.nih.gov/pubmed/31645650/ doi: 10.1038/s41598-019-51679-8 id: cord-317579-ige2h4pd author: Nie, Lei title: Nanostructured selenium-doped biphasic calcium phosphate with in situ incorporation of silver for antibacterial applications date: 2020-08-13 words: 6082.0 sentences: 354.0 pages: flesch: 47.0 cache: ./cache/cord-317579-ige2h4pd.txt txt: ./txt/cord-317579-ige2h4pd.txt summary: The results confirmed that the SeO(3)(2−) was doped at the PO(4)(3−) position and silver nanoparticles were deposited on the surface of SeB-NPs. Next, Transmission Electron Microscopy (TEM) analysis displayed that the prepared (Ag)SeB-NPs had a needle-cluster-like morphology. At the same time, biphasic calcium phosphate nanoparticles (BCP-NPs) and selenium-doped hydroxyapatite nanoparticles (SeHA-NPs) were prepared for comparison (Electronic Supplementary Material). Compared with the control group, the doping selenium into BCP-NPs had slight influence on the antibacterial activity, and it had a slight inhibitory effect against bacteria of SeB-NPs after 12 h of culture. The stated objective of this study was to synthesis new-style biphasic calcium phosphate nanoparticles (BCP-NPs) with excellent cytocompatibility and antibacterial activity for further hard-tissue engineering applications. After the deposition of silver, cells cultured with all Ag SeB-NPs samples had similar proliferation profiles compared with SeB-NPs. Not only can the addition of selenium and silver improve the growth of the cells with BCP-NPs, but the antibacterial activity was acquired, which has potential for infection-resistant replacement materials 61, 62 . abstract: Selenium-doped nanostructure has been considered as an attractive approach to enhance the antibacterial activity of calcium phosphate (CaP) materials in diverse medical applications. In this study, the selenium-doped biphasic calcium phosphate nanoparticles (SeB-NPs) were first synthesized. Then, silver was in situ incorporated into SeB-NPs to obtain nanostructured composite nanoparticles ((Ag)SeB-NPs). Both SeB-NPs and (Ag)SeB-NPs were characterized by Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), ultraviolet–visible spectroscopy (UV–Vis), X-ray photoelectron spectroscopy (XPS), and Raman spectra. The results confirmed that the SeO(3)(2−) was doped at the PO(4)(3−) position and silver nanoparticles were deposited on the surface of SeB-NPs. Next, Transmission Electron Microscopy (TEM) analysis displayed that the prepared (Ag)SeB-NPs had a needle-cluster-like morphology. CCK-8 analysis revealed SeB-NPs and (Ag)SeB-NPs had good cytocompatibility with osteoblasts. The antibacterial activity of the prepared (Ag)SeB-NPs was confirmed by using Gram-negative E. coli and Gram-positive S. aureus. The above results manifested the significance of the final (Ag)SeB-NPs for biomedical applications. url: https://www.ncbi.nlm.nih.gov/pubmed/32792661/ doi: 10.1038/s41598-020-70776-7 id: cord-001116-2yvyiiuy author: Nikas, Jason B. title: Inflammation and Immune System Activation in Aging: A Mathematical Approach date: 2013-11-19 words: 4534.0 sentences: 199.0 pages: flesch: 49.0 cache: ./cache/cord-001116-2yvyiiuy.txt txt: ./txt/cord-001116-2yvyiiuy.txt summary: Since those functions are associated with the hippocampus, I analyzed the global gene expression data from post-mortem hippocampal tissue of 25 old (age ≥ 60 yrs) and 15 young (age ≤ 45 yrs) cognitively intact human subjects. Having employed three different and independent methods of statistical significance, namely, ROC curve analysis, fold change, and P-value, I was able to identify 36 genes that were the most significant in terms of differential expression. The seven genes [C4A (C4B), ADORA3, MS4A7, BCL6, CD44, C3AR1, and HLA-DRB1], which are the constituent input variables of the model (F 1 super variable), and all of which are -in terms of function -inflammation or immune system activation genes (Table 1) , were all found to be over-expressed in the old subjects compared with the young subjects (Table 1) . abstract: Memory and learning declines are consequences of normal aging. Since those functions are associated with the hippocampus, I analyzed the global gene expression data from post-mortem hippocampal tissue of 25 old (age ≥ 60 yrs) and 15 young (age ≤ 45 yrs) cognitively intact human subjects. By employing a rigorous, multi-method bioinformatic approach, I identified 36 genes that were the most significant in terms of differential expression; and by employing mathematical modeling, I demonstrated that 7 of the 36 genes were able to discriminate between the old and young subjects with high accuracy. Remarkably, 90% of the known genes from those 36 most significant genes are associated with either inflammation or immune system activation. This suggests that chronic inflammation and immune system over-activity may underlie the aging process of the human brain, and that potential anti-inflammatory treatments targeting those genes may slow down this process and alleviate its symptoms. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3832874/ doi: 10.1038/srep03254 id: cord-003166-k3jxvzfi author: Noh, Ji Yeong title: Isolation and characterization of novel bat paramyxovirus B16-40 potentially belonging to the proposed genus Shaanvirus date: 2018-08-22 words: 4670.0 sentences: 244.0 pages: flesch: 51.0 cache: ./cache/cord-003166-k3jxvzfi.txt txt: ./txt/cord-003166-k3jxvzfi.txt summary: Even though the HN amino acids sequences were similar to those from viruses in the proposed genera Shaanvirus, it was also related to that of Sendai virus and human parainfluenza virus 1, which belong to a different genus, Respirovirus showing (Table 1) . In addition, among three pooled sera (two mouse sera each) against human parainfluenza virus 1 (KBPV-VR-44), one pooled serum was cross-reactive to the bat paramyxovirus B16-40 with 40 as the end-point titer for the fluorescent signal ( Table 2 , Fig. 4 ). Notably, even though the HN amino acids sequences were similar to those from viruses in the proposed genera Shaanvirus, it was also related to that of Sendai virus and human parainfluenza virus 1, which belong to a different genus, Respirovirus (Table 1) . In fact, in this study, when mouse antisera were made and tested against bat paramyxovirus B16-40 and human parainfluenza virus 1 (KBPV-VR-44), the two viruses were partially cross-reactive to each other in an indirect immunofluorescence assay. abstract: The bat paramyxovirus B16-40 was first isolated in Korea in this study. Using the isolated virus, we could obtain not only genomic information, but also several biological characteristics of the virus. In the phylogenetic analysis, the virus was found to belong to the recently proposed genus Shaanvirus. Through sequence analyses and in vitro testing, the isolated virus was also found to have haemagglutinin-neuraminidase (HN) protein as one of the structural proteins. When mouse antiserum was generated against the isolated virus and tested, it was cross-reactive to human parainfluenza virus 1 in an indirect immunofluorescence assay but could not cross-neutralize human parainfluenza virus 1. In addition, the bat paramyxovirus B16-40 was not infectious in the mouse model. Collectively, this study provided basic information on further classification of the bat paramyxovirus B16-40 and related viruses in the proposed genus Shaanvirus. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6105681/ doi: 10.1038/s41598-018-30319-7 id: cord-034746-uxhpufnv author: Nusshag, Christian title: Glomerular filtration barrier dysfunction in a self-limiting, RNA virus-induced glomerulopathy resembles findings in idiopathic nephrotic syndromes date: 2020-11-05 words: 3642.0 sentences: 194.0 pages: flesch: 36.0 cache: ./cache/cord-034746-uxhpufnv.txt txt: ./txt/cord-034746-uxhpufnv.txt summary: We therefore analyzed standard markers of glomerular proteinuria (e.g. immunoglobulin G [IgG]), urinary nephrin excretion (podocyte injury) and serum levels of the soluble urokinase plasminogen activator receptor (suPAR), a proposed pathomechanically involved molecule in INS, in PUUV-infected patients. On admission, patients suffering from hantavirus infection showed significantly increased urinary nephrin, IgG, α1-MG and serum suPAR levels compared to healthy controls (Fig. 3A ). Though, urinary biomarker levels decreased in both groups over time, patients with severe PCR showed significantly higher levels of nephrin, IgG, ACR and PCR during the first 48 h after admission ( Table 2 ). Our data show a strong association between urinary nephrin levels and the extent of (non-selective) glomerular proteinuria, suggesting that hantavirus infection causes a pronounced podocyte damage and subsequent impairment of the GFB. To date, one other study showed significantly elevated blood suPAR levels and their association with hantavirus disease severity but did not include nephrinuria and the extent of proteinuria in their analysis 19 . abstract: Podocyte injury has recently been described as unifying feature in idiopathic nephrotic syndromes (INS). Puumala hantavirus (PUUV) infection represents a unique RNA virus-induced renal disease with significant proteinuria. The underlying pathomechanism is unclear. We hypothesized that PUUV infection results in podocyte injury, similar to findings in INS. We therefore analyzed standard markers of glomerular proteinuria (e.g. immunoglobulin G [IgG]), urinary nephrin excretion (podocyte injury) and serum levels of the soluble urokinase plasminogen activator receptor (suPAR), a proposed pathomechanically involved molecule in INS, in PUUV-infected patients. Hantavirus patients showed significantly increased urinary nephrin, IgG and serum suPAR concentrations compared to healthy controls. Nephrin and IgG levels were significantly higher in patients with severe proteinuria than with mild proteinuria, and nephrin correlated strongly with biomarkers of glomerular proteinuria over time. Congruently, electron microcopy analyses showed a focal podocyte foot process effacement. suPAR correlated significantly with urinary nephrin, IgG and albumin levels, suggesting suPAR as a pathophysiological mediator in podocyte dysfunction. In contrast to INS, proteinuria recovered autonomously in hantavirus patients. This study reveals podocyte injury as main cause of proteinuria in hantavirus patients. A better understanding of the regenerative nature of hantavirus-induced glomerulopathy may generate new therapeutic approaches for INS. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7644703/ doi: 10.1038/s41598-020-76050-0 id: cord-004150-ybikajhh author: Nyarko, Prince B. title: Investigating a Plasmodium falciparum erythrocyte invasion phenotype switch at the whole transcriptome level date: 2020-01-14 words: 6221.0 sentences: 323.0 pages: flesch: 39.0 cache: ./cache/cord-004150-ybikajhh.txt txt: ./txt/cord-004150-ybikajhh.txt summary: The genes with most markedly increased expression included members of the erythrocyte binding antigens (EBA), reticulocyte binding homologues (RH), surface associated interspersed proteins (SURFIN), exported protein family 1 (EPF1) and Plasmodium Helical Interspersed Sub-Telomeric (PHIST) gene families. The data indicate changes in expression of a repertoire of genes not previously associated with erythrocyte invasion phenotypes, suggesting the possibility that moving suspension culture may also select for other traits. Additionally, a large number of virulence associated genes, including members of the surface-associated interspersed protein (SURFIN) family, exported protein family 1 (EPF1), ring exported protein 1 (REX1) and interspersed repeat antigen (FIRA); all of which are exported into host erythrocytes, were significantly expressed at higher levels in SP parasites relative to BL (Fig. 2) . A comparison of the levels of differential expression of the eba and rh gene between ST and SP parasites in the current RNA sequencing study and our previous RT-qPCR analysis shows a strong positive correlation of results from the two studies ( Supplementary Fig. 12 ). abstract: The central role that erythrocyte invasion plays in Plasmodium falciparum survival and reproduction makes this process an attractive target for therapeutic or vaccine development. However, multiple invasion-related genes with complementary and overlapping functions afford the parasite the plasticity to vary ligands used for invasion, leading to phenotypic variation and immune evasion. Overcoming the challenge posed by redundant ligands requires a deeper understanding of conditions that select for variant phenotypes and the molecular mediators. While host factors including receptor heterogeneity and acquired immune responses may drive parasite phenotypic variation, we have previously shown that host-independent changes in invasion phenotype can be achieved by continuous culturing of the W2mef and Dd2 P. falciparum strains in moving suspension as opposed to static conditions. Here, we have used a highly biologically replicated whole transcriptome sequencing approach to identify the molecular signatures of variation associated with the phenotype switch. The data show increased expression of particular invasion-related genes in switched parasites, as well as a large number of genes encoding proteins that are either exported or form part of the export machinery. The genes with most markedly increased expression included members of the erythrocyte binding antigens (EBA), reticulocyte binding homologues (RH), surface associated interspersed proteins (SURFIN), exported protein family 1 (EPF1) and Plasmodium Helical Interspersed Sub-Telomeric (PHIST) gene families. The data indicate changes in expression of a repertoire of genes not previously associated with erythrocyte invasion phenotypes, suggesting the possibility that moving suspension culture may also select for other traits. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6959351/ doi: 10.1038/s41598-019-56386-y id: cord-345359-okmkgsbr author: Ohno, Marumi title: Influenza virus infection affects insulin signaling, fatty acid-metabolizing enzyme expressions, and the tricarboxylic acid cycle in mice date: 2020-07-02 words: 6474.0 sentences: 314.0 pages: flesch: 45.0 cache: ./cache/cord-345359-okmkgsbr.txt txt: ./txt/cord-345359-okmkgsbr.txt summary: After infecting mice with intranasal applications of 500 plaque-forming units of A/Puerto Rico/8/34 (H1N1; PR8) virus, the serum levels of most intermediates in the tricarboxylic acid (TCA) cycle and related metabolic pathways were significantly reduced. www.nature.com/scientificreports/ investigated metabolic changes by determining the serum levels of metabolites, insulin sensitivity in the liver, glucose availability, and hepatic gene expressions in the early stages of symptom onset as well as the lethal phase of influenza in a mouse model. The results of this study indicate that influenza virus infection dysregulates glucose and fatty acid metabolism and decreases tricarboxylic acid (TCA) cycle activity, leading to enhanced degradation of adenosine triphosphate (ATP) and guanosine triphosphate (GTP). Metabolites that were present at reduced levels in the sera of PR8 virus-infected mice were mainly related to the TCA cycle, urea cycle, and amino acid metabolism, as indicated by the serum levels of metabolite in these pathways at 1, 3, and 6 dpi (Fig. 2) . abstract: Although the severity of influenza virus infections has been associated with host energy metabolism, the related mechanisms have not yet been clarified. Here we examined the effects of influenza virus infection on host energy metabolism in mice. After infecting mice with intranasal applications of 500 plaque-forming units of A/Puerto Rico/8/34 (H1N1; PR8) virus, the serum levels of most intermediates in the tricarboxylic acid (TCA) cycle and related metabolic pathways were significantly reduced. These data suggest that substrate supply to the TCA cycle is reduced under these conditions, rather than specific metabolic reactions being inhibited. Then, we focused on glucose and fatty acid metabolism that supply substrates to the TCA cycle. Akt phosphorylation following insulin injections was attenuated in the livers of PR8 virus-infected mice. Furthermore, glucose tolerance tests revealed that the PR8 virus-infected mice showed higher blood glucose levels than the vehicle-inoculated control mice. These results suggest that influenza virus infection impairs insulin signaling, which regulates glucose uptake. However, increases in the hepatic expressions of fatty acid-metabolizing enzymes suggest that fatty acids accumulate in liver cells of infected mice. Collectively, our data indicate that influenza virus infection dysregulates host energy metabolism. This line of investigation provides novel insights into the pathogenesis of influenza. url: https://doi.org/10.1038/s41598-020-67879-6 doi: 10.1038/s41598-020-67879-6 id: cord-302080-fegcf1fu author: Oliveira-de-Souza, Deivide title: Aging increases the systemic molecular degree of inflammatory perturbation in patients with tuberculosis date: 2020-07-09 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Tuberculosis (TB) is a chronic infection that can affect individuals of all ages. The description of determinants of immunopathogenesis in TB is of tremendous interest due to the perspective of finding a reliable host-directed therapy to reduce disease burden. The association between specific biomarker profiles related to inflammation and the diverse clinical disease presentations in TB has been extensively studied in adults. However, relatively scarce data on profiling the inflammatory responses in pediatric TB are available. Here, we employed the molecular degree of perturbation (MDP) score adapted to plasma biomarkers in two distinct databanks from studies that examined either adults or children presenting with pulmonary or extrapulmonary disease. We used multidimensional statistical analyses to characterize the impact of age on the overall changes in the systemic inflammation profiles in subpopulation of TB patients. Our findings indicate that TB results in significant increases in molecular perturbation, with the highest values being detected in adult patients. Furthermore, there were unique differences in the biomarker perturbation patterns and the overall degree of inflammation according to disease site and age. Importantly, the molecular degree of perturbation was not influenced by sex. Our results revealed that aging is an important determinant of the differences in quality and magnitude of systemic inflammatory perturbation in distinct clinical forms of TB. url: https://doi.org/10.1038/s41598-020-68255-0 doi: 10.1038/s41598-020-68255-0 id: cord-322486-qwl7nzkr author: Omori, Ryosuke title: The age distribution of mortality from novel coronavirus disease (COVID-19) suggests no large difference of susceptibility by age date: 2020-10-06 words: 4857.0 sentences: 247.0 pages: flesch: 52.0 cache: ./cache/cord-322486-qwl7nzkr.txt txt: ./txt/cord-322486-qwl7nzkr.txt summary: We estimated the parameter which describes the age-dependency of susceptibility by fitting the model to reported data, including the effect of change in contact patterns during the epidemics of COVID-19, and the fraction of symptomatic infections. Our study revealed that if the mortality rate or the fraction of symptomatic infections among all COVID-19 cases does not depend on age, then unrealistically different age-dependencies of susceptibilities against COVID-19 infections between Italy, Japan, and Spain are required to explain the similar age distribution of mortality but different basic reproduction numbers (R(0)). Assuming that the age-dependency of mortality by COVID-19 is determined by only age-dependent susceptibility (model 1), i.e., the mortality rate does not depend on age, the exponent parameter, φ, describing the variation of susceptibility among age groups for each country, Italy, Japan, and Spain, was estimated as shown in Fig. 4 . abstract: Among Italy, Spain, and Japan, the age distributions of COVID-19 mortality show only small variation even though the number of deaths per country shows large variation. To understand the determinant for this situation, we constructed a mathematical model describing the transmission dynamics and natural history of COVID-19 and analyzed the dataset of mortality in Italy, Spain, and Japan. We estimated the parameter which describes the age-dependency of susceptibility by fitting the model to reported data, including the effect of change in contact patterns during the epidemics of COVID-19, and the fraction of symptomatic infections. Our study revealed that if the mortality rate or the fraction of symptomatic infections among all COVID-19 cases does not depend on age, then unrealistically different age-dependencies of susceptibilities against COVID-19 infections between Italy, Japan, and Spain are required to explain the similar age distribution of mortality but different basic reproduction numbers (R(0)). Variation of susceptibility by age itself cannot explain the robust age distribution in mortality by COVID-19 infections in those three countries, however it does suggest that the age-dependencies of (i) the mortality rate and (ii) the fraction of symptomatic infections among all COVID-19 cases determine the age distribution of mortality by COVID-19. url: https://doi.org/10.1038/s41598-020-73777-8 doi: 10.1038/s41598-020-73777-8 id: cord-002758-d86hnox1 author: Opuu, Vaitea title: Computational design of fully overlapping coding schemes for protein pairs and triplets date: 2017-11-20 words: 5501.0 sentences: 303.0 pages: flesch: 64.0 cache: ./cache/cord-002758-d86hnox1.txt txt: ./txt/cord-002758-d86hnox1.txt summary: We have examined the possibility to encode an arbitrary pair of protein domains as a dual gene, with the shorter coding sequence completely embedded in the longer one. An example of a designed overlapping gene was produced recently, where each DNA strand coded for a simplified but functional aminoacyl-tRNA synthetase "Urzyme" [13] [14] [15] [16] , with the two enzymes being homologous to the two modern synthetase classes. Considering all three reading frames, we found that over 16% of the (X, Y) pairs have homologous pairs (X′, Y′) that can be encoded in a fully overlapping manner, with a level of X/X′ and Y/Y′ homology corresponding to Blast E-values of 10 −10 or less and a match length of at least 85% of the total sequence length. Given the level of success and the generality of our algorithm, we also designed 200 triple genes, with three proteins encoded by the same DNA segment using both strands and three different reading frames. abstract: Gene pairs that overlap in their coding regions are rare except in viruses. They may occur transiently in gene creation and are of biotechnological interest. We have examined the possibility to encode an arbitrary pair of protein domains as a dual gene, with the shorter coding sequence completely embedded in the longer one. For 500 × 500 domain pairs (X, Y), we computationally designed homologous pairs (X′, Y′) coded this way, using an algorithm that provably maximizes the sequence similarity between (X′, Y′) and (X, Y). Three schemes were considered, with X′ and Y′ coded on the same or complementary strands. For 16% of the pairs, an overlapping coding exists where the level of homology of X′, Y′ to the natural proteins represents an E-value of 10(−10) or better. Thus, for an arbitrary domain pair, it is surprisingly easy to design homologous sequences that can be encoded as a fully-overlapping gene pair. The algorithm is general and was used to design 200 triple genes, with three proteins encoded by the same DNA segment. The ease of design suggests overlapping genes may have occurred frequently in evolution and could be readily used to compress or constrain artificial genomes. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5696523/ doi: 10.1038/s41598-017-16221-8 id: cord-318314-oxlv847d author: O’Boyle, Nicky title: Differentiated ovine tracheal epithelial cells support the colonisation of pathogenic and non-pathogenic strains of Mannheimia haemolytica date: 2020-09-11 words: 5482.0 sentences: 266.0 pages: flesch: 39.0 cache: ./cache/cord-318314-oxlv847d.txt txt: ./txt/cord-318314-oxlv847d.txt summary: Comparison of single representative pathogenic and non-pathogenic ovine isolates over ten time-points by enumeration of tissue-associated bacteria, histology, immunofluorescence microscopy and scanning electron microscopy revealed temporal differences in adhesion, proliferation, bacterial cell physiology and host cell responses. Comparison of eight isolates of bovine and ovine origin at three key time-points (2 h, 48 h and 72 h), revealed that colonisation was not strictly pathogen or serotype specific, with isolates of serotype A1, A2, A6 and A12 being capable of colonising the cell layer regardless of host species or disease status of the host. haemolytica 11, 38 , coupled with a suggested role for the polysaccharide capsule (on which the serotyping classification is based) in cell adhesion 17 , indicates that isolates may be specifically adapted to colonising the airway tissues of discrete hosts. We assessed whether interactions with differentiated OTECs could reflect this species-specificity by analysing colonisation of pathogenic and non-pathogenic isolates of both bovine and ovine origin. abstract: Mannheimia haemolytica is the primary bacterial species associated with respiratory disease of ruminants. A lack of cost-effective, reproducible models for the study of M. haemolytica pathogenesis has hampered efforts to better understand the molecular interactions governing disease progression. We employed a highly optimised ovine tracheal epithelial cell model to assess the colonisation of various pathogenic and non-pathogenic M. haemolytica isolates of bovine and ovine origin. Comparison of single representative pathogenic and non-pathogenic ovine isolates over ten time-points by enumeration of tissue-associated bacteria, histology, immunofluorescence microscopy and scanning electron microscopy revealed temporal differences in adhesion, proliferation, bacterial cell physiology and host cell responses. Comparison of eight isolates of bovine and ovine origin at three key time-points (2 h, 48 h and 72 h), revealed that colonisation was not strictly pathogen or serotype specific, with isolates of serotype A1, A2, A6 and A12 being capable of colonising the cell layer regardless of host species or disease status of the host. A trend towards increased proliferative capacity by pathogenic ovine isolates was observed. These results indicate that the host-specific nature of M. haemolytica infection may result at least partially from the colonisation-related processes of adhesion, invasion and proliferation at the epithelial interface. url: https://www.ncbi.nlm.nih.gov/pubmed/32917945/ doi: 10.1038/s41598-020-71604-8 id: cord-312777-5925lvue author: Pan, Feng title: Different computed tomography patterns of Coronavirus Disease 2019 (COVID-19) between survivors and non-survivors date: 2020-07-09 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: This study aimed to compare the chest computed tomography (CT) findings between survivors and non-survivors with Coronavirus Disease 2019 (COVID-19). Between 12 January 2020 and 20 February 2020, the records of 124 consecutive patients diagnosed with COVID-19 were retrospectively reviewed and divided into survivor (83/124) and non-survivor (41/124) groups. Chest CT findings were qualitatively compared on admission and serial chest CT scans were semi-quantitively evaluated between two groups using curve estimations. On admission, significantly more bilateral (97.6% vs. 73.5%, p = 0.001) and diffuse lesions (39.0% vs. 8.4%, p < 0.001) with higher total CT score (median 10 vs. 4, p < 0.001) were observed in non-survivor group compared with survivor group. Besides, crazy-paving pattern was more predominant in non-survivor group than survivor group (39.0% vs. 12.0%, p < 0.001). From the prediction of curve estimation, in survivor group total CT score increased in the first 20 days reaching a peak of 6 points and then gradually decreased for more than other 40 days (R(2) = 0.545, p < 0.001). In non-survivor group, total CT score rapidly increased over 10 points in the first 10 days and gradually increased afterwards until ARDS occurred with following death events (R(2) = 0.711, p < 0.001). In conclusion, persistent progression with predominant crazy-paving pattern was the major manifestation of COVID-19 in non-survivors. Understanding this CT feature could help the clinical physician to predict the prognosis of the patients. url: https://doi.org/10.1038/s41598-020-68057-4 doi: 10.1038/s41598-020-68057-4 id: cord-002842-4evbeijx author: Pandey, Rajan Kumar title: Novel Immunoinformatics Approaches to Design Multi-epitope Subunit Vaccine for Malaria by Investigating Anopheles Salivary Protein date: 2018-01-18 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Malaria fever has been pervasive for quite a while in tropical developing regions causing high morbidity and mortality. The causal organism is a protozoan parasite of genus Plasmodium which spreads to the human host by the bite of hitherto infected female Anopheles mosquito. In the course of biting, a salivary protein of Anopheles helps in blood feeding behavior and having the ability to elicit the host immune response. This study represents a series of immunoinformatics approaches to design multi-epitope subunit vaccine using Anopheles mosquito salivary proteins. Designed subunit vaccine was evaluated for its immunogenicity, allergenicity and physiochemical parameters. To enhance the stability of vaccine protein, disulfide engineering was performed in a region of high mobility. Codon adaptation and in silico cloning was also performed to ensure the higher expression of designed subunit vaccine in E. coli K12 expression system. Finally, molecular docking and simulation study was performed for the vaccine protein and TLR-4 receptor, to determine the binding free energy and complex stability. Moreover, the designed subunit vaccine was found to induce anti-salivary immunity which may have the ability to prevent the entry of Plasmodium sporozoites into the human host. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5773588/ doi: 10.1038/s41598-018-19456-1 id: cord-321667-jkzxjk54 author: Papineau, Amber title: Genome Organization of Canada Goose Coronavirus, A Novel Species Identified in a Mass Die-off of Canada Geese date: 2019-04-11 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The complete genome of a novel coronavirus was sequenced directly from the cloacal swab of a Canada goose that perished in a die-off of Canada and Snow geese in Cambridge Bay, Nunavut, Canada. Comparative genomics and phylogenetic analysis indicate it is a new species of Gammacoronavirus, as it falls below the threshold of 90% amino acid similarity in the protein domains used to demarcate Coronaviridae. Additional features that distinguish the genome of Canada goose coronavirus include 6 novel ORFs, a partial duplication of the 4 gene and a presumptive change in the proteolytic processing of polyproteins 1a and 1ab. url: https://www.ncbi.nlm.nih.gov/pubmed/30976080/ doi: 10.1038/s41598-019-42355-y id: cord-284374-sqxlnk9e author: Park, Jiyeon title: Infection Prevention Measures for Surgical Procedures during a Middle East Respiratory Syndrome Outbreak in a Tertiary Care Hospital in South Korea date: 2020-01-15 words: 4252.0 sentences: 208.0 pages: flesch: 44.0 cache: ./cache/cord-284374-sqxlnk9e.txt txt: ./txt/cord-284374-sqxlnk9e.txt summary: title: Infection Prevention Measures for Surgical Procedures during a Middle East Respiratory Syndrome Outbreak in a Tertiary Care Hospital in South Korea Our experience with setting up a temporary negative-pressure operation room and our conservative approach for managing MERS-related patients can be referred in cases of future unexpected MERS outbreaks in non-endemic countries. Anesthesiologists were recommended to apply enhanced PPE (including PAPR from the middle of the outbreak) when managing all MERS-related patients because they were most directly exposed to the aerosol-producing high-risk procedures, such as endotracheal intubation and extubation. Almost all hospitals generally have positive-pressure operating rooms and they may experience an outbreak without facilities that are prepared for perioperative management of MERS patients, as our hospital did in 2015. First, although the previous guidelines recommended that asymptomatic MERS-exposed patients be managed as general patients undergoing surgery, we applied standard PPE to HCWs and we performed MERS-CoV PCR screening twice. abstract: In 2015, we experienced the largest in-hospital Middle East respiratory syndrome (MERS) outbreak outside the Arabian Peninsula. We share the infection prevention measures for surgical procedures during the unexpected outbreak at our hospital. We reviewed all forms of related documents and collected information through interviews with healthcare workers of our hospital. After the onset of outbreak, a multidisciplinary team devised institutional MERS-control guidelines. Two standard operating rooms were converted to temporary negative-pressure rooms by physically decreasing the inflow air volume (−4.7 Pa in the main room and −1.2 Pa in the anteroom). Healthcare workers were equipped with standard or enhanced personal protective equipment according to the MERS-related patient’s profile and symptoms. Six MERS-related patients underwent emergency surgery, including four MERS-exposed and two MERS-confirmed patients. Negative conversion of MERS-CoV polymerase chain reaction tests was noticed for MERS-confirmed patients before surgery. MERS-exposed patients were also tested twice preoperatively, all of which were negative. All operative procedures in MERS-related patients were performed without specific adverse events or perioperative MERS transmission. Our experience with setting up a temporary negative-pressure operation room and our conservative approach for managing MERS-related patients can be referred in cases of future unexpected MERS outbreaks in non-endemic countries. url: https://doi.org/10.1038/s41598-019-57216-x doi: 10.1038/s41598-019-57216-x id: cord-001858-nmi39n6h author: Petriccione, Milena title: Reference gene selection for normalization of RT-qPCR gene expression data from Actinidia deliciosa leaves infected with Pseudomonas syringae pv. actinidiae date: 2015-11-19 words: 5567.0 sentences: 286.0 pages: flesch: 50.0 cache: ./cache/cord-001858-nmi39n6h.txt txt: ./txt/cord-001858-nmi39n6h.txt summary: title: Reference gene selection for normalization of RT-qPCR gene expression data from Actinidia deliciosa leaves infected with Pseudomonas syringae pv. Primer sequence (5′-3′) BestKeeper and the deltaCt method) were used to evaluate the stability of expression of selected RGs. The analyses were performed for three comparison groups considering both low-and high-dose bacterial inocula in the leaves and their combined dataset. In kiwifruit leaves with a high dose of bacterial inoculum, BestKeeper revealed that only the expression of TUB overcame the stability threshold; CYP and GAPDH were considered to be the most stable genes, with SD values of 0.50 and 0.61, respectively (Table 3 ). The expression of three genes encoding the reactive oxygen species (ROS) scavenging enzymes ascorbate peroxidase (APX), superoxide dismutase (SOD) and catalase (CAT), induced during the systemic infection of kiwifruit leaves with PSA, were chosen to further validate the reliability of the selected RGs for the normalization of RT-qPCR data. abstract: Normalization of data, by choosing the appropriate reference genes (RGs), is fundamental for obtaining reliable results in reverse transcription-quantitative PCR (RT-qPCR). In this study, we assessed Actinidia deliciosa leaves inoculated with two doses of Pseudomonas syringae pv. actinidiae during a period of 13 days for the expression profile of nine candidate RGs. Their expression stability was calculated using four algorithms: geNorm, NormFinder, BestKeeper and the deltaCt method. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and protein phosphatase 2A (PP2A) were the most stable genes, while β-tubulin and 7s-globulin were the less stable. Expression analysis of three target genes, chosen for RGs validation, encoding the reactive oxygen species scavenging enzymes ascorbate peroxidase (APX), superoxide dismutase (SOD) and catalase (CAT) indicated that a combination of stable RGs, such as GAPDH and PP2A, can lead to an accurate quantification of the expression levels of such target genes. The APX level varied during the experiment time course and according to the inoculum doses, whereas both SOD and CAT resulted down-regulated during the first four days, and up-regulated afterwards, irrespective of inoculum dose. These results can be useful for better elucidating the molecular interaction in the A. deliciosa/P. s. pv. actinidiae pathosystem and for RGs selection in bacteria-plant pathosystems. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4652207/ doi: 10.1038/srep16961 id: cord-002111-mmpijsqb author: Philp, Lisa K. title: Small Glutamine-Rich Tetratricopeptide Repeat-Containing Protein Alpha (SGTA) Ablation Limits Offspring Viability and Growth in Mice date: 2016-06-30 words: 7064.0 sentences: 399.0 pages: flesch: 53.0 cache: ./cache/cord-002111-mmpijsqb.txt txt: ./txt/cord-002111-mmpijsqb.txt summary: title: Small Glutamine-Rich Tetratricopeptide Repeat-Containing Protein Alpha (SGTA) Ablation Limits Offspring Viability and Growth in Mice Small glutamine-rich tetratricopeptide repeat-containing protein α (SGTA) has been implicated as a co-chaperone and regulator of androgen and growth hormone receptor (AR, GHR) signalling. As some, but not all, androgen-regulated organs displayed potential signs of hyperandrogenisation during development in Sgta +/− and Sgta −/− mutants, we measured Ar mRNA expression in androgen-regulated tissues, the brain, and the prostate and testis in males, and the mammary and ovary in females (Fig. 4C) . However, the relative weights of vital and sex organs, adipose tissue, muscle and bone were not affected by a genotype* age interaction, suggesting that Sgta-null mice are not any more vulnerable to age-related stress than WT. Small glutamine-rich tetratricopeptide repeat-containing protein (SGT) interacts with the ubiquitin-dependent endocytosis (UbE) motif of the growth hormone receptor abstract: Small glutamine-rich tetratricopeptide repeat-containing protein α (SGTA) has been implicated as a co-chaperone and regulator of androgen and growth hormone receptor (AR, GHR) signalling. We investigated the functional consequences of partial and full Sgta ablation in vivo using Cre-lox Sgta-null mice. Sgta(+/−) breeders generated viable Sgta(−/−) offspring, but at less than Mendelian expectancy. Sgta(−/−) breeders were subfertile with small litters and higher neonatal death (P < 0.02). Body size was significantly and proportionately smaller in male and female Sgta(−/−) (vs WT, Sgta(+/−) P < 0.001) from d19. Serum IGF-1 levels were genotype- and sex-dependent. Food intake, muscle and bone mass and adiposity were unchanged in Sgta(−/−). Vital and sex organs had normal relative weight, morphology and histology, although certain androgen-sensitive measures such as penis and preputial size, and testis descent, were greater in Sgta(−/−). Expression of AR and its targets remained largely unchanged, although AR localisation was genotype- and tissue-dependent. Generally expression of other TPR-containing proteins was unchanged. In conclusion, this thorough investigation of SGTA-null mutation reports a mild phenotype of reduced body size. The model’s full potential likely will be realised by genetic crosses with other models to interrogate the role of SGTA in the many diseases in which it has been implicated. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4928056/ doi: 10.1038/srep28950 id: cord-350255-tthttyl3 author: Poirier, Canelle title: The role of environmental factors on transmission rates of the COVID-19 outbreak: an initial assessment in two spatial scales date: 2020-10-12 words: 4288.0 sentences: 205.0 pages: flesch: 47.0 cache: ./cache/cord-350255-tthttyl3.txt txt: ./txt/cord-350255-tthttyl3.txt summary: To disentangle if our reproductive number estimates could be explained by importation of cases from Wuhan, Hubei, alone; and if they could be interpreted as indicators of local transmission, we formulated a linear model with the local R proxy as the response variable, and human mobility as a predictor at the province level. In all steps of filtering at the province-level, and for both time periods, τ 1 and τ 2 , absolute humidity was not associated to R proxy , with P values ranging between 0.161 and 0.922 (Tables 9, 10 , 11, 12, 13, 14, 15) . For cities, for time-period τ 1 , and after the first step of filtering, absolute humidity appeared to be associate with R proxy with a p value equal to 0.004 (Supplementary Table S5 ). abstract: First identified in Wuhan, China, in December 2019, a novel coronavirus (SARS-CoV-2) has affected over 16,800,000 people worldwide as of July 29, 2020 and was declared a pandemic by the World Health Organization on March 11, 2020. Influenza studies have shown that influenza viruses survive longer on surfaces or in droplets in cold and dry air, thus increasing the likelihood of subsequent transmission. A similar hypothesis has been postulated for the transmission of COVID-19, the disease caused by SARS-CoV-2. It is important to propose methodologies to understand the effects of environmental factors on this ongoing outbreak to support decision-making pertaining to disease control. Here, we examine the spatial variability of the basic reproductive numbers of COVID-19 across provinces and cities in China and show that environmental variables alone cannot explain this variability. Our findings suggest that changes in weather (i.e., increase of temperature and humidity as spring and summer months arrive in the Northern Hemisphere) will not necessarily lead to declines in case counts without the implementation of drastic public health interventions. url: https://doi.org/10.1038/s41598-020-74089-7 doi: 10.1038/s41598-020-74089-7 id: cord-330562-dabjcvno author: Poli, Piero title: The 2020 coronavirus lockdown and seismic monitoring of anthropic activities in Northern Italy date: 2020-06-10 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: In March/April 2020 the Italian government drastically reduced vehicle traffic and interrupted all non-essential industrial activities over the entire national territory. Italy thus became the first country in the world, with the exception of Hubei, to enact lockdown measures as a consequence of the COVID-19 outbreak and the need to contain it. Italy is also a seismically active area, and as such is monitored by a dense permanent network of seismic stations. We analyse continuous seismic data from many stations in northern and central Italy, and quantify the impact of the lockdown on seismic ambient noise, as a function of time and location. We find that the lockdown reduces ambient noise significantly in the 1–10 Hz frequency range; because natural sources of seismic noise are not affected by the lockdown, the seismic signature of anthropic noise can be characterised with unprecedented clarity, by simply comparing the signal recorded before and after the lockdown. Our results correlate well with independent evaluations of the impact of the lockdown (e.g., cell phone displacements), and we submit that ambient-noise seismology is a useful tool to monitor containment measures such as the coronavirus lockdowns. url: https://doi.org/10.1038/s41598-020-66368-0 doi: 10.1038/s41598-020-66368-0 id: cord-344953-gtg12hiu author: Prather, Randall S. title: Knockout of maternal CD163 protects fetuses from infection with porcine reproductive and respiratory syndrome virus (PRRSV) date: 2017-10-17 words: 2628.0 sentences: 158.0 pages: flesch: 55.0 cache: ./cache/cord-344953-gtg12hiu.txt txt: ./txt/cord-344953-gtg12hiu.txt summary: title: Knockout of maternal CD163 protects fetuses from infection with porcine reproductive and respiratory syndrome virus (PRRSV) After infection of the porcine dam at about 90 days of gestation, porcine reproductive and respiratory syndrome virus (PRRSV) crosses the placenta and begins to infect fetuses. In this study, CD163-positive fetuses, recovered between 109 days of gestation or 20 days after maternal infection, were completely protected from PRRSV in dams possessing a complete knockout of the CD163 receptor. The hypothesis to be tested was that the presence of the CD163 KO genotype of the dam would be sufficient to protect fetuses following maternal infection with PRRSV. PRRSV nucleic acid, measured at 7 dpi, showed a viremia level for Dam No. 139 of 5.5 log 10 templates per reaction, demonstrating the presence of a productive PRRSV infection. Gene-edited pigs are protected from porcine reproductive and respiratory syndrome virus abstract: After infection of the porcine dam at about 90 days of gestation, porcine reproductive and respiratory syndrome virus (PRRSV) crosses the placenta and begins to infect fetuses. Outcomes of include abortion, fetal death and respiratory disease in newborn piglets. CD163 is the receptor for the virus. In this study, CD163-positive fetuses, recovered between 109 days of gestation or 20 days after maternal infection, were completely protected from PRRSV in dams possessing a complete knockout of the CD163 receptor. The results demonstrate a practical means to eliminate PRRSV-associated reproductive disease, a major source of economic hardship to agriculture. url: https://doi.org/10.1038/s41598-017-13794-2 doi: 10.1038/s41598-017-13794-2 id: cord-288731-x2cwyvb7 author: Puenpa, Jiratchaya title: Molecular epidemiology of the first wave of severe acute respiratory syndrome coronavirus 2 infection in Thailand in 2020 date: 2020-10-06 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The coronavirus disease 2019 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a major global concern. Several SARS-CoV-2 gene mutations have been reported. In the current study associations between SARS-CoV-2 gene variation and exposure history during the first wave of the outbreak in Thailand between January and May 2020 were investigated. Forty samples were collected at different time points during the outbreak, and parts of the SARS-CoV-2 genome sequence were used to assess genomic variation patterns. The phylogenetics of the 40 samples were clustered into L, GH, GR, O and T types. T types were predominant in Bangkok during the first local outbreak centered at a boxing stadium and entertainment venues in March 2020. Imported cases were infected with various types, including L, GH, GR and O. In southern Thailand introductions of different genotypes were identified at different times. No clinical parameters were significantly associated with differences in genotype. The results indicated local transmission (type T, Spike protein (A829T)) and imported cases (types L, GH, GR and O) during the first wave in Thailand. Genetic and epidemiological data may contribute to national policy formulation, transmission tracking and the implementation of measures to control viral spread. url: https://www.ncbi.nlm.nih.gov/pubmed/33024144/ doi: 10.1038/s41598-020-73554-7 id: cord-004181-exbs3tz7 author: Pumchan, Ansaya title: Novel Chimeric Multiepitope Vaccine for Streptococcosis Disease in Nile Tilapia (Oreochromis niloticus Linn.) date: 2020-01-17 words: 5769.0 sentences: 291.0 pages: flesch: 42.0 cache: ./cache/cord-004181-exbs3tz7.txt txt: ./txt/cord-004181-exbs3tz7.txt summary: The efficacy of the chimeric multiepitope construct as a recombinant protein vaccine and DNA vaccine was evaluated in Nile tilapia, followed by S. The epitopes of immunogenic proteins were predicted by the BCPREDS server based on B cell epitopes to be used in chimeric multiepitope vaccine construction. In this study, not only immunogenic proteins from the immunoproteomics analysis were used but also other subunit vaccine candidates were subjected to epitope prediction and combined to produce a chimeric multiepitope vaccine. The recombinant chimeric multiepitope protein vaccination showed that 45F2 and 42E2 produced cumulative mortality rates of 30.00 ± 10.00% and 26.67 ± 5.77%, respectively, which were significantly lower than those of the negative control group, at 70% (P < 0.05) (Fig. 6A) . agalactiae serotype Ia and III demonstrated that fish vaccinated with recombinant protein vaccine 42E2 and 45F2 showed cross-reactivity to whole cell lysate of S. abstract: Streptococcus agalactiae is a causative agent of streptococcosis disease in various fish species, including Nile tilapia (Oreochromis niloticus Linn.). Vaccination is an effective disease prevention and control method, but limitations remain for protecting against catastrophic mortality of fish infected with different strains of streptococci. Immunoproteomics analysis of S. agalactiae was used to identify antigenic proteins and construct a chimeric multiepitope vaccine. Epitopes from five antigenic proteins were shuffled in five helices of a flavodoxin backbone, and in silico analysis predicted a suitable RNA and protein structure for protein expression. 45F2 and 42E2 were identified as the best candidates for a chimeric multiepitope vaccine. Recombinant plasmids were constructed to produce a recombinant protein vaccine and DNA vaccine system. Overexpressed proteins were determined to be 30 kDa and 25 kDa in the E. coli and TK1 systems, respectively. The efficacy of the chimeric multiepitope construct as a recombinant protein vaccine and DNA vaccine was evaluated in Nile tilapia, followed by S. agalactiae challenge at 1 × 10(7) CFU/mL. Relative percentage survival (RPS) and cumulative mortality were recorded at approximately 57–76% and 17–30%, respectively. These chimeric multiepitope vaccines should be applied in streptococcosis disease control and developed into a multivalent vaccine to control multiple diseases. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6969146/ doi: 10.1038/s41598-019-57283-0 id: cord-002644-yzan95du author: Ren, Rongrong title: The H7N9 influenza A virus infection results in lethal inflammation in the mammalian host via the NLRP3-caspase-1 inflammasome date: 2017-08-08 words: 5599.0 sentences: 371.0 pages: flesch: 58.0 cache: ./cache/cord-002644-yzan95du.txt txt: ./txt/cord-002644-yzan95du.txt summary: Thus, our study reveals that the NLRP3 inflammasome is deleterious for the host during H7N9 infection in mice, which is due to an overwhelming inflammatory response via caspase-1 activation and associated IL-1 signal. To note, the production of above mentioned cytokines and chemokines from Nlrp3 −/− mice showed a similar pattern as that from Casp1/11 −/− mice (Fig. 5b) , indicating that deficiency of NLRP3 inflammasome genes reduced the secretion of several critical proinflammatory mediators in the lung of mice upon H7N9 IAV challenge. Pathology analysis showed that there were inflammatory responses in the infected lungs of all strains of mice, both at 3 d.p.i and at 7 d.p.i; and the pulmonary inflammations at 7 d.p.i. were more severe than that at 3 d.p.i.; moreover, the pulmonary inflammations of the WT mice were stronger than Casp1/11 −/− , Asc −/− and Nlrp3 −/− mice (Figs 3 and 7) . abstract: The avian origin influenza A virus (IAV) H7N9 has caused a considerable number of human infections associated with high rates of death since its emergence in 2013. As a vital component of the host innate immune system, the nucleotide-binding domain leucine-rich repeat containing receptor, pyrin domain containing 3 (NLRP3) inflammasome plays a critical role against H1N1 viral infection. However, the function of NLRP3 inflammasome in host immunological responses to the lethal H7N9 virus is still obscure. Here, we demonstrated that mice deficient for NLRP3 inflammasome components, including NLRP3, caspase-1, and Apoptosis-associated speck-like protein containing a CARD (ASC), were less susceptible to H7N9 viral challenge than wild type (WT) controls. Inflammasome deficiency in these animals led to significantly milder mortality and less pulmonary inflammation compared with WT mice. Furthermore, IL-1 receptor deficient mice also exhibited a higher survival rate than WT controls. Thus, our study reveals that the NLRP3 inflammasome is deleterious for the host during H7N9 infection in mice, which is due to an overwhelming inflammatory response via caspase-1 activation and associated IL-1 signal. Therefore, fine-tuning the activity of NLRP3 inflammasome or IL-1 signaling may be beneficial for the host to control H7N9 associated lethal pathogenesis. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5548739/ doi: 10.1038/s41598-017-07384-5 id: cord-009691-gkynxdz3 author: Rizzato, Cosmeri title: Variations in cag pathogenicity island genes of Helicobacter pylori from Latin American groups may influence neoplastic progression to gastric cancer date: 2020-04-16 words: 4504.0 sentences: 239.0 pages: flesch: 47.0 cache: ./cache/cord-009691-gkynxdz3.txt txt: ./txt/cord-009691-gkynxdz3.txt summary: The present study revealed that several cagPAI genes from Latin American Western HP strains contains a number of non-synonymous variants in relatively high frequencies which could influence on the clinical outcome. When comparing the frequency of the 520 selected alleles between the isolates from subjects with gastritis and isolates from subjects with IM or GC we found statistically significant differences in allele distribution for three polymorphisms in cagA gene (Q/K427R, N467G and V1041T), three in cagC gene (V22I, V37I, I45V), one in the cagE gene (K981E), one in cagL gene (S10F), one in cagX gene (G11N), one in cagS (G146D), one in cagζ (S35A), three in cagδ (V353I, P406L, N407E) and one in cagβ (N125A) ( Table 2) . In a previous study conducted with amplicon sequencing by 454 for 84 Mexican and 11 Venezuelan samples we reported 10 non-synonymous SNPs with differential allelic distribution between gastritis and gastric cancer at conventional P-values between 0.01-0.05 28 . abstract: Helicobacter pylori (HP) colonizes the human stomach and induces acute gastritis, peptic ulcer disease, atrophic gastritis, and gastric adenocarcinoma. Increased virulence in HP isolates derives from harboring the cag (cytotoxin-associated genes) pathogenicity island (cagPAI). We analyzed the microvariants in cagPAI genes with the hypothesis that they may play an important role in determining HP virulence. We tested DNAs from cagA positive patients HP isolates; a total of 74 patients with chronic gastritis (CG, N = 37), intestinal metaplasia (IM, N = 21) or gastric cancer (GC, N = 16) from Mexico and Colombia. We selected 520 non-synonymous variants with at least 7.5% frequency in the original sequence outputs or with a minimum of 5 isolates with minor allele. After adjustment for multiple comparisons, no variants were statistically significantly associated with IM or GC. However, 19 non-synonymous showed conventional P-values < 0.05 comparing the frequency of the alleles between the isolates from subjects with gastritis and isolates from subjects with IM or GC; 12 of these showed a significant correlation with the severity of the disease. The present study revealed that several cagPAI genes from Latin American Western HP strains contains a number of non-synonymous variants in relatively high frequencies which could influence on the clinical outcome. However, none of the associations remained statistically significant after adjustment for multiple comparison. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7162905/ doi: 10.1038/s41598-020-63463-0 id: cord-276444-jidvkij5 author: Robitaille, Alexa C. title: DUSP1 regulates apoptosis and cell migration, but not the JIP1-protected cytokine response, during Respiratory Syncytial Virus and Sendai Virus infection date: 2017-12-12 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The host antiviral response involves the induction of interferons and proinflammatory cytokines, but also the activation of cell death pathways, including apoptosis, to limit viral replication and spreading. This host defense is strictly regulated to eliminate the infection while limiting tissue damage that is associated with virus pathogenesis. Post-translational modifications, most notably phosphorylation, are key regulators of the antiviral defense implying an important role of protein phosphatases. Here, we investigated the role of the dual-specificity phosphatase 1 (DUSP1) in the host defense against human respiratory syncytial virus (RSV), a pathogenic virus of the Pneumoviridae family, and Sendai virus (SeV), a model virus being developed as a vector for anti-RSV vaccine. We found that DUSP1 is upregulated before being subjected to proteasomal degradation. DUSP1 does not inhibit the antiviral response, but negatively regulates virus-induced JNK/p38 MAPK phosphorylation. Interaction with the JNK-interacting protein 1 scaffold protein prevents dephosphorylation of JNK by DUSP1, likely explaining that AP-1 activation and downstream cytokine production are protected from DUSP1 inhibition. Importantly, DUSP1 promotes SeV-induced apoptosis and suppresses cell migration in RSV-infected cells. Collectively, our data unveils a previously unrecognized selective role of DUSP1 in the regulation of tissue damage and repair during infections by RSV and SeV. url: https://www.ncbi.nlm.nih.gov/pubmed/29234123/ doi: 10.1038/s41598-017-17689-0 id: cord-003667-u1xa44nw author: Rodriguez, Sergio E. title: Vesicular Stomatitis Virus-Based Vaccine Protects Mice against Crimean-Congo Hemorrhagic Fever date: 2019-05-23 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Crimean-Congo hemorrhagic fever virus (CCHFV), a tick-borne bunyavirus, can cause a life-threatening hemorrhagic syndrome in humans but not in its animal host. The virus is widely distributed throughout southeastern Europe, the Middle East, Africa, and Asia. Disease management has proven difficult and there are no broadly licensed vaccines or therapeutics. Recombinant vesicular stomatitis viruses (rVSV) expressing foreign glycoproteins (GP) have shown promise as experimental vaccines for several viral hemorrhagic fevers. Here, we developed and assessed a replication competent rVSV vector expressing the CCHFV glycoprotein precursor (GPC), which encodes CCHFV structural glycoproteins. This construct drives strong expression of CCHFV-GP, in vitro. Using these vectors, we vaccinated STAT-1 knock-out mice, an animal model for CCHFV. The vector was tolerated and 100% efficacious against challenge from a clinical strain of CCHFV. Anti-CCHFV-GP IgG and neutralizing antibody titers were observed in surviving animals. This study demonstrates that a rVSV expressing only the CCHFV-GP has the potential to serve as a replication competent vaccine platform against CCHF infections. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6533279/ doi: 10.1038/s41598-019-44210-6 id: cord-003444-dmpoy0b1 author: Rowe, John C. title: A Novel Supplementation Approach to Enhance Host Response to Sublingual Vaccination date: 2019-01-24 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Sublingual immunization is emerging as an alternative to nasal immunization and induction of mucosal IgA responses. Using Bacillus anthracis edema toxin (EdTx) as an adjuvant, we previously showed that innate responses triggered after sublingual immunization could limit generation of IgA responses. We tested whether co-administration of a neutrophil elastase inhibitor (NEI) could rescue the ability of EdTx to induce broad antibody responses, including mucosal IgA. NEI supplementation of sublingual vaccines containing EdTx promoted antigen-specific serum IgA responses but also enhanced serum IgG1, and IgG2b responses. This enhancing effect of NEI did not extend to all antibody isotypes and IgG sublclasses, since NEI reduced serum IgE responses and did not affect IgG2a/c and IgG3 responses. NEI supplementation also promoted anti-Bacillus anthracis protective antigen (PA) neutralizing antibodies and enhanced high affinity IgG1 and IgA antibodies. In addition to serum IgA, NEI supplementation stimulated antigen-specific mucosal IgA responses in the GI tract, and enhanced antigen-specific IgG responses in vaginal washes. Analysis of CD4(+) T helper cell responses revealed that co-administration of NEI broadened the profile of cytokine responses, by stimulating Th1, Th2, Th17, and Tfh cytokines. We also noted that NEI had a higher stimulatory effect on IL-5, IL-10, IL-17 responses. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6346055/ doi: 10.1038/s41598-018-36370-8 id: cord-342122-certy2v8 author: Ruscitti, Piero title: Pro-inflammatory properties of H-ferritin on human macrophages, ex vivo and in vitro observations date: 2020-07-22 words: 4624.0 sentences: 236.0 pages: flesch: 44.0 cache: ./cache/cord-342122-certy2v8.txt txt: ./txt/cord-342122-certy2v8.txt summary: In this work, we tested (1) FeH and FeL in bone marrow (BM) and sera in patients with macrophage activation syndrome (MAS); (2) pro-inflammatory effects of ferritin, FeL, and FeH on macrophages; (3) ability of FeH-stimulated macrophages to stimulate the proliferation of peripheral blood mononuclear cells (PBMCs); (4) production of mature IL-1β and IL-12p70 in extracellular compartments of FeH-stimulated macrophages. Finally, www.nature.com/scientificreports/ FeH-treated macrophages enhanced the proliferation of co-cultured PBMCs. Taking together all these results and considering that AOSD and MAS could be included in the so-called "hyperferritinaemic syndrome" 14 , our data could reinforce the hypothesis that higher levels of ferritin may not only be considered a consequence or an epiphenomenon of the inflammation, but it may actively play a role in pathogenic mechanisms of those diseases, thus enhancing the inflammatory burden. abstract: Ferritin is an iron-binding molecule, which comprises 24 subunits, heavy (FeH) and light (FeL) subunits, suggested to have a pathogenic role by the ‘hyperferritinemic syndrome’. In this work, we tested (1) FeH and FeL in bone marrow (BM) and sera in patients with macrophage activation syndrome (MAS); (2) pro-inflammatory effects of ferritin, FeL, and FeH on macrophages; (3) ability of FeH-stimulated macrophages to stimulate the proliferation of peripheral blood mononuclear cells (PBMCs); (4) production of mature IL-1β and IL-12p70 in extracellular compartments of FeH-stimulated macrophages. Immunofluorescence analysis and liquid chromatography mass spectrometry (LC–MS/MS) based proteomics were performed to identify FeL and FeH in BM and sera, respectively, in the same patients. Macrophages were stimulated with ferritin, FeH, and FeL to assess pro-inflammatory effects by RT-PCR and western blot. The proliferation of co-cultured PBMCs with FeH-stimulated macrophages was tested. Immunofluorescence showed an increased FeH expression in BMs, whereas LC–MS/MS identified that FeL was mainly represented in sera. FeH induced a significant increase of gene expressions of IL-1β, IL-6, IL-12, and TNF-α, more marked with FeH, which also stimulated NLRP3. FeH-stimulated macrophages enhanced the proliferation of PBMCs. The ELISA assays showed that mature form of IL-1β and IL-12p70 were increased, in extracellular compartments of FeH-stimulated macrophages. Our results showed FeH in BM biopsies of MAS patients, whereas, LC–MS/MS identified FeL in the sera. FeH showed pro-inflammatory effects on macrophages, stimulated NLRP3, and increased PBMCs proliferation. url: https://doi.org/10.1038/s41598-020-69031-w doi: 10.1038/s41598-020-69031-w id: cord-269270-i2odcsx7 author: Sahlol, Ahmed T. title: COVID-19 image classification using deep features and fractional-order marine predators algorithm date: 2020-09-21 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Currently, we witness the severe spread of the pandemic of the new Corona virus, COVID-19, which causes dangerous symptoms to humans and animals, its complications may lead to death. Although convolutional neural networks (CNNs) is considered the current state-of-the-art image classification technique, it needs massive computational cost for deployment and training. In this paper, we propose an improved hybrid classification approach for COVID-19 images by combining the strengths of CNNs (using a powerful architecture called Inception) to extract features and a swarm-based feature selection algorithm (Marine Predators Algorithm) to select the most relevant features. A combination of fractional-order and marine predators algorithm (FO-MPA) is considered an integration among a robust tool in mathematics named fractional-order calculus (FO). The proposed approach was evaluated on two public COVID-19 X-ray datasets which achieves both high performance and reduction of computational complexity. The two datasets consist of X-ray COVID-19 images by international Cardiothoracic radiologist, researchers and others published on Kaggle. The proposed approach selected successfully 130 and 86 out of 51 K features extracted by inception from dataset 1 and dataset 2, while improving classification accuracy at the same time. The results are the best achieved on these datasets when compared to a set of recent feature selection algorithms. By achieving 98.7%, 98.2% and 99.6%, 99% of classification accuracy and F-Score for dataset 1 and dataset 2, respectively, the proposed approach outperforms several CNNs and all recent works on COVID-19 images. url: https://doi.org/10.1038/s41598-020-71294-2 doi: 10.1038/s41598-020-71294-2 id: cord-331475-mmcu18c8 author: Sahu, Amit Ranjan title: Selection and validation of suitable reference genes for qPCR gene expression analysis in goats and sheep under Peste des petits ruminants virus (PPRV), lineage IV infection date: 2018-10-29 words: 4735.0 sentences: 257.0 pages: flesch: 49.0 cache: ./cache/cord-331475-mmcu18c8.txt txt: ./txt/cord-331475-mmcu18c8.txt summary: title: Selection and validation of suitable reference genes for qPCR gene expression analysis in goats and sheep under Peste des petits ruminants virus (PPRV), lineage IV infection In this study, we evaluated the expression stability of ten most commonly used reference genes (GAPDH, ACTB, HSP90, HMBS, 18S rRNA, B2M, POLR2A, HPRT1, ACAC, YWHAZ) in fourteen different Peste des petits ruminants virus (PPRV) infected tissues of goats and sheep. GAPDH (Glyceraldehyde-3-phosphate dehydrogenase), 18S rRNA (18S ribosomal RNA), B2M (β 2 microglobulin), HSP 90 (heat shock protein 90), ACAC-alpha (Acetyl coenzyme carboxylase alpha), HMBS (Hydroxymethylbilane synthase), YWHAZ (Tyrosine 3-monooxygenase activation protein zeta polypeptide), POLR2A (Polymerase 32 II (DNA directed) polypeptide A), ACTB (beta actin) and HPRT1 (Hypoxanthin Phosphoribosyl transferase 1) in fourteen different tissues obtained from healthy and PPRV infected goats and sheep to identify the best possible reference gene(s) for qRT-PCR normalization. abstract: Identification of suitable candidate reference genes is an important prerequisite for validating the gene expression data obtained from downstream analysis of RNA sequencing using quantitative real time PCR (qRT-PCR). Though existence of a universal reference gene is myth, commonly used reference genes can be assessed for expression stability to confer their suitability to be used as candidate reference genes in gene expression studies. In this study, we evaluated the expression stability of ten most commonly used reference genes (GAPDH, ACTB, HSP90, HMBS, 18S rRNA, B2M, POLR2A, HPRT1, ACAC, YWHAZ) in fourteen different Peste des petits ruminants virus (PPRV) infected tissues of goats and sheep. RefFinder and RankAggreg software were used to deduce comprehensive ranking of reference genes. Our results suggested HMBS and B2M in goats and HMBS and HPRT1 in sheep can be used as suitable endogenous controls in gene expression studies of PPRV infection irrespective of tissues and condition as a whole, thus eliminating the use of tissue specific/ condition specific endogenous controls. We report for the first time suitable reference genes for gene expression studies in PPRV infected tissues. The reference genes determined here can be useful for future studies on gene expression in sheep and goat infected with PPRV, thus saving extra efforts and time of repeating the reference gene determination and validation. url: https://doi.org/10.1038/s41598-018-34236-7 doi: 10.1038/s41598-018-34236-7 id: cord-001862-a097byk5 author: Saisawang, Chonticha title: Chikungunya nsP2 protease is not a papain-like cysteine protease and the catalytic dyad cysteine is interchangeable with a proximal serine date: 2015-11-24 words: 4515.0 sentences: 226.0 pages: flesch: 50.0 cache: ./cache/cord-001862-a097byk5.txt txt: ./txt/cord-001862-a097byk5.txt summary: The proteolytic activity of nsP2 has been characterized in other alphaviruses, such as Sindbis virus (SINV), Semliki forest virus (SFV) and Venezuelan Equine Encephalitis virus (VEEV), as a papain-like cysteine protease with a cysteine-histidine catalytic dyad in the active site 11, 12, [16] [17] [18] [19] . Although the dyad residues have been identified previously in other alphavirus nsP2 proteins; in SINV, SFV and VEEV 11, 12, [16] [17] [18] , the CHIKV nsP2 protease active site has not been experimentally characterized. In performing this study a structural comparison showed that CHIKV nsP2 protease is not papain-like, and we have found what appears to be a unique feature of CHIKV nsP2 protease, in which the cysteine dyad residue can be catalytically replaced by a vicinal serine. In our study the protease inhibitors leupeptin and E-64 showed little to no effect on wild type, Cys478Ala and Ser482Ala enzyme activities for all 3 substrates (Table 2) . abstract: Chikungunya virus is the pathogenic alphavirus that causes chikungunya fever in humans. In the last decade millions of cases have been reported around the world from Africa to Asia to the Americas. The alphavirus nsP2 protein is multifunctional and is considered to be pivotal to viral replication, as the nsP2 protease activity is critical for proteolytic processing of the viral polyprotein during replication. Classically the alphavirus nsP2 protease is thought to be papain-like with the enzyme reaction proceeding through a cysteine/histidine catalytic dyad. We performed structure-function studies on the chikungunya nsP2 protease and show that the enzyme is not papain-like. Characterization of the catalytic dyad cysteine residue enabled us to identify a nearby serine that is catalytically interchangeable with the dyad cysteine residue. The enzyme retains activity upon alanine replacement of either residue but a replacement of both cysteine and serine residues results in no detectable activity. Protein dynamics appears to allow the use of either the cysteine or the serine residue in catalysis. This switchable dyad residue has not been previously reported for alphavirus nsP2 proteases and would have a major impact on the nsP2 protease as an anti-viral target. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4657084/ doi: 10.1038/srep17125 id: cord-304040-64obh7i3 author: Sande, Charles J. title: Untargeted analysis of the airway proteomes of children with respiratory infections using mass spectrometry based proteomics date: 2018-09-14 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The upper airway – which consists mainly of the naso- and oro-pharynx - is the first point of contact between the respiratory system and microbial organisms that are ubiquitous in the environment. It has evolved highly specialised functions to address these constant threats whilst facilitating seamless respiratory exchange with the lower respiratory tract. Dysregulation of its critical homeostatic and defence functions can lead to ingress of pathogens into the lower respiratory tract, potentially leading to serious illness. Systems-wide proteomic tools may facilitate a better understanding of mechanisms in the upper airways in health and disease. In this study, we aimed to develop a mass spectrometry based proteomics method for characterizing the upper airways proteome. Naso- and oropharyngeal swab samples used in all our experiments had been eluted in the Universal Transport Media (UTM) containing significantly high levels of bovine serum albumin. Our proteomic experiments tested the optimal approach to characterize airway proteome on swab samples eluted in UTM based on the number of proteins identified without BSA depletion (Total proteome: Protocol A) and with its depletion using a commercial kit; Allprep, Qiagen (cellular proteome: Protocol B, Ci, and Cii). Observations and lessons drawn from protocol A, fed into the design and implementation of protocol B, and from B to protocol Ci and finally Cii. Label free proteome quantification was used in Protocol A (n = 6) and B (n = 4) while commercial TMT 10plex reagents were used for protocols Ci and ii (n = 83). Protocols Ci and ii were carried out under similar conditions except for the elution gradient: 3 h and 6 h respectively. Swab samples tested in this study were from infants and children with and without upper respiratory tract infections from Kilifi County Hospital on the Kenyan Coast. Protocol A had the least number of proteins identified (215) while B produced the highest number of protein identifications (2396). When Protocol B was modified through sample multiplexing with TMT to enable higher throughput (Protocol Ci), the number of protein identified reduced to 1432. Modification of protocol Ci by increasing the peptide elution time generated Protocol Cii that substantially increased the number of proteins identified to 1875. The coefficient of variation among the TMT runs in Protocol Cii was <20%. There was substantial overlap in the identity of proteins using the four protocols. Our method was were able to identify marker proteins characteristically expressed in the upper airway. We found high expression levels of signature nasopharyngeal and oral proteins, including BPIFA1/2 and AMY1A, as well as a high abundance of proteins related to innate and adaptive immune function in the upper airway. We have developed a sensitive systems-level proteomic assay for the systematic quantification of naso-oro-pharyngeal proteins. The assay will advance mechanistic studies of respiratory pathology, by providing an untargeted and hypothesis-free approach of examining the airway proteome. url: https://doi.org/10.1038/s41598-018-32072-3 doi: 10.1038/s41598-018-32072-3 id: cord-315483-l6dm82pp author: Santhakumar, Diwakar title: Chicken Interferon-induced Protein with Tetratricopeptide Repeats 5 Antagonizes Replication of RNA Viruses date: 2018-05-01 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The intracellular actions of interferon (IFN)-regulated proteins, including IFN-induced proteins with tetratricopeptide repeats (IFITs), attribute a major component of the protective antiviral host defense. Here we applied genomics approaches to annotate the chicken IFIT locus and currently identified a single IFIT (chIFIT5) gene. The profound transcriptional level of this effector of innate immunity was mapped within its unique cis-acting elements. This highly virus- and IFN-responsive chIFIT5 protein interacted with negative sense viral RNA structures that carried a triphosphate group on its 5′ terminus (ppp-RNA). This interaction reduced the replication of RNA viruses in lentivirus-mediated IFIT5-stable chicken fibroblasts whereas CRISPR/Cas9-edited chIFIT5 gene knockout fibroblasts supported the replication of RNA viruses. Finally, we generated mosaic transgenic chicken embryos stably expressing chIFIT5 protein or knocked-down for endogenous chIFIT5 gene. Replication kinetics of RNA viruses in these transgenic chicken embryos demonstrated the antiviral potential of chIFIT5 in ovo. Taken together, these findings propose that IFIT5 specifically antagonize RNA viruses by sequestering viral nucleic acids in chickens, which are unique in innate immune sensing and responses to viruses of both poultry and human health significance. url: https://www.ncbi.nlm.nih.gov/pubmed/29717152/ doi: 10.1038/s41598-018-24905-y id: cord-288761-fyvr0tc1 author: Santiago, César title: Allosteric inhibition of aminopeptidase N functions related to tumor growth and virus infection date: 2017-04-10 words: 5859.0 sentences: 342.0 pages: flesch: 58.0 cache: ./cache/cord-288761-fyvr0tc1.txt txt: ./txt/cord-288761-fyvr0tc1.txt summary: These structures identified three distinct APN conformations, based on active site accessibility, which we termed closed, intermediate and open forms (Fig. 1a) . The phenylalanine was located in the loop that connects α 26 and α 27 in the single domain IV ARM repeat of human and pig APN (Fig. 2a) ; it penetrated the active site groove in the closed conformation and locked the peptide, ready for hydrolysis. CoV binding to APN would lock the protein in its open conformation (Fig. 2b) , preventing the ectodomain movement probably necessary for peptide hydrolysis (Fig. 2a) . In flow cytometry, we determined the binding of an RBD-Fc fusion protein to cells that expressed pAPN or an active site mutant (pAPN-HH/AA), alone or with various drugs (Fig. 4a,b) . Disulfide bonds that lock the APN closed conformation or drugs that prevent opening of the ectodomain inhibited CoV protein binding and cell infection, whereas porcine CoV S proteins probably hinder APN transition to the closed form and peptide hydrolysis. abstract: Cell surface aminopeptidase N (APN) is a membrane-bound ectoenzyme that hydrolyzes proteins and peptides and regulates numerous cell functions. APN participates in tumor cell expansion and motility, and is a target for cancer therapies. Small drugs that bind to the APN active site inhibit catalysis and suppress tumor growth. APN is also a major cell entry receptor for coronavirus, which binds to a region distant from the active site. Three crystal structures that we determined of human and pig APN ectodomains defined the dynamic conformation of the protein. These structures offered snapshots of closed, intermediate and open APN, which represent distinct functional states. Coronavirus envelope proteins specifically recognized the open APN form, prevented ectodomain progression to the closed form and substrate hydrolysis. In addition, drugs that bind the active site inhibited both coronavirus binding to cell surface APN and infection; the drugs probably hindered APN transition to the virus-specific open form. We conclude that allosteric inhibition of APN functions occurs by ligand suppression of ectodomain motions necessary for catalysis and virus cell entry, as validated by locking APN with disulfides. Blocking APN dynamics can thus be a valuable approach to development of drugs that target this ectoenzyme. url: https://www.ncbi.nlm.nih.gov/pubmed/28393915/ doi: 10.1038/srep46045 id: cord-344344-q32b742a author: Sato, Shintaro title: Alcohol abrogates human norovirus infectivity in a pH-dependent manner date: 2020-09-28 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Alcohol-based disinfectants are widely used for the sanitization of microorganisms, especially those that cause infectious diseases, including viruses. However, since the germicidal mechanism of alcohol is lipolysis, alcohol-based disinfectants appear to have a minimal effect on non-enveloped viruses, such as noroviruses. Because there is no cultivation method for human norovirus (HuNoV) in vitro, murine norovirus and feline calicivirus have been used as surrogates for HuNoV to analyze the efficacy of disinfectant regents. Therefore, whether these disinfectants and their conditions are effective against HuNoVs remain unknown. In this study, we report that ethanol or isopropanol alone can sufficiently suppress GII.4 genotype HuNoV replication in human iPSC-derived intestinal epithelial cells. Additionally, pH adjustments and salting-out may contribute toward the virucidal effect of alcohol against other HuNoV genotypes and cancel the impediment of organic substance contamination, respectively. Therefore, similar to sodium hypochlorite, alcohol-based disinfectants containing electrolytes can be used for HuNoV inactivation. url: https://doi.org/10.1038/s41598-020-72609-z doi: 10.1038/s41598-020-72609-z id: cord-272092-ko9y5m2s author: Scalabrin, Matteo title: The cellular protein hnRNP A2/B1 enhances HIV-1 transcription by unfolding LTR promoter G-quadruplexes date: 2017-03-24 words: 4096.0 sentences: 246.0 pages: flesch: 58.0 cache: ./cache/cord-272092-ko9y5m2s.txt txt: ./txt/cord-272092-ko9y5m2s.txt summary: title: The cellular protein hnRNP A2/B1 enhances HIV-1 transcription by unfolding LTR promoter G-quadruplexes Surface plasmon resonance confirmed G-quadruplex specificity over linear sequences and fluorescence resonance energy transfer analysis indicated that hnRNP A2/B1 is able to efficiently unfold the LTR G-quadruplexes. Our data highlight a tightly regulated control of transcription based on G-quadruplex folding/unfolding, which depends on interacting cellular proteins. Silencing of the LTR G4 folding/stabilizing protein nucleolin significantly increased promoter activity, indicating the inhibitory effect of nucleolin on LTR-driven transcription 22 . Our results showing decreased transcriptional activity upon depletion of hnRNP A2/B1 indicate a possible additional mechanism of inhibition of virus production mediated by increased G4 folding in the HIV-1 LTR promoter in the absence of hnRNP A2/B1. Nucleolin stabilizes G-quadruplex structures folded by the LTR promoter and silences HIV-1 viral transcription Protein hnRNP A1 and its derivative Up1 unfold quadruplex DNA in the human KRAS promoter: implications for transcription abstract: G-quadruplexes are four-stranded conformations of nucleic acids that act as cellular epigenetic regulators. A dynamic G-quadruplex forming region in the HIV-1 LTR promoter represses HIV-1 transcription when in the folded conformation. This activity is enhanced by nucleolin, which induces and stabilizes the HIV-1 LTR G-quadruplexes. In this work by a combined pull-down/mass spectrometry approach, we consistently found hnRNP A2/B1 as an additional LTR-G-quadruplex interacting protein. Surface plasmon resonance confirmed G-quadruplex specificity over linear sequences and fluorescence resonance energy transfer analysis indicated that hnRNP A2/B1 is able to efficiently unfold the LTR G-quadruplexes. Evaluation of the thermal stability of the LTR G-quadruplexes in different-length oligonucleotides showed that the protein is fit to be most active in the LTR full-length environment. When hnRNP A2/B1 was silenced in cells, LTR activity decreased, indicating that the protein acts as a HIV-1 transcription activator. Our data highlight a tightly regulated control of transcription based on G-quadruplex folding/unfolding, which depends on interacting cellular proteins. These findings provide a deeper understanding of the viral transcription mechanism and may pave the way to the development of drugs effective against the integrated HIV-1, present both in actively and latently infected cells. url: https://www.ncbi.nlm.nih.gov/pubmed/28338097/ doi: 10.1038/srep45244 id: cord-326868-3az13h1h author: Schiller, Bastian title: Temporal dynamics of resting EEG networks are associated with prosociality date: 2020-08-03 words: 5310.0 sentences: 278.0 pages: flesch: 39.0 cache: ./cache/cord-326868-3az13h1h.txt txt: ./txt/cord-326868-3az13h1h.txt summary: The present study takes a neural trait approach, examining whether the temporal dynamics of resting EEG networks are associated with inter-individual differences in prosociality. In two experimental sessions, we collected 55 healthy males'' resting EEG, their self-reported prosocial concern and values, and their incentivized prosocial behavior across different reward domains (money, time) and social contexts (collective, individual). On the basis of resting EEG networks'' significance for non-social behavior, personality, and psychiatric conditions 20,31 , we expected that revealing an individual''s tendency to engage these networks at rest would help explain inter-individual differences in prosociality and illuminate the potential psychological processes that underlie these differences. Correlative analyses revealed that participants with more transitions from microstate C to A were more prosocial [R(53) = 0.414, P = 0.002, Scientific RepoRtS | (2020) 10:13066 | https://doi.org/10.1038/s41598-020-69999-5 www.nature.com/scientificreports/ significant after Bonferroni-correction for multiple testing; prosocial concern: R s (53) = 0.261, P = 0.054; prosocial values: R s (53) = 0.366, P = 0.006; collective prosocial behavior: R s (53) = 0.081, P > 0.20; individual prosocial behavior: R s (53) = 0.261, P = 0.054, see Fig. 4 ]. abstract: As prosociality is key to facing many of our societies’ global challenges (such as fighting a global pandemic), we need to better understand why some individuals are more prosocial than others. The present study takes a neural trait approach, examining whether the temporal dynamics of resting EEG networks are associated with inter-individual differences in prosociality. In two experimental sessions, we collected 55 healthy males’ resting EEG, their self-reported prosocial concern and values, and their incentivized prosocial behavior across different reward domains (money, time) and social contexts (collective, individual). By means of EEG microstate analysis we identified the temporal coverage of four canonical resting networks (microstates A, B, C, and D) and their mutual communication in order to examine their association with an aggregated index of prosociality. Participants with a higher coverage of microstate A and more transitions from microstate C to A were more prosocial. Our study demonstrates that temporal dynamics of intrinsic brain networks can be linked to complex social behavior. On the basis of previous findings on links of microstate A with sensory processing, our findings suggest that participants with a tendency to engage in bottom-up processing during rest behave more prosocially than others. url: https://www.ncbi.nlm.nih.gov/pubmed/32747655/ doi: 10.1038/s41598-020-69999-5 id: cord-288721-3bv3aak6 author: Schneider, Annika title: Single organelle analysis to characterize mitochondrial function and crosstalk during viral infection date: 2019-06-11 words: 5604.0 sentences: 309.0 pages: flesch: 39.0 cache: ./cache/cord-288721-3bv3aak6.txt txt: ./txt/cord-288721-3bv3aak6.txt summary: Thus, single-organelle and multi-parameter resolution allows to explore altered energy metabolism and antiviral defence by tagged mitochondria selectively in virus-infected cells and will be instrumental to identify viral immune escape and to develop and monitor novel mitochondrial-targeted therapies. When challenged with high concentrations of calcium (100 µM), mitochondria isolated from virus-infected livers are much more fragile shown by time-dependent loss of membrane potential and change of their morphology indicated by decrease in side-scatter (Fig. 2F ). Number of viable mitochondria detected per second by flow-cytometry declined after calcium challenge, consistent with loss of mitochondrial integrity, and did so much faster in samples from virus-infected livers (Fig. 2F ). In order to further evaluate mitochondrial functionality, we challenged mitochondria with Ca 2+ as stress test and performed time kinetic measurements of DilC 1 (5) fluorescence and side-scatter of mito-DsRed + and mito-DsRed − mitochondria isolated from Ad-CMV-mitoRL infected livers. abstract: Mitochondria are key for cellular metabolism and signalling processes during viral infection. We report a methodology to analyse mitochondrial properties at the single-organelle level during viral infection using a recombinant adenovirus coding for a mitochondrial tracer protein for tagging and detection by multispectral flow cytometry. Resolution at the level of tagged individual mitochondria revealed changes in mitochondrial size, membrane potential and displayed a fragile phenotype during viral infection of cells. Thus, single-organelle and multi-parameter resolution allows to explore altered energy metabolism and antiviral defence by tagged mitochondria selectively in virus-infected cells and will be instrumental to identify viral immune escape and to develop and monitor novel mitochondrial-targeted therapies. url: https://www.ncbi.nlm.nih.gov/pubmed/31186476/ doi: 10.1038/s41598-019-44922-9 id: cord-003623-n01rgqyv author: Schuh, Amy J. title: Comparative analysis of serologic cross-reactivity using convalescent sera from filovirus-experimentally infected fruit bats date: 2019-04-30 words: 6363.0 sentences: 277.0 pages: flesch: 37.0 cache: ./cache/cord-003623-n01rgqyv.txt txt: ./txt/cord-003623-n01rgqyv.txt summary: To evaluate the ability of our system comprising seven filovirus-specific indirect ELISAs to predict the filovirus species most antigenically similar to the species responsible for past infection, we tested seven Marburg virus convalescent serum 35 or whole blood 36 samples collected from experimentally inoculated ERBs. Five of these samples www.nature.com/scientificreports www.nature.com/scientificreports/ were collected four weeks post primary Marburg virus inoculation 35, 36 , while two of the samples were collected at 23 and 27 weeks post primary inoculation following a "natural" boost (i.e., Marburg virus-specific antibody levels waned in these bats and then increased following contact with infectious cagemates) 36 . Although significant levels of serological IgG cross-reactivity were observed between the prime-boost filovirus-specific antisera and some of the filovirus antigens, when the overall covariance of the seven-individual indirect ELISAs in the system were considered, we were able to predict the filovirus species responsible for past infection 100% of the time using as little as 25 μL of sera (each serum was tested against each antigen in duplicate). abstract: With the exception of Reston and Bombali viruses, the marburgviruses and ebolaviruses (family Filoviridae) cause outbreaks of viral hemorrhagic fever in sub-Saharan Africa. The Egyptian rousette bat (ERB) is a natural reservoir host for the marburgviruses and evidence suggests that bats are also natural reservoirs for the ebolaviruses. Although the search for the natural reservoirs of the ebolaviruses has largely involved serosurveillance of the bat population, there are no validated serological assays to screen bat sera for ebolavirus-specific IgG antibodies. Here, we generate filovirus-specific antisera by prime-boost immunization of groups of captive ERBs with all seven known culturable filoviruses. After validating a system of filovirus-specific indirect ELISAs utilizing infectious-based virus antigens for detection of virus-specific IgG antibodies from bat sera, we assess the level of serological cross-reactivity between the virus-specific antisera and heterologous filovirus antigens. This data is then used to generate a filovirus antibody fingerprint that can predict which of the filovirus species in the system is most antigenically similar to the species responsible for past infection. Our filovirus IgG indirect ELISA system will be a critical tool for identifying bat species with high ebolavirus seroprevalence rates to target for longitudinal studies aimed at establishing natural reservoir host-ebolavirus relationships. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6491471/ doi: 10.1038/s41598-019-43156-z id: cord-001823-v60vv99o author: Shen, Mingwang title: Modeling the effect of comprehensive interventions on Ebola virus transmission date: 2015-10-30 words: 5364.0 sentences: 303.0 pages: flesch: 56.0 cache: ./cache/cord-001823-v60vv99o.txt txt: ./txt/cord-001823-v60vv99o.txt summary: By fitting the model to reported cumulative cases and deaths in Guinea, Sierra Leone and Liberia until March 22, 2015, we estimate the basic reproduction number in these countries as 1.2552, 1.6093 and 1.7994, respectively. The objective of this paper is to assess the effect of all possible intervention strategies (isolation, media impact, safe burial, and vaccination) on controlling the spread of Ebola virus in Guinea, Sierra Leone, Liberia. Using the model, we evaluate the potential effect of increasing the fraction of latent individuals prior to symptoms onset, shortening the duration between symptoms onset and isolation, improving media coverage, following restrict burial procedures, and administrating timely vaccine on the epidemic of Ebola infection. If the effectiveness of isolation increases to 80%, i.e., the relative transmissibility  of isolated individuals decreases to 20% (magenta lines in Fig. 5 ), then about 35%, 65%, 60% of pre-symptomatic patients need to be detected in Guinea, Sierra Leone and Liberia to control the disease. abstract: Since the re-emergence of Ebola in West Africa in 2014, comprehensive and stringent interventions have been implemented to decelerate the spread of the disease. The effectiveness of interventions still remains unclear. In this paper, we develop an epidemiological model that includes various controlling measures to systematically evaluate their effects on the disease transmission dynamics. By fitting the model to reported cumulative cases and deaths in Guinea, Sierra Leone and Liberia until March 22, 2015, we estimate the basic reproduction number in these countries as 1.2552, 1.6093 and 1.7994, respectively. Model analysis shows that there exists a threshold of the effectiveness of isolation, below which increasing the fraction of latent individuals diagnosed prior to symptoms onset or shortening the duration between symptoms onset and isolation may lead to more Ebola infection. This challenges an existing view. Media coverage plays a substantial role in reducing the final epidemic size. The response to reported cumulative infected cases and deaths may have a different effect on the epidemic spread in different countries. Among all the interventions, we find that shortening the duration between death and burial and improving the effectiveness of isolation are two effective interventions for controlling the outbreak of Ebola virus infection. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4626779/ doi: 10.1038/srep15818 id: cord-350957-10wcqgaq author: Shen, Zu T. title: SARS Coronavirus Fusion Peptide-Derived Sequence Suppresses Collagen-Induced Arthritis in DBA/1J Mice date: 2016-06-28 words: 5609.0 sentences: 265.0 pages: flesch: 48.0 cache: ./cache/cord-350957-10wcqgaq.txt txt: ./txt/cord-350957-10wcqgaq.txt summary: Recently, based on our model of immune signaling, the Signaling Chain HOmoOLigomerization (SCHOOL) model, we suggested specific molecular mechanisms used by different viruses such as severe acute respiratory syndrome coronavirus (SARS-CoV) to modulate the host immune response mediated by members of the family of multichain immune recognition receptors (MIRRs). Previously, we reported that incorporation of another immunomodulatory peptide, GF9, that employs the SCHOOL mechanisms of action and targets triggering receptor expressed on myeloid cells 1 (TREM-1), into synthetic HDL-like nanoparticles of spherical shape (sHDL) significantly reduces the effective therapeutic dosage of GF9 in animal models of sepsis, lung cancer, and RA 33, 34 . As expected from the anti-arthritic activities demonstrated in animal models of autoimmune arthritis for TCR CP 20,21,23 and HIV gp41 FP 18 , the SARS-CoV FP-derived peptide sequence MG11 significantly suppresses CIA in mice: the peptide at 25 mg/kg/day inhibits inflammation in CIA as assessed by clinical evaluation and scoring of the disease (Fig. 2) . abstract: During the co-evolution of viruses and their hosts, the viruses have evolved numerous strategies to counter and evade host antiviral immune responses in order to establish a successful infection, replicate and persist in the host. Recently, based on our model of immune signaling, the Signaling Chain HOmoOLigomerization (SCHOOL) model, we suggested specific molecular mechanisms used by different viruses such as severe acute respiratory syndrome coronavirus (SARS-CoV) to modulate the host immune response mediated by members of the family of multichain immune recognition receptors (MIRRs). This family includes T cell receptor (TCR) that is critically involved in immune diseases such as autoimmune arthritis. In the present study, we provide compelling experimental in vivo evidence in support of our hypothesis. Using the SCHOOL approach and the SARS-CoV fusion peptide sequence, we rationally designed a novel immunomodulatory peptide that targets TCR. We showed that this peptide ameliorates collagen-induced arthritis in DBA/1J mice and protects against bone and cartilage damage. Incorporation of the peptide into self-assembling lipopeptide nanoparticles that mimic native human high density lipoproteins significantly increases peptide dosage efficacy. Together, our data further confirm that viral immune evasion strategies that target MIRRs can be transferred to therapeutic strategies that require similar functionalities. url: https://doi.org/10.1038/srep28672 doi: 10.1038/srep28672 id: cord-259794-6qoksn00 author: Shi, Da title: Nucleocapsid Interacts with NPM1 and Protects it from Proteolytic Cleavage, Enhancing Cell Survival, and is Involved in PEDV Growth date: 2017-01-03 words: 7086.0 sentences: 400.0 pages: flesch: 50.0 cache: ./cache/cord-259794-6qoksn00.txt txt: ./txt/cord-259794-6qoksn00.txt summary: Porcine epidemic diarrhea virus (PEDV) replicates in the cytoplasm of infected cells, but its nucleocapsid (N) protein localizes specifically to the nucleolus. The results suggest potential linkages among viral strategies for the regulation of cell survival activities, possibly through an interaction of N protein with NPM1 which prevents its proteolytic cleavage and enhances cell survival, thus ultimately promoting the replication of PEDV. In this study, to determine the intracellular distribution of N protein at the protein level, PEDV-infected Vero E6 cells were lysed, separated into nuclear and cytoplasmic fractions, and analyzed by western blotting. This study was based on different lines of evidence, reflecting both in vivo and in vitro situations, and demonstrated that PEDV N protein is able to associate with the major nucleolar protein NPM1 of Vero E6 cells (Fig. 2) ; we failed to detect an interaction with the fibrillarin or nucleolin (See Supplementary Fig. S2 ). abstract: Porcine epidemic diarrhea virus (PEDV) replicates in the cytoplasm of infected cells, but its nucleocapsid (N) protein localizes specifically to the nucleolus. The mechanism of nuclear translocation, and whether N protein associates with particular nucleolar components, is unknown. In this study, we confirm that a nucleolar phosphoprotein nucleophosmin (NPM1) interacts and co-localizes with the N protein in the nucleolus. In vitro binding studies indicated that aa 148–294 of N and aa 118–188 of NPM1 were required for binding. Interestingly, N protein importation into the nucleolus is independent of the ability of NPM1 to shuttle between the nucleus and the cytoplasm. Furthermore, overexpression of NPM1 promoted PEDV growth, while knockdown of NPM1 suppressed PEDV growth. In addition, binding of N protein to NPM1 protects it from proteolytic degradation by caspase-3, leading to increased cell survival. Taken together, our studies demonstrate a specific interaction of the N protein with the host cell protein NPM1 in the nucleolus. The results suggest potential linkages among viral strategies for the regulation of cell survival activities, possibly through an interaction of N protein with NPM1 which prevents its proteolytic cleavage and enhances cell survival, thus ultimately promoting the replication of PEDV. url: https://www.ncbi.nlm.nih.gov/pubmed/28045037/ doi: 10.1038/srep39700 id: cord-003148-o7y3wygc author: Shirvani, Edris title: A Recombinant Newcastle Disease Virus (NDV) Expressing S Protein of Infectious Bronchitis Virus (IBV) Protects Chickens against IBV and NDV date: 2018-08-10 words: 8668.0 sentences: 423.0 pages: flesch: 55.0 cache: ./cache/cord-003148-o7y3wygc.txt txt: ./txt/cord-003148-o7y3wygc.txt summary: However, the results of the inoculation of the tracheal swab samples into 10-day-old embrynated chicken eggs showed that 14 out of 15 (93.3%) chickens vaccinated with rNDV expressing codon optimized S protein of IBV and 0 out of 5 (0%) of non-infected chickens were shedding virus in trachea, respectively, whereas 15 out of 15 (100%) of chickens of all other groups were shedding virus in the trachea (data not shown). To evaluate the effect of the route of inoculation of virulent IB challenge virus on the outcomes of the protective efficacy of rNDV expressing codon optimized S protein of IBV, SPF chicks were immunized at 1-day-old age. The protective efficacy of rNDV expressing codon optimized S gene of IBV was determined by challenging the immunized chickens with 10 4 EID 50 virulent IBV strain Mass-41 by the intraocular route at 3 week post-immunization. abstract: Infectious bronchitis virus (IBV) causes a highly contagious respiratory, reproductive and urogenital tract disease in chickens worldwide, resulting in substantial economic losses for the poultry industry. Currently, live-attenuated IBV vaccines are used to control the disease. However, safety, attenuation and immunization outcomes of current vaccines are not guaranteed. Several studies indicate that attenuated IBV vaccine strains contribute to the emergence of variant viruses in the field due to mutations and recombination. Therefore, there is a need to develop a stable and safe IBV vaccine that will not create variant viruses. In this study, we generated recombinant Newcastle disease viruses (rNDVs) expressing the S1, S2 and S proteins of IBV using reverse genetics technology. Our results showed that the rNDV expressing the S protein of IBV provided better protection than the rNDV expressing S1 or S2 protein of IBV, indicating that the S protein is the best protective antigen of IBV. Immunization of 4-week-old SPF chickens with the rNDV expressing S protein elicited IBV-specific neutralizing antibodies and provided complete protection against virulent IBV and virulent NDV challenges. These results suggest that the rNDV expressing the S protein of IBV is a safe and effective bivalent vaccine candidate for both IBV and NDV. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6086832/ doi: 10.1038/s41598-018-30356-2 id: cord-350468-32qin4ak author: Song, Cong-Ying title: Immune dysfunction following COVID-19, especially in severe patients date: 2020-09-28 words: 2958.0 sentences: 177.0 pages: flesch: 55.0 cache: ./cache/cord-350468-32qin4ak.txt txt: ./txt/cord-350468-32qin4ak.txt summary: Multivariate logistic regression analysis showed that CD4(+) cell count, neutrophil-to-lymphocyte ratio (NLR) and D-dimer were risk factors for severe cases. Afterward, the CD4 + cell count (P = 0.015), NLR (P = 0.032) and D-dimer (P = 0.016) were considered the independent risk factors of the severe COVID-19 cases (Table 3) www.nature.com/scientificreports/ To evaluate the predictive value of CT score, CPIS, and three independent risk factors, the ROC curve analysis was performed (Fig. 7) . In our study, we compared clinical characteristics between healthy people and COVID-19 patients, and then compared these features between severe and mild cases. Parameters including CD4 + T cell count, NLR, and D-dimer, CT score, and CPIS had quite great value for predicting disease severity, which could be considered in early warning of severe patients. Several studies have shown that severe SARS-CoV-2-infected patients have a higher NLR 11, 12 , an independent risk factor for mortality in COVID-19 patients 13 . abstract: The coronavirus disease 2019 (COVID-19) has been spreading worldwide. Severe cases quickly progressed with unfavorable outcomes. We aim to investigate the clinical features of COVID-19 and identify the risk factors associated with its progression. Data of confirmed SARS-CoV-2-infected patients and healthy participants were collected. Thirty-seven healthy people and 79 confirmed patients, which include 48 severe patients and 31 mild patients, were recruited. COVID-19 patients presented with dysregulated immune response (decreased T, B, and NK cells and increased inflammatory cytokines). Also, they were found to have increased levels of white blood cell, neutrophil count, and D-dimer in severe cases. Moreover, lymphocyte, CD4(+) T cell, CD8(+) T cell, NK cell, and B cell counts were lower in the severe group. Multivariate logistic regression analysis showed that CD4(+) cell count, neutrophil-to-lymphocyte ratio (NLR) and D-dimer were risk factors for severe cases. Both CT score and clinical pulmonary infection score (CPIS) were associated with disease severity. The receiver operating characteristic (ROC) curve analysis has shown that all these parameters and scores had quite a high predictive value. Immune dysfunction plays critical roles in disease progression. Early and constant surveillance of complete blood cell count, T lymphocyte subsets, coagulation function, CT scan and CPIS was recommended for early screening of severe cases. url: https://doi.org/10.1038/s41598-020-72718-9 doi: 10.1038/s41598-020-72718-9 id: cord-004016-iaktm72a author: Soto-Quintero, Albanelly title: Curcumin to Promote the Synthesis of Silver NPs and their Self-Assembly with a Thermoresponsive Polymer in Core-Shell Nanohybrids date: 2019-12-03 words: 6440.0 sentences: 364.0 pages: flesch: 52.0 cache: ./cache/cord-004016-iaktm72a.txt txt: ./txt/cord-004016-iaktm72a.txt summary: The Ag@cur-P(MEO 2 MA) core-doped shell hybrid NPs were prepared by free radical precipitation polymerization (FRPP) of the stimuli-responsive MEO 2 MA monomer in the presence of TEGDMA (crosslinking agent), using curcumin-decorated Ag@cur NPs as seeds (Fig. 1) . However, the dual key-role of curcumin, as reducing agent and growth-polymerization promoter in this specific synthesis, required additional investigation to understand and optimize the chemical variables (solubility, concentration and reaction temperature) in order to achieve homogeneous, monodisperse and mononuclear Ag@cur-P(MEO 2 MA) core-shell nanohybrids. The presence of hydrophobic curcumin nearby the metallic surface led to precipitation-polymerization of P(MEO 2 MA) around the AgNPs previously formed (Fig. 1B,C) ; and the resulting Ag@cur-P(MEO 2 MA) nanoparticles were born negatively charged due to the persulfate groups from the APS initiator, which promotes their colloidal stability. abstract: This work presents a simple one-pot protocol to achieve core-doped shell nanohybrids comprising silver nanoparticles, curcumin and thermoresponsive polymeric shell taking advantage of the reducing properties of phenolic curcumin substance and its ability to decorate metallic surfaces. Silver nanoparticles were synthesized, via sodium citrate and silver nitrate addition into a boiling aqueous solution of curcumin, monomers and surfactant. Curcumin and sodium citrate promoted silver nucleation, acting as reducing and stabilizing agents. These curcumin-capped AgNPs enabled, after adding the radical polymerization initiator, the assembling of the growing polymer chains around the hydrophobic AgNP surface. The resultant core-doped shell nanohybrids exhibit plasmonic, luminescent and volume thermoresponsive properties, with improved possibilities to be used as successful therapeutic platforms. In fact, the possibility to nanoconfine the synergistic antioxidant, antiviral, antibacterial features of silver and curcumin in one bioavailable hybrid paves the way to promising applications in the biomedical field. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6890765/ doi: 10.1038/s41598-019-54752-4 id: cord-318587-ewvnkdr2 author: Steeds, Kimberley title: Pseudotyping of VSV with Ebola virus glycoprotein is superior to HIV-1 for the assessment of neutralising antibodies date: 2020-08-31 words: 4973.0 sentences: 244.0 pages: flesch: 46.0 cache: ./cache/cord-318587-ewvnkdr2.txt txt: ./txt/cord-318587-ewvnkdr2.txt summary: We evaluated the suitability of EBOV GP pseudotyped human immunodeficiency virus type 1 (HIV-1) and vesicular stomatitis virus (VSV) to measure the neutralising ability of plasma from EVD survivors, when compared to results from a live EBOV neutralisation assay. The aim of this study was to assess the suitability of EBOV GP pseudotyped HIV-1 and VSV systems to measure neutralisation by EVD survivor plasma, in comparison with results from a live EBOV neutralisation assay. To determine the optimal pseudotyped virus input to use in the HIV-and VSV-based assays, neutralisation of different amounts of the EBOV GP pseudotyped viruses by plasma from a Guinean EVD survivor donor or human anti-EBOV GP mAb KZ52 was assessed. When IC 50 values of EBOV GP pseudotyped HIV-1 neutralisation of the 30 EVD survivor and 10 negative plasma samples were compared with GMT values for the live EBOV neutralisation assay, a positive correlation (r s = 0.54) was determined using the nonparametric Spearman correlation coefficient (Fig. 5a) and this was statistically significant (p = 0.0004). abstract: Ebola virus (EBOV) is an enveloped, single-stranded RNA virus that can cause Ebola virus disease (EVD). It is thought that EVD survivors are protected against subsequent infection with EBOV and that neutralising antibodies to the viral surface glycoprotein (GP) are potential correlates of protection. Serological studies are vital to assess neutralising antibodies targeted to EBOV GP; however, handling of EBOV is limited to containment level 4 laboratories. Pseudotyped viruses can be used as alternatives to live viruses, which require high levels of bio-containment, in serological and viral entry assays. However, neutralisation capacity can differ among pseudotyped virus platforms. We evaluated the suitability of EBOV GP pseudotyped human immunodeficiency virus type 1 (HIV-1) and vesicular stomatitis virus (VSV) to measure the neutralising ability of plasma from EVD survivors, when compared to results from a live EBOV neutralisation assay. The sensitivity, specificity and correlation with live EBOV neutralisation were greater for the VSV-based pseudotyped virus system, which is particularly important when evaluating EBOV vaccine responses and immuno-therapeutics. Therefore, the EBOV GP pseudotyped VSV neutralisation assay reported here could be used to provide a better understanding of the putative correlates of protection against EBOV. url: https://www.ncbi.nlm.nih.gov/pubmed/32868837/ doi: 10.1038/s41598-020-71225-1 id: cord-342676-ykog278j author: Stewart, H. title: Identification of novel RNA secondary structures within the hepatitis C virus genome reveals a cooperative involvement in genome packaging date: 2016-03-14 words: 6858.0 sentences: 338.0 pages: flesch: 46.0 cache: ./cache/cord-342676-ykog278j.txt txt: ./txt/cord-342676-ykog278j.txt summary: To identify the regions of the viral genome involved in this process, we used SELEX (systematic evolution of ligands by exponential enrichment) to identify RNA aptamers which bind specifically to Core in vitro. Comparison of these aptamers to multiple HCV genomes revealed the presence of a conserved terminal loop motif within short RNA stem-loop structures. We wished to investigate the possibility that similar specific secondary structures are present within HCV RNAs destined for packaging, and whether their interactions with Core cooperatively drive the RNA encapsidation and nucleocapsid assembly processes. A mutant genome unable to form such structures displays impaired viral infectivity whilst RNA replication is unaffected, indicating these motifs may interact specifically with Core. Role of RNA structures in genome terminal sequences of the hepatitis C virus for replication and assembly abstract: The specific packaging of the hepatitis C virus (HCV) genome is hypothesised to be driven by Core-RNA interactions. To identify the regions of the viral genome involved in this process, we used SELEX (systematic evolution of ligands by exponential enrichment) to identify RNA aptamers which bind specifically to Core in vitro. Comparison of these aptamers to multiple HCV genomes revealed the presence of a conserved terminal loop motif within short RNA stem-loop structures. We postulated that interactions of these motifs, as well as sub-motifs which were present in HCV genomes at statistically significant levels, with the Core protein may drive virion assembly. We mutated 8 of these predicted motifs within the HCV infectious molecular clone JFH-1, thereby producing a range of mutant viruses predicted to possess altered RNA secondary structures. RNA replication and viral titre were unaltered in viruses possessing only one mutated structure. However, infectivity titres were decreased in viruses possessing a higher number of mutated regions. This work thus identified multiple novel RNA motifs which appear to contribute to genome packaging. We suggest that these structures act as cooperative packaging signals to drive specific RNA encapsidation during HCV assembly. url: https://www.ncbi.nlm.nih.gov/pubmed/26972799/ doi: 10.1038/srep22952 id: cord-002929-oqe3gjcs author: Strano, Emanuele title: Mapping road network communities for guiding disease surveillance and control strategies date: 2018-03-16 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Human mobility is increasing in its volume, speed and reach, leading to the movement and introduction of pathogens through infected travelers. An understanding of how areas are connected, the strength of these connections and how this translates into disease spread is valuable for planning surveillance and designing control and elimination strategies. While analyses have been undertaken to identify and map connectivity in global air, shipping and migration networks, such analyses have yet to be undertaken on the road networks that carry the vast majority of travellers in low and middle income settings. Here we present methods for identifying road connectivity communities, as well as mapping bridge areas between communities and key linkage routes. We apply these to Africa, and show how many highly-connected communities straddle national borders and when integrating malaria prevalence and population data as an example, the communities change, highlighting regions most strongly connected to areas of high burden. The approaches and results presented provide a flexible tool for supporting the design of disease surveillance and control strategies through mapping areas of high connectivity that form coherent units of intervention and key link routes between communities for targeting surveillance. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5856805/ doi: 10.1038/s41598-018-22969-4 id: cord-001675-9717nzr7 author: Sugiyama, Michael G. title: The Tie2-agonist Vasculotide rescues mice from influenza virus infection date: 2015-06-05 words: 4824.0 sentences: 260.0 pages: flesch: 47.0 cache: ./cache/cord-001675-9717nzr7.txt txt: ./txt/cord-001675-9717nzr7.txt summary: Here we demonstrate that the Tie2-agonist tetrameric peptide Vasculotide improves survival in murine models of severe influenza, even if administered as late as 72 hours after infection; the benefit was observed using three strains of the virus and two strains of mice. While the drug had no effect on human lung endothelial proliferation (Supplemental Figure 8) , it significantly attenuated lung endothelial apoptosis in vitro in response to influenza virus, as assessed by cleavage of caspase-3 (Supplemental Figure 7c ); we observed a similar reduction in cleaved caspase-3 in lungs from infected mice who received Vasculotide (Supplemental Figure 7d ). First, these data strongly implicate failure of the lung endothelial barrier as the cause of death in murine models of severe influenza, as Vasculotide conferred a significant survival benefit against multiple strains of the virus in two strains of mice. abstract: Seasonal influenza virus infections cause hundreds of thousands of deaths annually while viral mutation raises the threat of a novel pandemic strain. Antiviral drugs exhibit limited efficacy unless administered early and may induce viral resistance. Thus, targeting the host response directly has been proposed as a novel therapeutic strategy with the added potential benefit of not eliciting viral resistance. Severe influenza virus infections are complicated by respiratory failure due to the development of lung microvascular leak and acute lung injury. We hypothesized that enhancing lung endothelial barrier integrity could improve the outcome. Here we demonstrate that the Tie2-agonist tetrameric peptide Vasculotide improves survival in murine models of severe influenza, even if administered as late as 72 hours after infection; the benefit was observed using three strains of the virus and two strains of mice. The effect required Tie2, was independent of viral replication and did not impair lung neutrophil recruitment. Administration of the drug decreased lung edema, arterial hypoxemia and lung endothelial apoptosis; importantly, Vasculotide is inexpensive to produce, is chemically stable and is unrelated to any Tie2 ligands. Thus, Vasculotide may represent a novel and practical therapy for severe infections with influenza. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4457136/ doi: 10.1038/srep11030 id: cord-272623-j5gpww9q author: Sun, Wei title: The pathogenesis of multifocal osteonecrosis date: 2016-07-11 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Our objective was to study the incidence, etiology, and diagnosis of multifocal osteonecrosis (MFON) and its treatment options to facilitate an earlier diagnosis and to optimize treatment. A radiological investigation was performed in osteonecrosis patients with a high risk of MFON for a more accurate diagnosis between January 2010 and June 2015. For patients with osteonecrosis of both the hip and knee joints or for patients with a history of corticosteroid use or alcohol abuse who had osteonecrosis of one or more joints in the shoulder, ankle, wrist or elbow, magnetic resonance imaging (MRI) was also performed on other joints, regardless of whether these joints were symptomatic. Furthermore, we performed a radiological screening of 102 patients who had a negative diagnosis of MFON but were at a high risk; among them, another 31 MFON cases were successfully identified (30.4%). Thus, the incidence of MFON during the study period increased from 3.1% to 5.2%. Patients diagnosed with osteonecrosis and who are at a high risk of MFON should have their other joints radiologically examined when necessary. This will reduce missed diagnosis of MFON and facilitate an earlier diagnosis and treatment to achieve an optimal outcome. url: https://www.ncbi.nlm.nih.gov/pubmed/27404962/ doi: 10.1038/srep29576 id: cord-003505-qr6ukfti author: Tabraue-Chávez, Mavys title: A colorimetric strategy based on dynamic chemistry for direct detection of Trypanosomatid species date: 2019-03-06 words: 5655.0 sentences: 331.0 pages: flesch: 50.0 cache: ./cache/cord-003505-qr6ukfti.txt txt: ./txt/cord-003505-qr6ukfti.txt summary: In this work, we have developed a novel colorimetric molecular assay that integrates nucleic acid analysis by dynamic chemistry (ChemNAT) with reverse dot-blot hybridization in an array format for a rapid and easy discrimination of Leishmania major and Trypanosoma cruzi. Once the abasic PNA probes hybridize with target sequences, the SMART-C-Biotin dynamic incorporation takes place, enabling the unequivocal identification of the parasite present in the amplicon sample, because of the unique colorimetric pattern that each Trypanosomatid amplicon generates. DNA amplicon products were denatured and then together with the dynamic chemistry reaction reagents added directly into the internal column of the Spin-Tube that supports the nylon membrane for the color-development assay (Fig. 4) . 20 ng of human gDNA were used as PCR template for its amplification with the set of primers described in our study and neither colorimetric signals nor bands were detected using the Spin-Tube and capillary electrophoresis analysis respectively (Fig. 5 , column 2: 2A and 2B), hence probing the specificity when human gDNA is present. abstract: Leishmaniasis and Chagas disease are endemic in many countries, and re-emerging in the developed countries. A rapid and accurate diagnosis is important for early treatment for reducing the duration of infection as well as for preventing further potential health complications. In this work, we have developed a novel colorimetric molecular assay that integrates nucleic acid analysis by dynamic chemistry (ChemNAT) with reverse dot-blot hybridization in an array format for a rapid and easy discrimination of Leishmania major and Trypanosoma cruzi. The assay consists of a singleplex PCR step that amplifies a highly homologous DNA sequence which encodes for the RNA component of the large ribosome subunit. The amplicons of the two different parasites differ between them by single nucleotide variations, known as “Single Nucleotide Fingerprint” (SNF) markers. The SNF markers can be easily identified by naked eye using a novel micro Spin-Tube device "Spin-Tube", as each of them creates a specific spot pattern. Moreover, the direct use of ribosomal RNA without requiring the PCR pre-amplification step is also feasible, further increasing the simplicity of the assay. The molecular assay delivers sensitivity capable of identifying up to 8.7 copies per µL with single mismatch specificity. The Spin-Tube thus represents an innovative solution providing benefits in terms of time, cost, and simplicity, all of which are crucial for the diagnosis of infectious disease in developing countries. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6403333/ doi: 10.1038/s41598-019-39946-0 id: cord-338041-gl65i3s0 author: Tang, Qin title: Inferring the hosts of coronavirus using dual statistical models based on nucleotide composition date: 2015-11-26 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Many coronaviruses are capable of interspecies transmission. Some of them have caused worldwide panic as emerging human pathogens in recent years, e.g., severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). In order to assess their threat to humans, we explored to infer the potential hosts of coronaviruses using a dual-model approach based on nineteen parameters computed from spike genes of coronaviruses. Both the support vector machine (SVM) model and the Mahalanobis distance (MD) discriminant model achieved high accuracies in leave-one-out cross-validation of training data consisting of 730 representative coronaviruses (99.86% and 98.08% respectively). Predictions on 47 additional coronaviruses precisely conformed to conclusions or speculations by other researchers. Our approach is implemented as a web server that can be accessed at http://bioinfo.ihb.ac.cn/seq2hosts. url: https://doi.org/10.1038/srep17155 doi: 10.1038/srep17155 id: cord-344421-rmnck42f author: Theuns, Sebastiaan title: Nanopore sequencing as a revolutionary diagnostic tool for porcine viral enteric disease complexes identifies porcine kobuvirus as an important enteric virus date: 2018-06-29 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Enteric diseases in swine are often caused by different pathogens and thus metagenomics are a useful tool for diagnostics. The capacities of nanopore sequencing for viral diagnostics were investigated here. First, cell culture-grown porcine epidemic diarrhea virus and rotavirus A were pooled and sequenced on a MinION. Reads were already detected at 7 seconds after start of sequencing, resulting in high sequencing depths (19.2 to 103.5X) after 3 h. Next, diarrheic feces of a one-week-old piglet was analyzed. Almost all reads (99%) belonged to bacteriophages, which may have reshaped the piglet’s microbiome. Contigs matched Bacteroides, Escherichia and Enterococcus phages. Moreover, porcine kobuvirus was discovered in the feces for the first time in Belgium. Suckling piglets shed kobuvirus from one week of age, but an association between peak of viral shedding (10(6.42)–10(7.01) copies/swab) and diarrheic signs was not observed during a follow-up study. Retrospective analysis showed the widespread (n = 25, 56.8% positive) of genetically moderately related kobuviruses among Belgian diarrheic piglets. MinION enables rapid detection of enteric viruses. Such new methodologies will change diagnostics, but more extensive validations should be conducted. The true enteric pathogenicity of porcine kobuvirus should be questioned, while its subclinical importance cannot be excluded. url: https://doi.org/10.1038/s41598-018-28180-9 doi: 10.1038/s41598-018-28180-9 id: cord-009690-kbwz7xop author: Toubanaki, Dimitra K. title: Development of a Nanoparticle-based Lateral Flow Strip Biosensor for Visual Detection of Whole Nervous Necrosis Virus Particles date: 2020-04-16 words: 6767.0 sentences: 381.0 pages: flesch: 47.0 cache: ./cache/cord-009690-kbwz7xop.txt txt: ./txt/cord-009690-kbwz7xop.txt summary: title: Development of a Nanoparticle-based Lateral Flow Strip Biosensor for Visual Detection of Whole Nervous Necrosis Virus Particles The principle of viral particles detection based on lateral flow biosensor with functionalized nanoparticles is presented in Fig. 1 . Nodavirus intact particles (virions), obtained either from SSN-1 cell culture supernatants or homogenized tissue samples, are directly applied on the LFB. The sample contains the nodavirus particles (virions) and is applied on the conjugation pad next to functionalized gold nanoparticles (Au) with polyclonal anti-nodavirus antibody. Application of that conjugate on the LFB resulted in a strong signal in the control zone, confirming the successful conjugation of anti-nodavirus antibody to Au nanoparticles (Fig. 2e) . To enable on site analysis of nodavirus, we developed and optimized a paper LFB based on gold nanoparticles for easy, specific and sensitive visual detection of nodavirus viral particles (virions) in biological samples. abstract: Effective analysis of pathogens causing human and veterinary diseases demands rapid, specific and sensitive detection methods which can be applied in research laboratory setups and in field for routine diagnosis. Paper lateral flow biosensors (LFBs) have been established as attractive tools for such analytical applications. In the present study a prototype LFB was designed for whole particles (virions) detection of nodavirus or fish nervous necrosis virus. Nodavirus is an important threat in the aquaculture industry, causing severe economic losses and environmental problems. The LFB was based on polyclonal antibodies conjugated on gold nanoparticles for signal visualization. Brain and retinas from fish samples were homogenized, centrifuged and the supernatant was directly applied on the LFB. Formation of a red test line was indicative of nodavirus virions presence. Nodavirus visual detection was completed in short time (30 min). Key factors of the LFB development influencing the assays’ detection limit were characterized and the optimum parameters were determined, enabling increased efficiency, excluding non-specific interactions. Therefore, the proposed LFB assay consists a robust, simple, low cost and accurate method for detection of nodavirus virions in fish samples. The proposed biosensor is ideal for development of a commercial kit to be used on aquaculture facilities by fish farmers. It is anticipated that disease monitoring and environmental safety will benefit from the simplification of time consuming and costly procedures. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7162894/ doi: 10.1038/s41598-020-63553-z id: cord-284429-d7qxfo6d author: Trezza, Alfonso title: An integrated drug repurposing strategy for the rapid identification of potential SARS-CoV-2 viral inhibitors date: 2020-08-17 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The Coronavirus disease 2019 (COVID-19) is an infectious disease caused by the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2). The virus has rapidly spread in humans, causing the ongoing Coronavirus pandemic. Recent studies have shown that, similarly to SARS-CoV, SARS-CoV-2 utilises the Spike glycoprotein on the envelope to recognise and bind the human receptor ACE2. This event initiates the fusion of viral and host cell membranes and then the viral entry into the host cell. Despite several ongoing clinical studies, there are currently no approved vaccines or drugs that specifically target SARS-CoV-2. Until an effective vaccine is available, repurposing FDA approved drugs could significantly shorten the time and reduce the cost compared to de novo drug discovery. In this study we attempted to overcome the limitation of in silico virtual screening by applying a robust in silico drug repurposing strategy. We combined and integrated docking simulations, with molecular dynamics (MD), Supervised MD (SuMD) and Steered MD (SMD) simulations to identify a Spike protein – ACE2 interaction inhibitor. Our data showed that Simeprevir and Lumacaftor bind the receptor-binding domain of the Spike protein with high affinity and prevent ACE2 interaction. url: https://doi.org/10.1038/s41598-020-70863-9 doi: 10.1038/s41598-020-70863-9 id: cord-335576-b34nc3ay author: Tsai, Andrew title: Impact of tocilizumab administration on mortality in severe COVID-19 date: 2020-11-05 words: 2917.0 sentences: 180.0 pages: flesch: 44.0 cache: ./cache/cord-335576-b34nc3ay.txt txt: ./txt/cord-335576-b34nc3ay.txt summary: Patients were stratified according to the receipt of tocilizumab for cytokine storm and matched to controls using propensity scores. The current analysis does not support the use of tocilizumab for the management of cytokine storm in patients with COVID-19. The objective of this analysis was to evaluate the clinical outcome of in-hospital mortality in patients with COVID-19 treated with tocilizumab in a single medical center. Subsequently, propensity score matching was performed to account for treatment strategy influenced by confounding by indication (the tendency of clinicians to prescribe tocilizumab in patients perceived to have cytokine storm and worsening trajectory). Currently Food and Drug Administration approved for use in the management of rheumatoid conditions and cytokine release storm-related to chimeric antigen receptor (CAR)-T cell therapy, tocilizumab has gained momentum as a potentially effective option in reducing IL-6 associated fevers and preventing clinical deterioration in COVID-19. abstract: The novel coronavirus disease 2019 (COVID-19) worldwide pandemic has placed a significant burden on hospitals and healthcare providers. The immune response to this disease is thought to lead to an aberrant inflammatory response or cytokine storm, which contributes to the severity of illness. There is an urgent need to confirm whether the use of tocilizumab provides a benefit in individuals with COVID-19. A single-center propensity-score matched cohort study, including all consecutive COVID-19 patients, admitted to the medical center who were either discharged from the medical center or expired between March 1, 2020, and May 5, 2020, was performed. Patients were stratified according to the receipt of tocilizumab for cytokine storm and matched to controls using propensity scores. The primary outcome was in-hospital mortality. A total of 274 patients meeting inclusion and exclusion criteria were identified and 132 patients were included in the matched dataset (tocilizumab = 66; no tocilizumab = 66). Approximately 73% of the patients were male. Hypertension (55%), diabetes mellitus (31%), and chronic pulmonary disease (15%) were the most common comorbidities present. There were 18 deaths (27.3%) in the tocilizumab group and 18 deaths (27.3%) in the no tocilizumab group (odds ratio, 1.0; 95% confidence interval, 0.465 – 2.151; p = 1.00). Advanced age, history of myocardial infarction, dementia, chronic pulmonary disease, heart failure, and malignancy were significantly more common in patients who died. The current analysis does not support the use of tocilizumab for the management of cytokine storm in patients with COVID-19. Use of this therapeutic agent should be limited to the context of a clinical trial until more evidence is available. url: https://www.ncbi.nlm.nih.gov/pubmed/33154452/ doi: 10.1038/s41598-020-76187-y id: cord-303601-o8uk6if2 author: Tsay, Calvin title: Modeling, state estimation, and optimal control for the US COVID-19 outbreak date: 2020-07-01 words: 6180.0 sentences: 331.0 pages: flesch: 49.0 cache: ./cache/cord-303601-o8uk6if2.txt txt: ./txt/cord-303601-o8uk6if2.txt summary: This includes modeling the dynamics of affected populations, estimating the model parameters and hidden states from data, and an optimal control strategy for sequencing social distancing and testing events such that the number of infections is minimized. Figure 2 shows the predicted values obtained by solving the parameter estimation problem and the historical data by country, retrieved by the Center for Systems Science and Engineering (CSSE) at Johns Hopkins University (https ://githu b.com/CSSEG ISand Data/COVID -19; accessed April 16, 2020). For the estimated parameter values as described previously, we simulate the results of implementing two different simplistic control policies: (i) continuing with strict social distancing, quarantining, and testing, policies that result from continuing to lower the asymptomatic ( α a ) and infected ( α i ) exposures shown in Fig. 2 ; and (ii) a relaxed policy with more lenient measures and reduced testing, in this case the values of α a and α i are increased to 0.2 and 0.02, respectively, while κ is decreased to 0.2. abstract: The novel coronavirus SARS-CoV-2 and resulting COVID-19 disease have had an unprecedented spread and continue to cause an increasing number of fatalities worldwide. While vaccines are still under development, social distancing, extensive testing, and quarantining of confirmed infected subjects remain the most effective measures to contain the pandemic. These measures carry a significant socioeconomic cost. In this work, we introduce a novel optimization-based decision-making framework for managing the COVID-19 outbreak in the US. This includes modeling the dynamics of affected populations, estimating the model parameters and hidden states from data, and an optimal control strategy for sequencing social distancing and testing events such that the number of infections is minimized. The analysis of our extensive computational efforts reveals that social distancing and quarantining are most effective when implemented early, with quarantining of confirmed infected subjects having a much higher impact. Further, we find that “on-off” policies alternating between strict social distancing and relaxing such restrictions can be effective at “flattening” the curve while likely minimizing social and economic cost. url: https://doi.org/10.1038/s41598-020-67459-8 doi: 10.1038/s41598-020-67459-8 id: cord-001868-utsvsja0 author: Uematsu, Takayuki title: Loss of CARD9-mediated innate activation attenuates severe influenza pneumonia without compromising host viral immunity date: 2015-12-02 words: 4974.0 sentences: 284.0 pages: flesch: 53.0 cache: ./cache/cord-001868-utsvsja0.txt txt: ./txt/cord-001868-utsvsja0.txt summary: In this study, we focused on CARD9, a signaling adaptor known to regulate innate immune activation through multiple innate sensor proteins, and investigated its role in anti-IFV defense and lung pathogenesis in a mouse model recapitulating severe influenza pneumonia with ARDS. Our results showed that the CARD9 pathway was involved in fatal influenza pneumonia mediated by inflammatory cytokine/chemokine production, whereas it was dispensable for type-I interferon production as well as the development of anti-viral acquired immunity. adapted IFV A/PR/8/34 strain (PR8) shows similar lung pathology to human ARDS 10-12 , we intratracheally infected wild-type (WT: C57BL/6) and Card9 -/mice with a lethal dose (10 4 PFU/mouse) of PR8 to determine whether CARD9-mediated innate immune responses contributed to severe influenza pneumonia. However, no reduction in cytokine/chemokine levels was evident on day 8, indicating that a CARD9-mediated innate response controls cytokine/chemokine production at an early time point after IFV infection and influences subsequent inflammatory cell recruitment and lung pathology at a later time point. abstract: Influenza virus (IFV) infection is a common cause of severe viral pneumonia associated with acute respiratory distress syndrome (ARDS), which is difficult to control with general immunosuppressive therapy including corticosteroids due to the unfavorable effect on viral replication. Studies have suggested that the excessive activation of the innate immunity by IFV is responsible for severe pathologies. In this study, we focused on CARD9, a signaling adaptor known to regulate innate immune activation through multiple innate sensor proteins, and investigated its role in anti-IFV defense and lung pathogenesis in a mouse model recapitulating severe influenza pneumonia with ARDS. We found that influenza pneumonia was dramatically attenuated in Card9-deficient mice, which showed improved mortality with reduced inflammatory cytokines and chemokines in the infected lungs. However, viral clearance, type-I interferon production, and the development of anti-viral B and T cell immunity were not compromised by CARD9 deficiency. Syk or CARD9-deficient DCs but not macrophages showed impaired cytokine but not type-I interferon production in response to IFV in vitro, indicating a possible role for the Syk-CARD9 pathway in DCs in excessive inflammation of IFV-infected lungs. Therefore, inhibition of this pathway is an ideal therapeutic target for severe influenza pneumonia without affecting viral clearance. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4667252/ doi: 10.1038/srep17577 id: cord-031937-qhlatg84 author: Verma, Anukriti title: Elucidating potential molecular signatures through host-microbe interactions for reactive arthritis and inflammatory bowel disease using combinatorial approach date: 2020-09-15 words: 6760.0 sentences: 326.0 pages: flesch: 31.0 cache: ./cache/cord-031937-qhlatg84.txt txt: ./txt/cord-031937-qhlatg84.txt summary: In-silico analysis involving text mining, metabolic network reconstruction, simulation, filtering, host-microbe interaction, docking and molecular mimicry studies results in robust drug target/s and biomarker/s for co-evolved IBD and ReA. The contributions of the microorganisms in the co-evolved IBD and ReA as part of the disease network was created through the interactive maps of the essential host interaction proteins (verified using literature survey) and the information processed through gene expression data analysis 64 . The pathways of the above host interacting proteins were found out using KEGG database that provides ontologies for proteins related to biological processes 67 www.nature.com/scientificreports/ Subsequently, the role of drugs or inhibitors used to suppress the effect of IBD and ReA such as indomethacin, prednisone, ciprofloxacin, sulfasalazine, azathioprine, methotrexate and hydroxychloroquine was scored in the disease network through their docking studies against the potential targets (both host as well microbial targets) as per published methodologies 68, 69 . abstract: Reactive Arthritis (ReA), a rare seronegative inflammatory arthritis, lacks exquisite classification under rheumatic autoimmunity. ReA is solely established using differential clinical diagnosis of the patient cohorts, where pathogenic triggers linked to enteric and urogenital microorganisms e.g. Salmonella, Shigella, Yersinia, Campylobacter, Chlamydia have been reported. Inflammatory Bowel Disease (IBD), an idiopathic enteric disorder co-evolved and attuned to present gut microbiome dysbiosis, can be correlated to the genesis of enteropathic arthropathies like ReA. Gut microbes symbolically modulate immune system homeostasis and are elementary for varied disease patterns in autoimmune disorders. The gut-microbiota axis structured on the core host-microbe interactions execute an imperative role in discerning the etiopathogenesis of ReA and IBD. This study predicts the molecular signatures for ReA with co-evolved IBD through the enveloped host-microbe interactions and microbe-microbe ‘interspecies communication’, using synonymous gene expression data for selective microbes. We have utilized a combinatorial approach that have concomitant in-silico work-pipeline and experimental validation to corroborate the findings. In-silico analysis involving text mining, metabolic network reconstruction, simulation, filtering, host-microbe interaction, docking and molecular mimicry studies results in robust drug target/s and biomarker/s for co-evolved IBD and ReA. Cross validation of the target/s or biomarker/s was done by targeted gene expression analysis following a non-probabilistic convenience sampling. Studies were performed to substantiate the host-microbe disease network consisting of protein-marker-symptom/disease-pathway-drug associations resulting in possible identification of vital drug targets, biomarkers, pathways and inhibitors for IBD and ReA. Our study identified Na((+))/H((+)) anti-porter (NHAA) and Kynureninase (KYNU) to be robust early and essential host-microbe interacting targets for IBD co-evolved ReA. Other vital host-microbe interacting genes, proteins, pathways and drugs include Adenosine Deaminase (ADA), Superoxide Dismutase 2 (SOD2), Catalase (CAT), Angiotensin I Converting Enzyme (ACE), carbon metabolism (folate biosynthesis) and methotrexate. These can serve as potential prognostic/theranostic biomarkers and signatures that can be extrapolated to stratify ReA and related autoimmunity patient cohorts for further pilot studies. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7492238/ doi: 10.1038/s41598-020-71674-8 id: cord-010675-acdfvjm5 author: Vila-Vicent, Susana title: Sero-epidemiological study of the rotavirus VP8* protein from different P genotypes in Valencia, Spain date: 2020-05-08 words: 4595.0 sentences: 272.0 pages: flesch: 54.0 cache: ./cache/cord-010675-acdfvjm5.txt txt: ./txt/cord-010675-acdfvjm5.txt summary: The aims of the present work were to determine the prevalence and titer of serum antibodies against several rotavirus VP8* proteins from different P genotypes in children and adults in Valencia, Spain; and to determine the role of the secretor status (FUT2(G428A) polymorphism) in the antibody response. Significant differences in the antibody titers between secretors and non-secretors were found when the whole viral particles from the Wa rotavirus strain (G1P[8]) were used as the antigen. Sero-epidemiological studies are of importance to elucidate the different viral agents and genotypes that are circulating in a particular area, for this reason the main aim of this work was to determine the serum antibody prevalence and titer to a panel of VP8* proteins from different rotavirus genotypes (P [4] , P [6] , P [8] , P [9] , P [11] , P [14] and P [25] ) in children and adults. abstract: The aims of the present work were to determine the prevalence and titer of serum antibodies against several rotavirus VP8* proteins from different P genotypes in children and adults in Valencia, Spain; and to determine the role of the secretor status (FUT2(G428A) polymorphism) in the antibody response. The VP8* protein from the P[4], P[6], P[8], P[9], P[11], P[14] and P[25] genotypes were produced in E. coli. These proteins were tested with 88 serum samples from children (n = 41, 3.5 years old in average) and from adults (n = 47, 58 years old in average) by ELISA. A subset of 55 samples were genotyped for the FUT2(G428A) polymorphism and the antibody titers compared. The same subset of samples was also analysed by ELISA using whole rotavirus Wa particles (G1P[8]) as antigen. Ninety-three per cent of the samples were positive for at least one of the VP8* antigens. Differences in the IgG seroprevalence were found between children and adults for the P[4], P[8] and P[11] genotypes. Similarly, significant differences were found between adults and children in their antibody titers against the P[4], P[8], and P[11] VP8* genotypes, having the children higher antibody titers than adults. Interestingly, positive samples against rare genotypes such as P[11] (only in children), P[14] and P[25] were found. While no statistical differences in the antibody titers between secretors and non-secretors were found for any of the tested P genotypes studied, a higher statistic significant prevalence for the P[25] genotype was found in secretors compared to non-secretors. Significant differences in the antibody titers between secretors and non-secretors were found when the whole viral particles from the Wa rotavirus strain (G1P[8]) were used as the antigen. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7210269/ doi: 10.1038/s41598-020-64767-x id: cord-272576-ez731lif author: Wada, Yoshiko title: Directional and reoccurring sequence change in zoonotic RNA virus genomes visualized by time-series word count date: 2016-11-03 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Ebolavirus, MERS coronavirus and influenza virus are zoonotic RNA viruses, which mutate very rapidly. Viral growth depends on many host factors, but human cells may not provide the ideal growth conditions for viruses invading from nonhuman hosts. The present time-series analyses of short and long oligonucleotide compositions in these genomes showed directional changes in their composition after invasion from a nonhuman host, which are thought to recur after future invasions. In the recent West Africa Ebola outbreak, directional time-series changes in a wide range of oligonucleotides were observed in common for three geographic areas, and the directional changes were observed also for the recent MERS coronavirus epidemics starting in the Middle East. In addition, common directional changes in human influenza A viruses were observed for three subtypes, whose epidemics started independently. Long oligonucleotides that showed an evident directional change observed in common for the three subtypes corresponded to some of influenza A siRNAs, whose activities have been experimentally proven. Predicting directional and reoccurring changes in oligonucleotide composition should become important for designing diagnostic RT-PCR primers and therapeutic oligonucleotides with long effectiveness. url: https://www.ncbi.nlm.nih.gov/pubmed/27808119/ doi: 10.1038/srep36197 id: cord-277816-ncdy9qgb author: Wang, Ji-gan title: Gastrointestinal symptoms and fecal nucleic acid testing of children with 2019 coronavirus disease: a systematic review and meta-analysis date: 2020-10-20 words: 3600.0 sentences: 202.0 pages: flesch: 48.0 cache: ./cache/cord-277816-ncdy9qgb.txt txt: ./txt/cord-277816-ncdy9qgb.txt summary: title: Gastrointestinal symptoms and fecal nucleic acid testing of children with 2019 coronavirus disease: a systematic review and meta-analysis In order to understand the clinical manifestations and incidence of gastrointestinal symptoms of coronavirus disease (COVID-19) in children and discuss the importance of fecal nucleic acid testing.We retrospectively analyzed studies on gastrointestinal symptoms and fecal nucleic acid detection in pediatric COVID-19 patients from January 1, 2020 to August 10, 2020, including prospective clinical studies and case reports. Stata12.0 software was used for meta-analysis.The results showed that the most common gastrointestinal symptoms in children with COVID-19 were vomiting and diarrhea, with a total incidence of 17.7% (95% Cl 13.9–21.5%). At present, there is no relevant study on whether there is a difference in the positive rate of fecal nucleic acid testing in COVID-19 children with and without diarrhea. Clinical features of 33 cases in children infected with SARS-CoV-2 in Anhui Province, China: a multi-center retrospective cohort study. abstract: In order to understand the clinical manifestations and incidence of gastrointestinal symptoms of coronavirus disease (COVID-19) in children and discuss the importance of fecal nucleic acid testing.We retrospectively analyzed studies on gastrointestinal symptoms and fecal nucleic acid detection in pediatric COVID-19 patients from January 1, 2020 to August 10, 2020, including prospective clinical studies and case reports. The results of fecal nucleic acid detection were analyzed systematically. Stata12.0 software was used for meta-analysis.The results showed that the most common gastrointestinal symptoms in children with COVID-19 were vomiting and diarrhea, with a total incidence of 17.7% (95% Cl 13.9–21.5%). However, the prevalence of gastrointestinal symptoms in other countries (21.1%, 95% CI 16.5–25.7%) was higher compared to China (12.9%, 95% CI 8–17.7%). In Wuhan, the pooled prevalence was much higher (41.3%, 95% CI 3.2–79.4%) compared to areas outside Wuhan in China (7.1%, 95% CI 4.0–10.3%). The positive rate of fecal nucleic acid testing in COVID-19 children was relatively high at 85.8% (91/106). Additionally, 71.2% (52/73) were still positive for fecal nucleic acid after respiratory tract specimens turned negative. One and two weeks after the respiratory tract specimens turned nucleic acid-negative, 45.2% (33/73) and 34.2% (25/73) patients, respectively, remained fecal nucleic acid-positive. The longest interval between the respiratory tract specimens turning negative and fecal specimens turning negative exceeded 70 days. Conclusions and relevance: gastrointestinal symptoms in pediatric COVID-19 are relatively common. Attention should be paid to the detection of fecal nucleic acids in children. Fecal nucleic acid-negative status should be considered as one of the desegregation standards. url: https://www.ncbi.nlm.nih.gov/pubmed/33082472/ doi: 10.1038/s41598-020-74913-0 id: cord-002932-5e7xrd1y author: Watanabe, Tokiko title: Experimental infection of Cynomolgus Macaques with highly pathogenic H5N1 influenza virus through the aerosol route date: 2018-03-19 words: 4497.0 sentences: 212.0 pages: flesch: 44.0 cache: ./cache/cord-002932-5e7xrd1y.txt txt: ./txt/cord-002932-5e7xrd1y.txt summary: In the ferret model, these studies demonstrated that the inoculation of animals with highly pathogenic avian influenza H5N1 virus via the aerosol route led to higher nasal wash virus titers, earlier onset of clinical signs, and/or a broader spectrum of disease compared with infection via intranasal inoculation despite no difference in lethality [9] [10] [11] . On day 3 post-infection, VN3040 virus was recovered from nasal swabs of two and three animals in the conventional and aerosol method groups, respectively, and the mean virus titers were comparable between the two groups. Cynomolgus macaques were inoculated with 4 ml of a 10 7 PFU/ml solution of the highly pathogenic H5N1 avian influenza virus A/Vietnam/ UT3040/2004 strain (VN3040) through the aerosol route by using the ultrasonic nebulizer NE-U17 (defined as "the aerosol method group"). In contrast, VN3040 replicated well in the right-and left-lower lung lobes of the infected animals in the conventional method group [the virus mean titers were 3.51 and 4.75 log 10 (PFU/g), respectively]. abstract: Several animal models are used to study influenza viruses. Intranasal inoculation of animals with a liquid inoculum is one of the main methods used to experimentally infect animals with influenza virus; however, this method does not reflect the natural infection with influenza virus by contact or aerosol route. Aerosol inhalation methods have been established with several influenza viruses for mouse and ferret models, but few studies have evaluated inoculation routes in a nonhuman primates (NHP) model. Here, we performed the experimental infection of NHPs with a highly pathogenic H5N1 influenza virus via the aerosol route and demonstrated that aerosol infection had no effect on clinical outcome, but caused broader infection throughout all of the lobes of the lung compared with a non-aerosolized approach. Aerosol infection therefore represents an option for inoculation of NHPs in future studies. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5859186/ doi: 10.1038/s41598-018-23022-0 id: cord-002874-9rxv6fy9 author: Welch, David title: Far-UVC light: A new tool to control the spread of airborne-mediated microbial diseases date: 2018-02-09 words: 3266.0 sentences: 166.0 pages: flesch: 47.0 cache: ./cache/cord-002874-9rxv6fy9.txt txt: ./txt/cord-002874-9rxv6fy9.txt summary: Here we applied this approach to test the efficacy of the 222-nm far-UVC light to inactivate influenza A virus (H1N1) carried by aerosols in a benchtop aerosol UV irradiation chamber, which generated aerosol droplets of sizes similar to those generated by human coughing and breathing. If these results are confirmed in other scenarios, it follows that the use of overhead low-level far-UVC light in public locations may represent a safe and efficient methodology for limiting the transmission and spread of airborne-mediated microbial diseases such as influenza and tuberculosis. In conclusion, we have shown for the first time that very low doses of far-UVC light efficiently inactivate airborne viruses carried by aerosols. If these results are confirmed in other scenarios, it follows that the use of overhead very low level far-UVC light in public locations may represent a safe and efficient methodology for limiting the transmission and spread of airborne-mediated microbial diseases. abstract: Airborne-mediated microbial diseases such as influenza and tuberculosis represent major public health challenges. A direct approach to prevent airborne transmission is inactivation of airborne pathogens, and the airborne antimicrobial potential of UVC ultraviolet light has long been established; however, its widespread use in public settings is limited because conventional UVC light sources are both carcinogenic and cataractogenic. By contrast, we have previously shown that far-UVC light (207–222 nm) efficiently inactivates bacteria without harm to exposed mammalian skin. This is because, due to its strong absorbance in biological materials, far-UVC light cannot penetrate even the outer (non living) layers of human skin or eye; however, because bacteria and viruses are of micrometer or smaller dimensions, far-UVC can penetrate and inactivate them. We show for the first time that far-UVC efficiently inactivates airborne aerosolized viruses, with a very low dose of 2 mJ/cm(2) of 222-nm light inactivating >95% of aerosolized H1N1 influenza virus. Continuous very low dose-rate far-UVC light in indoor public locations is a promising, safe and inexpensive tool to reduce the spread of airborne-mediated microbial diseases. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5807439/ doi: 10.1038/s41598-018-21058-w id: cord-323087-3cxyogor author: Widagdo, W. title: Tissue Distribution of the MERS-Coronavirus Receptor in Bats date: 2017-04-26 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Middle East respiratory syndrome coronavirus (MERS-CoV) has been shown to infect both humans and dromedary camels using dipeptidyl peptidase-4 (DPP4) as its receptor. The distribution of DPP4 in the respiratory tract tissues of humans and camels reflects MERS-CoV tropism. Apart from dromedary camels, insectivorous bats are suggested as another natural reservoir for MERS-like-CoVs. In order to gain insight on the tropism of these viruses in bats, we studied the DPP4 distribution in the respiratory and extra-respiratory tissues of two frugivorous bat species (Epomophorus gambianus and Rousettus aegyptiacus) and two insectivorous bat species (Pipistrellus pipistrellus and Eptesicus serotinus). In the frugivorous bats, DPP4 was present in epithelial cells of both the respiratory and the intestinal tract, similar to what has been reported for camels and humans. In the insectivorous bats, however, DPP4 expression in epithelial cells of the respiratory tract was almost absent. The preferential expression of DPP4 in the intestinal tract of insectivorous bats, suggests that transmission of MERS-like-CoVs mainly occurs via the fecal-oral route. Our results highlight differences in the distribution of DPP4 expression among MERS-CoV susceptible species, which might influence variability in virus tropism, pathogenesis and transmission route. url: https://www.ncbi.nlm.nih.gov/pubmed/28446791/ doi: 10.1038/s41598-017-01290-6 id: cord-308302-5yns1hg9 author: Wu, Gang title: A prediction model of outcome of SARS-CoV-2 pneumonia based on laboratory findings date: 2020-08-20 words: 2966.0 sentences: 202.0 pages: flesch: 48.0 cache: ./cache/cord-308302-5yns1hg9.txt txt: ./txt/cord-308302-5yns1hg9.txt summary: We used machine learning for processing laboratory findings of 110 patients with SARS-CoV-2 pneumonia (including 51 non-survivors and 59 discharged patients). Thus it is feasible to establish an accurate prediction model of outcome of SARS-CoV-2 pneumonia based on laboratory findings. Laboratory tests for SARS-CoV-2 pneumonia included: blood routine test, serum biochemical (including glucose, renal and liver function, creatine kinase, lactate dehydrogenase, and electrolytes), coagulation profile, cytokine test, markers of myocardial injury, infection-related makers, and other enzymes. 68 discharged patients with SARS-CoV-2 pneumonia whose age and gender matched the non-survivors were selected (46 male, median age 66 years). A number of laboratory features were compared between non-survivors and discharged patients with SARS-CoV-2 pneumonia. With machine learning methods previously used in radiomics, a prediction model combining seven out of thirty-eight laboratory features was built for predicting the outcome of SARS-CoV-2 pneumonia. abstract: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in thousands of deaths in the world. Information about prediction model of prognosis of SARS-CoV-2 infection is scarce. We used machine learning for processing laboratory findings of 110 patients with SARS-CoV-2 pneumonia (including 51 non-survivors and 59 discharged patients). The maximum relevance minimum redundancy (mRMR) algorithm and the least absolute shrinkage and selection operator logistic regression model were used for selection of laboratory features. Seven laboratory features selected in the model were: prothrombin activity, urea, white blood cell, interleukin-2 receptor, indirect bilirubin, myoglobin, and fibrinogen degradation products. The signature constructed using the seven features had 98% [93%, 100%] sensitivity and 91% [84%, 99%] specificity in predicting outcome of SARS-CoV-2 pneumonia. Thus it is feasible to establish an accurate prediction model of outcome of SARS-CoV-2 pneumonia based on laboratory findings. url: https://www.ncbi.nlm.nih.gov/pubmed/32820210/ doi: 10.1038/s41598-020-71114-7 id: cord-344871-486sk4wc author: Wu, Jianping title: Biochemical and structural characterization of the interface mediating interaction between the influenza A virus non-structural protein-1 and a monoclonal antibody date: 2016-09-16 words: 6992.0 sentences: 379.0 pages: flesch: 58.0 cache: ./cache/cord-344871-486sk4wc.txt txt: ./txt/cord-344871-486sk4wc.txt summary: We have previously shown that a non-structural protein 1 (NS1)-binding monoclonal antibody, termed as 2H6, can significantly reduce influenza A virus (IAV) replication when expressed intracellularly. As comparative ELISA in this and previous studies 29 showed that residues N48 and T49 in NS1(RBD) are important for the interaction with mAb 2H6, they were defined as active residues involved in the binding interaction to generate a series of models of the NS1(RBD) and 2H6-Fab complex. Overall, the predicted model from cluster 2 is consistent with our comparative ELISA data and suggests that residues N48 and T49 are important for the binding between NS1(RBD) and 2H6-Fab because their side-chains could make hydrogen bonds with residues in the VH-CDR2 of the Fab. In addition, R44 of NS1(RBD) was distal from the antibody-antigen interface, which is consistent with the results from comparative ELISA ( Figure S1 ) showing that substitution of R44 of NS1(RBD) with K did not affect its interaction with mAb 2H6. abstract: We have previously shown that a non-structural protein 1 (NS1)-binding monoclonal antibody, termed as 2H6, can significantly reduce influenza A virus (IAV) replication when expressed intracellularly. In this study, we further showed that 2H6 binds stronger to the NS1 of H5N1 than A/Puerto Rico/8/1934(H1N1) because of an amino acid difference at residue 48. A crystal structure of 2H6 fragment antigen-binding (Fab) has also been solved and docked onto the NS1 structure to reveal the contacts between specific residues at the interface of antibody-antigen complex. In one of the models, the predicted molecular contacts between residues in NS1 and 2H6-Fab correlate well with biochemical results. Taken together, residues N48 and T49 in H5N1 NS1 act cooperatively to maintain a strong interaction with mAb 2H6 by forming hydrogen bonds with residues found in the heavy chain of the antibody. Interestingly, the pandemic H1N1-2009 and the majority of seasonal H3N2 circulating in humans since 1968 has N48 in NS1, suggesting that mAb 2H6 could bind to most of the currently circulating seasonal influenza A virus strains. Consistent with the involvement of residue T49, which is well-conserved, in RNA binding, mAb 2H6 was also found to inhibit the interaction between NS1 and double-stranded RNA. url: https://doi.org/10.1038/srep33382 doi: 10.1038/srep33382 id: cord-001852-c79vwr6t author: Xiao, Qiuyan title: Prevalence and molecular characterizations of enterovirus D68 among children with acute respiratory infection in China between 2012 and 2014 date: 2015-11-16 words: 3562.0 sentences: 197.0 pages: flesch: 56.0 cache: ./cache/cord-001852-c79vwr6t.txt txt: ./txt/cord-001852-c79vwr6t.txt summary: In conclusion, our results found that a history of recurrent wheezing may be a risk factor for the detection of EV-D68 and viral-induced asthma exacerbation may be a clinical feature of EV-D68 infection. In a previous hospital-based viral surveillance study of RTI cases in Chongqing, China, from 2009 to 2012, the detection rate of EV-D68 was 0.4% (7/1565) 11 . In our study, most children infected with EV-D68 had a history of recurrent wheezing or asthma and a diagnosis of acute asthma exacerbation. Our study found that a history of recurrent wheezing or asthma may be a risk factor for the detection of EV-D68 and viral-induced acute asthma exacerbation may be a clinical feature of EV-D68 infection in Chongqing area. A history of recurrent wheezing or asthma appeared to be a risk factor for the detection of EV-D68 and viral-induced acute asthma exacerbation might be a clinical feature of EV-D68 infection. abstract: EV-D68 is associated with respiratory tract infections (RTIs). Since its first isolation, EV-D68 has been detected sporadically. However, the US and Canada have experienced outbreaks of EV-D68 infections between August and December 2014. This study aimed to investigate the molecular epidemiology and clinical characteristics of EV-D68 in Chongqing, Southwestern China. From January 2012 to November 2014, 1876 nasopharyngeal aspirate specimens (NPAs) were collected from hospitalized children with RTIs. Among the 1876 NPAs, EV-D68 was detected in 19 samples (1.0%, 19/1876). Of these, 13 samples were detected in September and October 2014 (9.8%, 13/132). Phylogenetic analysis showed that all 13 strains detected in the 2014 Chongqing had high homology with the main strains of the 2014 US outbreak. Among the children with EV-D68 infection, 13 (68%) had a history of recurrent wheezing. A total of 13 children had a discharge diagnosis of asthma. Of these, 11 children were diagnosed with acute asthma exacerbation. EV-D68 was the predominant pathogen that evoked asthma exacerbation in September and October 2014. In conclusion, our results found that a history of recurrent wheezing may be a risk factor for the detection of EV-D68 and viral-induced asthma exacerbation may be a clinical feature of EV-D68 infection. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4644992/ doi: 10.1038/srep16639 id: cord-001712-a1sbdhhn author: Xiaokaiti, Yilixiati title: EGCG reverses human neutrophil elastase-induced migration in A549 cells by directly binding to HNE and by regulating α1-AT date: 2015-07-16 words: 5801.0 sentences: 333.0 pages: flesch: 51.0 cache: ./cache/cord-001712-a1sbdhhn.txt txt: ./txt/cord-001712-a1sbdhhn.txt summary: title: EGCG reverses human neutrophil elastase-induced migration in A549 cells by directly binding to HNE and by regulating α1-AT The mechanism underlying this effect may include two processes: EGCG directly binds to neutrophil elastase and inhibits its enzymatic activity; EGCG enhances the expression of α1-antitrypsin by regulating the PI3K/AKT pathway. In this study, we demonstrated additional contributions of inflammation to the progression of lung cancer metastasis and a novel molecular target of EGCG, human neutrophil elastase, which induces lung cancer cell migration. 14 demonstrated that the natural polyphenol product curcumin inhibits tumor proliferation induced by neutrophil elastase via the upregulation of AAT in lung cancer. These results indicated that treatment with EGCG at a concentration between 10 and 20 μ M induces a substantial anti-migratory effect without affecting the proliferation of A549 cells exposed to neutrophil elastase. Our results showed that the neutrophil elastase-induced decrease in IRS-1 expression was significantly inhibited by EGCG in A549 cells. abstract: Lung carcinogenesis is a complex process that occurs in unregulated inflammatory environment. EGCG has been extensively investigated as a multi-targeting anti-tumor and anti-inflammatory compound. In this study, we demonstrated a novel mechanism by which EGCG reverses the neutrophil elastase-induced migration of A549 cells. We found that neutrophil elastase directly triggered human adenocarcinoma A549 cell migration and that EGCG suppressed the elevation of tumor cell migration induced by neutrophil elastase. We observed that EGCG directly binds to neutrophil elastase and inhibits its enzymatic activity based on the CDOCKER algorithm, MD stimulation by GROMACS, SPR assay and elastase enzymatic activity assay. As the natural inhibitor of neutrophil elastase, α1-antitrypsin is synthesized in tumor cells. We further demonstrated that the expression of α1-antitrypsin was up-regulated after EGCG treatment in neutrophil elastase-treated A549 cells. We preliminarily discovered that the EGCG-mediated induction of α1-antitrypsin expression might be correlated with the regulatory effect of EGCG on the PI3K/Akt pathway. Overall, our results suggest that EGCG ameliorates the neutrophil elastase-induced migration of A549 cells. The mechanism underlying this effect may include two processes: EGCG directly binds to neutrophil elastase and inhibits its enzymatic activity; EGCG enhances the expression of α1-antitrypsin by regulating the PI3K/AKT pathway. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4503950/ doi: 10.1038/srep11494 id: cord-001704-pdxm0iiw author: Xiong, Siping title: A Novel Chimeric Anti-PA Neutralizing Antibody for Postexposure Prophylaxis and Treatment of Anthrax date: 2015-07-02 words: 4546.0 sentences: 269.0 pages: flesch: 55.0 cache: ./cache/cord-001704-pdxm0iiw.txt txt: ./txt/cord-001704-pdxm0iiw.txt summary: hmPA6 injection before or after LeTx administration protected all rats from developing anthrax (Fig. 6C) . In the present study, we developed four murine mAbs that could well neutralize LeTx in vitro, and one clone was selected to form a human/mouse chimeric antibody known as hmPA6. In the in vivo test in the present study, irrespective of whether LF was injected before or after hmPA6, the antibody protected the rats from death provided that it was administered before or simultaneously with PA. In summary, we reported a human/murine chimeric IgG, namely, hmPA6, which can specifically identify PA with high affinity, neutralize LeTx, and protect macrophages and F344 rats from anthrax-related death. In vitro and in vivo characterization of anthrax anti-protective antigen and anti-lethal factor monoclonal antibodies after passive transfer in a mouse lethal toxin challenge model to define correlates of immunity An anthrax lethal factor-neutralizing monoclonal antibody protects rats before and after challenge with anthrax toxin abstract: Anthrax is a highly lethal infectious disease caused by the bacterium Bacillus anthracis, and the associated shock is closely related to the lethal toxin (LeTx) produced by the bacterium. The central role played by the 63 kDa protective antigen (PA63) region of LeTx in the pathophysiology of anthrax makes it an excellent therapeutic target. In the present study, a human/murine chimeric IgG mAb, hmPA6, was developed by inserting murine antibody variable regions into human constant regions using antibody engineering technology. hmPA6 expressed in 293F cells could neutralize LeTx both in vitro and in vivo. At a dose of 0.3 mg/kg, it could protect all tested rats from a lethal dose of LeTx. Even administration of 0.6 mg/kg hmPA6 48 h before LeTx challenge protected all tested rats. The results indicate that hmPA6 is a potential candidate for clinical application in anthrax treatment. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4488766/ doi: 10.1038/srep11776 id: cord-001522-82plcxv9 author: Xu, Zhiwei title: Exploration of diarrhoea seasonality and its drivers in China date: 2015-02-04 words: 3337.0 sentences: 161.0 pages: flesch: 47.0 cache: ./cache/cord-001522-82plcxv9.txt txt: ./txt/cord-001522-82plcxv9.txt summary: In this study, we reviewed the data on ''''other infectious diarrhoea'''' in China from 2005-2012 obtained from CISDCP, aiming to characterize the seasonality of diarrhoea in China and identify its potential drivers, as well as explore potential opportunities for future diarrhoea control and prevention. In terms of the amplitude distribution by age and region (seasonal amplitude refers to the relative fluctuation of diarrhoea within a certain period of time, and it provides pivotal information on the possibility of diarrhoea outbreaks), we found that adults (.515 years) had much greater diarrhoea amplitudes than children (,15 years) (Figure 4 ), but the amplitude in persons .520 years declined progressively with increasing age, reaching its valley in elderly .585 years (Figure 4) , and this decreasing trend was remarkably consistent across years ( Figure S4 (supplementary material)). Demographic, economic, geographic and climate information in all 31 provinces from 2005 to 2012, including population, per capita gross regional product (PGRP), latitude, longitude, monthly average mean temperature, monthly average relative humidity, and monthly average rainfall, were collected from China Statistical Yearbook 27 to identify the putative drivers of diarrhoea seasonality. abstract: This study investigated the diarrhoea seasonality and its potential drivers as well as potential opportunities for future diarrhoea control and prevention in China. Data on weekly infectious diarrhoea cases in 31 provinces of China from 2005 to 2012, and data on demographic and geographic characteristics, as well as climatic factors, were complied. A cosinor function combined with a Poisson regression was used to calculate the three seasonal parameters of diarrhoea in different provinces. Regression tree analysis was used to identify the predictors of diarrhoea seasonality. Diarrhoea cases in China showed a bimodal distribution. Diarrhoea in children <5 years was more likely to peak in fall-winter seasons, while diarrhoea in persons > = 5 years peaked in summer. Latitude was significantly associated with spatial pattern of diarrhoea seasonality, with peak and trough times occurring earlier at high latitudes (northern areas), and later at low latitudes (southern areas). The annual amplitudes of diarrhoea in persons > = 5 years increased with latitude (r = 0.62, P<0.001). Latitude 27.8° N and 38.65° N were the latitudinal thresholds for diarrhoea seasonality in China. Regional-specific diarrhoea control and prevention strategies may be optimal for China. More attention should be paid to diarrhoea in children <5 years during fall-winter seasons. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4316158/ doi: 10.1038/srep08241 id: cord-254090-x8tnweih author: Yang, Szu-Chi title: Efficient Structure Resonance Energy Transfer from Microwaves to Confined Acoustic Vibrations in Viruses date: 2015-12-09 words: 6073.0 sentences: 302.0 pages: flesch: 53.0 cache: ./cache/cord-254090-x8tnweih.txt txt: ./txt/cord-254090-x8tnweih.txt summary: It is interesting to notice that the required threshold electric field magnitudes at the resonant frequency (86.9 V/m) to fracture H3N2 viruses as shown in Fig. 3 (c) are within the IEEE Microwave Safety Standard (106 V/m), indicating high SRET efficiency, even though the quality factor of the H3N2 virus is low. To further investigate the efficiency of this SRET effect from microwave to virus and the threshold effect, we further measured the inactivation ratio of H3N2 virus with different power densities at the resonant frequency ~8 GHz of the confined acoustic dipolar mode. Second, at the resonant frequency, we do observe H3N2 virus inactivation by illuminating 82 W/m 2 (lower than the IEEE safety standard in public space) 8 GHz microwaves on our viral solution, corresponding to an average 87 V/m electric field intensity inside the solution, confirming that our proposed simple model to estimate the field threshold (86.9 V/m) to structurally fracture the virus is quantitatively correct, especially combining the observed threshold effect as discussed above. abstract: Virus is known to resonate in the confined-acoustic dipolar mode with microwave of the same frequency. However this effect was not considered in previous virus-microwave interaction studies and microwave-based virus epidemic prevention. Here we show that this structure-resonant energy transfer effect from microwaves to virus can be efficient enough so that airborne virus was inactivated with reasonable microwave power density safe for the open public. We demonstrate this effect by measuring the residual viral infectivity of influenza A virus after illuminating microwaves with different frequencies and powers. We also established a theoretical model to estimate the microwaves power threshold for virus inactivation and good agreement with experiments was obtained. Such structure-resonant energy transfer induced inactivation is mainly through physically fracturing the virus structure, which was confirmed by real-time reverse transcription polymerase chain reaction. These results provide a pathway toward establishing a new epidemic prevention strategy in open public for airborne virus. url: https://www.ncbi.nlm.nih.gov/pubmed/26647655/ doi: 10.1038/srep18030 id: cord-004170-ri5qsarz author: Yashima, Nozomi title: Leukocyte-derived extracellular DNA contributes to abnormal pressure elevation in the extracorporeal circulation circuit date: 2020-01-16 words: 3584.0 sentences: 234.0 pages: flesch: 44.0 cache: ./cache/cord-004170-ri5qsarz.txt txt: ./txt/cord-004170-ri5qsarz.txt summary: title: Leukocyte-derived extracellular DNA contributes to abnormal pressure elevation in the extracorporeal circulation circuit Abnormal in-circuit elevation in pressure was associated with deposition of extracellular DNA on the outlet surface of the filter. In-circuit pressure was elevated at the oxygenator if heparin was administered in whole blood that was stored for 7 days (Fig. S1B) . Then, we examined whether leukocyte stimulation results in elevation of in-circuit pressure since previous studies have suggested that stimulated leukocytes are prone to releasing DNA into the extracellular space 13 . Our study showed that leukocyte-derived extracellular DNA induced an elevation of in-circuit pressure. Our study suggested that extracellular DNA from disrupted leukocytes contributed to elevation of in-circuit pressure. In conclusion, our study shows that leukocyte-derived extracellular DNA contributes to abnormal in-circuit elevation of pressure in an ex vivo circuit. abstract: An abnormal elevation in pressure is a serious complication involving the extracorporeal circulation circuit. Clot formation might be associated with this complication, but the precise mechanism of an abnormal elevation in pressure has not been identified. We investigated sufficient conditions for in-circuit elevation in pressure using an ex vivo re-circulation circuit with porcine blood. Specifically, we investigated the effect of blood conditions, the type of anticoagulation, and pro-inflammatory stimulation on in-circuit pressure. We also examined the cause of an abnormal elevation of in-circuit pressure by specifically degrading DNA, RNA, or protein components of an obstructed filter and by using immunofluorescent techniques. Neither a change in temperature nor change in pH in the blood increased in-circuit pressure. In contrast, long-term storage of blood, pro-inflammatory stimulation by phorbol myristate acetate, and heparin administration significantly increased in-circuit pressure. Abnormal in-circuit elevation in pressure was associated with deposition of extracellular DNA on the outlet surface of the filter. Administration of DNase resulted in a rapid decline of in-circuit pressure. In an ex vivo re-circulation circuit system, extracellular DNA deposition on the filter is responsible for an abnormal in-circuit elevation in pressure. Senescent leukocytes, stimulated leukocytes, and heparin exposure are associated with extracellular DNA deposition. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6965310/ doi: 10.1038/s41598-019-57173-5 id: cord-288451-npefpo3t author: Yinda, Claude Kwe title: Novel highly divergent reassortant bat rotaviruses in Cameroon, without evidence of zoonosis date: 2016-09-26 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Bats are an important reservoir for zoonotic viruses. To date, only three RVA strains have been reported in bats in Kenya and China. In the current study we investigated the genetic diversity of RVAs in fecal samples from 87 straw-colored fruit bats living in close contact with humans in Cameroon using viral metagenomics. Five (near) complete RVA genomes were obtained. A single RVA strain showed a partial relationship with the Kenyan bat RVA strain, whereas the other strains were completely novel. Only the VP7 and VP4 genes showed significant variability, indicating the occurrence of frequent reassortment events. Comparing these bat RVA strains with currently used human RVA screening primers indicated that most of the novel VP7 and VP4 segments would not be detected in routine epidemiological screening studies. Therefore, novel consensus screening primers were developed and used to screen samples from infants with gastroenteritis living in close proximity with the studied bat population. Although RVA infections were identified in 36% of the infants, there was no evidence of zoonosis. This study identified multiple novel bat RVA strains, but further epidemiological studies in humans will have to assess if these viruses have the potential to cause gastroenteritis in humans. url: https://www.ncbi.nlm.nih.gov/pubmed/27666390/ doi: 10.1038/srep34209 id: cord-004418-08dljap3 author: Young, Ginger title: Complete Protection in Macaques Conferred by Purified Inactivated Zika Vaccine: Defining a Correlate of Protection date: 2020-02-26 words: 4619.0 sentences: 265.0 pages: flesch: 53.0 cache: ./cache/cord-004418-08dljap3.txt txt: ./txt/cord-004418-08dljap3.txt summary: In this study we evaluated the antibody responses and efficacy of an aluminum hydroxide adjuvanted purified inactivated Zika vaccine (PIZV) against challenge with Zika virus (ZIKV) strain PRVABC59. As with neutralizing antibodies, all PIZV doses were immunogenic and no anti-Zika IgG was detected in the control group prior to ZIKV challenge. PIZV elicited a dose dependent neutralizing antibody immune response and an anti-Zika IgG response which correlated with a reduction in ZIKV vRNA post-challenge (Table 2 ). Vaccinating with a broad range of PIZV dose levels enabled us to correlate both neutralizing and anti-Zika IgG antibody titers to protection against ZIKV infection. A Zika RVP assay (Sonnberg et al., manuscript in preparation) was used to determine neutralizing antibody titers in serum following the administration of PIZV (study days 1, 29, 57, and 71), and 30 days post-ZIKV challenge (day 101). abstract: A critical global health need exists for a Zika vaccine capable of mitigating the effects of future Zika epidemics. In this study we evaluated the antibody responses and efficacy of an aluminum hydroxide adjuvanted purified inactivated Zika vaccine (PIZV) against challenge with Zika virus (ZIKV) strain PRVABC59. Indian rhesus macaques received two doses of PIZV at varying concentrations ranging from 0.016 µg − 10 µg and were subsequently challenged with ZIKV six weeks or one year following the second immunization. PIZV induced a dose-dependent immune response that was boosted by a second immunization. Complete protection against ZIKV infection was achieved with the higher PIZV doses of 0.4 µg, 2 µg, and 10 µg at 6 weeks and with 10 ug PIZV at 1 year following vaccination. Partial protection was achieved with the lower PIZV doses of 0.016 µg and 0.08 µg. Based on these data, a neutralizing antibody response above 3.02 log(10) EC50 was determined as a correlate of protection in macaques. PIZV elicited a dose-dependent neutralizing antibody response which is protective for at least 1 year following vaccination. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7044319/ doi: 10.1038/s41598-020-60415-6 id: cord-319118-47ovbto5 author: Yu, Xiaojuan title: Structural basis for the neutralization of MERS-CoV by a human monoclonal antibody MERS-27 date: 2015-08-18 words: 4796.0 sentences: 254.0 pages: flesch: 53.0 cache: ./cache/cord-319118-47ovbto5.txt txt: ./txt/cord-319118-47ovbto5.txt summary: We previously reported two human monoclonal antibodies that target the receptor binding domain (RBD) of the spike and exhibit strong neutralization activity against live and pesudotyped MERS-CoV infection. We found Trp535 as an anchor residue in the RBD for MERS-27 recognition, and its interaction with N-linked carbohydrates of DPP4 is important for the binding to DPP4 and for viral entry of MERS-CoV. In sum, results of viral entry, neutralization, and binding assays consistently indicated that Trp535 and Asp539 are critical for both MERS-CoV spike glycoprotein recognition by MERS-27 and binding with receptor DPP4. The interaction between Trp535 of RBD and the DPP4 carbohydrate is also important for receptor binding and viral entry of MERS-CoV. The receptor binding domain of the new Middle East respiratory syndrome coronavirus maps to a 231-residue region in the spike protein that efficiently elicits neutralizing antibodies A conformation-dependent neutralizing monoclonal antibody specifically targeting receptor-binding domain in Middle East respiratory syndrome coronavirus spike protein abstract: The recently reported Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe respiratory illness in humans with an approximately 30% mortality rate. The envelope spike glycoprotein on the surface of MERS-CoV mediates receptor binding, membrane fusion, and viral entry. We previously reported two human monoclonal antibodies that target the receptor binding domain (RBD) of the spike and exhibit strong neutralization activity against live and pesudotyped MERS-CoV infection. Here we determined the crystal structure of MERS-CoV RBD bound to the Fab fragment of MERS-27 antibody at 3.20 Å resolution. The MERS-27 epitope in the RBD overlaps with the binding site of the MERS-CoV receptor DPP4. Further biochemical, viral entry, and neutralization analyses identified two critical residues in the RBD for both MERS-27 recognition and DPP4 binding. One of the residues, Trp535, was found to function as an anchor residue at the binding interface with MERS-27. Upon receptor binding, Trp535 interacts with the N-linked carbohydrate moiety of DPP4. Thus, MERS-27 inhibits MERS-CoV infection by directly blocking both protein-protein and protein-carbohydrate interactions between MERS-CoV RBD and DPP4. These results shed light on the molecular basis of MERS-27 neutralization and will assist in the optimization of MERS-27 as a tool to combat MERS-CoV infection. url: https://www.ncbi.nlm.nih.gov/pubmed/26281793/ doi: 10.1038/srep13133 id: cord-352020-9wxwktck author: Zhang, Baoshan title: A platform incorporating trimeric antigens into self-assembling nanoparticles reveals SARS-CoV-2-spike nanoparticles to elicit substantially higher neutralizing responses than spike alone date: 2020-10-23 words: 4914.0 sentences: 266.0 pages: flesch: 46.0 cache: ./cache/cord-352020-9wxwktck.txt txt: ./txt/cord-352020-9wxwktck.txt summary: To alleviate this issue, we developed a plug-and-play platform using the spontaneous isopeptide-bond formation of the SpyTag:SpyCatcher system to display trimeric antigens on self-assembling nanoparticles, including the 60-subunit Aquifex aeolicus lumazine synthase (LuS) and the 24-subunit Helicobacter pylori ferritin. The versatile platform described here thus allows for multivalent plug-and-play presentation on self-assembling nanoparticles of trimeric viral antigens, with SARS-CoV-2 spike-LuS nanoparticles inducing particularly potent neutralizing responses. To improve protein solubility and expression, we added glycans to the surface of the nanoparticles, designing a panel of LuS and ferritin constructs with SpyTag and SpyCatcher (Table 1 and Supplementary Table S1 ). To demonstrate the versatility of our SpyTag-displaying nanoparticles in immunogen development, we conjugated them to three viral antigens of vaccine interest, the DS2-preF stabilized RSV F 33 , a DS2-stabilized version of PIV3 F 34 , and the 2P-stabilized version of SARS-CoV-2 spike 24 . abstract: Antigens displayed on self-assembling nanoparticles can stimulate strong immune responses and have been playing an increasingly prominent role in structure-based vaccines. However, the development of such immunogens is often complicated by inefficiencies in their production. To alleviate this issue, we developed a plug-and-play platform using the spontaneous isopeptide-bond formation of the SpyTag:SpyCatcher system to display trimeric antigens on self-assembling nanoparticles, including the 60-subunit Aquifex aeolicus lumazine synthase (LuS) and the 24-subunit Helicobacter pylori ferritin. LuS and ferritin coupled to SpyTag expressed well in a mammalian expression system when an N-linked glycan was added to the nanoparticle surface. The respiratory syncytial virus fusion (F) glycoprotein trimer—stabilized in the prefusion conformation and fused with SpyCatcher—could be efficiently conjugated to LuS-SpyTag or ferritin-SpyTag, enabling multivalent display of F trimers with prefusion antigenicity. Similarly, F-glycoprotein trimers from human parainfluenza virus-type 3 and spike-glycoprotein trimers from SARS-CoV-2 could be displayed on LuS nanoparticles with decent yield and antigenicity. Notably, murine vaccination with 0.08 µg of SARS-CoV-2 spike-LuS nanoparticle elicited similar neutralizing responses as 2.0 µg of spike, which was ~ 25-fold higher on a weight-per-weight basis. The versatile platform described here thus allows for multivalent plug-and-play presentation on self-assembling nanoparticles of trimeric viral antigens, with SARS-CoV-2 spike-LuS nanoparticles inducing particularly potent neutralizing responses. url: https://www.ncbi.nlm.nih.gov/pubmed/33097791/ doi: 10.1038/s41598-020-74949-2 id: cord-002081-vi6rth9o author: Zhang, Chao title: Establishment and application of a real-time loop-mediated isothermal amplification system for the detection of CYP2C19 polymorphisms date: 2016-06-01 words: 3387.0 sentences: 211.0 pages: flesch: 49.0 cache: ./cache/cord-002081-vi6rth9o.txt txt: ./txt/cord-002081-vi6rth9o.txt summary: In this work, a rapid one-step SNP detection method, real-time loop-mediated isothermal amplification (RT-LAMP), was first applied for CYP2C19 polymorphisms testing. The optimized method was established with specifically designed primers for target amplification by real-time detection in approximately 30 min under isothermal conditions. The successful establishment of an inexpensive, rapid and real-time LAMP protocol for CYP2C19*2 and CYP2C19*3 detection is significant for the extension of this technique for genotyping other SNPs. Our results suggest applications for this RT-LAMP assay system for both basic research and clinical diagnosis in pharmacogenomics. In this study, the successful establishment of an inexpensive, rapid and real-time LAMP protocol for CYP2C19 SNP genotyping expanded the scope of application of this technique to human gene mutation detection. In summary, as a rapid, feasible and cost-efficient point-of-care (POC) SNP detection method, we demonstrated that RT-LAMP could quantitatively detect human genomic DNA with high specificity and sensitivity in a single step. abstract: Single-nucleotide polymorphisms (SNPs) represent the most widespread type of genetic variation (approximately 90%) in the human genome, and the demand to overcome such variation has received more attention now than ever before. The capacity to rapidly assess SNPs that correlate with disease predisposition, drug efficacy and drug toxicity is a key step for the development of personalized medicine. In this work, a rapid one-step SNP detection method, real-time loop-mediated isothermal amplification (RT-LAMP), was first applied for CYP2C19 polymorphisms testing. The optimized method was established with specifically designed primers for target amplification by real-time detection in approximately 30 min under isothermal conditions. RT-LAMP amplified few copies of template to produce significant amounts of product and quantitatively detected human DNA with compatible specificity and sensitivity. The success in the establishment of this RT-LAMP protocol for CYP2C19 polymorphism testing is significant for the extension of this technique for the detection of other SNPs, which will further facilitate the development of personalized medicine. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4887897/ doi: 10.1038/srep26533 id: cord-283583-pwlbrxn3 author: Zhang, Xiao-Ai title: Prevalence and genetic characteristics of Saffold cardiovirus in China from 2009 to 2012 date: 2015-01-09 words: 3779.0 sentences: 207.0 pages: flesch: 51.0 cache: ./cache/cord-283583-pwlbrxn3.txt txt: ./txt/cord-283583-pwlbrxn3.txt summary: A higher frequency of severe clinical outcome and nervous system manifestation were also observed in the SAFV-positive HFMD patients. A patient was considered to be infected with SAFV when positive detection was obtained in any type of the samples. Genetic characterization of SAFVs. A phylogenetic tree was constructed based on the VP1 nucleotide sequences of Saffold cardiovirus detected in clinical samples of 82 patients in the current study, and sequences downloaded from GenBank by maximum likelihood method using MEGA 6.0 (Figure 1) . Detection of SAFV in sera and CSFs. Additional 171 CSFs were collected from patients with HFMD-associated encephalitis, and six (3.5%) were found to be SAFV-positive using real-time RT-PCR, and five were further confirmed by nested RT-PCR targeting the 59-UTR. In our study, SAFVs were co-detected with other viruses in 14 (82.4%), 9 (75.0%), and 28 (32.6) specimens in ARTI, diarrhea and HFMD patients respectively. abstract: The epidemiology and clinical features of the Saffold cardiovirus (SAFV) remain ambiguous. The present study was designed to systematically and intensively investigate the epidemiological features of SAFV in pediatric patients in China. Three cohorts of pediatric patients were recruited from 2009 to 2012. Cohort 1 comprised patients with acute respiratory tract infections. Cohort 2 comprised patients with diarrhea. Cohort 3 comprised hand, foot, and mouth disease (HFMD) patients. A total of 115 patients (1.6%) among 6052 (17/1647, 12/2013, and 86/2392 in cohorts 1, 2, and 3, respectively) were SAFV-positive. The samples from 82 SAFV-positive patients were successfully sequenced, and four genotypes were identified: 8 SAFV-1, 41 SAFV-2, 29 SAFV-3, and 4 SAFV-6. A significantly higher detection rate was found in the HFMD patients than in other two cohorts (both P <0.001). A higher frequency of severe clinical outcome and nervous system manifestation were also observed in the SAFV-positive HFMD patients. Additionally, 6 (3.5%) cerebrospinal fluid and 7 (2.2%) serum samples from the HFMD-associated encephalitis patients were SAFV-positive. Based on the VP1 sequences, all four genotypes displayed distinct geographical clustering. SAFV infection might be associated with a wide clinical spectrum and contribute to HFMD. url: https://www.ncbi.nlm.nih.gov/pubmed/25572936/ doi: 10.1038/srep07704 id: cord-004060-nxw5k9y1 author: Zhang, Yewu title: Spatiotemporal Analysis of Influenza in China, 2005–2018 date: 2019-12-23 words: 5547.0 sentences: 301.0 pages: flesch: 47.0 cache: ./cache/cord-004060-nxw5k9y1.txt txt: ./txt/cord-004060-nxw5k9y1.txt summary: After adjusting for other covariates, a spatially unstructured random effect term (v i ), a spatially structured conditional autoregression term (υ i ), a first-order random walk-correlated time variable (γ 1j ), and an interaction term for time and place (δ ij ) in the multivariate adjusted spatiotemporal model, the flu vaccines (per million doses), flu surveillance protocols, rate of influenza A (H1N1)pdm09, latitude and longitude still remain statistically significant. Based on the incidence data of influenza gained from the Chinese Notifiable Infectious Disease Reporting System, we used the Bayesian spatiotemporal model in this study to assess the space-time patterns of the influenza epidemic at the prefecture level in mainland China from 2005 to 2018 and explored several factors that may be associated with the changing spatial and temporal patterns in the influenza incidence risk. abstract: Influenza is a major cause of morbidity and mortality worldwide, as well as in China. Knowledge of the spatial and temporal characteristics of influenza is important in evaluating and developing disease control programs. This study aims to describe an accurate spatiotemporal pattern of influenza at the prefecture level and explore the risk factors associated with influenza incidence risk in mainland China from 2005 to 2018. The incidence data of influenza were obtained from the Chinese Notifiable Infectious Disease Reporting System (CNIDRS). The Besag York Mollié (BYM) model was extended to include temporal and space-time interaction terms. The parameters for this extended Bayesian spatiotemporal model were estimated through integrated nested Laplace approximations (INLA) using the package R-INLA in R. A total of 702,226 influenza cases were reported in mainland China in CNIDRS from 2005–2018. The yearly reported incidence rate of influenza increased 15.6 times over the study period, from 3.51 in 2005 to 55.09 in 2008 per 100,000 populations. The temporal term in the spatiotemporal model showed that much of the increase occurred during the last 3 years of the study period. The risk factor analysis showed that the decreased number of influenza vaccines for sale, the new update of the influenza surveillance protocol, the increase in the rate of influenza A (H1N1)pdm09 among all processed specimens from influenza-like illness (ILI) patients, and the increase in the latitude and longitude of geographic location were associated with an increase in the influenza incidence risk. After the adjusting for fixed covariate effects and time random effects, the map of the spatial structured term shows that high-risk areas clustered in the central part of China and the lowest-risk areas in the east and west. Large space-time variations in influenza have been found since 2009. In conclusion, an increasing trend of influenza was observed from 2005 to 2018. The insufficient flu vaccine supplements, the newly emerging influenza A (H1N1)pdm09 and expansion of influenza surveillance efforts might be the major causes of the dramatic changes in outbreak and spatio-temporal epidemic patterns. Clusters of prefectures with high relative risks of influenza were identified in the central part of China. Future research with more risk factors at both national and local levels is necessary to explain the changing spatiotemporal patterns of influenza in China. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6928232/ doi: 10.1038/s41598-019-56104-8 id: cord-002802-594mmlk8 author: Zhang, Yun title: Recombinant influenza H9N2 virus with a substitution of H3 hemagglutinin transmembrane domain showed enhanced immunogenicity in mice and chicken date: 2017-12-20 words: 4269.0 sentences: 246.0 pages: flesch: 47.0 cache: ./cache/cord-002802-594mmlk8.txt txt: ./txt/cord-002802-594mmlk8.txt summary: Further, the recombinant TM-replaced H9N2-TM virus could provide better inter-clade protection in both mice and chickens against H9N2, suggesting that the H3-TM-replacement could be considered as a strategy to develop efficient subtype-specific H9N2 influenza vaccines. However, the biological characteristics, such as virus growth, ratio of trimer, thermal stability, acidic resistance and fusion activity were altered, suggesting an important role of the TM domain in viral replication and pathogenicity. Taken together, the increased thermal and acidic resistances of the recombinant H9N2-TM virus suggest that the substitution in the transmembrane (TM) domain can affect the stability of the HA, therefore alters viral biological characteristics. To explore whether the increased HA trimers and increased thermal and acidic resistances could result in better immune responses thus providing better protection in mice, we first vaccinated six-week-old mice with inactivated recombinant H9N2-WT and H9N2-TM viruses twice to check antibody responses. abstract: In recent years, avian influenza virus H9N2 undergoing antigenic drift represents a threat to poultry farming as well as public health. Current vaccines are restricted to inactivated vaccine strains and their related variants. In this study, a recombinant H9N2 (H9N2-TM) strain with a replaced H3 hemagglutinin (HA) transmembrane (TM) domain was generated. Virus assembly and viral protein composition were not affected by the transmembrane domain replacement. Further, the recombinant TM-replaced H9N2-TM virus could provide better inter-clade protection in both mice and chickens against H9N2, suggesting that the H3-TM-replacement could be considered as a strategy to develop efficient subtype-specific H9N2 influenza vaccines. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5738434/ doi: 10.1038/s41598-017-18054-x id: cord-343528-5283jsnu author: Zhang, Zhao title: Evolutionary Dynamics of MERS-CoV: Potential Recombination, Positive Selection and Transmission date: 2016-05-04 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Middle East respiratory syndrome coronavirus (MERS-CoV) belongs to beta group of coronavirus and was first discovered in 2012. MERS-CoV can infect multiple host species and cause severe diseases in human. We conducted a series of phylogenetic and bioinformatic analyses to study the evolution dynamics of MERS-CoV among different host species with genomic data. Our analyses show: 1) 28 potential recombinant sequences were detected and they can be classified into seven potential recombinant types; 2) The spike (S) protein of MERS-CoV was under strong positive selection when MERS-CoV transmitted from their natural host to human; 3) Six out of nine positive selection sites detected in spike (S) protein are located in its receptor-binding domain which is in direct contact with host cells; 4) MERS-CoV frequently transmitted back and forth between human and camel after it had acquired the human-camel infection capability. Together, these results suggest that potential recombination events might have happened frequently during MERS-CoV’s evolutionary history and the positive selection sites in MERS-CoV’s S protein might enable it to infect human. url: https://doi.org/10.1038/srep25049 doi: 10.1038/srep25049 id: cord-348515-bqqyly23 author: Zhao, Suhui title: Re-emergent Human Adenovirus Genome Type 7d Caused an Acute Respiratory Disease Outbreak in Southern China After a Twenty-one Year Absence date: 2014-12-08 words: 6569.0 sentences: 323.0 pages: flesch: 43.0 cache: ./cache/cord-348515-bqqyly23.txt txt: ./txt/cord-348515-bqqyly23.txt summary: Recombination analysis reveals this genome differs from the 1950s-era prototype and vaccine strains by a lateral gene transfer, substituting the coding region for the L1 52/55 kDa DNA packaging protein from HAdV-16. Recombination analysis reveals this genome differs from the 1950s-era prototype and vaccine strains by a lateral gene transfer, substituting the coding region for the L1 52/55 kDa DNA packaging protein from HAdV-16. Thorough characterization of these pathogens is evidenced by the availability of two genome sequences (JF800905 and JX625134), both of which are further identified as the HAdV-7d genome type in this report, and shown to be nearly identical to this report of an isolate from a 2011 ARD outbreak in Guangdong Province (strain DG01_2011) by comparative genomics and, in particular, in silico REA pattern analysis, as presented in Figure 2 . abstract: Human adenoviruses (HAdVs) are highly contagious pathogens causing acute respiratory disease (ARD), among other illnesses. Of the ARD genotypes, HAdV-7 presents with more severe morbidity and higher mortality than the others. We report the isolation and identification of a genome type HAdV-7d (DG01_2011) from a recent outbreak in Southern China. Genome sequencing, phylogenetic analysis, and restriction endonuclease analysis (REA) comparisons with past pathogens indicate HAdV-7d has re-emerged in Southern China after an absence of twenty-one years. Recombination analysis reveals this genome differs from the 1950s-era prototype and vaccine strains by a lateral gene transfer, substituting the coding region for the L1 52/55 kDa DNA packaging protein from HAdV-16. DG01_2011 descends from both a strain circulating in Southwestern China (2010) and a strain from Shaanxi causing a fatality and outbreak (Northwestern China; 2009). Due to the higher morbidity and mortality rates associated with HAdV-7, the surveillance, identification, and characterization of these strains in population-dense China by REA and/or whole genome sequencing are strongly indicated. With these accurate identifications of specific HAdV types and an epidemiological database of regional HAdV pathogens, along with the HAdV genome stability noted across time and space, the development, availability, and deployment of appropriate vaccines are needed. url: https://www.ncbi.nlm.nih.gov/pubmed/25482188/ doi: 10.1038/srep07365 id: cord-356027-ckdx56j1 author: Zheng, Shou-Yan title: Association between secondary thrombocytosis and viral respiratory tract infections in children date: 2016-03-11 words: 3340.0 sentences: 194.0 pages: flesch: 49.0 cache: ./cache/cord-356027-ckdx56j1.txt txt: ./txt/cord-356027-ckdx56j1.txt summary: Compared with the normal group, the detection rates of respiratory syncytial virus (RSV) and human rhinovirus (HRV) were significantly higher in the thrombocytosis group (P = 0.017 and 0.042, respectively). Multiplex nested polymerase chain reaction (PCR) was used to detect the following common respiratory viruses, as described previously [11] [12] [13] [14] [15] : RSV subtypes A and B (RSVA, RSVB); influenza virus (IFV) subtypes A, B and C (IFVA, IFVB, IFVC); human coronaviruses (HCoV); metapneumovirus (MPV); parainfluenza virus type 1 to 4 (PIV1-4); adenovirus (ADV); human bocavirus type 1 (HBoV1) and human rhinovirus (HRV) subtypes A and C (HRVA, HRVC). Compared with the normal group, the total detection rates of RSV and HRV were both significantly higher (P = 0.001 and 0.033, respectively) in the thrombocytosis group, and ADV and IFV were lower (P = 0.001 and 0.007, respectively). ST was especially common in patients with lower respiratory tract infections and occurred most frequently in the mild thrombocytosis group (500-699 × 10 9 /L). abstract: Secondary thrombocytosis (ST) is frequently observed in children with a variety of clinical conditions. The leading cause of ST is respiratory tract infection (RTI) in children. Nasopharyngeal aspirate samples were collected and assessed for common respiratory viruses. The relationships between virus infections and secondary thrombocytosis were analyzed retrospectively. The blood platelet count and the presence of respiratory viruses were determined for 3156 RTI patients, and 817 (25.9%) cases with platelet ≥500 × 10(9)/L were considered as the thrombocytosis group. Compared with the normal group, the detection rates of respiratory syncytial virus (RSV) and human rhinovirus (HRV) were significantly higher in the thrombocytosis group (P = 0.017 and 0.042, respectively). HRV single infection was a risk factor associated with thrombocytosis [odds ratio (OR) = 1.560, 95% confidence interval (CI) = 1.108–2.197]. Furthermore, ST was more likely to occur in younger patients who had clinical manifestations of wheezing and dyspnea and who had been diagnosed with bronchiolitis. Furthermore, the course of disease lasted longer in these patients. ST is associated with viral respiratory tract infections, especially RSV and HRV infections. HRV single infection is a risk factor associated with thrombocytosis. url: https://www.ncbi.nlm.nih.gov/pubmed/26965460/ doi: 10.1038/srep22964 id: cord-002013-rb9xdzro author: Zheng, Xuexing title: Treatment with hyperimmune equine immunoglobulin or immunoglobulin fragments completely protects rodents from Ebola virus infection date: 2016-04-12 words: 6027.0 sentences: 286.0 pages: flesch: 56.0 cache: ./cache/cord-002013-rb9xdzro.txt txt: ./txt/cord-002013-rb9xdzro.txt summary: To investigate whether EBOV infections can be controlled by virus neutralization alone, and to prevent the possible induction of serum sickness in humans that would be administered antisera, the post-exposure efficacy of F(ab′ ) 2 (immunoglobulin treated with pepsin to remove the Fc regions of the antibody) were also investigated side-by-side with equine antisera in all experiments as a potential alternate treatment. Three horses were immunized intramuscularly (IM) with 7 injections of eVLP over 11 weeks and the hyperimmune sera were collected from each animal at specified timepoints ( Fig. 1A) to determine the serum titers by neutralization assay against a recombinant HIV-1 virus pseudotyped with EBOV GP. The observation that administering F(ab′ ) 2 at 1 dpi is more efficacious than when the same treatment was given at 30 minutes post-exposure (Fig. 5A ) was also observed in past studies with therapeutic EBOV GP-specific monoclonal antibodies 25, 26 , and suggests that virus neutralization may play a bigger role in protection at a later timepoint after EBOV challenge. abstract: Recent successes with monoclonal antibody cocktails ZMapp(TM) and MIL77 against Ebola virus (EBOV) infections have reignited interest in antibody-based therapeutics. Since the production process for monoclonal antibodies can be prolonged and costly, alternative treatments should be investigated. We produced purified equine antisera from horses hyperimmunized with EBOV virus-like particles, and tested the post-exposure efficacy of the antisera in a mouse model of infection. BALB/c mice were given up to 2 mg of purified equine antisera per animal, at 30 minutes, 1 or 2 days post-infection (dpi), in which all animals survived. To decrease the possibility of serum sickness, the equine antisera was digested with pepsin to generate F(ab′)(2) fragments, with in vitro neutralizing activity comparable to whole immunoglobulin. Full protection was achieved with when treatment was initiated at 1 dpi, but the suboptimal protection observed with the 30 minute and 2 dpi groups demonstrate that in addition to virus neutralization, other Fc-dependent antibody mechanisms may also contribute to survival. Guinea pigs given 20 mg of antisera or F(ab′)(2) at or starting at 1 or 2 dpi were also fully protected from EBOV infection. These results justify future efficacy studies for purified equine products in NHPs. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4828711/ doi: 10.1038/srep24179 id: cord-004385-xna32qve author: Zhou, Yuqing title: Use of corticosteroids in influenza-associated acute respiratory distress syndrome and severe pneumonia: a systemic review and meta-analysis date: 2020-02-20 words: 4494.0 sentences: 234.0 pages: flesch: 39.0 cache: ./cache/cord-004385-xna32qve.txt txt: ./txt/cord-004385-xna32qve.txt summary: title: Use of corticosteroids in influenza-associated acute respiratory distress syndrome and severe pneumonia: a systemic review and meta-analysis We obtained the following data: (a) characteristics of studies (design, setting, country, period, methodological details for quality assessment); (b) characteristics of participants (demographics, co-morbid illnesses, disease severity, numbers in each group, influenza virus type); (c) characteristics of interventions (type, dose, timing and duration of corticosteroid use); and (d) outcomes. Another study reporting the result of 62 patients with acute respiratory failure due to influenza showed no statistically significant difference between low dose and high dose corticosteroid therapy (8/19 versus 7/19, p > 0.05) 16 . The overall findings of this meta-analysis indicated that patients with pneumonia or acute respiratory distress syndrome who were administered corticosteroids had significantly higher mortality and incidence of nosocomial infection but the use of corticosteroids did not influence the length of hospital stay. abstract: Influenza-related severe pneumonia and acute respiratory distress syndrome (ARDS) are severe threats to human health. The objective of this study was to assess the effects of systematic corticosteroid therapy in patients with pneumonia or ARDS. The PubMed, EMBASE, Web of Science and SCOPUS databases were searched up to July, 2019. Nineteen studies including 6637 individuals were identified, and fifteen studies (6427 patients) were included in the meta-analysis of mortality. Eighteen were observational studies and one was a randomized controlled trial (RCT). The meta-analysis results showed that corticosteroid therapy was associated with significantly higher mortality (OR 1.53, 95% CI [1.16, 2.01]) and incidence of nosocomial infection (OR 3.15, 95% CI [1.54, 6.45]). Subgroup analysis showed that among patients with unadjusted estimates, the odds of mortality were higher in patients receiving corticosteroid treatment (OR 1.98, 95% CI [1.23, 3.17]), however, among patients with adjusted estimates, the result showed no statistically significant difference between corticosteroid group and control group (OR 1.31, 95% CI [0.95, 1.80]). Current data do not support the routine use of corticosteroids in patients with influenza severe pneumonia or ARDS. RCTs are needed to provide more robust evidence. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7033254/ doi: 10.1038/s41598-020-59732-7 id: cord-003011-vclnb0eh author: de Almeida, Carlos Podalirio Borges title: Predictors of In-Hospital Mortality among Patients with Pulmonary Tuberculosis: A Systematic Review and Meta-analysis date: 2018-05-08 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Background: There is uncertainty regarding which factors are associated with in-hospital mortality among patients with pulmonary TB (PTB). The aim of this systematic review and meta-analysis is to identify predictors of in-hospital mortality among patients with PTB. Methods: We searched MEDLINE, EMBASE, and Global Health, for cohort and case-control studies that reported risk factors for in-hospital mortality in PTB. We pooled all factors that were assessed for an association, and presented relative associations as pooled odds ratios (ORs). Results: We identified 2,969 records, of which we retrieved 51 in full text; 11 cohort studies that evaluated 5,468 patients proved eligible. Moderate quality evidence suggested an association with co-morbid malignancy and in-hospital mortality (OR 1.85; 95% CI 1.01–3.40). Low quality evidence showed no association with positive sputum smear (OR 0.99; 95% CI 0.40–2.48), or male sex (OR 1.09, 95% CI 0.84–1.41), and very low quality evidence showed no association with diabetes mellitus (OR 1.31, 95% IC 0.38–4.46), and previous TB infection (OR 2.66, 95% CI 0.48–14.87). Conclusion: Co-morbid malignancy was associated with increased risk of in-hospital death among pulmonary TB patients. There is insufficient evidence to confirm positive sputum smear, male sex, diabetes mellitus, and previous TB infection as predictors of in-hospital mortality in TB patients. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5940698/ doi: 10.1038/s41598-018-25409-5 ==== make-pages.sh questions [ERIC WAS HERE] ==== make-pages.sh search /data-disk/reader-compute/reader-cord/bin/make-pages.sh: line 77: /data-disk/reader-compute/reader-cord/tmp/search.htm: No such file or directory Traceback (most recent call last): File "/data-disk/reader-compute/reader-cord/bin/tsv2htm-search.py", line 51, in with open( TEMPLATE, 'r' ) as handle : htm = handle.read() FileNotFoundError: [Errno 2] No such file or directory: '/data-disk/reader-compute/reader-cord/tmp/search.htm' ==== make-pages.sh topic modeling corpus Zipping study carrel