Carrel name: journal-medHypotheses-cord Creating study carrel named journal-medHypotheses-cord Initializing database parallel: Warning: Only enough available processes to run 15 jobs in parallel. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf parallel: Warning: or /proc/sys/kernel/pid_max may help. parallel: Warning: No more processes: Decreasing number of running jobs to 14. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. file: cache/cord-254162-tu81j66h.json key: cord-254162-tu81j66h authors: Bai, Xiyuan; Hippensteel, Joseph; Leavitt, Alida; Maloney, James P.; Beckham, David; Garcia, Cindy; Li, Qing; Freed, Brian M.; Ordway, Diane; Sandhaus, Robert A.; Chan, Edward D. title: Hypothesis: alpha-1-antitrypsin is a promising treatment option for COVID-19 date: 2020-11-12 journal: Med Hypotheses DOI: 10.1016/j.mehy.2020.110394 sha: doc_id: 254162 cord_uid: tu81j66h file: cache/cord-258670-dphg8ukj.json key: cord-258670-dphg8ukj authors: Karaahmet, Fatih; Altan Kocaman, Sinan title: Endothelial progenitor cells and mesenchymal stem cells to overcome vascular deterioration and cytokine storm in critical patients with COVID-19 date: 2020-06-10 journal: Med Hypotheses DOI: 10.1016/j.mehy.2020.109973 sha: doc_id: 258670 cord_uid: dphg8ukj file: cache/cord-254411-e9vvjv8w.json key: cord-254411-e9vvjv8w authors: Taghizadeh-Hesary, Farzad; Akbari, Hassan title: The Powerful Immune System Against Powerful COVID-19: A Hypothesis date: 2020-04-22 journal: Med Hypotheses DOI: 10.1016/j.mehy.2020.109762 sha: doc_id: 254411 cord_uid: e9vvjv8w file: cache/cord-258272-uu6t6tnh.json key: cord-258272-uu6t6tnh authors: Dabaghian, Farid; Khanavi, Mahnaz; Zarshenas, Mohammad M. title: Bioactive compounds with possible inhibitory activity of Angiotensin-Converting Enzyme-II; a gate to manage and prevent COVID-19 date: 2020-05-16 journal: Med Hypotheses DOI: 10.1016/j.mehy.2020.109841 sha: doc_id: 258272 cord_uid: uu6t6tnh file: cache/cord-261574-zcazhkad.json key: cord-261574-zcazhkad authors: García, Néstor H.; Porta, Daniela J.; Alasino, Roxana V.; Muñoz, Sonia E.; Beltramo, Dante M. title: Ibuprofen, a traditional drug that may impact the course of COVID-19 New effective formulation in nebulizable solution date: 2020-07-07 journal: Med Hypotheses DOI: 10.1016/j.mehy.2020.110079 sha: doc_id: 261574 cord_uid: zcazhkad file: cache/cord-253312-bf35afpj.json /data-disk/reader-compute/reader-cord/bin/json2txt-carrel.sh: fork: retry: Resource temporarily unavailable key: cord-253312-bf35afpj authors: Unal, Gokhan; Turan, Bahadir; Hasan Balcioglu, Yasin title: Immunopharmacological management of COVID-19: Potential therapeutic role of valproic acid date: 2020-05-27 journal: Med Hypotheses DOI: 10.1016/j.mehy.2020.109891 sha: doc_id: 253312 cord_uid: bf35afpj file: cache/cord-261370-jp5sqqwc.json key: cord-261370-jp5sqqwc authors: Bollag, Wendy B.; Gonzales, Joyce N. title: Phosphatidylglycerol and Surfactant: A Potential Treatment for COVID-19? date: 2020-09-16 journal: Med Hypotheses DOI: 10.1016/j.mehy.2020.110277 sha: doc_id: 261370 cord_uid: jp5sqqwc file: cache/cord-253468-pf0xubii.json /data-disk/reader-compute/reader-cord/bin/json2txt-carrel.sh: fork: retry: Resource temporarily unavailable key: cord-253468-pf0xubii authors: Emara, Mohamed H; Mazid, Usama; Ali Atta, Mohamed; Elshahat, Sahar; Mohamed Mahros, Aya title: Ketonuria with or without ketoacidosis as the presenting manifestation of SARS-CoV-2 (COVID-19) among uncontrolled Type 2 Diabetic patients date: 2020-09-02 journal: Med Hypotheses DOI: 10.1016/j.mehy.2020.110226 sha: doc_id: 253468 cord_uid: pf0xubii file: cache/cord-256092-bph9ys72.json /data-disk/reader-compute/reader-cord/bin/json2txt-carrel.sh: fork: retry: No child processes key: cord-256092-bph9ys72 authors: Hussain, Aneela N.; Hussain, Fazal; Hashmi, Shahrukh K. title: Role of testosterone in COVID-19 patients - a double-edged sword? date: 2020-09-17 journal: Med Hypotheses DOI: 10.1016/j.mehy.2020.110287 sha: doc_id: 256092 cord_uid: bph9ys72 file: cache/cord-265724-fdt00qw1.json key: cord-265724-fdt00qw1 authors: Varadarajan, Saranya; Madapusi Balaji, Thodur; Sarode, Sachin C.; Sarode, Gargi S.; Sharma, Nilesh K.; Gondivkar, Shailesh; Gadbail, Amol; Patil, Shankargouda title: EMMPRIN/BASIGIN as a biological modulator of oral cancer and COVID-19 interaction: novel propositions date: 2020-07-09 journal: Med Hypotheses DOI: 10.1016/j.mehy.2020.110089 sha: doc_id: 265724 cord_uid: fdt00qw1 file: cache/cord-265322-3854ddb9.json key: cord-265322-3854ddb9 authors: Vavougios, George D. title: A data-driven hypothesis on the epigenetic dysregulation of host metabolism by SARS coronaviral infection: potential implications for the SARS-CoV-2 modus operandi date: 2020-04-23 journal: Med Hypotheses DOI: 10.1016/j.mehy.2020.109759 sha: doc_id: 265322 cord_uid: 3854ddb9 file: cache/cord-264916-c4n0kyog.json key: cord-264916-c4n0kyog authors: Zimmerman, Keith; Kearns, Fiona; Tzekov, Radouil title: Natural protection of ocular surface from viral infections – a hypothesis date: 2020-07-09 journal: Med Hypotheses DOI: 10.1016/j.mehy.2020.110082 sha: doc_id: 264916 cord_uid: c4n0kyog file: cache/cord-267612-1h7xpkbe.json key: cord-267612-1h7xpkbe authors: Lipsker, Dan title: A chilblain epidemic during the COVID-19 pandemic. A sign of natural resistance to SARS-CoV-2? date: 2020-06-06 journal: Med Hypotheses DOI: 10.1016/j.mehy.2020.109959 sha: doc_id: 267612 cord_uid: 1h7xpkbe file: cache/cord-254094-ed1epul1.json /data-disk/reader-compute/reader-cord/bin/json2txt-carrel.sh: fork: retry: No child processes key: cord-254094-ed1epul1 authors: Mayoral, Eduardo Pérez-Campos; Hernández-Huerta, María Teresa; Pérez-Campos Mayoral, Laura; Matias-Cervantes, Carlos Alberto; Mayoral-Andrade, Gabriel; Barrios, Luis Ángel Laguna; Pérez-Campos, Eduardo title: Factors related to asymptomatic or severe COVID-19 infection date: 2020-09-24 journal: Med Hypotheses DOI: 10.1016/j.mehy.2020.110296 sha: doc_id: 254094 cord_uid: ed1epul1 file: cache/cord-268425-xg8xnjf9.json key: cord-268425-xg8xnjf9 authors: DiNicolantonio, James J.; Barroso-Aranda, Jorge title: Harnessing Adenosine A2A Receptors as a Strategy for Suppressing the Lung Inflammation and Thrombotic Complications of COVID-19: Potential of Pentoxifylline and Dipyridamole date: 2020-07-02 journal: Med Hypotheses DOI: 10.1016/j.mehy.2020.110051 sha: doc_id: 268425 cord_uid: xg8xnjf9 file: cache/cord-270805-o6rbfmie.json key: cord-270805-o6rbfmie authors: Hussein, Osama title: Second wave of of Covid-19 is determined by immune mechanism date: 2020-09-02 journal: Med Hypotheses DOI: 10.1016/j.mehy.2020.110238 sha: doc_id: 270805 cord_uid: o6rbfmie file: cache/cord-270740-3su8pc3f.json key: cord-270740-3su8pc3f authors: Sultan, Sherif; Sultan, Mohamed title: COVID-19 Cytokine Storm and Novel Truth date: 2020-05-22 journal: Med Hypotheses DOI: 10.1016/j.mehy.2020.109875 sha: doc_id: 270740 cord_uid: 3su8pc3f file: cache/cord-274698-i3mzzxwq.json key: cord-274698-i3mzzxwq authors: Stief, Thomas W title: The physiology and pharmacology of singlet oxygen date: 2003-02-19 journal: Med Hypotheses DOI: 10.1016/s0306-9877(03)00026-4 sha: doc_id: 274698 cord_uid: i3mzzxwq file: cache/cord-271785-vmnc8yg6.json key: cord-271785-vmnc8yg6 authors: Minetti, Giampaolo title: Mevalonate pathway, selenoproteins, redox balance, immune system, Covid-19: Reasoning about connections date: 2020-07-21 journal: Med Hypotheses DOI: 10.1016/j.mehy.2020.110128 sha: doc_id: 271785 cord_uid: vmnc8yg6 file: cache/cord-269563-2979u47a.json key: cord-269563-2979u47a authors: Caetano Silva-Filho, José; Germoglio Farias de Melo, Cynthia; Lima de Oliveira, Janaína title: The influence of ABO blood groups on COVID-19 susceptibility and severity: a molecular hypothesis based on carbohydrate-carbohydrate interactions date: 2020-08-02 journal: Med Hypotheses DOI: 10.1016/j.mehy.2020.110155 sha: doc_id: 269563 cord_uid: 2979u47a file: cache/cord-274715-dcs1rgd0.json key: cord-274715-dcs1rgd0 authors: Mani Mishra, Pushpendra; Uversky, Vladimir N.; Nandi, Chayan K. title: Serum albumin-mediated strategy for the effective targeting of SARS-CoV-2 date: 2020-04-24 journal: Med Hypotheses DOI: 10.1016/j.mehy.2020.109790 sha: doc_id: 274715 cord_uid: dcs1rgd0 file: cache/cord-276564-o21ncldx.json key: cord-276564-o21ncldx authors: Miller, R.; Wentzel, A.R.; Richards, G. title: COVID-19: NAD(+) deficiency may predispose the aged, obese and type2 diabetics to mortality through its effect on SIRT1 activity date: 2020-06-29 journal: Med Hypotheses DOI: 10.1016/j.mehy.2020.110044 sha: doc_id: 276564 cord_uid: o21ncldx file: cache/cord-275569-i5y23mmz.json key: cord-275569-i5y23mmz authors: de Bernardis, E.; Busà, L. title: A putative role for the tobacco mosaic virus in smokers’ resistance to COVID-19 date: 2020-07-31 journal: Med Hypotheses DOI: 10.1016/j.mehy.2020.110153 sha: doc_id: 275569 cord_uid: i5y23mmz file: cache/cord-277931-3hxhsmw8.json key: cord-277931-3hxhsmw8 authors: Khitan, Zeid J.; Khawaja, Imran; Mufson, Maurice A.; Sanabria, Juan R.; Abraham, Nader G.; Peterson, Stephen J.; Sundaram, Uma; Shapiro, Joseph I. title: SCan Charcoal Improve Outcomes in COVID-19 Infections? date: 2020-08-10 journal: Med Hypotheses DOI: 10.1016/j.mehy.2020.110176 sha: doc_id: 277931 cord_uid: 3hxhsmw8 file: cache/cord-278271-rpq62xhl.json key: cord-278271-rpq62xhl authors: Lyu, Jinglu; Miao, Tianyu; Dong, Jiajia; Cao, Ranran; Li, Yan; Chen, Qianming title: Reflection on lower rates of COVID-19 in children: does childhood immunizations offer unexpected protection? date: 2020-05-15 journal: Med Hypotheses DOI: 10.1016/j.mehy.2020.109842 sha: doc_id: 278271 cord_uid: rpq62xhl file: cache/cord-276715-d1nh2dvb.json key: cord-276715-d1nh2dvb authors: Raha, Syamal; Mallick, Rahul; Basak, Sanjay; Duttaroy, Asim K. title: Is Copper beneficial for COVID-19 patients? date: 2020-05-05 journal: Med Hypotheses DOI: 10.1016/j.mehy.2020.109814 sha: doc_id: 276715 cord_uid: d1nh2dvb file: cache/cord-274510-fo7p98np.json key: cord-274510-fo7p98np authors: Spadera, Lucrezia; Spadera, Maria title: Potential Role of GcMAF in suppressing the severity of COVID-19-induced immune responses: lesson learned from HIV date: 2020-09-24 journal: Med Hypotheses DOI: 10.1016/j.mehy.2020.110293 sha: doc_id: 274510 cord_uid: fo7p98np file: cache/cord-275353-ezrmuw48.json key: cord-275353-ezrmuw48 authors: Donma, Mustafa Metin; Donma, Orkide title: The Effects of Allium Sativum on Immunity within the Scope of COVID-19 Infection date: 2020-06-02 journal: Med Hypotheses DOI: 10.1016/j.mehy.2020.109934 sha: doc_id: 275353 cord_uid: ezrmuw48 file: cache/cord-279084-bbae1qyx.json key: cord-279084-bbae1qyx authors: Liu, Bin title: Free DNA, a reason for severe COVID-19 infection? date: 2020-05-05 journal: Med Hypotheses DOI: 10.1016/j.mehy.2020.109812 sha: doc_id: 279084 cord_uid: bbae1qyx file: cache/cord-279138-dmhphgp5.json key: cord-279138-dmhphgp5 authors: Deek, Sarah A. title: Chronic Exposure to Air Pollution Implications on COVID-19 Severity date: 2020-09-28 journal: Med Hypotheses DOI: 10.1016/j.mehy.2020.110303 sha: doc_id: 279138 cord_uid: dmhphgp5 file: cache/cord-281354-sa27k8o3.json key: cord-281354-sa27k8o3 authors: Takahashi, Harutaka title: Role of Latent Tuberculosis Infections in Reduced COVID-19 Mortality: Evidence from an Instrumental Variable Method Analysis date: 2020-08-26 journal: Med Hypotheses DOI: 10.1016/j.mehy.2020.110214 sha: doc_id: 281354 cord_uid: sa27k8o3 file: cache/cord-286038-a62k3lma.json key: cord-286038-a62k3lma authors: Klimke, A.; Hefner, G.; Will, B.; Voss, U. title: Hydroxychloroquine as an aerosol might markedly reduce and even prevent severe clinical symptoms after SARS-CoV-2 infection date: 2020-04-27 journal: Med Hypotheses DOI: 10.1016/j.mehy.2020.109783 sha: doc_id: 286038 cord_uid: a62k3lma file: cache/cord-282853-l0c69uul.json key: cord-282853-l0c69uul authors: Massad, Eduardo; Burattini, Marcelo N.; Lopez, Luis F.; Coutinho, Francisco A.B. title: Forecasting versus projection models in epidemiology: The case of the SARS epidemics date: 2005-03-30 journal: Med Hypotheses DOI: 10.1016/j.mehy.2004.09.029 sha: doc_id: 282853 cord_uid: l0c69uul file: cache/cord-287824-zg5akivn.json key: cord-287824-zg5akivn authors: Chan, Yinghan; Ng, Sin Wi; Mehta, Meenu; Anand, Krishnan; Kumar Singh, Sachin; Gupta, Gaurav; Chellappan, Dinesh Kumar; Dua, Kamal title: Advanced drug delivery systems can assist in managing influenza virus infection: A hypothesis date: 2020-09-24 journal: Med Hypotheses DOI: 10.1016/j.mehy.2020.110298 sha: doc_id: 287824 cord_uid: zg5akivn file: cache/cord-288009-8i3gsq9p.json key: cord-288009-8i3gsq9p authors: Javor, S.; Salsano, A. title: Why not consider an endothelin receptor antagonist against SARS‐CoV‐2? date: 2020-04-25 journal: Med Hypotheses DOI: 10.1016/j.mehy.2020.109792 sha: doc_id: 288009 cord_uid: 8i3gsq9p file: cache/cord-289049-4ozwhcyi.json key: cord-289049-4ozwhcyi authors: Roncati, Luca; Gallo, Graziana; Manenti, Antonio; Palmieri, Beniamino title: Renin-angiotensin system: The unexpected flaw inside the human immune system revealed by SARS-CoV-2 date: 2020-03-21 journal: Med Hypotheses DOI: 10.1016/j.mehy.2020.109686 sha: doc_id: 289049 cord_uid: 4ozwhcyi file: cache/cord-282899-kp114q7n.json key: cord-282899-kp114q7n authors: Biswas, Saurav; Thakur, Vikram; Kaur, Parneet; Khan, Azhar; Kulshrestha, Saurabh; Kumar, Pradeep title: Blood clots in COVID-19 patients: Simplifying the curious mystery date: 2020-11-06 journal: Med Hypotheses DOI: 10.1016/j.mehy.2020.110371 sha: doc_id: 282899 cord_uid: kp114q7n file: cache/cord-290803-v5ndlk9c.json key: cord-290803-v5ndlk9c authors: Khan, Imran; Aziz Hatiboglu, Mustafa title: Can COVID-19 induce glioma tumorogenesis through binding cell receptors? date: 2020-06-19 journal: Med Hypotheses DOI: 10.1016/j.mehy.2020.110009 sha: doc_id: 290803 cord_uid: v5ndlk9c file: cache/cord-289332-hvakv08t.json key: cord-289332-hvakv08t authors: Chen, Guoqian; Chen, Da-zhi; Li, Jianhua; Czura, Christopher J.; Tracey, Kevin J.; Sama, Andrew E.; Wang, Haichao title: Pathogenic role of HMGB1 in SARS? date: 2004-04-30 journal: Med Hypotheses DOI: 10.1016/j.mehy.2004.01.037 sha: doc_id: 289332 cord_uid: hvakv08t file: cache/cord-289905-dvl2pud2.json key: cord-289905-dvl2pud2 authors: Gan, Rosemary; Rosoman, Nicholas P.; Henshaw, David J.E.; Noble, Euan P.; Georgius, Peter; Sommerfeld, Nigel title: COVID-19 as a Viral Functional ACE2 Deficiency Disorder with ACE2 Related Multi-organ Disease date: 2020-06-23 journal: Med Hypotheses DOI: 10.1016/j.mehy.2020.110024 sha: doc_id: 289905 cord_uid: dvl2pud2 file: cache/cord-291037-19csqq89.json key: cord-291037-19csqq89 authors: Janssen, Rob; Walk, Jona title: Vitamin K epoxide reductase complex subunit 1 (VKORC1) gene polymorphism as determinant of differences in Covid-19-related disease severity date: 2020-08-25 journal: Med Hypotheses DOI: 10.1016/j.mehy.2020.110218 sha: doc_id: 291037 cord_uid: 19csqq89 file: cache/cord-288733-c51lfwd6.json key: cord-288733-c51lfwd6 authors: Kavanagh, Oisín; Marie Healy, Anne; Dayton, Francis; Robinson, Shane; O'Reilly, Niall J.; Mahoney, Brian; Arthur, Aisling; Walker, Gavin; Farragher, John P. title: Inhaled Hydroxychloroquine to Improve Efficacy and Reduce Harm in the Treatment of COVID-19 date: 2020-07-15 journal: Med Hypotheses DOI: 10.1016/j.mehy.2020.110110 sha: doc_id: 288733 cord_uid: c51lfwd6 file: cache/cord-291722-xnfdjriz.json key: cord-291722-xnfdjriz authors: Meenakshisundaram, Ramachandran; Senthilkumaran, Subramanian; Thirumalaikolundusubramanian, Ponniah title: Protective effects of vaccinations and endemic infections on COVID-19: A Hypothesis date: 2020-05-26 journal: Med Hypotheses DOI: 10.1016/j.mehy.2020.109849 sha: doc_id: 291722 cord_uid: xnfdjriz file: cache/cord-291781-gs81g1db.json key: cord-291781-gs81g1db authors: Caruso, Arturo Armone; Prete, Antonio Del; Lazzarino, Antonio Ivan title: Hydrogen peroxide and viral infections: a literature review with research hypothesis definition in relation to the current covid-19 pandemic date: 2020-06-01 journal: Med Hypotheses DOI: 10.1016/j.mehy.2020.109910 sha: doc_id: 291781 cord_uid: gs81g1db file: cache/cord-293059-2iwzieqm.json key: cord-293059-2iwzieqm authors: Tao, Huaqiang; Ge, Gaoran; Li, Wenming; Liang, Xiaolong; Wang, Hongzhi; Li, Ning; Sun, Houyi; Zhang, Wei; Geng, Dechun title: Dysimmunity and inflammatory storm: Watch out for bone lesions in COVID-19 infection date: 2020-10-06 journal: Med Hypotheses DOI: 10.1016/j.mehy.2020.110332 sha: doc_id: 293059 cord_uid: 2iwzieqm file: cache/cord-301619-0ojayw16.json key: cord-301619-0ojayw16 authors: Adamowicz, Jan; Juszczak, Kajetan; Drewa, Tomasz title: May patients receiving 5-alpha-reductase inhibitors be in higher risk of COVID-19 complications ? date: 2020-04-22 journal: Med Hypotheses DOI: 10.1016/j.mehy.2020.109751 sha: doc_id: 301619 cord_uid: 0ojayw16 file: cache/cord-297178-moxhk2e0.json key: cord-297178-moxhk2e0 authors: Novaes Rocha, Vinicius title: Viral replication of SARS-CoV-2 could be self-limitative - the role of the renin-angiotensin system on COVID-19 pathophysiology date: 2020-10-01 journal: Med Hypotheses DOI: 10.1016/j.mehy.2020.110330 sha: doc_id: 297178 cord_uid: moxhk2e0 file: cache/cord-296253-bxyzhsfs.json key: cord-296253-bxyzhsfs authors: Elham, Elzat; Wumaier, Reziya; Wang, Chengji; Luo, Xiangying; Chen, Tao; Zhong, Nanshan title: Anatomic evidence shows that lymphatic drainage exists in the pituitary to loop the cerebral lymphatic circulation date: 2020-05-30 journal: Med Hypotheses DOI: 10.1016/j.mehy.2020.109898 sha: doc_id: 296253 cord_uid: bxyzhsfs file: cache/cord-302212-zt4lv5g4.json key: cord-302212-zt4lv5g4 authors: Patruno, Cataldo; Paul Nisticò, Steven; Fabbrocini, Gabriella; Napolitano, Maddalena title: COVID-19, QUARANTINE, AND ATOPIC DERMATITIS date: 2020-05-19 journal: Med Hypotheses DOI: 10.1016/j.mehy.2020.109852 sha: doc_id: 302212 cord_uid: zt4lv5g4 file: cache/cord-293860-6kz0iws6.json key: cord-293860-6kz0iws6 authors: Qutayba Almerie, Muhammad; Daniel Kerrigan, David title: The Association between Obesity and Poor Outcome after COVID-19 Indicates a Potential Therapeutic Role for Montelukast date: 2020-05-27 journal: Med Hypotheses DOI: 10.1016/j.mehy.2020.109883 sha: doc_id: 293860 cord_uid: 6kz0iws6 file: cache/cord-303022-9hqoq7tf.json key: cord-303022-9hqoq7tf authors: Madapusi Balaji, Thodur; Varadarajan, Saranya; Vishal Rao, U.S.; Thirumal Raj, A.; Patil, Shankaragouda; Arakeri, Gururaj; Brennan, Peter A title: Oral cancer and periodontal disease increase the risk of COVID 19? A mechanism mediated through furin and cathepsin overexpression date: 2020-06-01 journal: Med Hypotheses DOI: 10.1016/j.mehy.2020.109936 sha: doc_id: 303022 cord_uid: 9hqoq7tf file: cache/cord-308279-gsk4qel5.json key: cord-308279-gsk4qel5 authors: Suzuki, Yuichiro J. title: The viral protein fragment theory of COVID-19 pathogenesis date: 2020-09-11 journal: Med Hypotheses DOI: 10.1016/j.mehy.2020.110267 sha: doc_id: 308279 cord_uid: gsk4qel5 file: cache/cord-299911-v95pf3eg.json key: cord-299911-v95pf3eg authors: El-Ghiaty, Mahmoud A.; Shoieb, Sherif M.; El-Kadi, Ayman O.S. title: Cytochrome P450-mediated drug interactions in COVID-19 patients: current findings and possible mechanisms date: 2020-06-26 journal: Med Hypotheses DOI: 10.1016/j.mehy.2020.110033 sha: doc_id: 299911 cord_uid: v95pf3eg file: cache/cord-304658-vxu33v7i.json key: cord-304658-vxu33v7i authors: Brenner, Steven R. title: Covid-19, TMPRSS2, and whether android regulation affects pandemic virus gender incidence and age distribution of disease date: 2020-04-22 journal: Med Hypotheses DOI: 10.1016/j.mehy.2020.109773 sha: doc_id: 304658 cord_uid: vxu33v7i file: cache/cord-310217-p9nqcz5d.json key: cord-310217-p9nqcz5d authors: Nikolina, Basic-Jukic title: Can hyperimmune anti-CMV globuline substitute for convalescent plasma for treatment of COVID-19? date: 2020-05-31 journal: Med Hypotheses DOI: 10.1016/j.mehy.2020.109903 sha: doc_id: 310217 cord_uid: p9nqcz5d file: cache/cord-306146-i4a74j3r.json key: cord-306146-i4a74j3r authors: Fitzgerald, Paul J. title: Noradrenergic and serotonergic drugs may have opposing effects on COVID-19 cytokine storm and associated psychological effects date: 2020-06-09 journal: Med Hypotheses DOI: 10.1016/j.mehy.2020.109985 sha: doc_id: 306146 cord_uid: i4a74j3r file: cache/cord-310928-g553afo9.json key: cord-310928-g553afo9 authors: Murch, Simon H title: Common determinants of severe Covid-19 infection are explicable by SARS-CoV-2 secreted glycoprotein interaction with the CD33-related Siglecs, Siglec-3 and Siglec-5/14 date: 2020-08-07 journal: Med Hypotheses DOI: 10.1016/j.mehy.2020.110168 sha: doc_id: 310928 cord_uid: g553afo9 file: cache/cord-311673-z4hkw17g.json key: cord-311673-z4hkw17g authors: Uzzan, Mathieu; Corcos, Olivier; Martin, Jerome; Treton, Xavier; Bouhnik, Yoram title: Why is SARS-CoV-2 infection more severe in obese men? The gut lymphatics - lung axis hypothesis date: 2020-06-23 journal: Med Hypotheses DOI: 10.1016/j.mehy.2020.110023 sha: doc_id: 311673 cord_uid: z4hkw17g file: cache/cord-312912-i1yyz5lg.json key: cord-312912-i1yyz5lg authors: Bou Khalil, Rami title: Lithium chloride combination with rapamycin for the treatment of COVID-19 pneumonia date: 2020-05-01 journal: Med Hypotheses DOI: 10.1016/j.mehy.2020.109798 sha: doc_id: 312912 cord_uid: i1yyz5lg file: cache/cord-313382-prxc0lue.json key: cord-313382-prxc0lue authors: Hossein Norooznezhad, Amir; Hantoushzadeh, Sedigheh; Shamshirsaz, Alireza A. title: Empiric Antibiotics in Management of Inpatient Pregnant Women Infected with Coronavirus Disease 2019 (COVID-19): Focusing on Inflammation and Preterm Labor date: 2020-09-12 journal: Med Hypotheses DOI: 10.1016/j.mehy.2020.110269 sha: doc_id: 313382 cord_uid: prxc0lue file: cache/cord-317238-uszhwugw.json key: cord-317238-uszhwugw authors: Parodi, Aurora; Cozzani, Emanuele title: Coronavirus disease 2019 (COVID 19) and Malaria. Have anti glycoprotein antibodies a role? date: 2020-06-25 journal: Med Hypotheses DOI: 10.1016/j.mehy.2020.110036 sha: doc_id: 317238 cord_uid: uszhwugw file: cache/cord-315576-bgcqkz0p.json key: cord-315576-bgcqkz0p authors: Yamamoto, Naoki; Bauer, Georg title: Apparent difference in fatalities between Central Europe and East Asia due to SARS-COV-2 and COVID-19: Four hypotheses for possible explanation date: 2020-08-05 journal: Med Hypotheses DOI: 10.1016/j.mehy.2020.110160 sha: doc_id: 315576 cord_uid: bgcqkz0p file: cache/cord-314679-lmfalzni.json key: cord-314679-lmfalzni authors: Sangith, Nikhil; Diagnotek, Xact title: Unique Fibrinogen-binding motifs in the Nucleocapsid Phosphoprotein of SARS CoV-2: Potential Implications in Host-Pathogen Interactions date: 2020-06-24 journal: Med Hypotheses DOI: 10.1016/j.mehy.2020.110030 sha: doc_id: 314679 cord_uid: lmfalzni file: cache/cord-318114-q29zax2j.json key: cord-318114-q29zax2j authors: Bara, Gregor A.; de Ridder, Dirk; Maciaczyk, Jaroslaw title: Can neuromodulation support the fight against the COVID19 pandemic? Transcutaneous non-invasive vagal nerve stimulation as a potential targeted treatment of fulminant acute respiratory distress syndrome date: 2020-07-18 journal: Med Hypotheses DOI: 10.1016/j.mehy.2020.110093 sha: doc_id: 318114 cord_uid: q29zax2j file: cache/cord-320508-egw7bvzf.json key: cord-320508-egw7bvzf authors: Kennedy, James R. title: Phosphatidylserine’s role in Ebola’s inflammatory cytokine storm and hemorrhagic consumptive coagulopathy and the therapeutic potential of annexin V date: 2019-10-28 journal: Med Hypotheses DOI: 10.1016/j.mehy.2019.109462 sha: doc_id: 320508 cord_uid: egw7bvzf file: cache/cord-320959-sgdqhtns.json key: cord-320959-sgdqhtns authors: Lee, Hanjun title: Vitamin E Acetate as Linactant in the Pathophysiology of EVALI date: 2020-08-12 journal: Med Hypotheses DOI: 10.1016/j.mehy.2020.110182 sha: doc_id: 320959 cord_uid: sgdqhtns file: cache/cord-322880-zfc9w5y6.json key: cord-322880-zfc9w5y6 authors: Rohit, Anusha; Rajasekaran, Shankar; Karunasagar, Indrani; Karunasagar, Iddya title: Respiratory droplets get suspended longer and spread wider in temperate environments compared to tropics and implications for SARS-CoV-2 transmission date: 2020-06-09 journal: Med Hypotheses DOI: 10.1016/j.mehy.2020.109958 sha: doc_id: 322880 cord_uid: zfc9w5y6 file: cache/cord-319822-h1zm94p4.json key: cord-319822-h1zm94p4 authors: Carelli, Pasquale title: A physicist's approach to COVID-19 transmission via expiratory droplets date: 2020-06-17 journal: Med Hypotheses DOI: 10.1016/j.mehy.2020.109997 sha: doc_id: 319822 cord_uid: h1zm94p4 file: cache/cord-323310-tq9muytr.json key: cord-323310-tq9muytr authors: Ozdemir, Burak; Yazici, Ahmet title: Could the decrease in the endothelial nitric oxide (NO) production and NO bioavailability be the crucial cause of COVID-19 related deaths? date: 2020-06-07 journal: Med Hypotheses DOI: 10.1016/j.mehy.2020.109970 sha: doc_id: 323310 cord_uid: tq9muytr file: cache/cord-324949-sqy03dks.json key: cord-324949-sqy03dks authors: Poe, Francis L.; Corn, Joshua title: N-Acetylcysteine: a potential therapeutic agent for SARS-CoV-2 date: 2020-05-30 journal: Med Hypotheses DOI: 10.1016/j.mehy.2020.109862 sha: doc_id: 324949 cord_uid: sqy03dks file: cache/cord-323749-lvtfv7ny.json key: cord-323749-lvtfv7ny authors: Sai Suresh Chalichem, Nehru; Bethapudi, Bharathi; Mundkinajeddu, Deepak title: Aminoglycosides can be a better choice over Macrolides in COVID-19 regimen: Plausible Mechanism for repurposing strategy date: 2020-06-10 journal: Med Hypotheses DOI: 10.1016/j.mehy.2020.109984 sha: doc_id: 323749 cord_uid: lvtfv7ny file: cache/cord-331140-5b0y1xzb.json key: cord-331140-5b0y1xzb authors: Cardona Maya, Walter D.; Carvajal, Alejandro title: SARS-CoV-2 and Prostatitis: dangerous relationship for male sexual and reproductive health date: 2020-06-01 journal: Med Hypotheses DOI: 10.1016/j.mehy.2020.109914 sha: doc_id: 331140 cord_uid: 5b0y1xzb file: cache/cord-328587-vctvcyim.json key: cord-328587-vctvcyim authors: Jun, Sun title: The hypothesis that SARS-CoV-2 affects male reproductive ability by regulating autophagy date: 2020-07-10 journal: Med Hypotheses DOI: 10.1016/j.mehy.2020.110083 sha: doc_id: 328587 cord_uid: vctvcyim file: cache/cord-327809-9uhhqasl.json key: cord-327809-9uhhqasl authors: Dimitriu, Mihai C.T.; Pantea-Stoian, Anca; Smaranda, Alexandru C.; Nica, Anca A.; Carap, Alexandru C.; Constantin, Vlad D.; Davitoiu, Ana M.; Cirstoveanu, Catalin; Bacalbasa, Nicolae; Bratu, Ovidiu G.; Jacota-Alexe, Florentina; Badiu, Cristinel D.; Smarandache, Catalin G.; Socea, Bogdan title: Burnout syndrome in Romanian medical residents in time of the COVID-19 pandemic date: 2020-06-07 journal: Med Hypotheses DOI: 10.1016/j.mehy.2020.109972 sha: doc_id: 327809 cord_uid: 9uhhqasl file: cache/cord-326849-vqpwdlj7.json key: cord-326849-vqpwdlj7 authors: Rao US, Vishal; Thakur, Shalini; Rao, Jyothsna; Arakeri, Gururaj; Brennan, Peter A; Jadhav, Sachin; Suhail Sayeed, Mufti; Rao, Gururaj title: Mesenchymal Stem Cells -Bridge Catalyst Between Innte And Adaptive Immunity In Covid 19 date: 2020-05-18 journal: Med Hypotheses DOI: 10.1016/j.mehy.2020.109845 sha: doc_id: 326849 cord_uid: vqpwdlj7 file: cache/cord-337493-8yhd697t.json key: cord-337493-8yhd697t authors: Choquenaira-Quispe, Celia; Saldaña-Bobadilla, Vanessa; Kenedy Ramirez, J. title: Factors involved in low susceptibility to covid-19: an adaptation of high altitude inhabitants date: 2020-07-02 journal: Med Hypotheses DOI: 10.1016/j.mehy.2020.110068 sha: doc_id: 337493 cord_uid: 8yhd697t file: cache/cord-338585-ep9r1n8t.json key: cord-338585-ep9r1n8t authors: Perrin, David M. title: A hypothesis for examining dihydroxyacetone, the active component in self-tanning products, as a topical prophylactic against SARS-COV-2 transmission date: 2020-09-16 journal: Med Hypotheses DOI: 10.1016/j.mehy.2020.110280 sha: doc_id: 338585 cord_uid: ep9r1n8t file: cache/cord-332365-20u06444.json key: cord-332365-20u06444 authors: Raciti, Loredana; Calabrò, Rocco Salvatore title: Can volcanic trace elements facilitate Covid-19 diffusion? A hypothesis stemming from the Mount Etna area, Sicily date: 2020-06-27 journal: Med Hypotheses DOI: 10.1016/j.mehy.2020.110058 sha: doc_id: 332365 cord_uid: 20u06444 file: cache/cord-334709-z70oevy2.json key: cord-334709-z70oevy2 authors: Niv, Yaron title: Defensin 5 for prevention of SARS-CoV-2 invasion and Covid-19 Disease date: 2020-09-04 journal: Med Hypotheses DOI: 10.1016/j.mehy.2020.110244 sha: doc_id: 334709 cord_uid: z70oevy2 file: cache/cord-331428-6pvr2vew.json key: cord-331428-6pvr2vew authors: Heffernan, Kevin S.; Ranadive, Sushant; Jae, Sae Young title: Exercise as medicine for COVID-19: on PPAR with emerging pharmacotherapy date: 2020-08-17 journal: Med Hypotheses DOI: 10.1016/j.mehy.2020.110197 sha: doc_id: 331428 cord_uid: 6pvr2vew file: cache/cord-344170-qrupbtem.json key: cord-344170-qrupbtem authors: Biswas, Subrata K; Mudi, Sonchita R title: Genetic variation in SARS-CoV-2 may explain variable severity of COVID-19 date: 2020-05-24 journal: Med Hypotheses DOI: 10.1016/j.mehy.2020.109877 sha: doc_id: 344170 cord_uid: qrupbtem file: cache/cord-334543-gavnscor.json key: cord-334543-gavnscor authors: Lim, Rachel K.; Wambier, Carlos G.; Goren, Andy title: Are night shift workers at an increased risk for COVID-19? date: 2020-07-29 journal: Med Hypotheses DOI: 10.1016/j.mehy.2020.110147 sha: doc_id: 334543 cord_uid: gavnscor file: cache/cord-337627-1a2gpqdl.json key: cord-337627-1a2gpqdl authors: Alvarado-Vasquez, Noé title: Could a family history of type 2 diabetes be a risk factor to the endothelial damage in the patient with COVID-19? date: 2020-11-06 journal: Med Hypotheses DOI: 10.1016/j.mehy.2020.110378 sha: doc_id: 337627 cord_uid: 1a2gpqdl file: cache/cord-349718-x5i460bc.json key: cord-349718-x5i460bc authors: Chandrasekaran, Baskaran title: Dr. Chandrasekaran’s reply to “Exercising and face masks: an important hypothesis buried in a selective review” date: 2020-09-23 journal: Med Hypotheses DOI: 10.1016/j.mehy.2020.110302 sha: doc_id: 349718 cord_uid: x5i460bc file: cache/cord-352911-9wbq9qo2.json key: cord-352911-9wbq9qo2 authors: de Oliveira, Pedro Gonçalves; Termini, Lara; Durigon, Edison Luiz; Lepique, Ana Paula; Sposito, Andrei C; Pierulivo, Enrique Mario Boccardo title: Diacerein: a potential multi-target therapeutic drug for COVID-19 date: 2020-06-01 journal: Med Hypotheses DOI: 10.1016/j.mehy.2020.109920 sha: doc_id: 352911 cord_uid: 9wbq9qo2 file: cache/cord-353716-gxgvhhv1.json key: cord-353716-gxgvhhv1 authors: Kumar, Ashutosh; Narayan, Ravi K.; Kumari, Chiman; Faiq, Muneeb A.; Kulandhasamy, Maheswari; Kant, Kamla; Pareek, Vikas title: SARS-CoV-2 cell entry receptor ACE2 mediated endothelial dysfunction leads to vascular thrombosis in COVID-19 patients date: 2020-09-30 journal: Med Hypotheses DOI: 10.1016/j.mehy.2020.110320 sha: doc_id: 353716 cord_uid: gxgvhhv1 file: cache/cord-346281-sma6e891.json key: cord-346281-sma6e891 authors: Maldonado, Valente; Loza-Mejía; Chávez Alderete, Jaime title: Repositioning of pentoxifylline as an immunomodulator and regulator of the renin-angiotensin system in the treatment of COVID-19 date: 2020-06-09 journal: Med Hypotheses DOI: 10.1016/j.mehy.2020.109988 sha: doc_id: 346281 cord_uid: sma6e891 Reading metadata file and updating bibliogrpahics === updating bibliographic database Building study carrel named journal-medHypotheses-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: 34880 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: 36248 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: 33794 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: 35045 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: 35437 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: 36136 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: 33019 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: 36141 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: 34060 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: 36034 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: 34555 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: 32668 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: 36725 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: 33198 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: 36836 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: 37877 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: 35754 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: 35749 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: 34332 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: 33758 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: 36003 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: 35764 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: 34948 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: 34621 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: 35746 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-349718-x5i460bc author: Chandrasekaran, Baskaran title: Dr. Chandrasekaran’s reply to “Exercising and face masks: an important hypothesis buried in a selective review” date: 2020-09-23 pages: extension: .txt txt: ./txt/cord-349718-x5i460bc.txt cache: ./cache/cord-349718-x5i460bc.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-349718-x5i460bc.txt' === file2bib.sh === id: cord-270805-o6rbfmie author: Hussein, Osama title: Second wave of of Covid-19 is determined by immune mechanism date: 2020-09-02 pages: extension: .txt txt: ./txt/cord-270805-o6rbfmie.txt cache: ./cache/cord-270805-o6rbfmie.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 1 resourceName b'cord-270805-o6rbfmie.txt' === file2bib.sh === id: cord-290803-v5ndlk9c author: Khan, Imran title: Can COVID-19 induce glioma tumorogenesis through binding cell receptors? date: 2020-06-19 pages: extension: .txt txt: ./txt/cord-290803-v5ndlk9c.txt cache: ./cache/cord-290803-v5ndlk9c.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-290803-v5ndlk9c.txt' === file2bib.sh === id: cord-253468-pf0xubii author: Emara, Mohamed H title: Ketonuria with or without ketoacidosis as the presenting manifestation of SARS-CoV-2 (COVID-19) among uncontrolled Type 2 Diabetic patients date: 2020-09-02 pages: extension: .txt txt: ./txt/cord-253468-pf0xubii.txt cache: ./cache/cord-253468-pf0xubii.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-253468-pf0xubii.txt' === file2bib.sh === id: cord-275569-i5y23mmz author: de Bernardis, E. title: A putative role for the tobacco mosaic virus in smokers’ resistance to COVID-19 date: 2020-07-31 pages: extension: .txt txt: ./txt/cord-275569-i5y23mmz.txt cache: ./cache/cord-275569-i5y23mmz.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-275569-i5y23mmz.txt' === file2bib.sh === id: cord-323749-lvtfv7ny author: Sai Suresh Chalichem, Nehru title: Aminoglycosides can be a better choice over Macrolides in COVID-19 regimen: Plausible Mechanism for repurposing strategy date: 2020-06-10 pages: extension: .txt txt: ./txt/cord-323749-lvtfv7ny.txt cache: ./cache/cord-323749-lvtfv7ny.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-323749-lvtfv7ny.txt' === file2bib.sh === id: cord-287824-zg5akivn author: Chan, Yinghan title: Advanced drug delivery systems can assist in managing influenza virus infection: A hypothesis date: 2020-09-24 pages: extension: .txt txt: ./txt/cord-287824-zg5akivn.txt cache: ./cache/cord-287824-zg5akivn.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-287824-zg5akivn.txt' === file2bib.sh === id: cord-310217-p9nqcz5d author: Nikolina, Basic-Jukic title: Can hyperimmune anti-CMV globuline substitute for convalescent plasma for treatment of COVID-19? date: 2020-05-31 pages: extension: .txt txt: ./txt/cord-310217-p9nqcz5d.txt cache: ./cache/cord-310217-p9nqcz5d.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-310217-p9nqcz5d.txt' === file2bib.sh === id: cord-288733-c51lfwd6 author: Kavanagh, Oisín title: Inhaled Hydroxychloroquine to Improve Efficacy and Reduce Harm in the Treatment of COVID-19 date: 2020-07-15 pages: extension: .txt txt: ./txt/cord-288733-c51lfwd6.txt cache: ./cache/cord-288733-c51lfwd6.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 333 resourceName b'cord-288733-c51lfwd6.txt' === file2bib.sh === id: cord-306146-i4a74j3r author: Fitzgerald, Paul J. title: Noradrenergic and serotonergic drugs may have opposing effects on COVID-19 cytokine storm and associated psychological effects date: 2020-06-09 pages: extension: .txt txt: ./txt/cord-306146-i4a74j3r.txt cache: ./cache/cord-306146-i4a74j3r.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-306146-i4a74j3r.txt' === file2bib.sh === id: cord-289049-4ozwhcyi author: Roncati, Luca title: Renin-angiotensin system: The unexpected flaw inside the human immune system revealed by SARS-CoV-2 date: 2020-03-21 pages: extension: .txt txt: ./txt/cord-289049-4ozwhcyi.txt cache: ./cache/cord-289049-4ozwhcyi.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 83 resourceName b'cord-289049-4ozwhcyi.txt' === file2bib.sh === id: cord-265724-fdt00qw1 author: Varadarajan, Saranya title: EMMPRIN/BASIGIN as a biological modulator of oral cancer and COVID-19 interaction: novel propositions date: 2020-07-09 pages: extension: .txt txt: ./txt/cord-265724-fdt00qw1.txt cache: ./cache/cord-265724-fdt00qw1.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-265724-fdt00qw1.txt' === file2bib.sh === id: cord-320508-egw7bvzf author: Kennedy, James R. title: Phosphatidylserine’s role in Ebola’s inflammatory cytokine storm and hemorrhagic consumptive coagulopathy and the therapeutic potential of annexin V date: 2019-10-28 pages: extension: .txt txt: ./txt/cord-320508-egw7bvzf.txt cache: ./cache/cord-320508-egw7bvzf.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-320508-egw7bvzf.txt' === file2bib.sh === id: cord-265322-3854ddb9 author: Vavougios, George D. title: A data-driven hypothesis on the epigenetic dysregulation of host metabolism by SARS coronaviral infection: potential implications for the SARS-CoV-2 modus operandi date: 2020-04-23 pages: extension: .txt txt: ./txt/cord-265322-3854ddb9.txt cache: ./cache/cord-265322-3854ddb9.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-265322-3854ddb9.txt' === file2bib.sh === id: cord-254094-ed1epul1 author: Mayoral, Eduardo Pérez-Campos title: Factors related to asymptomatic or severe COVID-19 infection date: 2020-09-24 pages: extension: .txt txt: ./txt/cord-254094-ed1epul1.txt cache: ./cache/cord-254094-ed1epul1.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-254094-ed1epul1.txt' === file2bib.sh === id: cord-279084-bbae1qyx author: Liu, Bin title: Free DNA, a reason for severe COVID-19 infection? date: 2020-05-05 pages: extension: .txt txt: ./txt/cord-279084-bbae1qyx.txt cache: ./cache/cord-279084-bbae1qyx.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-279084-bbae1qyx.txt' === file2bib.sh === id: cord-302212-zt4lv5g4 author: Patruno, Cataldo title: COVID-19, QUARANTINE, AND ATOPIC DERMATITIS date: 2020-05-19 pages: extension: .txt txt: ./txt/cord-302212-zt4lv5g4.txt cache: ./cache/cord-302212-zt4lv5g4.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-302212-zt4lv5g4.txt' === file2bib.sh === id: cord-286038-a62k3lma author: Klimke, A. title: Hydroxychloroquine as an aerosol might markedly reduce and even prevent severe clinical symptoms after SARS-CoV-2 infection date: 2020-04-27 pages: extension: .txt txt: ./txt/cord-286038-a62k3lma.txt cache: ./cache/cord-286038-a62k3lma.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-286038-a62k3lma.txt' === file2bib.sh === id: cord-256092-bph9ys72 author: Hussain, Aneela N. title: Role of testosterone in COVID-19 patients - a double-edged sword? date: 2020-09-17 pages: extension: .txt txt: ./txt/cord-256092-bph9ys72.txt cache: ./cache/cord-256092-bph9ys72.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-256092-bph9ys72.txt' === file2bib.sh === id: cord-301619-0ojayw16 author: Adamowicz, Jan title: May patients receiving 5-alpha-reductase inhibitors be in higher risk of COVID-19 complications ? date: 2020-04-22 pages: extension: .txt txt: ./txt/cord-301619-0ojayw16.txt cache: ./cache/cord-301619-0ojayw16.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-301619-0ojayw16.txt' === file2bib.sh === id: cord-334709-z70oevy2 author: Niv, Yaron title: Defensin 5 for prevention of SARS-CoV-2 invasion and Covid-19 Disease date: 2020-09-04 pages: extension: .txt txt: ./txt/cord-334709-z70oevy2.txt cache: ./cache/cord-334709-z70oevy2.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-334709-z70oevy2.txt' === file2bib.sh === id: cord-281354-sa27k8o3 author: Takahashi, Harutaka title: Role of Latent Tuberculosis Infections in Reduced COVID-19 Mortality: Evidence from an Instrumental Variable Method Analysis date: 2020-08-26 pages: extension: .txt txt: ./txt/cord-281354-sa27k8o3.txt cache: ./cache/cord-281354-sa27k8o3.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-281354-sa27k8o3.txt' === file2bib.sh === id: cord-331140-5b0y1xzb author: Cardona Maya, Walter D. title: SARS-CoV-2 and Prostatitis: dangerous relationship for male sexual and reproductive health date: 2020-06-01 pages: extension: .txt txt: ./txt/cord-331140-5b0y1xzb.txt cache: ./cache/cord-331140-5b0y1xzb.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-331140-5b0y1xzb.txt' === file2bib.sh === id: cord-274715-dcs1rgd0 author: Mani Mishra, Pushpendra title: Serum albumin-mediated strategy for the effective targeting of SARS-CoV-2 date: 2020-04-24 pages: extension: .txt txt: ./txt/cord-274715-dcs1rgd0.txt cache: ./cache/cord-274715-dcs1rgd0.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-274715-dcs1rgd0.txt' === file2bib.sh === id: cord-303022-9hqoq7tf author: Madapusi Balaji, Thodur title: Oral cancer and periodontal disease increase the risk of COVID 19? A mechanism mediated through furin and cathepsin overexpression date: 2020-06-01 pages: extension: .txt txt: ./txt/cord-303022-9hqoq7tf.txt cache: ./cache/cord-303022-9hqoq7tf.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-303022-9hqoq7tf.txt' === file2bib.sh === id: cord-308279-gsk4qel5 author: Suzuki, Yuichiro J. title: The viral protein fragment theory of COVID-19 pathogenesis date: 2020-09-11 pages: extension: .txt txt: ./txt/cord-308279-gsk4qel5.txt cache: ./cache/cord-308279-gsk4qel5.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-308279-gsk4qel5.txt' === file2bib.sh === id: cord-279138-dmhphgp5 author: Deek, Sarah A. title: Chronic Exposure to Air Pollution Implications on COVID-19 Severity date: 2020-09-28 pages: extension: .txt txt: ./txt/cord-279138-dmhphgp5.txt cache: ./cache/cord-279138-dmhphgp5.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-279138-dmhphgp5.txt' === file2bib.sh === id: cord-337493-8yhd697t author: Choquenaira-Quispe, Celia title: Factors involved in low susceptibility to covid-19: an adaptation of high altitude inhabitants date: 2020-07-02 pages: extension: .txt txt: ./txt/cord-337493-8yhd697t.txt cache: ./cache/cord-337493-8yhd697t.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-337493-8yhd697t.txt' === file2bib.sh === id: cord-334543-gavnscor author: Lim, Rachel K. title: Are night shift workers at an increased risk for COVID-19? date: 2020-07-29 pages: extension: .txt txt: ./txt/cord-334543-gavnscor.txt cache: ./cache/cord-334543-gavnscor.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-334543-gavnscor.txt' === file2bib.sh === id: cord-258272-uu6t6tnh author: Dabaghian, Farid title: Bioactive compounds with possible inhibitory activity of Angiotensin-Converting Enzyme-II; a gate to manage and prevent COVID-19 date: 2020-05-16 pages: extension: .txt txt: ./txt/cord-258272-uu6t6tnh.txt cache: ./cache/cord-258272-uu6t6tnh.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 1 resourceName b'cord-258272-uu6t6tnh.txt' === file2bib.sh === id: cord-296253-bxyzhsfs author: Elham, Elzat title: Anatomic evidence shows that lymphatic drainage exists in the pituitary to loop the cerebral lymphatic circulation date: 2020-05-30 pages: extension: .txt txt: ./txt/cord-296253-bxyzhsfs.txt cache: ./cache/cord-296253-bxyzhsfs.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-296253-bxyzhsfs.txt' === file2bib.sh === id: cord-319822-h1zm94p4 author: Carelli, Pasquale title: A physicist's approach to COVID-19 transmission via expiratory droplets date: 2020-06-17 pages: extension: .txt txt: ./txt/cord-319822-h1zm94p4.txt cache: ./cache/cord-319822-h1zm94p4.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-319822-h1zm94p4.txt' === file2bib.sh === id: cord-258670-dphg8ukj author: Karaahmet, Fatih title: Endothelial progenitor cells and mesenchymal stem cells to overcome vascular deterioration and cytokine storm in critical patients with COVID-19 date: 2020-06-10 pages: extension: .txt txt: ./txt/cord-258670-dphg8ukj.txt cache: ./cache/cord-258670-dphg8ukj.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-258670-dphg8ukj.txt' === file2bib.sh === id: cord-289332-hvakv08t author: Chen, Guoqian title: Pathogenic role of HMGB1 in SARS? date: 2004-04-30 pages: extension: .txt txt: ./txt/cord-289332-hvakv08t.txt cache: ./cache/cord-289332-hvakv08t.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-289332-hvakv08t.txt' === file2bib.sh === id: cord-254411-e9vvjv8w author: Taghizadeh-Hesary, Farzad title: The Powerful Immune System Against Powerful COVID-19: A Hypothesis date: 2020-04-22 pages: extension: .txt txt: ./txt/cord-254411-e9vvjv8w.txt cache: ./cache/cord-254411-e9vvjv8w.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-254411-e9vvjv8w.txt' === file2bib.sh === id: cord-322880-zfc9w5y6 author: Rohit, Anusha title: Respiratory droplets get suspended longer and spread wider in temperate environments compared to tropics and implications for SARS-CoV-2 transmission date: 2020-06-09 pages: extension: .txt txt: ./txt/cord-322880-zfc9w5y6.txt cache: ./cache/cord-322880-zfc9w5y6.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 1 resourceName b'cord-322880-zfc9w5y6.txt' === file2bib.sh === id: cord-311673-z4hkw17g author: Uzzan, Mathieu title: Why is SARS-CoV-2 infection more severe in obese men? The gut lymphatics - lung axis hypothesis date: 2020-06-23 pages: extension: .txt txt: ./txt/cord-311673-z4hkw17g.txt cache: ./cache/cord-311673-z4hkw17g.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-311673-z4hkw17g.txt' === file2bib.sh === id: cord-291037-19csqq89 author: Janssen, Rob title: Vitamin K epoxide reductase complex subunit 1 (VKORC1) gene polymorphism as determinant of differences in Covid-19-related disease severity date: 2020-08-25 pages: extension: .txt txt: ./txt/cord-291037-19csqq89.txt cache: ./cache/cord-291037-19csqq89.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-291037-19csqq89.txt' === file2bib.sh === id: cord-293059-2iwzieqm author: Tao, Huaqiang title: Dysimmunity and inflammatory storm: Watch out for bone lesions in COVID-19 infection date: 2020-10-06 pages: extension: .txt txt: ./txt/cord-293059-2iwzieqm.txt cache: ./cache/cord-293059-2iwzieqm.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-293059-2iwzieqm.txt' === file2bib.sh === id: cord-277931-3hxhsmw8 author: Khitan, Zeid J. title: SCan Charcoal Improve Outcomes in COVID-19 Infections? date: 2020-08-10 pages: extension: .txt txt: ./txt/cord-277931-3hxhsmw8.txt cache: ./cache/cord-277931-3hxhsmw8.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-277931-3hxhsmw8.txt' === file2bib.sh === id: cord-291781-gs81g1db author: Caruso, Arturo Armone title: Hydrogen peroxide and viral infections: a literature review with research hypothesis definition in relation to the current covid-19 pandemic date: 2020-06-01 pages: extension: .txt txt: ./txt/cord-291781-gs81g1db.txt cache: ./cache/cord-291781-gs81g1db.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-291781-gs81g1db.txt' === file2bib.sh === id: cord-328587-vctvcyim author: Jun, Sun title: The hypothesis that SARS-CoV-2 affects male reproductive ability by regulating autophagy date: 2020-07-10 pages: extension: .txt txt: ./txt/cord-328587-vctvcyim.txt cache: ./cache/cord-328587-vctvcyim.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-328587-vctvcyim.txt' === file2bib.sh === id: cord-276715-d1nh2dvb author: Raha, Syamal title: Is Copper beneficial for COVID-19 patients? date: 2020-05-05 pages: extension: .txt txt: ./txt/cord-276715-d1nh2dvb.txt cache: ./cache/cord-276715-d1nh2dvb.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-276715-d1nh2dvb.txt' === file2bib.sh === id: cord-275353-ezrmuw48 author: Donma, Mustafa Metin title: The Effects of Allium Sativum on Immunity within the Scope of COVID-19 Infection date: 2020-06-02 pages: extension: .txt txt: ./txt/cord-275353-ezrmuw48.txt cache: ./cache/cord-275353-ezrmuw48.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-275353-ezrmuw48.txt' === file2bib.sh === id: cord-332365-20u06444 author: Raciti, Loredana title: Can volcanic trace elements facilitate Covid-19 diffusion? A hypothesis stemming from the Mount Etna area, Sicily date: 2020-06-27 pages: extension: .txt txt: ./txt/cord-332365-20u06444.txt cache: ./cache/cord-332365-20u06444.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-332365-20u06444.txt' === file2bib.sh === id: cord-338585-ep9r1n8t author: Perrin, David M. title: A hypothesis for examining dihydroxyacetone, the active component in self-tanning products, as a topical prophylactic against SARS-COV-2 transmission date: 2020-09-16 pages: extension: .txt txt: ./txt/cord-338585-ep9r1n8t.txt cache: ./cache/cord-338585-ep9r1n8t.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-338585-ep9r1n8t.txt' === file2bib.sh === id: cord-353716-gxgvhhv1 author: Kumar, Ashutosh title: SARS-CoV-2 cell entry receptor ACE2 mediated endothelial dysfunction leads to vascular thrombosis in COVID-19 patients date: 2020-09-30 pages: extension: .txt txt: ./txt/cord-353716-gxgvhhv1.txt cache: ./cache/cord-353716-gxgvhhv1.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-353716-gxgvhhv1.txt' === file2bib.sh === id: cord-282853-l0c69uul author: Massad, Eduardo title: Forecasting versus projection models in epidemiology: The case of the SARS epidemics date: 2005-03-30 pages: extension: .txt txt: ./txt/cord-282853-l0c69uul.txt cache: ./cache/cord-282853-l0c69uul.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-282853-l0c69uul.txt' === file2bib.sh === id: cord-327809-9uhhqasl author: Dimitriu, Mihai C.T. title: Burnout syndrome in Romanian medical residents in time of the COVID-19 pandemic date: 2020-06-07 pages: extension: .txt txt: ./txt/cord-327809-9uhhqasl.txt cache: ./cache/cord-327809-9uhhqasl.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-327809-9uhhqasl.txt' === file2bib.sh === id: cord-352911-9wbq9qo2 author: de Oliveira, Pedro Gonçalves title: Diacerein: a potential multi-target therapeutic drug for COVID-19 date: 2020-06-01 pages: extension: .txt txt: ./txt/cord-352911-9wbq9qo2.txt cache: ./cache/cord-352911-9wbq9qo2.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-352911-9wbq9qo2.txt' === file2bib.sh === id: cord-274698-i3mzzxwq author: Stief, Thomas W title: The physiology and pharmacology of singlet oxygen date: 2003-02-19 pages: extension: .txt txt: ./txt/cord-274698-i3mzzxwq.txt cache: ./cache/cord-274698-i3mzzxwq.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-274698-i3mzzxwq.txt' === file2bib.sh === id: cord-271785-vmnc8yg6 author: Minetti, Giampaolo title: Mevalonate pathway, selenoproteins, redox balance, immune system, Covid-19: Reasoning about connections date: 2020-07-21 pages: extension: .txt txt: ./txt/cord-271785-vmnc8yg6.txt cache: ./cache/cord-271785-vmnc8yg6.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-271785-vmnc8yg6.txt' === file2bib.sh === id: cord-276564-o21ncldx author: Miller, R. title: COVID-19: NAD(+) deficiency may predispose the aged, obese and type2 diabetics to mortality through its effect on SIRT1 activity date: 2020-06-29 pages: extension: .txt txt: ./txt/cord-276564-o21ncldx.txt cache: ./cache/cord-276564-o21ncldx.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-276564-o21ncldx.txt' === file2bib.sh === id: cord-268425-xg8xnjf9 author: DiNicolantonio, James J. title: Harnessing Adenosine A2A Receptors as a Strategy for Suppressing the Lung Inflammation and Thrombotic Complications of COVID-19: Potential of Pentoxifylline and Dipyridamole date: 2020-07-02 pages: extension: .txt txt: ./txt/cord-268425-xg8xnjf9.txt cache: ./cache/cord-268425-xg8xnjf9.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-268425-xg8xnjf9.txt' === file2bib.sh === id: cord-297178-moxhk2e0 author: Novaes Rocha, Vinicius title: Viral replication of SARS-CoV-2 could be self-limitative - the role of the renin-angiotensin system on COVID-19 pathophysiology date: 2020-10-01 pages: extension: .txt txt: ./txt/cord-297178-moxhk2e0.txt cache: ./cache/cord-297178-moxhk2e0.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-297178-moxhk2e0.txt' === file2bib.sh === id: cord-346281-sma6e891 author: Maldonado, Valente title: Repositioning of pentoxifylline as an immunomodulator and regulator of the renin-angiotensin system in the treatment of COVID-19 date: 2020-06-09 pages: extension: .txt txt: ./txt/cord-346281-sma6e891.txt cache: ./cache/cord-346281-sma6e891.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 27 resourceName b'cord-346281-sma6e891.txt' === file2bib.sh === id: cord-264916-c4n0kyog author: Zimmerman, Keith title: Natural protection of ocular surface from viral infections – a hypothesis date: 2020-07-09 pages: extension: .txt txt: ./txt/cord-264916-c4n0kyog.txt cache: ./cache/cord-264916-c4n0kyog.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-264916-c4n0kyog.txt' === file2bib.sh === id: cord-274510-fo7p98np author: Spadera, Lucrezia title: Potential Role of GcMAF in suppressing the severity of COVID-19-induced immune responses: lesson learned from HIV date: 2020-09-24 pages: extension: .txt txt: ./txt/cord-274510-fo7p98np.txt cache: ./cache/cord-274510-fo7p98np.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 7 resourceName b'cord-274510-fo7p98np.txt' === file2bib.sh === id: cord-299911-v95pf3eg author: El-Ghiaty, Mahmoud A. title: Cytochrome P450-mediated drug interactions in COVID-19 patients: current findings and possible mechanisms date: 2020-06-26 pages: extension: .txt txt: ./txt/cord-299911-v95pf3eg.txt cache: ./cache/cord-299911-v95pf3eg.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-299911-v95pf3eg.txt' === file2bib.sh === id: cord-320959-sgdqhtns author: Lee, Hanjun title: Vitamin E Acetate as Linactant in the Pathophysiology of EVALI date: 2020-08-12 pages: extension: .txt txt: ./txt/cord-320959-sgdqhtns.txt cache: ./cache/cord-320959-sgdqhtns.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-320959-sgdqhtns.txt' === file2bib.sh === id: cord-261370-jp5sqqwc author: Bollag, Wendy B. title: Phosphatidylglycerol and Surfactant: A Potential Treatment for COVID-19? date: 2020-09-16 pages: extension: .txt txt: ./txt/cord-261370-jp5sqqwc.txt cache: ./cache/cord-261370-jp5sqqwc.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-261370-jp5sqqwc.txt' === file2bib.sh === id: cord-254162-tu81j66h author: Bai, Xiyuan title: Hypothesis: alpha-1-antitrypsin is a promising treatment option for COVID-19 date: 2020-11-12 pages: extension: .txt txt: ./txt/cord-254162-tu81j66h.txt cache: ./cache/cord-254162-tu81j66h.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-254162-tu81j66h.txt' Que is empty; done journal-medHypotheses-cord === reduce.pl bib === id = cord-254411-e9vvjv8w author = Taghizadeh-Hesary, Farzad title = The Powerful Immune System Against Powerful COVID-19: A Hypothesis date = 2020-04-22 pages = extension = .txt mime = text/plain words = 1878 sentences = 130 flesch = 49 summary = In this article, we provide a novel hypothesis to describe how an increase in cellular adenosine triphosphate (c-ATP) can potentially improve the efficiency of innate and adaptive immune systems to either prevent and fight off COVID-19. In this article, we aim to provide a new hypothesis to describe how the repletion of cellular adenosine triphosphate (c-ATP) can promote immunity against COVID-19. Secondly, ATP-depletion can potentially prone the recruited immune cells to earlier exhaustion against COVID-19. Therefore, one may conclude that ATP-repletion can prevent the so-called "cytokine storm" and improve the cellular energy to better counteract with COVID-19. From the perspective of cellular energy, this process potentially occurs through IFN-mediated T-cell activation that results in c-ATP depletion. have shown that following IFN-γ stimulation, mitochondrial hyperpolarization and ATP depletion occurs in T-cells that results in apoptosis (10) . It demonstrates how an increase in c-ATP can decrease the effect of COVID-19 on immune dysregulation. cache = ./cache/cord-254411-e9vvjv8w.txt txt = ./txt/cord-254411-e9vvjv8w.txt === reduce.pl bib === id = cord-258272-uu6t6tnh author = Dabaghian, Farid title = Bioactive compounds with possible inhibitory activity of Angiotensin-Converting Enzyme-II; a gate to manage and prevent COVID-19 date = 2020-05-16 pages = extension = .txt mime = text/plain words = 302 sentences = 27 flesch = 50 summary = key: cord-258272-uu6t6tnh title: Bioactive compounds with possible inhibitory activity of Angiotensin-Converting Enzyme-II; a gate to manage and prevent COVID-19 cord_uid: uu6t6tnh Angiotensin-Converting Enzyme-II (ACE-II) receptor, most likely the COVID-19 target, plays essential roles in virus transmission to the alveolar cells (2) . Accordingly, agents with potential inhibition or regulation of ACE-II receptors might be effective in COVID-19 management (3) . Glycyrrhizin can inhibit COVID-19 S-protein binding to ACE-II receptors (7) . Emodin, a bioactive antiviral agent may prevent S-protein binding to ACE-II receptors. Thus, Emodin and probably Aloe-emodin can stave off the COVID-19 infection via competing with S-protein in binding to ACE-II (7) . Angiotensin converting enzyme 2: SARS-CoV-2 receptor and regulator of the renin-angiotensin system Potential natural compounds for preventing 2019-nCoV infection Emodin blocks the SARS coronavirus spike protein and angiotensin-converting enzyme 2 interaction Anti-SARS coronavirus 3C-like protease effects of Rheum palmatum L. The authors of this manuscript have no conflict of interest. cache = ./cache/cord-258272-uu6t6tnh.txt txt = ./txt/cord-258272-uu6t6tnh.txt === reduce.pl bib === id = cord-258670-dphg8ukj author = Karaahmet, Fatih title = Endothelial progenitor cells and mesenchymal stem cells to overcome vascular deterioration and cytokine storm in critical patients with COVID-19 date = 2020-06-10 pages = extension = .txt mime = text/plain words = 599 sentences = 40 flesch = 35 summary = title: Endothelial progenitor cells and mesenchymal stem cells to overcome vascular deterioration and cytokine storm in critical patients with COVID-19 In light of this information, the sufficient repair of the endothelial lining of blood vessels with Endothelial progenitor cells (EPCs) treatment may have a crucial role to overcome the vascular collapse driving forces in COVID-19 patients, as well as to modulate human immune system. Accumulating evidence leads to suggest that bone marrow-derived EPCs for repairing endothelial damage is now considered as an important novel potential therapeutic option for vascular repair (7, 8) . In critical patients in the course of COVID-19, EPCs may have an important contribution to stem cell treatments to maintain vascular endothelin functions. In critical patients who do not respond to current treatment, the restoration of vascular endothelial function and modulation of immune system by synergistic use of EPCs and MSCs may have a crucial role to overcome the vascular collapse driving forces in COVID-19 patients. cache = ./cache/cord-258670-dphg8ukj.txt txt = ./txt/cord-258670-dphg8ukj.txt === reduce.pl bib === id = cord-254162-tu81j66h author = Bai, Xiyuan title = Hypothesis: alpha-1-antitrypsin is a promising treatment option for COVID-19 date = 2020-11-12 pages = extension = .txt mime = text/plain words = 5512 sentences = 286 flesch = 39 summary = Sixth, AAT inhibition of elastase can antagonize the formation of neutrophil extracellular traps (NETs), a complex extracellular structure comprised of neutrophil-derived DNA, histones, and proteases, and implicated in the immunothrombosis of COVID-19; indeed, AAT has been shown to change the shape and adherence of non-COVID-19-related NETs. Seventh, AAT inhibition of endothelial cell apoptosis may limit the endothelial injury linked to severe COVID-19-associated acute lung injury, multi-organ dysfunction, and pre-eclampsia-like syndrome seen in gravid women. First, AAT is a serine protease inhibitor (SERPIN) shown to inhibit TMPRSS-2, the host serine protease that cleaves the spike protein of SARS-CoV-2, a necessary preparatory step for the virus to bind its cell surface receptor ACE2 to gain intracellular entry. First, AAT is a serine protease inhibitor (SERPIN) shown to inhibit TMPRSS-2, the host serine protease that cleaves the spike protein of SARS-CoV-2, a necessary preparatory step for the virus to bind its cell surface receptor ACE2 to gain intracellular entry. cache = ./cache/cord-254162-tu81j66h.txt txt = ./txt/cord-254162-tu81j66h.txt === reduce.pl bib === === reduce.pl bib === id = cord-261370-jp5sqqwc author = Bollag, Wendy B. title = Phosphatidylglycerol and Surfactant: A Potential Treatment for COVID-19? date = 2020-09-16 pages = extension = .txt mime = text/plain words = 4096 sentences = 177 flesch = 33 summary = It is thought that surfactant, which is already approved by the Food and Drug Administration for intratracheal administration to treat neonatal respiratory distress syndrome in infants, could benefit COVID-19-infected individuals by: (1) restoring surfactant damaged by lung infection and/or decreased due to the virus-induced death of the type II pneumocytes that produce it and (2) reducing surface tension to decrease the work of breathing and limit pulmonary edema. In addition, a constituent of surfactant, phosphatidylglycerol, could mitigate COVID-19-induced lung pathology by: (3) decreasing excessive innate immune system activation via its inhibition of toll-like receptor-2 and -4 activation by microbial components and cellular proteins released by damaged cells, thereby limiting inflammation and the resultant pulmonary edema, and (4) possibly blocking spread of the viral infection to non-infected cells in the lung. cache = ./cache/cord-261370-jp5sqqwc.txt txt = ./txt/cord-261370-jp5sqqwc.txt === reduce.pl bib === id = cord-253468-pf0xubii author = Emara, Mohamed H title = Ketonuria with or without ketoacidosis as the presenting manifestation of SARS-CoV-2 (COVID-19) among uncontrolled Type 2 Diabetic patients date = 2020-09-02 pages = extension = .txt mime = text/plain words = 986 sentences = 57 flesch = 58 summary = title: Ketonuria with or without ketoacidosis as the presenting manifestation of SARS-CoV-2 (COVID-19) among uncontrolled Type 2 Diabetic patients We hereby present the data of 3 patients presented to our OPD and were admitted as diabetic ketoacidosis (DKA) and 2-3 days later they developed manifestations suggestive of and proved by swabbing as positive cases. Chest auscultation and chest X ray were unremarkable and hence chest CT scan was requested ( Figure 1 ) and showed picture suggestive of mild-moderate COVID-19, swabbing was done and came positive Case 2: A 51-year-old male, presented by dizziness over last 2-3 days and when examined found to have high RBS and ketonuria, and hence admitted as KDA, and was acidotic (PH 7). A 62-year-old male patient who was not compliant with his medicines over the last 2 months, presented for renewal of medicine without any clinical manifestations, found to have panic RBS measurement, and was positive for urine ketones. cache = ./cache/cord-253468-pf0xubii.txt txt = ./txt/cord-253468-pf0xubii.txt === reduce.pl bib === id = cord-256092-bph9ys72 author = Hussain, Aneela N. title = Role of testosterone in COVID-19 patients - a double-edged sword? date = 2020-09-17 pages = extension = .txt mime = text/plain words = 1574 sentences = 93 flesch = 43 summary = Current data suggest a direct correlation between the lower level of serum testosterone, inflammatory cytokines, disease severity, and poor clinical outcomes among male patients with COVID-19. Current data suggest a direct correlation between the lower level of serum testosterone, inflammatory cytokines, disease severity, and poor clinical outcomes among male patients with COVID-19. Lower levels of testosterone result in the upregulation of ACE2 and TMPRSS2 receptors, facilitating SARS-CoV-1 entry into the alveolar cells, and deregulating a lung-protective pathway (4) . Thereby we hypothesize that low testosterone levels in males have a direct correlation with the severity of disease and a worse outcome in COVID-19. Patients with low testosterone have reportedly developed severe manifestations requiring assisted ventilation because of the upregulation of ACE-2 receptors in lower respiratory cells, increased risk of lung damage, and respiratory muscle catabolism. Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China cache = ./cache/cord-256092-bph9ys72.txt txt = ./txt/cord-256092-bph9ys72.txt === reduce.pl bib === id = cord-254094-ed1epul1 author = Mayoral, Eduardo Pérez-Campos title = Factors related to asymptomatic or severe COVID-19 infection date = 2020-09-24 pages = extension = .txt mime = text/plain words = 1665 sentences = 98 flesch = 48 summary = In particular, we refer to the TMPRSS2 expression profile, balance of androgen and estrogen, blood group-A and/or B, nonsynonymous mutations in ORF3, and proteins NS7b and NS8 in SARS-CoV-2. In the first months of the COVID-19 pandemic, most authors focused their attention on features such as the high expression of ACE2 in the salivary glands in asymptomatic infection [4] , and the maturity and binding capacity of ACE2 [5, 6] . A higher 2D:4D ratio is associated with COVID-19 severity in men [14] , this means that sex hormones play a role in protection, thus, causing women to develop less serious complications or an asymptomatic COVID-19 Infection [12] . An in-depth study of the factors associated with asymptomatic subjects can provide information to limit severe COVID-19 as much as possible. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is likely to be androgen mediated cache = ./cache/cord-254094-ed1epul1.txt txt = ./txt/cord-254094-ed1epul1.txt === reduce.pl bib === id = cord-265724-fdt00qw1 author = Varadarajan, Saranya title = EMMPRIN/BASIGIN as a biological modulator of oral cancer and COVID-19 interaction: novel propositions date = 2020-07-09 pages = extension = .txt mime = text/plain words = 1761 sentences = 105 flesch = 39 summary = Apart from ACE-2, recently EMMPRIN, has been regarded as a target for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) attachment and entry into the host cell. Since one of the routes of entry for the virus is the oral cavity, it becomes imperative to percept oral comorbidities such oral squamous cell carcinoma (OSCC) and oral potentially malignant disorders (OPMDs) in terms of EMMPRIN as a target for SARS-CoV-2. 1 Angiotensin-Converting Enzyme 2 (ACE-2) on the host cells is the attachment protein for the spike receptor present on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). [4] [5] [6] Apart from ACE-2, recently extracellular matrix metalloproteinase inducer (EMMPRIN), which is also called BASIGIN/CD147, has been regarded as a target for SARS-CoV-2 attachment and its entry into the host cell. OSCC, by the virtue of upregulation of EMMPRIN expression (potential and alternative site for 'S' receptor), increases the susceptibility to SARS-CoV-2 infection. cache = ./cache/cord-265724-fdt00qw1.txt txt = ./txt/cord-265724-fdt00qw1.txt === reduce.pl bib === id = cord-264916-c4n0kyog author = Zimmerman, Keith title = Natural protection of ocular surface from viral infections – a hypothesis date = 2020-07-09 pages = extension = .txt mime = text/plain words = 4671 sentences = 225 flesch = 46 summary = A pandemic outbreak of a viral respiratory infection (COVID-19) caused by a coronavirus (SARS-CoV-2) prompted a multitude of research focused on various aspects of this disease. In this work, we discuss the significance of natural protective factors related to anatomical and physiological properties of the eyes and preventing the deposition of large number of virus-loaded particles on the ocular surface. Specifically, we advance the hypothesis that the standing potential of the eye plays an important role in repelling aerosol particles (microdroplets) from the surface of the eye and discuss factors associated with this hypothesis, possible ways to test it and its implications in terms of prevention of ocular infections. This hypothesis could be tested by measuring the electrical charge of bioaerosol generated by normal breathing in healthy subjects and in patients with viral infections caused by different viruses, causing respiratory infections or with suspected aerosol transmission pathway. cache = ./cache/cord-264916-c4n0kyog.txt txt = ./txt/cord-264916-c4n0kyog.txt === reduce.pl bib === id = cord-265322-3854ddb9 author = Vavougios, George D. title = A data-driven hypothesis on the epigenetic dysregulation of host metabolism by SARS coronaviral infection: potential implications for the SARS-CoV-2 modus operandi date = 2020-04-23 pages = extension = .txt mime = text/plain words = 1252 sentences = 72 flesch = 41 summary = Based on both structural and syndromic similarities with SARS-CoV, a hypothesis is formed on SARS-CoV-2 potential to affect the host's metabolism as part of its lifecycle. In the literature, SARS-CoV has been known to cause de novo diabetes by ACE2-dependent uptake on pancreatic isle cells, and furthermore dysregulate lipid autophagy in favor of the viral lifecycle. Their study provided the foundation for a hypothesis put forth by Fang and colleagues indicating that diabetic and hypertensive patients exposed to ACE2 inhibitors may be at an increased risk of more severe COVID-19 (7) . In another study, SARS-CoV was shown to cause diabetes by ACE2-dependent infection of pancreatic isle cells (10) . Future studies should determine SARS-CoV-2 interaction and effect on the human transcriptome, further identifying drug targets using pharmacogenomic enrichment analyses. Natural small molecules as inhibitors of coronavirus lipid-dependent attachment to host cells: a possible strategy for reducing SARS-COV-2 infectivity? cache = ./cache/cord-265322-3854ddb9.txt txt = ./txt/cord-265322-3854ddb9.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-268425-xg8xnjf9 author = DiNicolantonio, James J. title = Harnessing Adenosine A2A Receptors as a Strategy for Suppressing the Lung Inflammation and Thrombotic Complications of COVID-19: Potential of Pentoxifylline and Dipyridamole date = 2020-07-02 pages = extension = .txt mime = text/plain words = 3891 sentences = 251 flesch = 41 summary = 5 Importantly, neutrophils, whose activation and transit into lung interstitial tissue and alveolar space is a key mediator of the respiratory distress syndrome associated with COVID-19, are highly responsive to the functionally suppressive effects of A2AR, as are the endothelial cells whose activation attracts and enables transendothelial passage of activated neutrophils. Most studies with DIP have focused on its platelet-stabilizing effects -which presumably could provide some protection from SARS-CoV-2's pro-thrombotic effects -but experimental studies also show that DIP can act on neutrophils to suppress superoxide production, adhesion to endothelial cells, and, in a mouse model of anti-phospholipid syndrome (a sometime feature of COVID-19), NETosis formation. 79 Supplemental glucosamine may likewise up-regulate the type 1 interferon responses to viruses, while exerting anti-inflammatory effects that render it protective in rodent models of sepsis and lung inflammation induced by LPS or cigarette smoke. cache = ./cache/cord-268425-xg8xnjf9.txt txt = ./txt/cord-268425-xg8xnjf9.txt === reduce.pl bib === id = cord-270805-o6rbfmie author = Hussein, Osama title = Second wave of of Covid-19 is determined by immune mechanism date = 2020-09-02 pages = extension = .txt mime = text/plain words = 622 sentences = 47 flesch = 53 summary = In this letter, the author describes an immunological explanation for the double-peaked epidemic curve of new viral diseases including Covid-19. This theory claims that a double-peaked pattern of new cases in a new viral epidemic is intrinsically determined by the pattern of pathogen interaction with the host. According to this hypothesis, relaxation of the community control measures is not responsible; at least in part, for resurgence of cases. Assuming the above hypothesis is true; a viral epidemic curve will show an early upstroke corresponding to persons who pass into viremia upon initial exposure to the virus followed by a second slower rise due to cases who develop the disease after repeated process of inoculation and clearance at the point of entry. In conclusion, the author describes an immunological explanation for a double-peaked epidemic curve of Covid-19 and other new viral diseases. cache = ./cache/cord-270805-o6rbfmie.txt txt = ./txt/cord-270805-o6rbfmie.txt === reduce.pl bib === id = cord-276564-o21ncldx author = Miller, R. title = COVID-19: NAD(+) deficiency may predispose the aged, obese and type2 diabetics to mortality through its effect on SIRT1 activity date = 2020-06-29 pages = extension = .txt mime = text/plain words = 3229 sentences = 205 flesch = 44 summary = This hypothesis suggests that a deficiency of nicotinamide adenine dinucleotide (NAD + ) may be the primary factor related to the SARS-Cov-2 disease spectrum and the risk for mortality, as subclinical nutritional deficiencies may be unmasked by any significant increase in oxidative stress. This hypothesis suggests that a deficiency of nicotinamide adenine dinucleotide (NAD + ) may be the primary factor related to the SARS-Cov-2 disease spectrum and the risk for mortality, as subclinical nutritional deficiencies may be unmasked by any significant increase in oxidative stress. Vulnerable patient groups would potentially be less likely or unable to ensure sufficient activation of SIRT1 due to low NAD + levels or associated nutritional deficiencies including Zn ++ , and as such contribute to an inability to control viral replication and reduce the uncontrolled expression of pro-inflammatory cytokines. cache = ./cache/cord-276564-o21ncldx.txt txt = ./txt/cord-276564-o21ncldx.txt === reduce.pl bib === id = cord-274715-dcs1rgd0 author = Mani Mishra, Pushpendra title = Serum albumin-mediated strategy for the effective targeting of SARS-CoV-2 date = 2020-04-24 pages = extension = .txt mime = text/plain words = 2145 sentences = 121 flesch = 45 summary = Novel coronavirus (NCoV-19), also known as SARS CoV-2, is a pathogen causing an emerging infection that rapidly increases in incidence and geographic range, is associated with the ever-increasing morbidity and mortality rates, and shows sever economic impact worldwide. We are suggesting here a strategy for the COVID-19 treatment that could be effective in curing the patients in the current scenario when no efficient medicine or Vaccine is currently available, and Clinicians solely depend upon the performing trials with drugs with known antiviral activities. If the albumin is used to stabilize and deliver the EGCG and Curcumin for targeting the intracellular virus components in combination with the drug that could block the virus fusion and/or entry to a cell, this strategy might represent an effective way of treating the SARS CoV-2 infection. cache = ./cache/cord-274715-dcs1rgd0.txt txt = ./txt/cord-274715-dcs1rgd0.txt === reduce.pl bib === id = cord-271785-vmnc8yg6 author = Minetti, Giampaolo title = Mevalonate pathway, selenoproteins, redox balance, immune system, Covid-19: Reasoning about connections date = 2020-07-21 pages = extension = .txt mime = text/plain words = 2551 sentences = 137 flesch = 38 summary = As competitive inhibitors of HMG-CoA-reductase, the key enzyme of the "mevalonate pathway" through which essential compounds, not only cholesterol, are synthesized, statins decrease the levels of cholesterol, and thus LDLs, as an innate defense mechanism, with controversial results in decreasing mortality from cardiovascular disease. In the attempt to decipher the enigma of SARS-CoV-2 infectivology, the hypothesis should be tested whether the population of subjects who succumbed to Covid-19 may have developed a compromised immunity at sub-clinical levels and have become more susceptible to fatal consequences from SARS-Cov-2 infection due to statin therapy. Statins are cholesterol-lowering drugs that act as competitive inhibitors of the enzyme -Hydroxy--Methyl-Glutaryl-Coenzyme-A (HMG-CoA)-reductase, the key enzyme of the "mevalonate pathway". 27 Thus, subjects with already low LDL levels and possibly weakened leukocyte function because of statin treatment would be even more susceptible to infection and its fatal consequences. cache = ./cache/cord-271785-vmnc8yg6.txt txt = ./txt/cord-271785-vmnc8yg6.txt === reduce.pl bib === === reduce.pl bib === id = cord-275569-i5y23mmz author = de Bernardis, E. title = A putative role for the tobacco mosaic virus in smokers’ resistance to COVID-19 date = 2020-07-31 pages = extension = .txt mime = text/plain words = 1500 sentences = 69 flesch = 41 summary = Though it is intuitively tempting, on the basis of physiopathological common knowledge, to predict a greater risk of contracting the SARS-CoV-2 infection in tobacco smokers, an analysis of studies from various countries shows that hospitalized COVID-19 patients have a lower, and apparently inversely proportional, rate of current tobacco smoking, in comparison with the respective general population, although once the disease has developed meta-analyses suggest that smoking is associated with a worse prognosis [1] . Incidentally, this behavior reminds the proposed effects of tobacco smoking, protective against initial SARS-CoV-2 infection and deleterious in the florid phase of the COVID-19 disease. Taken together, all these elements suggest that the oral use of tobacco, continuously exposing to non-pathogenic but immunogenic TMV particles, and chronically stimulating a natural antiviral response, may induce a state of resistance to the initial SARS-CoV-2 infection. cache = ./cache/cord-275569-i5y23mmz.txt txt = ./txt/cord-275569-i5y23mmz.txt === reduce.pl bib === === reduce.pl bib === id = cord-277931-3hxhsmw8 author = Khitan, Zeid J. title = SCan Charcoal Improve Outcomes in COVID-19 Infections? date = 2020-08-10 pages = extension = .txt mime = text/plain words = 1090 sentences = 60 flesch = 44 summary = We propose to examine the potential utility of oral activated charcoal with the hypothesis that such treatment would lower absorption of microbiome derived toxins and ameliorate systemic oxidant stress and inflammation. We propose to examine the potential utility of oral activated charcoal with the hypothesis that such treatment would lower absorption of microbiome derived toxins and ameliorate systemic oxidant stress and inflammation. It appears that age, renal dysfunction and obesity are amongst the most important risk factors for serious or fatal COVID-19 infection 3, 4 . To test this hypothesis, we would suggest first a proof of concept study where a relatively small group of patients at high risk for COVID-19 complications are given activated charcoal at doses similar to that used in previous renal failure studies 18, 19 when the diagnosis is first made. Uremic Toxins Activates Na/K-ATPase Oxidant Amplification Loop Causing Phenotypic Changes in Adipocytes in In Vitro Models Protein-bound uremic toxins, inflammation and oxidative stress: a cross-sectional study in stage 3-4 chronic kidney disease cache = ./cache/cord-277931-3hxhsmw8.txt txt = ./txt/cord-277931-3hxhsmw8.txt === reduce.pl bib === id = cord-274510-fo7p98np author = Spadera, Lucrezia title = Potential Role of GcMAF in suppressing the severity of COVID-19-induced immune responses: lesson learned from HIV date = 2020-09-24 pages = extension = .txt mime = text/plain words = 4050 sentences = 217 flesch = 40 summary = Based on the aforementioned findings and on documented analogies between SARS-CoV-2 and HIV [13] , we hypothesized that the reduced conversion activity of the Gc protein (human groupspecific component (Gc)) into the macrophage activating factor (MAF) could have a key role in the dysregulate immune response induced by SARS-CoV-2, just like for HIV infected patients [14] [15] . In particular, based on their antiviral activity [68] , chloroquine and hydroxychloroquine, initially conceived as antimalarial therapeutics, were proposed to treat patients hospitalized with COVID-19, better if associated to azithromycin, showing promising efficacy in "inhibiting the exacerbation of pneumonia, improving lung imaging findings, promoting a virus negative conversion and shortening the disease course" [69] [70] . So, in sight of this, given its multifunctional properties, we believe that GcMAF could have a very important role in the pathophysiology of organ damage induced by SARS-CoV-2, providing explanations which are consistent with the clinical, radiological and histopathological findings observed in patients with COVID-19. Effects of vitamin D(3)-binding protein-derived macrophage activating factor (GcMAF) on angiogenesis cache = ./cache/cord-274510-fo7p98np.txt txt = ./txt/cord-274510-fo7p98np.txt === reduce.pl bib === id = cord-276715-d1nh2dvb author = Raha, Syamal title = Is Copper beneficial for COVID-19 patients? date = 2020-05-05 pages = extension = .txt mime = text/plain words = 1610 sentences = 103 flesch = 50 summary = Besides, Cu can kill several infectious viruses such as bronchitis virus, poliovirus, human immunodeficiency virus type 1(HIV-1), other enveloped or nonenveloped, singleor double-stranded DNA and RNA viruses. Based on available data, we hypothesize that enrichment of plasma copper levels will boost both the innate and adaptive immunity in people. Copper exposure to human coronavirus 229E destroyed the viral genomes and irreversibly affected virus morphology, including disintegration of envelope and dispersal of surface spikes [16] . Copper deficiency could lead a decreased number of circulatory blood cells with a greater susceptibility towards infection in older people In a study of 11 men on a low-Cu diet (0.66 mg Cu/day for 24 days and 0.38 mg/day for another 40 days) showed a decreased proliferation response of their white blood cells when presented with an immune challenge in cell culture [33] . Thujaplicin-copper chelates inhibit replication of human influenza viruses Effects of low-copper diets on human immune response cache = ./cache/cord-276715-d1nh2dvb.txt txt = ./txt/cord-276715-d1nh2dvb.txt === reduce.pl bib === === reduce.pl bib === id = cord-275353-ezrmuw48 author = Donma, Mustafa Metin title = The Effects of Allium Sativum on Immunity within the Scope of COVID-19 Infection date = 2020-06-02 pages = extension = .txt mime = text/plain words = 2510 sentences = 156 flesch = 42 summary = Compounds derived from Allium sativum (garlic) have the potential to decrease the expression of proinflammatory cytokines and to reverse the immunological abnormalities to more acceptable levels. Leptin's role in boosting proinflammatory cytokines and in appetite decreasing suggest the possible beneficial effect of decreasing the concentration of this proinflammatory adipose tissue hormone in relieving some symptoms detected during COVID-19 infection. In conclusion, Allium sativum may be an acceptable preventive measure against COVID-19 infection to boost immune system cells and to repress the production and secretion of proinflammatory cytokines as well as an adipose tissue derived hormone leptin having the proinflammatory nature. It is a well-known fact that immune dysfunction plays an important role in the development and progress of several diseases and this functional food may contribute to the prevention and treatment of pathologies such as obesity, metabolic syndrome, cardiovascular disorders, gastric ulcer, and even cancer [17, 18] . Decreased leptin concentrations caused by garlic may be helpful to alleviate appetite loss observed in patients with COVID-19 infection. cache = ./cache/cord-275353-ezrmuw48.txt txt = ./txt/cord-275353-ezrmuw48.txt === reduce.pl bib === id = cord-279084-bbae1qyx author = Liu, Bin title = Free DNA, a reason for severe COVID-19 infection? date = 2020-05-05 pages = extension = .txt mime = text/plain words = 799 sentences = 61 flesch = 63 summary = I hypothesized that the damage induced by free DNA is a reason for severe COVID-19, which can explain many symptoms of this disease, such as cytokine storm, acute respiratory distress syndrome (ARDS) and muscus plug, acute injuries of heart, liver and kidney, and some special symptoms of COVID-19. I hypothesized that the damage induced by free DNA is a reason for severe 23 COVID-19, which can explain many symptoms of this disease, such as cytokine 24 storm, ARDS and muscus plug, acute injuries of heart, liver and kidney, and some 25 special symptoms of COVID-19. Level 60 of lymphocytes is thought as the early identification of risk factors for severe 61 COVID-19, [1] [2] [3] 8 while I hypothesized that it was related to free DNA-related cytokine 62 storm and blood vessel damage, which can explain many symptoms of this disease, 63 including some "special" symptoms in COVID-19, as shown in Figure 1 . cache = ./cache/cord-279084-bbae1qyx.txt txt = ./txt/cord-279084-bbae1qyx.txt === reduce.pl bib === id = cord-274698-i3mzzxwq author = Stief, Thomas W title = The physiology and pharmacology of singlet oxygen date = 2003-02-19 pages = extension = .txt mime = text/plain words = 3339 sentences = 213 flesch = 39 summary = Chloramines at blood concentrations between 1 and 2 mmol/L inactivate lipid enveloped virus and chloramines at blood concentrations below 0.5 mmol/L, i.e. at oxidant concentrations that do not affect thrombocytes or hemostasis factors, act antithrombotically by activation of the physiologic PMN mediated fibrinolysis; this thrombolysis is of selective nature, i.e. it does not impair the hemostasis system of the patient allowing the antithrombotic treatment in patients where the current risky thrombolytic treatment is contraindicated. The 60 mM NH 2 Cl (about 10 times the concentration generated by activated PMN!) is ulcerogenic in rat stomachs, taurine application (1 ml 200 mM) attenuates the deleterious action of NH 2 Cl (102), NH 2 Cl induces apoptosis in gastric mucosa (103) . Singlet oxygen ð 1 O 2 Þ-generating chloramines at concentrations that are tolerable for normal hemostasis function inactivate the lipid enveloped vesicular stomatitis virus in human blood Taurine chloramine inhibits prostaglandin E2 production in activated RAW 264.7 cells by post-transcriptional effects on inducible cyclooxygenase expression cache = ./cache/cord-274698-i3mzzxwq.txt txt = ./txt/cord-274698-i3mzzxwq.txt === reduce.pl bib === id = cord-286038-a62k3lma author = Klimke, A. title = Hydroxychloroquine as an aerosol might markedly reduce and even prevent severe clinical symptoms after SARS-CoV-2 infection date = 2020-04-27 pages = extension = .txt mime = text/plain words = 2336 sentences = 104 flesch = 45 summary = The antimalarial drugs chloroquine phosphate (CQ) and hydroxychloroquine (HCQ) impair in vitro the terminal glycosylation of ACE2 without significant change of cell-surface ACE2 and, therefore, might be potent inhibitors of SARS-CoV-2 infections. We hypothesize that HCQ especially as an aerosol application will prevent or at least markedly reduce the replication rate of the SARS-CoV-2 virus in the early phase of the infection and subsequently substantially lower the number of severe pneumonias and casualties. This hypothesis is new since the major assumption in ongoing clinical studies and actual recommendations is that HCQ and CQ should be used in oral application form in patients with severe covid-19 pneumonia and only when other treatment strategies have failed. If our hypothesis is true, HCQ as an aerosol might not only reduce the side effect potential of the oral application form but can also be clinically used as an efficient antiviral agent in the early phase of COVID-19 and eventually lower the rate of severely ill patients and fatalities. cache = ./cache/cord-286038-a62k3lma.txt txt = ./txt/cord-286038-a62k3lma.txt === reduce.pl bib === id = cord-282853-l0c69uul author = Massad, Eduardo title = Forecasting versus projection models in epidemiology: The case of the SARS epidemics date = 2005-03-30 pages = extension = .txt mime = text/plain words = 3085 sentences = 173 flesch = 56 summary = In this work we propose a simple mathematical model for the analysis of the impact of control measures against an emerging infection, namely, the severe acute respiratory syndrome (SARS). The model provides a testable hypothesis by considering a dynamical equation for the contact parameter, which drops exponentially with time, simulating control measures. In contrast, with control measures, which reduce the contact rate to about 25% of its initial value, the expected final number of cases is reduced to 1778 in Hong Kong and 226 in Toronto (Canada). The aim of this work is to provide a projection of what would have happened with the course of severe acute respiratory syndrome (SARS) epidemic if the universal procedures to reduce contact were not implemented in the affected areas. The model projects that, in the absence of control, the final number of cases would be 320,000 in Hong Kong and 36,900 in Toronto (Canada). cache = ./cache/cord-282853-l0c69uul.txt txt = ./txt/cord-282853-l0c69uul.txt === reduce.pl bib === === reduce.pl bib === id = cord-281354-sa27k8o3 author = Takahashi, Harutaka title = Role of Latent Tuberculosis Infections in Reduced COVID-19 Mortality: Evidence from an Instrumental Variable Method Analysis date = 2020-08-26 pages = extension = .txt mime = text/plain words = 1439 sentences = 89 flesch = 47 summary = title: Role of Latent Tuberculosis Infections in Reduced COVID-19 Mortality: Evidence from an Instrumental Variable Method Analysis However, these studies ignore an important fact: according to World Health Organization estimates, about a quarter of the world's population may have latent tuberculosis infection (LTBI), a condition in which there is no evidence of clinically active tuberculosis but persistent immune responses are stimulated by Mycobacterium tuberculosis antigens. However, such studies ignore the important fact that about one-quarter of the world's population may have latent TB infection (LTBI), a condition in which there is no evidence of clinically active TB but persistent immune responses are stimulated by Mycobacterium tuberculosis antigens. As explained above, the logarithm of the number of TB infections per 100,000 individuals (lntb10) can be used as a proxy variable for LTBIs. For this regression analysis to be statistically accurate, the explanatory variable X must first be correlated with the error term u (i.e., the covariance of X and u must be zero). cache = ./cache/cord-281354-sa27k8o3.txt txt = ./txt/cord-281354-sa27k8o3.txt === reduce.pl bib === id = cord-287824-zg5akivn author = Chan, Yinghan title = Advanced drug delivery systems can assist in managing influenza virus infection: A hypothesis date = 2020-09-24 pages = extension = .txt mime = text/plain words = 1158 sentences = 84 flesch = 33 summary = title: Advanced drug delivery systems can assist in managing influenza virus infection: A hypothesis This article provides an insight into a novel hypothesis that describes how the integration of nanomedicine, with the development of drugs and vaccines can potentially enhance body immune response and the efficacies of anti-viral therapeutics to combat influenza infections. In the recent years, an 66 increasing trend of influenza outbreaks have been observed, prompting medical researchers to 67 design and develop suitable vaccines and novel therapeutic modalities [10] . Targeting 411 neutrophils using novel drug delivery systems in chronic respiratory diseases Increasing 440 complexity and interactions of oxidative stress in chronic respiratory diseases: An 441 emerging need for novel drug delivery systems Interactions 501 with the macrophages: An emerging targeted approach using novel drug delivery 502 systems in respiratory diseases Inhibition of H1N1 influenza virus infection by zinc oxide nanoparticles: 537 Another emerging application of nanomedicine cache = ./cache/cord-287824-zg5akivn.txt txt = ./txt/cord-287824-zg5akivn.txt === reduce.pl bib === id = cord-290803-v5ndlk9c author = Khan, Imran title = Can COVID-19 induce glioma tumorogenesis through binding cell receptors? date = 2020-06-19 pages = extension = .txt mime = text/plain words = 909 sentences = 58 flesch = 48 summary = Therefore in the light of these known facts we hypothesized that viral S protein molecule may bind to the other overexpressed receptor molecules in glioma cells and may play some role in glioma tumorogenesis. Thus we leverage docking analysis (HEX and Z-DOCK) between viral S protein and epidermal growth factor receptors (EGFR), vascular endothelial growth factor receptors (VEGFR) and hepatocyte growth factor receptors (HGFR/c-MET) to investigate the oncogenic potential of COVID-19. Thus we leverage docking analysis (HEX and Z-DOCK) between viral S protein and epidermal growth factor receptors (EGFR), vascular endothelial growth factor receptors (VEGFR) and hepatocyte growth factor receptors (HGFR/c-MET) to investigate the oncogenic potential of COVID-19. Considering the importance of these surface receptors on glioma cells, we studied the interaction between EGFR, VEGFR and c-MET receptor proteins with S protein of COVID-19. Our preliminary findings suggested that COVID-19 S protein might have a binding affinity to EGFR, c-MET and VEGFR on glioma cells. cache = ./cache/cord-290803-v5ndlk9c.txt txt = ./txt/cord-290803-v5ndlk9c.txt === reduce.pl bib === id = cord-288733-c51lfwd6 author = Kavanagh, Oisín title = Inhaled Hydroxychloroquine to Improve Efficacy and Reduce Harm in the Treatment of COVID-19 date = 2020-07-15 pages = extension = .txt mime = text/plain words = 769 sentences = 51 flesch = 55 summary = An analysis of clinical trials registered on ClinicalTrials.gov revealed that this may continue as many studies combine HCQ with agents that prolong the QT interval. Here we describe an inhaled formulation of HCQ which has passed safety studies in clinical trials for the treatment of asthma and discuss how this approach may reduce side-effects and improve efficacy. Chloroquine and hydroxychloroquine (HCQ) were two of the earliest drugs to 33 receive attention as possible repurposable treatment options for COVID-19 3 . Concerns associated with severe side effects 41 are such that the FDA and EMA now formally recommend against taking HCQ for COVIDEffects of chloroquine on 178 viral infections: An old drug against today's diseases? FDA Drug Safety Communication: FDA cautions 199 against use of hydroxychloroquine or chloroquine for COVID-19 outside of the 200 hospital setting or a clinical trial due to risk of heart rhythm problems Optimizing hydroxychloroquine 210 dosing for patients with COVID-19: An integrative modeling approach for effective 211 drug repurposing cache = ./cache/cord-288733-c51lfwd6.txt txt = ./txt/cord-288733-c51lfwd6.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-291037-19csqq89 author = Janssen, Rob title = Vitamin K epoxide reductase complex subunit 1 (VKORC1) gene polymorphism as determinant of differences in Covid-19-related disease severity date = 2020-08-25 pages = extension = .txt mime = text/plain words = 2200 sentences = 118 flesch = 41 summary = title: Vitamin K epoxide reductase complex subunit 1 (VKORC1) gene polymorphism as determinant of differences in Covid-19-related disease severity A genetic polymorphism in the vitamin K epoxide reductase complex 1, VKORC1 -1639A, is particularly prevalent in East Asia and associates with low vitamin K recycling rates. A genetic polymorphism in the vitamin K epoxide reductase complex 1, VKORC1 -1639A, is particularly prevalent in East Asia and associates with low vitamin K recycling rates. We speculate that the disparity in morbidity and mortality from Covid-19 between East and West may be at least partially explained by differences in the allele distribution of a VKORC1 polymorphism determining the rate of vitamin K recycling. If the VKORC1 -1639A allele is shown to be associated with decreased thrombotic complications and/or death, it would further support the hypothesis that vitamin K metabolism is an important determinant of Covid-19-related disease severity. cache = ./cache/cord-291037-19csqq89.txt txt = ./txt/cord-291037-19csqq89.txt === reduce.pl bib === id = cord-289332-hvakv08t author = Chen, Guoqian title = Pathogenic role of HMGB1 in SARS? date = 2004-04-30 pages = extension = .txt mime = text/plain words = 1670 sentences = 90 flesch = 37 summary = High mobility group box 1 protein (HMGB1) is released by necrotic cells or activated macrophages/monocytes, and functions as a late mediator of lethal systemic and local pulmonary inflammation. In light of observations that three Chinese herbal formulations recommended for treatment of severe acute respiratory syndrome (SARS) specifically inhibited the release of HMGB1 from innate immune cells, we hypothesize that HMGB1 might occupy a pathogenic role in SARS by mediating an injurious pulmonary inflammatory response. High mobility group box 1 protein (HMGB1, formerly known as HMG-1 or amphoterin) has recently been identified as a new proinflammatory cytokine and a late mediator of inflammation, sepsis, and acute lung injury. In light of observations that several Chinese herbal remedies recommended for treatment of SARS specifically inhibited the release of HMGB1 from activated innate immune cells, we hypothesize that HMGB1 might occupy a pathogenic role in SARS by mediating an injurious pulmonary inflammatory response. cache = ./cache/cord-289332-hvakv08t.txt txt = ./txt/cord-289332-hvakv08t.txt === reduce.pl bib === id = cord-293059-2iwzieqm author = Tao, Huaqiang title = Dysimmunity and inflammatory storm: Watch out for bone lesions in COVID-19 infection date = 2020-10-06 pages = extension = .txt mime = text/plain words = 1818 sentences = 104 flesch = 38 summary = It has been approved that inflammation-induced pathogenesis in COVID-19 infection has a strong correlation with incidence of cardiovascular metabolic diseases and gastrointestinal injury (1) . However, studies on the correlation between pro-inflammatory cytokine responses and bone metabolism in COVID-19 patients are still lacking. In this special background, will inflammatory disorder and immune imbalance affect bone metabolism after COVID-19 infection? Simultaneously, hypoxia inducible factor (HIF-1) was proven to facilitate osteoclast differentiation by overexpressing RANKL and nuclear factor of activated T cells cytoplasmic 1 (NFATc1) (14) . As osteoblasts and osteoclasts exist in approach with immune cells in medullary cavity, it's no wonder that immune system shares massive regulatory cytokines, signaling molecules and transcription factors with bone biology. Apart from that, NF-κB and AP-1 stimulate the expression of many elements which required for inflammatory cytokines, driving up osteoclast activity and usually implicated inhibition on proliferation and differentiation of osteoblasts (22) . cache = ./cache/cord-293059-2iwzieqm.txt txt = ./txt/cord-293059-2iwzieqm.txt === reduce.pl bib === id = cord-291781-gs81g1db author = Caruso, Arturo Armone title = Hydrogen peroxide and viral infections: a literature review with research hypothesis definition in relation to the current covid-19 pandemic date = 2020-06-01 pages = extension = .txt mime = text/plain words = 1379 sentences = 83 flesch = 37 summary = We reviewed the literature concerning the innate response from nasal and oral epithelial cells and their reaction to hydrogen peroxide (H(2)O(2)). Therefore, nose/mouth/throat washing with hydrogen peroxide may enhance those local innate responses to viral infections and help protect against the current coronavirus pandemic. [2] We reviewed the literature concerning the innate response from nasal and oral epithelial cells to evaluate the role of hydrogen peroxide (H 2 O 2 ). [5] Virus-induced oxidative stress plays an important role in the regulation of the host immune system and the specific oxidant-sensitive pathway is one of the effective strategies against viral infections. [5] Virus-induced oxidative stress plays an important role in the regulation of the host immune system and the specific oxidant-sensitive pathway is one of the effective strategies against viral infections. There are no randomized controlled trials or clinical observational studies concerning the curative or preventive effect of hydrogen peroxide against viral infections. cache = ./cache/cord-291781-gs81g1db.txt txt = ./txt/cord-291781-gs81g1db.txt === reduce.pl bib === === reduce.pl bib === id = cord-296253-bxyzhsfs author = Elham, Elzat title = Anatomic evidence shows that lymphatic drainage exists in the pituitary to loop the cerebral lymphatic circulation date = 2020-05-30 pages = extension = .txt mime = text/plain words = 1686 sentences = 87 flesch = 41 summary = To determine whether the perinasal lymphatic system or lymphatic vessels are involved in cerebral immune defence and play a role in causing CNS infections (especially respiratory tract-related infections), we performed an anatomic study to investigate the drainage differences between the perinasal and intracerebral lymphatic systems by using injection of Evans blue and anatomic surgery, together with immunohistochemistry and immunofluorescence assays. To determine whether the perinasal lymphatic system or lymphatic vessels are involved in cerebral immune defence and play a role in causing CNS infections (especially respiratory tract-related infections), we performed an anatomic study to investigate the drainage differences between the perinasal and intracerebral lymphatic systems by using injection of Evans blue and anatomic surgery, together with immunohistochemistry and immunofluorescence assays. Under an anatomic (20× magnification) microscope, we dissected the mouse intracranial nervous system after injection of Evans blue (perinasal lymphatic reflux assay) and found that lymphatic vessels that exist in the pituitary and loop the cerebral lymphatic circulation are responsible for the perinasal-pituitary lymphatic drainage. cache = ./cache/cord-296253-bxyzhsfs.txt txt = ./txt/cord-296253-bxyzhsfs.txt === reduce.pl bib === id = cord-303022-9hqoq7tf author = Madapusi Balaji, Thodur title = Oral cancer and periodontal disease increase the risk of COVID 19? A mechanism mediated through furin and cathepsin overexpression date = 2020-06-01 pages = extension = .txt mime = text/plain words = 888 sentences = 54 flesch = 47 summary = In addition to furin, another protease cathepsin L is also elevated in chronic periodontitis and oral cancer, which in turn could be a result of the interleukin 6 mediated activation of the caveolin -1 mediated JNK-AP-1 signaling pathway [8] [9] [10] . 3) Following binding of the S1 subunit to the ACE-2 receptors, the virus fuses with the host cell in two mechanisms: (a) endosomal fusion which is mediated by cysteine proteases cathepsin B/L and (b) plasma membrane fusion mediated by the serine protease TMPRSS2. Based on the above-mentioned data, it can be hypothesized that the increased protease levels in chronic periodontitis and oral cancer could potentially increase the risk of an oral mucosa mediated SARS-corona virus-2 infection (figure 1). In addition to increasing proteases, chronic periodontitis, and oral cancer patients have also reported having a low melatonin level [14, 15] . cache = ./cache/cord-303022-9hqoq7tf.txt txt = ./txt/cord-303022-9hqoq7tf.txt === reduce.pl bib === === reduce.pl bib === id = cord-301619-0ojayw16 author = Adamowicz, Jan title = May patients receiving 5-alpha-reductase inhibitors be in higher risk of COVID-19 complications ? date = 2020-04-22 pages = extension = .txt mime = text/plain words = 1203 sentences = 76 flesch = 36 summary = Based on this observation, our proposed hypothesis is that 5-alpha-reductase inhibitors, that are commonly used for BPH treatment, may be one of the factors contributing to poorer prognosis in males. Based on this observation, our proposed hypothesis is that 5-alpha-reductase inhibitors, that are commonly used for BPH treatment, may be one of the factors contributing to poorer prognosis in males. Consequently, we introduce hypothesis that 5-alpha-reductase inhibitors may disrupt androgens metabolism in lungs, which in turn may have a negative impact on course of COVID-19 infection. Under this assumption, 5-alpha-reductase inhibitors might increase androgen concentration in lungs hampering their regeneration. Due to high prevalence of 5-alpha-reductase inhibitor in BPH treatment, its potential negative influence on recovery after COVID-19 infection, should be established. According to presented hypothesis, patients receiving 5-alpha-reductase inhibitors, might be vulnerable to COVID-19 infection with poorer prognosis. May patients receiving 5 alpha-reductase inhibitors be in higher risk of COVID-19 complications cache = ./cache/cord-301619-0ojayw16.txt txt = ./txt/cord-301619-0ojayw16.txt === reduce.pl bib === === reduce.pl bib === id = cord-308279-gsk4qel5 author = Suzuki, Yuichiro J. title = The viral protein fragment theory of COVID-19 pathogenesis date = 2020-09-11 pages = extension = .txt mime = text/plain words = 1397 sentences = 70 flesch = 44 summary = I herein propose the viral protein fragment theory of COVID-19 pathogenesis based on my observations in cultured human vascular cells that SARS-CoV-2 spike protein can activate cell signaling events without the rest of the viral components. I hypothesize that, as humans are infected with SARS-CoV-2, the virus releases a fragment of the spike protein that can target host cells for eliciting cell signaling without the rest of the viral components. This hypothesis is based on my experimental observations in cultured human vascular cells that the recombinant full length S1 subunit of SARS-CoV-2 spike protein can activate cell signaling events without the rest of the viral components. I propose a scenario that, as humans are infected with SARS-CoV-2, the virus releases a fragment of the spike protein that can target host cells for eliciting cell signaling. cache = ./cache/cord-308279-gsk4qel5.txt txt = ./txt/cord-308279-gsk4qel5.txt === reduce.pl bib === id = cord-297178-moxhk2e0 author = Novaes Rocha, Vinicius title = Viral replication of SARS-CoV-2 could be self-limitative - the role of the renin-angiotensin system on COVID-19 pathophysiology date = 2020-10-01 pages = extension = .txt mime = text/plain words = 3272 sentences = 184 flesch = 46 summary = Caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the coronavirus disease 2019 (COVID-19) is provoking devastating consequences on economic and social fields throughout all continents. Amongst the components of rennin-angiotensin system (RAS), the angiotensin-converting enzyme 2 (ACE2) has gained great prominence for being directly associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the coronavirus related to COVID-19 [4, 5] . ACE2 is a fundamental piece in the pathophysiology of COVID-19, since the high replication capacity of SAR-CoV-2 is directly related to the coupling to ACE2 and cell infection. The ACE2 level reduction caused by SARS-CoV-2 infection may be directly related to the pathogenesis of COVID-19 [26] . The reduction in ACE2 expression may be related to pulmonary inflammation and subsequent cytokine storm seen in patients with severe COVID-19. Tumor necrosis factor-alpha convertase (ADAM17) mediates regulated ectodomain shedding of the severeacute respiratory syndrome-coronavirus (SARS-CoV) receptor, angiotensinconverting enzyme-2 (ACE2) cache = ./cache/cord-297178-moxhk2e0.txt txt = ./txt/cord-297178-moxhk2e0.txt === reduce.pl bib === id = cord-302212-zt4lv5g4 author = Patruno, Cataldo title = COVID-19, QUARANTINE, AND ATOPIC DERMATITIS date = 2020-05-19 pages = extension = .txt mime = text/plain words = 418 sentences = 27 flesch = 41 summary = Atopic dermatitis (AD) is a chronic inflammatory skin disease affecting up to 20% of children and up to 10% of adults (1) . Its pathogenesis involves environmental factors that interact with genetic skin barrier defects and immune Th2 Adverse psychological effects induced by the COVID-19 quarantine have been associated with increase of itch in some chronic skin disease, also due to neuroendocrine modulation of skin inflammation (4). Obviously, quarantine is associated with less exposure to sunlight that, together with high temperature and low humidity, may exert an immunosuppressive effect on skin inflammation of AD (2) . All these considerations suggest the hypothesis that COVID-19 pandemic may be associated with changes in lifestyle of AD patients that can significantly influence their clinical disease activity. Effects of climate change on skin diseases Mass quarantine measures of COVID-19 pandemic: psychosocial implications for chronic skin conditions and a call for qualitative studies cache = ./cache/cord-302212-zt4lv5g4.txt txt = ./txt/cord-302212-zt4lv5g4.txt === reduce.pl bib === id = cord-311673-z4hkw17g author = Uzzan, Mathieu title = Why is SARS-CoV-2 infection more severe in obese men? The gut lymphatics - lung axis hypothesis date = 2020-06-23 pages = extension = .txt mime = text/plain words = 2969 sentences = 154 flesch = 40 summary = As the visceral fat possesses an intense immune activity, is involved in metabolic syndrome and is at the crossroad between the intestines, the systemic circulation and the lung, we hypothesized that it plays a major role in severe forms of SARS-CoV-2 infection. Several factors may increase intestinal permeability including, direct enterocyte damage by SARS-CoV2, systemic inflammatory response syndrome (SIRS) and epithelial ischemia secondary to SARS-CoV2associated endothelial dysfunction. This increase permeability further leads to translocation of microbial components such as MAMPS (microbial-associated molecular pattern), triggering an inflammatory immune response by TLR-expressing cells of the mesentery fat (mostly macrophages and adipocytes). As the increased volume of mesentery fat in overweight men play a key role in the occurrence of metabolic syndrome [8] , we hypothesized that the visceral adipose tissue plays a central role in severe forms of COVID-19. cache = ./cache/cord-311673-z4hkw17g.txt txt = ./txt/cord-311673-z4hkw17g.txt === reduce.pl bib === id = cord-306146-i4a74j3r author = Fitzgerald, Paul J. title = Noradrenergic and serotonergic drugs may have opposing effects on COVID-19 cytokine storm and associated psychological effects date = 2020-06-09 pages = extension = .txt mime = text/plain words = 573 sentences = 37 flesch = 33 summary = In addition to its role in various psychiatric, neurologic, and cardiovascular functions, there is increasing evidence that NE plays a role in the symptomatology associated with serious systemic infections such as influenza, including activation of cytokine signaling such as IL-6 as well as the manifestation of psychological effects associated with infection 3 . I suggest here that this cytokine storm may be counteracted by a range of clinically used drugs that reduce NE transmission (but that may not act through direct effects on viral replication or viral entry into cells) 5 : alpha2 agonists such as clonidine, guanfacine, dexmedetomidine; various beta blockers such as propranolol, nebivolol, carvedilol, atenolol; and various alpha1 antagonists such as prazosin 4 . If COVID-19 is accompanied by systemically elevated NE signaling, the various drugs listed above may also counteract deleterious psychological effects associated with this infection 3 . Conflicts of interest The author reports no conflicts of interest, and no funding source directly supported this work cache = ./cache/cord-306146-i4a74j3r.txt txt = ./txt/cord-306146-i4a74j3r.txt === reduce.pl bib === id = cord-310217-p9nqcz5d author = Nikolina, Basic-Jukic title = Can hyperimmune anti-CMV globuline substitute for convalescent plasma for treatment of COVID-19? date = 2020-05-31 pages = extension = .txt mime = text/plain words = 648 sentences = 43 flesch = 40 summary = Currently available expert opinions suggest reduction of immunosuppression therapy for renal transplant recipients with symptomatic COVID-19 infection with either antiviral drugs, hydroxychloroquine and/or azithromycin. Currently available expert opinions suggest reduction of immunosuppression therapy for renal transplant recipients with symptomatic COVID-19 Inspired by our experience in treatment of CMV pneumonia and literature data on the potential benefit of convalescent plasma for treatment of different viral diseases we suggest use of the hyperimmune anti-CMV gamma globulins in addition to other available therapies. Inspired by our experience in treatment of CMV pneumonia and literature data on the potential benefit of convalescent plasma for treatment of different viral diseases we suggest use of the hyperimmune anti-CMV gamma globulins in addition to other available therapies. In conclusion, we suggest the use of hyperimmune anti-CMV immunoglobulins for treatment of COVID-19 especially when occur as coinfection with CMV instead of the convalescent plasma which may be unavailable for majority of patient. cache = ./cache/cord-310217-p9nqcz5d.txt txt = ./txt/cord-310217-p9nqcz5d.txt === reduce.pl bib === === reduce.pl bib === id = cord-289049-4ozwhcyi author = Roncati, Luca title = Renin-angiotensin system: The unexpected flaw inside the human immune system revealed by SARS-CoV-2 date = 2020-03-21 pages = extension = .txt mime = text/plain words = 383 sentences = 27 flesch = 44 summary = title: Renin-angiotensin system: The unexpected flaw inside the human immune system revealed by SARS-CoV-2 Medical Hypotheses journal homepage: www.elsevier.com/locate/mehy Renin-angiotensin system: The unexpected flaw inside the human immune system revealed by SARS-CoV-2 In humans the renin-angiotensin system is the hormone system which regulates blood pressure and vascular resistances, as well as electrolytic balance; within this important system, the angiotensinconverting enzyme (ACE), present on the surface of vascular endothelial cells, in particular those of the lungs, is deputed to the conversion of angiotensin I to angiotensin II (AII), a potent vasoconstrictive peptide [1] . In addition, homologous ACE2 receptors have been identified on the oral mucosa, in type-II pneumocytes, along the intestine and on the kidney and heart endothelia [1, 2] ; these receptors have been found overexpressed in course of ACE inhibitors and AII receptor antagonists administration in murine models [3, 4] . Angiotensin-converting enzyme 2-a new cardiac regulator Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential therapeutic target Upregulation of angiotensin-converting enzyme (ACE) 2 in hepatic fibrosis by ACE inhibitors cache = ./cache/cord-289049-4ozwhcyi.txt txt = ./txt/cord-289049-4ozwhcyi.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-322880-zfc9w5y6 author = Rohit, Anusha title = Respiratory droplets get suspended longer and spread wider in temperate environments compared to tropics and implications for SARS-CoV-2 transmission date = 2020-06-09 pages = extension = .txt mime = text/plain words = 1852 sentences = 92 flesch = 55 summary = title: Respiratory droplets get suspended longer and spread wider in temperate environments compared to tropics and implications for SARS-CoV-2 transmission The combined effect of change in size of the droplet as well as the density amplifies the influence that environmental relative humidity would have on the particle settling velocity. It is possible that droplets discharged from infected individuals in places like New York City could shrink in size quickly and remain airborne for considerable period of time. A simple understanding of the mechanics of droplet size, dispersion and displacement could help infection control and public health measures to minimize spread and mitigate the risk of people getting infected especially in hotspots like hospital environments or other closed spaces. A simple understanding of the mechanics of droplet size, dispersion and displacement could help infection control and public health measures to minimize spread and mitigate the risk of people getting infected especially in hotspots like hospital environments or other closed spaces. cache = ./cache/cord-322880-zfc9w5y6.txt txt = ./txt/cord-322880-zfc9w5y6.txt === reduce.pl bib === id = cord-319822-h1zm94p4 author = Carelli, Pasquale title = A physicist's approach to COVID-19 transmission via expiratory droplets date = 2020-06-17 pages = extension = .txt mime = text/plain words = 1412 sentences = 61 flesch = 58 summary = My thesis is supported and described on the basis of a physicist's model which studies the droplets behavior when emitted by the respiratory apparatus of an infected person, symptomatic or not. The intermediate dimensioned droplets are proved to be changed into aerosol, losing their water content and becoming seriously contagious, but in their initial phase they could be easily caught by a simple surgical mask. This habit, There are non doubts about the fact that expiratory particles transmit the pandemic, but we must make a coarse distinction among droplets and their dynamic evolutions when emitted by infected people. These droplets have a substantial viral load, they are quite numerous, some thousands of them can contain just one single virion each and they are probably the most contagious and dangerous elements[14]; if not stopped on time, they constitute the real element of airborne infection [15] . cache = ./cache/cord-319822-h1zm94p4.txt txt = ./txt/cord-319822-h1zm94p4.txt === reduce.pl bib === === reduce.pl bib === id = cord-331140-5b0y1xzb author = Cardona Maya, Walter D. title = SARS-CoV-2 and Prostatitis: dangerous relationship for male sexual and reproductive health date = 2020-06-01 pages = extension = .txt mime = text/plain words = 326 sentences = 30 flesch = 58 summary = key: cord-331140-5b0y1xzb title: SARS-CoV-2 and Prostatitis: dangerous relationship for male sexual and reproductive health cord_uid: 5b0y1xzb . Recently, SARS-CoV-2 was detected in semen samples (5) . Therefore, it is not unreasonable to believe that the latest coronavirus could potentially be transmitted via semen (6) . It was also reported that angiotensin converting enzyme 2 (ACE2) is a functional receptor that mediates the entry of SARS-CoV-1 (7) and 2 (8) , and this receptor is expressed in the prostate. Perhaps in the coming years, the real effect of SARS-CoV-2 on prostatitis cases will be evaluated and scope for researching factors that cause the clinical syndrome will be expanded. Male infertility: a public health issue caused by sexually transmitted pathogens Clinical Characteristics and Results of Semen Tests Among Men With Coronavirus Disease SARS-CoV-2 and the Testis: similarity to other viruses and routes of infection Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus cache = ./cache/cord-331140-5b0y1xzb.txt txt = ./txt/cord-331140-5b0y1xzb.txt === reduce.pl bib === id = cord-320959-sgdqhtns author = Lee, Hanjun title = Vitamin E Acetate as Linactant in the Pathophysiology of EVALI date = 2020-08-12 pages = extension = .txt mime = text/plain words = 6709 sentences = 305 flesch = 34 summary = In membrane biophysics, Vitamin E is a linactant and a potent modulator of lateral phase separation that effectively reduces the line tension at the two-dimensional phase boundaries and thereby exponentially increases the surface viscosity of the pulmonary surfactant. Supplementation of pulmonary surfactants which retain moderate level of cholesterol and 10 controlled hypothermia for patients are recommended when the hypothesis that the line-active property of the vitamin derivative drives the pathogenesis of EVALI holds. Currently, there are 5 five established non-antioxidative properties of Vitamin E in the biological system: i) its ability to induce gel-liquid crystalline phase transition, ii) its active deposition in the lipid droplet of macrophages, iii) its modulation of the antidiabetic cascade involving diacylglycerol kinase (DGK) and protein kinase C (PKC), iv) its activation of the xenobiotic-sensing pregnane X receptor (PXR) signaling, and v) its ability to modulate lateral phase separation. cache = ./cache/cord-320959-sgdqhtns.txt txt = ./txt/cord-320959-sgdqhtns.txt === reduce.pl bib === id = cord-337493-8yhd697t author = Choquenaira-Quispe, Celia title = Factors involved in low susceptibility to covid-19: an adaptation of high altitude inhabitants date = 2020-07-02 pages = extension = .txt mime = text/plain words = 312 sentences = 36 flesch = 49 summary = key: cord-337493-8yhd697t authors: Choquenaira-Quispe, Celia; Saldaña-Bobadilla, Vanessa; Kenedy Ramirez, J. title: Factors involved in low susceptibility to covid-19: an adaptation of high altitude inhabitants cord_uid: 8yhd697t Consequently, populations from high altitude areas would be less susceptible to hypoxia during the infection. Consequently, SARS-CoV-2 infected populations from high altitude areas have greater lung adaptive capacity than those that live at low altitude. The three factors above would perform an important role in high altitude inhabitants, because they decrease the susceptibility to develop severe symptoms in SARS-CoV-2 infection. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study Hepcidin and anemia: A tight relationship Does the pathogenesis of SARS-CoV-2 virus decrease at high-altitude? HIF stabilizers in the management of renal anemia: from bench to bedside to pediatrics The authors declare that there is no conflict of interest. The authors declare that there is no conflict of interest. cache = ./cache/cord-337493-8yhd697t.txt txt = ./txt/cord-337493-8yhd697t.txt === reduce.pl bib === id = cord-323749-lvtfv7ny author = Sai Suresh Chalichem, Nehru title = Aminoglycosides can be a better choice over Macrolides in COVID-19 regimen: Plausible Mechanism for repurposing strategy date = 2020-06-10 pages = extension = .txt mime = text/plain words = 938 sentences = 61 flesch = 46 summary = Although macrolides like azithromycin and clarithromycin etc., have been reported to act against respiratory infections but they lack the ability of immunity enhancement through defensins. The aminoglycosides were proved to have defensin mediated antiviral activity, that could enhance the immunity. So, Consideration of aminoglycosides can be a double edge sword viz., against respiratory infection as well as Immunity enhancer (along with anti-virals) for COVID-19 regimen. Although various nations throughout the globe making several strategies viz, different drug combinations, proposing lock downs and herd immunity etc., to control the wide spread of COVID-19 and to tolerate its severity, the radical behaviour of virus is evident. In the instances like current pandemic of COVID-19, where infection control becomes a great challenge, immune mediators could be a vital link. However, aminoglycosides (AGs) were proved to produce functional peptides from theta defensins (called as retrocyclins) that are active against HIV 10 . cache = ./cache/cord-323749-lvtfv7ny.txt txt = ./txt/cord-323749-lvtfv7ny.txt === reduce.pl bib === id = cord-327809-9uhhqasl author = Dimitriu, Mihai C.T. title = Burnout syndrome in Romanian medical residents in time of the COVID-19 pandemic date = 2020-06-07 pages = extension = .txt mime = text/plain words = 3109 sentences = 164 flesch = 49 summary = A study in China, comparing burnout of front line workers with that of normal ward staff, in COVID context, used Maslach questionnaire for medical workers and the results were interesting and quite unexpected [3] . The aim of our study was to compare the frequency of burnout syndrome between medical residents considered to work on the front line (emergency unit, radiology and intensive care unit) and those working in normal hospital wards (surgery, obstetrics and gynecology, obstetrics). The burnout was significantly more frequent in normal wards workers (lot B) (prevalence 86%) compared to medical residents working in places that we considered front-line departments: emergency unit, radiology, including CT/MRI department and intensive care unit -lot A in our study, that showed a prevalence of burnout of only 66% (p<0.05, from chi-square statistic test) (table 2). cache = ./cache/cord-327809-9uhhqasl.txt txt = ./txt/cord-327809-9uhhqasl.txt === reduce.pl bib === id = cord-338585-ep9r1n8t author = Perrin, David M. title = A hypothesis for examining dihydroxyacetone, the active component in self-tanning products, as a topical prophylactic against SARS-COV-2 transmission date = 2020-09-16 pages = extension = .txt mime = text/plain words = 1800 sentences = 84 flesch = 42 summary = title: A hypothesis for examining dihydroxyacetone, the active component in self-tanning products, as a topical prophylactic against SARS-COV-2 transmission This hypothesis raises the interesting prospect that dihydroxyacetone (DHA), the key ingredient in self-tanning creams, when applied daily to the face and hands may have prophylactic action against SARS-COV-2 transmission and infection. The Maillard Reaction, comprises a manifold of reactions including Schiff-base formation, aldol-type condensations, Amadori rearrangements, and dehydrative and/or oxidative aromatization events that modify lysine amines and give rise to crosslinks, (12) which are consistent with other advanced glycation events seen in diabetic patients. Together, such studies would systematically advance this hypothesis from well-established in vitro results to an easily monitored clinical trial, that would lead to a medically justified recommendation for daily topical prophylactic application of DHA to the face and hands for reducing SARS-COV-2 infection. cache = ./cache/cord-338585-ep9r1n8t.txt txt = ./txt/cord-338585-ep9r1n8t.txt === reduce.pl bib === id = cord-332365-20u06444 author = Raciti, Loredana title = Can volcanic trace elements facilitate Covid-19 diffusion? A hypothesis stemming from the Mount Etna area, Sicily date = 2020-06-27 pages = extension = .txt mime = text/plain words = 3653 sentences = 188 flesch = 47 summary = We suppose that ash and gases emitted from the Mount Etna contributed to air pollution, potentially favouring the major contagion of COVID-19 in the eastern flank of the mountain, as in Catania city. Heavy metals have been dosed in the groundwater of the Etna (used for water plants or to drink), especially in the eastern and southern sectors of the volcano, and they are believed to contribute to intoxication of public health and to pulmonary or neurodegenerative diseases [12, 14, 15] . This is the first paper that elaborates the hypothesis of a potential role of volcanic gases and heavy metals-related air pollution, combined to specific climatic conditions and regional topography, in favouring severe COVID-19 diffusion in Sicily. This is the first paper that elaborates the hypothesis of a potential role of volcanic gases and heavy metals-related air pollution, combined to specific climatic conditions and regional topography, in favouring severe COVID-19 diffusion in Sicily. cache = ./cache/cord-332365-20u06444.txt txt = ./txt/cord-332365-20u06444.txt === reduce.pl bib === id = cord-328587-vctvcyim author = Jun, Sun title = The hypothesis that SARS-CoV-2 affects male reproductive ability by regulating autophagy date = 2020-07-10 pages = extension = .txt mime = text/plain words = 2990 sentences = 143 flesch = 47 summary = According to the existing clinical data, some patients not only suffer from respiratory diseases, but also have complications such as acute renal injury and even renal necrosis [2] [3] [4] , in addition, SARS-CoV-2 was also found in recent semen analysis of male patients [5] . Previous clinical data have shown that in addition to respiratory diseases, some male patients with COVID-19 are accompanied by kidney damage and even renal failure [2] [4], which suggest that SARS-CoV-2 may affect male fertility. Furthermore, clinical data also show that the receptor protein ACE2 that mediates the entry of SARS-CoV-2 into host cells is not only expressed in alveolar cells, but also highly expressed in male renal tubular cells [4] [21] [30] .All these suggest that SARS-CoV-2 not only causes damage to the respiratory system of patients, but also has a certain impact on the reproductive system of male patients. cache = ./cache/cord-328587-vctvcyim.txt txt = ./txt/cord-328587-vctvcyim.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-320508-egw7bvzf author = Kennedy, James R. title = Phosphatidylserine’s role in Ebola’s inflammatory cytokine storm and hemorrhagic consumptive coagulopathy and the therapeutic potential of annexin V date = 2019-10-28 pages = extension = .txt mime = text/plain words = 2478 sentences = 113 flesch = 45 summary = The phosphatidylserine (PS) molecule is present in cell membranes where it is actively kept on their inner leaflets but when cells are damaged it moves to the surface and become a signal for their removal, the platform upon which the coagulation cascade takes place and a ligand that activates a feedback cycle of inflammatory cytokine secretion and initiates the wakeup call for the innate immune response. The phosphatidylserine (PS) molecule is present in cell membranes where it is actively kept on their inner leaflets but when cells are damaged it moves to the surface and become a signal for their removal, the platform upon which the coagulation cascade takes place and a ligand that activates a feedback cycle of inflammatory cytokine secretion and initiates the wakeup call for the innate immune response. The hypothesis presented here is that annexin V's therapeutic administration in Ebola can prevent its Th1 cell generated inflammatory cytokine storm, stop the cascade generated hemorrhagic consumptive coagulopathy and prevent macrophage and dendritic cell infection. cache = ./cache/cord-320508-egw7bvzf.txt txt = ./txt/cord-320508-egw7bvzf.txt === reduce.pl bib === === reduce.pl bib === id = cord-299911-v95pf3eg author = El-Ghiaty, Mahmoud A. title = Cytochrome P450-mediated drug interactions in COVID-19 patients: current findings and possible mechanisms date = 2020-06-26 pages = extension = .txt mime = text/plain words = 5319 sentences = 272 flesch = 37 summary = Based on the conclusions drawn from the currently rapidly evolving knowledge about COVID-19, our hypothesis is built on the potential modulation of CYPs activity by the inflammatory environment provoked by SARS-CoV-2 infection, as well as the pathologic involvement of the liver which harbors the majority of the drug metabolizing enzymes (DMEs). Systemic inflammation and immune response represent a substantial element in many acute and chronic diseases which is strongly implicated in altering drug pharmacokinetics through, mainly, modulating the expression and activity of DMEs. As a main contributor to the metabolic biotransformation of most drugs, CYPs are widely involved in such disease-drug interactions [19] . For decades, IL-6 has been recognized as the major inflammatory element that provokes a significant repressive effect on the expression and activity of different CYPs. Human recombinant interleukin 6 (rhIL-6) has shown concentration-dependent blocking of phenobarbital-mediated induction of CYP2B1/2 mRNA and activity in rat hepatocytes [48] . cache = ./cache/cord-299911-v95pf3eg.txt txt = ./txt/cord-299911-v95pf3eg.txt === reduce.pl bib === id = cord-279138-dmhphgp5 author = Deek, Sarah A. title = Chronic Exposure to Air Pollution Implications on COVID-19 Severity date = 2020-09-28 pages = extension = .txt mime = text/plain words = 1544 sentences = 88 flesch = 35 summary = Populations in areas with higher levels of air pollution both indoors and outdoors show increased mortality rates when infected with coronavirus disease 2019 (COVID-19). In this paper, fine particulate matter (PM) is identified as a source of disrupted activation of the hypothalamic–pituitary–adrenal (HPA) axis; therefore, a contributable variable to COVID-19 mortality. Populations in areas with higher levels of air pollution both indoors and outdoors show increased mortality rates when infected with coronavirus disease 2019 . In this paper, fine particulate matter (PM) is identified as a source of disrupted activation of the hypothalamicpituitary-adrenal (HPA) axis; therefore, a contributable variable to COVID-19 mortality. Therefore, chronic exposure to fine PM may be contributable variable that disrupts HPA system activation typically associated with the altered regulation of circulating glucocorticoids resulting in inefficient or delayed immune response to COVID-19 infection. cache = ./cache/cord-279138-dmhphgp5.txt txt = ./txt/cord-279138-dmhphgp5.txt === reduce.pl bib === id = cord-349718-x5i460bc author = Chandrasekaran, Baskaran title = Dr. Chandrasekaran’s reply to “Exercising and face masks: an important hypothesis buried in a selective review” date = 2020-09-23 pages = extension = .txt mime = text/plain words = 1271 sentences = 57 flesch = 45 summary = Dr. Chandrasekaran's reply to "Exercising and face masks: an important hypothesis buried in a selective review" This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. Dr. Chandrasekaran's reply to "Exercising and face masks: an important hypothesis buried in a selective review" Thank you very much for your interest and critical feedback on our recent hypothesis article published in "Medical Hypotheses" journal. Firstly, we would like to clarify to the authors and readers that our article focuses only on the possible physiological mechanisms that could be associated with wearing the tight custom made cloth masks during moderate to heavy exercise (60 -80% VO2 max or above anaerobic threshold). Our hypothesis pertains to the use of tight custom made masks during moderate to vigorous exercise, not general household work nor in healthcare professionals. cache = ./cache/cord-349718-x5i460bc.txt txt = ./txt/cord-349718-x5i460bc.txt === reduce.pl bib === id = cord-353716-gxgvhhv1 author = Kumar, Ashutosh title = SARS-CoV-2 cell entry receptor ACE2 mediated endothelial dysfunction leads to vascular thrombosis in COVID-19 patients date = 2020-09-30 pages = extension = .txt mime = text/plain words = 2300 sentences = 136 flesch = 40 summary = title: SARS-CoV-2 cell entry receptor ACE2 mediated endothelial dysfunction leads to vascular thrombosis in COVID-19 patients Based on the circumstantial evidence present in the literature, we propose a SARS-CoV-2 cell entry receptor ACE2 based mechanism for vascular thrombosis in COVID-19 patients. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative pathogen for COVID-19 has been shown to bind to angiotensin converting enzyme 2 (ACE2) protein in human epithelial cells, which facilitates its entry in the organ and mediate tissue specific pathogenesis (4,5). Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative pathogen for COVID-19 has been shown to bind to angiotensin converting enzyme 2 (ACE2) protein in human epithelial cells, which facilitates its entry in the organ and mediate tissue specific pathogenesis (4,5). SARS-CoV-2 binding to the cell entry receptor ACE2 downregulates receptor expression that in turn induces vascular endothelial dysfunction, which activates prothrombotic cascade and eventually leads to vascular thrombosis observed in COVID-19 patients. cache = ./cache/cord-353716-gxgvhhv1.txt txt = ./txt/cord-353716-gxgvhhv1.txt === reduce.pl bib === id = cord-352911-9wbq9qo2 author = de Oliveira, Pedro Gonçalves title = Diacerein: a potential multi-target therapeutic drug for COVID-19 date = 2020-06-01 pages = extension = .txt mime = text/plain words = 2539 sentences = 135 flesch = 45 summary = The mortality related to severe acute respiratory distress syndrome (ARDS) and multi-organ failure in COVID-19 patients has been suggested to be connected with cytokine storm syndrome (CSS), an excessive immune response that severely damages healthy lung tissue. Total extracts from monolayer cell cultures infected with SARS-CoV-2 and treated with rhein under the conditions described above will be analysed using commercially available protein arrays to determine the levels and activation state of proteins involved in the TLR-, Akt-, MAPK-, and NF-B-regulated signalling pathways. The mechanisms of action involved include the control of hyperinflammatory conditions by multi-faceted cytokine inhibition of IL-1, IL-2, IL-6, IL-8, IL-12, IL-18 and TNF-α; anti-platelet aggregation activity; and potential effects on viral infection and replication. Rhein suppresses lung inflammatory injury induced by human respiratory syncytial virus through inhibiting NLRP3 inflammasome activation via NF-κB pathway in mice cache = ./cache/cord-352911-9wbq9qo2.txt txt = ./txt/cord-352911-9wbq9qo2.txt === reduce.pl bib === id = cord-346281-sma6e891 author = Maldonado, Valente title = Repositioning of pentoxifylline as an immunomodulator and regulator of the renin-angiotensin system in the treatment of COVID-19 date = 2020-06-09 pages = extension = .txt mime = text/plain words = 5711 sentences = 260 flesch = 35 summary = Pentoxifylline (PTX) is a phosphodiesterase inhibitor that increases cyclic adenosine monophosphate levels, which in turn activate protein kinase, leading to a reduction in the synthesis of proinflammatory cytokines to ultimately influence the renin-angiotensin system (RAS) in vitro by inhibiting angiotensin 1 receptor (AT1R) expression. The rheological, anti-inflammatory, and renin-angiotensin axis properties of PTX highlight this drug as a therapeutic treatment alternative for patients with COVID-19 by helping reduce the production of the inflammatory cytokines without deleterious effects on the immune system to delay viral clearance. 5 Overall, the rheological, anti-inflammatory, and renin-angiotensin axis properties of PTX highlight this drug as a therapeutic treatment alternative for patients with COVID-19, which can help reduce the production of the inflammatory cytokines TNF-α, IL-6, IFN-γ, and IL-17 and increase the anti-inflammatory cytokine IL-10. cache = ./cache/cord-346281-sma6e891.txt txt = ./txt/cord-346281-sma6e891.txt === reduce.pl bib === === reduce.pl bib === id = cord-334543-gavnscor author = Lim, Rachel K. title = Are night shift workers at an increased risk for COVID-19? date = 2020-07-29 pages = extension = .txt mime = text/plain words = 894 sentences = 57 flesch = 49 summary = This potential relationship between SARS-CoV-2 infection and clock genes, coupled with previously reported effects of night shift work on health leads us to hypothesize that night shift workers may be at an increased physiological risk of coronavirus disease-19 (COVID19) . This potential relationship between SARS-CoV-2 infection and clock genes, coupled with previously reported effects of night shift work on health leads us to hypothesize that night shift workers may be at an increased physiological risk of coronavirus disease-19 (COVID19) . The mechanisms that drive these associations are not well understood; however, current literature suggests that the disruption of circadian rhythms may cause downstream hormonal and immune effects that render night shift workers more susceptible to disease. The mechanisms that drive these associations are not well understood; however, current literature suggests that the disruption of circadian rhythms may cause downstream hormonal and immune effects that render night shift workers more susceptible to disease. cache = ./cache/cord-334543-gavnscor.txt txt = ./txt/cord-334543-gavnscor.txt === reduce.pl bib === === reduce.pl bib === id = cord-334709-z70oevy2 author = Niv, Yaron title = Defensin 5 for prevention of SARS-CoV-2 invasion and Covid-19 Disease date = 2020-09-04 pages = extension = .txt mime = text/plain words = 1372 sentences = 72 flesch = 51 summary = Similarly, to other corona viruses and influenza A, the receptor for adherence of SARS-CoV-2 is ACE2 which is abundant on respiratory and gastrointestinal mucosal cells, especially on alveolar type 2 pneumocytes [2] . Theoretically using of recombinant S1 protein, which will attach to the ACE2 receptors, may actively compete with the SARS-CoV-19 and prevent infection. They found affinity of HDEF5 binding to ACE2 of 76.2 nM, efficient blocking of SARS-CoV-2 receptor binding domain (RBD), and significant inhibition of invasion into Caco-2 cells. The next step, after preparing recombinant HDEF5, active and functioning, with high affinity to both receptor and ligand, is to make the protein available in powder, with small enough particles to be aerosolized and sprayed. Blocking the receptor for SARS-CoV-2 virus, ACE2, on the respiratory tract epithelium, especially the alveolar type 2 pneumocytes, will probably prevent invasion of the virus, at least for a short while. cache = ./cache/cord-334709-z70oevy2.txt txt = ./txt/cord-334709-z70oevy2.txt === reduce.pl bib === ===== Reducing email addresses cord-324949-sqy03dks cord-318114-q29zax2j cord-338585-ep9r1n8t cord-327809-9uhhqasl /data-disk/reader-compute/reader-cord/bin/reduce.sh: fork: retry: No child processes Creating transaction Updating adr table ===== Reducing keywords parallel: Warning: Only enough available processes to run 1 jobs in parallel. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf parallel: Warning: or /proc/sys/kernel/pid_max may help. cord-258670-dphg8ukj cord-254162-tu81j66h cord-254411-e9vvjv8w cord-253312-bf35afpj cord-261574-zcazhkad cord-261370-jp5sqqwc cord-256092-bph9ys72 cord-253468-pf0xubii cord-258272-uu6t6tnh cord-264916-c4n0kyog cord-267612-1h7xpkbe cord-268425-xg8xnjf9 cord-254094-ed1epul1 cord-270740-3su8pc3f cord-271785-vmnc8yg6 cord-274698-i3mzzxwq cord-265322-3854ddb9 cord-265724-fdt00qw1 cord-269563-2979u47a cord-270805-o6rbfmie cord-274715-dcs1rgd0 cord-276564-o21ncldx cord-275569-i5y23mmz cord-274510-fo7p98np cord-275353-ezrmuw48 cord-282853-l0c69uul cord-279138-dmhphgp5 cord-289049-4ozwhcyi cord-282899-kp114q7n cord-289905-dvl2pud2 cord-293059-2iwzieqm cord-286038-a62k3lma cord-288009-8i3gsq9p cord-281354-sa27k8o3 cord-291722-xnfdjriz cord-287824-zg5akivn cord-290803-v5ndlk9c cord-279084-bbae1qyx cord-291037-19csqq89 cord-291781-gs81g1db cord-297178-moxhk2e0 cord-302212-zt4lv5g4 cord-288733-c51lfwd6 cord-301619-0ojayw16 cord-304658-vxu33v7i cord-310928-g553afo9 cord-299911-v95pf3eg cord-312912-i1yyz5lg cord-303022-9hqoq7tf cord-306146-i4a74j3r cord-308279-gsk4qel5 cord-293860-6kz0iws6 cord-310217-p9nqcz5d cord-311673-z4hkw17g cord-318114-q29zax2j cord-314679-lmfalzni cord-313382-prxc0lue cord-317238-uszhwugw cord-331140-5b0y1xzb cord-320508-egw7bvzf cord-327809-9uhhqasl cord-315576-bgcqkz0p cord-326849-vqpwdlj7 cord-323310-tq9muytr cord-337493-8yhd697t cord-289332-hvakv08t cord-276715-d1nh2dvb cord-320959-sgdqhtns cord-323749-lvtfv7ny cord-322880-zfc9w5y6 cord-319822-h1zm94p4 cord-324949-sqy03dks cord-278271-rpq62xhl cord-296253-bxyzhsfs cord-328587-vctvcyim cord-277931-3hxhsmw8 cord-338585-ep9r1n8t cord-334709-z70oevy2 cord-337627-1a2gpqdl cord-332365-20u06444 cord-349718-x5i460bc cord-331428-6pvr2vew cord-344170-qrupbtem cord-352911-9wbq9qo2 cord-346281-sma6e891 cord-353716-gxgvhhv1 cord-334543-gavnscor Creating transaction Updating wrd table ===== Reducing urls cord-269563-2979u47a cord-275569-i5y23mmz cord-274715-dcs1rgd0 cord-286038-a62k3lma cord-289905-dvl2pud2 cord-281354-sa27k8o3 cord-349718-x5i460bc cord-314679-lmfalzni cord-344170-qrupbtem Creating transaction Updating url table ===== Reducing named entities cord-254162-tu81j66h cord-253312-bf35afpj cord-254411-e9vvjv8w cord-258670-dphg8ukj cord-258272-uu6t6tnh cord-261370-jp5sqqwc cord-265322-3854ddb9 cord-253468-pf0xubii cord-267612-1h7xpkbe cord-264916-c4n0kyog cord-254094-ed1epul1 cord-261574-zcazhkad cord-265724-fdt00qw1 cord-276715-d1nh2dvb cord-270805-o6rbfmie cord-279138-dmhphgp5 cord-286038-a62k3lma cord-274510-fo7p98np cord-271785-vmnc8yg6 cord-268425-xg8xnjf9 cord-278271-rpq62xhl cord-269563-2979u47a cord-279084-bbae1qyx cord-274698-i3mzzxwq cord-274715-dcs1rgd0 cord-291781-gs81g1db cord-276564-o21ncldx cord-275569-i5y23mmz cord-282853-l0c69uul cord-270740-3su8pc3f cord-293059-2iwzieqm cord-289332-hvakv08t cord-256092-bph9ys72 cord-301619-0ojayw16 cord-296253-bxyzhsfs cord-290803-v5ndlk9c cord-297178-moxhk2e0 cord-291037-19csqq89 cord-303022-9hqoq7tf cord-293860-6kz0iws6 cord-289049-4ozwhcyi cord-308279-gsk4qel5 cord-299911-v95pf3eg cord-311673-z4hkw17g cord-304658-vxu33v7i cord-312912-i1yyz5lg cord-313382-prxc0lue cord-310217-p9nqcz5d cord-306146-i4a74j3r cord-288733-c51lfwd6 cord-322880-zfc9w5y6 cord-302212-zt4lv5g4 cord-319822-h1zm94p4 cord-315576-bgcqkz0p cord-289905-dvl2pud2 cord-318114-q29zax2j cord-331140-5b0y1xzb cord-288009-8i3gsq9p cord-291722-xnfdjriz cord-314679-lmfalzni cord-320508-egw7bvzf cord-317238-uszhwugw cord-320959-sgdqhtns cord-323310-tq9muytr cord-327809-9uhhqasl cord-323749-lvtfv7ny cord-328587-vctvcyim cord-324949-sqy03dks cord-326849-vqpwdlj7 cord-332365-20u06444 cord-338585-ep9r1n8t cord-353716-gxgvhhv1 cord-346281-sma6e891 cord-282899-kp114q7n cord-281354-sa27k8o3 cord-287824-zg5akivn cord-277931-3hxhsmw8 cord-275353-ezrmuw48 cord-344170-qrupbtem cord-337627-1a2gpqdl cord-331428-6pvr2vew cord-310928-g553afo9 cord-334543-gavnscor cord-337493-8yhd697t cord-352911-9wbq9qo2 cord-334709-z70oevy2 cord-349718-x5i460bc Creating transaction Updating ent table ===== Reducing parts of speech cord-258670-dphg8ukj cord-253312-bf35afpj cord-256092-bph9ys72 cord-270805-o6rbfmie cord-268425-xg8xnjf9 cord-277931-3hxhsmw8 cord-265322-3854ddb9 cord-271785-vmnc8yg6 cord-261574-zcazhkad cord-253468-pf0xubii cord-258272-uu6t6tnh cord-275569-i5y23mmz cord-270740-3su8pc3f cord-279084-bbae1qyx cord-254411-e9vvjv8w cord-275353-ezrmuw48 cord-290803-v5ndlk9c cord-276715-d1nh2dvb cord-254162-tu81j66h cord-264916-c4n0kyog cord-276564-o21ncldx cord-274510-fo7p98np cord-269563-2979u47a cord-297178-moxhk2e0 cord-296253-bxyzhsfs cord-274698-i3mzzxwq cord-287824-zg5akivn cord-274715-dcs1rgd0 cord-286038-a62k3lma cord-281354-sa27k8o3 cord-265724-fdt00qw1 cord-267612-1h7xpkbe cord-282853-l0c69uul cord-291037-19csqq89 cord-261370-jp5sqqwc cord-289905-dvl2pud2 cord-288009-8i3gsq9p cord-279138-dmhphgp5 cord-289332-hvakv08t cord-278271-rpq62xhl cord-254094-ed1epul1 cord-293059-2iwzieqm cord-308279-gsk4qel5 cord-302212-zt4lv5g4 cord-291722-xnfdjriz cord-289049-4ozwhcyi cord-311673-z4hkw17g cord-301619-0ojayw16 cord-293860-6kz0iws6 cord-313382-prxc0lue cord-310217-p9nqcz5d cord-314679-lmfalzni cord-317238-uszhwugw cord-319822-h1zm94p4 cord-318114-q29zax2j cord-312912-i1yyz5lg cord-310928-g553afo9 cord-304658-vxu33v7i cord-324949-sqy03dks cord-291781-gs81g1db cord-306146-i4a74j3r cord-303022-9hqoq7tf cord-299911-v95pf3eg cord-331140-5b0y1xzb cord-288733-c51lfwd6 cord-323749-lvtfv7ny cord-338585-ep9r1n8t cord-334709-z70oevy2 cord-323310-tq9muytr cord-332365-20u06444 cord-331428-6pvr2vew cord-326849-vqpwdlj7 cord-320508-egw7bvzf cord-337627-1a2gpqdl cord-352911-9wbq9qo2 cord-353716-gxgvhhv1 cord-328587-vctvcyim cord-337493-8yhd697t cord-349718-x5i460bc cord-322880-zfc9w5y6 cord-334543-gavnscor cord-315576-bgcqkz0p cord-327809-9uhhqasl cord-344170-qrupbtem cord-282899-kp114q7n cord-346281-sma6e891 cord-320959-sgdqhtns Creating transaction Updating pos table Building ./etc/reader.txt cord-254162-tu81j66h cord-269563-2979u47a cord-278271-rpq62xhl cord-261370-jp5sqqwc cord-346281-sma6e891 cord-254162-tu81j66h number of items: 87 sum of words: 128,361 average size in words: 2,070 average readability score: 44 nouns: patients; cells; infection; virus; disease; cell; coronavirus; protein; lung; response; receptor; treatment; effects; syndrome; system; role; inflammation; vitamin; blood; activity; levels; risk; expression; cases; effect; study; studies; injury; hypothesis; activation; mortality; factor; infections; authors; cytokine; angiotensin; type; drug; production; factors; cytokines; covid-19; influenza; host; surface; function; enzyme; people; tissue; damage verbs: induce; increased; shown; associated; caused; used; reduce; inhibits; include; suggest; bind; reported; leads; activated; mediated; known; infected; found; related; based; decrease; prevent; result; converting; considered; affect; compared; involve; propose; signaling; observed; plays; developed; treated; provide; regulated; support; given; seen; indicated; covid-19; presents; improve; expressed; identifying; demonstrated; requires; contribute; controlling; occurring adjectives: respiratory; severe; immune; viral; inflammatory; clinical; acute; covid-19; human; high; endothelial; pulmonary; anti; potential; vascular; new; therapeutic; novel; important; low; higher; possible; different; specific; innate; key; several; non; early; significant; pro; oxidative; oral; chronic; many; antiviral; recent; cellular; major; lower; epithelial; infectious; systemic; current; cardiovascular; male; effective; critical; infected; various adverbs: also; well; however; therefore; even; especially; moreover; potentially; highly; currently; particularly; significantly; recently; furthermore; critically; indeed; clinically; thereby; relatively; much; widely; often; directly; now; still; together; rather; rapidly; mainly; first; previously; already; far; likely; less; strongly; similarly; finally; yet; interestingly; usually; specifically; respectively; additionally; probably; worldwide; severely; single; possibly; markedly pronouns: it; its; we; their; our; they; i; them; us; itself; my; one; he; your; you; his; her; yours; themselves; me; u; siglec-14; she; ours; interaction/; him; -14; 's proper nouns: SARS; COVID-19; CoV-2; ACE2; Coronavirus; China; CoV; II; T; IL-6; ARDS; TNF; Med; Hypotheses; AAT; Wuhan; DOI; sha; Disease; RNA; PTX; TMPRSS2; α; NAC; East; Covid-19; BCG; S; PS; HCQ; CD8; RAS; MERS; HIV; Ang; ATP; Health; EMMPRIN; Novel; ICU; CD4; Asia; ACE; Italy; HMGB1; Angiotensin; Europe; Cu; CD33; GcMAF keywords: sars; covid-19; ace2; cell; patient; virus; tnf; ptx; high; hcq; drug; bcg; ang; vitamin; vaccine; tmv; tmprss2; system; surfactant; statin; sirt1; siglec-5; sicily; shift; resident; ras; pulmonary; peroxide; particle; p450; oxygen; oxide; ocular; nitric; nih; nad; nac; mount; medical; mdsc; lymphatic; influenza; infection; il-6; ibuprofen; hydrogen; hpa; hmgb1; garlic; exercise one topic; one dimension: covid file(s): https://www.sciencedirect.com/science/article/pii/S0306987720332850?v=s5 titles(s): Hypothesis: alpha-1-antitrypsin is a promising treatment option for COVID-19 three topics; one dimension: covid; covid; virus file(s): https://api.elsevier.com/content/article/pii/S0306987720315188, https://www.sciencedirect.com/science/article/pii/S0306987720314912?v=s5, https://www.ncbi.nlm.nih.gov/pubmed/32679424/ titles(s): Vitamin E Acetate as Linactant in the Pathophysiology of EVALI | Apparent difference in fatalities between Central Europe and East Asia due to SARS-COV-2 and COVID-19: Four hypotheses for possible explanation | Natural protection of ocular surface from viral infections – a hypothesis five topics; three dimensions: covid sars cov; covid sars patients; covid sars cov; vitamin respiratory air; covid drug disease file(s): https://www.sciencedirect.com/science/article/pii/S0306987720314912?v=s5, https://www.sciencedirect.com/science/article/pii/S0306987720332850?v=s5, https://doi.org/10.1016/j.mehy.2020.109972, https://api.elsevier.com/content/article/pii/S0306987720315188, https://www.sciencedirect.com/science/article/pii/S0306987720311750?v=s5 titles(s): Apparent difference in fatalities between Central Europe and East Asia due to SARS-COV-2 and COVID-19: Four hypotheses for possible explanation | Hypothesis: alpha-1-antitrypsin is a promising treatment option for COVID-19 | Burnout syndrome in Romanian medical residents in time of the COVID-19 pandemic | Vitamin E Acetate as Linactant in the Pathophysiology of EVALI | Cytochrome P450-mediated drug interactions in COVID-19 patients: current findings and possible mechanisms Type: cord title: journal-medHypotheses-cord date: 2021-05-30 time: 15:05 username: emorgan patron: Eric Morgan email: emorgan@nd.edu input: facet_journal:"Med Hypotheses" ==== make-pages.sh htm files ==== make-pages.sh complex files ==== make-pages.sh named enities ==== making bibliographics id: cord-301619-0ojayw16 author: Adamowicz, Jan title: May patients receiving 5-alpha-reductase inhibitors be in higher risk of COVID-19 complications ? date: 2020-04-22 words: 1203.0 sentences: 76.0 pages: flesch: 36.0 cache: ./cache/cord-301619-0ojayw16.txt txt: ./txt/cord-301619-0ojayw16.txt summary: Based on this observation, our proposed hypothesis is that 5-alpha-reductase inhibitors, that are commonly used for BPH treatment, may be one of the factors contributing to poorer prognosis in males. Based on this observation, our proposed hypothesis is that 5-alpha-reductase inhibitors, that are commonly used for BPH treatment, may be one of the factors contributing to poorer prognosis in males. Consequently, we introduce hypothesis that 5-alpha-reductase inhibitors may disrupt androgens metabolism in lungs, which in turn may have a negative impact on course of COVID-19 infection. Under this assumption, 5-alpha-reductase inhibitors might increase androgen concentration in lungs hampering their regeneration. Due to high prevalence of 5-alpha-reductase inhibitor in BPH treatment, its potential negative influence on recovery after COVID-19 infection, should be established. According to presented hypothesis, patients receiving 5-alpha-reductase inhibitors, might be vulnerable to COVID-19 infection with poorer prognosis. May patients receiving 5 alpha-reductase inhibitors be in higher risk of COVID-19 complications abstract: COVID-19 pandemic is a major challenge for global and national healthcare providers. Number of new cases is continuously increasing with an emerging trend showing worse prognosis in males in comparison to females. Based on this observation, our proposed hypothesis is that 5-alpha-reductase inhibitors, that are commonly used for BPH treatment, may be one of the factors contributing to poorer prognosis in males. BACKGROUND: With increasing number of COVID-19 cases, an evident sex- dependent difference in disease outcomes can be observed. Based on published studies with short term follow-up, males have 65% higher mortality rate (1). The question remains, whether long term observational studies will confirm improved recovery in females. url: https://api.elsevier.com/content/article/pii/S0306987720305909 doi: 10.1016/j.mehy.2020.109751 id: cord-337627-1a2gpqdl author: Alvarado-Vasquez, Noé title: Could a family history of type 2 diabetes be a risk factor to the endothelial damage in the patient with COVID-19? date: 2020-11-06 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: In December 2019, in China, a disease derived from a new beta coronavirus (SARS-CoV-2) was reported, which was termed coronavirus disease 2019 (COVID-19). Currently, it is known that endothelial cell dysfunction is a critical event in the infection by this virus. However, in a representative percentage of patients with COVID-19, neither cardiovascular disease nor diabetes mellitus, which could be linked with endothelial dysfunction, has been reported. Previous evidence has shown the presence of early endothelial dysfunction in healthy subjects but with a family history of type 2 diabetes (FH-DM2), where glucose metabolism, the synthesis of nitric oxide (NO), reactive oxygen species (ROS), as well as expression of genes involved with their synthesis are impaired. Besides, in subjects with an FH-DM2, the presence of hyperinsulinemia and high glucose levels are common events that could favor the infection of endothelial cells by the coronavirus. Interestingly, both events have been reported in patients with COVID-19, in whom hyperinsulinemia increases the surface expression of ACE2 through a diminution of ADAMTS17 activity; whereas hyperglycemia induces higher expression of ACE2 in different tissues, including microvascular endothelial cells from the pancreatic islets, favoring chronic hyperglycemia and affecting the release of insulin. Therefore, we hypothesized that an FH-DM2 should be considered an important risk factor, since the individuals with this background develop an early endothelial dysfunction, which would increase the susceptibility and severity of infection and damage to the endothelium, in the patient infected with the SARS-CoV-2. url: https://api.elsevier.com/content/article/pii/S0306987720332692 doi: 10.1016/j.mehy.2020.110378 id: cord-254162-tu81j66h author: Bai, Xiyuan title: Hypothesis: alpha-1-antitrypsin is a promising treatment option for COVID-19 date: 2020-11-12 words: 5512.0 sentences: 286.0 pages: flesch: 39.0 cache: ./cache/cord-254162-tu81j66h.txt txt: ./txt/cord-254162-tu81j66h.txt summary: Sixth, AAT inhibition of elastase can antagonize the formation of neutrophil extracellular traps (NETs), a complex extracellular structure comprised of neutrophil-derived DNA, histones, and proteases, and implicated in the immunothrombosis of COVID-19; indeed, AAT has been shown to change the shape and adherence of non-COVID-19-related NETs. Seventh, AAT inhibition of endothelial cell apoptosis may limit the endothelial injury linked to severe COVID-19-associated acute lung injury, multi-organ dysfunction, and pre-eclampsia-like syndrome seen in gravid women. First, AAT is a serine protease inhibitor (SERPIN) shown to inhibit TMPRSS-2, the host serine protease that cleaves the spike protein of SARS-CoV-2, a necessary preparatory step for the virus to bind its cell surface receptor ACE2 to gain intracellular entry. First, AAT is a serine protease inhibitor (SERPIN) shown to inhibit TMPRSS-2, the host serine protease that cleaves the spike protein of SARS-CoV-2, a necessary preparatory step for the virus to bind its cell surface receptor ACE2 to gain intracellular entry. abstract: No definitive treatment for COVID-19 exists although promising results have been reported with remdesivir and glucocorticoids. Short of a truly effective preventive or curative vaccine against SARS-CoV-2, it is becoming increasingly clear that multiple pathophysiologic processes seen with COVID-19 as well as SARS-CoV-2 itself should be targeted. Because alpha-1-antitrypsin (AAT) embraces a panoply of biologic activities that may antagonize several pathophysiologic mechanisms induced by SARS-CoV-2, we hypothesize that this naturally occurring molecule is a promising agent to ameliorate COVID-19. We posit at least seven different mechanisms by which AAT may alleviate COVID-19. First, AAT is a serine protease inhibitor (SERPIN) shown to inhibit TMPRSS-2, the host serine protease that cleaves the spike protein of SARS-CoV-2, a necessary preparatory step for the virus to bind its cell surface receptor ACE2 to gain intracellular entry. Second, AAT has anti-viral activity against other RNA viruses HIV and influenza as well as induces autophagy, a known host effector mechanism against MERS-CoV, a related coronavirus that causes the Middle East Respiratory Syndrome. Third, AAT has potent anti-inflammatory properties, in part through inhibiting both nuclear factor-kappa B (NFκB) activation and ADAM17 (also known as tumor necrosis factor-alpha converting enzyme), and thus may dampen the hyper-inflammatory response of COVID-19. Fourth, AAT inhibits neutrophil elastase, a serine protease that helps recruit potentially injurious neutrophils and implicated in acute lung injury. AAT inhibition of ADAM17 also prevents shedding of ACE2 and hence may preserve ACE2 inhibition of bradykinin, reducing the ability of bradykinin to cause a capillary leak in COVID-19. Fifth, AAT inhibits thrombin, and venous thromboembolism and in situ microthrombi and macrothrombi are increasingly implicated in COVID-19. Sixth, AAT inhibition of elastase can antagonize the formation of neutrophil extracellular traps (NETs), a complex extracellular structure comprised of neutrophil-derived DNA, histones, and proteases, and implicated in the immunothrombosis of COVID-19; indeed, AAT has been shown to change the shape and adherence of non-COVID-19-related NETs. Seventh, AAT inhibition of endothelial cell apoptosis may limit the endothelial injury linked to severe COVID-19-associated acute lung injury, multi-organ dysfunction, and pre-eclampsia-like syndrome seen in gravid women. Furthermore, because both NETs formation and the presence of anti-phospholipid antibodies are increased in both COVID-19 and non-COVID pre-eclampsia, it suggests a similar vascular pathogenesis in both disorders. As a final point, AAT has an excellent safety profile when administered to patients with AAT deficiency and is dosed intravenously once weekly but also comes in an inhaled preparation. Thus, AAT is an appealing drug candidate to treat COVID-19 and should be studied. url: https://www.sciencedirect.com/science/article/pii/S0306987720332850?v=s5 doi: 10.1016/j.mehy.2020.110394 id: cord-318114-q29zax2j author: Bara, Gregor A. title: Can neuromodulation support the fight against the COVID19 pandemic? Transcutaneous non-invasive vagal nerve stimulation as a potential targeted treatment of fulminant acute respiratory distress syndrome date: 2020-07-18 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The COVID-19 pandemic has rapidly spread all over the world and caused a major health care crisis. About 20% of patients develop severe disease and require hospitalisation, which is associated with a high mortality rate of up to 97% in those being ventilated and respiratory failure being the leading cause of death. Despite many therapeutic agents being under current investigation there is yet no panacea available. With increasing rates of infection throughout the world, there is an urgent need for new therapeutic approaches to counteract the infection. As the nervous system has shown to be a strong modulator of respiratory function and the immune response, we want to highlight pathways involved in regulation of respiratory function, the neuro-immune axis as well as the rationale for a potential targeted treatment of fulminant acute respiratory distress syndrome via transcutaneous non-invasive vagal nerve stimulation in critically-ill COVID-19 patients. url: https://api.elsevier.com/content/article/pii/S0306987720312615 doi: 10.1016/j.mehy.2020.110093 id: cord-282899-kp114q7n author: Biswas, Saurav title: Blood clots in COVID-19 patients: Simplifying the curious mystery date: 2020-11-06 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The universal phenomenon of blood clotting is well known to be protective in external cellular/ tissue injury. However, the emergence of unusual thrombotic presentations in COVID-19 patients is the real concern. Interaction of the spike glycoprotein with ACE2 receptor present in the host cell surface mediates the entry of SARS-CoV-2 causing COVID-19 infection. New clinical findings of SARS-CoV-2 pathogenesis are coming out every day, and one such mystery is the formation of mysterious blood clots in the various tissues and organs of COVID-19 patients, which needs critical attention. To address this issue, we hypothesis that, high ACE2 expression in the endothelium of blood vessels facilitates the high-affinity binding of SARS-CoV-2 using spike protein, causing infection and internal injury inside the vascular wall of blood vessels. This viral associated injury may directly/indirectly initiate activation of coagulation and clotting cascades forming internal blood clots. However, the presence of these clots is undesirable as they are responsible for thrombosis and need to be treated with anti-thrombotic intervention. url: https://api.elsevier.com/content/article/pii/S030698772033262X doi: 10.1016/j.mehy.2020.110371 id: cord-344170-qrupbtem author: Biswas, Subrata K title: Genetic variation in SARS-CoV-2 may explain variable severity of COVID-19 date: 2020-05-24 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: nan url: https://www.ncbi.nlm.nih.gov/pubmed/32464496/ doi: 10.1016/j.mehy.2020.109877 id: cord-261370-jp5sqqwc author: Bollag, Wendy B. title: Phosphatidylglycerol and Surfactant: A Potential Treatment for COVID-19? date: 2020-09-16 words: 4096.0 sentences: 177.0 pages: flesch: 33.0 cache: ./cache/cord-261370-jp5sqqwc.txt txt: ./txt/cord-261370-jp5sqqwc.txt summary: It is thought that surfactant, which is already approved by the Food and Drug Administration for intratracheal administration to treat neonatal respiratory distress syndrome in infants, could benefit COVID-19-infected individuals by: (1) restoring surfactant damaged by lung infection and/or decreased due to the virus-induced death of the type II pneumocytes that produce it and (2) reducing surface tension to decrease the work of breathing and limit pulmonary edema. In addition, a constituent of surfactant, phosphatidylglycerol, could mitigate COVID-19-induced lung pathology by: (3) decreasing excessive innate immune system activation via its inhibition of toll-like receptor-2 and -4 activation by microbial components and cellular proteins released by damaged cells, thereby limiting inflammation and the resultant pulmonary edema, and (4) possibly blocking spread of the viral infection to non-infected cells in the lung. abstract: A hypothesis concerning the potential utility of surfactant supplementation for the treatment of critically ill patients with COVID-19 is proposed, along with a brief summary of the data in the literature supporting this idea. It is thought that surfactant, which is already approved by the Food and Drug Administration for intratracheal administration to treat neonatal respiratory distress syndrome in infants, could benefit COVID-19-infected individuals by: (1) restoring surfactant damaged by lung infection and/or decreased due to the virus-induced death of the type II pneumocytes that produce it and (2) reducing surface tension to decrease the work of breathing and limit pulmonary edema. In addition, a constituent of surfactant, phosphatidylglycerol, could mitigate COVID-19-induced lung pathology by: (3) decreasing excessive innate immune system activation via its inhibition of toll-like receptor-2 and -4 activation by microbial components and cellular proteins released by damaged cells, thereby limiting inflammation and the resultant pulmonary edema, and (4) possibly blocking spread of the viral infection to non-infected cells in the lung. Therefore, it is suggested that surfactant preparations containing phosphatidylglycerol be tested for their ability to improve lung function in critically ill patients with COVID-19. url: https://api.elsevier.com/content/article/pii/S0306987720320454 doi: 10.1016/j.mehy.2020.110277 id: cord-312912-i1yyz5lg author: Bou Khalil, Rami title: Lithium chloride combination with rapamycin for the treatment of COVID-19 pneumonia date: 2020-05-01 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: nan url: https://www.ncbi.nlm.nih.gov/pubmed/32413699/ doi: 10.1016/j.mehy.2020.109798 id: cord-304658-vxu33v7i author: Brenner, Steven R. title: Covid-19, TMPRSS2, and whether android regulation affects pandemic virus gender incidence and age distribution of disease date: 2020-04-22 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: nan url: https://doi.org/10.1016/j.mehy.2020.109773 doi: 10.1016/j.mehy.2020.109773 id: cord-269563-2979u47a author: Caetano Silva-Filho, José title: The influence of ABO blood groups on COVID-19 susceptibility and severity: a molecular hypothesis based on carbohydrate-carbohydrate interactions date: 2020-08-02 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The world is experiencing one of the most difficult moments in history with the COVID-19 pandemic, a disease caused by SARS-CoV-2, a new type of coronavirus. Virus infectivity is mediated by the binding of Spike transmembrane glycoprotein to specific protein receptors present on cell host surface. Spike is a homotrimer that emerges from the virion, each monomer containing two subunits named S1 and S2, which are related to cell recognition and membrane fusion, respectively. S1 is subdivided in domains S1A (or NTD) and S1B (or RBD), with experimental and in silico studies suggesting that the former binds to sialic acid-containing glycoproteins, such as CD147, whereas the latter binds to ACE2 receptor. Recent findings indicate that the ABO blood system modulates susceptibility and progression of infection, with type-A individuals being more susceptible to infection and/or manifestation of a severe condition. Seeking to understand the molecular mechanisms underlying this susceptibility, we carried out an extensive bibliographic survey on the subject. Based on this survey, we hypothesize that the correlation between the ABO blood system and susceptibility to SARS-CoV-2 infection can be presumably explained by the modulation of sialic acid-containing receptors distribution on host cell surface induced by ABO antigens through carbohydrate-carbohydrate interactions, which could maximize or minimize the virus Spike protein binding to the host cell. This model could explain previous sparse observations on the molecular mechanism of infection and can direct future research to better understand of COVID-19 pathophysiology. url: https://api.elsevier.com/content/article/pii/S0306987720322581 doi: 10.1016/j.mehy.2020.110155 id: cord-331140-5b0y1xzb author: Cardona Maya, Walter D. title: SARS-CoV-2 and Prostatitis: dangerous relationship for male sexual and reproductive health date: 2020-06-01 words: 326.0 sentences: 30.0 pages: flesch: 58.0 cache: ./cache/cord-331140-5b0y1xzb.txt txt: ./txt/cord-331140-5b0y1xzb.txt summary: key: cord-331140-5b0y1xzb title: SARS-CoV-2 and Prostatitis: dangerous relationship for male sexual and reproductive health cord_uid: 5b0y1xzb . Recently, SARS-CoV-2 was detected in semen samples (5) . Therefore, it is not unreasonable to believe that the latest coronavirus could potentially be transmitted via semen (6) . It was also reported that angiotensin converting enzyme 2 (ACE2) is a functional receptor that mediates the entry of SARS-CoV-1 (7) and 2 (8) , and this receptor is expressed in the prostate. Perhaps in the coming years, the real effect of SARS-CoV-2 on prostatitis cases will be evaluated and scope for researching factors that cause the clinical syndrome will be expanded. Male infertility: a public health issue caused by sexually transmitted pathogens Clinical Characteristics and Results of Semen Tests Among Men With Coronavirus Disease SARS-CoV-2 and the Testis: similarity to other viruses and routes of infection Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus abstract: nan url: https://www.ncbi.nlm.nih.gov/pubmed/32505071/ doi: 10.1016/j.mehy.2020.109914 id: cord-319822-h1zm94p4 author: Carelli, Pasquale title: A physicist''s approach to COVID-19 transmission via expiratory droplets date: 2020-06-17 words: 1412.0 sentences: 61.0 pages: flesch: 58.0 cache: ./cache/cord-319822-h1zm94p4.txt txt: ./txt/cord-319822-h1zm94p4.txt summary: My thesis is supported and described on the basis of a physicist''s model which studies the droplets behavior when emitted by the respiratory apparatus of an infected person, symptomatic or not. The intermediate dimensioned droplets are proved to be changed into aerosol, losing their water content and becoming seriously contagious, but in their initial phase they could be easily caught by a simple surgical mask. This habit, There are non doubts about the fact that expiratory particles transmit the pandemic, but we must make a coarse distinction among droplets and their dynamic evolutions when emitted by infected people. These droplets have a substantial viral load, they are quite numerous, some thousands of them can contain just one single virion each and they are probably the most contagious and dangerous elements[14]; if not stopped on time, they constitute the real element of airborne infection [15] . abstract: In this paper, a physicist's approach is given to support the necessity to wear surgical masks during the COVID-19 pandemics; they have become compulsory in Eastern countries, while in Western countries they are still an optional. My thesis is supported and described on the basis of a physicist's model which studies the droplets behavior when emitted by the respiratory apparatus of an infected person, symptomatic or not. The intermediate dimensioned droplets are proved to be changed into aerosol, losing their water content and becoming seriously contagious, but in their initial phase they could be easily caught by a simple surgical mask. The actual efficiency of FFP3 masks has been examined and found to be lower than expected. url: https://api.elsevier.com/content/article/pii/S0306987720311853 doi: 10.1016/j.mehy.2020.109997 id: cord-291781-gs81g1db author: Caruso, Arturo Armone title: Hydrogen peroxide and viral infections: a literature review with research hypothesis definition in relation to the current covid-19 pandemic date: 2020-06-01 words: 1379.0 sentences: 83.0 pages: flesch: 37.0 cache: ./cache/cord-291781-gs81g1db.txt txt: ./txt/cord-291781-gs81g1db.txt summary: We reviewed the literature concerning the innate response from nasal and oral epithelial cells and their reaction to hydrogen peroxide (H(2)O(2)). Therefore, nose/mouth/throat washing with hydrogen peroxide may enhance those local innate responses to viral infections and help protect against the current coronavirus pandemic. [2] We reviewed the literature concerning the innate response from nasal and oral epithelial cells to evaluate the role of hydrogen peroxide (H 2 O 2 ). [5] Virus-induced oxidative stress plays an important role in the regulation of the host immune system and the specific oxidant-sensitive pathway is one of the effective strategies against viral infections. [5] Virus-induced oxidative stress plays an important role in the regulation of the host immune system and the specific oxidant-sensitive pathway is one of the effective strategies against viral infections. There are no randomized controlled trials or clinical observational studies concerning the curative or preventive effect of hydrogen peroxide against viral infections. abstract: We reviewed the literature concerning the innate response from nasal and oral epithelial cells and their reaction to hydrogen peroxide (H(2)O(2)). Hydrogen peroxide is produced physiologically by oral bacteria and plays a significant role in the balance of oral microecology since it is an important antimicrobial agent. In the epithelial cells, the enzyme superoxide dismutase catalyzes a reaction leading from hydrogen peroxide to the ion superoxide. The induced oxidative stress stimulates a local innate response via activation of the toll-like receptors and the NF-κB. Those kinds of reactions are also activated by viral infections. Virus-induced oxidative stress plays an important role in the regulation of the host immune system and the specific oxidant-sensitive pathway is one of the effective strategies against viral infections. Therefore, nose/mouth/throat washing with hydrogen peroxide may enhance those local innate responses to viral infections and help protect against the current coronavirus pandemic. We strongly encourage the rapid development of randomized controlled trials in both SARS-CoV-2 positive and negative subjects to test the preliminary findings from the in-vitro and in-vivo observational studies that we identified. url: https://doi.org/10.1016/j.mehy.2020.109910 doi: 10.1016/j.mehy.2020.109910 id: cord-287824-zg5akivn author: Chan, Yinghan title: Advanced drug delivery systems can assist in managing influenza virus infection: A hypothesis date: 2020-09-24 words: 1158.0 sentences: 84.0 pages: flesch: 33.0 cache: ./cache/cord-287824-zg5akivn.txt txt: ./txt/cord-287824-zg5akivn.txt summary: title: Advanced drug delivery systems can assist in managing influenza virus infection: A hypothesis This article provides an insight into a novel hypothesis that describes how the integration of nanomedicine, with the development of drugs and vaccines can potentially enhance body immune response and the efficacies of anti-viral therapeutics to combat influenza infections. In the recent years, an 66 increasing trend of influenza outbreaks have been observed, prompting medical researchers to 67 design and develop suitable vaccines and novel therapeutic modalities [10] . Targeting 411 neutrophils using novel drug delivery systems in chronic respiratory diseases Increasing 440 complexity and interactions of oxidative stress in chronic respiratory diseases: An 441 emerging need for novel drug delivery systems Interactions 501 with the macrophages: An emerging targeted approach using novel drug delivery 502 systems in respiratory diseases Inhibition of H1N1 influenza virus infection by zinc oxide nanoparticles: 537 Another emerging application of nanomedicine abstract: Outbreaks of influenza infections in the past have severely impacted global health and socioeconomic growth. Antivirals and vaccines are remarkable medical innovations that have been successful in reducing the rates of morbidity and mortality from this disease. However, the relentless emergence of drug resistance has led to a worrisome increase in the trend of influenza outbreaks, characterized by worsened clinical outcomes as well as increased economic burden. This has prompted the need for breakthrough innovations that can effectively manage influenza outbreaks. This article provides an insight into a novel hypothesis that describes how the integration of nanomedicine, with the development of drugs and vaccines can potentially enhance body immune response and the efficacies of anti-viral therapeutics to combat influenza infections. url: https://www.sciencedirect.com/science/article/pii/S0306987720326529?v=s5 doi: 10.1016/j.mehy.2020.110298 id: cord-349718-x5i460bc author: Chandrasekaran, Baskaran title: Dr. Chandrasekaran’s reply to “Exercising and face masks: an important hypothesis buried in a selective review” date: 2020-09-23 words: 1271.0 sentences: 57.0 pages: flesch: 45.0 cache: ./cache/cord-349718-x5i460bc.txt txt: ./txt/cord-349718-x5i460bc.txt summary: Dr. Chandrasekaran''s reply to "Exercising and face masks: an important hypothesis buried in a selective review" This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. Dr. Chandrasekaran''s reply to "Exercising and face masks: an important hypothesis buried in a selective review" Thank you very much for your interest and critical feedback on our recent hypothesis article published in "Medical Hypotheses" journal. Firstly, we would like to clarify to the authors and readers that our article focuses only on the possible physiological mechanisms that could be associated with wearing the tight custom made cloth masks during moderate to heavy exercise (60 -80% VO2 max or above anaerobic threshold). Our hypothesis pertains to the use of tight custom made masks during moderate to vigorous exercise, not general household work nor in healthcare professionals. abstract: nan url: https://api.elsevier.com/content/article/pii/S0306987720329996 doi: 10.1016/j.mehy.2020.110302 id: cord-289332-hvakv08t author: Chen, Guoqian title: Pathogenic role of HMGB1 in SARS? date: 2004-04-30 words: 1670.0 sentences: 90.0 pages: flesch: 37.0 cache: ./cache/cord-289332-hvakv08t.txt txt: ./txt/cord-289332-hvakv08t.txt summary: High mobility group box 1 protein (HMGB1) is released by necrotic cells or activated macrophages/monocytes, and functions as a late mediator of lethal systemic and local pulmonary inflammation. In light of observations that three Chinese herbal formulations recommended for treatment of severe acute respiratory syndrome (SARS) specifically inhibited the release of HMGB1 from innate immune cells, we hypothesize that HMGB1 might occupy a pathogenic role in SARS by mediating an injurious pulmonary inflammatory response. High mobility group box 1 protein (HMGB1, formerly known as HMG-1 or amphoterin) has recently been identified as a new proinflammatory cytokine and a late mediator of inflammation, sepsis, and acute lung injury. In light of observations that several Chinese herbal remedies recommended for treatment of SARS specifically inhibited the release of HMGB1 from activated innate immune cells, we hypothesize that HMGB1 might occupy a pathogenic role in SARS by mediating an injurious pulmonary inflammatory response. abstract: High mobility group box 1 protein (HMGB1) is released by necrotic cells or activated macrophages/monocytes, and functions as a late mediator of lethal systemic and local pulmonary inflammation. Passive immunization with anti-HMGB1 antibodies confers significant protection against lethal endotoxemia, sepsis, and acute lung injury, even when antibodies are administered after the onset of these diseases. In light of observations that three Chinese herbal formulations recommended for treatment of severe acute respiratory syndrome (SARS) specifically inhibited the release of HMGB1 from innate immune cells, we hypothesize that HMGB1 might occupy a pathogenic role in SARS by mediating an injurious pulmonary inflammatory response. url: https://www.sciencedirect.com/science/article/pii/S0306987704002208 doi: 10.1016/j.mehy.2004.01.037 id: cord-337493-8yhd697t author: Choquenaira-Quispe, Celia title: Factors involved in low susceptibility to covid-19: an adaptation of high altitude inhabitants date: 2020-07-02 words: 312.0 sentences: 36.0 pages: flesch: 49.0 cache: ./cache/cord-337493-8yhd697t.txt txt: ./txt/cord-337493-8yhd697t.txt summary: key: cord-337493-8yhd697t authors: Choquenaira-Quispe, Celia; Saldaña-Bobadilla, Vanessa; Kenedy Ramirez, J. title: Factors involved in low susceptibility to covid-19: an adaptation of high altitude inhabitants cord_uid: 8yhd697t Consequently, populations from high altitude areas would be less susceptible to hypoxia during the infection. Consequently, SARS-CoV-2 infected populations from high altitude areas have greater lung adaptive capacity than those that live at low altitude. The three factors above would perform an important role in high altitude inhabitants, because they decrease the susceptibility to develop severe symptoms in SARS-CoV-2 infection. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study Hepcidin and anemia: A tight relationship Does the pathogenesis of SARS-CoV-2 virus decrease at high-altitude? HIF stabilizers in the management of renal anemia: from bench to bedside to pediatrics The authors declare that there is no conflict of interest. The authors declare that there is no conflict of interest. abstract: nan url: https://www.ncbi.nlm.nih.gov/pubmed/32634733/ doi: 10.1016/j.mehy.2020.110068 id: cord-258272-uu6t6tnh author: Dabaghian, Farid title: Bioactive compounds with possible inhibitory activity of Angiotensin-Converting Enzyme-II; a gate to manage and prevent COVID-19 date: 2020-05-16 words: 302.0 sentences: 27.0 pages: flesch: 50.0 cache: ./cache/cord-258272-uu6t6tnh.txt txt: ./txt/cord-258272-uu6t6tnh.txt summary: key: cord-258272-uu6t6tnh title: Bioactive compounds with possible inhibitory activity of Angiotensin-Converting Enzyme-II; a gate to manage and prevent COVID-19 cord_uid: uu6t6tnh Angiotensin-Converting Enzyme-II (ACE-II) receptor, most likely the COVID-19 target, plays essential roles in virus transmission to the alveolar cells (2) . Accordingly, agents with potential inhibition or regulation of ACE-II receptors might be effective in COVID-19 management (3) . Glycyrrhizin can inhibit COVID-19 S-protein binding to ACE-II receptors (7) . Emodin, a bioactive antiviral agent may prevent S-protein binding to ACE-II receptors. Thus, Emodin and probably Aloe-emodin can stave off the COVID-19 infection via competing with S-protein in binding to ACE-II (7) . Angiotensin converting enzyme 2: SARS-CoV-2 receptor and regulator of the renin-angiotensin system Potential natural compounds for preventing 2019-nCoV infection Emodin blocks the SARS coronavirus spike protein and angiotensin-converting enzyme 2 interaction Anti-SARS coronavirus 3C-like protease effects of Rheum palmatum L. The authors of this manuscript have no conflict of interest. abstract: nan url: https://www.sciencedirect.com/science/article/pii/S0306987720306952?v=s5 doi: 10.1016/j.mehy.2020.109841 id: cord-279138-dmhphgp5 author: Deek, Sarah A. title: Chronic Exposure to Air Pollution Implications on COVID-19 Severity date: 2020-09-28 words: 1544.0 sentences: 88.0 pages: flesch: 35.0 cache: ./cache/cord-279138-dmhphgp5.txt txt: ./txt/cord-279138-dmhphgp5.txt summary: Populations in areas with higher levels of air pollution both indoors and outdoors show increased mortality rates when infected with coronavirus disease 2019 (COVID-19). In this paper, fine particulate matter (PM) is identified as a source of disrupted activation of the hypothalamic–pituitary–adrenal (HPA) axis; therefore, a contributable variable to COVID-19 mortality. Populations in areas with higher levels of air pollution both indoors and outdoors show increased mortality rates when infected with coronavirus disease 2019 . In this paper, fine particulate matter (PM) is identified as a source of disrupted activation of the hypothalamicpituitary-adrenal (HPA) axis; therefore, a contributable variable to COVID-19 mortality. Therefore, chronic exposure to fine PM may be contributable variable that disrupts HPA system activation typically associated with the altered regulation of circulating glucocorticoids resulting in inefficient or delayed immune response to COVID-19 infection. abstract: Populations in areas with higher levels of air pollution both indoors and outdoors show increased mortality rates when infected with coronavirus disease 2019 (COVID-19). The association between air quality and COVID-19 is commonly attributed to the risk of transmission. Although controlled transmission is crucial, further investigation into air quality traits that contribute to the lethality of COVID-19 in infected persons enables risk stratification and optimization of the allocation of resources. There is a need for a valid basis for the proactive identification of indicators of COVID-19 severity in air quality that allow for the implementation of systematic environmental improvements aimed at preventing COVID-19 mortality. In this paper, fine particulate matter (PM) is identified as a source of disrupted activation of the hypothalamic–pituitary–adrenal (HPA) axis; therefore, a contributable variable to COVID-19 mortality. url: https://doi.org/10.1016/j.mehy.2020.110303 doi: 10.1016/j.mehy.2020.110303 id: cord-268425-xg8xnjf9 author: DiNicolantonio, James J. title: Harnessing Adenosine A2A Receptors as a Strategy for Suppressing the Lung Inflammation and Thrombotic Complications of COVID-19: Potential of Pentoxifylline and Dipyridamole date: 2020-07-02 words: 3891.0 sentences: 251.0 pages: flesch: 41.0 cache: ./cache/cord-268425-xg8xnjf9.txt txt: ./txt/cord-268425-xg8xnjf9.txt summary: 5 Importantly, neutrophils, whose activation and transit into lung interstitial tissue and alveolar space is a key mediator of the respiratory distress syndrome associated with COVID-19, are highly responsive to the functionally suppressive effects of A2AR, as are the endothelial cells whose activation attracts and enables transendothelial passage of activated neutrophils. Most studies with DIP have focused on its platelet-stabilizing effects -which presumably could provide some protection from SARS-CoV-2''s pro-thrombotic effects -but experimental studies also show that DIP can act on neutrophils to suppress superoxide production, adhesion to endothelial cells, and, in a mouse model of anti-phospholipid syndrome (a sometime feature of COVID-19), NETosis formation. 79 Supplemental glucosamine may likewise up-regulate the type 1 interferon responses to viruses, while exerting anti-inflammatory effects that render it protective in rodent models of sepsis and lung inflammation induced by LPS or cigarette smoke. abstract: Counterproductive lung inflammation and dysregulated thrombosis contribute importantly to the lethality of advanced COVID-19. Adenosine A2A receptors (A2AR), expressed by a wide range of immune cells, as well as endothelial cells and platelets, exert cAMP-mediated anti-inflammatory and anti-thrombotic effects that potentially could be highly protective in this regard. The venerable drug pentoxifylline (PTX) exerts both anti-inflammatory and antithrombotic effects that reflect its ability to boost the responsiveness of A2AR to extracellular adenosine. The platelet-stabilizing drug dipyridamole (DIP) blocks intracellular uptake of extracellularly-generated adenosine, thereby up-regulating A2AR signaling in a way that should be functionally complementary to the impact of PTX in that regard. Moreover, DIP has recently been reported to slow the cellular replication of SARS-CoV-2 in clinically feasible concentrations. Both PTX and DIP are reasonably safe, well-tolerated, widely available, and inexpensive drugs. When COVID-19 patients can be treated within several days of symptom onset, using PTX + DIP in conjunction with hydroxychloroquine (HCQ) and an antibiotic - azithromycin (AZM) or doxycycline – might be warranted. HCQ and AZM can suppress SARS-CoV-2 proliferation in vitro and may slow the cell-to-cell spread of the virus; a large case series evaluating this combination in early-stage patients reported an impressively low mortality rate. However, whereas HCQ and AZM can promote QT interval lengthening and may be contraindicated in more advanced COVID-19 entailing cardiac damage, doxycycline has no such effect and exerts a potentially beneficial anti-inflammatory action. In contrast to HCQ, we propose that the combination of PTX + DIP can be used in both early and advanced stages of COVID-19. Concurrent use of certain nutraceuticals – yeast beta-glucan, zinc, vitamin D, spirulina, phase 2 inducers, N-acetylcysteine, glucosamine, quercetin, and magnesium – might also improve therapeutic outcomes in COVID-19. url: https://api.elsevier.com/content/article/pii/S0306987720317382 doi: 10.1016/j.mehy.2020.110051 id: cord-327809-9uhhqasl author: Dimitriu, Mihai C.T. title: Burnout syndrome in Romanian medical residents in time of the COVID-19 pandemic date: 2020-06-07 words: 3109.0 sentences: 164.0 pages: flesch: 49.0 cache: ./cache/cord-327809-9uhhqasl.txt txt: ./txt/cord-327809-9uhhqasl.txt summary: A study in China, comparing burnout of front line workers with that of normal ward staff, in COVID context, used Maslach questionnaire for medical workers and the results were interesting and quite unexpected [3] . The aim of our study was to compare the frequency of burnout syndrome between medical residents considered to work on the front line (emergency unit, radiology and intensive care unit) and those working in normal hospital wards (surgery, obstetrics and gynecology, obstetrics). The burnout was significantly more frequent in normal wards workers (lot B) (prevalence 86%) compared to medical residents working in places that we considered front-line departments: emergency unit, radiology, including CT/MRI department and intensive care unit -lot A in our study, that showed a prevalence of burnout of only 66% (p<0.05, from chi-square statistic test) (table 2). abstract: Burnout is a state of physical or mental collapse caused by overwork or stress. Burnout during residency training has gained significant attention secondary to concerns regarding job performance and patient care. The new COVID-19 pandemic has raised public health problems around the world and required a reorganization of health services. In this context, burnout syndrome and physical exhaustion have become even more pronounced. Resident doctors, and especially those in certain specialties, seem even more exposed due to the higher workload, prolonged exposure and first contact with patients. This article is a short review of the literature and a presentation of some considerations regarding the activity of the medical residents in a non-Covid emergency hospital in Romania, based on the responses obtained via a questionnaire. Burnout prevalence is not equal in different specialties. We studied its impact and imagine the potential steps that can be taken in order to reduce the increasing rate of burnout syndrome in the pandemics. url: https://doi.org/10.1016/j.mehy.2020.109972 doi: 10.1016/j.mehy.2020.109972 id: cord-275353-ezrmuw48 author: Donma, Mustafa Metin title: The Effects of Allium Sativum on Immunity within the Scope of COVID-19 Infection date: 2020-06-02 words: 2510.0 sentences: 156.0 pages: flesch: 42.0 cache: ./cache/cord-275353-ezrmuw48.txt txt: ./txt/cord-275353-ezrmuw48.txt summary: Compounds derived from Allium sativum (garlic) have the potential to decrease the expression of proinflammatory cytokines and to reverse the immunological abnormalities to more acceptable levels. Leptin''s role in boosting proinflammatory cytokines and in appetite decreasing suggest the possible beneficial effect of decreasing the concentration of this proinflammatory adipose tissue hormone in relieving some symptoms detected during COVID-19 infection. In conclusion, Allium sativum may be an acceptable preventive measure against COVID-19 infection to boost immune system cells and to repress the production and secretion of proinflammatory cytokines as well as an adipose tissue derived hormone leptin having the proinflammatory nature. It is a well-known fact that immune dysfunction plays an important role in the development and progress of several diseases and this functional food may contribute to the prevention and treatment of pathologies such as obesity, metabolic syndrome, cardiovascular disorders, gastric ulcer, and even cancer [17, 18] . Decreased leptin concentrations caused by garlic may be helpful to alleviate appetite loss observed in patients with COVID-19 infection. abstract: The severity of coronavirus disease 2019 (COVID‐19) infection is quite variable and the manifestations varies from asymptomatic disease to severe acute respiratory infection. Fever, dry cough, dyspnea, myalgia, fatigue, loss of appetite, olfactory and gustatory dysfunctions are the most prevalent general symptoms. Decreased immune system cells such as suppressed regulatory T cells, cytotoxic and helper T cells, natural killer cells, monocytes/macrophages and increased proinflammatory cytokines are the characteristic features. Compounds derived from Allium sativum (garlic) have the potential to decrease the expression of proinflammatory cytokines and to reverse the immunological abnormalities to more acceptable levels. Allium sativum is suggested as a beneficial preventive measure before being infected with SARS‐CoV‐2 virus. Allium sativum is a functional food well-known for its immunomodulatory, antimicrobial, antiinflammatory, antimutagenic, antitumor properties. Its antiviral efficiency was also demonstrated. Some constituents of this plant were found to be active against protozoan parasites. Within this context, it appears to reverse most immune system dysfunctions observed in patients with COVID-19 infection. The relations among immune system parameters, leptin, leptin receptor, adenosin mono phosphate-activated protein kinase, peroxisome proliferator activated receptor-gamma have also been interpreted. Leptin’s role in boosting proinflammatory cytokines and in appetite decreasing suggest the possible beneficial effect of decreasing the concentration of this proinflammatory adipose tissue hormone in relieving some symptoms detected during COVID-19 infection. In conclusion, Allium sativum may be an acceptable preventive measure against COVID-19 infection to boost immune system cells and to repress the production and secretion of proinflammatory cytokines as well as an adipose tissue derived hormone leptin having the proinflammatory nature. url: https://www.sciencedirect.com/science/article/pii/S0306987720313487?v=s5 doi: 10.1016/j.mehy.2020.109934 id: cord-299911-v95pf3eg author: El-Ghiaty, Mahmoud A. title: Cytochrome P450-mediated drug interactions in COVID-19 patients: current findings and possible mechanisms date: 2020-06-26 words: 5319.0 sentences: 272.0 pages: flesch: 37.0 cache: ./cache/cord-299911-v95pf3eg.txt txt: ./txt/cord-299911-v95pf3eg.txt summary: Based on the conclusions drawn from the currently rapidly evolving knowledge about COVID-19, our hypothesis is built on the potential modulation of CYPs activity by the inflammatory environment provoked by SARS-CoV-2 infection, as well as the pathologic involvement of the liver which harbors the majority of the drug metabolizing enzymes (DMEs). Systemic inflammation and immune response represent a substantial element in many acute and chronic diseases which is strongly implicated in altering drug pharmacokinetics through, mainly, modulating the expression and activity of DMEs. As a main contributor to the metabolic biotransformation of most drugs, CYPs are widely involved in such disease-drug interactions [19] . For decades, IL-6 has been recognized as the major inflammatory element that provokes a significant repressive effect on the expression and activity of different CYPs. Human recombinant interleukin 6 (rhIL-6) has shown concentration-dependent blocking of phenobarbital-mediated induction of CYP2B1/2 mRNA and activity in rat hepatocytes [48] . abstract: At the end of 2019, the entire world has witnessed the birth of a new member of coronavirus family in Wuhan, China. Ever since, the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has swiftly invaded every corner on the planet. By the end of April 2020, almost 3.5 million cases have been reported worldwide, with a death toll of about 250000 deaths. It is currently well-recognized that patient’s immune response plays a pivotal role in the pathogenesis of Coronavirus Disease 2019 (COVID-19). This inflammatory element was evidenced by its elevated mediators that, in severe cases, reach their peak in a cytokine storm. Together with the reported markers of liver injury, such hyperinflammatory state may trigger significant derangements in hepatic cytochrome P450 metabolic machinery, and subsequent modulation of drug clearance that may result in unexpected therapeutic/toxic response. We hypothesize that COVID-19 patients are potentially vulnerable to a significant disease-drug interaction, and therefore, suitable dosing guidelines with therapeutic drug monitoring should be implemented to assure optimal clinical outcomes. url: https://www.sciencedirect.com/science/article/pii/S0306987720311750?v=s5 doi: 10.1016/j.mehy.2020.110033 id: cord-296253-bxyzhsfs author: Elham, Elzat title: Anatomic evidence shows that lymphatic drainage exists in the pituitary to loop the cerebral lymphatic circulation date: 2020-05-30 words: 1686.0 sentences: 87.0 pages: flesch: 41.0 cache: ./cache/cord-296253-bxyzhsfs.txt txt: ./txt/cord-296253-bxyzhsfs.txt summary: To determine whether the perinasal lymphatic system or lymphatic vessels are involved in cerebral immune defence and play a role in causing CNS infections (especially respiratory tract-related infections), we performed an anatomic study to investigate the drainage differences between the perinasal and intracerebral lymphatic systems by using injection of Evans blue and anatomic surgery, together with immunohistochemistry and immunofluorescence assays. To determine whether the perinasal lymphatic system or lymphatic vessels are involved in cerebral immune defence and play a role in causing CNS infections (especially respiratory tract-related infections), we performed an anatomic study to investigate the drainage differences between the perinasal and intracerebral lymphatic systems by using injection of Evans blue and anatomic surgery, together with immunohistochemistry and immunofluorescence assays. Under an anatomic (20× magnification) microscope, we dissected the mouse intracranial nervous system after injection of Evans blue (perinasal lymphatic reflux assay) and found that lymphatic vessels that exist in the pituitary and loop the cerebral lymphatic circulation are responsible for the perinasal-pituitary lymphatic drainage. abstract: Respiratory infections can result in intracranial infections and unknown neurological symptoms. The central nervous system lacks classical meningeal lymphatic (circulation) drainage, and the exact underlying mechanisms of how immune cells from the peripheral lymphatic system enter the central nervous system (CNS) remain unknown. To determine whether the perinasal lymphatic system or lymphatic vessels are involved in cerebral immune defence and play a role in causing CNS infections (especially respiratory tract-related infections), we performed an anatomic study to investigate the drainage differences between the perinasal and intracerebral lymphatic systems by using injection of Evans blue and anatomic surgery, together with immunohistochemistry and immunofluorescence assays. Surprisingly, we found that (1) the pituitary (adenohypophysis) is involved and is rich in lymphatic vessels and (2) perinasal tissue could communicate with central pituitary lymphatic vessels in a specific and unidirectional manner. Taken together, our study may be the first to anatomically demonstrate the existence of novel lymphatic vessel structures in the pituitary, as well as their communication with the perinasal (lymphatic) tissue. Our findings suggest the existence of an ultimate loop for “classical” meningeal lymphatic drainage and are relevant to cerebral infection and immune defence. url: https://www.sciencedirect.com/science/article/pii/S0306987720313293?v=s5 doi: 10.1016/j.mehy.2020.109898 id: cord-253468-pf0xubii author: Emara, Mohamed H title: Ketonuria with or without ketoacidosis as the presenting manifestation of SARS-CoV-2 (COVID-19) among uncontrolled Type 2 Diabetic patients date: 2020-09-02 words: 986.0 sentences: 57.0 pages: flesch: 58.0 cache: ./cache/cord-253468-pf0xubii.txt txt: ./txt/cord-253468-pf0xubii.txt summary: title: Ketonuria with or without ketoacidosis as the presenting manifestation of SARS-CoV-2 (COVID-19) among uncontrolled Type 2 Diabetic patients We hereby present the data of 3 patients presented to our OPD and were admitted as diabetic ketoacidosis (DKA) and 2-3 days later they developed manifestations suggestive of and proved by swabbing as positive cases. Chest auscultation and chest X ray were unremarkable and hence chest CT scan was requested ( Figure 1 ) and showed picture suggestive of mild-moderate COVID-19, swabbing was done and came positive Case 2: A 51-year-old male, presented by dizziness over last 2-3 days and when examined found to have high RBS and ketonuria, and hence admitted as KDA, and was acidotic (PH 7). A 62-year-old male patient who was not compliant with his medicines over the last 2 months, presented for renewal of medicine without any clinical manifestations, found to have panic RBS measurement, and was positive for urine ketones. abstract: We present three diabetic patients cases presented with kentonuria as the presenting manifestation of SARS-CoV-2 infection. url: https://api.elsevier.com/content/article/pii/S0306987720324828 doi: 10.1016/j.mehy.2020.110226 id: cord-306146-i4a74j3r author: Fitzgerald, Paul J. title: Noradrenergic and serotonergic drugs may have opposing effects on COVID-19 cytokine storm and associated psychological effects date: 2020-06-09 words: 573.0 sentences: 37.0 pages: flesch: 33.0 cache: ./cache/cord-306146-i4a74j3r.txt txt: ./txt/cord-306146-i4a74j3r.txt summary: In addition to its role in various psychiatric, neurologic, and cardiovascular functions, there is increasing evidence that NE plays a role in the symptomatology associated with serious systemic infections such as influenza, including activation of cytokine signaling such as IL-6 as well as the manifestation of psychological effects associated with infection 3 . I suggest here that this cytokine storm may be counteracted by a range of clinically used drugs that reduce NE transmission (but that may not act through direct effects on viral replication or viral entry into cells) 5 : alpha2 agonists such as clonidine, guanfacine, dexmedetomidine; various beta blockers such as propranolol, nebivolol, carvedilol, atenolol; and various alpha1 antagonists such as prazosin 4 . If COVID-19 is accompanied by systemically elevated NE signaling, the various drugs listed above may also counteract deleterious psychological effects associated with this infection 3 . Conflicts of interest The author reports no conflicts of interest, and no funding source directly supported this work abstract: nan url: https://www.ncbi.nlm.nih.gov/pubmed/32554324/ doi: 10.1016/j.mehy.2020.109985 id: cord-289905-dvl2pud2 author: Gan, Rosemary title: COVID-19 as a Viral Functional ACE2 Deficiency Disorder with ACE2 Related Multi-organ Disease date: 2020-06-23 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: SARS-CoV-2, the agent of COVID-19, shares a lineage with SARS-CoV-1, and a common fatal pulmonary profile but with striking differences in presentation, clinical course, and response to treatment. In contrast to SARS-CoV-1 (SARS), COVID-19 has presented as an often bi-phasic, multi-organ pathology, with a proclivity for severe disease in the elderly and those with hypertension, diabetes and cardiovascular disease. Whilst death is usually related to respiratory collapse, autopsy reveals multi-organ pathology. Chronic pulmonary disease is underrepresented in the group with severe COVID-19. A commonality of aberrant renin angiotensin system (RAS) is suggested in the at-risk group. The identification of angiotensin-converting-enzyme 2 (ACE2) as the receptor allowing viral entry to cells precipitated our interest in the role of ACE2 in COVID-19 pathogenesis. We propose that COVID-19 is a viral multisystem disease, with dominant vascular pathology, mediated by global reduction in ACE2 function, pronounced in disease conditions with RAS bias toward angiotensin-converting-enzyme (ACE) over ACE2. It is further complicated by organ specific pathology related to loss of ACE2 expressing cells particularly affecting the endothelium, alveolus, glomerulus and cardiac microvasculature. The possible upregulation in ACE2 receptor expression may predispose individuals with aberrant RAS status to higher viral load on infection and relatively more cell loss. Relative ACE2 deficiency leads to enhanced and protracted tissue, and vessel exposure to angiotensin II, characterised by vasoconstriction, enhanced thrombosis, cell proliferation and recruitment, increased tissue permeability, and cytokine production (including IL-6) resulting in inflammation. Additionally, there is a profound loss of the “protective” angiotensin (1-7), a vasodilator with anti-inflammatory, anti-thrombotic, antiproliferative, antifibrotic, anti-arrhythmic, and antioxidant activity. Our model predicts global vascular insult related to direct endothelial cell damage, vasoconstriction and thrombosis with a disease specific cytokine profile related to angiotensin II rather than “cytokine storm”. Our proposed mechanism of lung injury provides an explanation for early hypoxia without reduction in lung compliance and suggests a need for revision of treatment protocols to address vasoconstriction, thromboprophylaxis, and to minimize additional small airways and alveolar trauma via ventilation choice. Our model predicts long term sequelae of scarring/fibrosis in vessels, lungs, renal and cardiac tissue with protracted illness in at-risk individuals. It is hoped that our model stimulates review of current diagnostic and therapeutic intervention protocols, particularly with respect to early anticoagulation, vasodilatation and revision of ventilatory support choices. url: https://doi.org/10.1016/j.mehy.2020.110024 doi: 10.1016/j.mehy.2020.110024 id: cord-261574-zcazhkad author: García, Néstor H. title: Ibuprofen, a traditional drug that may impact the course of COVID-19 New effective formulation in nebulizable solution date: 2020-07-07 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The traditional formulation of ibuprofen is poorly soluble in water, so the administered dose must be 10 times higher than the dose required for a therapeutic effect. The development of a hydrosoluble form of ibuprofen can be a strategy to reach a high concentration in the lungs by using modern inhalation devices. Therefore, the development of an inhalable formulation with high bioavailability in the lungs was the leitmotiv of our investigation. The hypertonic ibuprofen solution to be nebulized (NIH) presents great relevant characteristics: bactericidal, virucidal, mucolytic and has a known anti-inflammatory property. Bactericidal and virucidal effects are related to the physico-chemical properties of Na-ibuprofenate as an amphipathic molecule. It has the capability to insert into the bilayer membranes destabilizing the structure, altering its biological properties and avoiding the duplication or infection. Our preliminary results indicate that the presence of this high ionic strength solution reduces 10 times the amount of ibuprofen necessary to kill bacteria, but also the time to kill 1x10(6) bacteria, from 4 hours (in its absence) to only three minutes (in its presence). That was observed using Pseudomona aeruginosa, methicillin-resistant Staphylococcus aureus and Burkholderia cepacia. Also, “in vitro'' ibuprofen demonstrated virucidal activity against the so-called enveloped virus, a family that includes coronavirus strain (2019-nCoV). We observed too, the markedly reduced local inflammation in the airways after administering NIH lays on its ability to inhibit the enzyme cyclooxygenase and to markedly diminish reactive oxygen species (ROS). Other investigators also showed the importance of actin in the rapid spread of virus infection. Furthermore, reorganization of the actin filaments is a key step in lung inflammation induced by systemic inflammatory responses caused by SARS-CoV-2. These findings suggest that the interaction between actin proteins and S1 is involved in the 2019-nCoV infection and pathogenesis. Consequently, the possibility of interfering in this interaction could represent a valid hypothesis for the development of promising therapeutic and prevention strategies. In conclusion, we consider that treating people with COVID-19 with NIH may be beneficial and an opportunity to contribute for the current global health emergency. url: https://api.elsevier.com/content/article/pii/S0306987720320077 doi: 10.1016/j.mehy.2020.110079 id: cord-331428-6pvr2vew author: Heffernan, Kevin S. title: Exercise as medicine for COVID-19: on PPAR with emerging pharmacotherapy date: 2020-08-17 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Coronavirus disease 2019 (COVID-19) may have a metabolic origin given strong links with risk factors such as lipids and glucose and co-morbidities such as obesity and type 2 diabetes mellitus. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein mediates viral cellular entry via the ACE2 receptor. The cytoplasmic tail of this spike protein is heavily palmitoylated. Emerging studies suggest that SARS-CoV-2 alters lipid metabolism in the lung epithelial cells by modulating peroxisome proliferator-activated receptor alpha (PPARα), possibly contributing to lipotoxicity, inflammation and untoward respiratory effects. Disruption of this process may affect palmitoylation of SARS-CoV spike protein and thus infectivity and viral assembly. COVID-19 is also increasingly being recognized as a vascular disease, with several studies noting prominent systemic endothelial dysfunction. The pathogenesis of endothelial dysfunction may also be linked to COVID-19-mediated metabolic and inflammatory effects. Herein, exercise will be compared to fenofibrate as a possible therapeutic strategy to bolster resilience against (and help manage recovery from) COVID-19. This paper will explore the hypothesis that exercise may be a useful adjuvant in a setting of COVID-19 management/rehabilitation due to its effects on PPARα and vascular endothelial function. url: https://www.ncbi.nlm.nih.gov/pubmed/33017906/ doi: 10.1016/j.mehy.2020.110197 id: cord-313382-prxc0lue author: Hossein Norooznezhad, Amir title: Empiric Antibiotics in Management of Inpatient Pregnant Women Infected with Coronavirus Disease 2019 (COVID-19): Focusing on Inflammation and Preterm Labor date: 2020-09-12 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: nan url: https://www.sciencedirect.com/science/article/pii/S0306987720326608?v=s5 doi: 10.1016/j.mehy.2020.110269 id: cord-256092-bph9ys72 author: Hussain, Aneela N. title: Role of testosterone in COVID-19 patients - a double-edged sword? date: 2020-09-17 words: 1574.0 sentences: 93.0 pages: flesch: 43.0 cache: ./cache/cord-256092-bph9ys72.txt txt: ./txt/cord-256092-bph9ys72.txt summary: Current data suggest a direct correlation between the lower level of serum testosterone, inflammatory cytokines, disease severity, and poor clinical outcomes among male patients with COVID-19. Current data suggest a direct correlation between the lower level of serum testosterone, inflammatory cytokines, disease severity, and poor clinical outcomes among male patients with COVID-19. Lower levels of testosterone result in the upregulation of ACE2 and TMPRSS2 receptors, facilitating SARS-CoV-1 entry into the alveolar cells, and deregulating a lung-protective pathway (4) . Thereby we hypothesize that low testosterone levels in males have a direct correlation with the severity of disease and a worse outcome in COVID-19. Patients with low testosterone have reportedly developed severe manifestations requiring assisted ventilation because of the upregulation of ACE-2 receptors in lower respiratory cells, increased risk of lung damage, and respiratory muscle catabolism. Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China abstract: COVID-19 affects males twice as frequently as females with significantly increased severity and mortality. Current data suggest a direct correlation between the lower level of serum testosterone, inflammatory cytokines, disease severity, and poor clinical outcomes among male patients with COVID-19. The gradual decline in total and free testosterone levels has a direct correlation with serious pulmonary complications requiring advanced care (ICU, ventilators, ECMO, etc.). SARS-CoV-2 utilizes Angiotensin-Converting Enzyme II (ACE2) for entry in the host cell, and Transmembrane Protease, Serine 2 (TMPRSS2) to prime spike protein of SARS-CoV-2. Testosterone induces ACE-2 expression, a critical pulmonary protective enzyme. Low testosterone levels in males have a direct correlation with the high probability of ICU admission and the worse disease outcome (ARDS, duration of ICU stay, mortality). On the contrary, however, high testosterone levels can lead to thrombosis which is also one of the fatal manifestations in COVID-19 patients. A critical evaluation of the serum testosterone and its relevance to COVID-19 is warranted to re-evaluate strategies to effectively triage, prioritize, and manage high-risk patients for ICU admission, survival outcomes, targeted solutions, and operational algorithms. url: https://api.elsevier.com/content/article/pii/S0306987720321915 doi: 10.1016/j.mehy.2020.110287 id: cord-270805-o6rbfmie author: Hussein, Osama title: Second wave of of Covid-19 is determined by immune mechanism date: 2020-09-02 words: 622.0 sentences: 47.0 pages: flesch: 53.0 cache: ./cache/cord-270805-o6rbfmie.txt txt: ./txt/cord-270805-o6rbfmie.txt summary: In this letter, the author describes an immunological explanation for the double-peaked epidemic curve of new viral diseases including Covid-19. This theory claims that a double-peaked pattern of new cases in a new viral epidemic is intrinsically determined by the pattern of pathogen interaction with the host. According to this hypothesis, relaxation of the community control measures is not responsible; at least in part, for resurgence of cases. Assuming the above hypothesis is true; a viral epidemic curve will show an early upstroke corresponding to persons who pass into viremia upon initial exposure to the virus followed by a second slower rise due to cases who develop the disease after repeated process of inoculation and clearance at the point of entry. In conclusion, the author describes an immunological explanation for a double-peaked epidemic curve of Covid-19 and other new viral diseases. abstract: A second wave of new severe acute respiratory syndrome coronavirus 2 (Covid-19) cases is widely feared. In fact resurgence of cases has been clearly observed in several countries that had seen flattening of the epidemic curve. In general, relaxation of community control measures is almost always blamed for the resurgence of cases. In this letter, the author describes an immunological explanation for the double-peaked epidemic curve of new viral diseases including Covid-19. According to this hypothesis, a second wave of cases is due to the effective innate immunity in some of the population. These individuals may later develop clinical disease upon repeated exposure. This theory claims that a double-peaked pattern of new cases in a new viral epidemic is intrinsically determined by the pattern of pathogen interaction with the host. According to this hypothesis, relaxation of the community control measures is not responsible; at least in part, for resurgence of cases. url: https://api.elsevier.com/content/article/pii/S0306987720324579 doi: 10.1016/j.mehy.2020.110238 id: cord-291037-19csqq89 author: Janssen, Rob title: Vitamin K epoxide reductase complex subunit 1 (VKORC1) gene polymorphism as determinant of differences in Covid-19-related disease severity date: 2020-08-25 words: 2200.0 sentences: 118.0 pages: flesch: 41.0 cache: ./cache/cord-291037-19csqq89.txt txt: ./txt/cord-291037-19csqq89.txt summary: title: Vitamin K epoxide reductase complex subunit 1 (VKORC1) gene polymorphism as determinant of differences in Covid-19-related disease severity A genetic polymorphism in the vitamin K epoxide reductase complex 1, VKORC1 -1639A, is particularly prevalent in East Asia and associates with low vitamin K recycling rates. A genetic polymorphism in the vitamin K epoxide reductase complex 1, VKORC1 -1639A, is particularly prevalent in East Asia and associates with low vitamin K recycling rates. We speculate that the disparity in morbidity and mortality from Covid-19 between East and West may be at least partially explained by differences in the allele distribution of a VKORC1 polymorphism determining the rate of vitamin K recycling. If the VKORC1 -1639A allele is shown to be associated with decreased thrombotic complications and/or death, it would further support the hypothesis that vitamin K metabolism is an important determinant of Covid-19-related disease severity. abstract: Covid-19, caused by SARS-CoV-2, has major world-wide health-related and socio-economic consequences. There are large disparities in the burden of Covid-19 with an apparent lower risk of poor outcomes in East Asians compared to populations in the West. A recent study suggested that Covid-19 leads to a severe extrahepatic vitamin K insufficiency, which could lead to impaired activation of extrahepatic proteins like endothelial anticoagulant protein S in the presence of normal hepatic procoagulant activity. This would be compatible with the enhanced thrombogenicity in severe Covid-19. The same study showed that vitamin K antagonists (VKA) that inhibit vitamin K recycling, had a greater impact on procoagulant activity than on the activation of extrahepatic vitamin K-dependent proteins during SARS-CoV-2 infections. A genetic polymorphism in the vitamin K epoxide reductase complex 1, VKORC1 -1639A, is particularly prevalent in East Asia and associates with low vitamin K recycling rates. Carriage of the allele may be regarded as bioequivalent to low-dose VKA use. We speculate that VKORC1 -1639A confers protection against thrombotic complications of Covid-19 and that differences in its allele frequency are partially responsible for the differences in Covid-19 severity between East and West. url: https://www.sciencedirect.com/science/article/pii/S0306987720324713?v=s5 doi: 10.1016/j.mehy.2020.110218 id: cord-288009-8i3gsq9p author: Javor, S. title: Why not consider an endothelin receptor antagonist against SARS‐CoV‐2? date: 2020-04-25 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: nan url: https://api.elsevier.com/content/article/pii/S0306987720305739 doi: 10.1016/j.mehy.2020.109792 id: cord-328587-vctvcyim author: Jun, Sun title: The hypothesis that SARS-CoV-2 affects male reproductive ability by regulating autophagy date: 2020-07-10 words: 2990.0 sentences: 143.0 pages: flesch: 47.0 cache: ./cache/cord-328587-vctvcyim.txt txt: ./txt/cord-328587-vctvcyim.txt summary: According to the existing clinical data, some patients not only suffer from respiratory diseases, but also have complications such as acute renal injury and even renal necrosis [2] [3] [4] , in addition, SARS-CoV-2 was also found in recent semen analysis of male patients [5] . Previous clinical data have shown that in addition to respiratory diseases, some male patients with COVID-19 are accompanied by kidney damage and even renal failure [2] [4], which suggest that SARS-CoV-2 may affect male fertility. Furthermore, clinical data also show that the receptor protein ACE2 that mediates the entry of SARS-CoV-2 into host cells is not only expressed in alveolar cells, but also highly expressed in male renal tubular cells [4] [21] [30] .All these suggest that SARS-CoV-2 not only causes damage to the respiratory system of patients, but also has a certain impact on the reproductive system of male patients. abstract: The outbreak of CoronaVirus Disease19 (COVID19) in December 2019 posed a serious threat to public safety, and its rapid spread caused a global health emergency. Clinical data show that in addition to respiratory system damage, some male patients with COVID-19 are also accompanied by abnormal renal function and even renal damage. As the main receptor of syndrome coronavirus 2 (SARS-CoV-2), angiotensin converting enzyme 2 (ACE2) is also found to be highly expressed not only in respiratory mucosa and alveolar epithelial cells, but also in renal tubule cells, testicular Leydig cells and seminiferous tubule cells. This suggests that SARS-CoV-2 has the possibility of infecting the male reproductive system, and the recent detection of SARS-CoV-2 in the patient's semen further confirms this theory. In previous studies, it has been found that ACE2 has the ability to regulate autophagy. Not only that, recent studies have also found that SARS-CoV-2 infection can also lead to a reduction in autophagy. All of these associate SARS-CoV-2 with autophagy. Furthermore, autophagy has been shown to have an effect on male reproduction in many studies. Based on these, we propose the hypothesis that SARS-CoV-2 affects male reproductive function by regulating autophagy. This hypothesis may provide a new idea for future treatment of COVID-19 male patients with reproductive function injury, and it can also prompt medical staff and patients to consciously check their reproductive function. url: https://doi.org/10.1016/j.mehy.2020.110083 doi: 10.1016/j.mehy.2020.110083 id: cord-258670-dphg8ukj author: Karaahmet, Fatih title: Endothelial progenitor cells and mesenchymal stem cells to overcome vascular deterioration and cytokine storm in critical patients with COVID-19 date: 2020-06-10 words: 599.0 sentences: 40.0 pages: flesch: 35.0 cache: ./cache/cord-258670-dphg8ukj.txt txt: ./txt/cord-258670-dphg8ukj.txt summary: title: Endothelial progenitor cells and mesenchymal stem cells to overcome vascular deterioration and cytokine storm in critical patients with COVID-19 In light of this information, the sufficient repair of the endothelial lining of blood vessels with Endothelial progenitor cells (EPCs) treatment may have a crucial role to overcome the vascular collapse driving forces in COVID-19 patients, as well as to modulate human immune system. Accumulating evidence leads to suggest that bone marrow-derived EPCs for repairing endothelial damage is now considered as an important novel potential therapeutic option for vascular repair (7, 8) . In critical patients in the course of COVID-19, EPCs may have an important contribution to stem cell treatments to maintain vascular endothelin functions. In critical patients who do not respond to current treatment, the restoration of vascular endothelial function and modulation of immune system by synergistic use of EPCs and MSCs may have a crucial role to overcome the vascular collapse driving forces in COVID-19 patients. abstract: nan url: https://www.ncbi.nlm.nih.gov/pubmed/32590321/ doi: 10.1016/j.mehy.2020.109973 id: cord-288733-c51lfwd6 author: Kavanagh, Oisín title: Inhaled Hydroxychloroquine to Improve Efficacy and Reduce Harm in the Treatment of COVID-19 date: 2020-07-15 words: 769.0 sentences: 51.0 pages: flesch: 55.0 cache: ./cache/cord-288733-c51lfwd6.txt txt: ./txt/cord-288733-c51lfwd6.txt summary: An analysis of clinical trials registered on ClinicalTrials.gov revealed that this may continue as many studies combine HCQ with agents that prolong the QT interval. Here we describe an inhaled formulation of HCQ which has passed safety studies in clinical trials for the treatment of asthma and discuss how this approach may reduce side-effects and improve efficacy. Chloroquine and hydroxychloroquine (HCQ) were two of the earliest drugs to 33 receive attention as possible repurposable treatment options for COVID-19 3 . Concerns associated with severe side effects 41 are such that the FDA and EMA now formally recommend against taking HCQ for COVIDEffects of chloroquine on 178 viral infections: An old drug against today''s diseases? FDA Drug Safety Communication: FDA cautions 199 against use of hydroxychloroquine or chloroquine for COVID-19 outside of the 200 hospital setting or a clinical trial due to risk of heart rhythm problems Optimizing hydroxychloroquine 210 dosing for patients with COVID-19: An integrative modeling approach for effective 211 drug repurposing abstract: Current formulations and dose regimens of hydroxychloroquine (HCQ) put patients at risk of harm. An analysis of clinical trials registered on ClinicalTrials.gov revealed that this may continue as many studies combine HCQ with agents that prolong the QT interval. Further, almost all of the trials registered do not consider dosage adjustment in the elderly, a patient population most likely to require HCQ treatment. Here we describe an inhaled formulation of HCQ which has passed safety studies in clinical trials for the treatment of asthma and discuss how this approach may reduce side-effects and improve efficacy. As this simple formulation progressed to phase II studies, safety data can be used to immediately enable phase II trials in COVID-19. url: https://www.ncbi.nlm.nih.gov/pubmed/33017904/ doi: 10.1016/j.mehy.2020.110110 id: cord-320508-egw7bvzf author: Kennedy, James R. title: Phosphatidylserine’s role in Ebola’s inflammatory cytokine storm and hemorrhagic consumptive coagulopathy and the therapeutic potential of annexin V date: 2019-10-28 words: 2478.0 sentences: 113.0 pages: flesch: 45.0 cache: ./cache/cord-320508-egw7bvzf.txt txt: ./txt/cord-320508-egw7bvzf.txt summary: The phosphatidylserine (PS) molecule is present in cell membranes where it is actively kept on their inner leaflets but when cells are damaged it moves to the surface and become a signal for their removal, the platform upon which the coagulation cascade takes place and a ligand that activates a feedback cycle of inflammatory cytokine secretion and initiates the wakeup call for the innate immune response. The phosphatidylserine (PS) molecule is present in cell membranes where it is actively kept on their inner leaflets but when cells are damaged it moves to the surface and become a signal for their removal, the platform upon which the coagulation cascade takes place and a ligand that activates a feedback cycle of inflammatory cytokine secretion and initiates the wakeup call for the innate immune response. The hypothesis presented here is that annexin V''s therapeutic administration in Ebola can prevent its Th1 cell generated inflammatory cytokine storm, stop the cascade generated hemorrhagic consumptive coagulopathy and prevent macrophage and dendritic cell infection. abstract: The phosphatidylserine (PS) molecule is present in cell membranes where it is actively kept on their inner leaflets but when cells are damaged it moves to the surface and become a signal for their removal, the platform upon which the coagulation cascade takes place and a ligand that activates a feedback cycle of inflammatory cytokine secretion and initiates the wakeup call for the innate immune response. These are physiologic responses to PS but the Ebola virus displays PS molecules on its membrane’s surface and the huge numbers of viruses cause a pathologic inflammatory cytokine storm and a hemorrhagic consumptive coagulopathy. Annexin V is an innate molecule that can cloak membrane displayed PS and prevents its Th1 cell’s inflammatory cytokine generation and cascade thrombin generation. The hypothesis presented is that its administration will cloak PS and prevent Ebola’s consumptive coagulopathy and its cytokine storm. url: https://www.ncbi.nlm.nih.gov/pubmed/31731057/ doi: 10.1016/j.mehy.2019.109462 id: cord-290803-v5ndlk9c author: Khan, Imran title: Can COVID-19 induce glioma tumorogenesis through binding cell receptors? date: 2020-06-19 words: 909.0 sentences: 58.0 pages: flesch: 48.0 cache: ./cache/cord-290803-v5ndlk9c.txt txt: ./txt/cord-290803-v5ndlk9c.txt summary: Therefore in the light of these known facts we hypothesized that viral S protein molecule may bind to the other overexpressed receptor molecules in glioma cells and may play some role in glioma tumorogenesis. Thus we leverage docking analysis (HEX and Z-DOCK) between viral S protein and epidermal growth factor receptors (EGFR), vascular endothelial growth factor receptors (VEGFR) and hepatocyte growth factor receptors (HGFR/c-MET) to investigate the oncogenic potential of COVID-19. Thus we leverage docking analysis (HEX and Z-DOCK) between viral S protein and epidermal growth factor receptors (EGFR), vascular endothelial growth factor receptors (VEGFR) and hepatocyte growth factor receptors (HGFR/c-MET) to investigate the oncogenic potential of COVID-19. Considering the importance of these surface receptors on glioma cells, we studied the interaction between EGFR, VEGFR and c-MET receptor proteins with S protein of COVID-19. Our preliminary findings suggested that COVID-19 S protein might have a binding affinity to EGFR, c-MET and VEGFR on glioma cells. abstract: The outbreak of Novel Coronavirus 2019 (COVID-19) represents a global threat to the public healthcare. The viral spike (S) glycoprotein is the key molecule for viral entry through interaction with angiotensin converting enzyme 2 (ACE2) receptor molecules present on the cell membranes. Moreover, it has been established that COVID-19 interacts and infects brain cells in humans via ACE2. Therefore in the light of these known facts we hypothesized that viral S protein molecule may bind to the other overexpressed receptor molecules in glioma cells and may play some role in glioma tumorogenesis. Thus we leverage docking analysis (HEX and Z-DOCK) between viral S protein and epidermal growth factor receptors (EGFR), vascular endothelial growth factor receptors (VEGFR) and hepatocyte growth factor receptors (HGFR/c-MET) to investigate the oncogenic potential of COVID-19. Our findings suggested higher affinity of Viral S protein towards EGFR and VEGFR. Although, the data presented is preliminary and need to be validated further via molecular dynamics studies, however it paves platform to instigate further investigations on this aspect considering the aftermath of COVID-19 pandemic in oncogenic perspective. url: https://www.ncbi.nlm.nih.gov/pubmed/32758869/ doi: 10.1016/j.mehy.2020.110009 id: cord-277931-3hxhsmw8 author: Khitan, Zeid J. title: SCan Charcoal Improve Outcomes in COVID-19 Infections? date: 2020-08-10 words: 1090.0 sentences: 60.0 pages: flesch: 44.0 cache: ./cache/cord-277931-3hxhsmw8.txt txt: ./txt/cord-277931-3hxhsmw8.txt summary: We propose to examine the potential utility of oral activated charcoal with the hypothesis that such treatment would lower absorption of microbiome derived toxins and ameliorate systemic oxidant stress and inflammation. We propose to examine the potential utility of oral activated charcoal with the hypothesis that such treatment would lower absorption of microbiome derived toxins and ameliorate systemic oxidant stress and inflammation. It appears that age, renal dysfunction and obesity are amongst the most important risk factors for serious or fatal COVID-19 infection 3, 4 . To test this hypothesis, we would suggest first a proof of concept study where a relatively small group of patients at high risk for COVID-19 complications are given activated charcoal at doses similar to that used in previous renal failure studies 18, 19 when the diagnosis is first made. Uremic Toxins Activates Na/K-ATPase Oxidant Amplification Loop Causing Phenotypic Changes in Adipocytes in In Vitro Models Protein-bound uremic toxins, inflammation and oxidative stress: a cross-sectional study in stage 3-4 chronic kidney disease abstract: COVID-19 infection causes considerable morbidity and mortality, especially to those who are aged, have impaired renal function and are obese. We propose to examine the potential utility of oral activated charcoal with the hypothesis that such treatment would lower absorption of microbiome derived toxins and ameliorate systemic oxidant stress and inflammation. url: https://www.sciencedirect.com/science/article/pii/S0306987720324245?v=s5 doi: 10.1016/j.mehy.2020.110176 id: cord-286038-a62k3lma author: Klimke, A. title: Hydroxychloroquine as an aerosol might markedly reduce and even prevent severe clinical symptoms after SARS-CoV-2 infection date: 2020-04-27 words: 2336.0 sentences: 104.0 pages: flesch: 45.0 cache: ./cache/cord-286038-a62k3lma.txt txt: ./txt/cord-286038-a62k3lma.txt summary: The antimalarial drugs chloroquine phosphate (CQ) and hydroxychloroquine (HCQ) impair in vitro the terminal glycosylation of ACE2 without significant change of cell-surface ACE2 and, therefore, might be potent inhibitors of SARS-CoV-2 infections. We hypothesize that HCQ especially as an aerosol application will prevent or at least markedly reduce the replication rate of the SARS-CoV-2 virus in the early phase of the infection and subsequently substantially lower the number of severe pneumonias and casualties. This hypothesis is new since the major assumption in ongoing clinical studies and actual recommendations is that HCQ and CQ should be used in oral application form in patients with severe covid-19 pneumonia and only when other treatment strategies have failed. If our hypothesis is true, HCQ as an aerosol might not only reduce the side effect potential of the oral application form but can also be clinically used as an efficient antiviral agent in the early phase of COVID-19 and eventually lower the rate of severely ill patients and fatalities. abstract: Covid-19 is a new coronavirus disease first described in December 2019. This respiratory illness is severe and potentially fatal. Severe cases make up to 15%, lethality ranges between 1.5 and more than 10 %. What is urgently needed is an efficient pharmacological treatment for the treatment of severe cases. During the infection of alveolar epithelial cells of the lung, the ACE2 receptor has a central function. The antimalarial drugs chloroquine phosphate (CQ) and hydroxychloroquine (HCQ) impair in vitro the terminal glycosylation of ACE2 without significant change of cell-surface ACE2 and, therefore, might be potent inhibitors of SARS-CoV-2 infections. Starting inhibition at 0.1 µM, CQ completely prevented in vitro infections at 10 µM, suggesting a prophylactic effect and preventing the virus spread 5 hours after infection. In a first clinical trial, CQ was effective in inhibiting exacerbation of pneumonia, improving lung imaging findings, promotion of virus-negative conversion, and shortening the disease. In addition, HCQ, which is three times more potent than CQ in SARS-CoV-2 infected cells (EC50 0.72 µM), was significantly associated with viral load reduction/disappearance in COVID-19 patients compared to controls. Theoretically, CQ and HCQ could thus be effectively used in the treatment of SARS-CoV pneumonia. From a pharmacological standpoint, however, the major problems of oral treatment with these drugs are possible severe side effects and toxicity. Concretely, this relates to (a) the inconsistent individual bioavailability of these drugs at the alveolar target cells, depending on intestinal resorption, hepatic first-pass metabolism and accumulation in liver, spleen and lung, and (b) the need for a relatively high concentration of 1-5 µM at the alveolar surface. Therefore, we propose in a first dose estimation the use of HCQ as an aerosol in a dosage of 2-4 mg per inhalation in order to reach sufficient therapeutic levels at the alveolar epithelial cells. By using a low-dose non-systemic aerosol, adverse drug reactions will markedly be reduced compared with oral application. This increase in tolerability enables a broader use for prevention and after contact with an infected person, which would be an advantage especially for the high-risk, often multi-morbid and elderly patients. Empirical data on self-medication with a one-week aerosol application by two of the authors is presented. Inhalation was well tolerated without relevant side effects. url: https://doi.org/10.1016/j.mehy.2020.109783 doi: 10.1016/j.mehy.2020.109783 id: cord-353716-gxgvhhv1 author: Kumar, Ashutosh title: SARS-CoV-2 cell entry receptor ACE2 mediated endothelial dysfunction leads to vascular thrombosis in COVID-19 patients date: 2020-09-30 words: 2300.0 sentences: 136.0 pages: flesch: 40.0 cache: ./cache/cord-353716-gxgvhhv1.txt txt: ./txt/cord-353716-gxgvhhv1.txt summary: title: SARS-CoV-2 cell entry receptor ACE2 mediated endothelial dysfunction leads to vascular thrombosis in COVID-19 patients Based on the circumstantial evidence present in the literature, we propose a SARS-CoV-2 cell entry receptor ACE2 based mechanism for vascular thrombosis in COVID-19 patients. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative pathogen for COVID-19 has been shown to bind to angiotensin converting enzyme 2 (ACE2) protein in human epithelial cells, which facilitates its entry in the organ and mediate tissue specific pathogenesis (4,5). Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative pathogen for COVID-19 has been shown to bind to angiotensin converting enzyme 2 (ACE2) protein in human epithelial cells, which facilitates its entry in the organ and mediate tissue specific pathogenesis (4,5). SARS-CoV-2 binding to the cell entry receptor ACE2 downregulates receptor expression that in turn induces vascular endothelial dysfunction, which activates prothrombotic cascade and eventually leads to vascular thrombosis observed in COVID-19 patients. abstract: Several studies have described unusually high incidence of vascular thrombosis in coronavirus disease-2019 (COVID-19) patients. Pathogenesis of the vascular thrombosis in COVID-19 is least understood for now and presents a challenge to the treating physicians. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative pathogen for COVID-19, has been shown to bind to angiotensin converting enzyme 2 (ACE2) protein in human epithelial cells which facilitates its entry in the organ and mediate tissue specific pathogenesis. For ACE2 mediated cell entry of the SARS-CoV-2, co-expression of one more protein—Transmembrane protease serine 2 (TMPRSS2) is essential. Existing studies suggested significant expression of ACE2 and TMPRSS2 in human vascular endothelium. Vascular endothelial dysfunction can potentially activate coagulation cascade eventually resulting in thrombosis. ACE2 has proven role in the maintenance of endothelial integrity inside the vessels. Existing in situ evidence for SARS-CoV-1 (the causative agent for SARS pandemic of 2002, which shared ACE2 as cell entry receptor) suggested that virus binding can downregulate ACE2, thus can induce endothelial dysfunction. Recently, in situ evidence has been presented that SARS-CoV-2 can infect cells in engineered human vascular endothelium, which can be effectively blocked by using clinical-grade recombinant human ACE2. Based on the circumstantial evidence present in the literature, we propose a SARS-CoV-2 cell entry receptor ACE2 based mechanism for vascular thrombosis in COVID-19 patients. url: https://www.ncbi.nlm.nih.gov/pubmed/33032170/ doi: 10.1016/j.mehy.2020.110320 id: cord-320959-sgdqhtns author: Lee, Hanjun title: Vitamin E Acetate as Linactant in the Pathophysiology of EVALI date: 2020-08-12 words: 6709.0 sentences: 305.0 pages: flesch: 34.0 cache: ./cache/cord-320959-sgdqhtns.txt txt: ./txt/cord-320959-sgdqhtns.txt summary: In membrane biophysics, Vitamin E is a linactant and a potent modulator of lateral phase separation that effectively reduces the line tension at the two-dimensional phase boundaries and thereby exponentially increases the surface viscosity of the pulmonary surfactant. Supplementation of pulmonary surfactants which retain moderate level of cholesterol and 10 controlled hypothermia for patients are recommended when the hypothesis that the line-active property of the vitamin derivative drives the pathogenesis of EVALI holds. Currently, there are 5 five established non-antioxidative properties of Vitamin E in the biological system: i) its ability to induce gel-liquid crystalline phase transition, ii) its active deposition in the lipid droplet of macrophages, iii) its modulation of the antidiabetic cascade involving diacylglycerol kinase (DGK) and protein kinase C (PKC), iv) its activation of the xenobiotic-sensing pregnane X receptor (PXR) signaling, and v) its ability to modulate lateral phase separation. abstract: The recent identification of Vitamin E acetate as one of the causal agents for the e-cigarette, or vaping, product use associated lung injury (EVALI) is a major milestone. In membrane biophysics, Vitamin E is a linactant and a potent modulator of lateral phase separation that effectively reduces the line tension at the two-dimensional phase boundaries and thereby exponentially increases the surface viscosity of the pulmonary surfactant. Disrupted dynamics of respiratory compression-expansion cycling may result in an extensive hypoxemia, leading to an acute respiratory distress entailing the formation of intraalveolar lipid-laden macrophages. Supplementation of pulmonary surfactants which retain moderate level of cholesterol and controlled hypothermia for patients are recommended when the hypothesis that the line-active property of the vitamin derivative drives the pathogenesis of EVALI holds. url: https://api.elsevier.com/content/article/pii/S0306987720315188 doi: 10.1016/j.mehy.2020.110182 id: cord-334543-gavnscor author: Lim, Rachel K. title: Are night shift workers at an increased risk for COVID-19? date: 2020-07-29 words: 894.0 sentences: 57.0 pages: flesch: 49.0 cache: ./cache/cord-334543-gavnscor.txt txt: ./txt/cord-334543-gavnscor.txt summary: This potential relationship between SARS-CoV-2 infection and clock genes, coupled with previously reported effects of night shift work on health leads us to hypothesize that night shift workers may be at an increased physiological risk of coronavirus disease-19 (COVID19) . This potential relationship between SARS-CoV-2 infection and clock genes, coupled with previously reported effects of night shift work on health leads us to hypothesize that night shift workers may be at an increased physiological risk of coronavirus disease-19 (COVID19) . The mechanisms that drive these associations are not well understood; however, current literature suggests that the disruption of circadian rhythms may cause downstream hormonal and immune effects that render night shift workers more susceptible to disease. The mechanisms that drive these associations are not well understood; however, current literature suggests that the disruption of circadian rhythms may cause downstream hormonal and immune effects that render night shift workers more susceptible to disease. abstract: Recent data has revealed an association between coronavirus disease-19 (COVID-19) incidence and seasonally regulated androgen sensitivity. This potential relationship between SARS-CoV-2 infection and clock genes, coupled with previously reported effects of night shift work on health leads us to hypothesize that night shift workers may be at an increased physiological risk of coronavirus disease-19 (COVID-19). Shift work, especially night shift work, has long been associated with several chronic health conditions. The mechanisms that drive these associations are not well understood; however, current literature suggests that the disruption of circadian rhythms may cause downstream hormonal and immune effects that render night shift workers more susceptible to disease. First, circadian rhythms may play a role in the mechanism of viral infection, as viral vaccines administered in the morning elicit greater immune responses than those administered in the afternoon. Next, increased exposure to light at night may inhibit melatonin production, which has been observed to enhance DNA repair and shown to upregulate expression of Bmal1, an established as an inhibitor of herpes simplex virus and influenza. Finally, abnormal immune cell and cytokine levels have been observed following night-shift work. These data suggest that further research is warranted and that high-risk occupations should be considered as public health policies are introduced and evolve. url: https://doi.org/10.1016/j.mehy.2020.110147 doi: 10.1016/j.mehy.2020.110147 id: cord-267612-1h7xpkbe author: Lipsker, Dan title: A chilblain epidemic during the COVID-19 pandemic. A sign of natural resistance to SARS-CoV-2? date: 2020-06-06 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: nan url: https://www.sciencedirect.com/science/article/pii/S0306987720313414?v=s5 doi: 10.1016/j.mehy.2020.109959 id: cord-279084-bbae1qyx author: Liu, Bin title: Free DNA, a reason for severe COVID-19 infection? date: 2020-05-05 words: 799.0 sentences: 61.0 pages: flesch: 63.0 cache: ./cache/cord-279084-bbae1qyx.txt txt: ./txt/cord-279084-bbae1qyx.txt summary: I hypothesized that the damage induced by free DNA is a reason for severe COVID-19, which can explain many symptoms of this disease, such as cytokine storm, acute respiratory distress syndrome (ARDS) and muscus plug, acute injuries of heart, liver and kidney, and some special symptoms of COVID-19. I hypothesized that the damage induced by free DNA is a reason for severe 23 COVID-19, which can explain many symptoms of this disease, such as cytokine 24 storm, ARDS and muscus plug, acute injuries of heart, liver and kidney, and some 25 special symptoms of COVID-19. Level 60 of lymphocytes is thought as the early identification of risk factors for severe 61 COVID-19, [1] [2] [3] 8 while I hypothesized that it was related to free DNA-related cytokine 62 storm and blood vessel damage, which can explain many symptoms of this disease, 63 including some "special" symptoms in COVID-19, as shown in Figure 1 . abstract: The fast-growing outbreak of 2019 novel coronaviruses (SARS-CoV-2) reached all continents except the Antarctica in merely three months. Severe SARS-CoV-2 infection (COVID-19) has a bad clinical outcome, and some reports emphasized the role of cytokine storm and dysfunctions of multiple organs. However, the etiology of severe COVID-19 has been largely unknown. Similar as SARS-CoV and MERS-CoV, SARS-CoV-2 is also thought derived from bat coronaviruses. However, it is not pathogenic for bat at all, because free DNA in cytoplasm or blood cannot bring up violent immune response in bat; but it can produce severe inflammations in human. I hypothesized that the damage induced by free DNA is a reason for severe COVID-19, which can explain many symptoms of this disease, such as cytokine storm, acute respiratory distress syndrome (ARDS) and muscus plug, acute injuries of heart, liver and kidney, and some special symptoms of COVID-19. My hypothesis will be helpful for better understand the etiology of severe COVID-19. url: https://www.ncbi.nlm.nih.gov/pubmed/32416412/ doi: 10.1016/j.mehy.2020.109812 id: cord-278271-rpq62xhl author: Lyu, Jinglu title: Reflection on lower rates of COVID-19 in children: does childhood immunizations offer unexpected protection? date: 2020-05-15 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The incidence of COVID-19 in children and teenagers is only about 2% in China. Children had mild symptoms and hardly infected other children or adults. It is worth considering that children are the most vulnerable to respiratory pathogens, but fatal SARS-like virus had not caused severe cases among them. According to the pathological studies of COVID-19 and SARS, a sharp decrease in T lymphocytes leads to the breakdown of the immune system. The cellular immune system of children differs from that of adults may be the keystone of atypical clinical manifestations or even covert infection. The frequent childhood vaccinations and repeated pathogens infections might be resulting in trained immunity of innate immune cells, immune fitness of adaptive immune cells or cross-protection of antibodies in the children. Therefore, due to lack of specific vaccine, some vaccines for tuberculosis, influenza and pneumonia may have certain application potential for the front-line health workers in the prevention and control of COVID-19. However, for high-risk susceptible populations, such as the elderly with basic diseases such as hypertension and diabetes, it is necessary to explore the acclimatization effect of the planned immune process on their immunity to achieve the trained immunity or immune fitness, so as to improve their own antiviral ability. url: https://www.sciencedirect.com/science/article/pii/S0306987720305090?v=s5 doi: 10.1016/j.mehy.2020.109842 id: cord-303022-9hqoq7tf author: Madapusi Balaji, Thodur title: Oral cancer and periodontal disease increase the risk of COVID 19? A mechanism mediated through furin and cathepsin overexpression date: 2020-06-01 words: 888.0 sentences: 54.0 pages: flesch: 47.0 cache: ./cache/cord-303022-9hqoq7tf.txt txt: ./txt/cord-303022-9hqoq7tf.txt summary: In addition to furin, another protease cathepsin L is also elevated in chronic periodontitis and oral cancer, which in turn could be a result of the interleukin 6 mediated activation of the caveolin -1 mediated JNK-AP-1 signaling pathway [8] [9] [10] . 3) Following binding of the S1 subunit to the ACE-2 receptors, the virus fuses with the host cell in two mechanisms: (a) endosomal fusion which is mediated by cysteine proteases cathepsin B/L and (b) plasma membrane fusion mediated by the serine protease TMPRSS2. Based on the above-mentioned data, it can be hypothesized that the increased protease levels in chronic periodontitis and oral cancer could potentially increase the risk of an oral mucosa mediated SARS-corona virus-2 infection (figure 1). In addition to increasing proteases, chronic periodontitis, and oral cancer patients have also reported having a low melatonin level [14, 15] . abstract: nan url: https://doi.org/10.1016/j.mehy.2020.109936 doi: 10.1016/j.mehy.2020.109936 id: cord-346281-sma6e891 author: Maldonado, Valente title: Repositioning of pentoxifylline as an immunomodulator and regulator of the renin-angiotensin system in the treatment of COVID-19 date: 2020-06-09 words: 5711.0 sentences: 260.0 pages: flesch: 35.0 cache: ./cache/cord-346281-sma6e891.txt txt: ./txt/cord-346281-sma6e891.txt summary: Pentoxifylline (PTX) is a phosphodiesterase inhibitor that increases cyclic adenosine monophosphate levels, which in turn activate protein kinase, leading to a reduction in the synthesis of proinflammatory cytokines to ultimately influence the renin-angiotensin system (RAS) in vitro by inhibiting angiotensin 1 receptor (AT1R) expression. The rheological, anti-inflammatory, and renin-angiotensin axis properties of PTX highlight this drug as a therapeutic treatment alternative for patients with COVID-19 by helping reduce the production of the inflammatory cytokines without deleterious effects on the immune system to delay viral clearance. 5 Overall, the rheological, anti-inflammatory, and renin-angiotensin axis properties of PTX highlight this drug as a therapeutic treatment alternative for patients with COVID-19, which can help reduce the production of the inflammatory cytokines TNF-α, IL-6, IFN-γ, and IL-17 and increase the anti-inflammatory cytokine IL-10. abstract: Pentoxifylline (PTX) is a phosphodiesterase inhibitor that increases cyclic adenosine monophosphate levels, which in turn activate protein kinase, leading to a reduction in the synthesis of proinflammatory cytokines to ultimately influence the renin-angiotensin system (RAS) in vitro by inhibiting angiotensin 1 receptor (AT1R) expression. The rheological, anti-inflammatory, and renin-angiotensin axis properties of PTX highlight this drug as a therapeutic treatment alternative for patients with COVID-19 by helping reduce the production of the inflammatory cytokines without deleterious effects on the immune system to delay viral clearance. Moreover, PTX can restore the balance of the immune response, reduce damage to the endothelium and alveolar epithelial cells, improve circulation, and prevent microvascular thrombosis. There is further evidence that PTX can improve ventilatory parameters. Therefore, we propose repositioning PTX in the treatment of COVID-19. The main advantage of repositioning PTX is that it is an affordable drug that is already available worldwide with an established safety profile, further offering the possibility of immediately analysing the result of its use and associated success rates. Another advantage is that PTX selectively reduces the concentration of TNF-α mRNA in cells, which, in the case of an acute infectious state such as COVID-19, would seem to offer a more strategic approach. url: https://www.ncbi.nlm.nih.gov/pubmed/32540603/ doi: 10.1016/j.mehy.2020.109988 id: cord-274715-dcs1rgd0 author: Mani Mishra, Pushpendra title: Serum albumin-mediated strategy for the effective targeting of SARS-CoV-2 date: 2020-04-24 words: 2145.0 sentences: 121.0 pages: flesch: 45.0 cache: ./cache/cord-274715-dcs1rgd0.txt txt: ./txt/cord-274715-dcs1rgd0.txt summary: Novel coronavirus (NCoV-19), also known as SARS CoV-2, is a pathogen causing an emerging infection that rapidly increases in incidence and geographic range, is associated with the ever-increasing morbidity and mortality rates, and shows sever economic impact worldwide. We are suggesting here a strategy for the COVID-19 treatment that could be effective in curing the patients in the current scenario when no efficient medicine or Vaccine is currently available, and Clinicians solely depend upon the performing trials with drugs with known antiviral activities. If the albumin is used to stabilize and deliver the EGCG and Curcumin for targeting the intracellular virus components in combination with the drug that could block the virus fusion and/or entry to a cell, this strategy might represent an effective way of treating the SARS CoV-2 infection. abstract: Novel coronavirus (NCoV-19), also known as SARS CoV-2, is a pathogen causing an emerging infection that rapidly increases in incidence and geographic range, is associated with the ever-increasing morbidity and mortality rates, and shows sever economic impact worldwide. The WHO declares the NCoV-19 infection disease (COVID-19) a Public Health Emergency of International Concern on 30 January 2020 and subsequently, on March 11, 2020, declared it a Global Pandemic. Although some people infected with SARS CoV-2 have no symptoms, the spectrum of symptomatic infection ranges from mild to critical, with most COVID-19 infections being not severe. The common mild symptoms include body aches, dry cough, fatigue, low-grade fever, nasal congestion, and sore throat. More severe COVID-19 symptoms are typical of pneumonia, and upon progression, the patient’s condition can worsen with severe respiratory and cardiac problems. Currently, there is no drug or vaccine for curing patients. It has been observed that people with challenged immunity are highly prone to SARS CoV-2 infection and least likely to recover. Also, older adults and people of any age with serious underlying medical conditions might be at higher risk for severe forms of COVID-19. We are suggesting here a strategy for the COVID-19 treatment that could be effective in curing the patients in the current scenario when no efficient medicine or Vaccine is currently available, and Clinicians solely depend upon the performing trials with drugs with known antiviral activities. Our proposed strategy is based on the compilation of published scientific research and concepts. The different published research indicates the success of a similar strategy in different physiological conditions, and such a strategy is widely studied at the cellular level and in animal models. url: https://www.ncbi.nlm.nih.gov/pubmed/32353740/ doi: 10.1016/j.mehy.2020.109790 id: cord-282853-l0c69uul author: Massad, Eduardo title: Forecasting versus projection models in epidemiology: The case of the SARS epidemics date: 2005-03-30 words: 3085.0 sentences: 173.0 pages: flesch: 56.0 cache: ./cache/cord-282853-l0c69uul.txt txt: ./txt/cord-282853-l0c69uul.txt summary: In this work we propose a simple mathematical model for the analysis of the impact of control measures against an emerging infection, namely, the severe acute respiratory syndrome (SARS). The model provides a testable hypothesis by considering a dynamical equation for the contact parameter, which drops exponentially with time, simulating control measures. In contrast, with control measures, which reduce the contact rate to about 25% of its initial value, the expected final number of cases is reduced to 1778 in Hong Kong and 226 in Toronto (Canada). The aim of this work is to provide a projection of what would have happened with the course of severe acute respiratory syndrome (SARS) epidemic if the universal procedures to reduce contact were not implemented in the affected areas. The model projects that, in the absence of control, the final number of cases would be 320,000 in Hong Kong and 36,900 in Toronto (Canada). abstract: In this work we propose a simple mathematical model for the analysis of the impact of control measures against an emerging infection, namely, the severe acute respiratory syndrome (SARS). The model provides a testable hypothesis by considering a dynamical equation for the contact parameter, which drops exponentially with time, simulating control measures. We discuss the role of modelling in public health and we analyse the distinction between forecasting and projection models as assessing tools for the estimation of the impact of intervention strategies. The model is applied to the communities of Hong Kong and Toronto (Canada) and it mimics those epidemics with fairly good accuracy. The estimated values for the basic reproduction number, R(0), were 1.2 for Hong Kong and 1.32 for Toronto (Canada). The model projects that, in the absence of control, the final number of cases would be 320,000 in Hong Kong and 36,900 in Toronto (Canada). In contrast, with control measures, which reduce the contact rate to about 25% of its initial value, the expected final number of cases is reduced to 1778 in Hong Kong and 226 in Toronto (Canada). Although SARS can be a devastating infection, early recognition, prompt isolation, and appropriate precaution measures, can be very effective to limit its spread. url: https://www.sciencedirect.com/science/article/pii/S0306987705000800 doi: 10.1016/j.mehy.2004.09.029 id: cord-254094-ed1epul1 author: Mayoral, Eduardo Pérez-Campos title: Factors related to asymptomatic or severe COVID-19 infection date: 2020-09-24 words: 1665.0 sentences: 98.0 pages: flesch: 48.0 cache: ./cache/cord-254094-ed1epul1.txt txt: ./txt/cord-254094-ed1epul1.txt summary: In particular, we refer to the TMPRSS2 expression profile, balance of androgen and estrogen, blood group-A and/or B, nonsynonymous mutations in ORF3, and proteins NS7b and NS8 in SARS-CoV-2. In the first months of the COVID-19 pandemic, most authors focused their attention on features such as the high expression of ACE2 in the salivary glands in asymptomatic infection [4] , and the maturity and binding capacity of ACE2 [5, 6] . A higher 2D:4D ratio is associated with COVID-19 severity in men [14] , this means that sex hormones play a role in protection, thus, causing women to develop less serious complications or an asymptomatic COVID-19 Infection [12] . An in-depth study of the factors associated with asymptomatic subjects can provide information to limit severe COVID-19 as much as possible. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is likely to be androgen mediated abstract: The factors that may contribute to a COVID-19 patient remaining in the asymptomatic stage, or to the infection evolving into the more serious stages are examined. In particular, we refer to the TMPRSS2 expression profile, balance of androgen and estrogen, blood group-A and/or B, nonsynonymous mutations in ORF3, and proteins NS7b and NS8 in SARS-CoV-2. Also, we review other factors related to the susceptibility and pathogenicity of SARS-CoV-2. url: https://api.elsevier.com/content/article/pii/S0306987720327328 doi: 10.1016/j.mehy.2020.110296 id: cord-291722-xnfdjriz author: Meenakshisundaram, Ramachandran title: Protective effects of vaccinations and endemic infections on COVID-19: A Hypothesis date: 2020-05-26 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: nan url: https://www.sciencedirect.com/science/article/pii/S0306987720308902?v=s5 doi: 10.1016/j.mehy.2020.109849 id: cord-276564-o21ncldx author: Miller, R. title: COVID-19: NAD(+) deficiency may predispose the aged, obese and type2 diabetics to mortality through its effect on SIRT1 activity date: 2020-06-29 words: 3229.0 sentences: 205.0 pages: flesch: 44.0 cache: ./cache/cord-276564-o21ncldx.txt txt: ./txt/cord-276564-o21ncldx.txt summary: This hypothesis suggests that a deficiency of nicotinamide adenine dinucleotide (NAD + ) may be the primary factor related to the SARS-Cov-2 disease spectrum and the risk for mortality, as subclinical nutritional deficiencies may be unmasked by any significant increase in oxidative stress. This hypothesis suggests that a deficiency of nicotinamide adenine dinucleotide (NAD + ) may be the primary factor related to the SARS-Cov-2 disease spectrum and the risk for mortality, as subclinical nutritional deficiencies may be unmasked by any significant increase in oxidative stress. Vulnerable patient groups would potentially be less likely or unable to ensure sufficient activation of SIRT1 due to low NAD + levels or associated nutritional deficiencies including Zn ++ , and as such contribute to an inability to control viral replication and reduce the uncontrolled expression of pro-inflammatory cytokines. abstract: The SARS-CoV-2 hyperinflammatory response is associated with high mortality. This hypothesis suggests that a deficiency of nicotinamide adenine dinucleotide (NAD(+)) may be the primary factor related to the SARS-Cov-2 disease spectrum and the risk for mortality, as subclinical nutritional deficiencies may be unmasked by any significant increase in oxidative stress. NAD(+) levels decline with age and are also reduced in conditions associated with oxidative stress as occurs with hypertension, diabetes and obesity. These groups have also been observed to have high mortality following infection with COVID-19. Further consumption of NAD(+) in a pre-existent depleted state is more likely to cause progression to the hyperinflammatory stage of the disease through its limiting effects on the production of SIRT1. This provides a unifying hypothesis as to why these groups are at high risk of mortality and suggests that nutritional support with NAD(+) and SIRT1 activators, could minimise disease severity if administered prophylactically and or therapeutically. The significance of this, if proven, has far-reaching consequences in the management of COVID-19 especially in third world countries, where resources and finances are limited. url: https://www.ncbi.nlm.nih.gov/pubmed/32758884/ doi: 10.1016/j.mehy.2020.110044 id: cord-271785-vmnc8yg6 author: Minetti, Giampaolo title: Mevalonate pathway, selenoproteins, redox balance, immune system, Covid-19: Reasoning about connections date: 2020-07-21 words: 2551.0 sentences: 137.0 pages: flesch: 38.0 cache: ./cache/cord-271785-vmnc8yg6.txt txt: ./txt/cord-271785-vmnc8yg6.txt summary: As competitive inhibitors of HMG-CoA-reductase, the key enzyme of the "mevalonate pathway" through which essential compounds, not only cholesterol, are synthesized, statins decrease the levels of cholesterol, and thus LDLs, as an innate defense mechanism, with controversial results in decreasing mortality from cardiovascular disease. In the attempt to decipher the enigma of SARS-CoV-2 infectivology, the hypothesis should be tested whether the population of subjects who succumbed to Covid-19 may have developed a compromised immunity at sub-clinical levels and have become more susceptible to fatal consequences from SARS-Cov-2 infection due to statin therapy. Statins are cholesterol-lowering drugs that act as competitive inhibitors of the enzyme -Hydroxy--Methyl-Glutaryl-Coenzyme-A (HMG-CoA)-reductase, the key enzyme of the "mevalonate pathway". 27 Thus, subjects with already low LDL levels and possibly weakened leukocyte function because of statin treatment would be even more susceptible to infection and its fatal consequences. abstract: It has been proposed that a degraded immune system is (one of) the condition(s) that predispose certain subjects to fatal consequences from infection by SARS-CoV-2. It is unknown whether therapeutic regimens to which these patients may have been subjected to in the months/years preceding the infection could be immunocompromising. Statins are among the most widely prescribed cholesterol-lowering drugs. As competitive inhibitors of HMG-CoA-reductase, the key enzyme of the “mevalonate pathway” through which essential compounds, not only cholesterol, are synthesized, statins decrease the levels of cholesterol, and thus LDLs, as an innate defense mechanism, with controversial results in decreasing mortality from cardiovascular disease. Moreover, statins have pleiotropic, mostly deleterious effects on many cell types, including immune cells. In the attempt to decipher the enigma of SARS-CoV-2 infectivology, the hypothesis should be tested whether the population of subjects who succumbed to Covid-19 may have developed a compromised immunity at sub-clinical levels and have become more susceptible to fatal consequences from SARS-Cov-2 infection due to statin therapy. url: https://www.ncbi.nlm.nih.gov/pubmed/32758903/ doi: 10.1016/j.mehy.2020.110128 id: cord-310928-g553afo9 author: Murch, Simon H title: Common determinants of severe Covid-19 infection are explicable by SARS-CoV-2 secreted glycoprotein interaction with the CD33-related Siglecs, Siglec-3 and Siglec-5/14 date: 2020-08-07 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: SARS-CoV-2 interaction with the ACE-2 receptor cannot alone explain the demography and remarkable variation in clinical progression of Covid-19 infection. Unlike SARS-CoV, the cause of SARS, several SARS-CoV-2 spike glycans contain sialic acid residues. In contrast to the SARS secreted glycoprotein (SGP), SARS-CoV-2 SGP are thus potential ligands for Sialic acid-binding Siglecs on host immune cells, known to regulate immune function. Such SARS-CoV-2 glycoproteins would contribute to immune deviation. CD33-related Siglecs are important immune regulators. Siglec-5 and -14 are paired receptors with opposed actions on the NLRP3 inflammasome, which is critical in early viral clearance. SGP binding in persons of Siglec-14 null genotype (30-70% in Black, Asian and Minority Ethnic (BAME) persons, 10% in North Europeans) would induce unopposed inhibitory signalling, causing viral persistence through inflammasome inhibition. Siglec-3 (CD33) and Siglec-5 are expressed on CD33 myeloid derived suppressor cells (CD33 MDSC). Immunosuppressive CD33 MDSC populations are increased in all groups at risk of severe Covid-19 infection. CD33 expression is increased in persons with the CD33 rs3865444 CC allele, associated with Alzheimer’s disease, who would thus show enhanced susceptibility. Viral SGP ligation of CD33, potentially in conjunction with Siglec-5, would promote expansion of CD33 MDSC cells, as occurs in cancers but at much greater scale. CD33 is expressed on CNS microglia, potentially activated by SGP penetration through the porous cribriform plate to cause anosmia. Genotyping of severe or fatal Covid-19 cases can confirm or refute this pathophysiological mechanism. Early data have confirmed extremely high-level increase of CD33 MDSC numbers in severe Covid-19 infection, consistent with the proposed mechanism. url: https://api.elsevier.com/content/article/pii/S0306987720313347 doi: 10.1016/j.mehy.2020.110168 id: cord-310217-p9nqcz5d author: Nikolina, Basic-Jukic title: Can hyperimmune anti-CMV globuline substitute for convalescent plasma for treatment of COVID-19? date: 2020-05-31 words: 648.0 sentences: 43.0 pages: flesch: 40.0 cache: ./cache/cord-310217-p9nqcz5d.txt txt: ./txt/cord-310217-p9nqcz5d.txt summary: Currently available expert opinions suggest reduction of immunosuppression therapy for renal transplant recipients with symptomatic COVID-19 infection with either antiviral drugs, hydroxychloroquine and/or azithromycin. Currently available expert opinions suggest reduction of immunosuppression therapy for renal transplant recipients with symptomatic COVID-19 Inspired by our experience in treatment of CMV pneumonia and literature data on the potential benefit of convalescent plasma for treatment of different viral diseases we suggest use of the hyperimmune anti-CMV gamma globulins in addition to other available therapies. Inspired by our experience in treatment of CMV pneumonia and literature data on the potential benefit of convalescent plasma for treatment of different viral diseases we suggest use of the hyperimmune anti-CMV gamma globulins in addition to other available therapies. In conclusion, we suggest the use of hyperimmune anti-CMV immunoglobulins for treatment of COVID-19 especially when occur as coinfection with CMV instead of the convalescent plasma which may be unavailable for majority of patient. abstract: Information on treatment of COVID-19 infection in renal transplant recipients is scarce, especially in symptomatic patients and patients with recent major clinical events. This group of patients suffers from different opportunistic infections which may coexist with COVID-19. Currently available expert opinions suggest reduction of immunosuppression therapy for renal transplant recipients with symptomatic COVID-19 infection with either antiviral drugs, hydroxychloroquine and/or azithromycin. Inspired by our experience in treatment of CMV pneumonia and literature data on the potential benefit of convalescent plasma for treatment of different viral diseases we suggest use of the hyperimmune anti-CMV gamma globulins in addition to other available therapies. Besides the immunosuppression reduction which is supposed to be beneficial, immunoglobulins with their immunomodulatory effects and possible antiviral role, may increase a possibility for favorable outcome. url: https://doi.org/10.1016/j.mehy.2020.109903 doi: 10.1016/j.mehy.2020.109903 id: cord-334709-z70oevy2 author: Niv, Yaron title: Defensin 5 for prevention of SARS-CoV-2 invasion and Covid-19 Disease date: 2020-09-04 words: 1372.0 sentences: 72.0 pages: flesch: 51.0 cache: ./cache/cord-334709-z70oevy2.txt txt: ./txt/cord-334709-z70oevy2.txt summary: Similarly, to other corona viruses and influenza A, the receptor for adherence of SARS-CoV-2 is ACE2 which is abundant on respiratory and gastrointestinal mucosal cells, especially on alveolar type 2 pneumocytes [2] . Theoretically using of recombinant S1 protein, which will attach to the ACE2 receptors, may actively compete with the SARS-CoV-19 and prevent infection. They found affinity of HDEF5 binding to ACE2 of 76.2 nM, efficient blocking of SARS-CoV-2 receptor binding domain (RBD), and significant inhibition of invasion into Caco-2 cells. The next step, after preparing recombinant HDEF5, active and functioning, with high affinity to both receptor and ligand, is to make the protein available in powder, with small enough particles to be aerosolized and sprayed. Blocking the receptor for SARS-CoV-2 virus, ACE2, on the respiratory tract epithelium, especially the alveolar type 2 pneumocytes, will probably prevent invasion of the virus, at least for a short while. abstract: Corona virus disease 2019 (Covid-19), a pandemia emerged recently, caused by severe acute respiratory syndrome corona virus 2 (SARS-CoV-2). The receptor for corona virus and influenza A is the mucosal cell membrane protein angiotensin converting enzyme 2 (ACE2), which is abundant on the membrane of alveolar cells and enterocytes. Viral spike protein 1 (S1) is the ligand, with an affinity of 14.7 nM to the receptor. The main port of entry for the virus is the upper respiratory tract, and the diagnosis is usually by PCR of the viral RNA with nasal and pharyngeal swab test. Human defensin 5 (HDEF5) is a protein encoded by the DEFA gene, secreted by Paneth cells in the small intestine and by granules of neutrophils. It has an affinity of 39.3 nM to ACE2, much higher than that of the corona S1. HDEF5 may also attach to glycosylated Corona S1 protein, make its efficiency even better. The issues to be investigated are the affinity of HDEF5 to S1 protein, the ability of recombinant HDEF5 function in attaching both ACE2 and S1, and the feasibility to perform aerosol spray of this protein. In addition, safety and efficiency should be studied in phases I, II and II clinical protocols. Thus, an aerosol spray of HDEF5 given through the nose and throat, once to several times a day, may be a very efficient approach to prevent infection with SARA-CoV-2 as well as influenza A. url: https://doi.org/10.1016/j.mehy.2020.110244 doi: 10.1016/j.mehy.2020.110244 id: cord-297178-moxhk2e0 author: Novaes Rocha, Vinicius title: Viral replication of SARS-CoV-2 could be self-limitative - the role of the renin-angiotensin system on COVID-19 pathophysiology date: 2020-10-01 words: 3272.0 sentences: 184.0 pages: flesch: 46.0 cache: ./cache/cord-297178-moxhk2e0.txt txt: ./txt/cord-297178-moxhk2e0.txt summary: Caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the coronavirus disease 2019 (COVID-19) is provoking devastating consequences on economic and social fields throughout all continents. Amongst the components of rennin-angiotensin system (RAS), the angiotensin-converting enzyme 2 (ACE2) has gained great prominence for being directly associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the coronavirus related to COVID-19 [4, 5] . ACE2 is a fundamental piece in the pathophysiology of COVID-19, since the high replication capacity of SAR-CoV-2 is directly related to the coupling to ACE2 and cell infection. The ACE2 level reduction caused by SARS-CoV-2 infection may be directly related to the pathogenesis of COVID-19 [26] . The reduction in ACE2 expression may be related to pulmonary inflammation and subsequent cytokine storm seen in patients with severe COVID-19. Tumor necrosis factor-alpha convertase (ADAM17) mediates regulated ectodomain shedding of the severeacute respiratory syndrome-coronavirus (SARS-CoV) receptor, angiotensinconverting enzyme-2 (ACE2) abstract: Currently, the world is suffering with one of the biggest pandemics of recent history. Caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the coronavirus disease 2019 (COVID-19) is provoking devastating consequences on economic and social fields throughout all continents. Therefore, pathophysiological knowledge about COVID-19 is imperative for better planning of preventive measures, diagnosis, and therapeutics of the disease. Based on previous studies, this work proposes new hypothesis related to the role of the renin-angiotensin system on the pathophysiology of COVID-19, and its purpose is to enrich the discussion and to offer alternative ways for experimental and clinical studies aiming at the formulation of new diagnosis and / or treatment methods. url: https://www.sciencedirect.com/science/article/pii/S0306987720320818?v=s5 doi: 10.1016/j.mehy.2020.110330 id: cord-323310-tq9muytr author: Ozdemir, Burak title: Could the decrease in the endothelial nitric oxide (NO) production and NO bioavailability be the crucial cause of COVID-19 related deaths? date: 2020-06-07 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: nan url: https://www.sciencedirect.com/science/article/pii/S0306987720310744?v=s5 doi: 10.1016/j.mehy.2020.109970 id: cord-317238-uszhwugw author: Parodi, Aurora title: Coronavirus disease 2019 (COVID 19) and Malaria. Have anti glycoprotein antibodies a role? date: 2020-06-25 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: nan url: https://www.sciencedirect.com/science/article/pii/S030698772031389X?v=s5 doi: 10.1016/j.mehy.2020.110036 id: cord-302212-zt4lv5g4 author: Patruno, Cataldo title: COVID-19, QUARANTINE, AND ATOPIC DERMATITIS date: 2020-05-19 words: 418.0 sentences: 27.0 pages: flesch: 41.0 cache: ./cache/cord-302212-zt4lv5g4.txt txt: ./txt/cord-302212-zt4lv5g4.txt summary: Atopic dermatitis (AD) is a chronic inflammatory skin disease affecting up to 20% of children and up to 10% of adults (1) . Its pathogenesis involves environmental factors that interact with genetic skin barrier defects and immune Th2 Adverse psychological effects induced by the COVID-19 quarantine have been associated with increase of itch in some chronic skin disease, also due to neuroendocrine modulation of skin inflammation (4). Obviously, quarantine is associated with less exposure to sunlight that, together with high temperature and low humidity, may exert an immunosuppressive effect on skin inflammation of AD (2) . All these considerations suggest the hypothesis that COVID-19 pandemic may be associated with changes in lifestyle of AD patients that can significantly influence their clinical disease activity. Effects of climate change on skin diseases Mass quarantine measures of COVID-19 pandemic: psychosocial implications for chronic skin conditions and a call for qualitative studies abstract: nan url: https://www.sciencedirect.com/science/article/pii/S0306987720310793?v=s5 doi: 10.1016/j.mehy.2020.109852 id: cord-338585-ep9r1n8t author: Perrin, David M. title: A hypothesis for examining dihydroxyacetone, the active component in self-tanning products, as a topical prophylactic against SARS-COV-2 transmission date: 2020-09-16 words: 1800.0 sentences: 84.0 pages: flesch: 42.0 cache: ./cache/cord-338585-ep9r1n8t.txt txt: ./txt/cord-338585-ep9r1n8t.txt summary: title: A hypothesis for examining dihydroxyacetone, the active component in self-tanning products, as a topical prophylactic against SARS-COV-2 transmission This hypothesis raises the interesting prospect that dihydroxyacetone (DHA), the key ingredient in self-tanning creams, when applied daily to the face and hands may have prophylactic action against SARS-COV-2 transmission and infection. The Maillard Reaction, comprises a manifold of reactions including Schiff-base formation, aldol-type condensations, Amadori rearrangements, and dehydrative and/or oxidative aromatization events that modify lysine amines and give rise to crosslinks, (12) which are consistent with other advanced glycation events seen in diabetic patients. Together, such studies would systematically advance this hypothesis from well-established in vitro results to an easily monitored clinical trial, that would lead to a medically justified recommendation for daily topical prophylactic application of DHA to the face and hands for reducing SARS-COV-2 infection. abstract: This hypothesis raises the interesting prospect that dihydroxyacetone (DHA), the key ingredient in self-tanning creams, when applied daily to the face and hands may have prophylactic action against SARS-COV-2 transmission and infection. The scientific and mechanistic basis for this hypothesis is elaborated based on our understanding of the chemical reactivity of DHA with proteins to afford advanced glycation products. This piece ends with a proposal for doing key experiments that can be run to test this hypothesis. As more than 20 million people have been infected with this disease world-wide, a safe method for stopping spread is worthy of consideration. Publication of this hypothesis would enable the scientific community at large to test this in a clinically meaningful setting to address the potential for DHA-based prophylaxis. Given the calamity of this crisis, it is anticipated that the publication of this hypothesis, which is supported by key studies on protein and nucleoside glycation, can be disseminated to as many researchers as possible. url: https://api.elsevier.com/content/article/pii/S0306987720325652 doi: 10.1016/j.mehy.2020.110280 id: cord-324949-sqy03dks author: Poe, Francis L. title: N-Acetylcysteine: a potential therapeutic agent for SARS-CoV-2 date: 2020-05-30 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: COVID-19, a respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continues to spread across the globe. Predisposing factors such as age, diabetes, cardiovascular disease, and lowered immune function increase the risk of disease severity. T cell exhaustion, high viral load, and high levels of TNF-ɑ, IL1β, IL6, IL10 have been associated with severe SARS-CoV-2. Cytokine and antigen overstimulation are potentially responsible for poor humoral response to the virus. Lower cellular redox status, which leads to pro-inflammatory states mediated by TNF-ɑ is also potentially implicated. In vivo, in vitro, and human clinical trials have demonstrated N-acetylcysteine (NAC) as an effective method of improving redox status, especially when under oxidative stress. In human clinical trials, NAC can be used to replenish glutathione stores and increase the proliferative response of T cells. NAC has also been shown to inhibit the NLRP3 inflammasome pathway (IL1β and IL18) in vitro, and decrease plasma TNF-ɑ in human clinical trials. Mediation of the viral load could occur through NAC’s ability to increase cellular redox status via maximizing the rate limiting step of glutathione synthesis, and thereby potentially decreasing the effects of virally induced oxidative stress and cell death. We hypothesize that NAC could act as a potential therapeutic agent in the treatment of COVID-19 through a variety of potential mechanisms, including increasing glutathione, improving T cell response, and modulating inflammation. In this article, we present evidence to support the use of NAC as a potential therapeutic agent in the treatment of COVID-19. url: https://www.sciencedirect.com/science/article/pii/S0306987720308811?v=s5 doi: 10.1016/j.mehy.2020.109862 id: cord-293860-6kz0iws6 author: Qutayba Almerie, Muhammad title: The Association between Obesity and Poor Outcome after COVID-19 Indicates a Potential Therapeutic Role for Montelukast date: 2020-05-27 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: It is widely believed that infection with the SARS-CoV2 virus triggers a disproportionate immune response which causes a devastating systemic injury, particularly in individuals with obesity, itself a chronic, multi-organ inflammatory disease. Immune cells accumulate in visceral adipose tissue and together with paracrine adipocytes release a wide range of biologically active cytokines (including IL-1β, IL5, IL6 and IL8) that can result in both local, pulmonary and systemic inflammation. A more intense ‘cytokine storm’ is postulated as the mechanism behind the extreme immune response seen in severe COVID-19. It is striking how dangerous the combination of obesity and COVID-19 is, resulting in a greater risk of ICU admission and a higher mortality. Furthermore, patients from a BAME background appear to have increased mortality after SARS-CoV2 infection; they also have a higher prevalence of central obesity and its metabolic complications. In the absence of an effective vaccine, the therapeutic potential of immune-modulating drugs is a priority, but the development of new drugs is expensive and time-consuming. A more pragmatic solution would be to seek to repurpose existing drugs, particularly those that might suppress the heightened cytokine activity seen in obesity, the major risk factor for a poor prognosis in COVID-19. Montelukast is a cysteinyl leukotriene receptor antagonist licensed to treat asthma and allergic rhinitis. It has been shown to diminish pulmonary response to antigen, tissue eosinophilia and IL-5 expression in inflammatory cells. It has also been shown to decrease elevated levels of IL-1β and IL8 in humans with viral upper respiratory tract infections compared with placebo-treated patients. In addition, in silico studies have demonstrated a high binding affinity of the montelukast molecule to the terminal site of the virus’s main protease enzyme which is needed for virus RNA synthesis and replication. Montelukast, which is cheap, safe and widely available would appear to have the potential to be an ideal candidate drug for clinical trials, particularly in early stage disease before irreparable tissue damage has already occurred. HYPOTHESIS: Through a direct anti-viral effect, or by suppression of heightened cytokine release in response to SARS-CoV2, montelukast will reduce the severity of immune-mediated multiorgan damage resulting from COVID-19, particularly in patients with central obesity and metabolic syndrome. url: https://www.sciencedirect.com/science/article/pii/S0306987720311488?v=s5 doi: 10.1016/j.mehy.2020.109883 id: cord-332365-20u06444 author: Raciti, Loredana title: Can volcanic trace elements facilitate Covid-19 diffusion? A hypothesis stemming from the Mount Etna area, Sicily date: 2020-06-27 words: 3653.0 sentences: 188.0 pages: flesch: 47.0 cache: ./cache/cord-332365-20u06444.txt txt: ./txt/cord-332365-20u06444.txt summary: We suppose that ash and gases emitted from the Mount Etna contributed to air pollution, potentially favouring the major contagion of COVID-19 in the eastern flank of the mountain, as in Catania city. Heavy metals have been dosed in the groundwater of the Etna (used for water plants or to drink), especially in the eastern and southern sectors of the volcano, and they are believed to contribute to intoxication of public health and to pulmonary or neurodegenerative diseases [12, 14, 15] . This is the first paper that elaborates the hypothesis of a potential role of volcanic gases and heavy metals-related air pollution, combined to specific climatic conditions and regional topography, in favouring severe COVID-19 diffusion in Sicily. This is the first paper that elaborates the hypothesis of a potential role of volcanic gases and heavy metals-related air pollution, combined to specific climatic conditions and regional topography, in favouring severe COVID-19 diffusion in Sicily. abstract: In December 2019, severe cases of pneumonia of unknown aetiology were reported in Wuhan city, in China. Lately, the pneumonia was related to the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), and the diseases was termed coronavirus disease-2019 (COVID-19). At the end of January 2020, the infection spread all over Italy, but with high infection rates and mortality in the northern part, especially in Lombardy, the most industrialized and polluted region of the country. It is noteworthy that a strong association between severe viral respiratory disease and air pollution has been described. Air pollutant could be solid particles, liquid droplets, or gases and can be of natural origin (such as ash from a volcanic eruption) or released from motor vehicle depletes (carbon monoxide gas) or factories (sulfur dioxide). Volcanic eruptions release large amounts of sulphuric acid, hydrogen sulfide, and hydrochloric acid into the atmosphere. Pulmunary diseases spread by means of small droplets in the breath, also called aerosols, and air pollution may facilitate the outside survival of viruses. We suppose that ash and gases emitted from the Mount Etna contributed to air pollution, potentially favouring the major contagion of COVID-19 in the eastern flank of the mountain, as in Catania city. In fact, ash and gases (with regard to radon) are usually particularly intense in winter, with a reduction of emission of specific metals with warmer weather. This is the first paper that elaborates the hypothesis of a potential role of volcanic gases and heavy metals-related air pollution, combined to specific climatic conditions and regional topography, in favouring severe COVID-19 diffusion in Sicily. Clinical and epidemiological studies are needed to support the hypothesis and plan the due prevention and awareness-raising campaigns. url: https://api.elsevier.com/content/article/pii/S0306987720316248 doi: 10.1016/j.mehy.2020.110058 id: cord-276715-d1nh2dvb author: Raha, Syamal title: Is Copper beneficial for COVID-19 patients? date: 2020-05-05 words: 1610.0 sentences: 103.0 pages: flesch: 50.0 cache: ./cache/cord-276715-d1nh2dvb.txt txt: ./txt/cord-276715-d1nh2dvb.txt summary: Besides, Cu can kill several infectious viruses such as bronchitis virus, poliovirus, human immunodeficiency virus type 1(HIV-1), other enveloped or nonenveloped, singleor double-stranded DNA and RNA viruses. Based on available data, we hypothesize that enrichment of plasma copper levels will boost both the innate and adaptive immunity in people. Copper exposure to human coronavirus 229E destroyed the viral genomes and irreversibly affected virus morphology, including disintegration of envelope and dispersal of surface spikes [16] . Copper deficiency could lead a decreased number of circulatory blood cells with a greater susceptibility towards infection in older people In a study of 11 men on a low-Cu diet (0.66 mg Cu/day for 24 days and 0.38 mg/day for another 40 days) showed a decreased proliferation response of their white blood cells when presented with an immune challenge in cell culture [33] . Thujaplicin-copper chelates inhibit replication of human influenza viruses Effects of low-copper diets on human immune response abstract: Copper (Cu) is an essential micronutrient for both pathogens and the hosts during viral infection. Cu is involved in the functions of critical immune cells such as T helper cells, B cells, neutrophils natural killer (NK) cells, and macrophages. These blood cells are involved in the killing of infectious microbes, in cell-mediated immunity and the production of specific antibodies against the pathogens. Cu-deficient humans show an exceptional susceptibility to infections due to the decreased number and function of these blood cells. Besides, Cu can kill several infectious viruses such as bronchitis virus, poliovirus, human immunodeficiency virus type 1(HIV-1), other enveloped or nonenveloped, single- or double-stranded DNA and RNA viruses. Moreover, Cu has the potent capacity of contact killing of several viruses, including SARS‐CoV‐2. Since the current outbreak of the COVID-19 continues to develop, and there is no vaccine or drugs are currently available, the critical option is now to make the immune system competent to fight against the SARS‐CoV‐2. Based on available data, we hypothesize that enrichment of plasma copper levels will boost both the innate and adaptive immunity in people. Moreover, owing to its potent antiviral activities, Cu may also act as a preventive and therapeutic regime against COVID-19. url: https://doi.org/10.1016/j.mehy.2020.109814 doi: 10.1016/j.mehy.2020.109814 id: cord-326849-vqpwdlj7 author: Rao US, Vishal title: Mesenchymal Stem Cells -Bridge Catalyst Between Innte And Adaptive Immunity In Covid 19 date: 2020-05-18 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Majority of patients infected with the COVID 19 virus display a mild to moderate course of disease and spontaneously recover at 14 - 20 days,. However, about 15 % of patients progress to severe stages and 2.5% of these patients succumb to this illness. Most patients with severe disease belong to the elderly age group (< 65 years of age) and have multiple associated co-morbidities. The immune responses induced by the COVID 19 virus, during the incubation and non-severe stages, requires the early initiation of a specific adaptive immune response to eliminate the virus and prevent the progress to severe stages. In patients with a dysfunctional bridge adaptive immunity, the innate immune response becomes exaggerated due to the lack of feedback from the adaptive immune cells. The resultant cytokine storm is responsible for the severe lung injury leading to acute respiratory distress syndrome seen in COVID 19 patients. Mesenchymal stem cells are known to suppress overactive immune responses as well as bring about tissue regeneration and repair. This immuno-modulatory effect of MSCs could hold potential to manage a patient with severe symptoms of COVID 19 infection due to a dysfunctional adaptive immune system. url: https://www.sciencedirect.com/science/article/pii/S0306987720309221?v=s5 doi: 10.1016/j.mehy.2020.109845 id: cord-322880-zfc9w5y6 author: Rohit, Anusha title: Respiratory droplets get suspended longer and spread wider in temperate environments compared to tropics and implications for SARS-CoV-2 transmission date: 2020-06-09 words: 1852.0 sentences: 92.0 pages: flesch: 55.0 cache: ./cache/cord-322880-zfc9w5y6.txt txt: ./txt/cord-322880-zfc9w5y6.txt summary: title: Respiratory droplets get suspended longer and spread wider in temperate environments compared to tropics and implications for SARS-CoV-2 transmission The combined effect of change in size of the droplet as well as the density amplifies the influence that environmental relative humidity would have on the particle settling velocity. It is possible that droplets discharged from infected individuals in places like New York City could shrink in size quickly and remain airborne for considerable period of time. A simple understanding of the mechanics of droplet size, dispersion and displacement could help infection control and public health measures to minimize spread and mitigate the risk of people getting infected especially in hotspots like hospital environments or other closed spaces. A simple understanding of the mechanics of droplet size, dispersion and displacement could help infection control and public health measures to minimize spread and mitigate the risk of people getting infected especially in hotspots like hospital environments or other closed spaces. abstract: The new pandemic of SARS-CoV-2 has shown stark differences in number of affected patients between countries in the tropics and those with temperate environments. Though there have been many theories on reasons for these differences, we hypothesise that this could be due to differences in the fate of respiratory droplets in the two environments. A simple understanding of the mechanics of droplet size, dispersion and displacement could help infection control and public health measures to minimize spread and mitigate the risk of people getting infected especially in hotspots like hospital environments or other closed spaces. This paper discusses the possibility of differences in number of infections and spread between different countries based on the spread of droplets. url: https://www.ncbi.nlm.nih.gov/pubmed/32575016/ doi: 10.1016/j.mehy.2020.109958 id: cord-289049-4ozwhcyi author: Roncati, Luca title: Renin-angiotensin system: The unexpected flaw inside the human immune system revealed by SARS-CoV-2 date: 2020-03-21 words: 383.0 sentences: 27.0 pages: flesch: 44.0 cache: ./cache/cord-289049-4ozwhcyi.txt txt: ./txt/cord-289049-4ozwhcyi.txt summary: title: Renin-angiotensin system: The unexpected flaw inside the human immune system revealed by SARS-CoV-2 Medical Hypotheses journal homepage: www.elsevier.com/locate/mehy Renin-angiotensin system: The unexpected flaw inside the human immune system revealed by SARS-CoV-2 In humans the renin-angiotensin system is the hormone system which regulates blood pressure and vascular resistances, as well as electrolytic balance; within this important system, the angiotensinconverting enzyme (ACE), present on the surface of vascular endothelial cells, in particular those of the lungs, is deputed to the conversion of angiotensin I to angiotensin II (AII), a potent vasoconstrictive peptide [1] . In addition, homologous ACE2 receptors have been identified on the oral mucosa, in type-II pneumocytes, along the intestine and on the kidney and heart endothelia [1, 2] ; these receptors have been found overexpressed in course of ACE inhibitors and AII receptor antagonists administration in murine models [3, 4] . Angiotensin-converting enzyme 2-a new cardiac regulator Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential therapeutic target Upregulation of angiotensin-converting enzyme (ACE) 2 in hepatic fibrosis by ACE inhibitors abstract: nan url: https://api.elsevier.com/content/article/pii/S0306987720304370 doi: 10.1016/j.mehy.2020.109686 id: cord-323749-lvtfv7ny author: Sai Suresh Chalichem, Nehru title: Aminoglycosides can be a better choice over Macrolides in COVID-19 regimen: Plausible Mechanism for repurposing strategy date: 2020-06-10 words: 938.0 sentences: 61.0 pages: flesch: 46.0 cache: ./cache/cord-323749-lvtfv7ny.txt txt: ./txt/cord-323749-lvtfv7ny.txt summary: Although macrolides like azithromycin and clarithromycin etc., have been reported to act against respiratory infections but they lack the ability of immunity enhancement through defensins. The aminoglycosides were proved to have defensin mediated antiviral activity, that could enhance the immunity. So, Consideration of aminoglycosides can be a double edge sword viz., against respiratory infection as well as Immunity enhancer (along with anti-virals) for COVID-19 regimen. Although various nations throughout the globe making several strategies viz, different drug combinations, proposing lock downs and herd immunity etc., to control the wide spread of COVID-19 and to tolerate its severity, the radical behaviour of virus is evident. In the instances like current pandemic of COVID-19, where infection control becomes a great challenge, immune mediators could be a vital link. However, aminoglycosides (AGs) were proved to produce functional peptides from theta defensins (called as retrocyclins) that are active against HIV 10 . abstract: In the current COVID-19 pandemic, prioritizing the immunity enhancers is equally important to anti-virals. Defensins are the forgotten molecules that enhance the innate immunity against various microbes. Although macrolides like azithromycin and clarithromycin etc., have been reported to act against respiratory infections but they lack the ability of immunity enhancement through defensins. The aminoglycosides were proved to have defensin mediated antiviral activity, that could enhance the immunity. So, Consideration of aminoglycosides can be a double edge sword viz., against respiratory infection as well as Immunity enhancer (along with anti-virals) for COVID-19 regimen. url: https://www.ncbi.nlm.nih.gov/pubmed/32554149/ doi: 10.1016/j.mehy.2020.109984 id: cord-314679-lmfalzni author: Sangith, Nikhil title: Unique Fibrinogen-binding motifs in the Nucleocapsid Phosphoprotein of SARS CoV-2: Potential Implications in Host-Pathogen Interactions date: 2020-06-24 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Novel Coronavirus (SARS CoV-2), the etiological agent for the highly contagious Corona virus disease-2019 (COVID-19) pandemic has threatened global health and economy infecting around 5.8 million people and causing over 359,200 deaths (as of 28(th) May, 2020, https://www.worldometers.info/coronavirus/). The clinical manifestations of infected patients generally range from asymptomatic or mild to severe illness, or even death. The ability of the virus to evade the host immune response have been major reasons for high morbidity and mortality. One of the important clinical observations under conditions of critical illness show increased risk of developing disseminated intravascular coagulation. Molecular mechanisms of how SARS CoV-2 induces such conditions still remain unclear. This report describes the presence of two unique motifs in the SARS CoV-2 nucleocapsid phosphoprotein (N-protein) that can potentially interact with fibrinogen and possibly prothrombin. This is based on an established function of secretory proteins in Staphylococcus aureus (S. aureus)- coagulase, Efb (Extracellular fibrinogen binding) and vWBP (von Willebrand factor Binding Protein), which are known to regulate the blood clotting cascade and the functions of host immune response. It is hypothesized that having protein interaction motifs that are homologous to these S. aureus proteins, the N-protein of this virus can mimic their functions, which may in turn play a crucial role in formation of blood clots in the host and help the virus evade host immune response. However, this hypothesis needs to be tested in vitro. Considering the overwhelming increase in the incidence of SARS CoV-2 infection globally, this information may be useful for further investigation and could help in deducing new therapeutic strategies to combat advanced stages of this disease. url: https://api.elsevier.com/content/article/pii/S0306987720313621 doi: 10.1016/j.mehy.2020.110030 id: cord-274510-fo7p98np author: Spadera, Lucrezia title: Potential Role of GcMAF in suppressing the severity of COVID-19-induced immune responses: lesson learned from HIV date: 2020-09-24 words: 4050.0 sentences: 217.0 pages: flesch: 40.0 cache: ./cache/cord-274510-fo7p98np.txt txt: ./txt/cord-274510-fo7p98np.txt summary: Based on the aforementioned findings and on documented analogies between SARS-CoV-2 and HIV [13] , we hypothesized that the reduced conversion activity of the Gc protein (human groupspecific component (Gc)) into the macrophage activating factor (MAF) could have a key role in the dysregulate immune response induced by SARS-CoV-2, just like for HIV infected patients [14] [15] . In particular, based on their antiviral activity [68] , chloroquine and hydroxychloroquine, initially conceived as antimalarial therapeutics, were proposed to treat patients hospitalized with COVID-19, better if associated to azithromycin, showing promising efficacy in "inhibiting the exacerbation of pneumonia, improving lung imaging findings, promoting a virus negative conversion and shortening the disease course" [69] [70] . So, in sight of this, given its multifunctional properties, we believe that GcMAF could have a very important role in the pathophysiology of organ damage induced by SARS-CoV-2, providing explanations which are consistent with the clinical, radiological and histopathological findings observed in patients with COVID-19. Effects of vitamin D(3)-binding protein-derived macrophage activating factor (GcMAF) on angiogenesis abstract: nan url: https://www.sciencedirect.com/science/article/pii/S030698772031392X?v=s5 doi: 10.1016/j.mehy.2020.110293 id: cord-274698-i3mzzxwq author: Stief, Thomas W title: The physiology and pharmacology of singlet oxygen date: 2003-02-19 words: 3339.0 sentences: 213.0 pages: flesch: 39.0 cache: ./cache/cord-274698-i3mzzxwq.txt txt: ./txt/cord-274698-i3mzzxwq.txt summary: Chloramines at blood concentrations between 1 and 2 mmol/L inactivate lipid enveloped virus and chloramines at blood concentrations below 0.5 mmol/L, i.e. at oxidant concentrations that do not affect thrombocytes or hemostasis factors, act antithrombotically by activation of the physiologic PMN mediated fibrinolysis; this thrombolysis is of selective nature, i.e. it does not impair the hemostasis system of the patient allowing the antithrombotic treatment in patients where the current risky thrombolytic treatment is contraindicated. The 60 mM NH 2 Cl (about 10 times the concentration generated by activated PMN!) is ulcerogenic in rat stomachs, taurine application (1 ml 200 mM) attenuates the deleterious action of NH 2 Cl (102), NH 2 Cl induces apoptosis in gastric mucosa (103) . Singlet oxygen ð 1 O 2 Þ-generating chloramines at concentrations that are tolerable for normal hemostasis function inactivate the lipid enveloped vesicular stomatitis virus in human blood Taurine chloramine inhibits prostaglandin E2 production in activated RAW 264.7 cells by post-transcriptional effects on inducible cyclooxygenase expression abstract: Reactive oxygen species (ROS) are generated by many different cells. Singlet oxygen (1O2) and a reaction product of it, excited carbonyls (CO(*)), are important ROS. 1O2 and CO(*) are nonradicalic and emit light (one photon/molecule) when returning to ground state oxygen. Especially activated polymorphonuclear neutrophil granulocytes (PMN) produce large amounts of 1O2. Via activation of the respiratory burst (NADPH oxidase and myeloperoxidase) they synthesize hypochlorite (NaOCl) and chloramines (in particular N-chlorotaurine). Chloramines are selective and stable chemical generators of 1O2. In the human organism, 1O2 is both a signal and a weapon with therapeutic potency against very different pathogens, such as microbes, virus, cancer cells and thrombi. Chloramines at blood concentrations between 1 and 2 mmol/L inactivate lipid enveloped virus and chloramines at blood concentrations below 0.5 mmol/L, i.e. at oxidant concentrations that do not affect thrombocytes or hemostasis factors, act antithrombotically by activation of the physiologic PMN mediated fibrinolysis; this thrombolysis is of selective nature, i.e. it does not impair the hemostasis system of the patient allowing the antithrombotic treatment in patients where the current risky thrombolytic treatment is contraindicated. The action of 1O2 might be compared to the signaling and destroying gunfire of soldiers directed against bandits at night, resulting in an autorecruitment of the physiological inflammatory response. Chloramines (such as the mild and untoxic oxidant chloramine T(®) (N-chloro-p-toluene-sulfonamide)) and their signaling and destroying reaction product 1O2 might be promising new therapeutic agents against a multitude of up to now refractory diseases. url: https://www.sciencedirect.com/science/article/pii/S0306987703000264 doi: 10.1016/s0306-9877(03)00026-4 id: cord-270740-3su8pc3f author: Sultan, Sherif title: COVID-19 Cytokine Storm and Novel Truth date: 2020-05-22 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: nan url: https://www.ncbi.nlm.nih.gov/pubmed/32593830/ doi: 10.1016/j.mehy.2020.109875 id: cord-308279-gsk4qel5 author: Suzuki, Yuichiro J. title: The viral protein fragment theory of COVID-19 pathogenesis date: 2020-09-11 words: 1397.0 sentences: 70.0 pages: flesch: 44.0 cache: ./cache/cord-308279-gsk4qel5.txt txt: ./txt/cord-308279-gsk4qel5.txt summary: I herein propose the viral protein fragment theory of COVID-19 pathogenesis based on my observations in cultured human vascular cells that SARS-CoV-2 spike protein can activate cell signaling events without the rest of the viral components. I hypothesize that, as humans are infected with SARS-CoV-2, the virus releases a fragment of the spike protein that can target host cells for eliciting cell signaling without the rest of the viral components. This hypothesis is based on my experimental observations in cultured human vascular cells that the recombinant full length S1 subunit of SARS-CoV-2 spike protein can activate cell signaling events without the rest of the viral components. I propose a scenario that, as humans are infected with SARS-CoV-2, the virus releases a fragment of the spike protein that can target host cells for eliciting cell signaling. abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is causing the current pandemic of coronavirus disease 2019 (COVID-19) that have killed nearly one million people so far. While this appears to be a respiratory virus, surprisingly, it has been recognized that patients with cardiovascular disease are likely to be affected severely and die of COVID-19. This phenomenon cannot be explained by the generally accepted logic that the SARS-CoV-2 infection/replication is the sole determinant of the actions of the virus to define the fate of host cells. I herein propose the viral protein fragment theory of COVID-19 pathogenesis based on my observations in cultured human vascular cells that SARS-CoV-2 spike protein can activate cell signaling events without the rest of the viral components. It is generally thought that SARS-CoV-2 and other single-stranded RNA viruses attach to the host cells through the interactions between surface proteins of the viral capsid and the host cell receptors; the fusion and the entry of the viral components, resulting in the replication of the viruses; and the host cell responses are the consequence of these events. I hypothesize that, as humans are infected with SARS-CoV-2, the virus releases a fragment of the spike protein that can target host cells for eliciting cell signaling without the rest of the viral components. Thus, COVID-19 patients are subjected to the intact virus infecting the host cells for the replication and the amplification as well as the spike protein fragment that are capable of affecting the host cells. I propose that cell signaling elicited by the spike protein fragment that occurs on cardiovascular cells would predispose infected individuals to develop complications that are seen in severe and fatal COVID-19 conditions. If this hypothesis is correct, then the strategies to treat COVID-19 should include, in addition to giving agents that inhibit the viral replication, therapeutics that inhibit the virus fragment-mediated cell signaling on cardiovascular cells. url: https://api.elsevier.com/content/article/pii/S0306987720326943 doi: 10.1016/j.mehy.2020.110267 id: cord-254411-e9vvjv8w author: Taghizadeh-Hesary, Farzad title: The Powerful Immune System Against Powerful COVID-19: A Hypothesis date: 2020-04-22 words: 1878.0 sentences: 130.0 pages: flesch: 49.0 cache: ./cache/cord-254411-e9vvjv8w.txt txt: ./txt/cord-254411-e9vvjv8w.txt summary: In this article, we provide a novel hypothesis to describe how an increase in cellular adenosine triphosphate (c-ATP) can potentially improve the efficiency of innate and adaptive immune systems to either prevent and fight off COVID-19. In this article, we aim to provide a new hypothesis to describe how the repletion of cellular adenosine triphosphate (c-ATP) can promote immunity against COVID-19. Secondly, ATP-depletion can potentially prone the recruited immune cells to earlier exhaustion against COVID-19. Therefore, one may conclude that ATP-repletion can prevent the so-called "cytokine storm" and improve the cellular energy to better counteract with COVID-19. From the perspective of cellular energy, this process potentially occurs through IFN-mediated T-cell activation that results in c-ATP depletion. have shown that following IFN-γ stimulation, mitochondrial hyperpolarization and ATP depletion occurs in T-cells that results in apoptosis (10) . It demonstrates how an increase in c-ATP can decrease the effect of COVID-19 on immune dysregulation. abstract: On March 11, 2020, the World Health Organization declared the coronavirus outbreak a pandemic. Since December 2019, the world has experienced an outbreak of coronavirus disease 2019 (COVID-19). Epidemiology, risk factors, and clinical characteristics of patients with COVID-19 have been reported but the factors affecting the immune system against COVID-19 have not been well described. In this article, we provide a novel hypothesis to describe how an increase in cellular adenosine triphosphate (c-ATP) can potentially improve the efficiency of innate and adaptive immune systems to either prevent and fight off COVID-19. url: https://api.elsevier.com/content/article/pii/S0306987720304874 doi: 10.1016/j.mehy.2020.109762 id: cord-281354-sa27k8o3 author: Takahashi, Harutaka title: Role of Latent Tuberculosis Infections in Reduced COVID-19 Mortality: Evidence from an Instrumental Variable Method Analysis date: 2020-08-26 words: 1439.0 sentences: 89.0 pages: flesch: 47.0 cache: ./cache/cord-281354-sa27k8o3.txt txt: ./txt/cord-281354-sa27k8o3.txt summary: title: Role of Latent Tuberculosis Infections in Reduced COVID-19 Mortality: Evidence from an Instrumental Variable Method Analysis However, these studies ignore an important fact: according to World Health Organization estimates, about a quarter of the world''s population may have latent tuberculosis infection (LTBI), a condition in which there is no evidence of clinically active tuberculosis but persistent immune responses are stimulated by Mycobacterium tuberculosis antigens. However, such studies ignore the important fact that about one-quarter of the world''s population may have latent TB infection (LTBI), a condition in which there is no evidence of clinically active TB but persistent immune responses are stimulated by Mycobacterium tuberculosis antigens. As explained above, the logarithm of the number of TB infections per 100,000 individuals (lntb10) can be used as a proxy variable for LTBIs. For this regression analysis to be statistically accurate, the explanatory variable X must first be correlated with the error term u (i.e., the covariance of X and u must be zero). abstract: Since the outbreak of the coronavirus disease 2019 (COVID-19) pandemic, there has been significant interest in the potential protective effect of the Bacillus Calmette-Guerin (BCG) vaccine against COVID-19 mortality. This effect has been attributed to innate immune responses induced by BCG vaccination. However, these studies ignore an important fact: according to World Health Organization estimates, about a quarter of the world's population may have latent tuberculosis infection (LTBI), a condition in which there is no evidence of clinically active tuberculosis but persistent immune responses are stimulated by Mycobacterium tuberculosis antigens. Thus, both LTBI and BCG induce lifelong immunity and may provide immunological protection against COVID-19. In this study, the relationship between LTBI and reduced COVID-19 mortality was analyzed using the instrumental variable method. The results showed with robust statistical support that LTBI was also associated with reduced COVID-19 mortality. url: https://www.sciencedirect.com/science/article/pii/S0306987720325305?v=s5 doi: 10.1016/j.mehy.2020.110214 id: cord-293059-2iwzieqm author: Tao, Huaqiang title: Dysimmunity and inflammatory storm: Watch out for bone lesions in COVID-19 infection date: 2020-10-06 words: 1818.0 sentences: 104.0 pages: flesch: 38.0 cache: ./cache/cord-293059-2iwzieqm.txt txt: ./txt/cord-293059-2iwzieqm.txt summary: It has been approved that inflammation-induced pathogenesis in COVID-19 infection has a strong correlation with incidence of cardiovascular metabolic diseases and gastrointestinal injury (1) . However, studies on the correlation between pro-inflammatory cytokine responses and bone metabolism in COVID-19 patients are still lacking. In this special background, will inflammatory disorder and immune imbalance affect bone metabolism after COVID-19 infection? Simultaneously, hypoxia inducible factor (HIF-1) was proven to facilitate osteoclast differentiation by overexpressing RANKL and nuclear factor of activated T cells cytoplasmic 1 (NFATc1) (14) . As osteoblasts and osteoclasts exist in approach with immune cells in medullary cavity, it''s no wonder that immune system shares massive regulatory cytokines, signaling molecules and transcription factors with bone biology. Apart from that, NF-κB and AP-1 stimulate the expression of many elements which required for inflammatory cytokines, driving up osteoclast activity and usually implicated inhibition on proliferation and differentiation of osteoblasts (22) . abstract: At the end of 2019, a new kind of pneumonia which was proven to be supported by novel coronaviruses named SARS-CoV-2 emerges and it seems to be more complicate in its clinical course and management. Related researches have demonstrated that SARS-CoV-2 serves roles in respiratory, intestinal and neuronal diseases. Given the growing cases of COVID-19, analyzing the relevance between COVID-19 and fragile patients who suffer from bone destruction is entirely indispensable. Accordingly, the recapitulatory commentary is necessary to advance our knowledge on COVID-19 and orthopedics. In this article, we particularly clarify the possible relationship between the newly COVID-19 infection and bone lesions from the standpoints of dysimmunity and inflammatory storm. url: https://api.elsevier.com/content/article/pii/S030698772032973X doi: 10.1016/j.mehy.2020.110332 id: cord-253312-bf35afpj author: Unal, Gokhan title: Immunopharmacological management of COVID-19: Potential therapeutic role of valproic acid date: 2020-05-27 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: nan url: https://www.ncbi.nlm.nih.gov/pubmed/32498007/ doi: 10.1016/j.mehy.2020.109891 id: cord-311673-z4hkw17g author: Uzzan, Mathieu title: Why is SARS-CoV-2 infection more severe in obese men? The gut lymphatics - lung axis hypothesis date: 2020-06-23 words: 2969.0 sentences: 154.0 pages: flesch: 40.0 cache: ./cache/cord-311673-z4hkw17g.txt txt: ./txt/cord-311673-z4hkw17g.txt summary: As the visceral fat possesses an intense immune activity, is involved in metabolic syndrome and is at the crossroad between the intestines, the systemic circulation and the lung, we hypothesized that it plays a major role in severe forms of SARS-CoV-2 infection. Several factors may increase intestinal permeability including, direct enterocyte damage by SARS-CoV2, systemic inflammatory response syndrome (SIRS) and epithelial ischemia secondary to SARS-CoV2associated endothelial dysfunction. This increase permeability further leads to translocation of microbial components such as MAMPS (microbial-associated molecular pattern), triggering an inflammatory immune response by TLR-expressing cells of the mesentery fat (mostly macrophages and adipocytes). As the increased volume of mesentery fat in overweight men play a key role in the occurrence of metabolic syndrome [8] , we hypothesized that the visceral adipose tissue plays a central role in severe forms of COVID-19. abstract: Consistent observations report increased severity of SARS-CoV-2 infection in overweight men with cardiovascular factors. As the visceral fat possesses an intense immune activity, is involved in metabolic syndrome and is at the crossroad between the intestines, the systemic circulation and the lung, we hypothesized that it plays a major role in severe forms of SARS-CoV-2 infection. SARS-CoV2 presents the ability to infect epithelial cells of the respiratory tract as well as the intestinal tract. Several factors may increase intestinal permeability including, direct enterocyte damage by SARS-CoV2, systemic inflammatory response syndrome (SIRS) and epithelial ischemia secondary to SARS-CoV2- associated endothelial dysfunction. This increase permeability further leads to translocation of microbial components such as MAMPS (microbial-associated molecular pattern), triggering an inflammatory immune response by TLR-expressing cells of the mesentery fat (mostly macrophages and adipocytes). The pro-inflammatory cytokines produced by the mesentery fat mediates systemic inflammation and aggravate acute respiratory distress syndrome (ARDS) through the mesenteric lymph drainage. url: https://www.sciencedirect.com/science/article/pii/S0306987720316662?v=s5 doi: 10.1016/j.mehy.2020.110023 id: cord-265724-fdt00qw1 author: Varadarajan, Saranya title: EMMPRIN/BASIGIN as a biological modulator of oral cancer and COVID-19 interaction: novel propositions date: 2020-07-09 words: 1761.0 sentences: 105.0 pages: flesch: 39.0 cache: ./cache/cord-265724-fdt00qw1.txt txt: ./txt/cord-265724-fdt00qw1.txt summary: Apart from ACE-2, recently EMMPRIN, has been regarded as a target for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) attachment and entry into the host cell. Since one of the routes of entry for the virus is the oral cavity, it becomes imperative to percept oral comorbidities such oral squamous cell carcinoma (OSCC) and oral potentially malignant disorders (OPMDs) in terms of EMMPRIN as a target for SARS-CoV-2. 1 Angiotensin-Converting Enzyme 2 (ACE-2) on the host cells is the attachment protein for the spike receptor present on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). [4] [5] [6] Apart from ACE-2, recently extracellular matrix metalloproteinase inducer (EMMPRIN), which is also called BASIGIN/CD147, has been regarded as a target for SARS-CoV-2 attachment and its entry into the host cell. OSCC, by the virtue of upregulation of EMMPRIN expression (potential and alternative site for ''S'' receptor), increases the susceptibility to SARS-CoV-2 infection. abstract: Extracellular matrix metalloproteinase inducer (EMMPRIN), which is also called BASIGIN/CD147, is a cell surface glycoprotein that belongs to the immunoglobulin superfamily and plays a significant role in intercellular recognition in immunology, cellular differentiation and development. Apart from ACE-2, recently EMMPRIN, has been regarded as a target for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) attachment and entry into the host cell. Since one of the routes of entry for the virus is the oral cavity, it becomes imperative to percept oral comorbidities such oral squamous cell carcinoma (OSCC) and oral potentially malignant disorders (OPMDs) in terms of EMMPRIN as a target for SARS-CoV-2. In the present paper, it is proposed that OSCC, by the virtue of upregulation of EMMPRIN expression, increases the susceptibility to coronavirus disease (COVID-19). In turn, COVID-19 in OSCC patients causes exhaustion of EMMPRIN receptor due to binding with ‘S’ receptor leading to a downregulation of related carcinogenesis events. We proposed that in the ACE-2 depleted situation in OSCC, EMMPRIN receptor might get high jacked by the COVID-19 virus for the entry into the host cells. Apart from the anti-monoclonal antibody, it is recommended to explore the use of grape seed and skin containing mouthwash as an adjunct, which could also have anti EMMPRIN effects in patients with OSCC and OPMDs. url: https://www.sciencedirect.com/science/article/pii/S0306987720319721?v=s5 doi: 10.1016/j.mehy.2020.110089 id: cord-265322-3854ddb9 author: Vavougios, George D. title: A data-driven hypothesis on the epigenetic dysregulation of host metabolism by SARS coronaviral infection: potential implications for the SARS-CoV-2 modus operandi date: 2020-04-23 words: 1252.0 sentences: 72.0 pages: flesch: 41.0 cache: ./cache/cord-265322-3854ddb9.txt txt: ./txt/cord-265322-3854ddb9.txt summary: Based on both structural and syndromic similarities with SARS-CoV, a hypothesis is formed on SARS-CoV-2 potential to affect the host''s metabolism as part of its lifecycle. In the literature, SARS-CoV has been known to cause de novo diabetes by ACE2-dependent uptake on pancreatic isle cells, and furthermore dysregulate lipid autophagy in favor of the viral lifecycle. Their study provided the foundation for a hypothesis put forth by Fang and colleagues indicating that diabetic and hypertensive patients exposed to ACE2 inhibitors may be at an increased risk of more severe COVID-19 (7) . In another study, SARS-CoV was shown to cause diabetes by ACE2-dependent infection of pancreatic isle cells (10) . Future studies should determine SARS-CoV-2 interaction and effect on the human transcriptome, further identifying drug targets using pharmacogenomic enrichment analyses. Natural small molecules as inhibitors of coronavirus lipid-dependent attachment to host cells: a possible strategy for reducing SARS-COV-2 infectivity? abstract: COVID-19, the disease caused by the novel SARS-CoV-2, a betacoronavirus structurally similar to SARS-CoV. Based on both structural and syndromic similarities with SARS-CoV, a hypothesis is formed on SARS-CoV-2 potential to affect the host’s metabolism as part of its lifecycle. This hypothesis is evaluated by (a) exploratory analysis of SARS-CoV / human transcriptomic interaction data and gene set enrichment analysis (b) a confirmatory, focused review of the literature based on the findings by (a). A STRING Viruses (available search for human – SARS-CoV (NCBI taxonomy Id: 9606 vs. NCBI taxonomy Id: 694009) genomic interactions reveals ten human proteins, interacting with SARS-CoV: SGTA, FGL2, SPECC1, STAT3, PHB, BCL2L1, PPP1CA, CAV1, JUN, XPO1. Gene set enrichment analyses (GSEA) with STRING on this network revealed their role as a putative protein – protein interaction network (PPI; Enrichment p-value=0.0296) mediating, viral parasitism, interleukin as well as insulin signaling, diabetes and triglyceride catabolism. In the literature, SARS-CoV has been known to cause de novo diabetes by ACE2-dependent uptake on pancreatic isle cells, and furthermore dysregulate lipid autophagy in favor of the viral lifecycle. Conversely, currently there are only non-causative, observational evidence of worse outcomes for COVID-19 patients with comorbid diabetes or hyperglycemia. No study has reported on the lipid profiles of COVID-19 patients; however, lipid-targeting molecules have been proposed as agents against SARS-CoV-2. Future studies, reporting on lipid and glucose metabolism of COVID-19 patients could help elucidate the disease’s seculae and aid drug design. url: https://www.sciencedirect.com/science/article/pii/S0306987720305600?v=s5 doi: 10.1016/j.mehy.2020.109759 id: cord-315576-bgcqkz0p author: Yamamoto, Naoki title: Apparent difference in fatalities between Central Europe and East Asia due to SARS-COV-2 and COVID-19: Four hypotheses for possible explanation date: 2020-08-05 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The comparison of the numbers of cases and deaths due to SARS-CoV-2 / COVID-19 shows that people in Central Europe are much more affected than people in East Asia where the disease originally occurred. Trying to explain this difference, this communication presents four hypotheses that propose the following reasons for the observed findings: 1) Differences in social behaviors and cultures of people in the two regions; 2) Possible outbreak of virulent viruses in Central Europe due to multiple viral infection, and the involvement of immuno-virological factors associated with it, 3) Possibility of corona resistance gene mutation occurring among East Asians as a result of long-term co-evolution of virus and host, and 4) possible involvement of hygienic factors. Direct or indirect supportive evidences for each one of our hypotheses are presented and experimental approaches for their evaluation are discussed. Finally, we suggest that the dynamics of the pandemic also shows that the problems of the new coronavirus can be overcome due to people's awareness of the epidemics, rational viral diagnostics and a high level of medical care. url: https://www.sciencedirect.com/science/article/pii/S0306987720314912?v=s5 doi: 10.1016/j.mehy.2020.110160 id: cord-264916-c4n0kyog author: Zimmerman, Keith title: Natural protection of ocular surface from viral infections – a hypothesis date: 2020-07-09 words: 4671.0 sentences: 225.0 pages: flesch: 46.0 cache: ./cache/cord-264916-c4n0kyog.txt txt: ./txt/cord-264916-c4n0kyog.txt summary: A pandemic outbreak of a viral respiratory infection (COVID-19) caused by a coronavirus (SARS-CoV-2) prompted a multitude of research focused on various aspects of this disease. In this work, we discuss the significance of natural protective factors related to anatomical and physiological properties of the eyes and preventing the deposition of large number of virus-loaded particles on the ocular surface. Specifically, we advance the hypothesis that the standing potential of the eye plays an important role in repelling aerosol particles (microdroplets) from the surface of the eye and discuss factors associated with this hypothesis, possible ways to test it and its implications in terms of prevention of ocular infections. This hypothesis could be tested by measuring the electrical charge of bioaerosol generated by normal breathing in healthy subjects and in patients with viral infections caused by different viruses, causing respiratory infections or with suspected aerosol transmission pathway. abstract: A pandemic outbreak of a viral respiratory infection (COVID-19) caused by a coronavirus (SARS-CoV-2) prompted a multitude of research focused on various aspects of this disease. One of the interesting aspects of the clinical manifestation of the infection is an accompanying ocular surface viral infection, viral conjunctivitis. Although occasional reports of viral conjunctivitis caused by this and the related SARS-CoV virus (causing the SARS outbreak in the early 2000s) are available, the prevalence of this complication among infected people appears low (∼1%). This is surprising, considering the recent discovery of the presence of viral receptors (ACE2 and TMPRSS2) in ocular surface tissue. The discrepancy between the theoretically expected high rate of concurrence of viral ocular surface inflammation and the observed relatively low occurrence can be explained by several factors. In this work, we discuss the significance of natural protective factors related to anatomical and physiological properties of the eyes and preventing the deposition of large number of virus-loaded particles on the ocular surface. Specifically, we advance the hypothesis that the standing potential of the eye plays an important role in repelling aerosol particles (microdroplets) from the surface of the eye and discuss factors associated with this hypothesis, possible ways to test it and its implications in terms of prevention of ocular infections. url: https://www.ncbi.nlm.nih.gov/pubmed/32679424/ doi: 10.1016/j.mehy.2020.110082 id: cord-275569-i5y23mmz author: de Bernardis, E. title: A putative role for the tobacco mosaic virus in smokers’ resistance to COVID-19 date: 2020-07-31 words: 1500.0 sentences: 69.0 pages: flesch: 41.0 cache: ./cache/cord-275569-i5y23mmz.txt txt: ./txt/cord-275569-i5y23mmz.txt summary: Though it is intuitively tempting, on the basis of physiopathological common knowledge, to predict a greater risk of contracting the SARS-CoV-2 infection in tobacco smokers, an analysis of studies from various countries shows that hospitalized COVID-19 patients have a lower, and apparently inversely proportional, rate of current tobacco smoking, in comparison with the respective general population, although once the disease has developed meta-analyses suggest that smoking is associated with a worse prognosis [1] . Incidentally, this behavior reminds the proposed effects of tobacco smoking, protective against initial SARS-CoV-2 infection and deleterious in the florid phase of the COVID-19 disease. Taken together, all these elements suggest that the oral use of tobacco, continuously exposing to non-pathogenic but immunogenic TMV particles, and chronically stimulating a natural antiviral response, may induce a state of resistance to the initial SARS-CoV-2 infection. abstract: Reports from various countries suggest that tobacco smoking might protect from SARS-CoV-2 infection, since the prevalence of smoking in COVID-19 hospitalized patients is lower than in the respective general population. Apart from nicotine or other chemicals contained in tobacco smoke, we propose that a single-stranded RNA virus that infects tobacco leaves, tobacco mosaic virus (TMV), might be implicated in this effect. TMV, though non-pathogenic, is found in smokers’ airways, and stimulates adaptive and innate immunity, with release of specific antibodies and interferons. The latter may have preventive and/or therapeutic effects against COVID-19. If confirmed by epidemiological and interventional studies, this might lead to the use of TMV as an immunological adjuvant against SARS-CoV-2 infection and COVID-19 disease. url: https://api.elsevier.com/content/article/pii/S0306987720322337 doi: 10.1016/j.mehy.2020.110153 id: cord-352911-9wbq9qo2 author: de Oliveira, Pedro Gonçalves title: Diacerein: a potential multi-target therapeutic drug for COVID-19 date: 2020-06-01 words: 2539.0 sentences: 135.0 pages: flesch: 45.0 cache: ./cache/cord-352911-9wbq9qo2.txt txt: ./txt/cord-352911-9wbq9qo2.txt summary: The mortality related to severe acute respiratory distress syndrome (ARDS) and multi-organ failure in COVID-19 patients has been suggested to be connected with cytokine storm syndrome (CSS), an excessive immune response that severely damages healthy lung tissue. Total extracts from monolayer cell cultures infected with SARS-CoV-2 and treated with rhein under the conditions described above will be analysed using commercially available protein arrays to determine the levels and activation state of proteins involved in the TLR-, Akt-, MAPK-, and NF-B-regulated signalling pathways. The mechanisms of action involved include the control of hyperinflammatory conditions by multi-faceted cytokine inhibition of IL-1, IL-2, IL-6, IL-8, IL-12, IL-18 and TNF-α; anti-platelet aggregation activity; and potential effects on viral infection and replication. Rhein suppresses lung inflammatory injury induced by human respiratory syncytial virus through inhibiting NLRP3 inflammasome activation via NF-κB pathway in mice abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 19 (COVID-19), was declared pandemic by the World Health Organization in March 2020. SARS-CoV-2 binds its host cell receptor, angiotensin-converting enzyme 2 (ACE2), through the viral spike (S) protein. The mortality related to severe acute respiratory distress syndrome (ARDS) and multi-organ failure in COVID-19 patients has been suggested to be connected with cytokine storm syndrome (CSS), an excessive immune response that severely damages healthy lung tissue. In addition, cardiac symptoms, including fulminant myocarditis, are frequent in patients in a severe state of illness. Diacerein (DAR) is an anthraquinone derivative drug whose active metabolite is rhein. Different studies have shown that this compound inhibits the IL-1, IL-2, IL-6, IL-8, IL-12, IL-18, TNF-α, NF-κB and NALP3 inflammasome pathways. The antiviral activity of rhein has also been documented. This metabolite prevents hepatitis B virus (HBV) replication and influenza A virus (IAV) adsorption and replication through mechanisms involving regulation of oxidative stress and alterations of the TLR4, Akt, MAPK, and NF-κB signalling pathways. Importantly, rhein inhibits the interaction between the SARS-CoV S protein and ACE2 in a dose-dependent manner, suggesting rhein as a potential therapeutic agent for the treatment of SARS-CoV infection. Based on these findings, we hypothesize that DAR is a multi-target drug useful for COVID-19 treatment. This anthraquinone may control hyperinflammatory conditions by multi-faceted cytokine inhibition and by reducing viral infection. url: https://www.sciencedirect.com/science/article/pii/S0306987720311828?v=s5 doi: 10.1016/j.mehy.2020.109920 ==== make-pages.sh questions [ERIC WAS HERE] parallel: Warning: No more processes: Decreasing number of running jobs to 86. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 85. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. ==== 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