Summary of your 'study carrel' ============================== This is a summary of your Distant Reader 'study carrel'. The Distant Reader harvested & cached your content into a collection/corpus. It then applied sets of natural language processing and text mining against the collection. The results of this process was reduced to a database file -- a 'study carrel'. The study carrel can then be queried, thus bringing light specific characteristics for your collection. These characteristics can help you summarize the collection as well as enumerate things you might want to investigate more closely. This report is a terse narrative report, and when processing is complete you will be linked to a more complete narrative report. Eric Lease Morgan Number of items in the collection; 'How big is my corpus?' ---------------------------------------------------------- 672 Average length of all items measured in words; "More or less, how big is each item?" ------------------------------------------------------------------------------------ 5383 Average readability score of all items (0 = difficult; 100 = easy) ------------------------------------------------------------------ 49 Top 50 statistically significant keywords; "What is my collection about?" ------------------------------------------------------------------------- 76 Fig 55 SARS 52 PCR 52 COVID-19 48 RNA 45 figure 39 cell 37 virus 28 covid-19 25 patient 24 respiratory 22 protein 20 IFN 18 China 17 dna 15 influenza 15 infection 14 H1N1 12 case 11 RSV 10 bat 10 HIV-1 10 HCV 9 study 9 MERS 9 HIV 9 H5N1 8 model 8 ICU 8 CD8 8 CD4 7 sequence 7 pneumonia 7 gene 7 Vero 7 PEDV 7 LPS 6 viral 6 sample 6 risk 6 health 6 USA 6 ILI 6 IBV 6 HRV 6 Ebola 5 table 5 peptide 5 outbreak 5 disease Top 50 lemmatized nouns; "What is discussed?" --------------------------------------------- 18642 cell 16311 virus 15530 % 12173 study 11590 infection 10606 protein 8085 patient 6727 case 6500 disease 6344 influenza 6221 analysis 6114 datum 5755 time 5651 sample 5445 model 5331 number 5168 result 4991 group 4985 level 4907 gene 4817 expression 4618 sequence 4590 response 4506 control 4172 day 4158 mouse 4046 effect 4017 antibody 3869 type 3616 population 3595 value 3514 factor 3342 rate 3267 health 3153 activity 3135 figure 3030 risk 2968 strain 2922 system 2900 year 2852 p 2835 method 2755 test 2746 assay 2713 outbreak 2713 animal 2669 detection 2666 t 2659 ml 2645 region Top 50 proper nouns; "What are the names of persons or places?" -------------------------------------------------------------- 5192 Fig 3756 RNA 3517 PCR 3355 SARS 2558 COVID-19 2227 C 2133 Table 1855 T 1825 China 1526 IFN 1449 RT 1399 CoV-2 1309 A 1307 Health 1287 CoV 1176 S1 1136 H1N1 1127 al 1098 mg 1051 HIV 1047 HIV-1 1006 M 995 USA 975 PBS 960 et 948 . 944 HCV 884 B 870 S 835 HA 828 CD4 758 N 743 MERS 740 RSV 737 II 735 Influenza 719 NP 717 Figure 709 ELISA 703 H5N1 695 CD8 666 PLoS 656 HRV 642 sha 637 United 609 a1111111111 603 DNA 597 Coronavirus 591 University 579 D Top 50 personal pronouns nouns; "To whom are things referred?" ------------------------------------------------------------- 12671 we 5930 it 2322 they 1813 i 768 them 355 us 171 one 161 you 142 itself 130 themselves 112 he 44 she 24 me 24 him 20 its 18 ours 14 pregn 13 myself 9 yourself 9 her 8 imagej 7 mrnas 7 ifitm3 6 em 5 ourselves 5 nsp10 5 ns3/4a 5 apod 5 9b 4 mg 4 interleukin-10 4 il-2rcc 4 herself 4 clustalx 3 oneself 2 ĝ 2 theirs 2 snoz40 2 s 2 p450s 2 mine 2 lc16m8 2 himself 2 carma1 2 's 2 'em 1 π 1 y122 1 xõ 1 usp14 Top 50 lemmatized verbs; "What do things do?" --------------------------------------------- 112333 be 15936 have 15069 use 7489 show 5030 include 3826 base 3765 report 3759 increase 3755 do 3751 find 3558 associate 3528 compare 3527 identify 3338 follow 3292 detect 3078 infect 3003 perform 2873 observe 2811 induce 2796 suggest 2778 indicate 2645 describe 2638 contain 2462 provide 2402 determine 2336 bind 2224 express 2211 test 2176 obtain 2056 confirm 1937 reduce 1772 collect 1760 require 1722 cause 1706 result 1706 relate 1684 analyze 1656 consider 1613 give 1609 develop 1607 demonstrate 1564 estimate 1529 see 1507 know 1505 assess 1459 affect 1458 represent 1452 lead 1421 measure 1416 take Top 50 lemmatized adjectives and adverbs; "How are things described?" --------------------------------------------------------------------- 10150 not 8156 - 7318 high 6334 viral 6207 also 5788 human 5470 other 5232 respiratory 4923 more 3978 low 3775 different 3686 only 3608 specific 3533 however 3329 clinical 3208 well 3164 positive 3107 such 3004 first 2879 most 2677 significant 2672 severe 2395 non 2355 acute 2268 further 2187 then 2178 anti 2167 similar 2113 large 2080 respectively 2070 infectious 2040 immune 2007 as 1968 significantly 1961 previously 1958 same 1914 negative 1870 total 1868 early 1808 important 1790 new 1750 thus 1717 single 1665 therefore 1663 small 1606 several 1566 infected 1550 less 1509 molecular 1496 social Top 50 lemmatized superlative adjectives; "How are things described to the extreme?" ------------------------------------------------------------------------- 912 most 701 high 482 least 365 good 257 Most 214 large 180 low 96 great 65 strong 56 close 47 near 46 late 44 bad 34 small 33 early 28 long 25 young 23 short 22 simple 20 big 19 few 17 old 12 poor 10 weak 9 steep 7 fast 5 outermost 4 vRNA 4 tt 4 deep 3 southernmost 3 gDNA 3 common 3 broad 3 Least 3 -I 2 � 2 www.plosone.org 2 wide 2 new 2 mild 2 light 2 easy 2 PICV 2 -t 2 -8 1 wtPEDV 1 wet 1 wealthy 1 warm Top 50 lemmatized superlative adverbs; "How do things do to the extreme?" ------------------------------------------------------------------------ 1967 most 603 least 79 well 9 hard 4 worst 2 youngest 2 vrna 2 lowest 2 long 2 clustalw 2 -tag 1 � 1 www.plosone.org 1 strongest 1 smallest 1 shortest 1 ribv 1 poorest 1 near 1 latest 1 highest 1 furthest 1 fewest 1 fast 1 early 1 -biotin Top 50 Internet domains; "What Webbed places are alluded to in this corpus?" ---------------------------------------------------------------------------- 133 doi.org 23 www 20 www.ncbi.nlm.nih.gov 14 www.who.int 14 github.com 6 tree.bio.ed.ac.uk 5 www.ncbi 5 www.genego.com 5 www.ebi.ac.uk 5 tools.iedb.org 4 www.drugbank.ca 4 blast.ncbi.nlm.nih.gov 3 www.niaid.nih.gov 3 www.fludb.org 3 www.cbs.dtu.dk 3 sourceforge.net 3 osf.io 3 endmemo.com 2 younghhk.shinyapps.io 2 www.worldometers.info 2 www.wild-one.org 2 www.uniprot.org 2 www.tripos.com 2 www.string-db.org 2 www.selectagents.gov 2 www.rcsb.org 2 www.r-project.org 2 www.proteinatlas.org 2 www.ncbi.nlm.nih 2 www.ncbi.nlm 2 www.mygov.in 2 www.megasoftware.net 2 www.genome.jp 2 www.ensembl.org 2 www.ch.embnet.org 2 www.cdc.gov 2 www.broad.mit.edu 2 www.animalgenome.org 2 www.r-project.org 2 string-db.org 2 riskcalc.org 2 podospora.igmors.u-psud.fr 2 pgrc.ipk-gatersleben.de 2 coronavirus.jhu.edu 2 compbio.dfci.harvard.edu 2 beast.bio.ed.ac.uk 2 140.113.239.111 1 zlab.bio 1 zinc.docking.org 1 zhanglab.ccmb.med.umich.edu Top 50 URLs; "What is hyperlinked from this corpus?" ---------------------------------------------------- 23 http://www 5 http://www.ncbi.nlm.nih.gov/ 5 http://www.ncbi 4 http://www.drugbank.ca/ 4 http://github.com/ 3 http://www.who.int/ 3 http://www.ncbi.nlm.nih.gov 3 http://www.genego.com/pdf/MC_legend 3 http://www.fludb.org 3 http://tree.bio.ed.ac.uk/ 3 http://blast.ncbi.nlm.nih.gov/Blast.cgi 2 http://www.uniprot.org/ 2 http://www.tripos.com/mol2/atom_types.html 2 http://www.string-db.org 2 http://www.rcsb.org/ 2 http://www.r-project.org/ 2 http://www.proteinatlas.org/ 2 http://www.ncbi.nlm.nih.gov/tools/ 2 http://www.ncbi.nlm.nih.gov/sra 2 http://www.ncbi.nlm.nih.gov/geo/ 2 http://www.ncbi.nlm.nih 2 http://www.ncbi.nlm 2 http://www.animalgenome.org/cgi-bin/QTLdb/index 2 http://tree.bio.ed.ac.uk/software/figtree/ 2 http://string-db.org/ 2 http://sourceforge.net/projects/buho/ 2 http://riskcalc.org/COVID19Hospitalization/ 2 http://pgrc.ipk-gatersleben.de/misa/ 2 http://osf.io/sb6ty/ 2 http://endmemo.com/bio/dnacopynum.php" 2 http://beast.bio.ed.ac.uk 2 http://140.113.239.111/~ps2v2/docs.php 1 http://zlab.bio/s/COVID-19-detection-v20200321.pdf 1 http://zinc.docking.org 1 http://zhanglab.ccmb.med.umich.edu/I-TASSER 1 http://youtu.be/mI-L_ZrL__U 1 http://younghhk.shinyapps.io/tvSIRforCOVID19/ 1 http://younghhk.shinyapps.io/ 1 http://www.worldometers.info/coronavirus/#countries 1 http://www.worldometers.info/ 1 http://www.worldclim.org/ 1 http://www.wjx.cn 1 http://www.wild-one.org/ 1 http://www.wild-one.org 1 http://www.who.int/mediacentre/factsheets/fs164/ 1 http://www.who.int/gho/en/ 1 http://www.who.int/foodsafety/areas_work/ 1 http://www.who.int/emergencies/diseases/novelcoronavirus-2019/situation-reports/ 1 http://www.who.int/emergencies/diseases/novel-coronavirus-2019/ 1 http://www.who.int/csr/sars/country/ Top 50 email addresses; "Who are you gonna call?" ------------------------------------------------- 1 mascar@ccf.org 1 frederic.dutheil@uca.fr 1 eticadeinvestigacion@uc.cl Top 50 positive assertions; "What sentences are in the shape of noun-verb-noun?" ------------------------------------------------------------------------------- 79 cells were then 34 results are consistent 34 study did not 24 cells were also 24 samples were then 21 samples were also 19 study has several 17 data are available 16 cells were co 16 studies have also 16 virus infected cells 14 cells were pre 14 data are consistent 13 group was significantly 13 infection was not 13 levels were significantly 13 patients were more 13 samples were not 13 virus does not 12 cases were not 12 cells were not 12 results were consistent 12 samples were positive 12 virus was not 11 cases were more 11 cells was not 11 data were available 11 data were not 11 group were significantly 11 results do not 11 results were not 11 study does not 10 analysis was not 10 data do not 10 data using real 10 expression was significantly 10 genes were up 10 group did not 10 protein was not 10 studies did not 10 study had several 10 study was not 9 case report form 9 cells did not 9 cells were again 9 cells were first 9 cells were further 9 cells were transiently 9 data did not 9 expression was not Top 50 negative assertions; "What sentences are in the shape of noun-verb-no|not-noun?" --------------------------------------------------------------------------------------- 5 group had no detectable 4 data were not available 3 results were not available 2 analysis was not possible 2 cases were not more 2 cells had no effect 2 cells was not different 2 cells were not significantly 2 cells were not susceptible 2 data were not normally 2 expression was not significantly 2 group is not directly 2 group was not obvious 2 levels did not significantly 2 levels were not different 2 model were not significantly 2 patients have not yet 2 proteins are not essential 2 virus has no reaction 1 % are not married 1 % had no alcohol 1 % had no degree 1 % had no formal 1 % had no soap 1 % had no stable 1 % is not strict 1 % reported no history 1 analyses did not materially 1 analyses did not meaningfully 1 analyses showed no changes 1 analyses showed no initial 1 analysis found no differences 1 analysis is not applicable 1 analysis was not available 1 analysis were not able 1 antibodies did not significantly 1 antibodies were not cross 1 antibody is not able 1 antibody is not directly 1 antibody is not well 1 case had no clear 1 case is not officially 1 case was not statistically 1 cases are not currently 1 cases are not routinely 1 cases had no differences 1 cases had no pathogen 1 cases is not available 1 cases is not nearly 1 cases is not significantly A rudimentary bibliography -------------------------- id = cord-000877-usz7pnvu author = Abdel-Moneim, Ahmed S. title = Detection of Bocavirus in Children Suffering from Acute Respiratory Tract Infections in Saudi Arabia date = 2013-01-30 keywords = Arabia; respiratory summary = title: Detection of Bocavirus in Children Suffering from Acute Respiratory Tract Infections in Saudi Arabia Swabs samples from 80 children with respiratory tract infections were examined for the presence of HBoV. Human bocavirus (HBoV) was first found in children with acute respiratory tract infections in 2005 [1] . The current study aims to screen the epidemiological status and molecular phylogeny of HBoV isolates prevailing in pediatric patients with respiratory infection in Saudi Arabia. The current study investigated the prevalence of HBoV in patients suffering from respiratory tract infections in Saudi Arabia. Furthermore, the phylogenetic analysis results of three selected sequences showed that the Saudi HBoV1 strains obtained from respiratory samples belonged to group I human bocaviruses (Fig. 1) . Detection of human bocavirus in Japanese children with lower respiratory tract infections Frequent detection of viral coinfection in children hospitalized with acute respiratory tract infection using a real-time polymerase chain reaction doi = 10.1371/journal.pone.0055500 id = cord-004091-gex0zvoa author = Abdulkareem, Shaheen A. title = Risk perception and behavioral change during epidemics: Comparing models of individual and collective learning date = 2020-01-06 keywords = Fig; agent; group; risk summary = For this study, we ran eight ABMs to test various combinations of individual and group learning, using different information sources-with or without interactions among agents-as factors in the BNs. We investigate the extent to which the epidemic spreads, depending on these different learning approaches regarding risk perception and coping decisions. The empirically-driven BNs model a two-stage decision process of people facing a disease risk: learning to update risk perceptions (threat appraisal, BN1 in Fig 1) and making decisions about how to adapt their behavior during the epidemic (coping appraisal, BN2 in Fig 1) . To evaluate the impact of individual and social intelligence on agents'' learning processes regarding risk perception and coping appraisal and the resulting patterns of disease spread, we used four output measures: disease diffusion, risk perception, spatial patterns, and model performance. Finally, in M7, where household agents learned risk perception in decentralized groups and learned to cope individually, 2,911 infected cases were recorded (Table 3) . doi = 10.1371/journal.pone.0226483 id = cord-292475-jrl1fowa author = Abry, Patrice title = Spatial and temporal regularization to estimate COVID-19 reproduction number R(t): Promoting piecewise smoothness via convex optimization date = 2020-08-20 keywords = France; datum; time summary = The novelty of the proposed approach is twofold: 1) the estimation of the reproduction number is achieved by convex optimization within a proximal-based inverse problem formulation, with constraints aimed at promoting piecewise smoothness; 2) the approach is developed in a multivariate setting, allowing for the simultaneous handling of multiple time series attached to different geographical regions, together with a spatial (graph-based) regularization of their evolutions in time. In that spirit, the overarching goal of the present work is twofold: (1) proposing a new, more versatile framework for the estimation of R(t) within the semi-parametric model of [8, 10] , reformulating its estimation as an inverse problem whose functional is minimized by using non smooth proximal-based convex optimization; (2) inserting this approach in an extended multivariate framework, with applications to various complementary datasets corresponding to different geographical regions. doi = 10.1371/journal.pone.0237901 id = cord-290773-kgb8r561 author = Ahn, Jong Gyun title = Clinical characteristics and cytokine profiles of children with acute lower respiratory tract infections caused by human rhinovirus date = 2018-07-03 keywords = HRV summary = title: Clinical characteristics and cytokine profiles of children with acute lower respiratory tract infections caused by human rhinovirus Therefore, in this study, we investigated the epidemiological, clinical, and virological characteristics of HRV infections in children with acute lower respiratory tract infections. This study demonstrates that HRV is an important cause of lower respiratory infection in young children that is associated with symptoms of respiratory distress, such as chest retraction and wheezing. In our study, there were no significant differences in the clinical features, laboratory data or NPA cytokine levels between HRV-A and -C infections. High prevalence of human rhinovirus C infection in Thai children with acute lower respiratory tract disease Human rhinovirus species C infection in young children with acute wheeze is associated with increased acute respiratory hospital admissions Rhinovirus load and disease severity in children with lower respiratory tract infections doi = 10.1371/journal.pone.0198624 id = cord-001145-hc9ssruz author = Akazawa, Yuko title = Endoplasmic Reticulum Stress Contributes to Helicobacter Pylori VacA-Induced Apoptosis date = 2013-12-13 keywords = cell; chop summary = We found that C/EBP homologous protein (CHOP), a key signaling protein of ER stress-induced apoptosis, was transcriptionally up-regulated following incubation of gastric epithelial cells with VacA. Phosphorylation of eukaryotic initiation factor 2 (eIF2)-alpha, which is known to occur downstream of the ER stress sensor PKR-like ER-localized eIF2-alpha kinase (PERK) and to regulate CHOP expression, was also observed following incubation with VacA in the presence of ammonium chloride. Further studies showed that silencing of the PERK gene with siRNA attenuated VacA-mediated phosphorylation of eIF2-alpha, CHOP induction, expression of BH3-only protein Bim and Bax activation, and cell death induced by VacA with ammonium chloride, indicating that ER stress may lead to mitochondrial dysfunction during VacA-induced toxicity. pylori-positive gastric mucosa, as well as transcriptional up-regulation of Bim in AZ-521 cells treated with VacA plus NH 4 Cl. Since knockdown of PERK decreased VacA-mediated Bim mRNA expression, activation of Bim likely occurred downstream of ER stress. doi = 10.1371/journal.pone.0082322 id = cord-320466-l7017jis author = Akgun, Emel title = Proteins associated with neutrophil degranulation are upregulated in nasopharyngeal swabs from SARS-CoV-2 patients date = 2020-10-20 keywords = ELANE; MPO; PRTN3; SARS summary = Neutrophil Elastase (ELANE), Azurocidin (AZU1), Myeloperoxidase (MPO), Myeloblastin (PRTN3), Cathepsin G (CTSG) and Transcobalamine-1 (TCN1) were found to be significantly altered in naso-oropharyngeal samples of SARS-CoV-2 patients. The identified up-regulated proteins Myeloperoxidase, Myeloblastin, Neutrophil Elastase, Cathepsin G, and Azurocidin (MPO, PRTN3, ELANE, CTSG, and AZU1) in nasooropharyngeal swab samples are discussed to highlight the molecular mechanism changes in the site of infection. Pathway analysis of the significantly altered protein levels between COVID-19 positive and negative patients'' naso-oropharyngeal swab samples were analyzed using the STRING online database. In SARS-CoV-2 patients'' naso-oropharyngeal samples, we have identified azurophilic granule (AG) proteins like Myeloperoxidase (MPO), elastase (ELANE), cathepsin G (CTSG), azurocidin 1 (AZU1) and proteinase 3 (PRTN3) to be highly overexpressed. The alterations of various proteins in SARS-CoV-2 infected patients'' naso-oropharyngeal samples depict the molecular changes that govern the host antiviral defense system. doi = 10.1371/journal.pone.0240012 id = cord-317912-v2wovcqd author = Akmatov, Manas K. title = Equivalence of Self- and Staff-Collected Nasal Swabs for the Detection of Viral Respiratory Pathogens date = 2012-11-14 keywords = ARI; self; swab summary = found similar detection rates for respiratory pathogens between self-and staffcollected midturbinate swabs when one staff-collected and one selfcollected swab were taken from opposite nostrils during the same visit to a campus health center [5] . In the study center, a trained staff member (A.G.) obtained a nasal swab (regular flocked swab, Copan, Brescia, Italy, product number 359C) from the participant''s left nostril and instructed him/her how to perform a self-swab. Sensitivity and specificity of self-collected swabs, obtained in the study center, to detect viral respiratory pathogens (compared to staff-collected swabs)*. The detection of a viral pathogen was independent of the amount of b-actin DNA in both staff-and self-swabs collected on day 1 (Fig. 4) . This prospective study comparing staff-and self-collected nasal swabs for the detection of ARI pathogens clearly demonstrated the validity of self-swabbing; specifically, self-swabbing was not inferior in terms of acceptance, satisfaction, sample adequacy, and viral detection rate. doi = 10.1371/journal.pone.0048508 id = cord-345019-i7zm9bt1 author = Al-Waleedi, Ali Ahmed title = The first 2 months of the SARS-CoV-2 epidemic in Yemen: Analysis of the surveillance data date = 2020-10-29 keywords = SARS; Yemen; case summary = A total of 268 individuals with confirmed SARS-CoV-2 infection were hospitalized (57%), among whom there were 95 in-hospital deaths, CONCLUSIONS: The surveillance strategy implemented in the first 2 months of the SARS CoV 2 in the southern and eastern governorates of Yemen, captured mainly severe cases. For early detection of SARS-CoV-2 in Yemen, as in other countries, a case definition, active surveillance, and contact tracing were required [10, 11] . The first 2 months after confirmation of the SARS-CoV-2 epidemic in Yemen was characterized by a 57% hospitalization rate in the southern and eastern parts of the country included in The First 2 Months of the SARS-CoV-2 Epidemic in Yemen our study, 63% of deaths occurring in individuals aged <60 years, confirmatory testing of <50% of the suspected cases, and majority of cases were not related to a defined chain of transmission. doi = 10.1371/journal.pone.0241260 id = cord-001639-p9mbmfaq author = Alfonso-Morales, Abdulahi title = Evaluation of a Phylogenetic Marker Based on Genomic Segment B of Infectious Bursal Disease Virus: Facilitating a Feasible Incorporation of this Segment to the Molecular Epidemiology Studies for this Viral Agent date = 2015-05-06 keywords = Fig; IBDV; cuban; segment summary = doi = 10.1371/journal.pone.0125853 id = cord-268429-drejl99k author = Almberg, Emily S. title = A Serological Survey of Infectious Disease in Yellowstone National Park’s Canid Community date = 2009-09-16 keywords = CDV; Interior; YNP summary = METHODOLOGY/PRINCIPAL FINDINGS: We analyzed sympatric wolf, coyote (Canis latrans), and red fox (Vulpes vulpes) serologic data from YNP, spanning 1991–2007, to identify long-term patterns of pathogen exposure, identify associated risk factors, and examine evidence for disease-induced mortality among wolves for which there were survival data. Wolf, coyote, and fox exposure to canine distemper virus (CDV) was temporally variable, with evidence for distinct multi-host outbreaks in 1999 and 2005, and perhaps a smaller, isolated outbreak among wolves in the interior of YNP in 2002. Thus we sought to use long-term serological data to identify temporal, spatial, and demographic patterns of pathogen exposure among wolves, coyotes (Canis latrans), and foxes (Vulpes vulpes) in YNP. In summary, the constant high canid exposure to CPV, CAV-1, and CHV in YNP suggest that these pathogens are established in the wolf and coyote populations and that they are unlikely to be causing acute mortality in their hosts [50, 51] . doi = 10.1371/journal.pone.0007042 id = cord-294768-bs6thjw2 author = Alonso-Fernández, Alberto title = Prevalence of pulmonary embolism in patients with COVID-19 pneumonia and high D-dimer values: A prospective study date = 2020-08-25 keywords = COVID-19; patient summary = title: Prevalence of pulmonary embolism in patients with COVID-19 pneumonia and high D-dimer values: A prospective study CONCLUSIONS: Patients with COVID-19 pneumonia and D-dimer values higher than 1 μg/mL presented a high prevalence of PE, regardless of clinical suspicion. [12] found, in a retrospective study in 184 intensive care unit (ICU) patients with severe COVID-19 pneumonia, a high prevalence of thrombotic complications and, by far, pulmonary embolism (PE) was the most frequent. Pulmonary embolism in COVID-19 pneumonia with high D-dimer values: A prospective study procoagulant (D-dimer) markers that correlated with the extend of the thromboembolic episode compared to those patients without PE. We included patients with D-dimer values higher than 1 μg/mL, which have been associated with disease severity and in-hospital mortality in patients with COVID-19 infection. Pulmonary embolism in COVID-19 pneumonia with high D-dimer values: A prospective study of our patients, allocated in the non-PE group, was not on enoxaparin prophylaxis during hospitalization. doi = 10.1371/journal.pone.0238216 id = cord-321855-7b1c2xdh author = Alshami, Alanoud title = Silent disease and loss of taste and smell are common manifestations of SARS-COV-2 infection in a quarantine facility: Saudi Arabia date = 2020-10-30 keywords = COV-2; PCR; SARS summary = title: Silent disease and loss of taste and smell are common manifestations of SARS-COV-2 infection in a quarantine facility: Saudi Arabia PRIMARY AND SECONDARY MEASURES: The clinical presentation, prevalence of asymptomatic carriers among SARS-COV-2 positive quarantined subjects, and the difference between virus clearance among symptomatic and asymptomatic individuals. The persistent positive PCR beyond 14 days observed in the mild symptomatic residents despite being symptoms free, warrant further studies to determine its implications on disease spread and control. have examined 24 asymptomatic infected individuals with a history of close contact with SARS-COV-2 confirmed cases and found that only 20% of them developed symptoms. Our findings are in light with a recent study that reported a 59% prevalence of loss of taste and smell in a cohort of COVID-19 patients [15] . Sudden onset of loss of smell and taste were prevalent in our study and were key symptoms of mild disease. doi = 10.1371/journal.pone.0241258 id = cord-294912-xl0wzi16 author = Alteri, Claudia title = Detection and quantification of SARS-CoV-2 by droplet digital PCR in real-time PCR negative nasopharyngeal swabs from suspected COVID-19 patients date = 2020-09-08 keywords = CoV-2; SARS; covid-19 summary = doi = 10.1371/journal.pone.0236311 id = cord-001571-drcfdv9z author = Alvarez, Julio title = Impact of Porcine Epidemic Diarrhea on Performance of Growing Pigs date = 2015-03-13 keywords = ped summary = Here, a retrospective cohort study to evaluate the impact of porcine epidemic diarrhea virus (PEDv) infection on growing pigs'' performance, as indicated by mortality, average daily gain (ADG), average daily feed intake (ADFI), and feed conversion ratio (FCR) was performed using production records from weaned pigs in nursery and wean-to-finish sites from sow farms that became PEDv-infected between May 2013 and June 2014. Collected data included information on the site in which pigs were located, site production type (nursery or wean to finish (WF)), pig source (sow farm from which pigs originated), start and close period on each site, number of pigs per batch, mortality (defined by percentage of total pigs started), average daily gain (ADG), average daily feed intake (ADFI), feed conversion (FCR), and status of the sow farm from which pigs were weaned for PRRS and PED. doi = 10.1371/journal.pone.0120532 id = cord-311074-j3fw4dfc author = Alviset, Sophie title = Continuous Positive Airway Pressure (CPAP) face-mask ventilation is an easy and cheap option to manage a massive influx of patients presenting acute respiratory failure during the SARS-CoV-2 outbreak: A retrospective cohort study date = 2020-10-14 keywords = COVID-19; CPAP; ICU; patient summary = title: Continuous Positive Airway Pressure (CPAP) face-mask ventilation is an easy and cheap option to manage a massive influx of patients presenting acute respiratory failure during the SARS-CoV-2 outbreak: A retrospective cohort study From 27th March to 23rd April, consecutive patients who had respiratory failure or were unable to maintain an SpO2 > 90%, despite receiving 10–15 l/min of oxygen with a non-rebreather mask, were treated by continuous positive airway pressure (CPAP) unless the ICU physician judged that immediate intubation was indicated. The following baseline patient characteristics were retrieved from patient electronic medical record: sex, age, comorbidities, body mass index (BMI), withholding / withdrawal of lifesustaining therapies, associated COVID-19 therapies administered before the primary outcome under study occurred (antivirals, corticosteroids, immuno-modulating therapies, prone positioning), oxygen flow rate and SpO2 before and after starting CPAP treatment, duration of CPAP treatment, medical unit where CPAP treatment was performed, duration of invasive mechanical ventilation, SAPS2 score for patients admitted in ICU, driving pressure and P/F ratio on first day of mechanical ventilation. doi = 10.1371/journal.pone.0240645 id = cord-287761-73qgx58i author = Aly, Mahmoud title = Occurrence of the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) across the Gulf Corporation Council countries: Four years update date = 2017-10-13 keywords = East; MERS; Middle summary = Within a time span of 4 years from June 2012 to July 2016, we collect samples form MERS-CoV infected individuals from National Guard Hospital, Riyadh, and Ministry of health Saudi Arabia and other GCC countries. GCC countries including Saudi Arabia now have the infrastructure in place that allows physicians and scientific community to identify and immediately respond to the potential risks posed by new outbreaks of MERS-CoV infections in the region. The emergence of MERS-CoV dates back to July 2012 when an elderly patient of age 60 years died from an acute pneumonia in Saudi Arabia, and a new coronavirus strain was isolated from his lung tissue [1] . With regard to viral origin and transmission, the first case of MERS-CoV infection did not relate it to any particular contact with animals before the disease onset; however, other studies did link it to Dromedary camels [5] [6] [7] [8] . doi = 10.1371/journal.pone.0183850 id = cord-266797-uglsx7se author = Anastassopoulou, Cleo title = Data-based analysis, modelling and forecasting of the COVID-19 outbreak date = 2020-03-31 keywords = February; January; SIRD summary = Our analysis further reveals a significant decline of the case fatality ratio from January 26 to which various factors may have contributed, such as the severe control measures taken in Hubei, China (e.g. quarantine and hospitalization of infected individuals), but mainly because of the fact that the actual cumulative numbers of infected and recovered cases in the population most likely are much higher than the reported ones. Based on the released data, we attempted to estimate the mean values of the main epidemiological parameters, i.e. the basic reproduction number R 0 , the case fatality (ĝ) and case recovery (b) ratios, along with their 90% confidence intervals. Then, as described above, we provide coarse estimations of the "effective" per day recovery and mortality rates of the SIRD model based on the reported data by solving the corresponding least squares problems. doi = 10.1371/journal.pone.0230405 id = cord-002305-qq73gr9y author = Anson, Marie title = Regulation and Maintenance of an Adoptive T-Cell Dependent Memory B Cell Pool date = 2016-11-23 keywords = HEL; YFP; cell summary = In conclusion, the adoptive cell transfer strategy allowed the development of a primary immune response with B cell activation and expansion, induction of AID expression, class switch recombination, antigen-specific IgM and IgG antibody production and germinal center formation. In this study we show that it is possible to fully reconstitute a primary response and the establishment of antibody memory in immune deficient mice after adoptive transfer of antigen-specific monoclonal B cells together with a population of monoclonal helper T cells. In contrast we showed that after adoptive transfer in immune deficient hosts antigen immunization induced B cell activation and expansion, induction of AID expression, class switch recombination, antigen-specific IgM and IgG antibody production, germinal center formation and the generation of two subsets of AID/YFP + IgM + IgGand AID/YFP + Ig-M -IgG + antigen-experienced B cell subsets able to persist in a lymphopenic environment by cell division mimicking responses obtained in intact non-Tg mice [4] . doi = 10.1371/journal.pone.0167003 id = cord-002601-d8908t93 author = Arellano-Llamas, Rocío title = Molecular features of influenza A (H1N1)pdm09 prevalent in Mexico during winter seasons 2012-2014 date = 2017-07-10 keywords = Mexico; PB2; virus summary = doi = 10.1371/journal.pone.0180419 id = cord-284501-5i0w74q4 author = Armesto, Maria title = The Replicase Gene of Avian Coronavirus Infectious Bronchitis Virus Is a Determinant of Pathogenicity date = 2009-10-09 keywords = Beau; IBV; M41-Struct-2; Rep summary = The IBV cDNA within pGPT-BeauR-Rep-M41-Struct-3UTR was introduced, by homologous recombination using the transient dominant selection (TDS) ( [25, 37] ), into the IBV Beaudette cDNA within the vaccinia virus genome in rVV-BeauR-Rep-DStruct containing Beau-R-derived sequence corresponding to the replicase gene followed by the first 376 nt of the S gene, part of the N gene and the 39-UTR (Fig. 1) . The samples were analysed for the presence of viable IBV by titration in TOCs or used for RNA extraction using the RNeasy method and analysed by RTThe M41-CK-derived cDNA, representing the M41 structural and accessory genes and the M41 39-UTR, within pGPT-BeauR-Rep-M41-Struct-3UTR was fused to the Beau-R replicase gene in the rVV by a homologous recombination event between the Beau-R replicase sequence common to both constructs. Analysis of the tracheal epithelial cells isolated from the infected chickens, for the presence of IBV by titration on TOCs, had indicated that either there was no Beau-R or rBeauR-Rep-M41-Struct-2 present or that the levels of both viruses were below detection. doi = 10.1371/journal.pone.0007384 id = cord-283976-jgae7r2q author = Armstrong, Melissa J. title = Research priorities of caregivers and individuals with dementia with Lewy bodies: An interview study date = 2020-10-07 keywords = DLB; Lewy; research summary = BACKGROUND: Funding bodies are placing increased emphasis on patient and public involvement in research, but the research priorities of individuals and caregivers living with dementia with Lewy bodies (DLB) are unknown. Funding should be informed by the priorities of all relevant stakeholders and support research investigating causes, natural history, biomarkers, and treatment in addition to research targeting themes regarding living with disease (e.g. independence, quality of life, caregiving, and education). The study guide queried a variety of research categories and individuals with DLB and caregivers identified topics important for research in all of them-focusing on awareness, determining the cause of DLB, improving diagnosis, investigating what to expect and disease stages, DLB symptoms needing additional research, therapies to prevent, cure, or slow the progression of DLB, targeting daily function and quality of life, caregiving, and improving education. doi = 10.1371/journal.pone.0239279 id = cord-002953-4rqoenhr author = Arruda, Andréia Gonçalves title = Time-series analysis for porcine reproductive and respiratory syndrome in the United States date = 2018-04-03 keywords = North; PRRS; U.S. summary = doi = 10.1371/journal.pone.0195282 id = cord-336364-2ust3qoq author = Artigas, Laura title = In-silico drug repurposing study predicts the combination of pirfenidone and melatonin as a promising candidate therapy to reduce SARS-CoV-2 infection progression and respiratory distress caused by cytokine storm date = 2020-10-02 keywords = ARD; SARS; protein; set summary = title: In-silico drug repurposing study predicts the combination of pirfenidone and melatonin as a promising candidate therapy to reduce SARS-CoV-2 infection progression and respiratory distress caused by cytokine storm This has provided 3 sets of proteins related with the infection process: 1) coronavirus-host interaction set (including SARS-CoV-2 entry points), 2) lungcells infection set, and 3) acute respiratory distress (ARD) set. According to the findings by GUILDify, we confirm the effect of the combination of pirfenidone and melatonin in the entry points of the SARS-CoV-2 infection, specifically the neighbours of furin and GRP-78, and some proteins associated with ARD. 1) coronavirus-host interaction set (including SARS-CoV-2 entry points), 2) lung-cells infection set, and 3) acute respiratory distress (ARD) set that is composed of 6 subsets (Alveolar macrophages, Monocytes, Neutrophils, Intermediate phase ARD, Late phase ARD and ARD cytokine storm). doi = 10.1371/journal.pone.0240149 id = cord-002621-sq5iod1w author = Attia, Mohamed I. title = New hydrazonoindolin-2-ones: Synthesis, exploration of the possible anti-proliferative mechanism of action and encapsulation into PLGA microspheres date = 2017-07-25 keywords = Fig; PLGA; cell summary = Compounds 7b, 7d and 7e were the most active congeners against the tested human cancer cell lines with average IC(50) values of 4.77, 3.39 and 2.37 μM, respectively, as compared with the reference isatin-based drug, sunitinib, which exhibited an average IC(50) value of 8.11 μM. Incorporation of 7e into PLGA microspheres improved its in vitro anti-proliferative activity toward the human cancer cell line A549 after 120 h incubation period with an IC(50) value less than 0.8 μM. The human lung cancer A549 cell line was incubated with various concentrations (0.8, 1.6, 3.13, 6.25, 12.5, 25 and 50 μM) of both free 7e and 7e-loaded microspheres to evaluate the anti-proliferative activity by assessing their effect on cell viability. Synthesis and anticancer activity of certain hydrazonoindolin-2-ones Fig 13B illustrates the obtained results when 7e-loaded microspheres were incubated with the human lung cancer cell lineA549for incubation periods and concentrations similar to that of the free 7e. doi = 10.1371/journal.pone.0181241 id = cord-001546-ndz3oarf author = Ayithan, Natarajan title = Virus-Like Particles Activate Type I Interferon Pathways to Facilitate Post-Exposure Protection against Ebola Virus Infection date = 2015-02-26 keywords = EBOV; IFN; Ifnar; VLP summary = Importantly, proinflammatory cytokine/chemokine expression was much higher in WT mice without VLPs than mice treated with VLPs. In EBOV infected Ifnar(-/-) mice, however, uninhibited viral replication and elevated proinflammatory factor expression ensued, irrespective of VLP treatment, supporting the view that type I IFN signaling helps to limit viral replication and attenuate inflammatory responses. Further analyses showed that VLP protection requires the transcription factor, IRF8 known to amplify type I IFN signaling in dendritic cells and macrophages, the probable sites of initial EBOV infection. The aim of this study was to further investigate molecular bases of postexposure protection by VLPs. Based on our previous report that VLPs stimulate type I IFN expression in DCs and macrophages, in vitro, we focused on the role of type I IFN signaling, and found that post-exposure VLP treatment leads to accelerated activation of IFN signaling, resulting in early induction of ISGs. Significantly, VLP stimulated ISG induction coincided with the attenuation of proinflammatory cytokine surge in EBOV infected mice. doi = 10.1371/journal.pone.0118345 id = cord-257603-ov0b8yub author = Azlan, Arina Anis title = Public knowledge, attitudes and practices towards COVID-19: A cross-sectional study in Malaysia date = 2020-05-21 keywords = COVID-19; MCO; Malaysia summary = To measure practices, participants were asked yes/no questions on whether they had avoided going to crowded places such as weddings; wore a face mask when leaving home; and whether they practiced proper hand hygiene in the week before the movement control order (MCO). The first question asked whether or not they agreed that the COVID-19 situation would be successfully controlled; second, whether they thought Malaysia would be able to win its battle against the virus; and third, whether they thought the Malaysian government was handling the health crisis well [Fig 1] . Practices toward COVID-19 were measured using three questions enquiring on: 1) avoidance of crowded places, 2) wearing of face masks; and 3) practising proper hand hygiene in the week before the Movement Control Order (MCO) was implemented in Malaysia [Fig 2] . Public knowledge, attitudes and practices towards COVID-19 in Malaysia residents in the Eastern region and retirees were among the highest percentage of participants who had not practised good hand hygiene in the week before the MCO. doi = 10.1371/journal.pone.0233668 id = cord-320091-2lrqubdl author = Badawi, Alaa title = Prevalence of chronic comorbidities in dengue fever and West Nile virus: A systematic review and meta-analysis date = 2018-07-10 keywords = DENV; Nile; WNV; West; study summary = The objective of this study is to systematically review the existing literature on the prevalence of the most common non-communicable comorbidities related to the cluster of metabolic syndromes-associated diseases, such as diabetes mellitus, heart diseases, hypertension, asthma, stroke and obesity in flavivirus infections and to evaluate the difference of their prevalence in severe vs. Data extracted from the selected studies in duplicate by two reviewers and included the first author''s name, publication date, country, dates of recruitment, total sample size (divided to males and females), age estimates (from reported mean, median or the mid-point for age range of the highest subject frequency), procedures for case identification, type of flavivirus infection, severity of infection, prevalence of clinical manifestations (mild symptoms such as fever, headache, muscle pain, rash, and malaise together with severe symptoms as described below) and percentage of comorbidities including diabetes (both type I and type II, if mentioned), hypertension, heart diseases (due to the small sample size of individual conditions, we (Table 1) . doi = 10.1371/journal.pone.0200200 id = cord-351918-pu7i1jfe author = Baek, Yae Jee title = A mathematical model of COVID-19 transmission in a tertiary hospital and assessment of the effects of different intervention strategies date = 2020-10-26 keywords = COVID-19; hospital summary = The effects of different intervention strategies such as front door screening, quarantine unit for newly admitted patients, early testing of suspected infected people, and personal protective equipment for both medical staff and visitors were evaluated. The model suggested that the early testing (within eight hours) of infected cases and monitoring the quarantine ward for newly hospitalized patients are effective measures for decreasing the incidence of COVID-19 within a hospital (81.3% and 70% decrease of number of incident cases, respectively, during 60 days). Setting the population vector η as the number of staff, and the stabilized number of inflow and outflow to each department for visitors, we construct the WAIFW matrix, W, by assuming that it is proportional to the contact rate matrix [8, 9] : The diagram for the SEIR (susceptible-exposed-infectious-recovered) model with compartments of doctor, nurse, patient, and caregiver. doi = 10.1371/journal.pone.0241169 id = cord-289892-yh1lioyz author = Bai, Bingke title = Virus-Like Particles of SARS-Like Coronavirus Formed by Membrane Proteins from Different Origins Demonstrate Stimulating Activity in Human Dendritic Cells date = 2008-07-16 keywords = SARS summary = Our data have demonstrated for the first time that SL-CoV VLPs formed by membrane proteins of different origins, one from SL-CoV isolated from bats (BS) and the other two from human SARS-CoV (E and M), activated immature DCs and enhanced the expression of co-stimulatory molecules and the secretion of cytokines. In addition, because in vitro infection model of bat SL-CoV has not so far been established, we intended to use VLPs as an alternative to study the immune responses induced in DCs. Therefore, we compared the phenotypic and functional changes of immature DCs inoculated with BVLPs or with SARS CoV VLPs. The S-specific immune activation was further confirmed in mice using S DNA vaccines. Combining the flow cytometry results in Fig. 2 , it is reasonable to draw a conclusion that the structure of BVLPs, not LPS contamination, contributed to cytokine production in BVLPs-treated DCs. We previously constructed SARS CoV VLPs and investigated the humoral and cellular immune responses induced by SARS CoV VLPs in mice [29] . doi = 10.1371/journal.pone.0002685 id = cord-295339-nzc47itk author = Baker, Marissa G. title = Estimating the burden of United States workers exposed to infection or disease: A key factor in containing risk of COVID-19 infection date = 2020-04-28 keywords = States; United summary = METHODS: To estimate the number of United States workers frequently exposed to infection and disease in the workplace, national employment data (by Standard Occupational Classification) maintained by the Bureau of Labor Statistics (BLS) was merged with a BLS O*NET survey measure reporting how frequently workers in each occupation are exposed to infection or disease at work. Given the proportion of the United States workforce exposed to disease or infection at work, this analysis also serves as an important reminder that the workplace is a key locus for public health interventions, which could protect both workers and the communities they serve. To estimate the number of United States workers frequently exposed to infection and disease in the workplace, national employment data (by Standard Occupational Classification) maintained by the Bureau of Labor Statistics (BLS) was merged with a BLS O*NET survey measure reporting how frequently workers in each occupation are exposed to infection or disease at work. doi = 10.1371/journal.pone.0232452 id = cord-282202-q2q4vies author = Banerjee, Amitava title = Clinical academic research in the time of Corona: A simulation study in England and a call for action date = 2020-08-13 keywords = COVID-19; England; academic; clinical summary = DESIGN: A stochastic model to determine clinical academic capacity in England, incorporating the following key factors which affect the ability to conduct research in the COVID-19 climate: (i) infection growth rate and population infection rate (from UK COVID-19 statistics and WHO); (ii) strain on the healthcare system (from published model); and (iii) availability of clinical academic staff with appropriate skillsets affected by frontline clinical activity and sickness (from UK statistics). "Learning is difficult in the midst of an emergency" [7] , but our ability to deliver timely, high-impact clinical research, relevant to patients and populations, is critical across the academic spectrum [8] , from "bench to bedside to big data", whether basic biology, repurposed and novel therapeutic approaches, vaccines or modelling. Our aims were to: (i) model potential impact of the pandemic on clinical academic capacity in England relating to COVID-19; and (ii) develop evidence-based recommendations to inform the optimal scientific response to COVID-19. doi = 10.1371/journal.pone.0237298 id = cord-258172-p54j4zzo author = Barker, Harlan title = Bioinformatic characterization of angiotensin-converting enzyme 2, the entry receptor for SARS-CoV-2 date = 2020-10-28 keywords = ACE2; RNA; SARS; cell; covid-19; expression summary = Single cell RNA-Seq data from trachea indicated positive signals along the respiratory tract in key protective cell types including club, goblet, proliferating, and ciliary epithelial cells; while in lung the ratio of ACE2-expressing cells was low in all cell types (<2.6%), but was highest in vascular endothelial and goblet cells. Analysis of ACE2 promoter regions was performed using the TFBSfootprinter tool (https:// github.com/thirtysix/TFBS_footprinting) which uses transcription-relevant data from several major databases to enhance prediction of putative TFBSs, including: all cell types aggregated and merged human ATAC-Seq data from ENCODE [43] , transcription start sites and expression data from FANTOM5 [44] , expression quantitative trail loci from GTEx [39] , TFBS metacluster data from GTRD [45] , TFBS binding profile data from JASPAR [46] , and sequence and conservation data from Ensembl [47] . doi = 10.1371/journal.pone.0240647 id = cord-003498-4ct0ywnw author = Bdeir, Najat title = A system for production of defective interfering particles in the absence of infectious influenza A virus date = 2019-03-01 keywords = DI-244; IAV; MDCK; PB2 summary = doi = 10.1371/journal.pone.0212757 id = cord-289093-si8btsab author = Beard, Philippa M. title = A Loss of Function Analysis of Host Factors Influencing Vaccinia virus Replication by RNA Interference date = 2014-06-05 keywords = RNA; VACV; figure; viral; virus summary = To explore these interactions a functional high throughput small interfering RNA (siRNA) screen targeting 6719 druggable cellular genes was undertaken to identify host factors (HF) influencing the replication and spread of an eGFP-tagged VACV. Multiple components of the AMPK complex were found to act as pro-viral HFs, while several septins, a group of highly conserved GTP binding proteins with a role in sequestering intracellular bacteria, were identified as strong anti-viral VACV HFs. This screen has identified novel and previously unexplored roles for cellular factors in poxvirus replication. The methodology in the previously published VACV screens varied considerably; Mercer et al [32] measured the growth of a thymidine-kinase-deficient VACV (strain Western Reserve) after only 8 h of infection, thereby identifying cellular proteins involved in the initial stages of virus replication but excluding analysis of viral spread. doi = 10.1371/journal.pone.0098431 id = cord-011857-brbqgbpz author = Beasley, Steven A. title = An Angelman syndrome substitution in the HECT E3 ubiquitin ligase C-terminal Lobe of E6AP affects protein stability and activity date = 2020-07-08 keywords = E6AP; HECT summary = doi = 10.1371/journal.pone.0235925 id = cord-000261-ip32y0j5 author = Becker, Pablo D. title = Generation of Human Antigen-Specific Monoclonal IgM Antibodies Using Vaccinated “Human Immune System” Mice date = 2010-10-04 keywords = BCR; cell; human; mouse summary = Following immunization, human CD19 + B cells were sorted based on surface CD27 expression, as a marker of memory phenotype, and the isotype of surface Igs. The sorted B cell populations were immortalized in vitro by retroviral transduction with human B cell lymphoma (BCL)-6 and BCL-XL genes and antigen-specific B cell clones were established and characterized. The obtained results provided the proof-of-concept for the usefulness of this generic approach based on HIS mice combined with immortalization of human B cells for the rapid and inexpensive development of human mAbs against a wide range of antigens. Since HIS mice contained broad naïve B cell repertoires, we analyzed the induction of human antigen-specific B cell responses after immunization with commercially available human vaccines. So far, humanized mouse models based on the transplantation of human HSC only -i.e. without additional human tissues -share these limitations, and immunization strategies result in the limited generation of class-switched antigen-specific B cell responses [14, 31, 32] . doi = 10.1371/journal.pone.0013137 id = cord-000895-z5rdf0mi author = Belalov, Ilya S. title = Causes and Implications of Codon Usage Bias in RNA Viruses date = 2013-02-25 keywords = ENC; RNA summary = doi = 10.1371/journal.pone.0056642 id = cord-303187-ny4qr2a2 author = Belo, Vinícius Silva title = Abundance, survival, recruitment and effectiveness of sterilization of free-roaming dogs: A capture and recapture study in Brazil date = 2017-11-01 keywords = capture; dog; model; population; study summary = Despite the perceived need and usefulness of such parameter estimates and recommendations for the most appropriate approaches applicable under such study designs [30] , survival and recruitment estimates of free-ranging dogs had not been obtained using methods of capture and recapture. In this study, we present estimates of abundance, survival and recruitment rates, and the probabilities of capture of two free-roaming dog populations by means of analytical models for open populations, so far unexplored in previous studies. We estimated critical parameters (survival, recruitment and abundance) that describe the population dynamics of free-roaming dogs based on a capture and recapture study design and on models suitable for open populations. Our study demonstrated the increase in population size in both areas, the predominance and greater recruitment of males, the temporal variability in recruitment and in survival probabilities, the lack of effect of sterilization on population dynamics, the influence of abandon and of density-independent factors and a high demographic turnover. doi = 10.1371/journal.pone.0187233 id = cord-000547-adfigzc1 author = Beniac, Daniel R. title = The Organisation of Ebola Virus Reveals a Capacity for Extensive, Modular Polyploidy date = 2012-01-11 keywords = EBOV; Ebola; RNA; figure summary = METHODOLOGY AND PRINCIPAL FINDINGS: We have investigated the structure of Ebola virus using a combination of cryo-electron microscopy, cryo-electron tomography, sub-tomogram averaging, and single particle image processing. Here we report the three-dimensional structure and architecture of Ebola virus and establish that multiple copies of the RNA genome can be packaged to produce polyploid virus particles, through an extreme degree of length polymorphism. From the same image data set, we combined extracted volumes from tomograms with 2-D single particle processing to determine the structure of the GP spikes ( Figure 5 ) to a resolution of 14 Å as measured by the Fourier Shell Correlation (FSC) 0.5 criterion. Analysis of 2090 distinct intact virions with a nucleocapsid from cryo-electron micrographs shows that the most common class length (53%) of virus particles is 982679 nm ( Figure 1A , Table S1 ). doi = 10.1371/journal.pone.0029608 id = cord-305274-mcsdem7y author = Beniac, Daniel R. title = Conformational Reorganization of the SARS Coronavirus Spike Following Receptor Binding: Implications for Membrane Fusion date = 2007-10-24 keywords = ACE2; SARS; fusion; spike summary = We have shown that ACE2 binding results in structural changes that appear to be the initial step in viral membrane fusion, and precisely localized the receptor-binding and fusion core domains within the entire spike. The SARS-CoV spike provides an ideal model system to study receptor binding and membrane fusion in the native state, employing cryo-electron microscopy and single-particle image analysis. The structures of ACE2 bound to a fragment of the SARS spike containing the receptor-binding domain and the pre-and postfusion configurations of the fusion core heptad repeats of the spike have been solved to atomic resolution [2, 3, [24] [25] [26] . In addition, the atomic resolution structures of two neutralizing antibodies bound to the SARS spike receptor-binding domain have been solved [27, 28] showing that blocking of the receptor binding domain, preventing attachment of virions to cell-surface ACE2, is the likely mechanism of virus neutralization by these antibodies. doi = 10.1371/journal.pone.0001082 id = cord-000638-ss1435el author = Beq, Stephanie title = Altered Thymic Function during Interferon Therapy in HCV-Infected Patients date = 2012-04-16 keywords = HCV; HIV; IL-7 summary = The evolution of T-cell subsets and T-cell homeostasis were estimated by flow cytometry while thymic function was measured through quantification of T-cell receptor excision circles (TREC) and estimation of intrathymic precursor T-cell proliferation during the first four months following the initiation of IFNα therapy. In contrast, Arizcorreta and colleagues showed that IFNa and ribavirin therapy induces a substantial reduction of circulating sjTRECs, in HIV/HCV co-infected patients, accompanied by sustained naïve CD4 + T-cell defect, suggesting thymic dysfunction [10] . While the number of RTEs was similar in HCV-infected patients at study entry and healthy individuals ( These data demonstrate that, as early as one month following treatment initiation, IFNa induces stronger alterations of naïve Tcell subsets, and more specifically in the RTE compartment than in any other T-cell subset, suggesting a specific effect on thymopoiesis. doi = 10.1371/journal.pone.0034326 id = cord-000248-zueoyesj author = Berretta, Regina title = Cancer Biomarker Discovery: The Entropic Hallmark date = 2010-08-18 keywords = BRCA1; Complexity; Entropy; Gleason; Jensen; Normalized; PSA; RNA; Shannon; Statistical; cancer; cell; dna; expression; gene; prostate summary = These authors cite, for example, ''''mitochondrial dysfunction'''' [5, 6] (including, but not limited to ''''glucose avidity'''' [7] and ''''a shift in glucosemetabolism from oxidative phosphorylation to glycolysis'''' [6, 8] , ''''altered glycolysis'''' [9] , ''''altered bioenergetic function of mitochondria'''' [10] ), ''''dysregulation of cell cycle and defective genome-integrity checkpoints'''' [11] , ''''aberrant DNA methylation'''' [12] (''''promoter hypermethylation of hallmark cancer genes'''' [13] and ''''CpG island hypermethylation and global genomic hypomethylation'''' [14] ), ''''shift in cellular metabolism'''' [15, 16, 17] , ''''regional hypoxia'''' [18] , ''''microenviroment acidosis'''' [19] , ''''abnormal microRNA regulation'''' [20, 21] , ''''aneuploidy'''' and ''''chromosome aberrations'''' [22, 23, 24, 25, 26] , ''''disruption of cellular junctions'''' [27] , ''''avoidance of the immune response'''' [28] , ''''pre-existing chronic inflammatory conditions'''' [29, 30] , ''''cancerrelated inflammation'''' [29] , ''''disabled autophagy'''' [28] , ''''impaired cellular senescence'''' [31] , ''''altered NF-kappaB signalling'''' [32] , ''''altered growth patterns, not altered growth per se'''' [33] , ''''disregulated DNA methylation and histone modifications'''' [34] , ''''tissue dedifferentiation'''' [35, 36] , and ''''somatically heritable molecular alterations'''' [37] . doi = 10.1371/journal.pone.0012262 id = cord-330537-xz0wt1sz author = Biermann, Olivia title = Active case-finding policy development, implementation and scale-up in high-burden countries: A mixed-methods survey with National Tuberculosis Programme managers and document review date = 2020-10-28 keywords = ACF; NTP; manager summary = title: Active case-finding policy development, implementation and scale-up in high-burden countries: A mixed-methods survey with National Tuberculosis Programme managers and document review BACKGROUND: The World Health Organization (WHO) stresses the importance of active case-finding (ACF) for early detection of tuberculosis (TB), especially in the 30 high-burden countries that account for almost 90% of cases globally. OBJECTIVE: To describe the attitudes of National TB Programme (NTP) managers related to ACF policy development, implementation and scale-up in the 30 high-burden countries, and to review national TB strategic plans. Moreover, this study focuses on National TB Programme (NTP) managers, key stakeholders in developing and implementing ACF policies [13] . The study comprised a cross-sectional survey with NTP managers from 30 high TB burden countries, which included closed and open-ended questions designed to elicit quantitative and qualitative information, enhancing each other [15] . doi = 10.1371/journal.pone.0240696 id = cord-333955-bnzbppof author = Biesold, Susanne E. title = Type I Interferon Reaction to Viral Infection in Interferon-Competent, Immortalized Cell Lines from the African Fruit Bat Eidolon helvum date = 2011-11-30 keywords = IFN; ONNV; cell; figure summary = Here, we investigated interferon (IFN) response, -induction, -secretion and -signaling in epithelial-like cells of the relevant and abundant African fruit bat species, Eidolon helvum (E. Cells from Pteropus species have been shown to produce high amounts of interferon (IFN)-l after stimulation with the double-strand (ds)RNA analogue poly IC, and after infection with the bat-associated paramyxovirus, Tioman [13] . In accordance with the IFN mRNA induction, the highest equivalent amount of bioactive secreted IFN upon RVFV 13 virus infection and poly IC transfection was measured in EidNi/41.3 cells, followed by MEF and MA104 (Figure 3 ). Increases of infectious virus formation were about 1000-fold within 24 hpi, and specific infectivities, expressed as PFU per genome equivalent (PCR units), were highly comparable between cell cultures ( Figure 4C) . doi = 10.1371/journal.pone.0028131 id = cord-340713-v5sdowb7 author = Bird, Jordan J. title = Country-level pandemic risk and preparedness classification based on COVID-19 data: A machine learning approach date = 2020-10-28 keywords = COVID-19; country; model; risk summary = The three four-class classification problems are then explored and benchmarked through leave-one-country-out cross validation to find the strongest model, producing a Stack of Gradient Boosting and Decision Tree algorithms for risk of transmission, a Stack of Support Vector Machine and Extra Trees for risk of mortality, and a Gradient Boosting algorithm for the risk of inability to test. The classification problem of risk is therefore formulated based on prior knowledge of the pandemic in terms of class only, but the attributes to attempt to classify them are purely country-level information regardless of number of cases, deaths and other coronavirus specific data. Country-level pandemic risk and preparedness classification based on COVID-19 data Fig 10 shows a comparison of other models that were explored. Country-level pandemic risk and preparedness classification based on COVID-19 data Table 1 shows the predicted class values for the best models applied to each of the respective risk classification problems. doi = 10.1371/journal.pone.0241332 id = cord-012891-heqsfzkm author = Blanco Vázquez, Cristina title = Detection of latent forms of Mycobacterium avium subsp. paratuberculosis infection using host biomarker-based ELISAs greatly improves paratuberculosis diagnostic sensitivity date = 2020-09-03 keywords = AUC; ELISA; MMP8; PTB; SPARC summary = doi = 10.1371/journal.pone.0236336 id = cord-013099-j816c3tw author = Blease, Charlotte title = US primary care in 2029: A Delphi survey on the impact of machine learning date = 2020-10-08 keywords = Delphi; round summary = To address this research gap, we designed a Delphi survey to explore leading health informaticians'' predictions about the impact of machine learning on primary care in the US in 2029. Acknowledging that heterogeneous panels have been shown to result in more accurate estimates [33] , and that what counts as an expert can be influenced by goals, values, and the manner in which knowledge is generated, we aimed to recruit diverse participants from across academia, healthcare, non-profit organizations, and industry; and to strive for panelists with a varied complementarity of interests within health informatics. In the first round, the Delphi survey requested demographic information; this was followed by 5 sections, with 7 open-ended questions, on the impact of machine learning on primary care by 2029 (see S1 Appendix; Table 1 We also included a final comment-box for feedback on the survey. doi = 10.1371/journal.pone.0239947 id = cord-003484-ylpa702c author = Blázquez, Elena title = Evaluation of the effectiveness of the SurePure Turbulator ultraviolet-C irradiation equipment on inactivation of different enveloped and non-enveloped viruses inoculated in commercially collected liquid animal plasma date = 2019-02-21 keywords = TCID summary = Specifically, Pseudorabies virus (PRV), Porcine reproductive and respiratory syndrome virus (PRRSV), Porcine epidemic diarrhea virus (PEDV), Bovine viral diarrhea virus (BVDV), Classical swine fever virus (CSFV), Swine influenza virus (SIV) as enveloped viruses and Porcine parvovirus (PPV), Swine vesicular disease virus (SVDV), Porcine circovirus type 2 (PCV-2) and Senecavirus A (SVA) as non-enveloped viruses, were inoculated in bovine or porcine plasma and subjected to different UV-C irradiation doses (0, 750, 1500, 3000, 6000 and 9000 J/L) using an UV-C device developed for opaque liquid working under turbulent flow. The objective of this study was to assess inactivation efficiency of the SurePure Turbulator UV-C irradiation system with selected swine enveloped viruses Pseudorabies virus (PRV), Porcine reproductive and respiratory syndrome virus (PRRSV), Porcine epidemic diarrhea virus (PEDV), Bovine viral diarrhea virus (BVDV), Swine influenza A virus (SIV) and Classical swine fever virus (CSFV) and non-enveloped viruses Porcine parvovirus (PPV), Swine vesicular disease virus (SVDV), Porcine circovirus 2 (PCV-2) and Senecavirus A (SVA) inoculated in liquid bovine or porcine plasma. doi = 10.1371/journal.pone.0212332 id = cord-001065-j4hvyyoi author = Boncristiani, Humberto F. title = In Vitro Infection of Pupae with Israeli Acute Paralysis Virus Suggests Disturbance of Transcriptional Homeostasis in Honey Bees (Apis mellifera) date = 2013-09-05 keywords = IAPV; PBS; bee; honey; virus summary = doi = 10.1371/journal.pone.0073429 id = cord-346347-r4ork18p author = Borrion, Hervé title = Measuring the resilience of criminogenic ecosystems to global disruption: A case-study of COVID-19 in China date = 2020-10-14 keywords = COVID-19; China; crime; resilience summary = There are reasons to believe that crime-related performance measures during a pandemic period, or other disasters, may not match the idealised resilience triangle, but rather resemble the dipper-shaped function depicted in Fig 2. Measuring the resilience of criminogenic ecosystems to global disruption: A case-study of COVID-19 in China RD(n) provides a useful measure to monitor the operating level (%) of offenders. In the case where the crime level in this phase exceeds the pre-Disruptive Event (t DE ) level (μ 7 �μ 1 ), two sub-indicators can be used to measure the ecosystem''s resilience during the recovery phase. Measuring the resilience of criminogenic ecosystems to global disruption: A case-study of COVID-19 in China between τ − and τ + shows it took significantly longer for crime to drop than to return to its expected level. doi = 10.1371/journal.pone.0240077 id = cord-256424-t3dtabi4 author = Bousbia, Sabri title = Repertoire of Intensive Care Unit Pneumonia Microbiota date = 2012-02-28 keywords = Fig; ICU; bal; pneumonia summary = Recently, the bacterial microbiota of patients with cystic fibrosis and ventilator-associated pneumonia (VAP) were studied using 16S rDNA gene amplification followed by clone libraries sequencing [9] [10] [11] . Bacterial microbiota as evaluated by 16S rDNA Molecular assays were positive for at least one bacterium for 129 out of 185 bronchoalveolar lavage (BAL) samples from patients with pneumonia as well as from 13 out of 25 from control individuals (p = 0.07). Fungal microbiota obtained from patients showed the presence of 22 different species belonging to 2 phyla (8 orders, 11 families and 12 genera) among which 6 phylotypes had not been previously identified in BAL fluids from pneumonia. Indeed, our study reveals that some pathogens that till now had been considered typical for ICU pneumonia, such as Pseudomonas aeruginosa and Streptococcus species, or viruses, such CMV and HSV, can be detected as commonly in controls as in patients (Fig. S1 and S2 ). doi = 10.1371/journal.pone.0032486 id = cord-293393-kbndie8e author = Braesch-Andersen, Sten title = ApoD Mediates Binding of HDL to LDL and to Growing T24 Carcinoma date = 2014-12-16 keywords = D544; ELISA; HDL; ldl summary = To investigate the presence of particles containing both apoD and apoB, we performed a dual-specific ELISA using the anti-apoD mAb D554 as a capture antibody and a biotinylated anti-apoB mAb, LDL20, for detection. To determine the importance of having intact lipoprotein particles, we repeated the dual-specific apoD/B ELISA in the presence of detergent, using anti-apoD-D544 as the capture mAb and anti-apoB-LDL20 as the detecting mAb. As seen in Fig. 4A , only small amounts of apoB bound to D544 when detergent was present, indicating that intact lipoprotein particles are needed for the apoD-LDL interaction. In agreement with this latter finding, apoD production was high in confluent, growth-arrested T24 cell cultures (2,5 million cells in 9 ml), but was not detectable in non-confluent proliferating Anti-apoD (D544) was used as the capture antibody and anti-apoB (LDL20-biotin) was used as the detection antibody in a detergent free dualspecific ELISA. doi = 10.1371/journal.pone.0115180 id = cord-001446-mpuovmeb author = Bratcher, Preston E. title = Factors Influencing the Measurement of Plasma/Serum Surfactant Protein D Levels by ELISA date = 2014-11-03 keywords = ELISA summary = Circulating levels of SP-D have been examined for their potential use as a biomarker in various diseases including dermatitis [2, 3] , acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] , periodontitis [14] , interstitial pulmonary fibrosis (IPF) [10, 12, [15] [16] [17] [18] [19] [20] [21] [22] [23] , chronic obstructive pulmonary disease (COPD) [15, [24] [25] [26] [27] [28] [29] [30] [31] [32] [33] [34] [35] [36] , emphysema [37] , cystic fibrosis (CF) [15, 38, 39] , coronary disease [40, 41] , sclerosis [42] [43] [44] [45] [46] , cancer [47, 48] , sarcoidosis [21, 49] , allergies [28, [50] [51] [52] , rheumatoid arthritis [53, 54] , and respiratory infections [18, [55] [56] [57] [58] [59] [60] . Serum levels of surfactant proteins A and D are useful biomarkers for interstitial lung disease in patients with progressive systemic sclerosis doi = 10.1371/journal.pone.0111466 id = cord-297287-0i4nc353 author = Braun, Benjamin title = Simulating phase transitions and control measures for network epidemics caused by infections with presymptomatic, asymptomatic, and symptomatic stages date = 2020-09-10 keywords = agent; social summary = Using agent-based simulations on small world networks, we observe phase transitions for epidemic spread related to: 1) Global social distancing with a fixed probability of adherence. Phase transitions and control measures for network epidemics self-isolate in response to one infected social contact) all the way up to 97% with low levels of any type of social distancing. Because our goal is to understand the behavior of phase transitions regarding total number of infections in our model, we conducted secondary simulations on a refined parameter space based on the results of our regression tree analysis. There is also a clear interaction between the social distance probability and viral shedding parameters and the resulting number of infected agents and the length of the epidemic. Social distancing controls in this model exhibit a phase transition regarding total number of infections, either when imposed globally or when based on individual response to infected contacts. doi = 10.1371/journal.pone.0238412 id = cord-267519-a0bcmjkn author = Bravi, Francesca title = Predictors of severe or lethal COVID-19, including Angiotensin Converting Enzyme inhibitors and Angiotensin II Receptor Blockers, in a sample of infected Italian citizens date = 2020-06-24 keywords = Angiotensin; COVID-19; ace summary = AIMS: This retrospective case-control study was aimed at identifying potential independent predictors of severe/lethal COVID-19, including the treatment with Angiotensin-Converting Enzyme inhibitors (ACEi) and/or Angiotensin II Receptor Blockers (ARBs). Observing that human pathogenic coronaviruses bind their target cells through angiotensin-converting enzyme 2 (ACE2) [5] [6] [7] [8] , and that a few studies reported an increase in ACE2 expression mediated by angiotensin II type-I receptor blockers (ARBs) and ACE inhibitors (more consistently on animals than in humans) [9] [10] [11] [12] [13] [14] [15] [16] , some hypothesized that the increased expression of ACE2 would facilitate infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), thus the hypertension treatment with ACE2-stimulating drugs, as well as ACE2 polymorphisms, might increase the risk of developing severe COVID-19 [17] [18] [19] . doi = 10.1371/journal.pone.0235248 id = cord-000006-104sqoxz author = Bray, Daniel P. title = Composition and Function of Haemolymphatic Tissues in the European Common Shrew date = 2008-10-15 keywords = Aselli; adult; cell; shrew summary = Here, we examined the unique haemolymphatic system of the European common shrew (Sorex araneus) to investigate the capacity of this short-lived mammal, restricted by a fast metabolism and extremely limited fat reserves, to defend against its unusually diverse parasite fauna, both as a young animal and an adult. We examined and compared the structure, composition and function of relevant haemolymphatic tissues including the pancreas of Aselli, in wild-caught common shrews of different ages pre and post maturation, and the extent and type of inflammatory reactions produced in response to naturally occurring parasitic infections. While some degree of lymphatic exhaustion was obvious in adult animals (perhaps as a result of age-related changes, or reduced investment in immunity as a consequence of breeding effort), there was also evidence of some degree of compensation, in the form of storage of plasma cells particularly in the pancreas of Aselli, possibly as a defence against previously encountered parasites. doi = 10.1371/journal.pone.0003413 id = cord-296635-8r3tm966 author = Breed, Andrew C. title = Evidence of Endemic Hendra Virus Infection in Flying-Foxes (Pteropus conspicillatus)—Implications for Disease Risk Management date = 2011-12-14 keywords = Hendra; Pteropus; infection; virus summary = title: Evidence of Endemic Hendra Virus Infection in Flying-Foxes (Pteropus conspicillatus)—Implications for Disease Risk Management This study investigated the seroepidemiology of Hendra virus in a spectacled flying-fox (Pteropus conspicillatus) population in northern Australia, near the location of an equine and associated human Hendra virus infection in late 2004. Hendra virus (HeV) and Nipah virus (NiV) are paramyxoviruses of the genus Henipavirus with pteropid bats (i.e. flying-foxes; Pteropus sp., Family Pteropodidae) being the primary wildlife reservoir [1] . Henipaviruses have the potential to infect a wide range of mammalian species, and Hendra virus has spread from flying-foxes to horses in Australia on at least 20 reported separate occasions (five involving horse-human transmission), most recently in 2011 [5, 6, 7] . [14] on the infection dynamics of HeV in the little red flying-fox, Pteropus scapulatus, in the Northern Territory of Australia suggested that viral transmission may be predominantly horizontal, with pregnancy and lactation suggested as risk factors for infection. doi = 10.1371/journal.pone.0028816 id = cord-296399-vvbjulm9 author = Brinkmann, Constantin title = The glycoprotein of vesicular stomatitis virus promotes release of virus-like particles from tetherin-positive cells date = 2017-12-07 keywords = EBOV; VSV; Vpu; tetherin summary = doi = 10.1371/journal.pone.0189073 id = cord-308261-hxlebas8 author = Broekhuis, Femke title = Using GPS collars to investigate the frequency and behavioural outcomes of intraspecific interactions among carnivores: A case study of male cheetahs in the Maasai Mara, Kenya date = 2019-04-03 keywords = Mara; encounter; individual summary = title: Using GPS collars to investigate the frequency and behavioural outcomes of intraspecific interactions among carnivores: A case study of male cheetahs in the Maasai Mara, Kenya To determine the static interactions between male cheetahs we calculated their space use and the amount of overlap for each dyad to determine the possibility that individuals could encounter each other either directly or indirectly. In general, cheetahs were closer to the encounter location after a possible encounter compared to before for all four time lags, apart from individual M03 in Dyad 3 where the opposite trend was Intraspecific interactions among carnivores: A case study of male cheetahs observed, however none of the results were significant (S1 Table) . Using GPS collar data we documented static and dynamic interactions between male cheetahs in Kenya''s Maasai Mara and investigated the outcomes of these interactions in terms of movement behaviour and mortalities. doi = 10.1371/journal.pone.0213910 id = cord-326568-twv2i3fb author = Bruminhent, Jackrapong title = Clinical characteristics and risk factors for coronavirus disease 2019 (COVID-19) among patients under investigation in Thailand date = 2020-09-15 keywords = COVID-19; SARS; Thailand summary = To manage coronavirus disease 2019 (COVID-19), a national health authority has implemented a case definition of patients under investigation (PUIs) to guide clinicians'' diagnoses. Multivariate analysis identified close contact with an index case (OR, 3.49; 95%CI, 1.49–8.15; P = 0.004), visiting high-risk places (OR, 1.92; 95%CI, 1.03–3.56; P = 0.039), productive cough (OR, 2.03; 95%CI, 1.05–3.92; P = 0.034), and no medical coverage (OR, 3.91; 95%CI, 1.35–11.32; P = 0.012) as independent risk factors for COVID-19 among the PUIs. The majority had favorable outcomes, though one (1.9%) died from severe pneumonia. Apart from close contact with an infected case and visiting high-risk places, we found that having no medical coverage and presenting with productive cough were predictors of being diagnosed with COVID-19 among PUIs. SARS-CoV-2 is an emerging respiratory virus that commonly causes no or mild respiratory tract infection and is occasionally complicated by severe pneumonia [1] . doi = 10.1371/journal.pone.0239250 id = cord-329999-flzqm3wh author = Buchanan, Tom title = Why do people spread false information online? The effects of message and viewer characteristics on self-reported likelihood of sharing social media disinformation date = 2020-10-07 keywords = Facebook; Study; Table; Twitter; share summary = Four studies (total N = 2,634) explored the effect of message attributes (authoritativeness of source, consensus indicators), viewer characteristics (digital literacy, personality, and demographic variables) and their interaction (consistency between message and recipient beliefs) on self-reported likelihood of spreading examples of disinformation. Descriptive statistics for participant characteristics (personality, conservatism, new media literacy and age) and their reactions to the stimuli (likelihood of sharing, belief the stories were likely to be true, and rating of likelihood that they had seen them before) are summarised in Table 2 . This evaluated the extent to which digital media literacy (NMLS), authority of the message source, consensus, belief in veracity of the messages, consistency with participant beliefs (operationalised as the total SECS conservatism scale score), age and personality (Extraversion, Conscientiousness, Agreeableness, Openness to Experience and Neuroticism), predicted self-rated likelihood of sharing the posts. doi = 10.1371/journal.pone.0239666 id = cord-351185-3y3gou6v author = Buckles, Thomas C. title = Rapid exposure of macrophages to drugs resolves four classes of effects on the leading edge sensory pseudopod: Non-perturbing, adaptive, disruptive, and activating date = 2020-05-29 keywords = Fig; PIP; cell; drug; pseudopod summary = However, rapid drug addition to cultured macrophages revealed four distinct classes of effects on the leading edge pseudopod: (i) non-perturbing drug exposures yielded no detectable change in pseudopod morphology (acetylsalicylic acid, diclofenac); (ii) adaptive exposures yielded temporary collapse of the extended pseudopod and its signature PI(3,4,5)P(3) lipid signal followed by slow recovery of extended pseudopod morphology (ibuprofen, acetaminophen); (iii) disruptive exposures yielded long-term pseudopod collapse (Gö6976, wortmannin); and (iv) activating exposures yielded pseudopod expansion (PDGF). In contrast, ibuprofen and acetaminophen are classified as adaptive because rapid addition of either drug to polarized cells yields short-term collapse of the leading edge pseudopod and loss of the PIP 3 signal, followed by slow recovery. In contrast to the four therapeutic adaptive drugs, the two non-clinical control inhibitors wortmannin and Gö6976 are each known to directly inhibit key components of the leading edge positive feedback loop and rapid addition is observed herein to trigger long term collapse of the pseudopod with no detected recovery as previously observed [26, 30, [50] [51] [52] [53] [54] . doi = 10.1371/journal.pone.0233012 id = cord-324405-6uanhe2p author = Burke, Rachel M. title = Enhanced contact investigations for nine early travel-related cases of SARS-CoV-2 in the United States date = 2020-09-02 keywords = COVID-19; SARS; case; travel summary = To interrupt transmission and facilitate early identification of secondary cases (i.e., transmissions of SARS-CoV-2 from the original travel-related case patient to a close contact), public health authorities at the state, county, and local levels, in consultation with subject-matter experts from the U.S. Centers for Disease Control and Prevention (CDC), mobilized rapidly to place the patients under appropriate isolation and identify contacts exposed to these patients. To understand the prevalence of asymptomatic or pre-symptomatic infection, a convenience sample of actively monitored close contacts was selected from whom to request respiratory (nasopharyngeal [NP] and oropharyngeal [OP]) samples outside of diagnostic specimen collection procedures (i.e., while contacts were asymptomatic or, in some cases, symptomatic with � 1 previous negative SARS-CoV-2 result); some sites were able to request at least one set of samples from all close contacts, but most sites targeted sample collection mainly to close contacts determined to have had high-risk exposures, such as household members and some healthcare personnel. doi = 10.1371/journal.pone.0238342 id = cord-001213-gxqufddb author = Butt, Azeem Mehmood title = Genome-Wide Analysis of Codon Usage and Influencing Factors in Chikungunya Viruses date = 2014-03-04 keywords = CHIKV; ECSA; codon summary = Therefore, from the similarity index analysis, we observed that selection pressure from hosts and vectors have contributed to shaping the molecular evolution of CHIKV at the respectively, on the formation of the overall codon usage patterns of CHIKV (Figure 2 ). Although, the nucleotide composition correlation analysis showed that codon usage in CHIKV genomes is mainly caused by compositional constraints or mutational pressure, we were interested to determine the possible influence of other factors, such as natural selection. However, in case of CHIKV genomes, variations in nucleotide base compositions were noted (Table 1 ), indicating that other factors, such as natural selection, could also influence overall synonymous codon usage bias. The RSCU values for all the coding sequences of CHIKV genomes were calculated to determine the characteristics of synonymous codon usage without the confounding influence of amino acid composition and the size of coding sequence of different gene samples, following a previously described method [18] . doi = 10.1371/journal.pone.0090905 id = cord-323133-gdg50omp author = Buzatto, G. P. title = The pathogens profile in children with otitis media with effusion and adenoid hypertrophy date = 2017-02-23 keywords = ear; middle; ome; patient summary = OBJECTIVES: To evaluate the presence of viruses and bacteria in middle ear and adenoids of patients with and without otitis media with effusion (OME). METHODS: Adenoid samples and middle ear washes (MEW) were obtained from children with OME associated with adenoid hypertrophy undergoing adenoidectomy and tympanostomy, and compared to those obtained from patients undergoing cochlear implant surgery, as a control group. Therefore, the present study was carried out to compare the detection of common respiratory viruses and bacteria in adenoids and middle ear fluid in children with OME and in controls. In our study, we used a sensitive method to detect nucleic acid of a comprehensive panel of respiratory viruses and bacteria to compare the microbial colonization of adenoid and its correspondence in the middle ear in both OME children and controls. Concluding, in children with OME and adenoid hypertrophy we observed higher detection rates of potentially pathogenic bacteria, but not respiratory viruses, by real-time PCR in middle ear samples, as compared to control patients without adenoid hypertrophy. doi = 10.1371/journal.pone.0171049 id = cord-000981-6vloa2w3 author = Bálint, Zoltán title = Double-Stranded RNA Attenuates the Barrier Function of Human Pulmonary Artery Endothelial Cells date = 2013-06-03 keywords = Poly; RNA; SERCA; figure summary = doi = 10.1371/journal.pone.0063776 id = cord-353596-8iqjugcx author = Bédubourg, Gabriel title = Evaluation and comparison of statistical methods for early temporal detection of outbreaks: A simulation-based study date = 2017-07-17 keywords = fpr; outbreak; pod summary = Based on a large dataset of simulated weekly surveillance time series, we performed a systematic assessment of 21 statistical algorithms, 19 implemented in the R package surveillance and two other methods. We estimated false positive rate (FPR), probability of detection (POD), probability of detection during the first week, sensitivity, specificity, negative and positive predictive values and F(1)-measure for each detection method. Then, to identify the factors associated with these performance measures, we ran multivariate Poisson regression models adjusted for the characteristics of the simulated time series (trend, seasonality, dispersion, outbreak sizes, etc.). The objective of this paper is to evaluate the performance of 21 statistical methods applied to large simulated datasets for outbreak detection in weekly health surveillance. Table 2 presents averaged FPR, specificity, POD, POD1week, sensitivity, negative predictive value, positive predictive value and F 1 -measure for all 42 scenarios and all past and current outbreak amplitude and duration and for α = 0.01. doi = 10.1371/journal.pone.0181227 id = cord-305547-e66o5j85 author = Bénet, Thomas title = Etiology and Factors Associated with Pneumonia in Children under 5 Years of Age in Mali: A Prospective Case-Control Study date = 2015-12-22 keywords = Mali; pneumonia summary = title: Etiology and Factors Associated with Pneumonia in Children under 5 Years of Age in Mali: A Prospective Case-Control Study pneumoniae (adjusted odds ratio [aOR] = 3.4, 95% confidence interval [95% CI]: 1.6–7.0), human metapneumovirus (aOR = 17.2, 95% CI: 2.0–151.4), respiratory syncytial virus [RSV] (aOR = 7.4, 95% CI: 2.3–23.3), and influenza A virus (aOR = 10.7, 95% CI: 1.0–112.2) were associated with pneumonia, independently of patient age, gender, period, and other pathogens. The primary objective of this prospective case-control study was to assess the etiology and factors associated with community-acquired pneumonia in hospitalized children in Mali. pneumoniae, human metapneumovirus, RSV, and influenza A were the main microbial agents associated with pneumonia among children in Mali, independently of patient age, gender, period, and other pathogens. recently observed, in a pneumonia cases-control study implemented in hospitals of Utah, that detection respiratory syncytial virus, human metapneumovirus and influenza from nasopharyngeal or oropharyngeal sample of patients with pneumonia probably indicates an etiologic role [24] . doi = 10.1371/journal.pone.0145447 id = cord-290539-8ak2tths author = Cagno, Valeria title = Novel broad spectrum virucidal molecules against enveloped viruses date = 2018-12-07 keywords = Fig; HSV-2; cell; compound; virus summary = To further elucidate the mechanism of action we performed a virucidal assay in which 9d was incubated with the virus at 10 μM 5μM or 1μM concentration for different times (Fig 6A) or for 1h with serial dilutions of compound ( Fig 6B) ; subsequently, the mixture was titrated on cells and the viral titer was evaluated at dilutions at which the compound concentration was known not to be active in plaquing efficiency assays. The irreversibility of the mechanism was also tested with an assay in which the compound was incubated with the virus for 1h and subsequently the mixture has been diluted in drug free medium for additional 1, 2, 3 or 4 hours before the addition on cells (S2 Fig) . doi = 10.1371/journal.pone.0208333 id = cord-003548-zuwt7gk5 author = Cai, Haiming title = Modulating the 3’ end-DNA and the fermentation process for enhanced production and biological activity of porcine interferon-gamma date = 2019-03-26 keywords = -his; Pichia; pifn summary = In this study, we optimized the pIFN-γ gene recombination sequence and mutated the 3'' end of the pIFN-γ gene, resulting in a higher expression level and stronger biological activity, as well as a significant upregulation in the expression of the interferon-stimulated genes Mx1 and OAS1 in IPEC-J2 jejunal epithelial cells. These data demonstrated, for the first time, that the expression level of pIFN-γ in Pichia pastoris was improved significantly by gene optimization with 3'' end mutation and a fermentation process that maintained good biological activity, which is beneficial to the application of pIFN-γ in animal husbandry. The expression of pIFN-γ protein was maximal when the concentration of DO in the substrate was 30%, especially for the recombinant Pichia pastoris with the optimized pIFN-γ gene and the 3'' signaling peptide mutation, which had significantly higher expression than that of the other treatment groups (p<0.05). doi = 10.1371/journal.pone.0214319 id = cord-048339-nzh87aux author = Caley, Peter title = The Waiting Time for Inter-Country Spread of Pandemic Influenza date = 2007-01-03 keywords = delay; epidemic; figure summary = On the other hand, the model predicts that border screening for symptomatic infection, wearing a protective mask during travel, promoting early presentation of cases arising among arriving passengers and moderate reduction in travel volumes increase the delay only by a matter of days or weeks. In this paper we demonstrate how the delay to importation of an epidemic of pandemic strain influenza may be quantified in terms of the growing infection incidence in the source region, traveler volumes, border screening measures, travel duration, inflight transmission and the delay until an infected arrival initiates a chain of transmission that gathers momentum. For example, if R = 1.5, and we reduce the number of intending travelers from 400 to 10 per day, implement 100% flight-based quarantining, implement compulsory mask wearing during travel and presentation at 6 hours following symptom onset then there is a substantial probability (0.74) that the pandemic strain will never be imported (assuming the epidemic is confined to the source country). doi = 10.1371/journal.pone.0000143 id = cord-305071-4ck8nd24 author = Calvo, Cristina title = Eight Year Prospective Study of Adenoviruses Infections in Hospitalized Children. Comparison with Other Respiratory Viruses date = 2015-07-06 keywords = RSV summary = Human adenovirus (HAdV), a double-stranded DNA virus, causes a wide range of clinical syndromes and is a well-recognized agent of upper and lower respiratory infections in children [1, 2] . Although the literature on adenoviral infections in children is increasing, there are few prospective, long term studies, designed specifically to evaluate the role of HAdV in acute respiratory infections requiring hospitalization. Patients with influenza have fever more frequently (p = 0.028) and have a lower leukocytes count in blood (p<0.001), than children infected by HAdV. HAdV frequently (11% of cases) caused lengthy hospitalizations (more than 7 days) 21% of the single infections were diagnosed with pneumonia. Jin et al [13] , in China, describe similar findings, that children with RSV are younger than patients with HAdV, and have lower respiratory tract infections such as bronchiolitis and bronchitis more frequently. doi = 10.1371/journal.pone.0132162 id = cord-292237-45hi4iz2 author = Calvo-Pinilla, Eva title = Establishment of a Bluetongue Virus Infection Model in Mice that Are Deficient in the Alpha/Beta Interferon Receptor date = 2009-04-09 keywords = BTV; BTV-4; IFNAR summary = Furthermore, IFNAR((−/−)) adult mice immunized with a BTV-4 inactivated vaccine showed the induction of neutralizing antibodies against BTV-4 and complete protection against challenge with a lethal dose of this virus. All these data, and the presence of an otherwise intact immune system in these mice [20, 22] suggest that IFNAR (2/2) mice could be a good animal model to study BTV infections and to evaluate vaccine strategies against this virus. By contrast, IFNAR (2/2) mice were susceptible to BTV-4 infection (Fig. 1A) , showing disease symptoms characterized by ocular discharges and apathy starting at 48 h.p.i. Disease progression led to animal death within 60 h.p.i. The LD 50 value was obtained by i.v. inoculation with 10-fold dilutions of BTV-4, resulting in a LD 50 value of 10 2.6 PFU (Fig. 1B) . Infectious viral titers were analyzed in the blood of immunized and nonimmunized IFNAR (2/2) mice by plaque assay after intravenous infection with BTV-4 (Fig. 5C ). doi = 10.1371/journal.pone.0005171 id = cord-000352-qzkpik3z author = Carvalho, Gabrielle title = Participation of the Cell Polarity Protein PALS1 to T-Cell Receptor-Mediated NF-κB Activation date = 2011-03-30 keywords = PALS1; TCR summary = doi = 10.1371/journal.pone.0018159 id = cord-340703-vtuy806l author = Cascio, Antonio title = Low bone mineral density in HIV-positive young Italians and migrants date = 2020-09-03 keywords = CD4; HIV; bmd; italian summary = We aimed to evaluate the bone mineral density (BMD) in naïve antiretroviral (ARV) treated HIV positive patients comparing native Italian group (ItG) to a Migrants group (MiG) upon arrival in Italy. Lumbar site low BMD is an initial condition of bone loss in HIV young patients, especially in female migrants. Our study aims to emphasize the burden of bone health in naïve ARV HIV positive patients and compare the bone density of the native Italian population group (ItG) with that of HIV Migrants (MiG) upon arrival in Italy. Finally, in Table 3 , we report the logistic regression analysis between Low BMD variable (dichotomous) and the independent variables: Gender (dichotomous), BMI (continuous), Hydroxy-Vitamin D (continuous), CD4 (continuous), and Previous Fractures (dichotomous) for the total sample, ItG, and MiG. Our previous reports [13, 14] on the prevalence of Low-BMD in HIV mono-infected patients who underwent ARV therapy showed higher percentage rates of osteopenia (44.9%) and osteoporosis (20.9%) than an agerelated healthy Italian population (18%) [16] . doi = 10.1371/journal.pone.0237984 id = cord-048358-z5klydpi author = Catic, André title = Screen for ISG15-crossreactive Deubiquitinases date = 2007-07-25 keywords = ISG15; dub; figure; isg15vs; usp14 summary = doi = 10.1371/journal.pone.0000679 id = cord-281364-syg0wo77 author = Caì, Yíngyún title = CD26/DPP4 Cell-Surface Expression in Bat Cells Correlates with Bat Cell Susceptibility to Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Infection and Evolution of Persistent Infection date = 2014-11-19 keywords = CD26; DPP4; MERS; cell summary = title: CD26/DPP4 Cell-Surface Expression in Bat Cells Correlates with Bat Cell Susceptibility to Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Infection and Evolution of Persistent Infection We found that the susceptibility or resistance of these bat cell lines directly correlates with the presence or absence of cell surface-expressed CD26/DPP4, the functional human receptor for MERS-CoV. Finally, we demonstrate that persistent MERS-CoV infections can be established in permissive bat cell lines after sequential virus passage, leading to downregulation of natural CD26/DPP4 cellsurface expression. None of the four MERS-CoV-resistant cell lines tested in this study (PESU-B5L, R05T, R06E, and Tb1Lu) were recognized by anti-human CD26/DPP4 antibody in this assay, whereas all susceptible bat cells (EidNi/41.3, EpoNi/22.1, HypLu/45.1, HypNi/1.1, RoNi/7.1, and RoNi/7.2) tested positive for CD26/DPP4 expression (Figure 2 ). Our study confirms the role of CD26/DPP4 as receptor for two divergent MERS-CoV isolates and correlates its presence or absence on the surface of bat cells directly with bat cell susceptibility or resistance to productive MERS-CoV infection (Figures 2 and 3 ). doi = 10.1371/journal.pone.0112060 id = cord-339869-euikj8fv author = Cebey-López, Miriam title = Does Viral Co-Infection Influence the Severity of Acute Respiratory Infection in Children? date = 2016-04-20 keywords = respiratory summary = However, bacterial superinfection was associated with increased severity (OR: 4.356; P-value = 0.005), PICU admission (OR: 3.342; P-value = 0.006), higher clinical score (1.988; P-value = 0.002) respiratory support requirement (OR: 7.484; P-value < 0.001) and longer hospital length of stay (OR: 1.468; P-value < 0.001). However, bacterial superinfection was associated with increased severity (OR: 4.356; P-value = 0.005), PICU admission (OR: 3.342; P-value = 0.006), higher clinical score (1.988; P-value = 0.002) respiratory Introduction Molecular techniques including polymerase chain reaction (PCR) have increased the sensitivity of detection for common and emerging respiratory viruses, and often reveal the presence of more than one pathogen in respiratory patients. Our study aims to analyze the relationship between viral or bacterial co-infection detected by molecular methods, and the clinical phenotype of children admitted to hospital with lower tract acute respiratory infections (LT-ARI). PICU admission, disease severity according to different scales, need for respiratory support, and length of hospital stay followed a similar pattern in viral mono-versus co-infected children. doi = 10.1371/journal.pone.0152481 id = cord-306135-pt4jsr6d author = Chan, Kamfai title = A Rapid and Low-Cost PCR Thermal Cycler for Infectious Disease Diagnostics date = 2016-02-12 keywords = PCR; TTC summary = Many molecular diagnostic assays are developed based on using thermal cyclers to carry out polymerase chain reaction (PCR) and reverse-transcription PCR for DNA and RNA amplification and detection, respectively. This thermos thermal cycler (TTC) uses a very simple design that performs PCR amplification based on the "archaic" method of hand-transferring reaction tubes through a series of water baths, minimizing the temperature ramping time needed for PCR tubes to reach thermal equilibrium (Fig 1) . The TTC RT-PCR was performed using protocols similar to the HIV test, with PCR tubes transferred between three thermoses (reverse transcription, denaturation, and annealing/extension) and an optional room-temperature water bath. The gel photo in Fig 3 shows that the TTC can produce multiplexed amplicons with the correct sizes and that the yield is similar to a three-step reaction performed in the commercial cycler with same number of PCR cycles. doi = 10.1371/journal.pone.0149150 id = cord-310438-744r7gc3 author = Chan, Ta-Chien title = The Impact of Matching Vaccine Strains and Post-SARS Public Health Efforts on Reducing Influenza-Associated Mortality among the Elderly date = 2010-06-25 keywords = H3N2; P&I; SARS; Taiwan summary = This study evaluated the effect of matching/mismatching vaccine strains, type/subtype pattern changes in Taiwan''s influenza viruses, and the impact of post-SARS (severe acute respiratory syndrome) public health efforts on excess influenza-associated mortalities among the elderly. The aims of this study were: (1) to evaluate the effectiveness of matching or mismatching influenza vaccine strains on influenzaassociated mortality, (2) to assess whether public health improvements during the post-SARS period might have decreased elderly mortality, and (3) to investigate molecular variation among vaccine-mismatched influenza viruses that may be associated with increased excess influenza-associated mortality. Explanatory variables for the above three outcome measures include monthly meteorological parameters (monthly means of temperature and humidity), annual periodic cycle (i.e., sine/cosine function of seasonal periodicity), monthly virus isolation rates for different subtypes/types of influenza viruses [A (H3N2) or A (H1N1) or B], matching status of different vaccine strains for each subtype/type in each of the studied years, post-SARS effect, and linear temporal monthly trends. doi = 10.1371/journal.pone.0011317 id = cord-000726-tonaaft2 author = Chang, Binggong title = Influence of Mabs on PrP(Sc) Formation Using In Vitro and Cell-Free Systems date = 2012-07-27 keywords = Mabs; prp summary = Two systems were used to analyze the effect of different antibodies on PrP(Sc) formation: (i) neuroblastoma cells persistently infected with the 22L mouse-adapted scrapie stain, and (ii) protein misfolding cyclic amplification (PMCA), which uses PrP(Sc) as a template or seed, and a series of incubations and sonications, to convert PrP(C) to PrP(Sc). Based on the numerous and varied Mabs analyzed, the inhibitory effect does not appear to be epitope specific, related to PrP(C) conformation, or to cell membrane localization, but is influenced by the targeted PrP region (amino vs carboxy). We compared the effect of individual PrP-specific monoclonal antibodies (Mabs) on the PrP C -PrP Sc conversion process using both an N2a/22L cell culture model and the test-tube PMCA system. To more completely explore the possible therapeutic effect of anti-PrP antibodies, and to establish another system to analyze the influence of Abs on the conversion process, we screened Mabs produced in our laboratory for their capacity to inhibit PrP Sc formation. doi = 10.1371/journal.pone.0041626 id = cord-342639-vf9n2vf9 author = Chang, Chung-ke title = Transient Oligomerization of the SARS-CoV N Protein – Implication for Virus Ribonucleoprotein Packaging date = 2013-05-23 keywords = CTD; SARS; protein summary = For disulfide trapping experiments, we chose mutation sites that would form disulfide linkages based on the crystal packing structures of the SARS-CoV N protein CTD ( Figure 1 ) [9] . Within the crystal asymmetric unit, the SARS-CoV N protein CTD packs as an octamer which stacks to form a helical arrangement with a continuous positively charged surface that could potentially allow the RNA to bind to it through electrostatic interactions ( Fig. 1 ) [9] . By disulfide trapping technique we measured the amount of transient oligomers of N protein mutants with strategically located cysteine residues and showed that SARS-CoV N protein is capable of transient oligomerization in solution through the CTD in the absence of nucleic acids. Structure of the SARS coronavirus nucleocapsid protein RNA-binding dimerization domain suggests a mechanism for helical packaging of viral RNA doi = 10.1371/journal.pone.0065045 id = cord-000765-r7y1cqou author = Chang, Yu-Ming title = Functional Studies of ssDNA Binding Ability of MarR Family Protein TcaR from Staphylococcus epidermidis date = 2012-09-21 keywords = GC33; TcaR; dna; figure; ssdna summary = title: Functional Studies of ssDNA Binding Ability of MarR Family Protein TcaR from Staphylococcus epidermidis However, the detailed mechanism of multiple antibiotic resistance regulator (MarR) family proteins such as TcaR is unclear and only restricted on the binding ability of double-strand DNA (dsDNA). Here we show by electrophoretic mobility shift assay (EMSA), electron microscopy (EM), circular dichroism (CD), and Biacore analysis that TcaR can interact strongly with single-stranded DNA (ssDNA), thereby identifying a new role in MarR family proteins. IcaR DNA1 probe duplex of 1 mM was pre-incubated with 2 mM TcaR (dimer) at room temperature for 15 min before mixing with increasing concentration of GC33 ssDNA, followed by the same procedure as described in the legend to Figure 1B . In the EMSA analysis, 1 mM IcaR DNA1 probe duplex was pre-incubated with 1 mM GC33 ssDNA fragment for 15 min at room temperature before mixing with TcaR protein of increasing concentration. doi = 10.1371/journal.pone.0045665 id = cord-320938-f526k9q1 author = Chen, Hongjun title = Partial and Full PCR-Based Reverse Genetics Strategy for Influenza Viruses date = 2012-09-28 keywords = Fig; PCR; PR8 summary = In order to determine whether a Flu PCR amplicon could be transfected into cells and be amplified by the influenza polymerase complex, a PCR product was produced encoding the GFP reporter gene in negative orientation flanked by the influenza segment 7 untranslated regions (UTRs) and further flanked by the human pol1 promoter and the mouse t1 termination signal, pol1EGFPt1 (Fig. 1A, Fig. S1A , Table S1 ). doi:10.1371/journal.pone.0046378.g001 Efficient influenza virus rescue using Flu PCR amplicons in either ''''1+7'''' or ''''2+6'''' modes The pol1HA pdm t1 or pol1HA D072 t1 HA PCR amplicons (Table 1) were co-transfected into co-cultured 293T/MDCK cells in a ''''1+7'''' mode along with 7 RG plasmids encoding the corresponding additional gene segments from the influenza A/Puerto Rico/ 8/1934 (H1N1) strain (PR8). doi = 10.1371/journal.pone.0046378 id = cord-258243-2utl2mfl author = Chen, Jeng-Wen title = Factors associated with changing indications for adenotonsillectomy: A population-based longitudinal study date = 2018-05-29 keywords = UAO; indication; surgical summary = We investigated the distribution of the three major categories of surgical indication according to sex, age group (<5 years, 5-11 years, 11-17 years, 18-40 years, and >40 years), hospital level (medical centers, regional hospitals, and local hospitals), and insured residence areas according to the NHI divisions (Taipei, Northern, Central, Southern, Kaoping, and Eastern). In the adult subgroup (Figs 2B and 3B) , the incidence and proportion of AT performed for RICI decreased from 46 (78%) in 1997 to 32 Table 3 indicates the number and percentage of the three categories of surgical indications according to sex, age groups, hospital level, and insured residence areas in the total study population. The trend in the AT rate and the proportion of surgical indications by the calendar year according to sex, age groups, hospital level, and insured residence areas in the total study population are shown in the supplemental data (S1 File). doi = 10.1371/journal.pone.0193317 id = cord-283604-fqc9jp0l author = Chen, Meng title = Adenoviruses Associated with Acute Respiratory Diseases Reported in Beijing from 2011 to 2013 date = 2015-03-27 keywords = Beijing; China; respiratory summary = To identify the types of human adenoviruses (HAdVs) causing respiratory illness in Beijing, a sentinel surveillance project on the viral aetiology of acute respiratory infection was initiated in 2011. The comparison results of the penton base, hexon, and fiber gene sequences of the Beijing HAdV-3, HAdV-4, HAdV-7, and HAdV-55 strains in this study and those from the GenBank database indicated significant spatial and temporal conservation and stability of sequences within the genome; however, the phylogenetic relationship indicated that both strain BJ04 and strain BJ09 isolated in 2012 and 2013, respectively, may have recombined between HAdV-1 genome and HAdV-2 genome within species HAdV-C, indicating intraspecies recombination. The comparison results of the penton base, hexon, and fiber gene sequences between the Beijing HAdV-3, HAdV-4, HAdV-7, and HAdV-55 strains in this study and the strains from the GenBank database indicated significant conservation and stability of the sequences within the genome across time and space. doi = 10.1371/journal.pone.0121375 id = cord-001078-5m29nugu author = Chen, Xiaorong title = Clinical Features and Factors Associated with Outcomes of Patients Infected with a Novel Influenza A (H7N9) Virus: A Preliminary Study date = 2013-09-17 keywords = H7N9; TCM; patient summary = title: Clinical Features and Factors Associated with Outcomes of Patients Infected with a Novel Influenza A (H7N9) Virus: A Preliminary Study OBJECTIVE: The present study aimed to analyze clinical features and factors associated with treatment outcomes of H7N9 influenza A virus infection. Factors analyzed for possible correlation with clinical features and treatment outcomes in patients included 1) baseline characteristics of patients, such as age, sex, occupation, underlying conditions, exposure to poultry and/or wild birds in the past seven days, date of symptom onset and hospital admission, date of specimen collection, and date of positive diagnosis; 2) results from laboratory tests and imaging examinations; 3) treatment regimen including basic supporting therapy, antibiotic therapy, antiviral therapy, traditional Chinese medicine (TCM) therapy, and other therapies if applicable; and 4) current condition of patients including the length of stay in the hospital. doi = 10.1371/journal.pone.0073362 id = cord-001275-a9o2dvke author = Chen, Xue title = A Vaccine of L2 Epitope Repeats Fused with a Modified IgG1 Fc Induced Cross-Neutralizing Antibodies and Protective Immunity against Divergent Human Papillomavirus Types date = 2014-05-06 keywords = E3R4; HPV summary = title: A Vaccine of L2 Epitope Repeats Fused with a Modified IgG1 Fc Induced Cross-Neutralizing Antibodies and Protective Immunity against Divergent Human Papillomavirus Types Current human papillomavirus (HPV) major capsid protein L1 virus-like particles (VLPs)-based vaccines in clinic induce strong HPV type-specific neutralizing antibody responses. To develop pan-HPV vaccines, here, we show that the fusion protein E3R4 consisting of three repeats of HPV16 L2 aa 17–36 epitope (E3) and a modified human IgG1 Fc scaffold (R4) induces cross-neutralizing antibodies and protective immunity against divergent HPV types. In this study, we showed for the first time that fusing HPV16 L2 aa 17-36 epitope repeats to a recombinant ligand for FccRs (designated L2R4, see Figure 1A -B) could significantly increase the immunogenicity of the L2 peptide and induce cross-neutralizing antibodies and protective immunity against a range of phylogenetically distant HPV types. doi = 10.1371/journal.pone.0095448 id = cord-302355-3se1wp8o author = Chen, Yi-Shiuan title = The conserved stem-loop II structure at the 3'' untranslated region of Japanese encephalitis virus genome is required for the formation of subgenomic flaviviral RNA date = 2018-07-26 keywords = Fig; JEV; RNA; XRN1 summary = Although XRN1 digestion of a 3''-terminal 800-nt RNA could stall at a position to generate the sfRNA in vitro, we found that knocking out XRN1 had no effect on the accumulation of sfRNA in Japanese encephalitis virus (JEV) infected cells. Furthermore, the minus-strand templates covering the putative promoter region used for an in vitro RdRp assay gave rise to synthetic products, suggesting that the JEV sfRNA could be initially transcribed from the antigenome and may be further trimmed by XRN1 or other unidentified exoribonucleases. Although efficient RNA replication is required for the detection of any flaviviral RNAs despite which mechanism used for the sfRNA formation, our results were clearly different from the observations from WNV that BHK-21 cells transfected with replicon constructs containing various deletions had no effect on the accumulation of sfRNA when compared to the WT [8] . doi = 10.1371/journal.pone.0201250 id = cord-282194-0sjmf1yn author = Cherak, Stephana J. title = Impact of social media interventions and tools among informal caregivers of critically ill patients after patient admission to the intensive care unit: A scoping review date = 2020-09-11 keywords = caregiver; medium; social; study summary = title: Impact of social media interventions and tools among informal caregivers of critically ill patients after patient admission to the intensive care unit: A scoping review The purpose of this scoping review was to summarize existing research on the impact of social media interventions and tools among informal caregivers of critically ill patients after patient admission to the intensive care unit (ICU). For the purposes of this review, we defined: (1) a caregiver as any informal (i.e., non-clinical) person who regularly provides support to the patient and is in some way directly implicated in the patient''s care or directly affected by the patient''s health problem (e.g., family, friend); (2) social media as any form of electronic communication that allow users to share information and other content and create online communities; and (3) critically ill patients as any persons who are currently admitted to an intensive care unit (ICU) or had previously been admitted to an ICU. doi = 10.1371/journal.pone.0238803 id = cord-310790-3ikgmiof author = Cherrak, Sabri Ahmed title = Potential bioactive glycosylated flavonoids as SARS-CoV-2 main protease inhibitors: A molecular docking and simulation studies date = 2020-10-15 keywords = Fig; Mpro; SARS summary = title: Potential bioactive glycosylated flavonoids as SARS-CoV-2 main protease inhibitors: A molecular docking and simulation studies Docking studies showed that glycosylated flavonoids are good inhibitors for the SARS-CoV-2 protease and could be further investigated by in vitro and in vivo experiments for further validation. The three compounds with highest affinity (Fig 2) for the active site are quercetin 3-rhamonoside, myricetin 3-rutinoside and rutin with binding energies of -9.7, -9,3 and -9.2 kcal.mol -1 respectively. Thirty eight flavonoids have been tested in this study by molecular docking against the active site of the SARS-CoV-2Mpro. Glycosylated flavonoids as SARS-CoV-2 Inhibitors: A molecular docking and simulation studies Elucidating biophysical basis of binding of inhibitors to SARS-CoV-2 main protease by using molecular dynamics simulations and free energy calculations Identification of potential natural inhibitors of SARS-CoV2 main protease by molecular docking and simulation studies doi = 10.1371/journal.pone.0240653 id = cord-260653-5qwtvm9x author = Chikhlikar, Priya title = DNA Encoding an HIV-1 Gag/Human Lysosome-Associated Membrane Protein-1 Chimera Elicits a Broad Cellular and Humoral Immune Response in Rhesus Macaques date = 2006-12-27 keywords = CD8; Gag; USA; dna summary = Thomas; Marques, Ernesto T.A. title: DNA Encoding an HIV-1 Gag/Human Lysosome-Associated Membrane Protein-1 Chimera Elicits a Broad Cellular and Humoral Immune Response in Rhesus Macaques Previous studies of HIV-1 p55Gag immunization of mice have demonstrated the usefulness of targeting antigens to the cellular compartment containing the major histocompatibility complex type II (MHC II) complex molecules by use of a DNA antigen formulation encoding Gag as a chimera with the mouse lysosome-associated membrane protein (mLAMP/gag). In the present study, we have analyzed the magnitude and breadth of Gag-specific T-lymphocyte and antibody responses elicited in Rhesus macaques after immunization with DNA encoding a human LAMP/gag (hLAMP/gag) chimera. This study demonstrates that Rhesus macaques immunized with a DNA plasmid vaccine-encoding gag as an hLAMP/gag chimera develops strong antigen-specific humoral responses as well as CD4 + and CD8 + T-cell responses. doi = 10.1371/journal.pone.0000135 id = cord-048353-hqc7u9w3 author = Chis Ster, Irina title = Transmission Parameters of the 2001 Foot and Mouth Epidemic in Great Britain date = 2007-06-06 keywords = February; farm; model summary = doi = 10.1371/journal.pone.0000502 id = cord-305811-987dhnf7 author = Cho, Che-Pei title = Regulation of Programmed Ribosomal Frameshifting by Co-Translational Refolding RNA Hairpins date = 2013-04-29 keywords = Fig; PRF; RNA summary = Because both 59CC-WT and 13363-13520 constructs share 27 identical nucleotides upstream of their slippery sites, the attenuation activity difference is not likely to be caused by an E-site flanking sequences effect [12, 13] but rather by the disruption of the two potential AU base pairs. We noticed a potential to form four extra base pairs between 59and 39-flanking sequences (GACG and CGUU, respectively) of the 6BPGC hairpin stem (and other deletion mutants) due to the existence of a 59 SalI cloning site (Fig. S1A ). The results (Fig. S1C ) indicate that the two potential base pairs involving E-site sequences are not the main cause of observed attenuation activity in 293T cell cultures. Furthermore, mutating two nucleotides (27 nucleotides upstream of the E site) to disrupt Watson-Crick base pairs in the lower hairpin stem dramatically impairs attenuation activity (Fig. 2) , indicating that attenuation is not caused by primary sequencemediated flanking-sequences effects [12, 13] . doi = 10.1371/journal.pone.0062283 id = cord-001280-skavefji author = Choi, Sang-Ho title = Usefulness of Cellular Analysis of Bronchoalveolar Lavage Fluid for Predicting the Etiology of Pneumonia in Critically Ill Patients date = 2014-05-13 keywords = BAL; WBC; pneumonia summary = This study investigated the ability of cellular analysis of BAL fluid to differentially diagnose bacterial pneumonia from viral pneumonia in adult patients who are admitted to intensive care unit. Exclusion criteria were as follows: (1) patients in whom the pathogen was not identified, (2) patients in whom BAL fluid analysis was impossible (due to severe neutropenia or clotting of specimen) or not performed, (3) patients with a mixed infection (identification of bacteria and virus), (4) patients who were treated with antimicrobial agents for more than 24 hours before bronchoscopic BAL, (5) patients with invasive pulmonary aspergillosis, (6) patients with mycobacterial infection, and (7) patients with Pneumocystis jirovecii pneumonia. Several authors of the current study previously investigated the diagnostic utility of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) in BAL fluid of various patient populations with bilateral lung infiltrates. doi = 10.1371/journal.pone.0097346 id = cord-003244-abs3tc3r author = Chong, Ka Chun title = Monitoring the age-specificity of measles transmissions during 2009-2016 in Southern China date = 2018-10-08 keywords = China; age summary = doi = 10.1371/journal.pone.0205339 id = cord-274268-0ucqp3uz author = Chorus, Caspar title = Diabolical dilemmas of COVID-19: An empirical study into Dutch society’s trade-offs between health impacts and other effects of the lockdown date = 2020-09-16 keywords = class; covid-19; dutch; policy summary = doi = 10.1371/journal.pone.0238683 id = cord-003062-qm8kalyt author = Chowdhury, Fazle Rabbi title = The association between temperature, rainfall and humidity with common climate-sensitive infectious diseases in Bangladesh date = 2018-06-21 keywords = Bangladesh; Climate; disease; study summary = This observational study examined the association of temperature, humidity and rainfall with six common climate-sensitive infectious diseases in adults (malaria, diarrheal disease, enteric fever, encephalitis, pneumonia and bacterial meningitis) in northeastern Bangladesh. Unfortunately, very few studies on the relationship between various environmental variables and trends of infectious disease incidence have been performed so far in Bangladesh, although there are reports of some infections increasing sporadically in different regions of the country [17] [18] [19] . This study examined six infectious diseases based on clinical syndromes and laboratory support (malaria, enteric fever, encephalitis, diarrheal disease, pneumonia and meningitis) to offer a broader scope on the trend of these infectious diseases and their possible relation to climate change in Bangladesh. W.H.O reported dengue, viral encephalitis, diarrheal disease, enteric fever, pneumonia and meningitis as most sensitive to climate factors, and predicted a huge rise of cases in tropical countries [25] . doi = 10.1371/journal.pone.0199579 id = cord-306958-8bx8kxxh author = Christensen, Sarah R. title = Political and personal reactions to COVID-19 during initial weeks of social distancing in the United States date = 2020-09-24 keywords = COVID-19; U.S.; pandemic summary = This study examines individual attitudes, behaviors, anxieties, mental health impacts, and knowledge early in the pandemic response, as well as those outcomes by sociodemographic characteristics and political ideology. Four items asked respondents to indicate agreement on a 7-point scale that "events related to COVID-19 had interrupted" their social life, home life, work or vocational life, and/or hurt their mental health. Chi-square, t, and F tests were used to examine the influence of demographic characteristics, political ideology, and mental health on attitudes, knowledge, anxieties, behavior change, and impact variables. Initial covariate selection included all variables that were significant (p <0.05) in bivariate tests, including: political ideology, bias score for consumed news media, attitudes toward global warming and vaccination, sex, race, poverty level, and education. In the adjusted logistic regression model ( Table 2 ) liberals had 5.7 (95%CI: 3.3-9.7) and moderates had 2.5 (95%CI 1.5-4.3) times the odds of responding that the government had not done enough in response to COVID-19 compared to conservatives. doi = 10.1371/journal.pone.0239693 id = cord-000786-ofpcgxce author = Chua, Brendon Y. title = Hepatitis C VLPs Delivered to Dendritic Cells by a TLR2 Targeting Lipopeptide Results in Enhanced Antibody and Cell-Mediated Responses date = 2012-10-16 keywords = Cys; HCV; Pam; VLP summary = doi = 10.1371/journal.pone.0047492 id = cord-286708-igu984oc author = Chua, Kaw Bing title = Identification and Characterization of a New Orthoreovirus from Patients with Acute Respiratory Infections date = 2008-11-25 keywords = Kampar; NBV; bat; virus summary = Recently, our group reported the isolation of the Melaka virus from a patient with acute respiratory disease and provided data suggesting that this new orthoreovirus is capable of human-to-human transmission and is probably of bat origin. Here we report yet another Melaka-like reovirus (named Kampar virus) isolated from the throat swab of a 54 year old male patient in Kampar, Perak, Malaysia who was suffering from high fever, acute respiratory disease and vomiting at the time of virus isolation. Here, we report the discovery and characterization of Kampar virus (KamV), the fourth member in the NBV species group and its isolation from a human patient with fever and acute respiratory illness. Due to the similar CPE morphology ( Figure 1 ) and cell line susceptibility patterns between KamV and the recently discovered Melaka virus (MelV), which also causes acute respiratory diseases in humans [5] , immunofluorescent antibody testing was conducted to examine cross reactivity. doi = 10.1371/journal.pone.0003803 id = cord-003551-jzfl4xuk author = Ciejka, Justyna title = Synthetic sulfonated derivatives of poly(allylamine hydrochloride) as inhibitors of human metapneumovirus date = 2019-03-28 keywords = Fig; NL63; cell summary = doi = 10.1371/journal.pone.0214646 id = cord-312367-24huwt3y author = Coelho, Camila title = Biochemical screening for SARS-CoV-2 main protease inhibitors date = 2020-10-06 keywords = SARS; pro summary = As proteases, together with polymerases, are main targets of antiviral drug design, we here have performed biochemical high throughput screening (HTS) with recombinantly expressed SARS-CoV-2 M(pro). As viral proteases, following polymerases, are the most prominent targets for antiviral drug design [9] , here we describe initial biochemical screenings with recombinant purified SARS-CoV-2 M pro performed in order to define possible candidates which could serve as lead compounds for the design of future COVID-19 therapies. In order to contribute to the ongoing worldwide research and development efforts to contain COVID-19, we cloned, expressed recombinantly in E.coli BL21(DE3) and purified an important drug target of SARS-CoV-2, its main protease (M pro ). From these obtained compounds, esculetin-4-carboxylic acid ethyl ester (IC 50 = 46 μM in M pro inhibition assays), a coumarin derivative and natural product, demonstrated an EC 50 of 112 μM (median toxic concentration TC 50 >800μM) in Vero-cell SARS-CoV assays [13] and MP576 (IC 50 = 2.5 μM), a quinolinecarboxylate, demonstrated an EC 50 of 7 μM (TC 50 >50μM) [15, 17] , thus validating the M pro biochemical screening approach for the development of SARS-CoV drugs. doi = 10.1371/journal.pone.0240079 id = cord-307540-dr5m9pfk author = Coelho, Flávio C. title = Assessing the spread of COVID-19 in Brazil: Mobility, morbidity and social vulnerability date = 2020-09-18 keywords = Paulo; covid-19; region summary = Probabilistic models were used to calculate the probability of COVID-19 spread from São Paulo and Rio de Janeiro, the initial hotspots, using mobility data from the pre-epidemic period, while multivariate cluster analysis of socio-economic indices was done to identify areas with similar social vulnerability. To identify regions with high geographical and social vulnerability, we proposed a classification scheme based on three main criteria: population mobility, socio-demographic-economic characteristics, and the available health care infrastructure in terms of hospital capacity. To assess the probability of COVID-19 spreading within Brazil, in the absence of mobility restrictions, we first calculated the effective distance (E f (i,j)) between micro-regions using the air travel data. We computed the effective distance, E f (i,j), between each micro-region and the two COVID-19''s hotspots, Rio de Janeiro and Sao Paulo. Mostly urban micro-regions, with above-average life expectancy, with comparatively less social inequality, less population living in extreme poverty, better access to water supply and sewage disposal services, higher education. doi = 10.1371/journal.pone.0238214 id = cord-001092-pkps5j8w author = Coleman, Ryan G. title = Ligand Pose and Orientational Sampling in Molecular Docking date = 2013-10-01 keywords = dock; docking; dud; figure; ligand; screening summary = doi = 10.1371/journal.pone.0075992 id = cord-289017-vwye3pk9 author = Comach, Guillermo title = Sentinel Surveillance of Influenza-Like Illness in Two Hospitals in Maracay, Venezuela: 2006–2010 date = 2012-09-11 keywords = ILI; PCR; Venezuela; virus summary = CONCLUSIONS/SIGNIFICANCE: Influenza viruses were the most commonly detected viral organisms among patients with acute febrile respiratory illnesses presenting at two hospitals in Maracay, Venezuela. Recent prospective studies, which utilized more sensitive methods for detecting respiratory viruses such as multiplex polymerase chain reaction (PCR), have similarly demonstrated that the highest rates of viral respiratory infection occur among children and the frequency of infection tends to decrease with age due to increasing acquired immunity [8] . On the other hand, the percentage of influenza viruses (not including pH1N1) detected in our study during a similar period of time, but in different years accounted for the significant differences found in both studies: a) the collection, preservation and further processing of respiratory samples, and b) the type of cells and IFA reagents used for virus isolation and identification. In contrast, a prospective study of ILI among Brazilian adults, which utilized viral isolation and RT-PCR testing on respiratory samples, detected rhinoviruses in 19.6% of patients [14] . doi = 10.1371/journal.pone.0044511 id = cord-276372-q1fzxt3r author = Conde, Dalia A. title = Zoos through the Lens of the IUCN Red List: A Global Metapopulation Approach to Support Conservation Breeding Programs date = 2013-12-11 keywords = ISIS; specie; zoo summary = To inform CBP policies for threatened terrestrial vertebrates, we evaluated the number and representation of threatened vertebrate species on the IUCN Red List held in the ISIS zoo network and estimated the complexity of their management as metapopulations. To understand the complexity of maintaining CBPs of threatened species across the ISIS zoo network, we developed a second algorithm to find the optimal radial distance from any given zoo at which the probability of finding a metapopulation size of at least 50, 100 or 250 recruited living individuals was highest relative to that radial distance. As expected, the optimal distance radii and the number of zoos required to maximize the probability of reaching a given population increase with the metapopulation size threshold (.50, .100 and .250 individuals) ( Figure 3) . Therefore, for the zoo community, one of the main challenges of managing their threatened species in CBPs is the complexity of moving individuals across borders and the coordination of conservation efforts among zoos and other institutions at a global level. doi = 10.1371/journal.pone.0080311 id = cord-349781-l93978vq author = Cong, Yu title = MERS-CoV pathogenesis and antiviral efficacy of licensed drugs in human monocyte-derived antigen-presenting cells date = 2018-03-22 keywords = CPZ; Fig; MERS; cell summary = Little is known about the pathogenesis and innate antiviral response in primary human monocyte-derived macrophages (MDMs) and dendritic cells (MDDCs) upon MERS-CoV infection. In this study, we assessed MERS-CoV replication as well as induction of inflammatory cytokines and chemokines in MDMs and immature and mature MDDCs. Immature MDDCs and MDMs were permissive for MERS-CoV infection, while mature MDDCs were not, with stimulation of proinflammatory cytokine and chemokine upregulation in MDMs, but not in MDDCs. To further evaluate the antiviral activity of well-defined drugs in primary antigen presenting cells (APCs), three compounds (chloroquine, chlorpromazine and toremifine), each with broad-spectrum antiviral activity in immortalized cell lines, were evaluated in MDMs and MDDCs to determine their antiviral effect on MERS-CoV infection. However, MERS-CoV continued to propagate in immature MDDCs up to 8 days pi, demonstrating differential infection and replication capabilities in MDMs and immature MDDCs. To compare the ability of MERS-CoV to induce innate immune responses in three types of APCs, the release of cytokines and chemokines was measured from virus-or mock-infected cells. doi = 10.1371/journal.pone.0194868 id = cord-000208-th0wddvc author = Cornelissen, Lisette A. H. M. title = A Single Immunization with Soluble Recombinant Trimeric Hemagglutinin Protects Chickens against Highly Pathogenic Avian Influenza Virus H5N1 date = 2010-05-14 keywords = Fig; H5N1; HPAI summary = title: A Single Immunization with Soluble Recombinant Trimeric Hemagglutinin Protects Chickens against Highly Pathogenic Avian Influenza Virus H5N1 Such HA trimers, expressed either in insect or mammalian cells, were indeed shown to elicit neutralizing antibodies [16] and to partially protect mice against HPAI H5N1 challenge infection [19] . In view of their promising potential we have evaluated recombinant soluble HA trimers in chickens and mice for their ability to induce protective immunity against infection with HPAI H5N1. Subsequently, vaccination with the sH5 3 preparation was shown to provide complete protection against challenge with HPAI H5N1 both in mice and in chickens, in the latter already after a single immunization. In the present study we evaluated the vaccine potential of a recombinant soluble H5 protein (sH5 3 ) to protect chickens and mice against a lethal infection with HPAI H5N1. A pseudotype baculovirusmediated vaccine confers protective immunity against lethal challenge with H5N1 avian influenza virus in mice and chickens doi = 10.1371/journal.pone.0010645 id = cord-000158-d08buwtu author = Corti, Davide title = Analysis of Memory B Cell Responses and Isolation of Novel Monoclonal Antibodies with Neutralizing Breadth from HIV-1-Infected Individuals date = 2010-01-20 keywords = HIV-1; HJ16; HK20; HR-1 summary = The 2G12 epitope is not present in the majority of clade C isolates [27] , but, of more concern, no 2G12-like activity has been detected in the sera of HIV-1 infected individuals [21, 22] , suggesting that this type of neutralizing antibody may not be generally amenable to elicitation by B cells. By using an improved memory B cell immortalization method [41] , combined with highthroughput parallel screening with a panel of recombinant Envbased antigens, we isolated a panel of 58 human mAbs which we have characterized with regard to epitope specificity and breadth of neutralization. The mAbs were purified and further characterized for binding specificity and neutralizing activity using an extended panel of recombinant Env proteins and pseudoviruses representative of several HIV-1 clades with diverse coreceptor usage, geographic origin and conformation. doi = 10.1371/journal.pone.0008805 id = cord-260647-7bjhobg7 author = Coudray-Meunier, Coralie title = A Novel High-Throughput Method for Molecular Detection of Human Pathogenic Viruses Using a Nanofluidic Real-Time PCR System date = 2016-01-29 keywords = PCR; RNA summary = A nanofluidic real-time PCR system was used to develop novel high-throughput methods for qualitative molecular detection (RT-qPCR array) and quantification of human pathogenic viruses by digital RT-PCR (RT-dPCR). The aim of this study was to develop real time RT-PCR assays for detection of a total of 19 human enteric viruses (including 3 genogroupes of norovirus and 4 coronaviruses) and two control process viruses (mengovirus and murine norovirus) generally used for monitoring the recovery of viral foodstuff extraction methods. The sensitivity of conventional qPCR assays targeting 21 viral genomes was compared to the quantitative digital RT-PCR array and to the qualitative nanofluidic real-time PCR array performed on Fluidigm''s BioMark System. Similarly, by testing genomes from viruses in stools and RNA from virus production in cells, the limit of detection (LOD) as determined by RT-dPCR was respectively 1.5 to 3.4 log 10 and 1.6 to 2.1 log 10 lower than the expected copy numbers calculated via the standard curve by RT-qPCR. doi = 10.1371/journal.pone.0147832 id = cord-258366-fu9b446y author = Couto, Carla R. title = Fighting Misconceptions to Improve Compliance with Influenza Vaccination among Health Care Workers: An Educational Project date = 2012-02-06 keywords = influenza; respiratory; vaccination summary = At Hospital das Clinicas, University of Sã o Paulo School of Medical Sciences, a previous study showed a 34% compliance with influenza vaccination among HCWs. In the mentioned study, the main reasons for non-compliance were the perception of vaccine inefficacy and the fear of adverse reactions [4] . To diminish the arguments of fear of adverse events or perception of vaccine inefficacy, this prospective study was conducted to demonstrate to a subset of HCWs from our hospital, that severe adverse events following influenza vaccination are rare and the episodes of respiratory symptoms occurring in the first four months after vaccination are generally caused by other respiratory viruses and not by influenza virus. As expected, no severe adverse event was observed in the present study, and the events more frequently reported, such as headache, myalgia and malaise could be related to influenza vaccine itself as well as to other causes, given their unspecificity. doi = 10.1371/journal.pone.0030670 id = cord-001142-puj74k7y author = Crescenzo-Chaigne, Bernadette title = The Panhandle Formed by Influenza A and C Virus NS Non-Coding Regions Determines NS Segment Expression date = 2013-11-21 keywords = virus summary = To investigate whether, or not, and how the complete NC regions of a given segment are involved in type specificity, we attempted to rescue, by reverse genetics, type A and C influenza viruses with chimeric non-coding sequences. The sole difference between 5''A/3''C(C5U) and wild-type 5''A/3''A viruses being the 3'' distal extremity of the NS segment suggested that the level of NS encoded proteins (i.e. NS1 or/and NS2/NEP) was affected at early stages of infection for this virus (5''A/3''C(C5U)). The major role of the proximal panhandle in type specificity that we identified and the hypothesized involvement of the distal panhandle in transcription need to be tested on the other (2 PFU/cell), viral vRNA and mRNA levels for each segment were evaluated by specific two-step RT-qPCRs previously described [23] . doi = 10.1371/journal.pone.0081550 id = cord-001420-b4zcvd04 author = Crescenzo-Chaigne, Bernadette title = Chimeric NP Non Coding Regions between Type A and C Influenza Viruses Reveal Their Role in Translation Regulation date = 2014-09-30 keywords = virus summary = Interestingly, in type A influenza virus infectious context, the length of the NP segment 5′ NC region once transcribed into mRNA was found to impact its translation, and the level of produced NP protein consequently affected the level of viral genome replication. The sequence of both ends of each segment of each rescued virus was verified as described [9] , and no Influenza NP Non Coding Region Role in Translation PLOS ONE | www.plosone.org genetics, type A and type C viruses with one or both heterotypic ends. These data based on type A influenza virus NP segment showed that it is possible to obtain virus by reverse genetics when a homotypic proximal panhandle and a homotypic strength of the initial distal panhandle are maintained, and that the length of the 59 end plays an important role in the efficiency of rescue. doi = 10.1371/journal.pone.0109046 id = cord-000013-pr9i9swk author = Croyle, Maria A. title = Nasal Delivery of an Adenovirus-Based Vaccine Bypasses Pre-Existing Immunity to the Vaccine Carrier and Improves the Immune Response in Mice date = 2008-10-29 keywords = Ebola; existing; figure; immunity; pre summary = We have previously found that a single dose of a recombinant adenovirus expressing Ebola Zaire GP given by either the oral or the nasal route is capable of affording protection against lethal challenge in naïve mice and that mucosal immunization can stimulate a broad, prolonged T cell-mediated immune response in both the systemic and mucosal compartments [37] . In an effort to correlate markers of immunity with protection against Ebola infection after mucosal immunization, T and B cell specific immune responses against Ebola glycoprotein were analyzed in mice in the presence or absence of pre-existing immunity (PEI) to adenovirus 10 days after vaccination with a first generation adenovirus serotype 5 vector expressing the Zaire Ebola glycoprotein (Ad5-ZGP). A single intranasal dose of a recombinant Ad5 vaccine expressing the Zaire Ebola glycoprotein conferred 100% protection in both naïve mice and those with pre-existing immunity despite the fact that the strength of the immune response generated by this route of administration was quantitatively lower than that seen in animals vaccinated by intramuscular injection. doi = 10.1371/journal.pone.0003548 id = cord-254340-e1x0z3rh author = Cruz, Christian Joy Pattawi title = Exploring the young demographic profile of COVID-19 cases in Hong Kong: Evidence from migration and travel history data date = 2020-06-26 keywords = Hong; Kong; case; covid-19 summary = Using detailed case data from Hong Kong''s Centre for Health Department and Immigration Department, we analyze the sex and age distribution of the confirmed cases along with their recent travel histories and immigration flows for the period January to April 2020. Our analysis highlights Hong Kong''s high proportion of imported cases and large overseas student population in developing COVID-19 hotspot areas such as the United Kingdom. Our study includes an examination of the age and sex distribution of the COVID-19 confirmed cases in Hong Kong and an exploration of how the different measures to combat this outbreak resulted in a relatively low number of cases and deaths. In this paper, we highlight the potential impact of the young profile of the confirmed cases on the total number of mortalities and the effect of early, aggressive policy measures including travel bans, enforced quarantines and contact-tracing imposed by the Hong Kong government as early as January 27, 2020 in containing the spread of the COVID-19. doi = 10.1371/journal.pone.0235306 id = cord-326011-5rmhjbri author = Cui, Dawei title = Clinical and Epidemiologic Characteristics of Hospitalized Patients with Laboratory-Confirmed Respiratory Syncytial Virus Infection in Eastern China between 2009 and 2013: A Retrospective Study date = 2016-11-01 keywords = China; RSV summary = title: Clinical and Epidemiologic Characteristics of Hospitalized Patients with Laboratory-Confirmed Respiratory Syncytial Virus Infection in Eastern China between 2009 and 2013: A Retrospective Study Respiratory syncytial virus (RSV) is a leading cause of morbidity and mortality worldwide in children aged <5 years and older adults with acute lower respiratory infections (ALRIs). Clinical and epidemiologic data pertaining to hospitalized patients of all ages with laboratory-confirmed RSV infection by PCR assay were collected and analyzed in this study. Respiratory syncytial virus (RSV) is a leading cause of viral infection in children and older adults worldwide, particularly young children aged <5 years [1] . In this study, we aimed to evaluate the epidemiology, clinical characteristics and management of ALRIs caused by RSV infection among hospitalized patients of all age groups in eastern China between 2009 and 2013 in a hospital-based surveillance study. Clinical characteristics and risk factors of severe respiratory syncytial virus-associated acute lower respiratory tract infections in hospitalized infants doi = 10.1371/journal.pone.0165437 id = cord-348807-9xxc5hyl author = Cuomo, Raphael E. title = Sub-national longitudinal and geospatial analysis of COVID-19 tweets date = 2020-10-28 keywords = COVID-19; States; United summary = METHODS: In an effort to better understand the impacts of COVID-19, we concurrently assessed the geospatial and longitudinal distributions of Twitter messages about COVID-19 which were posted between March 3rd and April 13th and compared these results with the number of confirmed cases reported for sub-national levels of the United States. This study suggests that, across subnational areas within the United States, there exists a highly variable threshold of perceived dangerousness and/or intrusiveness required to activate outbreak-related conversations on social media platforms such as Twitter, a finding that can inform future outbreak communication and health promotion strategies. Concurrent geospatial and longitudinal analyses also indicate that predominantly rural areas of the United States increased engagement in COVID-19 social media conversations at later stages of the study timeframe. This study is unique in that it uses Twitter data as a proxy measure for assessing the concurrent longitudinal and geospatial distributions of attention to COVID-19 across local and regional communities in the United States. doi = 10.1371/journal.pone.0241330 id = cord-293794-vudufao5 author = Cuthbertson, Leah title = Viral respiratory infections and the oropharyngeal bacterial microbiota in acutely wheezing children date = 2019-10-17 keywords = Fig; bacterial; significant summary = No significant difference in bacterial diversity was observed between samples from those with wheeze and healthy controls. Using 16s rRNA gene sequencing of respiratory samples from children presenting to hospital with acute wheezing, this study aimed to examine whether the bacterial community in the airways of children with acute respiratory wheeze was altered compared with that of nonwheezing children. However, when the microbiota in children with bronchiolitis were compared to those closest in age there was a significant reduction in alpha diversity (richness; p = 0.01, Shannon-Weiner, p = 0.003, inverse Simpsons, p = 0.005) that was not associated with change in bacterial biomass (p = 0.874). When those with a diagnosis of bronchiolitis were compared to other cases that wheezed or age matched control subjects, significant differences in alpha and beta diversity were observed however this may have been driven by subjects with bronchiolitis being significantly younger than other groups of subjects. doi = 10.1371/journal.pone.0223990 id = cord-000905-1rhlu59c author = Cyktor, Joshua C. title = Clonal Expansions of CD8(+) T Cells with IL-10 Secreting Capacity Occur during Chronic Mycobacterium tuberculosis Infection date = 2013-03-05 keywords = CBA; CD8 summary = doi = 10.1371/journal.pone.0058612 id = cord-349911-dx8wvqkm author = Dahl, Viktor title = Communicable Diseases Prioritized According to Their Public Health Relevance, Sweden, 2013 date = 2015-09-23 keywords = Health; Sweden summary = Ten pathogens in the highest priority group (Borrelia, calicivirus, Campylobacter, Echinococcus multilocularis, hepatitis C virus, HIV, respiratory syncytial virus, SARSand MERS coronavirus, tick-borne encephalitis virus and varicella-zoster virus) did not have any surveillance of typing results. The Public Health Agency of Sweden identified the need to use a structured method that takes relevant aspects into account in order to rationally prioritize between different pathogens when allocating resources for surveillance. The Robert Koch Institute invited ten senior external experts and ten internal experts and asked them to score the pathogens with -1, 0 or 1 for ten variables"Incidence", "Work and school absenteeism", "Health care utilization", "Chronicity of illness or sequelae", "Case fatality rate", "Proportion of events requiring public health actions", "Trend", "Public attention", "Prevention and Treatment possibilities") ( Table 1 ). We used a standardized procedure developed at the Robert Koch Institute to generate a list of pathogens prioritized for surveillance to be used by the Public Health Agency of Sweden. doi = 10.1371/journal.pone.0136353 id = cord-260843-c97kctjz author = Dai, Lei title = Transmissible Gastroenteritis Virus Infection Enhances SGLT1 and GLUT2 Expression to Increase Glucose Uptake date = 2016-11-16 keywords = EGFR; IPEC; TGEV; sglt1 summary = In vivo, TGEV primarily targets and infects intestinal epithelial cells, which play an important role in glucose absorption via the apical and basolateral transporters Na(+)-dependent glucose transporter 1 (SGLT1) and facilitative glucose transporter 2 (GLUT2), respectively. Our data demonstrate that infection with TGEV resulted in increased glucose uptake and augmented expression of EGFR, SGLT1 and GLUT2. Therefore, in the study, we aimed to examine the in vitro effects of TGEV infection on glucose uptake and the expression of SGLT1 and GLUT2 in porcine intestinal columnar epithelial (IPEC-J2) cells, which have been shown to offer a practical model for studying TGEV infection [11, 12] . Together, these results indicate that EGFR and p-EGFR regulates glucose uptake in mock-infected IPEC-J2 cells by modulation of SGLT1 protein expression. Together, these results indicate that EGFR influences glucose uptake in TGEV-infected cells by promoting both SGLT1 and GLUT2 expression. doi = 10.1371/journal.pone.0165585 id = cord-309981-4p3ybrn1 author = Dai, Ling-Ling title = Anxiety and depressive symptoms among COVID-19 patients in Jianghan Fangcang Shelter Hospital in Wuhan, China date = 2020-08-28 keywords = China; Fangcang; covid-19 summary = From February 23, 2020, to February 26, 2020, we obtained sociodemographic and clinical characteristics information of COVID-19 patients in Jianghan Fangcang Shelter Hospital (Wuhan, China) and assessed their mental health status and sleep quality. As with other infectious diseases, preliminary evidence suggests that COVID-19 also causes public panic and mental health stress; symptoms of anxiety and depression are common psychological reactions to the COVID-19 pandemic, and may be associated with sociodemographic factors and sleep quality [6] [7] [8] [9] . This cross-sectional study examined the prevalence of anxiety, depression, and poor sleep quality among 307 patients in Jianghan Fangcang Shelter Hospital in Wuhan, China, 2 months after the start of the COVID-19 pandemic. In addition, using one-sample-tests, it was determined that both SAS (42.92±7.30) and SDS (39.77±10.11) scores of the participants of our study were higher than Chinese norms (SAS, 29.78±10.07, n = 1158; SDS, 33.46±8.55, n = 1340) (both P<0.001) [26] , indicating more severe levels of anxiety and depressive symptoms among COVID-19 patients admitted to Fangcang hospitals, compared with the general public. doi = 10.1371/journal.pone.0238416 id = cord-316319-m6uha1qn author = Daleno, Cristina title = Phylogenetic Analysis of Human Rhinovirus Isolates Collected from Otherwise Healthy Children with Community-Acquired Pneumonia during Five Successive Years date = 2013-11-19 keywords = HRV summary = In order to evaluate the circulation of the different human rhinovirus (HRV) species and genotypes in Italian children with radiographically confirmed community-acquired pneumonia (CAP), a nasopharyngeal swab was obtained from 643 children admitted to hospital because of CAP during five consecutive winter and early spring seasons (2007-2012). However, most of these studies were carried out in a single year and involved a relatively small number of patients, and only a few analysed specific LRTIs. Consequently, there are few data concerning the circulation of HRVs over a long period of time or the real role of the different species and genotypes in causing LRTIs. The aim of this study was to evaluate the circulation of the different HRV species and genotypes in Italian children with radiographically confirmed CAP during the winter and early spring of five consecutive years as this information could help to develop tailored strategies for the prevention and treatment of pediatric HRV infections. doi = 10.1371/journal.pone.0080614 id = cord-002473-2kpxhzbe author = Das, Jayanta Kumar title = Chemical property based sequence characterization of PpcA and its homolog proteins PpcB-E: A mathematical approach date = 2017-03-31 keywords = acid; sequence summary = Secondly, we build a graph theoretic model on using amino acid sequences which is also applied to the cytochrome c7 family members and some unique characteristics and their domains are highlighted. The primary protein sequence is read as consecutive order pairs serially from first amino acid to the end of sequence, and each order pair is nothing but a connected edge between the two nodes where nodes in the graph are involved with different chemical groups of amino acids. Our method of phylogenetic tree formation used the dissimilarity matrix which is obtained for every pair of sequence on the basis of chemical group specific score of amino acids. Based on the phylogenetic tree of five members, we find that the PpcA and PpcD, PpcB and PpcE are mostly closed with regards to the frequency of amino acids of respective eight chemical groups. doi = 10.1371/journal.pone.0175031 id = cord-002180-gsdk5x3e author = Davies, Colin title = Expression of the NS5 (VPg) Protein of Murine Norovirus Induces a G1/S Phase Arrest date = 2016-08-24 keywords = RNA; ns5 summary = Amino acid substitutions of NS5(Y26A) and NS5(F123A) that inhibit the ability for NS5 to attach to RNA and recruit host eukaryotic translation initiation factors, respectively, retained the ability to induce an accumulation of cells in the G(0)/G(1) phase as identified for wild-type NS5. Several RNA viruses, including murine norovirus 1 (MNV-1) have been characterized to manipulate cell cycle progression at the G 1 /S restriction point, often creating favorable conditions for viral replication [14] [15] [16] [17] [18] [19] [20] [21] . The effect of NS5 on the host cell cycle was therefore determined by transfection of RAW-Blue cells with RNA transcripts, encoding individual viral genes, NS1-2 from MNV-1 was included as a negative control (Fig 1A) . Furthermore, the NS5(F123A) variant decreased cyclin A protein expression by 67% when compared to the mocktransfected population in a synonymous manner to NS5, strongly implying that the host eukaryotic initiation factor binding domain of NS5 does not play a role in its cell cycle manipulation (Fig 3D) . doi = 10.1371/journal.pone.0161582 id = cord-265812-1hcp36cw author = De Jong, Cornelis N. title = Etanercept for steroid-refractory acute graft-versus-host disease: A single center experience date = 2017-10-26 keywords = GVHD; patient summary = W.; Van der Klift, Marjolein; Cornelissen, Jan J.; Broers, Annoek E. High dose glucocorticosteroids, are currently recommended as first-line treatment for grade II-IV aGVHD resulting in overall complete responses (CR) in 40%-50% of patients. CONCLUSION: Second-line treatment with etanercept does induce responses in SR-aGVHD of the gut but appears to be associated with poor long-term survival even in responding patients. High dose systemic glucocorticosteroids (steroids) are currently recommended as first-line treatment for grade II-IV aGVHD resulting in overall complete responses (CR) in 40%-50% of patients [2, 3] . Studies evaluating second-line treatment with the anti-TFNα agent etanercept have shown promising results with overall response rates of 50-80% [8] [9] [10] . In conclusion, although second-line treatment of SR-aGVHD of the gut with etanercept was associated with a promising initial response rate, overall survival appeared very poor, mainly due to progression of GVHD and opportunistic infections. doi = 10.1371/journal.pone.0187184 id = cord-269690-6r2bfydw author = De Lorenzo, Rebecca title = Residual clinical damage after COVID-19: A retrospective and prospective observational cohort study date = 2020-10-14 keywords = COVID-19; follow; patient summary = doi = 10.1371/journal.pone.0239570 id = cord-001045-jm60nxc2 author = DeLisle, Sylvain title = Using the Electronic Medical Record to Identify Community-Acquired Pneumonia: Toward a Replicable Automated Strategy date = 2013-08-13 keywords = ARI; CDA; EMR summary = METHODS: A manual EMR review of 2747 outpatient ARI visits with associated chest imaging identified x-ray reports that could support the diagnosis of pneumonia (kappa score = 0.88 (95% CI 0.82∶0.93)), along with attendant cases with Possible Pneumonia (adds either cough, sputum, fever/chills/night sweats, dyspnea or pleuritic chest pain) or with Pneumonia-in-Plan (adds pneumonia stated as a likely diagnosis by the provider). The ARI CDA flagged an outpatient visit if the provider assigned it an ARI-related International Disease Classification, 9 th Revision, Clinical Modification (ICD-9) diagnostic code OR issued a prescription for a cough remedy OR documented at least two symptoms from the above ARI case definition in his/her clinical note, as retrieved by computerized text analysis [10] . Discussion Automated text analyses of chest imaging reports improved the performance of EMR-based CDAs that included structured data elements and free-text search for ARI symptoms. doi = 10.1371/journal.pone.0070944 id = cord-303845-y6ws3u6x author = DeLisle, Sylvain title = Combining Free Text and Structured Electronic Medical Record Entries to Detect Acute Respiratory Infections date = 2010-10-14 keywords = ARI; CDA; EMR; ICD-9 summary = Several factors, some of which have already been mentioned, may limit the generalizability of our results: 1) factors related to the performance of our study at the VA health care system: a) the veterans study population is mostly male and excludes the pediatric population, a key target for ARI surveillance [44] ; b) veterans health care utilization may differ from that observed in uninsured or privately insured individuals; c) clinical practices, documentation and coding habits by VA practitioners may differ from those observed in solo or group practices or in health systems subject to different financial or quality-control incentives; 2) factors related to our study period: optimal CDAs could differ outside the respiratory infection season, or during periods of heightened apprehension for an influenza epidemic; 3) factors related to our iterative CDA development process, which may have over adapted CDAs to VA''s particular EMR implementation and to our sample dataset in particular, this despite our efforts to maintain a separation between development and validation data subsets; 4) factors related to our text mining approach: a) we did not employ a spell checker prior to applying the NegEx algorithm. doi = 10.1371/journal.pone.0013377 id = cord-255384-tljyx6ua author = Decaro, Nicola title = Full-Genome Analysis of a Canine Pneumovirus Causing Acute Respiratory Disease in Dogs, Italy date = 2014-01-06 keywords = Bari/100; MPV; PCR; canine summary = The full-genomic characterisation showed that the causative agent (strain Bari/100-12) was closely related to CnPnVs that have been recently isolated in the USA, as well as to murine pneumovirus, which is responsible for respiratory disease in mice. In order to obtain new insights into the genetic diversity of CnPnV, the Italian prototype strain dog/Bari/100-12/ITA/2012 was submitted to RT-PCR amplification and subsequent sequence analysis of the full-length genome, using oligonucleotide retrieved from previous studies [13] [14] . When the analysis was restricted to the 8,600 and 8,598 nt available for reference CnPnV strains Brne17 and Ane4, respectively, that span from the very 39 end of the L gene to the 59end of the leader region (genome sense), an overall sequence identity of 96.5-96.6% was found against the canine strains. doi = 10.1371/journal.pone.0085220 id = cord-013263-xw611i8k author = Dederichs, Melina title = Students’ perspectives on interventions to reduce stress in medical school: A qualitative study date = 2020-10-15 keywords = group; intervention; medical; student summary = doi = 10.1371/journal.pone.0240587 id = cord-342730-b7y8mybg author = Dellagi, Koussay title = Pandemic Influenza Due to pH1N1/2009 Virus: Estimation of Infection Burden in Reunion Island through a Prospective Serosurvey, Austral Winter 2009 date = 2011-09-29 keywords = H1N1; HIA; Island; rate summary = In order to assess at the community level, the actual magnitude of the pH1N1/2009v pandemic and the extent of the herd immunity acquired after passage of the epidemic wave, a prospective population serosurvey was conducted in Reunion Island during the passage of the epidemic wave in the 2009 austral winter season (July-December 2009): prevalence of infection was assessed on a weekly basis and seroconversion rates were measured using paired sera. The CoPanFlu-RUN cohort was set up to conduct a prospective population-based study investigating the herd immunity induced by the 2009 pandemic influenza virus and identifying risk factors for pH1N1/2009v infection from paired sera collected in an entire community. Our study shows that a substantial proportion of Reunion Island''s population had pre-existing immunity to 2009 pandemic influenza virus with the highest baseline-proxy seroprevalence rate observed among adults aged of 60 years or more. doi = 10.1371/journal.pone.0025738 id = cord-003841-7uaj9hmx author = Desmonts de Lamache, D. title = Immuno-modulating properties of Tulathromycin in porcine monocyte-derived macrophages infected with porcine reproductive and respiratory syndrome virus date = 2019-08-23 keywords = Fig; PRRSV; ROS; TUL; USA; porcine summary = doi = 10.1371/journal.pone.0221560 id = cord-001447-oi7bkm4z author = Dhanasekaran, Sakthivel title = Toll-Like Receptor Responses to Peste des petits ruminants Virus in Goats and Water Buffalo date = 2014-11-04 keywords = Barbari; PBMC; PPRV; Salem; TLR7 summary = We examined the replication of PPRV in peripheral blood mononuclear cells (PBMC) of Indian domestic goats and water buffalo and demonstrated that the levels of TLR3 and TLR7 and downstream signalling molecules correlation with susceptibility vs resistance. Upon stimulation of PBMC with synthetic TLR3 and TLR7 agonists or PPRV, the levels of proinflammatory cytokines were found to be significantly higher while immunosuppressive interleukin (IL) 10 levels were lower in PPRV resistant Kanni and Salem Black breeds and water buffalo at transcriptional level, correlating with reduced viralloads in infected PBMC. Infection of peripheral blood mononuclear cells (PBMC) from four breeds of goats and water buffalo resulted in differential viral replication kinetics and inflammatory cytokine profile including IFNa, IFNc and TNFa with differential activation of TLR3 and TLR7. To determine whether the differential IFN and pro-inflammatory cytokine production between Kanni/Salem vs Barbari/ Tellicherry breeds of goats are dependent on single nucleotide polymorphisms (SNPs) in TLR genes, we examined the complete gene sequence of TLR7. doi = 10.1371/journal.pone.0111609 id = cord-308344-ao9z00t7 author = Diep, Nguyen Van title = Novel Porcine Epidemic Diarrhea Virus (PEDV) Variants with Large Deletions in the Spike (S) Gene Coexist with PEDV Strains Possessing an Intact S Gene in Domestic Pigs in Japan: A New Disease Situation date = 2017-01-17 keywords = PCR; PEDV summary = title: Novel Porcine Epidemic Diarrhea Virus (PEDV) Variants with Large Deletions in the Spike (S) Gene Coexist with PEDV Strains Possessing an Intact S Gene in Domestic Pigs in Japan: A New Disease Situation Among 17 PEDV samples isolated from individual pigs, all of them contained at least two distinct genotypes with large genomic deletions, and 94.1% of them were found to consist of strains with an intact S gene. In this study, variants with large deletions in the S gene were found in eight primary and nine recurrent outbreaks from 16 pig farms, and they mostly (94.1%) coexisted with PEDV strains with an intact S gene. Cell culture isolation and sequence analysis of genetically diverse US porcine epidemic diarrhea virus strains including a novel strain with a large deletion in the spike gene New porcine epidemic diarrhoea virus variant with a large deletion in the spike gene identified in domestic pigs doi = 10.1371/journal.pone.0170126 id = cord-309010-tmfm5u5h author = Dietert, Kristina title = Spectrum of pathogen- and model-specific histopathologies in mouse models of acute pneumonia date = 2017-11-20 keywords = Fig; IAV; MERS; model summary = Here, we systematically describe and compare the distinctive histopathological features of established models of acute pneumonia in mice induced by Streptococcus (S.) pneumoniae, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Legionella pneumophila, Escherichia coli, Middle East respiratory syndrome (MERS) coronavirus, influenza A virus (IAV) and superinfection of IAV-incuced pneumonia with S. Systematic comparisons of the models revealed striking differences in the distribution of lesions, the characteristics of pneumonia induced, principal inflammatory cell types, lesions in adjacent tissues, and the detectability of the pathogens in histological sections. Transnasal infection with MERS-CoV following adenoviral transduction of human DPP4 yielded an expansive, (Fig 7A) interstitial pneumonia with severe alveolar epithelial cell necrosis and infiltration of mainly macrophages, lymphocytes, and fewer neutrophils (Fig 7B) . Different mouse models of acute pneumonia differ widely, with an obvious strong dependence on pathogen-specific features of virulence and spread, route of infection, infectious dose and other factors. doi = 10.1371/journal.pone.0188251 id = cord-353730-owcapg8h author = Dietrich, Jes title = Inducing Dose Sparing with Inactivated Polio Virus Formulated in Adjuvant CAF01 date = 2014-06-23 keywords = CAF01; Fig; IPV; vaccine summary = The CAF01 adjuvant has previously been shown to be a safe and potent adjuvant with several antigens, and here we show that in mice IPV formulated with CAF01 induced increased systemic protective immunity measured by binding and neutralization antibody titers in serum. Based on neutralization titers obtained from mice vaccinated with a range of doses from 30 DU (D-Units) to 0.1 DU (data not shown) we choose 20 DU as a full mouse dose and 2 DU as the dose formulated into the CAF01 adjuvant (indicated dose units in the all experiments correspond to polio virus type-1 D antigen units). Taken together, compared to IM administration a side by side ID+IM administration with a CAF01-adjuvanted vaccine followed by an IM administration did not negatively affect systemic immunity, measured by antibody binding and neutralization titers and T cell IFN-c secretion (Fig. 6) . doi = 10.1371/journal.pone.0100879 id = cord-253056-765rs3e7 author = Dionne, Audrey title = Profile of resistance to IVIG treatment in patients with Kawasaki disease and concomitant infection date = 2018-10-17 keywords = IVIG; Kawasaki summary = title: Profile of resistance to IVIG treatment in patients with Kawasaki disease and concomitant infection Children with persistent or recurrent fever 36 hours after the end of intravenous immunoglobulin (IVIG) are considered to be resistant to treatment and are at increased risk for coronary complications. RESULTS: Children with concomitant infection were more likely to have fever 48 hours after initial IVIG treatment (36% vs 20%, p = 0.05) and to be treated with a second dose (33% vs 18%, p = 0.04). Children with concurrent infection had higher rates of IVIG resistance (19 (33%) versus 17 (18%) patients, p = 0.04), and higher temperature at 48 hours (Fig 1) . In this retrospective series, the presence of a concomitant infection was associated with a higher rate of resistance to IVIG treatment. In this study, patients with concomitant infection had a higher rate of resistance to IVIG treatment. doi = 10.1371/journal.pone.0206001 id = cord-267973-uvz7kavu author = Do, Lien Anh Ha title = Respiratory Syncytial Virus and Other Viral Infections among Children under Two Years Old in Southern Vietnam 2009-2010: Clinical Characteristics and Disease Severity date = 2016-08-08 keywords = RSV; infection; respiratory summary = title: Respiratory Syncytial Virus and Other Viral Infections among Children under Two Years Old in Southern Vietnam 2009-2010: Clinical Characteristics and Disease Severity This study aims to describe the viral etiologies, the demographic, epidemiological, and clinical characteristics of children under two years of age who were hospitalized with a lower respiratory tract infections (LRTI), focusing on RSV (prevalence, seasonality, subgroups, viral load) and its association with disease severity. However, information on detailed clinical, epidemiological features and virological characteristics of RSV infections (e.g. disease burden, demographics, seasonal variations of RSV and other viral infections, circulating genotypes and subgroups, viral load) or on the frequency / impact of other respiratory viruses among Vietnamese children under two years old are limited [6] . Here, we aimed to describe the viral etiologies and the demographic, epidemiological, and clinical characteristics of children under two years of age who were hospitalized with a LRTI, focusing on RSV (prevalence, seasonality, subgroups, viral load) and its association with disease severity. doi = 10.1371/journal.pone.0160606 id = cord-349029-zyfop43z author = Dobrovolny, Hana M. title = Modeling the role of asymptomatics in infection spread with application to SARS-CoV-2 date = 2020-08-10 keywords = SARS; asymptomatic summary = In order to estimate how effective these strategies will be, we will need a better understanding of the role of asymptomatic individuals in SARS-CoV-2 spread and the effect the proportion and relative infectiousness of asymptomatics have on the time course of the epidemic. In this paper, we study a compartmental epidemic model that includes asymptomatic infections to determine the role that asymptomatic individuals might play in the spread of SARS-CoV-2. We apply our model to data from SARS-CoV-2 epidemics in California, Florida, New York, and Texas, finding that a large number of infections in these states are unreported and that relaxing social distancing measures too early will cause a rapid spike in infections driven in part by these hidden infections. For the SARS-CoV epidemics examined here, the model predicts that there are far more asymptomatic or unreported cases at the peak of the infection, suggesting that there might be widespread community transmission if stay-at-home orders are relaxed too early. doi = 10.1371/journal.pone.0236976 id = cord-308249-es948mux author = Dokuka, Sofia title = How academic achievement spreads: The role of distinct social networks in academic performance diffusion date = 2020-07-27 keywords = academic; network; social summary = We examine the spread of academic achievements of first-year undergraduate students through friendship and study assistance networks, applying stochastic actor-oriented modeling. In this paper, we analyze the diffusion of academic performance across different types of student social networks. We analyze the spread of academic achievements within two different social networks of first-year undergraduate students. It was shown that achievements spread well within friendship networks, while other types of ties (e.g. online relationships) do not serve as channels for the performance transmission. In this paper, we examine the diffusion of academic achievements in two distinct social networks: friendship and study assistance. We analyze the longitudinal data on friendship and study assistance networks and GPA of a first-year student cohort of the Economics department in one of the leading Russian universities in 2013-2014 academic year. In this paper we explore the academic performance diffusion through two social networks of different natures: friendship and study assistance. doi = 10.1371/journal.pone.0236737 id = cord-352564-2j4pjjwk author = Dominguez, Samuel R. title = Human Coronavirus HKU1 Infection of Primary Human Type II Alveolar Epithelial Cells: Cytopathic Effects and Innate Immune Response date = 2013-07-24 keywords = HCoV; HKU1; alveolar; cell summary = Because they are the natural target cells for respiratory virus infection, primary human respiratory epithelial cell cultures provide the ideal in vitro systems for investigation of cell factors required for growth of respiratory human viruses, for analysis of their interactions with viruses and their innate immune responses to infection, and for isolation and propagation of novel respiratory pathogens. Here we demonstrate that HCoV-HKU1 can infect and be serially propagated in primary human alveolar type II cells but not in alveolar type I-like cells or alveolar macrophages at the air-liquid interface. Titers of viral RNA in the wash from the apical surface of the cells were determined by qRT-PCR at the indicated time points, and HCoV-HKU1 Infection of Type II Alveolar Cells PLOS ONE | www.plosone.org cultures were fixed and immunolabeled with antibodies to the HCoV-HKU1 spike glycoprotein to identify infected cells. In summary, HCoV-HKU1 can infect, be serially propagated, and induce an anti-viral response in human alveolar type II cells maintained at an air-liquid interface. doi = 10.1371/journal.pone.0070129 id = cord-000959-nk2thkme author = Downer, Eric J. title = Identifying Early Inflammatory Changes in Monocyte-Derived Macrophages from a Population with IQ-Discrepant Episodic Memory date = 2013-05-06 keywords = LPS; TLR2; TLR4 summary = METHODS: This study explored the expression of receptors (CD11b, TLR2 and TLR4) on circulating monocyte-derived macrophages (MDMs) and peripheral blood mononuclear cells (PBMCs) isolated from healthy elderly adults who we classified as either IQ memory-consistent (high-performing, HP) or IQ memory-discrepant (low-performing, LP). The purpose of the study was to compare the expression of receptors (CD11b, TLR2 and TLR4) on circulating monocyte-derived macrophages (MDMs) and the response of these cells to LPS in samples prepared from the LP cohort and a cohort which we classified as IQ memory-consistent (high-performing, HP) individuals. P) TLR4 expression on CD11b + MDMs was increased in the LP group compared with the HP group (P,0.05) and this is also shown in the representative dot plots of TLR4 + cells ( and following LPS stimulation [6] , while pro-inflammatory cytokine [52] and chemokine [53, 54] levels are elevated in peripheral blood monocytes isolated from the elderly after LPS stimulation. doi = 10.1371/journal.pone.0063194 id = cord-354763-odzrco6q author = Drake, John M. title = Societal Learning in Epidemics: Intervention Effectiveness during the 2003 SARS Outbreak in Singapore date = 2006-12-20 keywords = SARS; learning; outbreak summary = We estimated that if societal learning had occurred at half the actual rate, the expected final size of the outbreak would have reached nearly 800 cases, more than three times the observed number of infections. We also retrospectively explore the effect of societal learning during the 2003 outbreak of SARS in Singapore, using weekly data on the time between onset of symptoms and removal of infectious individuals. Finally, we discuss societal and epidemiological factors that might affect societal learning, we observe that a difficult task during the early stages of an outbreak is to estimate the learning rate and suggest that the rate estimated here might be used as prior information in future outbreaks, and we conclude by recommending rapid investment in research at the time of initial detection when actions taken to reduce disease spread can be most efficient and cost effective. doi = 10.1371/journal.pone.0000020 id = cord-268524-lr51ubz5 author = Droit-Volet, Sylvie title = Time and Covid-19 stress in the lockdown situation: Time free, «Dying» of boredom and sadness date = 2020-08-10 keywords = covid-19; lockdown; time summary = This time experience was not explained by the levels of perceived stress or anxiety, although these were considerable, but rather by the increase in boredom and sadness felt in the lockdown situation. The aim of the present study was thus to conduct a scale survey on a large sample of an as yet untested population-French people-in order to assess not only the perceived stress related to Covid-19 but also the emotions (happiness, boredom, arousal) felt during as compared to before the lockdown and their links to the subjective experience of time. There is thus a risk in this period of pandemic that the chronic stress related to Covid-19 and its corollaries (anxiety, fear of death) are particularly high and therefore impact the subjective experience of time by speeding up the perceived passage of time. doi = 10.1371/journal.pone.0236465 id = cord-259771-653opx0h author = Dwivedi, Varun title = Biodegradable Nanoparticle-Entrapped Vaccine Induces Cross-Protective Immune Response against a Virulent Heterologous Respiratory Viral Infection in Pigs date = 2012-12-11 keywords = Nano; PRRSV; figure summary = In a pre-challenge study, intranasal delivery of Nano-KAg resulted in induction of innate immune response at both mucosal and systemic sites, indicated by a significant increase in the frequency of NK cells, DCs, and cd T cells in the lung MNC ( Figure 2 , A-C); and cd T cells and DCs in the PBMC compared to K-Ag vaccinated pigs (Figure 2, H & I) . Lung homogenates of Nano-KAg immunized pigs contained significantly higher levels of virus specific IgA and IgG antibodies compared to unvaccinated and K-Ag vaccinated, MN184 challenged pigs (Figure 4, A & B) . The frequency of cd T cells and CD4 + (but not CD8 + ) T cells in the lungs of Nano-KAg vaccinated animals were significantly increased compared to K-Ag and unvaccinated, virus challenged pigs ( Figure 5 , D, E & F). doi = 10.1371/journal.pone.0051794 id = cord-352720-z1cvjc2y author = Díaz-Corvillón, Pilar title = Routine screening for SARS CoV-2 in unselected pregnant women at delivery date = 2020-09-29 keywords = COVID-19; PCR; SARS summary = While initial evidence suggests that pregnant women were not at increased risk for COVID-19, neither developed a more severe disease compared to non-pregnant adults [3, 4] , recent reports suggest increased rates of preterm birth [5] , pneumonia and intensive care unit admission [6] , and maternal mortality [6, 7] . The main objective of this study was to assess point-prevalence of SARS CoV-2 infection in unselected obstetrical population at the time of delivery and to describe the presentation and clinical evolution of confirmed cases. women were screened for COVID-19 clinical symptoms including fever, cough and shortness of breath by trained personnel, and RT-PCR for SARS CoV-2 (Allplex TM 2019-nCoV Assay [17] ) was performed by nasopharyngeal swab, unless a prior test with no more than 48 hours to admission was reported. doi = 10.1371/journal.pone.0239887 id = cord-012967-w1oc0wdd author = Eberle, Jaelyn J. title = Using tooth enamel microstructure to identify mammalian fossils at an Eocene Arctic forest date = 2020-09-23 keywords = Coryphodon; Eocene; Formation; NUFV summary = doi = 10.1371/journal.pone.0239073 id = cord-319706-2e9jrv0s author = Ebinger, Joseph E. title = Pre-existing traits associated with Covid-19 illness severity date = 2020-07-23 keywords = SARS; african; covid-19; patient summary = For all patients considered to have Covid-19, based on direct or documented laboratory test result and suggestive signs and/or symptoms, we obtained information from the electronic health record (EHR) and verified data for the following demographic and clinical characteristics: age at the time of diagnosis; sex; race; ethnicity; smoking status defined as current versus prior, never, or unknown; comorbidities, including obesity, as clinically assessed and documented by a provider with ICD-10 coding; and, chronic use of angiotensin converting enzyme (ACE) inhibitor or angiotensin II receptor blocker (ARB) medications. For the primary outcome of illness severity, categorized by escalating levels of care (i.e., hospitalization, intensive care, intubation), the pre-existing characteristics that demonstrated statistical significance in age-and sex-adjusted models included older age, male sex, African American race, obesity, hypertension, diabetes mellitus, and the Elixhauser comorbidity score ( Table 2 ; Fig 3) . doi = 10.1371/journal.pone.0236240 id = cord-262345-hti1jjpn author = Eddy, Lucy H. title = The validity and reliability of observational assessment tools available to measure fundamental movement skills in school-age children: A systematic review date = 2020-08-25 keywords = FMS; MABC; Motor; TGMD; study summary = title: The validity and reliability of observational assessment tools available to measure fundamental movement skills in school-age children: A systematic review METHODS: A pre-search of ''fundamental movement skills'' OR ''fundamental motor skills'' in seven online databases (PubMed, Ovid MEDLINE, Ovid Embase, EBSCO CINAHL, EBSCO SPORTDiscus, Ovid PsycINFO and Web of Science) identified 24 assessment tools for school-aged children that: (i) assess FMS; (ii) measure actual motor competence and (iii) evaluate performance on a standard battery of tasks. The psychometric properties of observational assessments of fundamental movement skills for school children correlations to evaluate the concurrent validity between the MOT 4-6 and the KTK, with results showing moderate correlations for children aged 5-6 (mean r = .63), as was hypothesised prior to testing (r >. doi = 10.1371/journal.pone.0237919 id = cord-000868-vnwpzsu8 author = Eissmann, Kristin title = HIV-1 Fusion Is Blocked through Binding of GB Virus C E2D Peptides to the HIV-1 gp41 Disulfide Loop date = 2013-01-22 keywords = CD4; GBV; HIV-1 summary = doi = 10.1371/journal.pone.0054452 id = cord-323330-ghwhgkdm author = Ekundayo, Temitope Cyrus title = A global bibliometric analysis of Plesiomonas-related research (1990 – 2017) date = 2018-11-29 keywords = Plesiomonas; research; shigelloide summary = Here, we carried out a bibliometric survey that aimed to examine publication trends in Plesiomonas-related research by time and place, international collaborative works, identify gaps and suggest directions for future research. The articles were evaluated in terms of annual and country-specific output, theme, domain clusters, international collaboration networks, citations, topical evolution related to keywords and co-occurrence networks, co-authorship, and funding. We used the search term "Plesiomonas shigelloides" to identify primary research articles published between 1990 and 2017. Health emergencies (e.g., outbreaks of infection) relating to emerging viral pathogens including Zika and Chikungunya viruses have driven the generation of new scientific knowledge, resulting in a significant increase in the number of research articles on these subjects [68] . The United States and Sweden dominated the list of top 20 countries most actively researching Plesiomonas in terms of numbers of articles and citations. doi = 10.1371/journal.pone.0207655 id = cord-302529-43pd2qsp author = El Moussi, Awatef title = Virological Surveillance of Influenza Viruses during the 2008–09, 2009–10 and 2010–11 Seasons in Tunisia date = 2013-09-19 keywords = Influenza; Tunisia; virus summary = METHOD: We describe in this report the findings of laboratory-based surveillance of human cases of influenza virus and other respiratory viruses'' infection during three seasons in Tunisia. A subset of sentinel primary care physicians participating in virological surveillance schemes in the community submits respiratory samples for virological testing from patients presenting in primary health care with an ILI, as well as all regional emergency centres and hospitals that take on surveillance of influenza from community, hospitalized and fatal cases. Phylogenetic analysis of the HA1 nucleotid sequence of 23 influenza A(H1N1)pdm09 viruses from mild, severe (patients hospitalized with severe pneumonia and severe acute respiratory syndrome) and fatal cases, shows that all viruses characterised in Tunisia during season 2009-2010 were outside the seven genetic groups described in the European Centre for Disease Prevention and Control (ECDC) report [19] . doi = 10.1371/journal.pone.0074064 id = cord-312678-81gnmxbk author = Elayeh, Eman title = Before and after case reporting: A comparison of the knowledge, attitude and practices of the Jordanian population towards COVID-19 date = 2020-10-15 keywords = COVID-19; Jordan; knowledge; participant summary = Our research group initiated a study to ascertain the knowledge, attitude and practices (KAP) of Jordanians toward COVID-19 prior to any initial case report in Jordan. Therefore, the initial aim of this study was to evaluate the overall knowledge, attitude and practices (KAP) of Jordanian citizens to the ongoing international situation regarding the emergence and pandemic nature of COVID-19. where N is the sample size, Zα: type one error = 1.96 when α = 5%; Zβ: type two error = 1.28 when β = 10%; Q = 1-P: expected non-prevalence; P = proportion in the population possessing the characteristic of interest (based on the estimate that 50% of the respondents knew general information about COVID-19, its routes of transmission and the main preventative measures), d = one-half of the desired interval of confidence, in this study d = 5%. doi = 10.1371/journal.pone.0240780 id = cord-333248-5342lyeu author = Elenius, Varpu title = The relationship of serum vitamins A, D, E and LL-37 levels with allergic status, tonsillar virus detection and immune response date = 2017-02-24 keywords = LL-37; vitamin summary = We studied how their serum levels were associated with allergy status, intratonsillar/nasopharyngeal virus detection and intratonsillar expression of T celland innate immune response-specific cytokines, transcription factors and type I/II/III interferons in patients undergoing tonsillectomy. We studied how serum vitamins and antimicrobial peptide LL-37 levels and allergic and tonsillar diseases were associated with direct in vivo detection of respiratory viruses and T cell subset-related transcription factors, cytokines as well as type I, II and III interferons in tonsils. The associations of serum levels of vitamins and LL-37, allergy status and virus detection with intratonsillar cytokine and transcription factor expressions were analyzed using univariable and age-adjusted linear regression. This study provides new insights into connections between serum levels of vitamins A, D, and E and antimicrobial peptide LL-37 and several important outcomes: allergy, respiratory virus detection and tonsillar immune responses. doi = 10.1371/journal.pone.0172350 id = cord-004017-gcmpatlb author = Errecaborde, Kaylee Myhre title = Factors that enable effective One Health collaborations - A scoping review of the literature date = 2019-12-04 keywords = Health; collaboration; factor; process; report summary = The review identified 12 factors that support successful One Health collaborations and a coordinated response to health events across three levels: two individual factors (education & training and prior experience & existing relationships), four organizational factors (organizational structures, culture, human resources and, communication), and six network factors (network structures, relationships, leadership, management, available & accessible resources, political environment). In this study, a multidisciplinary team of researchers reviewed a broad scope of literature describing collaborative and multi-sectoral approaches to past health events to understand how such collaborations are commonly described and evaluated and to identify and synthesize enabling factors for One Health collaborations. Starting condition factors reported to enable collaboration at the network level included network structures, existing relationships, available resources in the face of a health event, and the political environment in place to support these efforts. doi = 10.1371/journal.pone.0224660 id = cord-306278-c4q4la5c author = Esposito, Susanna title = Epidemiology and Clinical Characteristics of Respiratory Infections Due to Adenovirus in Children Living in Milan, Italy, during 2013 and 2014 date = 2016-04-05 keywords = PCR; infection; respiratory summary = To evaluate the predominant human adenovirus (HAdV) species and types associated with pediatric respiratory infections, nasopharyngeal swabs were collected from otherwise healthy children attending an emergency room in Milan, Italy, due to a respiratory tract infection from January 1 to February 28 of two subsequent years, 2013 and 2014. To evaluate the circulation of the different HAdV types and the possible relationship between viral load, viral genetic characteristics, and the severity of infection, nasopharyngeal swabs were collected from otherwise healthy children consecutively attending the Emergency Room of the Fondazione IRCCS Ca'' Granda Ospedale Maggiore Policlinico, University of Milan, Italy, due to a respiratory tract infection. However, further studies are needed to identify the potential pathogenetic role of the different species and types of HAdV and the importance of viral load in the severity of infection. doi = 10.1371/journal.pone.0152375 id = cord-347014-88zmtky7 author = Esposito, Susanna title = Sensitivity and Specificity of Soluble Triggering Receptor Expressed on Myeloid Cells-1, Midregional Proatrial Natriuretic Peptide and Midregional Proadrenomedullin for Distinguishing Etiology and to Assess Severity in Community-Acquired Pneumonia date = 2016-11-15 keywords = CRP; PCT; cap summary = STUDY DESIGN: This study aimed to evaluate the diagnostic accuracy of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1), midregional proatrial natriuretic peptide (MR-proANP) and midregional proadrenomedullin (MR-proADM) to distinguish bacterial from viral community-acquired pneumonia (CAP) and to identify severe cases in children hospitalized for radiologically confirmed CAP. CONCLUSIONS: This study indicates that in children with CAP, sTREM-1, MR-proANP, and MR-proADM blood levels have poor abilities to differentiate bacterial from viral diseases or to identify severe cases, highlighting that PCT maintains the main role at this regard. A global evaluation of the results of this study seemed to indicate that in children with CAP, sTREM-1, MR-proANP, and MR-proADM blood levels are unable to differentiate bacterial from viral diseases or to identify severe cases. doi = 10.1371/journal.pone.0163262 id = cord-001120-fxd533b4 author = Everitt, Aaron R. title = Defining the Range of Pathogens Susceptible to Ifitm3 Restriction Using a Knockout Mouse Model date = 2013-11-21 keywords = Ifitm3; RSV; figure; infection; virus summary = We showed that Ifitm3 does not impact on the restriction or pathogenesis of bacterial (Salmonella typhimurium, Citrobacter rodentium, Mycobacterium tuberculosis) or protozoan (Plasmodium berghei) pathogens, despite in vitro evidence. Here we sought therefore to expand and define the role of Ifitm3 in pathogen restriction by assessing the susceptibility of Ifitm3-deficient (Ifitm3 -/-) mice to bacteria (Salmonella Typhimurium, Citrobacter rodentium, Mycobacterium tuberculosis), a parasite (Plasmodium berghei) and a virus (respiratory syncytial virus, RSV) to determine the specificity of this crucial antimicrobial protein. Similarly, bacterial counts revealed no significant differences between wild type and Ifitm3 -/-mice; together showing that Ifitm3 does not play a role in resistance or susceptibility to Salmonella infection. The experimental challenge revealed there to be no significant difference in phenotype seen in Ifitm3 -/-mice compared with wild type littermate controls, with both showing susceptibility to ECM ( Figure 5A ). doi = 10.1371/journal.pone.0080723 id = cord-002426-5e1xn7kj author = Falcón-Lezama, Jorge Abelardo title = Analysis of spatial mobility in subjects from a Dengue endemic urban locality in Morelos State, Mexico date = 2017-02-22 keywords = DENV; case; control summary = MATERIALS AND METHODS: We carried out a cohort-nested, case-control study with 126 individuals (42 cases, 42 intradomestic controls and 42 population controls) with the goal of describing human mobility patterns of recently Dengue virus-infected subjects, and comparing them with those of non-infected subjects living in an urban endemic locality. CONCLUSIONS: Results of this study show that human mobility in a small urban setting exceeded that considered by local health authority''s administrative limits, and was different between recently infected and non-infected subjects living in the same household. These observations provide important insights about the role that human mobility may have in Dengue virus transmission and persistence across endemic geographic areas that need to be taken into account when planning preventive and control measures. Sample: 126 individuals (42 cases, 42 intradomestic controls and 42 population controls) with age older than 12, and residents in Axochiapan, Morelos State, México, were selected from the cohort "Peridomestic infection as determinant for Dengue virus transmission" [13] . doi = 10.1371/journal.pone.0172313 id = cord-268977-hcg2rrhl author = Feikin, Daniel R. title = Etiology and Incidence of Viral and Bacterial Acute Respiratory Illness among Older Children and Adults in Rural Western Kenya, 2007–2010 date = 2012-08-24 keywords = ARI; HIV; Kenya; Lwak; PCR summary = METHODOLOGY/PRINCIPAL FINDINGS: From March 1, 2007, to February 28, 2010, among a surveillance population of 21,420 persons >5 years old in rural western Kenya, we collected blood for culture and malaria smears, nasopharyngeal and oropharyngeal swabs for quantitative real-time PCR for ten viruses and three atypical bacteria, and urine for pneumococcal antigen testing on outpatients and inpatients meeting a ARI case definition (cough or difficulty breathing or chest pain and temperature >38.0°C or oxygen saturation <90% or hospitalization). CONCLUSIONS/SIGNFICANCE: Vaccination against influenza and pneumococcus (by potential herd immunity from childhood vaccination or of HIV-infected adults) might prevent much of the substantial ARI incidence among persons >5 years old in similar rural African settings. Compared with other regions, the mortality rate among older children and adults remains several-fold higher in sub-Saharan Africa, where acute respiratory infections (ARI) are a leading cause of this high mortality, as well as associated morbidity [1] . doi = 10.1371/journal.pone.0043656 id = cord-000947-psguw47w author = Feng, Jianyu title = A Study of the Mechanism of the Chaperone-like Function of an scFv of Human Creatine Kinase by Computer Simulation date = 2013-04-24 keywords = HCK; peptide summary = We built the model of the single chain antibody (scFv-A4) that increased the stability of human creatine kinase (HCK) by the homology modeling method. Epitopes of human creatine kinase were predicted by computer and then the binding of scFv-A4 and HCK was modeled with computer. To elucidate why scFv-A4 had the chaperone-like function, we combined computer modeling and peptide array membrane technique to study the interactions between scFv-A4 and HCK. Firstly, bioinformatics software tools were used to predict the interacting sites between scFv-A4 and HCK and then the results were combined with the peptide array membrane experiment results to build the 3D models of the binding complex. In complex model-I, scFv-A4 exhibits chaperone-like function by assisting the folding of HCK and stabilizing the whole structure. In this study we combined computer modeling and the peptide array membrane method to investigate the interaction between scFv-A4 and HCK. doi = 10.1371/journal.pone.0062147 id = cord-294568-12eyo13f author = Fernandes-Matano, Larissa title = Prevalence of non-influenza respiratory viruses in acute respiratory infection cases in Mexico date = 2017-05-03 keywords = HRSV; infection; respiratory; virus summary = Influenza viruses are one of the main causative agents of ARIs worldwide; however, many other respiratory viruses for which insufficient epidemiological information is available can also cause ARIs. Studies performed at the international level have frequently identified human respiratory syncytial virus (HRSV), human parainfluenza virus (HPIV), influenza virus (flu), human mastadenovirus (HMdV), rhinovirus (RV), and enterovirus (EV) and less frequently identified human metapneumovirus (HMPV), primate bocaparvovirus (PBpV), and human coronavirus (HCoV) [12] . Therefore, the objective of this study was to determine the viral aetiology of these infections and to analyse the behaviour of non-influenza respiratory viruses in the Mexican population. The importance of the differential diagnosis of other respiratory viruses in samples with negative influenza results becomes apparent when we observe the prevalence of the three main viruses identified in this study as well as their associations with severe cases and deaths, especially in the child population. doi = 10.1371/journal.pone.0176298 id = cord-341914-l2bomgji author = Flies, Andrew S. title = Markedly Elevated Antibody Responses in Wild versus Captive Spotted Hyenas Show that Environmental and Ecological Factors Are Important Modulators of Immunity date = 2015-10-07 keywords = KLH; captive; hyena; immune; wild summary = Our results show that wild hyenas have significantly higher serum antibody concentrations, including total IgG and IgM, natural antibodies, and autoantibodies than do captive hyenas; there was no difference in the bacterial killing capacity of sera collected from captive and wild hyenas. The striking differences in serum antibody concentrations observed here suggest that complementing traditional immunology studies, with comparative studies of wild animals in their natural environment may help to uncover links between environment and immune function, and facilitate progress towards answering immunological questions associated with the hygiene hypothesis. A more robust understanding of the effects of ecological variables such as pathogen exposure on immune function might be gained by studying immune function in non-traditional species, and assessing how basic immune defenses differ between wild and captive animals with similar genetic backgrounds. doi = 10.1371/journal.pone.0137679 id = cord-000425-isw6jeir author = Flori, Laurence title = Immunity Traits in Pigs: Substantial Genetic Variation and Limited Covariation date = 2011-07-29 keywords = CD16; CD4; France; LPS; trait summary = A study on Yorkshire pigs selected for eight generations for high and low adaptive IR (HIR and LIR, respectively) on an index combining four standardized measures of specific antibodies and cellmediated IR, after stimulation with specific antigens (bacillus Calmette-Guérin and hen egg white lysozyme), has revealed that HIR and LIR animals differ in response to immunization and infection [2, 11, 12, 13, 14] . Finally, several significant QTLs for total leukocyte count ( [20, 21] ; Animal-QTLdb, http://www.animalgenome.org/cgi-bin/QTLdb/index), mitogen-induced proliferation [20] , antibody response [20, 22] , cytokine production (IL10 and IFNc) [23] , complement activity [22] , and acute phase protein serum concentration [22] have been detected and mapped to different pig chromosomes. In this report, we present the results of a global genetic study, combining principal component analysis (PCA), and genetic parameter estimation applied to a large number of innate and adaptive ITs in a pig population vaccinated against Mycoplasma hyopneumoniae (M. doi = 10.1371/journal.pone.0022717 id = cord-048364-yfn8sy1m author = Fraser, Christophe title = Estimating Individual and Household Reproduction Numbers in an Emerging Epidemic date = 2007-08-22 keywords = household; number summary = doi = 10.1371/journal.pone.0000758 id = cord-294645-yzh8h7zo author = Freeman, David W. title = Association between GDF15, poverty and mortality in urban middle-aged African American and white adults date = 2020-08-07 keywords = GDF15; cause; mortality; poverty summary = Multivariable adjusted Cox regression models were used to assess the association between log-transformed GDF15 (logGDF15) and 12-year mortality outcomes (all-cause, cardiovascularand cancer-specific outcomes) and interactions with sex, race and poverty status. The objectives of the present study were to assess the association between serum GDF15 and all-cause and cause-specific mortality, and to identify interactions between GDF15 and sex, race and poverty status in a large cohort of community-based middle-aged adults recruited from Baltimore, Maryland. In a community-dwelling cohort of younger urban adults (mean age 49.6) with diverse racial and socioeconomic status, we found that elevated serum GDF15 level was strongly associated with all-cause mortality, CVD-and cancer-specific mortality risk. Our findings of increased risk of mortality due to all-causes and CVD and elevated GDF15 levels in a diverse cohort are consistent with results of previous studies conducted in apparently healthy, community-dwelling adults [12-15, 17, 18] . doi = 10.1371/journal.pone.0237059 id = cord-353869-l53ms3q8 author = Friesen, Robert H. E. title = New Class of Monoclonal Antibodies against Severe Influenza: Prophylactic and Therapeutic Efficacy in Ferrets date = 2010-02-08 keywords = CR6261; H5N1; influenza; virus summary = METHODOLOGY/PRINCIPAL FINDINGS: We evaluated the prophylactic and therapeutic efficacy of the human monoclonal antibody CR6261 against lethal challenge with the highly pathogenic avian H5N1 virus in ferrets, the optimal model of human influenza infection. CONCLUSIONS/SIGNIFICANCE: These data demonstrate the prophylactic and therapeutic efficacy of this new class of human monoclonal antibodies in a highly stringent and clinically relevant animal model of influenza and justify clinical development of this approach as intervention for both seasonal and pandemic influenza. Mean decline in body weight at the end of the experiment was 6.2% in the group of ferrets that received CR6261 4 hours after challenge ( Figure 2B) , which was significantly less (p = 0.025) than the 10.1% observed in control animals. These findings were in accordance with the observation that the mean lung weights of ferrets treated with CR6261 at 4 hours post challenge were lower compared to the control group (5.7 g versus 14.9 g, p,0.001; Figure 2F ). doi = 10.1371/journal.pone.0009106 id = cord-344357-ocyaqs1y author = Fu, Yue-Qiang title = Effect of blood analysis and immune function on the prognosis of patients with COVID-19 date = 2020-10-30 keywords = CD3; CD4; COVID-19 summary = INTRODUCTION: This retrospective study investigated the implications of changes in blood parameters and cellular immune function in patients with Coronavirus Disease 2019 (COVID-19). The percentage of neutrophil count > 6.3×10 9 /L in death group was significantly higher than that in survival group, and multivariate logistic regression showed neutrophil count > 6.3×10 9 /L was independently associated with mortality. The percentage of neutrophil count > 6.3×10 9 /L in death group was significantly higher than that in survival group, and multivariate logistic regression showed neutrophil count > 6.3×10 9 /L was independently associated with mortality. Another study also indicated that COVID-19 patients in the death group had significantly lower lymphocyte count on admission than the recovered group [8] . Collected information included: age; gender; concomitant disease; symptoms; hemoglobin; platelet; leukocyte, neutrophil, and lymphocyte counts; CRP, CD3+, CD4+, CD8+, CD4/8, CD19+, and CD16+56+;IgG, IgM, IgA, IgE, C3, and C4 chest CT; alanine aminotransferase, creatinine; arterial blood gas; procalcitonin; and the result of the RT-PCR assay of SARS-CoV-2 RNA. doi = 10.1371/journal.pone.0240751 id = cord-257077-cdnkk6ou author = Gabor, Kristin A. title = Super Resolution Microscopy Reveals that Caveolin-1 Is Required for Spatial Organization of CRFB1 and Subsequent Antiviral Signaling in Zebrafish date = 2013-07-09 keywords = CRFB1; FPALM; IFN; SHRV; figure summary = doi = 10.1371/journal.pone.0068759 id = cord-311065-ie3gty6e author = Gaddi, Pamela J. title = IL-10 Mediated Regulation of Liver Inflammation during Acute Murine Cytomegalovirus Infection date = 2012-08-03 keywords = CD8; IL-10; MCMV summary = Further work has described a role for IL-10 in reducing systemic IFN-c production, CD4+ and CD8+ T cell cytokine responses and viral elimination in the spleen during MCMV infection [28] . The absence of IL-10 during acute MCMV infection results in elevated levels of systemic and local proinflammatory cytokines and chemokines, as well as increased inflammatory cell infiltration into infected livers. MCMV infection in the liver results in increased infiltration of NK cells, T cells and macrophages that contribute to viral clearance through cytokine and chemokine production [20, 23, 27, [38] [39] [40] . Virus-specific CD8+ T cells are recruited to the liver within 4 days of infection and control viral replication through release of cytotoxic molecules and production of cytokines such as IFN-c and TNF-a [18, [21] [22] [23] 26] . doi = 10.1371/journal.pone.0042850 id = cord-000265-llilwq1u author = Gao, Rongbao title = A Systematic Molecular Pathology Study of a Laboratory Confirmed H5N1 Human Case date = 2010-10-12 keywords = H5N1; PCR; RNA; virus summary = Autopsy studies have shown that human highly pathogenic avian influenza virus (H5N1) can infect multiple human organs other than just the lungs, and that possible causes of organ damage are either viral replication and/or dysregulation of cytokines and chemokines. Although H5N1 virus infection of humans is primarily one of the lower respiratory tract, more recent reports suggested that influenza A H5N1 may in rare, severe cases, disseminate beyond the lungs and infect brain [26, 27] , intestines [20, 27] and lymphoid tissues [27] , and result in extra-pulmonary clinical manifestations including encephalopathy or encephalitis [15, 28] . To better understand the pathogenesis of human H5N1 virus infection, and investigate the route of virus dissemination in vivo, we report on the use of different techniques to detect virus distribution and infection of 5 organ systems in a laboratory confirmed fatal human H5N1 virus infection, and analyze the relationship between viral load in tissues and host response. doi = 10.1371/journal.pone.0013315 id = cord-000554-p4ufea6x author = Gao, Wei title = Distinct Regulation of Host Responses by ERK and JNK MAP Kinases in Swine Macrophages Infected with Pandemic (H1N1) 2009 Influenza Virus date = 2012-01-18 keywords = ERK1/2; Fig; IFN; JNK1/2 summary = title: Distinct Regulation of Host Responses by ERK and JNK MAP Kinases in Swine Macrophages Infected with Pandemic (H1N1) 2009 Influenza Virus We have also observed cross-talk between MAP kinase and NFkB pathways, and our data indicate that MAP kinase ERK1/2 and JNK1/2 may impact the activation of NFkB through the induction of RIG-1, leading to IFN-b induction in H1N1pdm-infected swine macrophages. To understand the mechanism of proinflammatory cytokine and TNF family ligand induction in H1N1pdm-infected swine macrophages, we investigated how MAP kinases were activated and whether their signaling pathways were involved in the regulation of various cytokines and TNF family ligands in pig immune cells. To evaluate the role of MAP kinases in the regulation of proinflammatory cytokine responses in H1N1pdm-infected swine macrophages, we pre-treated 3D/4 cells with specific inhibitors for ERK1/2, p38, and JNK1/2 1 hr prior to infection. doi = 10.1371/journal.pone.0030328 id = cord-339578-eg19rfvi author = Garcia-Garcia, Maria Luz title = Role of viral coinfections in asthma development date = 2017-12-05 keywords = RSV; asthma; infection summary = OBJECTIVE: Our aim was to compare the frequency of asthma development at 6–8 years in children with previous admission for bronchiolitis associated with single versus double or multiple viral infection. CONCLUSIONS: Asthma at 6–8 years is more frequent and severe in those children previously hospitalized with viral coinfection-bronchiolitis compared with those with single infection. Of the 351 children previously admitted with bronchiolitis, with positive viral detection and current age between 6 and 8 years, 244 (52 coinfections and 192 single infections) could be located and agreed to participate in the study. In conclusion, asthma at the age of 6-8 is more frequent and severe in those children previously hospitalized with viral coinfection bronchiolitis compared with those with single infection. Moreover, viral coinfection, allergic rhinitis and older age at admission seem also to be strong independent risk factors for asthma development in children previously hospitalised because of bronchiolitis. doi = 10.1371/journal.pone.0189083 id = cord-278087-0nicp0eq author = García-García, María Luz title = Human metapnuemovirus infections in hospitalized children and comparison with other respiratory viruses. 2005-2014 prospective study date = 2017-03-16 keywords = HMPV; HRSV summary = doi = 10.1371/journal.pone.0173504 id = cord-267042-nvwnbp2j author = Gaspard, Philippe title = Gastroenteritis and respiratory infection outbreaks in French nursing homes from 2007 to 2018: Morbidity and all-cause lethality according to the individual characteristics of residents date = 2019-09-24 keywords = LOS; RTI; flu+ summary = This study aimed to describe GE and RTI outbreaks with infection and all-cause lethality rates according to the individual characteristics of nursing home residents. In MH stratified analysis (virus, sex (female/male)) adjusted for LOS (<4 or ≥4 years), the odds of being infected remained significant among older residents (≥86 years): NoV+/male (Odds ratio (OR(MH)): 1.64, 95% confidence interval (CI): 1.16–2.30) and Flu+/female and male (respectively OR(MH): 1.50, CI: 1.27–1.79 and 1.73, CI: 1.28–2.33). Our objective was to describe GE and RTI infection and all-cause lethality rates according to the individual characteristics of nursing home residents (sex, age, length of stay, autonomy status), and to identify specific susceptibility patterns related to these types of viral outbreaks in these facilities. In the present study, surveillance data obtained during GE and RTI outbreaks in nursing homes were used to construct stratified analyses and to identify specific infection and all-cause lethality rates according to the residents'' individual characteristics. doi = 10.1371/journal.pone.0222321 id = cord-336843-c0sr3six author = Gerritsen, M. G. title = Improving early diagnosis of pulmonary infections in patients with febrile neutropenia using low-dose chest computed tomography date = 2017-02-24 keywords = CXR; IFD; LDCT summary = title: Improving early diagnosis of pulmonary infections in patients with febrile neutropenia using low-dose chest computed tomography We performed a prospective study in patients with chemotherapy induced febrile neutropenia to investigate the diagnostic value of low-dose computed tomography compared to standard chest radiography. Two studies comparing LDCT to CXR in patients with persistent febrile neutropenia demonstrated an increased detection of pulmonary abnormalities. The diagnosis of possible IFD in the patient with a negative LDCT scan was based on abnormalities on HRCT made on day 4 of fever. We conducted a prospective study to evaluate whether pulmonary focus detection would improve using a LDCT scan instead of CXR on the first day of febrile neutropenia. [3] In a retrospective study 1083 adult SCT patients were evaluated, but in none of the 242 CXRs performed in asymptomatic patients with febrile neutropenia pulmonary abnormalities indicative of infection were detected. doi = 10.1371/journal.pone.0172256 id = cord-000347-gdra8xhj author = Gibbons, Henry S. title = Genomic Signatures of Strain Selection and Enhancement in Bacillus atrophaeus var. globigii, a Historical Biowarfare Simulant date = 2011-03-25 keywords = ATCC; Camp; Detrick; bacillus; figure; isolate; strain summary = doi = 10.1371/journal.pone.0017836 id = cord-001716-lbtdex4p author = Gilca, Rodica title = Mid-Season Estimates of Influenza Vaccine Effectiveness against Influenza A(H3N2) Hospitalization in the Elderly in Quebec, Canada, January 2015 date = 2015-07-22 keywords = A(H3N2; Canada summary = Canada''s Sentinel Physician Surveillance Network (SPSN) measured vaccine effectiveness (VE) against medically-attended laboratory-confirmed outpatient A(H3N2) illness of -8% (95%CI:-50-23%) overall and 2% (95%CI:-49-36%) in non-elderly (<65-year-old) adults, indicating little or no vaccine protection even among individuals capable of mounting an effective immune response [2] . Although Canadian mid-season inpatient and outpatient VE findings for the 2014/15 season have been consistent with null vaccine effects (statistically non-significant and spanning zero) in both age groups, the CIRN finding of a lower and negative point estimate of VE against A(H3N2) hospitalization in the elderly, more closely broaching statistical significance, warrants further clarification. Multivariable analyses by logistic regression adjusted for age, underlying comorbidity placing individuals at higher risk of influenza-related complications [13] , interval between symptom onset and specimen collection (4 days, 5-7 days), hospital site, epidemic week based on hospital admission date (49-51, 52, 53 and 1-2), and primary residence (community, LTCF or other institutional/group setting). doi = 10.1371/journal.pone.0132195 id = cord-291176-evb6yt0r author = Giorgi Rossi, Paolo title = Characteristics and outcomes of a cohort of COVID-19 patients in the Province of Reggio Emilia, Italy date = 2020-08-27 keywords = SARS; covid-19; patient summary = In this report, based on the cohort of all residents in the province of Reggio Emilia who were SARS-CoV-2-positive at nasal and pharyngeal swab and with symptoms (COVID-19 cases) since the inception of the epidemic, we describe patient characteristics and explore their role as putative prognostic factors in predicting the occurrence of hospital admission or death. We considered the following patient characteristics: age, sex, place of birth (Italy or abroad), time span (in days) from symptom onset to diagnosis/ hospitalization, and comorbidities, whose prognostic role was explored both singly (chronic obstructive pulmonary disease, arrhythmia, diabetes, coronary heart disease, heart failure, vascular diseases, obesity) and by computing the Charlson Comorbidity Index, which provides an overall measure of an individual patient''s complexity [12] . While in this study we focused on the risk of hospitalization and death in a cohort of COVID-19 patients diagnosed during the epidemic in Northern Italy, it also provided us with the opportunity to describe the pattern of distribution of the disease in the whole population. doi = 10.1371/journal.pone.0238281 id = cord-316047-d9cpe9yl author = Gonzalez, T. title = Influence of COVID-19 confinement on students’ performance in higher education date = 2020-10-09 keywords = Fig; covid-19; student; test summary = doi = 10.1371/journal.pone.0239490 id = cord-277357-lpurk7pe author = González-González, Everardo title = Portable and accurate diagnostics for COVID-19: Combined use of the miniPCR thermocycler and a well-plate reader for SARS-CoV-2 virus detection date = 2020-08-13 keywords = COVID-19; PCR; SARS summary = title: Portable and accurate diagnostics for COVID-19: Combined use of the miniPCR thermocycler and a well-plate reader for SARS-CoV-2 virus detection Here, we demonstrate the use of the miniPCR, a commercial compact and portable PCR device recently available on the market, in combination with a commercial well-plate reader as a diagnostic system for detecting genetic material of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causal agent of COVID-19. Combined use of the miniPCR thermocycler and a well-plate reader for SARS-CoV-2 virus detection containing the amplification products of each one of three experiments, where the three different sets of primers (namely N1, N2, and N3) were used to amplify the same range of concentrations of template. Combined use of the miniPCR thermocycler and a well-plate reader for SARS-CoV-2 virus detection others), we observe differences in the performance of each primer pair. doi = 10.1371/journal.pone.0237418 id = cord-324091-nljd2ok1 author = Gordon, Jennifer L. title = The psychological impact of fertility treatment suspensions during the COVID-19 pandemic date = 2020-09-18 keywords = health; impact; treatment summary = PURPOSE: To examine the psychological impact of fertility treatment suspensions resulting from the COVID-19 pandemic and to clarify psychosocial predictors of better or worse mental health. Participants completed a battery of questionnaires assessing depressive symptoms, perceived mental health impact, and change in quality of life related to treatment suspensions. Table 2 depicts the correlation between three personality traits (trait optimism, defensive pessimism, and intolerance of uncertainty) that were considered potentially relevant under the current circumstances, in relation to the overall change in quality of life and the mental health impact attributed to fertility treatment suspensions. The psychological impact of fertility treatment suspensions during the COVID-19 pandemic the final subscales are as follows: 1) avoidance, α = 0.82, 2) active coping, α = 0.71, 3) finding meaning, α = 0.72, 4) defensive pessimism, α = 0.66, 5) optimism, α = 0.80, 6) seek social support, α = 0.77, and 7) behavioural engagement, α = 0.67. doi = 10.1371/journal.pone.0239253 id = cord-000478-88wo4xen author = Gowen, Brian B. title = Use of Recombinant Adenovirus Vectored Consensus IFN-α to Avert Severe Arenavirus Infection date = 2011-10-24 keywords = DEF201; IFN; PICV summary = Intranasal administration of DEF201 24 h prior to challenge with Pichindé virus (PICV) was highly effective at protecting animals from mortality and preventing viral replication and liver-associated disease. Interestingly, the 10 7 and 10 8 pfu DEF201 groups presented with little to no day-7 virus burden in the serum, liver, or spleen, while the 10 6 group developed viral titers that were comparable to the rAd EV and placebo controls ( Figure 2B-D) . This may not be the case with hamsters treated with DEF201 24 h prior to challenge since most had no detectable virus titers in spleen, liver, or serum on day 7 of PICV infection ( Figure 2B-D) . Animals were treated i.n. with a single dose 10 8 pfu of DEF201, the rAd EV control virus, or PBS placebo 7 or 14 days prior to PICV infection. doi = 10.1371/journal.pone.0026072 id = cord-340656-ltd6ueoi author = Grant, Michael C. title = The prevalence of symptoms in 24,410 adults infected by the novel coronavirus (SARS-CoV-2; COVID-19): A systematic review and meta-analysis of 148 studies from 9 countries date = 2020-06-23 keywords = COVID-19; SARS; clinical summary = title: The prevalence of symptoms in 24,410 adults infected by the novel coronavirus (SARS-CoV-2; COVID-19): A systematic review and meta-analysis of 148 studies from 9 countries Furthermore, with few included studies (30 in the largest and most recent [12] ), the range of symptoms were limited and the estimates of prevalence are likely to be upwardly biased because only unwell patients (largely those admitted to hospital) were tested in the early phase of the outbreak. We excluded case reports, articles which failed to disaggregate symptoms in adult and paediatric cohorts, studies of patients with prior respiratory infections (e.g. tuberculosis) or co-infections with other viruses (e.g. similar viruses SARS-CoV-1 or HCoV-EMC/2012, etc) and articles which we are unable to translate to English in a timely fashion. Clinical characteristics of laboratory confirmed positive cases of SARS-CoV-2 infection in Wuhan, China: A retrospective single center analysis Epidemiological, clinical and virological characteristics of 74 cases of coronavirus-infected disease 2019 (COVID-19) with gastrointestinal symptoms doi = 10.1371/journal.pone.0234765 id = cord-002957-gw2cow0d author = Gray, Darren W. title = DIVA metabolomics: Differentiating vaccination status following viral challenge using metabolomic profiles date = 2018-04-05 keywords = UPLC; animal; bpi3v; day; vaccinated summary = doi = 10.1371/journal.pone.0194488 id = cord-262846-1mhimfsf author = Gray, Nicholas title = Is “no test is better than a bad test”? Impact of diagnostic uncertainty in mass testing on the spread of COVID-19 date = 2020-10-21 keywords = population; test; testing summary = This strategy would involve detecting those who have successfully overcome the virus, and are likely to have some level of immunity (or at least reduced susceptibility to more serious illness if they are infected again), so are relatively safe to relax their personal lockdown measures. To explore the effect of imperfect testing on the disease dynamics when strategies testing regimes are employed to relax lockdown measures, three new classes were added to the model. implement quarantine in their model but do not incorporate the effects on the dynamics from imperfect testing, nor do they consider how the quality and scale of an available test affect the spread of a disease. Wide-scale screening for antibodies in the general population promises significant scientific value, and targeted antibody testing is likely to have value for reducing risks to NHS and care-sector staff, and other key workers who will need to have close contact with COVID-19 sufferers. doi = 10.1371/journal.pone.0240775 id = cord-000501-qz68gtd4 author = Greatorex, Jane S. title = Survival of Influenza A(H1N1) on Materials Found in Households: Implications for Infection Control date = 2011-11-22 keywords = PR8; surface; virus summary = METHODOLOGY AND PRINCIPAL FINDINGS: Influenza A/PuertoRico/8/34 (PR8) or A/Cambridge/AHO4/2009 (pandemic H1N1) viruses were inoculated onto a wide range of surfaces used in home and work environments, then sampled at set times following incubation at stabilised temperature and humidity. The potential for transmission of influenza by indirect contact (i.e. via fomites) is linked to the ability of virus to survive in transmissible titres on commonly touched surfaces; however few data exist on this subject. We evaluate the survival of influenza A (H1N1) viruses deliberately applied to a range of commonly touched household and workplace surfaces, using RT-PCR for genome detection and culture methods to determine viability. Our data are consistent with recent findings from a study of environmental deposition of pandemic H1N1 virus in the homes of infected patients, involving our laboratory, when almost 10% of tested surfaces yielded viable virus [15] . doi = 10.1371/journal.pone.0027932 id = cord-285546-5tjhdczt author = Green, Manfred S. title = The confounded crude case-fatality rates (CFR) for COVID-19 hide more than they reveal—a comparison of age-specific and age-adjusted CFRs between seven countries date = 2020-10-21 keywords = CFR; age summary = title: The confounded crude case-fatality rates (CFR) for COVID-19 hide more than they reveal—a comparison of age-specific and age-adjusted CFRs between seven countries BACKGROUND: Crude case-fatality rates (CFRs) for COVID-19 vary widely between countries. We examined how the age distribution of the cases is responsible for the COVID-19 CFR differences between countries. METHODS: COVID-19 cases and deaths, by ten-year age-groups, were available from the reports of seven countries. The age-adjusted CFRs were computed by the direct method, using the combined number of cases in all seven countries in each age group as the standard population. CONCLUSIONS: The age structure of the cases explains much of differences in the crude CFRs between countries and adjusting for age substantially reduces this variation. The age-specific number of cases, number of deaths and the crude CFRs by country are given in Table 1 . doi = 10.1371/journal.pone.0241031 id = cord-294372-pec1886j author = Greene, Dina N. title = Decreasing median age of COVID-19 cases in the United States—Changing epidemiology or changing surveillance? date = 2020-10-15 keywords = SARS summary = Result distributions by age and positivity were compared between early period (March-April 2020) and late periods (June-July 2020) of the COVID-19 pandemic. Overall, this suggests that observed age-related trends are driven by changes in testing patterns rather than true changes in the epidemiology of SARS-CoV-2 infection. In the United States, surveillance data suggest that mean age of infected patients is decreasing compared to the early stages of the COVID-19 pandemic. We used SARS-CoV-2 testing data from a national reference laboratory to characterize the age distribution of detected cases between March and July of 2020. Surveillance data in the United States have shown a trend toward decreasing age among persons with laboratory-confirmed SARS-CoV-2 infection. This study found a similar pattern among patients tested by a national reference laboratory, with the median age among patients testing positive being five years lower in June and early July compared to March and April. doi = 10.1371/journal.pone.0240783 id = cord-280846-bbv6f5gf author = Greninger, Alexander L. title = A Metagenomic Analysis of Pandemic Influenza A (2009 H1N1) Infection in Patients from North America date = 2010-10-18 keywords = Fig; H1N1; PCR; Virochip; read; sample summary = To determine whether a pan-viral microarray assay was capable of identifying novel 2009 H1N1 in the absence of a priori sequence information, we used the Virochip to comprehensively screen for viruses in 29 nasopharyngeal swab samples from individuals with influenza-like illness. To further characterize the metagenomics of 2009 H1N1 infection in humans, we labeled the 17 influenza samples positive for 2009 H1N1 by Virochip with distinct molecular barcodes and analyzed them by paired-end deep sequencing on three lanes of an Illumina Genome Analyzer IIx. After trimming reads to remove barcodes and exclude low-complexity or primer sequences, 11,427,212 high-quality 60-bp sequence reads were subjected to an iterative BLASTN analysis pipeline (Fig. 1B) . After stratifying by originating location and corresponding method of sample processing (pre-DNase and/or post-DNase treatment), the percentage of total reads aligning to influenza was linearly correlated with calculated viral titers by realtime quantitative RT-PCR for sites in the United States (California) and Canada but not in Mexico (Fig. 5A ). doi = 10.1371/journal.pone.0013381 id = cord-340763-cxnu9g8y author = Grimm, Sebastian K. title = Directed Evolution of a Yeast-Displayed HIV-1 SOSIP gp140 Spike Protein toward Improved Expression and Affinity for Conformational Antibodies date = 2015-02-17 keywords = Fig; HIV; HIV-1; SOSIP summary = title: Directed Evolution of a Yeast-Displayed HIV-1 SOSIP gp140 Spike Protein toward Improved Expression and Affinity for Conformational Antibodies Because the intrinsic instability and complexity of this trimeric glycoprotein has greatly impeded the development of immunogens that properly represent the structure of native envelope, this platform addresses an essential need for methodologies with the capacity to rapidly engineer HIV spike proteins towards improved homogeneity, stability, and presentation of neutralizing epitopes. The rationally designed d-SOSIP variant and a mutant with disrupted CD4 binding site (CD4bs)-specific Ab binding (d-SOSIP D368R) were displayed as Aga2 fusion proteins on yeast ( Fig. 2A ), and compared for display level and binding to a panel of HIV bnAbs together with the well-characterized and folded YU2 gp120 core [47] and an unrelated viral envelope protein (E2) derived from Hepatitis C virus (HCV E2) as positive and negative controls Fig. 2) . doi = 10.1371/journal.pone.0117227 id = cord-333522-zsdymkjd author = Gruse, Jeannine title = Quercetin Feeding in Newborn Dairy Calves Cannot Compensate Colostrum Deprivation: Study on Metabolic, Antioxidative and Inflammatory Traits date = 2016-01-11 keywords = Fig; calf; colostrum; day; feed summary = Blood samples were taken repeatedly to measure plasma concentrations of flavonols, glucose, lactate, total protein, albumin, urea, non-esterified fatty acids, triglycerides, cholesterol, insulin, glucagon, cortisol, immunoglobulins, fibrinogen, haptoglobin and serum amyloid A. Basal blood samples were taken before the morning feeding on days 1, 2, 4 and 7 from the jugular vein using evacuated tubes containing either potassium-EDTA (1.2-2 mg/mL EDTA) for analyses of plasma metabolites, insulin, glucagon, immunoglobulins and acute-phase proteins or Li-heparin (12-30 IU heparin) for the determination of the cortisol and flavonol concentrations and the antioxidative status in the plasma. Feed intake, body temperature, heart and respiratory rate and plasma concentrations of metabolites, hormones, flavonols and markers of antioxidative status were analyzed by repeated measurement ANOVA using the MIXED procedure of SAS/STAT software and a model with the fixed factors diet, quercetin and day of life (repeated variable) and all interactions between the fixed factors. doi = 10.1371/journal.pone.0146932 id = cord-319675-mwy3t1ny author = Gu, Li title = Sustained Viremia and High Viral Load in Respiratory Tract Secretions Are Predictors for Death in Immunocompetent Adults with Adenovirus Pneumonia date = 2016-08-17 keywords = respiratory; viral summary = At admission (on day 5–7 after illness onset), the patients in fatal cases presented higher initial viral loads in respiratory tract secretions (8.578 ± 2.115 vs 6.263 ± 1.225 Log(10) copies/ml, p = 0.023). Our results suggest that a higher initial viral load (10 8 copy/ml) in the respiratory tract samples on day 5-7 after disease onset is a predictor for fatal clinical outcome. In one case, as shown in Fig 2, even though the patient presented with a higher viral load (10 8.32 copies / ml) in tracheal aspiration, which may be associated fatal outcome, his clinical manifestation recovered gradually with a downward trend in the viral load in respiratory tract and whole blood samples. A higher initial viral load (10 8 copy/ml) in the respiratory tract on day 5-7 after disease onset and sustained viremia for 2 weeks or more may be associated with fatal clinical outcomes. doi = 10.1371/journal.pone.0160777 id = cord-322827-h33su548 author = Guan, Lili title = Unlocking Patients with Mental Disorders Who Were in Restraints at Home: A National Follow-Up Study of China’s New Public Mental Health Initiatives date = 2015-04-07 keywords = China; Program summary = BACKGROUND: In 2005, China implemented a demonstration program known as "686" to scale-up nation-wide basic mental health services designed to improve access to evidence-based care and to promote human rights for people with severe mental disorders. This program has contributed to improving care for patients with severe mental disorders, including schizophrenia, psychosis, bipolar disorder and schizoaffective disorder, through increasing access to treatment and integrating hospital and community services designed to provide continuity of evidence-based care and to address patients'' rights. Patients with severe mental disorders were followed-up about their medication adherence, mental health status, social functioning and family burden in 2009 and 2012 to investigate the changes over time following the unlocking efforts. The finding that more than 92% of those unlocked and entered into continuous treatment by the 686 Program remained free of restraints by 2012 demonstrates the feasibility of improving the human rights of persons with severe mental illness by increasing access to mental health care in the community [22] , even with limited societal resources. doi = 10.1371/journal.pone.0121425 id = cord-000237-mticfoic author = Guan, Xuhua title = Pneumonia Incidence and Mortality in Mainland China: Systematic Review of Chinese and English Literature, 1985–2008 date = 2010-07-23 keywords = China; pneumonia; year summary = We conducted a systematic review of the Chinese-and Englishlanguage literature in order to describe pneumonia incidence and mortality in China, evaluate the quality of published studies, and identify gaps in the literature that can be addressed through surveillance and epidemiologic research projects in the future. Based on published recommendations for measuring quality of epidemiologic studies of pneumonia [15] , we assessed quality using the following six criteria: (1) geographic location was reported, (2) study was conducted for a period of at least one year or multiples of one year to account for seasonal factors, (3) site of case detection or surveillance location was reported, (4) age and population size of cohort of at least 50 cases were reported, (5) quality assurance and monitoring methods were employed to assure that data was complete and high quality, and (6) a clearly defined case definition (e.g., not based solely on clinical diagnosis) was used and reported. In children aged ,5 years, the highest mortality rates were reported by four studies that were each conducted in multiple regions throughout mainland China (9.55±14.40 deaths from pneumonia per 1,000 live births; Table S3 ) [21, 23, 38, 48] . doi = 10.1371/journal.pone.0011721 id = cord-272971-9luzvzsu author = Guo, Hainan title = Hong Kong Hospital Authority resource efficiency evaluation: Via a novel DEA-Malmquist model and Tobit regression model date = 2017-09-08 keywords = DEA; GSBUP; HKHA; Hospital summary = doi = 10.1371/journal.pone.0184211 id = cord-001734-bbeznd3r author = Gupta, Garvita title = NMR and MD Studies Reveal That the Isolated Dengue NS3 Protease Is an Intrinsically Disordered Chymotrypsin Fold Which Absolutely Requests NS2B for Correct Folding and Functional Dynamics date = 2015-08-10 keywords = Fig; HSQC; NMR; NS2B; NS3pro summary = Taken together, CD and NMR results define the 172-residue NS3pro domain to be an intrinsically disordered protein which is lacking of both stable secondary and tertiary structures in the absence of the NS2B cofactor [22, [31] [32] [33] [34] [35] [36] . On the other hand, only a small set of broad peaks could be detected in its HSQC spectrum (Fig 4B) , indicating that the NS3B (1-130) in the LMPC micelle undergoes significant conformational exchanges on μs-ms time scale, or/and dynamic aggregation, which thus prevents from further high-resolution NMR studies. Interestingly, although NMR characterization deciphers that the NS3pro domains have different dynamics on the μs-ms time scale in the contexts of being complexed with NS (48-100) in buffer and with NS2B (1-130) in the LMPC micelle, they have very similar enzymatic activities. doi = 10.1371/journal.pone.0134823 id = cord-303034-w72oeoxq author = Haischer, Michael H. title = Who is wearing a mask? Gender-, age-, and location-related differences during the COVID-19 pandemic date = 2020-10-15 keywords = COVID-19; United; mask summary = To understand the demographics of mask wearers and resistors, and the impact of mandates on mask-wearing behavior, we observed shoppers (n = 9935) entering retail stores during periods of June, July, and August 2020. Wearing a mask in public is currently a controversial and politicized issue in the United States, even with case evidence from other countries that face coverings help to control the spread of coronavirus disease 2019 (COVID-19) [1] . To facilitate greater understanding and reliable experimental data on whether gender, age, location, and the presence of mask mandates influence mask wearing in the United States, we conducted a direct observational study at retail stores in Wisconsin. It is not surprising that our June data showed that older individuals wear masks more than middle-age and young people because older adults are at higher risk for more severe cases of COVID-19. doi = 10.1371/journal.pone.0240785 id = cord-338067-vjyad10p author = Hao, Yan title = Prediction and analysis of Corona Virus Disease 2019 date = 2020-10-05 keywords = LSTM; SVM; case summary = In this study, the development trend analysis of the cumulative confirmed cases, cumulative deaths, and cumulative cured cases was conducted based on data from Wuhan, Hubei Province, China from January 23, 2020 to April 6, 2020 using an Elman neural network, long short-term memory (LSTM), and support vector machine (SVM). In the present study, three methods, namely, an Elman neural network, LSTM, and SVM are applied to predict and analyze COVID-19 data from January 23, 2020 to April 6, 2020 in Wuhan, Hubei Province, China, including cumulative confirmed cases, confirmed new cases, cumulative deaths, new deaths, and cumulative cured cases and new cured cases. Experimental results showed that the Elman neural network and SVM adopted in this study can accurately predict the development trend of COVID-19, whereas LSTM is more suitable for the prediction of cumulative confirmed cases. doi = 10.1371/journal.pone.0239960 id = cord-322414-dpx191xh author = Harke, Nina N. title = To defer or not to defer? A German longitudinal multicentric assessment of clinical practice in urology during the COVID-19 pandemic date = 2020-09-15 keywords = April; COVID-19; March summary = MATERIAL AND METHODS: An email was sent to 66 urological hospitals with focus on robotic surgery (RS) including a link to a questionnaire (e.g. bed/staff capacity, surgical caseload, protection measures during RS) that covered three time points: a representative baseline week prior to COVID-19, the week of March 16(th)-22(nd) and April 20(th)-26(th) 2020. The complete survey (S1 File) included detailed queries on numbers of available hospital beds and operating room (OR) capacity, staff members, surgical caseloads with subcategorization of surgeries at three different time points: week 1) baseline week that portrays the numbers of a regular/representative week before the outbreak of COVID-19, week 2) March 16 th to 22 nd 2020 which represent the first week after the lockdown in Germany (confirmed cases in Germany on March 16 th 2020: 6,012 with 13 deaths) and week 3) April 20 th to 26 th (confirmed cases in Germany on April 20 th 2020: 141,672; 4,404 deaths and approximately 91,500 recovered) [1] . doi = 10.1371/journal.pone.0239027 id = cord-352403-4591ewsa author = Hartwig, Stacey M. title = Depletion of Alveolar Macrophages Ameliorates Virus-Induced Disease following a Pulmonary Coronavirus Infection date = 2014-03-07 keywords = CD4 summary = In addition, a significant increase in the frequency and total number of Tregs in the lung tissue and lung airways was observed following MHV-1 infection in mice depleted of AM. We have previously shown that intranasal MHV-1 infection of C3H/HeJ mice, which harbor a natural mutation in the gene that encodes toll-like receptor 4 (TLR4) [15, 16] , results in increased morbidity and mortality along with severe pulmonary disease as compared to the wild-type C3H/HeN mice [17] . We observed a significant (p,0.05) decrease in the total number of MHV-1-specific IFN-c-producing CD4 T cells in the BAL of CL-treated mice as compared to PBS controls ( Figure 4C ). We also observed a significant increase in the total number and frequency of Tregs following MHV-1 infection in both the airways and lung tissue of the CL-treated mice. doi = 10.1371/journal.pone.0090720 id = cord-278123-mq56em3z author = Hasan, Mohammad Rubayet title = Detection of SARS-CoV-2 RNA by direct RT-qPCR on nasopharyngeal specimens without extraction of viral RNA date = 2020-07-24 keywords = RNA; SARS summary = Nasopharyngeal specimens positive for SARS-CoV-2 and other coronaviruses collected in universal viral transport (UVT) medium were pre-processed by several commercial and laboratory-developed methods and tested by RT-qPCR assays without RNA extraction using different RT-qPCR master mixes. Standard approach for detection of SARS-CoV-2 RNA from nasopharyngeal specimens in our laboratory involves extraction of total nucleic acids from specimens in an IVD-labeled, automated extraction platform followed by RT-qPCR, based on one of the assays (Table 1) suggested by World Health Organization (WHO) [11] . Based on these results, the optimal pre-treatment and reaction conditions for the direct approach were: i) transfer and dilute (4-fold) 10 μl of NPFS specimen in NFW; ii) incubate at 65˚C for 10 min; and iii) test 8 μl of heat lysed specimen in a 20 μl reaction using TaqPath™ 1-Step RT-qPCR Master Mix. The analytical sensitivity of the direct RT-qPCR assay using specimens prepared in this manner was determined by serially diluting a specimen positive for SARS-CoV-2 with a negative specimen as a diluent. doi = 10.1371/journal.pone.0236564 id = cord-282303-idh7io9v author = Hassan, Md. Zakiul title = Contamination of hospital surfaces with respiratory pathogens in Bangladesh date = 2019-10-28 keywords = Bangladesh; respiratory; surface summary = With limited infection control practices in overcrowded Bangladeshi hospitals, surfaces may play an important role in the transmission of respiratory pathogens in hospital wards and pose a serious risk of infection for patients, health care workers, caregivers and visitors. With limited infection control practices in overcrowded Bangladeshi hospitals, surfaces may play an important role in the transmission of respiratory pathogens in hospital wards and pose a serious risk of infection for patients, health care workers, caregivers and visitors. Respiratory viral and bacterial pathogens, including Staphylococcus aureus, Streptococcus pyogenes, influenza viruses, respiratory syncytial virus, adenovirus, rhinoviruses and novel coronavirus strains, can survive on hospital surfaces for days, weeks or even months. This study identified that hospital surfaces in these Bangladeshi hospitals, were frequently contaminated with respiratory pathogens and pose a potential threat for fomite-borne transmission of respiratory infections to patients, healthcare workers and family caregivers. doi = 10.1371/journal.pone.0224065 id = cord-302962-qw6s1t7j author = Hause, Ben M. title = Bovine Rhinitis Viruses Are Common in U.S. Cattle with Bovine Respiratory Disease date = 2015-03-19 keywords = BRAV2; BRBV; BRDC; BRV summary = Metagenomic sequencing of a nasal swab from a bovine respiratory disease (BRD) diagnostic submission from Kansas identified contigs with approximately 90% nucleotide similarity to BRAV2 and BRBV. Altogether, these results demonstrate that BRV infections are common in cattle with respiratory disease and that BRAV1, BRAV2 and BRBV co-circulate in U.S. cattle and have high similarity to viruses isolated more than 30 years ago from diverse locations. The PCR assay specificity was confirmed using bovine rhinitis virus positive samples as determined by metagenomic sequencing as well as with cultures of common BRDC pathogens BVDV, BHV-1, BRSV, BCV, Mannheimia haemolytica, Histophilus somni, Pasteurella multocida and Mycoplasma bovis. As metagenomic sequencing of a nasal swab from a calf with acute respiratory disease identified concurrent infection with two bovine rhinitis virus species, we designed a 5''-nuclease reverse transcription PCR (rtPCR) assay targeting the conserved 3D polymerase gene to investigate the incidence of BRV in BRDC diagnostic submissions. doi = 10.1371/journal.pone.0121998 id = cord-001039-qocuprwb author = Hayasaka, Daisuke title = TNF-α Acts as an Immunoregulator in the Mouse Brain by Reducing the Incidence of Severe Disease Following Japanese Encephalitis Virus Infection date = 2013-08-05 keywords = IL-10; JEV; TNF; figure summary = doi = 10.1371/journal.pone.0071643 id = cord-255013-njpuc475 author = He, Xiaocui title = Establishment of Myotis myotis Cell Lines - Model for Investigation of Host-Pathogen Interaction in a Natural Host for Emerging Viruses date = 2014-10-08 keywords = Fig; IFN; PCR; cell summary = The usefulness of these cell lines to study antiviral responses has been confirmed by analysis of their susceptibility to lyssavirus infection and the mRNA patterns of immune-relevant genes after poly I:C stimulation. myotis cell lines present a valuable in vitro model to study the interactions between lyssaviruses and their natural host, and to shed light on the mechanisms of resistance in bat''s central nervous system (CNS). To further evaluate the cell line models for study of the different susceptibility between MmBr and other cell lines, mRNA expressions of PRRs and IFN induced genes were investigated in MmTo and MmBr after RABV infection (MOI 0.01 to 1.0). The increased expression of dsRNA receptor TLR3 and IFN induced genes ISG56, ISG43, Mx1 and IFIT3 after stimulation with poly I:C mimicking a viral infection indicates that these cell lines can be used as effective in vitro models to study the bat''s innate immune responses to virus infection [32, 44] . doi = 10.1371/journal.pone.0109795 id = cord-002100-dt5zvebj author = He, Yonghua title = Transgenic Soybean Production of Bioactive Human Epidermal Growth Factor (EGF) date = 2016-06-17 keywords = EGF; EGFR; NEC; protein; seed; soybean summary = Phosphorylation and immunohistochemical assays on the EGF receptor in HeLa cells indicate the EGF protein produced in soybean seed is bioactive and comparable to commercially available human EGF. Epidermal growth factor protein from humans was produced in soybean seeds by constructing a plant gene expression cassette that involved a synthetic codon optimized EGF nucleotide sequence (protein sequence from Genbank accession CCQ43157). To assess the bioactivity of soybean-produced hEGF, samples were prepared from both ShEGF transgenic soybean lines and nontransgenic controls that were used to stimulate HeLa cells to induce EGFR internalization, degradation and phosphorylation. In contrast, samples prepared from control nontransgenic soybeans exhibited no apparent bioactivity showing the degradation and phosphorylation of EGFR is the result of EGF binding of either commercial rhEGF added to the media or from the hEGF produced by the transgenic soybeans. doi = 10.1371/journal.pone.0157034 id = cord-000182-ni6iyzdn author = He, Zhisong title = Predicting Drug-Target Interaction Networks Based on Functional Groups and Biological Features date = 2010-03-11 keywords = Chou; drug; feature; protein summary = title: Predicting Drug-Target Interaction Networks Based on Functional Groups and Biological Features Many researchers have made lots of efforts to develop useful algorithms and softwares to investigate various drug-related biological problems, such as HIV protease cleavage site prediction [18, 19] , identification of GPCR (G protein-coupled receptors) type [20, 21] , protein signal peptide prediction [22] , protein subcellular location prediction [23, 24, 25] , analysis of specificity of GalNAc-transferase protein [26] , identification of protease type [27, 28] , membrane protein type prediction [29, 30, 31, 32] , and a series of relevant webserver predictors as summarized in a recent review [33] . The drug-target benchmark datasets thus obtained for enzymes, ion-channels, GPCRs, and nuclear receptors are given in Online Supporting Information S1, S2, S3, and S4, respectively. Prediction of G-protein-coupled receptor classes based on the concept of Chou''s pseudo amino acid composition: an approach from discrete wavelet transform doi = 10.1371/journal.pone.0009603 id = cord-000540-bbjmcdo5 author = Hellard, Eléonore title = True versus False Parasite Interactions: A Robust Method to Take Risk Factors into Account and Its Application to Feline Viruses date = 2012-01-03 keywords = FCV; FHV; FIV; FPV summary = By combining logistic regressions and chi-square tests, we are able to calculate the expected frequencies of co-infected individuals if parasites are independent considering their risk factors, and to compare them to the observed ones. The corrected chi-square approach is based on the idea that the coefficients of the logistic regression of the two viruses can be used to estimate the number of seronegative, single-and double-seropositive individuals expected if the two pathogens are independent. The two approaches (corrected chi-square and logistic regression) were used for the analysis of the interactions between four cat viruses ( Table 2) . Correcting for all risk factors, no pair of viruses involving the Feline Immunodeficiency Virus (FIV-FHV, FIV-FCV, FIV-FPV) was significantly associated. Table S1 Corrected chi-square tests and logistic regressions to search for feline viruses'' interactions using subsets randomly sampled in cat data such that the N F / n ratio takes various values. doi = 10.1371/journal.pone.0029618 id = cord-300859-nqklx0vn author = Henderson, Kelley C. title = Specificity and Strain-Typing Capabilities of Nanorod Array-Surface Enhanced Raman Spectroscopy for Mycoplasma pneumoniae Detection date = 2015-06-29 keywords = PLS; SERS summary = title: Specificity and Strain-Typing Capabilities of Nanorod Array-Surface Enhanced Raman Spectroscopy for Mycoplasma pneumoniae Detection pneumoniae with statistically significant specificity and sensitivity in simulated and true clinical throat swab samples, and the ability to distinguish between reference strains of the two main genotypes of M. pneumoniae clinical isolates from globally diverse origins and distinguished these from a panel of 12 other human commensal and pathogenic mycoplasma species with 100% cross-validated statistical accuracy. A total of n = 390 pre-processed NA-SERS spectra collected from both substrates were included in the model, consisting of 20 nanorod substrate background spectra, 20 growth medium control spectra, 25 M129 spectra, 25 FH spectra, and 10 spectra per additional clinical isolate. pneumoniae strains from all 12 other human Mollicutes species and the growth medium control with 100% cross-validated sensitivity and specificity (Fig 3A-3C ). doi = 10.1371/journal.pone.0131831 id = cord-002044-9xgt3tf4 author = Hendiger, Jacek title = Influence of the Pressure Difference and Door Swing on Heavy Contaminants Migration between Rooms date = 2016-05-12 keywords = door; room summary = This paper presents the results of investigations whose aim was to describe the influence of the pressure difference level on the ability of contaminants migration between neighbouring rooms in dynamic conditions associated with door swing. In health care facilities, this way of ventilation system operation is utilized in both the Airborne Infection Isolation and Protective Environment Rooms, however, the key difference is the required direction of airflow between the room and the adjacent space, such as a corridor, which determines the application of negative or positive pressure in the protected room, respectively. The research described in the available literature, concerning migration of air between rooms in the conditions of pressure difference was conducted using tracer gases, CFD simulations and smoke visualization. The tests were made with dense smoke visualization in order to investigate the relation between the value of pressure difference, door swing and migration level of heavy contaminants between the rooms. doi = 10.1371/journal.pone.0155159 id = cord-002811-5hrydciz author = Hercik, Christine title = A diagnostic and epidemiologic investigation of acute febrile illness (AFI) in Kilombero, Tanzania date = 2017-12-29 keywords = AFI; TAC; Tanzania summary = Furthermore, we examined numerous epidemiologic correlates of febrile illness, and conducted demographic, clinical, and behavioral domain-specific multivariate regression to statistically establish associations with agent detection. The objective of this hospital-based syndromic surveillance study was to examine exposure and epidemiologic associations with detection of bloodstream and respiratory agents among patients presenting to clinical settings with acute febrile illness (AFI) in Kilombero, Tanzania. Given the high frequency of detection of Plasmodium, we further examined detection status across three diagnostic platforms, and conducted a non-parametric tests Kruskal-Wallis test to compare mean C t values, as determined by qPCR, for patients grouped within each level of parasite intensity (1+, 2+, 3+, or 4+), as determined by blood smear. Clinical and epidemiologic correlates of agents detected among at least 10% of our patient population were evaluated using an agent-specific filtered multivariate logistic regression approach to determine statistically significant factors among test-positive participants against a test-negative control group. doi = 10.1371/journal.pone.0189712 id = cord-345695-5vi9wibk author = Hicks, Lorin L. title = A statistical approach to white-nose syndrome surveillance monitoring using acoustic data date = 2020-10-22 keywords = Montana; WNS; activity; bat summary = From these data, we developed site-specific prediction models for bat activity to account for seasonal and annual temperature variation prior to known occurrence of WNS. We propose this model-based method for future monitoring efforts that could be used to trigger targeted sampling of individual bats or hibernacula for WNS, in areas where traditional disease surveillance approaches are logistically difficult to implement or because of human-wildlife transmission concerns from COVID-19. We predicted that bat populations in the western U.S. would have low levels of activity during winter months, high levels of activity during the summer, and that acoustic monitoring could be used as an effective approach for disease surveillance in remote areas of the Intermountain West. The model was fit to data from all 41 sites to estimate among-site and among-year variation in activity, but we use the results to generate prediction intervals for four forest sites to depict how a landowner might implement this approach for WNS surveillance monitoring. doi = 10.1371/journal.pone.0241052 id = cord-000725-rafwlw0t author = Hindinger, Claudia title = IFN-γ Signaling to Astrocytes Protects from Autoimmune Mediated Neurological Disability date = 2012-07-27 keywords = CNS; EAE; Fig; IFN summary = Experimental autoimmune encephalomyelitis (EAE) was induced in transgenic mice expressing signaling defective dominant-negative interferon gamma (IFN-γ) receptors on astrocytes to determine the influence of inflammation on astrocyte activity. Inhibition of IFN-γ signaling to astrocytes did not influence disease incidence, onset, initial progression of symptoms, blood brain barrier (BBB) integrity or the composition of the acute CNS inflammatory response. GFAPcR1D and wt mice were compared at the peak of acute disease to determine if IFN-c signaling altered astrocyte activation or CNS inflammation. Despite elevated demyelination and axonal loss in the absence of IFN-c signaling to astrocytes, spinal cords showed no evidence of differential astrocyte activation by either immunohistochemistry (Fig. 4 ), or differences in GFAP mRNA expression during the peak of acute disease (Fig. 5 ). Although demyelination was increased in the CNS of GFAPcR1D mice, the extent of astrocyte activation associated with spinal cord white matter lesions was similar in both groups ( Fig. 6 ; ,60 GFAP + cells/mm 2 ). doi = 10.1371/journal.pone.0042088 id = cord-002023-7zd5zhbz author = Hiremath, Jagadish title = Entrapment of H1N1 Influenza Virus Derived Conserved Peptides in PLGA Nanoparticles Enhances T Cell Response and Vaccine Efficacy in Pigs date = 2016-04-19 keywords = H1N1; NPP; PLGA summary = doi = 10.1371/journal.pone.0151922 id = cord-356364-ipi81ce3 author = Ho, Bo-Lin title = Critical Assessment of the Important Residues Involved in the Dimerization and Catalysis of MERS Coronavirus Main Protease date = 2015-12-14 keywords = Fig; MERS; SARS summary = In the present study, MERS-CoV main protease (M(pro)) is expressed; the dimerization of the protein and its relationship to catalysis are investigated. The colorimetry-based peptide substrate, TSAVLQ-para-nitroanilide (TQ6-pNA) (purity 95-99% by HPLC; GL Biochem Ltd, Shanghai, China), was used to measure the proteolytic activity of MERS-CoV M pro and its mutants throughout the course of the study as described previously [25, 28] . In addition, although the K d values of wild-type SARS-CoV M pro without or with substrates show no significant difference (Table 2) , it was possible to detect substrate-induced dimerization at a protein concentration of 1 μM by AEC [33] . Biochemical and AUC studies indicated that MERS-CoV M pro shows almost the same proteolytic activity as SARS-CoV M pro ; although it is a monomer in aqueous buffer and displays substrate-induced dimerization (Fig 6) . doi = 10.1371/journal.pone.0144865 id = cord-285749-0ejhd9nw author = Hoffmann, Markus title = The Hemagglutinin of Bat-Associated Influenza Viruses Is Activated by TMPRSS2 for pH-Dependent Entry into Bat but Not Human Cells date = 2016-03-30 keywords = FLUAV; HAL; TMPRSS2; VSV summary = Generation of VSV pseudotypes (VSVpp) was performed as follows: HEK-293T cells were transfected by calcium-phosphate precipitation with expression plasmids encoding viral surface proteins, VSV-G (positive control) , NiV-F/G, FLUAV-HA and/or NA and bat-FLUAV-HAL and/or NAL, or empty plasmid (pCAGGS) as negative control. In order to investigate the potential of human TTSPs to proteolytically activate batFLUAV-HAL for host cell entry, we additionally cotransfected the cells with expression plasmids for TMPRSS2, DESC-1 or MSPL. Notably, three bat cell lines (EidNi/41, HypNi/1.1 and EpoNi/22.1) were susceptible to entry of pseudotypes bearing HAL and NAL of batFLUAV (Fig 2B) , demonstrating that surface glycoproteins of batFLUAV can mediate cellular entry. To assess proteolytic activation of HA/HAL proteins, vesicular stomatitis virus-based pseudotypes (VSVpp) were produced in cells transfected to express the indicated type II transmembrane serine proteases (B) or different amounts of TMPRSS2 (C). doi = 10.1371/journal.pone.0152134 id = cord-000346-9b6yz3f4 author = Holder, Benjamin P. title = Assessing the In Vitro Fitness of an Oseltamivir-Resistant Seasonal A/H1N1 Influenza Strain Using a Mathematical Model date = 2011-03-24 keywords = H1N1; H275Y; viral summary = In order to obtain two complementary views of the infection kinetics for the A/Brisbane/59/2007 WT and H275Y mutant strains, virus growth over time was observed in two different in vitro systems: the viral plaque assay and the multiple-cycle viral yield assay. We are left then with two experimental measures -the viral titer growth rate and the plaque velocity -whose values may depend on three unknown infection kinetics parameters: the infecting time, t inf ; the latent infection period, t L ; and the infectious lifespan of a cell, t I . To demonstrate this concept using the A/ Brisbane/59/2007 (H1N1) WT and H275Y mutant strains, we have plotted the experimentally-measured values of plaque velocity and viral titer growth rate as functions of the infecting time and latent infection period, using the model dependence determined above ( Figure 6 ). doi = 10.1371/journal.pone.0014767 id = cord-013334-cptu0k7s author = Holst-Hansen, Joachim A. title = Does the size of rewards influence performance in cognitively demanding tasks? date = 2020-10-21 keywords = high; reward; task summary = Empirical studies in sports settings show that athletes generally perform worse when the stakes are higher, while a range of lab studies involving cognitively demanding tasks have led to diverging results, supporting positive, negative and null-effects of higher (vs. Third, if the given task can''t be solved more efficiently than the level of performance a low monetary incentive allows, a higher stake can''t have an additional positive effect due to a ceiling effect [3] . Studies that have asked participants to solve various forms of cognitively demanding tasks have led to ambiguous findings; some studies find a positive effect on performance of higher stakes compared to lower [6, 16, 17] , some find a negative effect [5, 18] while others find no clear effect when comparing high vs. In order to further investigate how the reward size might influence behavior, we also assess if self-reported measures of effort [6] , intrinsic motivation [7] and focus [5] vary depending on the reward structure the participants have been exposed to. doi = 10.1371/journal.pone.0240291 id = cord-012889-dtil5xeo author = Holzer, Joshua title = The effect of copartisan justice ministers on human rights in presidential democracies date = 2020-09-02 keywords = CIRI; Index; PTS; justice; right summary = doi = 10.1371/journal.pone.0234938 id = cord-339789-151d1j4n author = Hong, Hyokyoung G. title = Estimation of time-varying reproduction numbers underlying epidemiological processes: A new statistical tool for the COVID-19 pandemic date = 2020-07-21 keywords = SIR; time summary = title: Estimation of time-varying reproduction numbers underlying epidemiological processes: A new statistical tool for the COVID-19 pandemic However, time-independent parameters in the classical models may not capture the dynamic transmission and removal processes, governed by virus containment strategies taken at various phases of the epidemic. We propose a Poisson model with time-dependent transmission and removal rates to account for possible random errors in reporting and estimate a time-dependent disease reproduction number, which may reflect the effectiveness of virus control strategies. To choose the optimal number of knots for each country when implementing the spline approach, we used 5-fold cross-validation by minimizing the combined mean squared error for the estimated infectious and removed cases. Our model accommodates possible random errors and estimates a timedependent disease reproduction number, R 0 ðtÞ, which can serve as a metric for timely evaluating the effects of health policies. doi = 10.1371/journal.pone.0236464 id = cord-000979-cav9n18w author = Hoppe, Sebastian title = Rapid Identification of Novel Immunodominant Proteins and Characterization of a Specific Linear Epitope of Campylobacter jejuni date = 2013-05-29 keywords = Campylobacter; PCR; RNA; protein summary = doi = 10.1371/journal.pone.0065837 id = cord-001435-ebl8yc92 author = Hoppe, Sebastian title = Identification of Antigenic Proteins of the Nosocomial Pathogen Klebsiella pneumoniae date = 2014-10-21 keywords = A.U.; KPN_00363; PCR; antibody; protein summary = Hence, a cDNA-based expression library was constructed and screened via microarrays to detect novel antigens of Klebsiella pneumoniae, a prominent agent of nosocomial infections well-known for its extensive antibiotics resistance, especially by extended-spectrum beta-lactamases (ESBL). After specificity analysis, homology survey and 3d structural modelling, one epitope sequence GAVVALSTTFA of KPN_00363, an ion channel protein, was identified harboring specificity for K. By identifying several novel antigens and their linear epitope sites, we have paved the way for crucial future research and applications including the design of point-of-care devices, vaccine development and serological screenings for a highly relevant nosocomial pathogen. Incubation with antibodies reactive to either of those two bacterial species resulted in signal intensities in the neighbourhood of the negative control independent of sequence alterations, see Figure 11 . In contrast, the other two proteins displaying linear epitopes, KPN_00363 and KPN_00459, indicated some specificity with the antibodies tested and two linear consensus sequences could be derived, GAVVALSTTFA and GIAFGAVELFD, respectively. doi = 10.1371/journal.pone.0110703 id = cord-346858-18q8rxzg author = Hossain, Md. Tanvir title = Social and electronic media exposure and generalized anxiety disorder among people during COVID-19 outbreak in Bangladesh: A preliminary observation date = 2020-09-11 keywords = EME; SME; covid-19 summary = Classified as a pandemic by the World Health Organization, the novel Coronavirus Disease (COVID-19) has spread to Bangladesh since early March of 2020, and people are getting daily updates from the social and electronic media. For this cross-sectional study, data were collected from 880 participants by a self-administered online-based questionnaire relating personal characteristics, self-rate health (SRH), SME, and EME with anxiety. The mental health burden of the COVID-19 infected patients and the healthcare professionals, fearing the persisting social prejudice and stigma generated from ''overexposure'' to media ''misinformation,'' forced some people to commit suicide [22] [23] [24] . At present, the level of anxiety generated from the exposure to social and electronic media during COVID-19 pandemic is not known in Bangladesh, while some other countries have addressed the issue vigorously [13, 18, 36] . doi = 10.1371/journal.pone.0238974 id = cord-296550-wkmnfph3 author = Hossain, Mohammad Anwar title = Knowledge, attitudes, and fear of COVID-19 during the Rapid Rise Period in Bangladesh date = 2020-09-24 keywords = Bangladesh; COVID-19; fear summary = The study aims to determine the level of Knowledge, Attitude, and Practice (KAP) related to COVID-19 preventive health habits and perception of fear towards COVID-19 in subjects living in Bangladesh. The study objectives were to determine the level of knowledge, attitudes, and practices related to COVID-19 preventive health habits and the underlying fear of COVID-19 in the Bangladeshi population and how they are affected by socio-demographic factors. The KAP section of the questionnaire related to a total of 12 score knowledge questions on COVID-19, categorical answers to attitudes towards the control of the pandemic, and practices of wearing masks and avoiding public gatherings. This study is similar to one study in China that found a significant relationship between knowledge and age and knowledge and educational level, with males reporting higher levels of knowledge than females regarding COVID-19 symptoms, precautions, and health advisory practices [16] . However, in our study, subjects living in Bangladesh reported similar knowledge for both males and females regarding COVID-19 symptoms, precautions, and health advisory practices. doi = 10.1371/journal.pone.0239646 id = cord-000255-73nlxqgk author = Hosseini, Parviez title = Predictive Power of Air Travel and Socio-Economic Data for Early Pandemic Spread date = 2010-09-15 keywords = H1N1; Mexico; country summary = CONCLUSIONS/SIGNIFICANCE: We conclude that strategies to prevent pandemic influenza virus emergence and spread in the future should include: 1) enhanced surveillance for strains resulting from reassortment in traded livestock; 2) rapid deployment of control measures in the initial spreading phase to countries where travel data predict the pathogen will reach and to countries where lower healthcare resources will likely cause delays in reporting. Of all the models evaluated, a multivariate model with three predictors, (1) total country-level healthcare spending per capita, (2) estimated passenger volume arriving from Mexico via direct flights (direct flight capacity), and (3) passenger volume from Mexico via indirect, or two-leg, flights (indirect flight capacity), provided the best fit to the data using AIC, as detailed under Methods (Table 1 , DAIC = 0, overall x 2 = 54.33 on 5 degrees of freedom, p-value,0.0001). We validated the model by determining how well a model fit to data up until May 8th predicted reporting dates for fourteen countries where the disease was detected between May 9 th and May 19 th (Supplemental Online Figure S2 ). doi = 10.1371/journal.pone.0012763 id = cord-321705-6a7avlro author = Hou, Tianya title = Social support and mental health among health care workers during Coronavirus Disease 2019 outbreak: A moderated mediation model date = 2020-05-29 keywords = health; mental; social; support summary = The current study examined the effect of social support on mental health of health care workers and its underlying mechanisms regarding the mediating role of resilience and moderating role of age during the epidemic. METHODS: Social Support Rating Scale (SSRS), Connor-Davidson Resilience scale (CD-RISC) and Symptom Checklist 90 (SCL-90) were administrated among 1472 health care workers from Jiangsu Province, China during the peak period of COVID-19 outbreak. Thus, the present research employed a sample of Chinese health care workers during COVID-19 outbreak to explore a conceptual model in which, on the one hand, resilience mediated the association between social support and mental health; On the other hand, the indirect relationships between social support and mental health via resilience were moderated by age group. Considering the present study was to compare the indirect effect of social support on mental health via resilience between the young and middle-aged heath care workers, participants aged 50 or over were excluded. doi = 10.1371/journal.pone.0233831 id = cord-000695-g5sum116 author = Hou, Yanxia title = Prediction and Identification of T Cell Epitopes in the H5N1 Influenza Virus Nucleoprotein in Chicken date = 2012-06-20 keywords = B19; MHC summary = doi = 10.1371/journal.pone.0039344 id = cord-262759-ec2c25q3 author = Hsieh, Yi-Ting title = Glucose-6-Phosphate Dehydrogenase (G6PD)-Deficient Epithelial Cells Are Less Tolerant to Infection by Staphylococcus aureus date = 2013-11-04 keywords = A549; G6PD; ROS; cell summary = The impairment of ROS removal is predicted to enhance apoptotic activity in G6PD-deficient cells, and this enhanced apoptosis was observed by annexin V/PI staining under a confocal fluorescence microscope and quantified by flow cytometry. We hypothesized that G6PD-deficient cells are less tolerant to oxidative stress upon bacterial infection, leading to the accumulation of more intracellular ROS when compared to the control scramble cells. To determine whether the reduced ROS accumulation and apoptotic activity, particularly in G6PD-deficient cells, was due to deceased αhemolysin expression upon VRSA infection in the presence of vancomycin, the production of intracellular ROS and cell apoptosis when the α-hemolysin inhibitor Oroxylin A was added to the media was quantified by flow cytometry. Our results presented here indicate that expression of active caspase-9, as well as the downstream caspase-3, was much higher in G6PD-deficient cells than in control scramble cells upon VRSA infection, suggesting that mitochondrial dysfunction may be the major cause of the increase in cell apoptosis (Figure 4) . doi = 10.1371/journal.pone.0079566 id = cord-000536-0mn1gbll author = Hu, Le-Le title = Predicting Biological Functions of Compounds Based on Chemical-Chemical Interactions date = 2011-12-29 keywords = class; compound; metabolic; pathway summary = In this study, based on the information of chemical-chemical interactions, a novel method was developed that can be used to identify which of the following eleven metabolic pathway classes a query compound may be involved with: (1) Carbohydrate Metabolism, (2) Energy Metabolism, (3) Lipid Metabolism, (4) Nucleotide Metabolism, (5) Amino Acid Metabolism, (6) Metabolism of Other Amino Acids, (7) Glycan Biosynthesis and Metabolism, (8) Metabolism of Cofactors and Vitamins, (9) Metabolism of Terpenoids and Polyketides, (10) Biosynthesis of Other Secondary Metabolites, (11) Xenobiotics Biodegradation and Metabolism. In this study, we proposed a multi-target model based on chemical-chemical interactions for predicting the metabolic pathways where compounds participate in. Listed in Table 2 are the accuracies by each of the 11 prediction orders for the 3,137 compounds about their involvement in the 11 metabolic pathway classes using the 5-fold crossvalidation test. doi = 10.1371/journal.pone.0029491 id = cord-294591-793ywpcd author = Hu, Xiaoyun title = Self-Reported Use of Personal Protective Equipment among Chinese Critical Care Clinicians during 2009 H1N1 Influenza Pandemic date = 2012-09-05 keywords = H1N1; ICU; PPE summary = doi = 10.1371/journal.pone.0044723 id = cord-321834-n5w88l23 author = Huang, Cheng-Yang title = Inhibition of a Putative Dihydropyrimidinase from Pseudomonas aeruginosa PAO1 by Flavonoids and Substrates of Cyclic Amidohydrolases date = 2015-05-19 keywords = Fig; dihydropyrimidinase; substrate summary = Although the inhibitory effects of these flavonoids on dihydropyrimidinase were substrate-dependent, dihydromyricetin significantly inhibited dihydropyrimidinase with IC(50) values of 48 and 40 μM for the substrates dihydrouracil and 5-propyl-hydantoin, respectively. In this study, we investigated the effects of the substrates and inhibitors of allantoinase and dihydroorotase, including the flavonols myricetin, quercetin, kaempferol, and galangin, on inhibiting the catalytic activity of a putative dihydropyrimidinase from P. Although dihydromyricetin and myricetin were docked Inhibition of Dihydropyrimidinase by Flavonoids into the active site pocket of dihydropyrimidinase, their binding modes differed. In this study, we showed that dihydromyricetin, a flavonol, significantly inhibited the catalytic activities of dihydropyrimidinase toward both the natural substrate dihydrouracil and xenobiotic substrate 5-propyl-hydantoin (Fig 3) . For example, as shown in Fig 3, the inhibitory effect of kaempferol on the activity of dihydropyrimidinase was significant only with dihydrouracil as a substrate (with IC 50 value of 50 ± 2 μM), but not with 5-propyl-hydantoin. doi = 10.1371/journal.pone.0127634 id = cord-001898-ntqyjqqk author = Huang, Chih-Wei title = Lys-315 at the Interfaces of Diagonal Subunits of δ-Crystallin Plays a Critical Role in the Reversibility of Folding and Subunit Assembly date = 2016-01-05 keywords = Fig; K315A; protein summary = The changes in tryptophan fluorescence were Dilution of monomeric K315A mutant protein denatured in 5 M GdmCl resulted in refolding to a similar conformation as the original monomeric state (Fig 5A and 5B) . Since refolding of partly unfolded monomeric mutant δ-crystallin resulted in a conformation with high exposure of hydrophobic regions, the occurrence of protein aggregation in the process was determined using light scattering measurement. An increase in fluorescence intensity resulting from binding of ThT with the aggregates over time was observed following dilution of 0.84 and 3 M GdmCl denatured monomeric mutant δ-crystallin into buffer (Fig 6B) . The unique stable conformation from unfolding of K315A mutant protein in the presence of urea suggests that the interactions provided by this residue at the interfaces may play a critical role in stabilization of the quaternary structure of δ-crystallin. doi = 10.1371/journal.pone.0145957 id = cord-000984-64p3wpav author = Huang, Shang-Hui title = Self-Oligomerization Is Essential for Enhanced Immunological Activities of Soluble Recombinant Calreticulin date = 2013-06-10 keywords = CRT; FITC; Fig; LPS summary = doi = 10.1371/journal.pone.0064951 id = cord-000082-jy7j8sh0 author = Huang, Ting title = Evidence of Recombination and Genetic Diversity in Human Rhinoviruses in Children with Acute Respiratory Infection date = 2009-07-27 keywords = HRV; table; vp2 summary = Most surprisingly, 20 of the 34 strains classified as HRV-C by comparative analysis of VP4/P2 sequences ( Table 2) were related more closely to HRV-A strains when their 59UTRs were analyzed, and showed incongruent clustering in phylogenetic trees (Figs. When sequencing the VP4/VP2 region of the HRV genome, several recent studies have identified new strains of viruses from children and adults with ARI, asthma, or otitis, which are clustered differently from HRV-A and HRV-B, and have been classified into a novel HRV-C species [7, 8, 17, 18, 19, 20, 21, 25, 26, 27, 28] . In our study, we identified 34 HRVs (51.5%) that clustered differently from HRV-A and HRV-B in a phylogenetic tree that was established on the basis of VP4/VP2 sequences, which were related to recent strains classified in the novel HRV-C species (Fig. 1, Table 2 ). doi = 10.1371/journal.pone.0006355 id = cord-287739-58fth3xl author = Huang, Yhu-Chering title = Successful Control of Methicillin-Resistant Staphylococcus aureus in Endemic Neonatal Intensive Care Units—A 7-Year Campaign date = 2011-08-12 keywords = MRSA; Staphylococcus; Taiwan summary = CONCLUSION/SIGNIFICANCE: Through infection control measures, MRSA HAIs can be successfully controlled, even in areas with high levels of endemic MRSA infections such as our NICUs. Methicillin-resistant Staphylococcus aureus (MRSA) is among the most important pathogens of bacteremia in the intensive care units (ICU). To reduce and control healthcare-associated infections (HAIs) caused by MRSA, a ''''search and destroy'''' strategy, which first detects the patients with MRSA colonization and then decolonizes the MRSA with certain antimicrobial agents, was recently proposed and implemented in some hospitals of different countries, with inconsistent effects [12] [13] [14] [15] [16] . Methicillin-resistant Staphylococcus aureus colonization and its association with infection among infants hospitalized in neonatal intensive care units doi = 10.1371/journal.pone.0023001 id = cord-001843-ceatyj3o author = Huang, Yong title = Ultrasensitive Detection of RNA and DNA Viruses Simultaneously Using Duplex UNDP-PCR Assay date = 2015-11-06 keywords = PCR; TGEV; UNDP summary = PCV2 DNA and TGEV RNA were simultaneously released from the serum sample by boiling with lysis buffer, then magnetic beads and gold nanoparticles coated with single and/or duplex specific probes for TGEV and PCV2 were added to form a sandwich-like complex with nucleic acids released from viruses. This duplex UNDP-PCR assay could detect TGEV (RNA virus) and PCV2 (DNA virus) from large-scale serum samples simultaneously without the need for DNA/RNA extraction, purification and reverse transcription of RNA, and showed a significantly increased positive detection rate for PCV2 (29%) and TGEV (11.7%) preclinical infection than conventional duplex PCR/RT-PCR. The duplex UNDP-PCR assay is suitable for simultaneous detection of RNA and DNA viruses in early viral infection, providing an effective approach for diagnosis of swine diseases. The duplex UNDP-PCR assay developed in this study provided a useful tool for simultaneous detection of RNA (TGEV) and DNA viruses (PCV2) without the need for viral nucleic acid extraction, purification and reverse transcription. doi = 10.1371/journal.pone.0141545 id = cord-293946-4bquxdqa author = Huong, Nguyen Quynh title = Coronavirus testing indicates transmission risk increases along wildlife supply chains for human consumption in Viet Nam, 2013-2014 date = 2020-08-10 keywords = Nam; Nguyen; SARS; Viet; bat summary = In this study we investigated the presence and diversity of coronavirus sequences in the field rat trade distribution chain, wildlife farms specializing in raising rodents for human consumption, and bat guano "farms" and roosts near human dwellings to better understand the natural hosts of coronaviruses and the risk for these interfaces to facilitate spillover into humans. Out of 70 sites, coronavirus positives were detected at 58 including 100% (24/24) of live rat trade sites, 60.7% (17/28) of rodent wildlife farm sites, 94.1% (16/17) of bat guano farm sites, and at the one natural pteropid bat roost. Significant findings of this study are the high proportion of coronavirus positive wildlife (bats and rodents) and the increasing proportion of positives found along the rat trade supply chain from sub-interfaces close to the capture site (rat traders) to restaurants. doi = 10.1371/journal.pone.0237129 id = cord-000079-533xlisc author = Huszthy, Peter C. title = Remission of Invasive, Cancer Stem-Like Glioblastoma Xenografts Using Lentiviral Vector-Mediated Suicide Gene Therapy date = 2009-07-20 keywords = LCMV; VSV; figure summary = Both, lymphocytic choriomeningitis virus glycoprotein (LCMV-GP) and vesicular stomatitis virus glycoprotein (VSV-G) pseudotyped lentiviral vectors very efficiently transduced human glioblastoma cells in vitro and in vivo. In a therapeutic approach using the suicide gene herpes simplex virus thymidine kinase (HSV-1-tk) fused to eGFP, both lentiviral vectors mediated a complete remission of solid tumors as seen on MRI resulting in a highly significant survival benefit (p<0.001) compared to control groups. Furthermore, we showed a significant therapeutic effect of LCMV-GP pseudotyped lentiviral vectors in the cell-line based 9L rat glioma model using the suicide gene HSV-1-tk. In the presented work, we showed that both, VSV-G and LCMV-GP pseudotyped lentiviruses efficiently transduced human glioma cells in vitro and in vivo, whereas gammaretroviral transduction was inefficient. When analyzed at higher magnification, both LCMV-GP and VSV-G pseudotyped lentiviral vectors showed efficient transgene delivery to nestin-positive tumor cells in solid ( Figure 3B ,E) and invasive tumor areas ( Figure 3C ,F). doi = 10.1371/journal.pone.0006314 id = cord-298679-w0yp4u19 author = Iftimie, Simona title = Risk factors associated with mortality in hospitalized patients with SARS-CoV-2 infection. A prospective, longitudinal, unicenter study in Reus, Spain date = 2020-09-03 keywords = COVID-19; SARS; patient summary = doi = 10.1371/journal.pone.0234452 id = cord-275058-61eof7y8 author = Inoue, Hiroyasu title = The propagation of economic impacts through supply chains: The case of a mega-city lockdown to prevent the spread of COVID-19 date = 2020-09-15 keywords = Japan; Tokyo summary = doi = 10.1371/journal.pone.0239251 id = cord-343973-n5ogyxz7 author = Ip, Andrew title = Hydroxychloroquine and tocilizumab therapy in COVID-19 patients—An observational study date = 2020-08-13 keywords = COVID-19; EHR; ICU; patient summary = In this retrospective observational cohort study drawn from electronic health records we sought to describe the association between mortality and hydroxychloroquine or tocilizumab therapy among hospitalized COVID-19 patients. Subsequently, an observational cohort study of 1376 hospitalized patients from a New York hospital using propensity modeling found no significant association between hydroxychloroquine use and intubation or death (hazard ratio, 1.04, 95% confidence interval, 0.82 to 1.32) [14] . A recently reported randomized Brazilian trial enrolling 504 hospitalized SARS-CoV-2 confirmed patients with mild-to-moderate disease (defined as not requiring significant supplemental oxygen support) found that a 7-day course of hydroxychloroquine either with azithromycin or alone did not result in better clinical outcomes as measured by a seven-level ordinal scale at 15 days [16] . In this observational cohort study we report our survival outcomes with hydroxychloroquine and tocilizumab among hospitalized patients with COVID-19. doi = 10.1371/journal.pone.0237693 id = cord-317779-j67vb7f3 author = Irizarry, Kristopher J. L. title = RNA sequencing demonstrates large-scale temporal dysregulation of gene expression in stimulated macrophages derived from MHC-defined chicken haplotypes date = 2017-08-28 keywords = B19; expression; gene; haplotype; macrophage summary = Our experimental design leveraged an initial 6 day window for monocytes to differentiate into macrophages, which was followed by IFNγ stimulation between 1 and 24 h to further characterize subsequent RNA gene expression and the molecular basis for dramatically different nitric oxide production and immune function between the B2 and the B19 haplotype chicken macrophages The t-3 day time point, representing 3 days of differentiation in cell culture, exhibited the greatest expression of genes with a total of 11,429 expressed in both B19 and B2 birds while just 4068 genes lacked evidence of expression in both haplotypes. Overall, the gene enrichment analysis of the RNA sequence data provides a cellular-level picture of the specific biological processes that occur over time following activation of monocyte-derived macrophages. doi = 10.1371/journal.pone.0179391 id = cord-252795-x66zqmgv author = Islam, Md. Akhtarul title = Depression and anxiety among university students during the COVID-19 pandemic in Bangladesh: A web-based cross-sectional survey date = 2020-08-26 keywords = Bangladesh; COVID-19; student summary = title: Depression and anxiety among university students during the COVID-19 pandemic in Bangladesh: A web-based cross-sectional survey Following the detection of first COVID-19 case on March 8, 2020 [6] , Bangladesh like many other countries put the lockdown strategy into effect on March 26, 2020 , to ensure ''social distance'' through ''home quarantine'' to curb the ''spread'' among its population [7] [8] [9] , since a precise treatment or vaccine for the infected and people at risk are yet to achieved by the global health community [10, 11] . The ongoing COVID-19 pandemic is creating a psycho-emotional chaotic situation as countries have been reporting a sharp rise of mental health problems, including anxiety, depression, stress, sleep disorder as well as fear, among its citizens [15] [16] [17] [18] [19] , that eventually increased the substance use [15] and sometimes suicidal behavior [20] [21] [22] . Researchers in China observed that the greater exposure to ''misinformation'' through social media are more likely contributing to the development of anxiety, depression, and other mental health problems among its population of different socioeconomic background [23] [24] [25] [26] . doi = 10.1371/journal.pone.0238162 id = cord-013265-qrfi6e5c author = Isono, Toshihito title = Treatment of severe pneumonia by hinokitiol in a murine antimicrobial-resistant pneumococcal pneumonia model date = 2020-10-15 keywords = BALF; PBS; hinokitiol summary = doi = 10.1371/journal.pone.0240329 id = cord-353253-kk2q71vg author = Itokawa, Kentaro title = Disentangling primer interactions improves SARS-CoV-2 genome sequencing by multiplex tiling PCR date = 2020-09-18 keywords = ARTIC; PCR; primer summary = Soon after the pandemic was recognized by epidemiologists, a group of biologists comprising the ARTIC Network, has devised a multiplexed polymerase chain reaction (PCR) protocol and primer set for targeted whole-genome amplification of SARS-CoV-2. In our experience, the low to zero depth for those two amplicons was the most frequent bottleneck for using the ARTIC primer set V1 to sequence all targeted genomic regions from samples with middle to low viral load (Ct > 27). The results indicated that preventing primer dimerformation is an effective measure to improve coverage bias in the ARTIC Network''s SARS-CoV-2 genome sequencing protocol, and may be applicable to other PrimalSeq methods in general. The formation of primer-dimers is a major cause of coverage bias in the ARTIC Network''s multiplex PCR protocol for SARS-CoV-2 genome sequencing. A proposal of an alternative primer for the ARTIC Network''s multiplex PCR to improve coverage of SARS-CoV-2 genome sequencing (manuscript version 1) doi = 10.1371/journal.pone.0239403 id = cord-304616-k92fa15l author = Izes, Aaron M. title = Assay validation and determination of in vitro binding of mefloquine to plasma proteins from clinically normal and FIP-affected cats date = 2020-08-05 keywords = fip; mefloquine; plasma; protein summary = title: Assay validation and determination of in vitro binding of mefloquine to plasma proteins from clinically normal and FIP-affected cats As cats with feline infectious peritonitis (FIP) demonstrate altered concentrations of plasma proteins, the proportion of mefloquine binding to plasma proteins in both clinically normal cats and FIP-affected cats was also investigated. Consequently, the aim of this study was two-fold: first, to develop and validate a high pressure liquid chromatography (HPLC) method to detect mefloquine in feline plasma, and second, to determine the in vitro plasma protein binding of mefloquine in both clinically normal and FIP-affected cats. Here, although a significant difference was found between the plasma protein binding of mefloquine in clinically normal and FIP-affected cats, due to the unknown biological variability of the assay, it is likely that this difference is equivocal. This study has validated an accurate and reliable assay to detect mefloquine in feline plasma and demonstrated that mefloquine is highly plasma protein bound in both clinically normal and FIP-affected cats. doi = 10.1371/journal.pone.0236754 id = cord-328627-cf8f71dr author = Jando, Julia title = Expression and regulation of the neutral amino acid transporter B(0)AT1 in rat small intestine date = 2017-09-15 keywords = ACE2; at1 summary = Protein abundance of B 0 AT1, ACE2 and CD13 along the small intestine was measured by Western blotting performed on brush-border membrane vesicles (bbmv) prepared from duodenum, proximal-, middle-and distal jejunum as well as ileum and quantified relative to the microvilli cytoskeletal protein β-actin,. Additionally, rats fed different diets (NP, HP and AA) were euthanized 3 h after light-onset (ZT3) or 3 h after light-offset The three proteins tested in these bbmv showed a clearly increasing expression level in distal direction along the small intestine, as shown for distal versus proximal jejunum at both time points (Fig 1C, right panels) . This suggested the possibility that rats on a HP or AA diet may have expressed more functional B 0 AT1 along the small intestine and performed a more efficient absorption of neutral amino acids like L-isoleucine. doi = 10.1371/journal.pone.0184845 id = cord-299852-t0mqe7yy author = Janssen, Loes H. C. title = Does the COVID-19 pandemic impact parents’ and adolescents’ well-being? An EMA-study on daily affect and parenting date = 2020-10-16 keywords = Model; affect; covid-19 summary = In this ecological momentary assessment study, we investigated if the COVID-19 pandemic affected positive and negative affect of parents and adolescents and parenting behaviors (warmth and criticism). However, Intolerance of uncertainty, nor any pandemic related characteristics (i.e. living surface, income, relatives with COVID-19, hours of working at home, helping children with school and contact with COVID-19 patients at work) were linked to the increase of parents'' negative affect during COVID-19. In addition, we asked parents and adolescents about daily difficulties and helpful activities during the COVID-19 pandemic that possibly influenced their affect in positive and negative ways. During the COVID-19 pandemic, the most reported daily difficulties across the 14 days of EMA for parents were (1) missing social contact with friends (14.6%), (2) concerns about the coronavirus in general (13.5%), (3) irritations with family members (12.8%), (4) worrying about health of others (8.3%), and (5) coronavirus-related news items (8.0%). doi = 10.1371/journal.pone.0240962 id = cord-346314-o9fjpqaj author = Jarboui, Mohamed Ali title = Nucleolar Protein Trafficking in Response to HIV-1 Tat: Rewiring the Nucleolus date = 2012-11-15 keywords = HIV-1; Jurkat; RNA; Tat; cell; figure; nucleolar; protein summary = Pathway analysis and network reconstruction revealed that Tat expression specifically resulted in the nucleolar enrichment of proteins collectively participating in ribosomal biogenesis, protein homeostasis, metabolic pathways including glycolytic, pentose phosphate, nucleotides and amino acids biosynthetic pathways, stress response, T-cell signaling pathways and genome integrity. Following the detailed annotation of the quantitative abundance changes in the nucleolar protein composition upon Tat expression, we focussed on the Tat-affected cellular complexes and signalling pathways associated with ribosome biogenesis, spliceosome, molecular chaperones, DNA replication and repair and metabolism and discuss their potential involvement in HIV-1 pathogenesis. In this study, we investigated the quantitative changes in the nucleolar proteome of Jurkat T cells constitutively expressing HIV-1 Tat (86aa) versus their Tat-negative counterpart, using stable isotope labelling with amino acids in cell culture (SILAC) technology, followed by ESI tandem mass spectrometry and implemented the experimental approach described in Figure 1A . doi = 10.1371/journal.pone.0048702 id = cord-353200-5csewb1k author = Jehi, Lara title = Development and validation of a model for individualized prediction of hospitalization risk in 4,536 patients with COVID-19 date = 2020-08-11 keywords = COVID-19; SARS; model; patient summary = OBJECTIVE: To characterize a large cohort of patients hospitalized with COVID-19, their outcomes, develop and validate a statistical model that allows individualized prediction of future hospitalization risk for a patient newly diagnosed with COVID-19. DESIGN: Retrospective cohort study of patients with COVID-19 applying a least absolute shrinkage and selection operator (LASSO) logistic regression algorithm to retain the most predictive features for hospitalization risk, followed by validation in a temporally distinct patient cohort. MEASUREMENTS: Demographic, clinical, social influencers of health, exposure risk, medical co-morbidities, vaccination history, presenting symptoms, medications, and laboratory values were collected on all patients, and considered in our model development. Hospitalization risk prediction and outcomes in COVID-19 PLOS ONE | https://doi.org/10.1371/journal.pone.0237419 August 11, 2020 2 / 15 ethical restrictions by the Cleveland clinic regulatory bodies including the institutional review Board and legal counsel. We also develop and validate a statistical model that can assist with individualized prediction of hospitalization risk for a patient with COVID-19. doi = 10.1371/journal.pone.0237419 id = cord-001117-llb4f74a author = Ji, Wen-Jie title = Spironolactone Attenuates Bleomycin-Induced Pulmonary Injury Partially via Modulating Mononuclear Phagocyte Phenotype Switching in Circulating and Alveolar Compartments date = 2013-11-19 keywords = BALF; USA; lung; macrophage summary = Moreover, serial flow cytometry analysis in blood, BALF and enzymatically digested lung tissue, revealed that spironolactone could partially inhibit bleomycin-induced circulating Ly6C(hi) monocyte expansion, and reduce alternative activation (F4/80+CD11c+CD206+) of mononuclear phagocyte in alveoli, whereas the phenotype of interstitial macrophage (F4/80+CD11c-) remained unaffected by spironolactone during investigation. CONCLUSIONS/SIGNIFICANCE: The present work provides the experimental evidence that spironolactone could attenuate bleomycin-induced acute pulmonary injury and fibrosis, partially via inhibition of MR-mediated circulating monocyte and alveolar macrophage phenotype switching. Based on current evidence, we speculated that pharmacological inhibition of MR with clinically approved drug, may regulate lung macrophage phenotype switching, as well as their progenitors, bone marrow-derived circulating monocytes, and may confer novel therapeutic potential in a murine model of bleomycin-induced acute pulmonary injury and fibrosis. doi = 10.1371/journal.pone.0081090 id = cord-288440-w7g2agaf author = Jia, Rui title = The C-Terminal Sequence of IFITM1 Regulates Its Anti-HIV-1 Activity date = 2015-03-04 keywords = BH10; HIV-1; IFITM1; NL4 summary = This inhibition appears to be specific to HIV-1, since neither the WT IFITM1 nor its C-terminal truncations affected entry that was mediated by the G protein of vesicular stomatitis virus (VSV) ( Fig. 2A and 2B) . Removing the last 9 or 14 amino acids from C-terminal sequence re-localized the majority of IFITM1 to the cell periphery (Fig. 3A) , indicating that these C-terminus truncated IFITM1 mutants are mostly positioned at the plasma membrane where HIV-1 entry occurs. We recently reported that HIV-1 BH10 became resistant to IFITM1 restriction in the spread infection through acquiring mutations in viral Env and Vpu proteins that together enhance the virus transmission between cells [27] . One possible scenario is that HIV-1 Env protein may modulate virus sensitivity to human IFITM1 restriction by virtue of its ability to mediate and regulate virus cell-to-cell transmission. doi = 10.1371/journal.pone.0118794 id = cord-319256-7pyinx1a author = Jin, Xin title = The values of coagulation function in COVID-19 patients date = 2020-10-29 keywords = PAIC; covid-19 summary = doi = 10.1371/journal.pone.0241329 id = cord-311941-0dpm35dd author = Jones, Bryony A. title = Calf-Level Factors Associated with Bovine Neonatal Pancytopenia – A Multi-Country Case-Control Study date = 2013-12-02 keywords = BNP; BVD; dam summary = Bovine neonatal pancytopenia (BNP), a high fatality condition causing haemorrhages in calves aged less than 4 weeks, was first reported in 2007 in Germany and subsequently observed at low incidence in other European countries and New Zealand. A case had 18 times the odds of being born to a dam that was PregSurevaccinated rather than unvaccinated compared with a control, if the dam was first lactation and the calf did not receive colostrum from other cows, adjusting for type of milk fed (amOR 17.8; ci. A case had 3 times the odds of having been fed raw milk only from its dam rather than other types of milk (with or without dams milk) compared with a control (amOR 3.4; ci 1.6, 7.5; p = 0.002) when adjusting for dam PregSure-vaccination, lactation number and source of colostrum. Case control study to investigate risk factors for bovine neonatal pancytopenia (BNP) in young calves in southern Germany doi = 10.1371/journal.pone.0080619 id = cord-000131-ugbwvy6j author = Jones, James Holland title = Early Assessment of Anxiety and Behavioral Response to Novel Swine-Origin Influenza A(H1N1) date = 2009-12-03 keywords = April; Influenza; respondent; survey summary = Here, we report the results from an online survey that gathered data (n = 6,249) about risk perception of the outbreak during the first few days of widespread media coverage (April 29 -May 5, 2009) of the emergence of novel swine-origin Influenza A(H1N1). To evaluate the hypothesis that respondents'' affective state (subjective anxiety, fatalism about infection) predicts protective measures, we include in the model demographic (age, gender), epidemiological (household size, number of contacts, survey day), and media (source of information on the outbreak) conditioning variables. While our sampling design is subject to many of the usual criticisms of internet-based surveys and is not necessarily representative of the general population, the unparalleled immediacy, longitudinal nature, and the large number of respondents it contains make our data set unique and scientifically important for the study of the spread of information and distribution of risk perception and behavioral change during the most uncertain time (i.e. the initial phase) of an epidemic of a virus novel to the human population. doi = 10.1371/journal.pone.0008032 id = cord-000719-o7ttiu97 author = Jonsson, Colleen B. title = Molecular Imaging Reveals a Progressive Pulmonary Inflammation in Lower Airways in Ferrets Infected with 2009 H1N1 Pandemic Influenza Virus date = 2012-07-20 keywords = DPI; H1N1; PET; TCID summary = doi = 10.1371/journal.pone.0040094 id = cord-335441-bj3me7p8 author = Jourdain, Elsa title = Influenza Virus in a Natural Host, the Mallard: Experimental Infection Data date = 2010-01-28 keywords = H7N7; LPAIV; RNA; duck; figure summary = Five of the six ducks excreted viral RNA in their feces on the first day post-inoculation (PI) and all samples (feces, cloacal and oral swabs) from all birds were positive on the second day PI (Figures 4 and S1 ). Intermittent and moderate (high ct-values) viral RNA shedding was detected for all birds in water, fecal or cloacal samples between day 1 and 7 after H7N7 re-inoculation ( Figure 4 ). Active H5 infection was confirmed only in one duck, by expression of H5-specific antibodies and detection of viral RNA in the various sample types (feces, water, oral and cloacal swabs) with a pattern similar to the H5-inoculated control bird. Eight 3-month-old male wild-type mallards (Anas platyrhynchos) of approximately the same body mass and size (measurement of the left wing, the right tarsus length and the distance from bill tip to back of the skull) were selected from a Swedish duck farm known from previous successive sampling to be free from IAV infection. doi = 10.1371/journal.pone.0008935 id = cord-003602-wtestt8i author = Jung, Eunok title = Strategies in regulating glioblastoma signaling pathways and anti-invasion therapy date = 2019-04-22 keywords = AMPK; Fig; cell; control; glucose summary = doi = 10.1371/journal.pone.0215547 id = cord-304993-t4rua95e author = Jung, Kwonil title = The Effects of Simvastatin or Interferon-α on Infectivity of Human Norovirus Using a Gnotobiotic Pig Model for the Study of Antivirals date = 2012-07-23 keywords = Fig; IFN; gii.4 summary = At 12 hours after treatment with 80 mM simvastatin, LDLR gene expression levels in IPEC-J2 cells were significantly increased compared to 0 to 20 mM treated groups (Fig. 1B) . Simvastatin Impaired TLR3-mediated Induction of IFN-a in Macrophages or Dendritic Cells, Possibly Due to Lowered Expression of TLR3 after Treatment Our in vivo data showing enhanced early infectivity of HuNoV suggested potential subversion of innate immunity related to simvasatin treatment. Oral treatment of Gn pigs with natural human IFN-a (nhIFN-a) [300 international unit (IU)/ kg/day] reduced or curtailed virus shedding in treated animals during the treatment period (PID 1 to 4), compared to untreated animals ( Fig. 7A-C) . In conclusion, simvastatin treatment increased HuNoV infectivity in the Gn pig model, possibly due to its inhibitory effect on innate immunity as well as its cholesterol lowering effect as reported previously [20] . doi = 10.1371/journal.pone.0041619 id = cord-048367-yya6w976 author = Jónsson, Stefán R. title = The Restriction of Zoonotic PERV Transmission by Human APOBEC3G date = 2007-09-12 keywords = APOBEC3; PK-15; perv summary = doi = 10.1371/journal.pone.0000893 id = cord-334695-cjxlw1tu author = Kam, Yiu-Wing title = Cleavage of the SARS Coronavirus Spike Glycoprotein by Airway Proteases Enhances Virus Entry into Human Bronchial Epithelial Cells In Vitro date = 2009-11-17 keywords = 16hbe; SARS; cell; figure summary = title: Cleavage of the SARS Coronavirus Spike Glycoprotein by Airway Proteases Enhances Virus Entry into Human Bronchial Epithelial Cells In Vitro We observed that SARS-CoV spike glycoprotein can be efficiently cleaved by several airway proteases and that this processing enhances entry of SARS-CoVpp. Furthermore, we have identified the putative cleavage sites of airway proteases and, by site-directed mutagenesis, have determined the role of specific amino acid residue for proteolytic processing of the envelope glycoprotein, and for SARS-CoVpp entry into human airway epithelial cells (16HBE) in vitro. In an effort to directly demonstrate that airway protease mediated virus entry enhancement is due to the presence of cleavage site on the SARS spike glycoprotein, 16HBE cells were pre-incubated with wild-type (SARS-CoVpp) or mutant (R667App) pseudotypes on ice, which allowed virus attachment but not entry. doi = 10.1371/journal.pone.0007870 id = cord-324359-88vy3dre author = Kamara, Foday Mamoud title = How villagers in central Sierra Leone understand infection risks under threat of Covid-19 date = 2020-06-24 keywords = Ebola; covid-19 summary = We undertook fieldwork in two villages in central Sierra Leone to gain insight into how rural people faced with Covid-19 assess epidemic infection risks. Asked to explain their choices 48% of players cited information on infection risks modelled by the game and 31% stated that their choices reflected awareness of the need for personal action and respect for local regulations. The data relate to rural populations in Sierra Leone exposed both to Ebola Virus Disease (EVD) in 2014-15 and now to Covid-19 in 2020. Three kinds of responses (Table 5 , 89% of all remarks) dominated comments after people made choices in the game-need for rules governing e.g. quarantine, comments on personal capacities to prevent or avoid infection (often made in the context of justifying a choice for disease "mango"), and comments about the relative risks to be inferred from "reading the stones" (i.e. recognition of a pattern in the way the stones were cast, as in divination practices). doi = 10.1371/journal.pone.0235108 id = cord-251979-j3mme15e author = Kandeel, Amr title = Morbidity, Mortality, and Seasonality of Influenza Hospitalizations in Egypt, November 2007-November 2014 date = 2016-09-08 keywords = Egypt; Health; influenza; sari summary = METHODS: Syndromic case definitions identified individuals with severe acute respiratory infection (SARI) admitted to eight hospitals in Egypt. The aims of this study were to (1) assess the proportion of SARI cases having influenza infection in Egypt; (2) examine the types and subtypes of detected influenza viruses in Egypt; (3) compare demographic and clinical characteristics of influenza-positive SARI cases to those of influenza-negative SARI cases in Egypt; (4) quantify influenza deaths and assess influenza mortality risk factors in Egypt; and (5) establish a defined period of influenza seasonality in Egypt. The odds of death among influenza-positive cases were modeled with logistic regression using different explanatory variables (age group: pediatric <15 years old versus adult 15 years old; sex: male versus female; days from symptom onset to hospitalization: 0-2 versus 3-4 versus 5; chronic conditions: at least one versus none; and influenza type: A versus B). doi = 10.1371/journal.pone.0161301 id = cord-263978-jk82bk1a author = Karaivanov, Alexander title = A social network model of COVID-19 date = 2020-10-29 keywords = Fig; NSIR; section summary = The proposed network-augmented (NSIR) model allows the evaluation, via simulations, of (i) health and economic policies and outcomes for all or subset of the population: lockdown/distancing, herd immunity, testing, contact tracing; (ii) behavioral responses and/or imposing or lifting policies at specific times or conditional on observed states. I construct and compute a dynamic social network-based model of the COVID-19 epidemic and use it to evaluate a range of simulated health and economic policies-herd immunity, distancing, lockdown, testing, quarantine, and contact tracing. While helpful for simplifying the dynamics and computing outcomes, this population-level random matching assumption abstracts from important elements of realism and locality: (i) people are more likely to interact with members of their social network, broadly defined (e.g., family, work, or distance based); (ii) health and economic policies targeting disease mitigation, as well as individual behavioral responses, can affect the rate of viral transmission via a person''s network of contacts vs. doi = 10.1371/journal.pone.0240878 id = cord-267307-kyh0xsrp author = Kasting, Monica L. title = Public perceptions of the effectiveness of recommended non-pharmaceutical intervention behaviors to mitigate the spread of SARS-CoV-2 date = 2020-11-04 keywords = COVID-19; SARS; effectiveness summary = Public health efforts should focus on increasing perceived severity and threat of SARS-CoV-2-related disease, while promoting NPI as effective in reducing threat. A six-item measure was used to assess participants'' perceptions of the effectiveness of NPIs to prevent SARS-CoV-2 infection and spread. Three of the six items measured the perceived effectiveness of preventing yourself from spreading COVID-19 to others and included: 1) wearing a mask anytime you leave the house to go out in public, 2) practicing social distancing by leaving at least six feet between you and other people (this does not include people you live with), and 3) covering your mouth when you cough. Any variable that was significant at p<0.01 in bivariate comparisons was included in an adjusted logistic regression model with the binary lower/ higher perceived effectiveness of COVID-19 prevention measures as the outcome. doi = 10.1371/journal.pone.0241662 id = cord-012387-1ogcxd7b author = Kaufman, Aaron R. title = The political consequences of opioid overdoses date = 2020-08-04 keywords = family; opioid; victim summary = doi = 10.1371/journal.pone.0236815 id = cord-003507-22ylifqo author = Kelly, J. Daniel title = Projections of Ebola outbreak size and duration with and without vaccine use in Équateur, Democratic Republic of Congo, as of May 27, 2018 date = 2019-03-07 keywords = EVD; Ebola; outbreak summary = As of May 27, 2018, 6 suspected, 13 probable and 35 confirmed cases of Ebola virus disease (EVD) had been reported in Équateur Province, Democratic Republic of Congo. We modeled Ebola virus transmission using a stochastic branching process model that included reproduction numbers from past Ebola outbreaks and a particle filtering method to generate a probabilistic projection of the outbreak size and duration conditioned on its reported trajectory to date; modeled using high (62%), low (44%), and zero (0%) estimates of vaccination coverage (after deployment). With the stochastic model, using high, low, and zero estimates of vaccination coverage, the median outbreak sizes for probable and confirmed cases were 82 cases (95% prediction interval [PI]: 55, 156), 104 cases (95% PI: 58, 271), and 213 cases (95% PI: 64, 1450), respectively. We modeled Ebola virus transmission using a stochastic branching process model, parameterized by transmission rates estimated from the dynamics of prior EVD outbreaks, and conditioned on agreement with reported case counts from the 2018 EVD outbreak to date. doi = 10.1371/journal.pone.0213190 id = cord-010368-plpghewn author = Kenmoe, Sebastien title = Association of early viral lower respiratory infections and subsequent development of atopy, a systematic review and meta-analysis of cohort studies date = 2020-04-24 keywords = LRTI; respiratory summary = doi = 10.1371/journal.pone.0231816 id = cord-318696-jheb2fnn author = Kesic, Matthew J. title = Exposure to Ozone Modulates Human Airway Protease/Antiprotease Balance Contributing to Increased Influenza A Infection date = 2012-04-09 keywords = SLPI; TMPRSS2; figure; influenza; ozone summary = doi = 10.1371/journal.pone.0035108 id = cord-001982-arczqdza author = Khajah, Maitham A. title = Anti-Inflammatory Action of Angiotensin 1-7 in Experimental Colitis date = 2016-03-10 keywords = ACE2; Ang; DSS; Fig summary = It is thought that the beneficial effects of ACE-inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) on blood pressure control and in delaying/inhibiting the cardiac remodeling process is through increasing serum levels of Ang1-7 [9] [10] [11] [12] . A seven fold decrease in the plasma level of Ang 1-7 was demonstrated in DSS treated mice compared to untreated (UT) group at day 7 post colitis induction (Fig 1A) . The level of phosphorylated forms of three key signaling intermediates, ERK1/2 (Fig 8) , p38 MAPK (Fig 9) and Akt (Fig 10) , were measured by immunofluorescence in sections from resected colon tissue of untreated mice or mice treated with DSS (for 7 days) plus daily Ang 1-7 or saline (vehicle) treatment. doi = 10.1371/journal.pone.0150861 id = cord-346819-11fkgzaa author = Khan, Mohd Imran title = Comparative genome analysis of novel coronavirus (SARS-CoV-2) from different geographical locations and the effect of mutations on major target proteins: An in silico insight date = 2020-09-03 keywords = CoV-2; Mpro; SARS; protein summary = title: Comparative genome analysis of novel coronavirus (SARS-CoV-2) from different geographical locations and the effect of mutations on major target proteins: An in silico insight A novel severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) causing COVID-19 pandemic in humans, recently emerged and has exported in more than 200 countries as a result of rapid spread. Main protease (Mpro), the therapeutic target protein of SARS with maximum reported inhibitors, was thoroughly investigated and the effect of mutation on the binding affinity and structural dynamics of Mpro was studied. The genome analysis of the SARS-CoV-2 strains from 13 different countries showed a large number of mutations within the major structural proteins. This study provides a deeper insight into the emergence of these mutations within the major structural as well as nsp encoded by the SARS-CoV-2 genome from different countries. Comparative genome analysis of novel coronavirus (SARS-CoV-2) from different geographical locations backbone RMSD was also noticed (Fig 4A) . doi = 10.1371/journal.pone.0238344 id = cord-351142-g20f6bxc author = Kiaghadi, Amin title = Assessing COVID-19 risk, vulnerability and infection prevalence in communities date = 2020-10-29 keywords = County; Fig; Harris; covid-19 summary = A finer spatial resolution is important from a vulnerability and risk standpoint as demonstrated in a recent study that showed that the poorest neighborhoods in Houston, Texas, might be at a higher risk of hospitalization from COVID-19 [14] based on an analysis of the Centers for Disease Control (CDC) underlying risk factors for severe COVID-19 cases [4] that include: asthma, Chronic Obstructive Pulmonary Disease (COPD), heart disease, hypertension, diabetes, and a history of heart attacks or strokes. In this study, we develop a rigorous planning tool at the census tract level that examines influential determinants of vulnerability to COVID-19 in 5 broad categories (with 46 variables) that include: 1) access to medical services, 2) underlying medical conditions, 3) environmental exposures, 4) vulnerability to natural disasters and 5) sociodemographic, behavioral, and lifestyle factors. Fig 9A shows the normalized total number of confirmed COVID-19 cases as of August 16, 2020, in Harris County at the census tract level. doi = 10.1371/journal.pone.0241166 id = cord-302200-9gekjgr0 author = Kilich, Eliz title = Factors that influence vaccination decision-making among pregnant women: A systematic review and meta-analysis date = 2020-07-09 keywords = Appendix; File; vaccination summary = Previous reviews have established a narrative of evidence that suggests a broad range of factors (vaccine cost, accessibility, maternal knowledge, social influences, context, healthcare professional (HCP) recommendation and the perception of risks and benefits) all contribute to vaccine uptake. Thus, we performed a systematic review and meta-analysis of qualitative and quantitative literature to provide comprehensive evidence on the magnitude of effect that factors influence maternal vaccination decisions globally with the aim to inform policy makers, public health strategists and researchers involved in designing vaccine interventions to increase uptake. For seasonal influenza, the data is inconclusive since women who believed that the disease could be harmful to their pregnancy or baby had four-times greater odds of being vaccinated than those who did not (OR 3.70, 95% CI 1.37-9.94) yet there was no evidence to suggest belief in the risk of the disease generally (OR 1.56, 95% CI 0.88-2.76) or its ability to result in hospitalisation (OR 0.57, 95% CI 0.22-1.45) were related to vaccine uptake. doi = 10.1371/journal.pone.0234827 id = cord-260572-vd65ygtm author = Kim, Curi title = Comparison of Nasopharyngeal and Oropharyngeal Swabs for the Diagnosis of Eight Respiratory Viruses by Real-Time Reverse Transcription-PCR Assays date = 2011-06-30 keywords = swab summary = BACKGROUND: Many acute respiratory illness surveillance systems collect and test nasopharyngeal (NP) and/or oropharyngeal (OP) swab specimens, yet there are few studies assessing the relative measures of performance for NP versus OP specimens. For respiratory disease surveillance programs using qRT-PCR that aim to maximize sensitivity for a large number of viruses, collecting combined NP and OP specimens would be the most effective approach. To evaluate the comparative yields of NP and OP swabs in detecting key respiratory viruses by real-time RT-PCR (qRT-PCR), we conducted a prospective study using paired NP and OP specimens from patients at two respiratory disease surveillance sites in Kenya. NP and OP specimens from each patient were separately tested by singleplex qRT-PCR for eight viral pathogens: adenovirus, influenza A virus, influenza B virus, human metapneumovirus (hMPV), parainfluenza viruses (PIV) 1-3, and respiratory syncytial virus (RSV). doi = 10.1371/journal.pone.0021610 id = cord-002913-k5b6abyk author = Kim, Ha Kyun title = Asymmetric expression level of clock genes in left vs. right nasal mucosa in humans with and without allergies and in rats: Circadian characteristics and possible contribution to nasal cycle date = 2018-03-13 keywords = PER1; PER2; clock; nasal summary = doi = 10.1371/journal.pone.0194018 id = cord-340766-aic570x8 author = Kim, Se Jin title = Outcomes of Early Administration of Cidofovir in Non-Immunocompromised Patients with Severe Adenovirus Pneumonia date = 2015-04-15 keywords = adv; patient; pneumonia summary = The present study describes in detail the clinical characteristics and favorable treatment outcomes of non-immunocompromised adults who had experienced severe AdV pneumonia and received early cidofovir administration. Only non-immunocompromised adult patients who fulfilled the criteria for severe community-acquired pneumonia, set out in the Infectious Diseases Society of America/American Thoracic Society Consensus Guidelines [23] , and admitted to the intensive care unit with progressive respiratory failure, defined as a partial pressure of arterial oxygen (PaO 2 )/fraction of inspired oxygen (FiO 2 ) ratio of < 300 mmHg and/or tachypnea (respiration rate >30 breaths/min) [24] , were included in the analysis. Our data suggest that early administration of cidofovir in the course of treatment for respiratory failure as a result of AdV pneumonia in non-immunocompromised patients could be a treatment strategy worth considering, especially in cases of HAdV-55 infection. Our data suggest that early administration of cidofovir in the course of treatment for respiratory failure as a result of AdV pneumonia in non-immunocompromised patients could be a treatment strategy worth considering, especially in cases of HAdV-55 infection. doi = 10.1371/journal.pone.0122642 id = cord-254825-c5d0wul9 author = Kim, Sei Won title = Containment of a healthcare-associated COVID-19 outbreak in a university hospital in Seoul, Korea: A single-center experience date = 2020-08-14 keywords = COVID-19; PCR; SARS summary = In this study, we retrospectively analyzed the results of SARS-CoV-2 RT-PCR testing, contact history, and presence of respiratory symptoms in a single center with a healthcare-associated COVID-19 outbreak. We reviewed the history of patients to assess whether they visited China or other high-risk countries within two weeks prior to the outbreak of healthcare-associated COVID-19, or if they came into contact with confirmed COVID-19 cases. After SARS-CoV-2 infection was confirmed, the Seoul city government announced the closure of the hospital on February 21, 2020, to prevent a healthcare-associated outbreak. After the hospital staff member responsible for transporting patients was confirmed as the first COVID-19 case, people with contact history, fever, or respiratory symptoms were tested for SARS-CoV-2 infection with RT-PCR (Fig 2) . After the first case was reported, epidemiologists from KCDC and the infection control unit of our hospital reviewed electronic medical charts, CCTV, and personal movements to identify individuals with potential contact with confirmed COVID-19 patients. doi = 10.1371/journal.pone.0237692 id = cord-001088-dugsh7mp author = Kim, So-Hee title = Mucosal Vaccination with Recombinant Adenovirus Encoding Nucleoprotein Provides Potent Protection against Influenza Virus Infection date = 2013-09-25 keywords = CD8; pfu summary = doi = 10.1371/journal.pone.0075460 id = cord-001014-8yrpcl94 author = Kitagawa, Hiroshi title = Intranasally Administered Antigen 85B Gene Vaccine in Non-Replicating Human Parainfluenza Type 2 Virus Vector Ameliorates Mouse Atopic Dermatitis date = 2013-07-03 keywords = EGFP; ag85b summary = title: Intranasally Administered Antigen 85B Gene Vaccine in Non-Replicating Human Parainfluenza Type 2 Virus Vector Ameliorates Mouse Atopic Dermatitis Ear swelling, dermal cell infiltrations and serum IgE level were significantly suppressed in the rhPIV2/Ag85B treated mouse group accompanied with elevated IFN-γ and IL-10 mRNA expressions, and suppressed IL-4, TNF-α and MIP-2 mRNA expressions. Expression of IL-4 mRNA was significantly decreased in the ear skin of intra-nasally rhPIV2/Ag85B treatment group compared to that of PBS treated mice (Fig. 4A) . mRNA expressions of TNF-a and MIP-2 were significantly decreased in both of intra-nasally and subcutaneously rhPIV2/Ag85B treated groups compared with PBS or vector treated group (Fig. 4E, F) . Ag85B is a conserved protein in mycobacterial species and can elicit a strong Th1-type immune Expressions of IL-4, TNF-a and MIP2-a mRNA were significantly decreased in the ear skin treated with intranasally rhPIV2/Ag85B treated group compared to those of control groups. doi = 10.1371/journal.pone.0066614 id = cord-254313-g2oc32dm author = Klink, Thomas title = Evaluating the diagnostic accuracy of the WHO Severe Acute Respiratory Infection (SARI) criteria in Middle Eastern children under two years over three respiratory seasons date = 2020-04-30 keywords = RSV; criterion; sari summary = Several studies, including at least nine in the Eastern Mediterranean region, have been published since 2011 using the SARI case definition as inclusion criteria to report a combination of clinical characteristics, risk factors, viral burden, or outcomes in adult and pediatric populations for flu and other respiratory viruses [5] [6] [7] [8] [9] [10] [11] [12] [13] . Only a handful of studies have evaluated the effectiveness of the criteria by including both SARI-positive and SARI-negative patients, allowing them to calculate the diagnostic accuracy of the criteria for detecting flu and respiratory syncytial virus (RSV) [14] [15] [16] [17] [18] [19] . The age distribution differences likely explain these discrepancies as our cohort consists only of children under two years, and the SARI criteria were the least sensitive (15.9%) and most specific (80.5%) for detecting flu in our patients under three months, who make up 45.4% of our study population. doi = 10.1371/journal.pone.0232188 id = cord-286837-j2sqs20q author = Koetsier, Antonie title = Do Intensive Care Data on Respiratory Infections Reflect Influenza Epidemics? date = 2013-12-31 keywords = ICU; ILI; week summary = METHODS: We calculated the time lag and correlation between ILI incidence (from ILI sentinel surveillance, based on general practitioners (GP) consultations) and percentages of ICU admissions with a respiratory infection (from the Dutch National Intensive Care Registry) over the years 2003–2011. In the season 2009/2010 as well as in the season 2010/2011, ILI incidence as measured by GP sentinel practices, reached the epidemic threshold of 5.1 consultations per 10.000 enlisted patients at a time when already more than 100 patients had been hospitalized, with several ICU admissions and deaths from laboratory confirmed Influenza (National Institute for Public Health and the Environment, unpublished surveillance data). In our study we built three additive Poisson GEE regression models with ICU data to predict the incidence of ILI patients, thereby detecting influenza epidemics and aimed at detecting opportunities for enhancing the current national surveillance method. doi = 10.1371/journal.pone.0083854 id = cord-344152-pb1e2w7s author = Kolatkar, Anand title = C-ME: A 3D Community-Based, Real-Time Collaboration Tool for Scientific Research and Training date = 2008-02-20 keywords = 3-d; MOSS; datum summary = Collaborative Molecular Modeling Environment (C-ME) is an interactive community-based collaboration system that allows researchers to organize information, visualize data on a two-dimensional (2-D) or three-dimensional (3-D) basis, and share and manage that information with collaborators in real time. These annotations provide additional information about the atomic structure or image data that can then be evaluated, amended or added to by other project members. For example, protein structure/activity data annotations and images may be kept in paper lab notebooks, manuscripts might be stored electronically in Portable Document Format (PDF), and molecular structure coordinate files may be stored on a hard disk to be viewed and analyzed in graphical molecular viewers, to name a few. Most recently we have developed the Collaborative Molecular Modeling Environment (C-ME), a new collaboratory system that integrates many of the key features available on Kinemage, MICE, iSee, and BioCoRE systems into one thin-client Windows application. doi = 10.1371/journal.pone.0001621 id = cord-329223-f84gjxm1 author = Kouokam, Joseph Calvin title = Investigation of Griffithsin''s Interactions with Human Cells Confirms Its Outstanding Safety and Efficacy Profile as a Microbicide Candidate date = 2011-08-02 keywords = E6E7; Fig; HIV-1; PBMC; grft summary = In contrast to several other antiviral lectins however, GRFT treatment induces only minimal changes in secretion of inflammatory cytokines and chemokines by epithelial cells or human PBMC, has no measureable effect on cell viability and does not significantly upregulate markers of T-cell activation. When freshly-isolated PBMC were pre-incubated for 24 hrs with GRFT at various concentrations, washed and then infected with HIV-1 R5 strain BaL (without adding new compound), GRFT inhibited viral replication for 9 days of cell culture (Fig. 2) . In addition, the numbers of CD4 2 /CD25 + cells were elevated when PBMC were cultured in presence of PHA or ConA compared to their PBS and GRFT counterpart (Fig. 6 , left panel and data not shown). The heat map shown in Fig. 9A indicates that cells exposed for 24 hours to GRFT Lec-(1 and 8 mM), and low concentrations of GRFT (0.1 mM ) and CV-N (0.05 mM) showed comparable gene expression profiles to those that were incubated in presence of PBS alone. doi = 10.1371/journal.pone.0022635 id = cord-321624-z2mntwef author = Kowitdamrong, Ekasit title = Antibody responses to SARS-CoV-2 in patients with differing severities of coronavirus disease 2019 date = 2020-10-09 keywords = CoV-2; SARS summary = AIM: To investigate SARS-CoV-2 IgA and IgG antibodies in Thai patients with differing severities of COVID-19. The objective of this study was to investigate the response of IgA and IgG antibodies to SARS--CoV-2 in serial blood samples collected from a population of Thai patients with confirmed COVID-19, and the association of these responses with the severity of the illness. The second subgroup included 49 plasma samples collected from May 1 to May 31, 2020, from patients under investigation (PUI) for COVID-19 with RT-PCR results that were negative for SARS-CoV-2. In the present study, 30% of COVID-19 patients developed positive IgA antibodies very early, within 3 days after the onset of symptoms. In the present study, 20% of the patients with mild symptoms did not develop any IgG antibodies specific to COVID-19, even after 2 weeks after the onset of symptoms. doi = 10.1371/journal.pone.0240502 id = cord-319538-bawzonq1 author = Krause, Martin title = Association between procalcitonin levels and duration of mechanical ventilation in COVID-19 patients date = 2020-09-18 keywords = COVID-19; mechanical summary = Based on observational studies from the epicenters of the pandemic in Wuhan, China, the Lombardy region in Italy, and the New York City area in the United States, a significant portion of patients diagnosed with coronavirus disease 2019 (COVID19) were admitted to the intensive care unit (ICU) for ventilatory support: Between 17%-24% of hospitalized patients and up to 72% of patients admitted to the ICU have required invasive mechanical ventilation [2] [3] [4] [5] . We aimed to identify if plasma procalcitonin levels on admission are associated with the duration of mechanical ventilation (primary outcome), 28-day mortality, and time to intubation (secondary outcomes) in a cohort of COVID-19 patients requiring mechanical ventilation. In the univariate analysis of our observational cohort study, procalcitonin levels >0.1 ng/ml on admission were associated with prolonged mechanical ventilation in critically ill COVID-19 patients. doi = 10.1371/journal.pone.0239174 id = cord-337879-liqhbqxl author = Kriesel, John D. title = Deep Sequencing for the Detection of Virus-Like Sequences in the Brains of Patients with Multiple Sclerosis: Detection of GBV-C in Human Brain date = 2012-03-08 keywords = GBV; RNA summary = Sequences from GB virus C (GBV-C), a flavivirus not previously isolated from brain, were enriched in one of the MS samples. This study shows the feasibility of deep sequencing for the detection of occult viral infections in the brains of deceased persons with MS. Multiple sclerosis (MS) is a chronic demyelinating disease of unknown cause, which affects the brain and spinal cord of about 400,000 individuals in the U.S. A number of viral infections of the CNS can lead to demyelination, including distemper (dogs), measles (SSPE, humans), and influenza (humans). To enhance the detection of non-human sequences, RNA samples that passed the quality control step above were subjected to rRNA removal using the RiboMinus kit (Invitrogen Inc., Carlsbad, CA). One subject who died with primary-progressive MS had .1000 36 bp sequences detected that mapped to GBV-C virus (hepatitis G), a human flavivirus not known to cause any persistent disease and never before detected in human brain. doi = 10.1371/journal.pone.0031886 id = cord-325113-sou8xyld author = Kuiper, Johannes W. P. title = Detection of SARS-CoV-2 from raw patient samples by coupled high temperature reverse transcription and amplification date = 2020-11-02 keywords = PCR; RNA; SARS summary = The use of unprocessed swap samples is enabled by employing a heat-stable RNAand DNA-dependent DNA polymerase, which performs the double task of stringent reverse transcription of RNA at elevated temperatures as well as PCR amplification of a SARS-CoV-2 specific target gene. A RNA-and DNA-reading heat-stable polymerase reverse transcribes and amplifies viral RNA Evidence of an acute SARS-CoV-2 infection depends on the detection of viral RNA species in patient samples, which necessitates reverse transcription of RNA followed by PCR amplification of the resulting DNA. To evaluate the potential of the high-temperature RT-PCR protocol using Volvano3G for the detection of viral RNAs in patient material, we assessed the presence of SARS-CoV-2 in RNA isolated from a small cohort of COVID-19 suspected cases. Interestingly, for most positive samples detected by the high-temperature RT-PCR with Volcano3G, the cq-values were lower compared to the standard RT-PCR (Fig 3C and 3D) , indicating that the detection of SARS-CoV-2 from unprocessed patient material is not limited by the sensitivity of this direct approach. doi = 10.1371/journal.pone.0241740 id = cord-000556-uu1oz2ei author = Kumar, Ranjit title = RNA-Seq Based Transcriptional Map of Bovine Respiratory Disease Pathogen “Histophilus somni 2336” date = 2012-01-20 keywords = RNA; Seq; genome summary = Whole genome transcriptome analysis is a complementary method to identify "novel" genes, small RNAs, regulatory regions, and operon structures, thus improving the structural annotation in bacteria. Therefore, genome structural annotation or the identification and demarcation of boundaries of functional elements in a genome (e.g., genes, non-coding RNAs, proteins, and regulatory elements) are critical elements in infectious disease systems biology. Whole genome transcriptome studies (such as whole genome tiling arrays [13, 14, 15] and high throughput sequencing [16, 17] ) are complementary experimental approaches for bacterial genome annotation and can identify ''''novel'''' genes, gene boundaries, regulatory regions, intergenic regions, and operon structures. We compared the RNA-Seq based transcriptome map with the available genome annotation to identify expressed, novel, and intergenic regions in the genome. The single nucleotide resolution map helped uncover the structure and complexity of this pathogen''s transcriptome and led to the identification of novel, small RNAs and protein coding genes as well as gene co-expression. doi = 10.1371/journal.pone.0029435 id = cord-278099-ypov9ha3 author = Kumar, Surender title = Molecular characterization of a novel cryptic virus infecting pigeonpea plants date = 2017-08-03 keywords = 3Dpol; Fig; RNA; motif; virus summary = The four dsRNAs eluted from the agarose gel were purified and have been used as templates for RT-PCR amplification employed in SISPA to generate fulllength cDNAs. It is of interest to examine if ArCV-1 RNA dependent RNA polymerase (RdRp) structurally resembles the known RdRp of the dsRNA bacteriophage Փ-6, reovirus, or with other viruses like calciviruses and picornaviruses [12] [13] [14] [15] [16] . We report here the results of elaborated computer-assisted analysis of ArCV-1 replicase which revealed the presence of conserved sequence motifs (A to G) present in the fingers and palm subdomains of the polymerase that are shared in most of the RdRps. Interestingly, ArCV-1 replicase has more structural resemblances with several members of ssRNA (+) mono-partite Picornaviruses (viral replication by primer-dependent initiation), than the de novo dsRNA bacteriophage Փ-6 and reovirus polymerases. Possible functions of the residues of the A to G motifs described for identical RdRps was conserved with respect to the ArCV-1 3Dpol structure and was discussed in structural analysis of ArCVTable 1 ) and the 3'' terminus contained the sequence "GCA CCCATATTC". doi = 10.1371/journal.pone.0181829 id = cord-347465-yu6oj30v author = Kurskaya, Olga title = Viral etiology of acute respiratory infections in hospitalized children in Novosibirsk City, Russia (2013 – 2017) date = 2018-09-18 keywords = Russia; respiratory; virus summary = METHODS: We tested nasal and throat swabs of 1560 children with upper or lower respiratory infection for main respiratory viruses (influenza viruses A and B, parainfluenza virus types 1–4, respiratory syncytial virus, metapneumovirus, four human coronaviruses, rhinovirus, adenovirus and bocavirus) using a RT-PCR Kit. RESULTS: We detected 1128 (72.3%) samples were positive for at least one virus. We detected significant decrease of the respiratory syncytial virus-infection incidence in children with increasing age, while the reverse relationship was observed for influenza viruses. We detected significant decrease of the respiratory syncytial virus-infection incidence in children with increasing age, while the reverse relationship was observed for influenza viruses. In conclusion, in our study we investigated the etiological structure of acute respiratory viral infections in hospitalized children in Novosibirsk, Russia, and evaluated age and seasonal distribution of the various respiratory viruses. doi = 10.1371/journal.pone.0200117 id = cord-298078-uqrwq5qk author = Kwak, Hoyun title = Annexin A2 Binds RNA and Reduces the Frameshifting Efficiency of Infectious Bronchitis Virus date = 2011-08-30 keywords = ANXA2; IBV; RNA; pseudoknot summary = The results suggest that ANXA2 is a cellular RBP that can modulate the frameshifting efficiency of viral RNA, enabling it to act as an anti-viral cellular protein, and hinting at roles in RNA metabolism for other cellular mRNAs. Ribosomal frameshifing is a recoding process of translation where a specific messenger RNA (mRNA)-mediated signal directs a ribosome to shift its reading frame and to continue in the new frame. To search for cellular proteins that directly interacted with IBV pseudoknot RNA, a RNA pull down assay was performed in the presence of cell extracts (Figure 2A ). Through the RNA-immunoprecipitation assay, we showed that ANXA2 specifically interacted with wild-type IBV pseudoknot RNA but not with mutant IBV RNA in LNCaP and HEK293T cells ( Figure 3C and 3D). To test how ANXA2 regulates the frameshifting efficiency of IBV pseudoknot RNA, we first overexpressed ANXA2 protein in the presence of the reporters and measured the luciferase activities. doi = 10.1371/journal.pone.0024067 id = cord-267566-gdjl0qmu author = Kweon, Oh Joo title = Antibody kinetics and serologic profiles of SARS-CoV-2 infection using two serologic assays date = 2020-10-22 keywords = COVID-19; PSO; SARS summary = This study aims to assess the serologic profiles and time kinetics of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in patients with COVID-19 using two immunoassays. METHODS: A total of 97 samples serially collected from 17 patients with COVID-19 and 137 negative control samples were analyzed for IgM and IgG against SARS-CoV-2 using the AFIAS COVID-19 Ab (Boditech Med Inc., Chuncheon, Republic of Korea) and the EDI(™) Novel Coronavirus COVID-19 ELISA Kit (Epitope Diagnostics, Inc., San Diego, CA). The diagnostic sensitivities of IgM/IgG for ≤14d PSO were 21.4%/35.7~57.1% and increased to 41.2~52.9%/88.2~94.1% at >14 d PSO with specificities of 98.5%/94.2% for AFIAS COVID-19 Ab and 100.0%/96.4% for EDI(™) Novel Coronavirus COVID-19 ELISA Kit. Among 137 negative controls, 12 samples (8.8%) showed positive or indeterminate results. doi = 10.1371/journal.pone.0240395 id = cord-307934-84zfabti author = Lai, Chao-Kuen title = Nonstructural Protein 5A Is Incorporated into Hepatitis C Virus Low-Density Particle through Interaction with Core Protein and Microtubules during Intracellular Transport date = 2014-06-06 keywords = Core; Fig; HCV; NS5A; RNA summary = Further studies by cofractionation analysis and immunoelectron microscopy of the released particles showed that NS5A-Core complexes, but not NS4B, were present in the low-density fractions, but not in the high-density fractions, of the HCV RNA-containing virions and associated with the internal virion core. Overall, our results suggest that HCV NS5A is associated with the core of the low-density virus particles which exit the cell through a preexisting endosome/exosome pathway and may contribute to HCV natural infection. Both NS5A and Core proteins are found to be closely associated with and co-transported along the microtubules from the perinuclear region of cells via the LDs and endosomes to the plasma membrane. (A) The HCV-infected cells (at day 10 p.i.) were labeled with antibodies specific for Core protein (red) and NS5A (green) (upper row) or NS4B (green) (lower row). doi = 10.1371/journal.pone.0099022 id = cord-261908-olcuq6tm author = Lai, Ka-Man title = Propagation of Respiratory Aerosols by the Vuvuzela date = 2011-05-23 keywords = particle; respiratory; vuvuzela summary = The fate of the droplet nuclei on inhalation also depends on their size; particles greater than five microns are likely to remain in the upper airways but smaller particles are more likely to deposit in the alveoli and so may transmit infections of the lower respiratory tract such as tuberculosis [22, 23] . The large number of aerosols emitted by the vuvuzela raises the possibility that, if used by persons with an infection of the respiratory tract, they could act a conduit for the spread of infectious particles. To obtain the desired trumpet sound when blowing the vuvuzela air is forced through the lips into the opening of the instrument which may serve to create further aerosols, or alter the size of droplets produced elsewhere in the respiratory tract. Exhale duration, peak air velocity, particle concentration and mean particle diameter recorded during playing the vuvuzela and shouting by four male and four female volunteers. doi = 10.1371/journal.pone.0020086 id = cord-305393-96mrxt8a author = Lai, Yvonne title = Viral Double-Strand RNA-Binding Proteins Can Enhance Innate Immune Signaling by Toll-Like Receptor 3 date = 2011-10-10 keywords = Fig; HCV; RNA; TLR3; il6 summary = Recombinant 1b hepatitis C virus polymerase was found to enhance TLR3 signaling in the lung epithelial BEAS-2B cells when added to the media along with either poly(I:C) or viral dsRNAs. The polymerase from the genotype 2a JFH-1 HCV was a poor enhancer of TLR3 signaling until it was mutated to favor a conformation that could bind better to a partially duplexed RNA. These results demonstrate that several viral RNA-binding proteins can enhance the dsRNA-dependent innate immune response initiated by TLR3. Transfection of two plasmids, one containing an interferon stimulated response element (ISRE) promoter-driven firefly luciferase and a second encoding a constitutively expressed Renilla luciferase allow the analysis of TLR3 activation by different RNAs. HEK 293T cells expressing WT TLR3 responded to poly(I:C) (1-2 mg/ml), better than viral dsRNAs (1-2 mg/ml) purified from Reovirus and BPEV (Fig. 1B) . doi = 10.1371/journal.pone.0025837 id = cord-291360-z19ri377 author = Lan, Fan-Yun title = COVID-19 symptoms predictive of healthcare workers’ SARS-CoV-2 PCR results date = 2020-06-26 keywords = PCR; SARS summary = Of 509 HCWs with initial negative SARS-CoV-2 assays, nine had symptom progression and positive re-tests, yielding an estimated negative predictive value of 98.2% (95% CI: 96.8–99.0%) for the exclusion of clinically relevant COVID-19. CONCLUSIONS: Symptom and temperature reports are useful screening tools for predicting SARS-CoV-2 assay results in HCWs. Anosmia/ageusia, fever, and myalgia were the strongest independent predictors of positive assays. Therefore, we investigated the presenting symptoms most predictive of positive/negative SARS-CoV-2 RT-PCR results among HCWs. Since March 9, 2020, the occupational health service of a Massachusetts community healthcare system has implemented a staff "hotline" system to maintain a viable/healthy workforce and operational continuity during the pandemic. The clinical COVID-19 attack rate during the study period was calculated as: (the number of initial positive SARS-CoV-2 assays + the number of false negatives) divided by the system''s estimated total HCW population (n = 4600). doi = 10.1371/journal.pone.0235460 id = cord-339724-roj8ksvc author = Lan, Jiaming title = Tailoring Subunit Vaccine Immunity with Adjuvant Combinations and Delivery Routes Using the Middle East Respiratory Coronavirus (MERS-CoV) Receptor-Binding Domain as an Antigen date = 2014-11-18 keywords = A+C; I+C; MERS; RBD summary = title: Tailoring Subunit Vaccine Immunity with Adjuvant Combinations and Delivery Routes Using the Middle East Respiratory Coronavirus (MERS-CoV) Receptor-Binding Domain as an Antigen Interestingly, robust RBD-specific antibody and T-cell responses were induced in mice immunized with the rRBD protein in combination with IFA and CpG ODN, but low level of neutralizing antibodies were elicited. In this study, different adjuvants combination regimens including alum, IFA, CpG and poly(I:C) were compared in an effort to promote balance between Th1 and Th2 immune response to bystander rRBD antigen spanning residues 367-606 of MERS-CoV S in a murine model to develop an effective vaccine against MERS-CoV infection. The results indicated that rRBD protein combined with any adjuvant, including alum, IFA, CpG or poly(I:C), could induce a RBD-specific IgG antibody response in the majority of mice after the second immunisation. doi = 10.1371/journal.pone.0112602 id = cord-255351-vp19ydce author = Lanata, Claudio F. title = Global Causes of Diarrheal Disease Mortality in Children <5 Years of Age: A Systematic Review date = 2013-09-04 keywords = child; pathogen; study summary = We present the results of a systematic literature review of studies of diarrhea etiology in hospitalized children and use these results to estimate the global burden of diarrhea mortality by pathogen for children under 5 years of age for 2011. From 22 643 citations identified in the electronic search, 1 003 articles were selected for further evaluation (Fig. 1) ; 840 articles were excluded because they had one or more of the exclusion criteria (About 35% because they were not longitudinal studies or inappropriate laboratory methods were used, 31% because no data was given for children ,5 years of age, 23% for studies that lasted less than 12 months of duration, and the rest because data were reported after rotavirus vaccine introduction, duplicate publications or reporting results on a pathogen not included in our list). doi = 10.1371/journal.pone.0072788 id = cord-352522-qnvgg2e9 author = Langille, Morgan G. I. title = BioTorrents: A File Sharing Service for Scientific Data date = 2010-04-14 keywords = BioTorrents; datum summary = In this study we present BioTorrents, a website that allows open access sharing of scientific data and uses the popular BitTorrent peer-to-peer file sharing technology. A BitTorrent software client (see Table 1 ) uses the data in the torrent file to contact the tracker and allow transferring of the data between computers containing either full or partial copies of the dataset. Information about each dataset on BioTorrents is supplied on a details page giving a description of the data, number of files, date added, user name of the person who created the dataset, and various other details including a link to the actual torrent file. As the number of datasets and users of BioTorrents increases, and to improve on transfer speeds on a geospatial scale (i.e. across countries and continents), we would encourage other institutions to automatically download and share all or some of the data on BioTorrents. doi = 10.1371/journal.pone.0010071 id = cord-001249-awn9ayy6 author = Lasecka, Lidia title = The Nairovirus Nairobi Sheep Disease Virus/Ganjam Virus Induces the Translocation of Protein Disulphide Isomerase-Like Oxidoreductases from the Endoplasmic Reticulum to the Cell Surface and the Extracellular Space date = 2014-04-08 keywords = Congo; NSDV; PDI; cell; figure summary = ERp57 while the structure of the ER, ERGIC and Golgi remains unchanged Two isolates of NSDV have been previously described by us [29] : a multiple-times passaged isolate of NSDV from Uganda, which appeared attenuated upon infection of a susceptible animal, and an isolate of GV from India which had been passaged a limited number of times in mouse brain or BHK21 clone 13 cells and which caused haemorrhagic gastroenteritis in sheep upon experimental inoculation. No change to the cellular distribution of calnexin was observed (Figure 2 j-l), indicating that, despite the disappearance of PDI and ERp57, the overall structure of the ER remains unchanged in NSDV-infected cells. Another flavivirus, Dengue virus (DENV) (which, like NSDV, can cause a haemorrhagic fever), increased surface levels of PDI in infected endothelial cells [86] . In this study we have demonstrated that NSDV induces the redistribution of soluble ER oxidoreductases, specifically PDI and ERp57, in infected cells, and that the viral PreGn glycoprotein appears to be involved in this process. doi = 10.1371/journal.pone.0094656 id = cord-295293-ickp2n47 author = Latsuzbaia, Ardashel title = Evolving social contact patterns during the COVID-19 crisis in Luxembourg date = 2020-08-06 keywords = IQR; contact summary = While the number of social contacts was substantially lower during the lockdown by more than 80% compared to the pre-pandemic period, we observed a more recent 121% increase during the post lockdown period showing an increased potential for COVID-19 spread. We repeatedly conducted an internet survey to follow up the impact of the local government interventions on social contact patterns in Luxembourg shortly after the lockdown was implemented due to the rapid local spread of the COVID-19. The average number of contacts reported by Luxembourg residents in a study before the pandemic was 17.5 [4] , suggesting that contacts during lockdown had decreased by 81.7%. Our study suggests that the strict physical distancing measures implemented in Luxembourg had a substantial and immediate impact on social mixing patterns resulting in a large reduction of the average number of contacts per day. In conclusion, our stud shows that physical distance measures resulted in significant reduction in social contacts and therefore decreased the spread of COVID-19 in Luxembourg. doi = 10.1371/journal.pone.0237128 id = cord-000937-8vk89i4h author = Law, John title = Identification of Hepatotropic Viruses from Plasma Using Deep Sequencing: A Next Generation Diagnostic Tool date = 2013-04-17 keywords = RNA; dna; figure; virus summary = doi = 10.1371/journal.pone.0060595 id = cord-290034-4b0mshqa author = Le, Yen H. title = Virus detections among patients with severe acute respiratory illness, Northern Vietnam date = 2020-05-12 keywords = SARI; Vietnam; virus summary = To examine evidence for select viral infections among patients with SARI in northern Vietnam, we studied 348 nasopharyngeal samples from military and civilian patients admitted to 4 hospitals in the greater Hanoi area from 2017–2019. Initial screening for human respiratory viral pathogens was performed in Hanoi, Vietnam at the National Institute of Hygiene and Epidemiology (NIHE) or the Military Institute of Preventative Medicine (MIPM), and an aliquot was shipped to Duke-NUS Medical School in Singapore for validation. There was one case of co-infection with enterovirus and coronavirus 229E including a female military hospital patient 28 years of age. Additionally, our results display enterovirus, adenovirus and coronavirus infections among the SARI cases, suggesting that cities in northern Vietnam could benefit also from local surveillance of non-influenza respiratory viruses. doi = 10.1371/journal.pone.0233117 id = cord-289305-mfjyjjer author = Lee, Min Hye title = A systematic review on the causes of the transmission and control measures of outbreaks in long-term care facilities: Back to basics of infection control date = 2020-03-10 keywords = gas; outbreak; study summary = title: A systematic review on the causes of the transmission and control measures of outbreaks in long-term care facilities: Back to basics of infection control Three studies on gastrointestinal infection, in which adherence to hand hygiene among HCWs was crucial to prevent its spread, reported control measures including stringent hand hygiene practice and reinforcement of standard precautions [23, 27, 31] . The study on the RSV and HMPV outbreak reported various measures including active surveillance, isolation, contact precaution, antiviral prophylaxis for residents and work restriction for ill staff to control respiratory pathogen transmission [50] . This update for understanding outbreaks in LTCFs by reviewing recent studies indicates that staff members and residents are still at risk for contagious disease outbreaks including influenza, gastroenteritis, and GAS infection. Influenza outbreak control practices and the effectiveness of interventions in long-term care facilities: a systematic review doi = 10.1371/journal.pone.0229911 id = cord-286613-cmtsu73g author = Lee, Sung Woo title = Risk Factors for Acute Kidney Injury and In-Hospital Mortality in Patients Receiving Extracorporeal Membrane Oxygenation date = 2015-10-15 keywords = AKI; ECMO; RDW summary = title: Risk Factors for Acute Kidney Injury and In-Hospital Mortality in Patients Receiving Extracorporeal Membrane Oxygenation BACKGROUND AND OBJECTIVES: Although acute kidney injury (AKI) is the most frequent complication in patients receiving extracorporeal membrane oxygenation (ECMO), few studies have been conducted on the risk factors of AKI. CONCLUSION: The initial pump speed of ECMO was a significant risk factor of in-hospital mortality and AKI in patients receiving ECMO. The initial pump speed of ECMO was a significant risk factor of in-hospital mortality and AKI in patients receiving ECMO. The cut-off values of SAPS2, serum sodium level, and ECMO pump speed for in-hospital mortality were a score of 69.5, 147.6 mmol/L, and 2.19 x 10 3 rpm, respectively (Table 3) . We showed that AKI, especially stage 3 AKI, was a significant risk factor for in-hospital mortality in patients receiving ECMO support. In conclusion, AKI is a significant risk factor for in-hospital mortality in patients receiving ECMO support. doi = 10.1371/journal.pone.0140674 id = cord-252347-vnn4135b author = Lee, Wai-Ming title = A Diverse Group of Previously Unrecognized Human Rhinoviruses Are Common Causes of Respiratory Illnesses in Infants date = 2007-10-03 keywords = HRV; P1-P2; PCR; sequence summary = doi = 10.1371/journal.pone.0000966 id = cord-292396-8w06oc5i author = Leger, Thomas title = Low-dose chest CT for diagnosing and assessing the extent of lung involvement of SARS-CoV-2 pneumonia using a semi quantitative score date = 2020-11-03 keywords = COVID-19; LDCT summary = OBJECTIVES: The purpose is to assess the ability of low-dose CT (LDCT) to determine lung involvement in SARS-CoV-2 pneumonia and to describe a COVID19-LDCT severity score. The objective is to evaluate the ability of (LDCT) to analyze well-known imaging abnormalities as well as to establish a COVID19-LDCT score reflecting disease severity and correlate it with clinical risk scores to allow better selection and follow-up of patients. For each patient, the following clinical parameters were recorded: age, sex, date of first symptoms, date of chest CT scan, delay between the first symptom and chest CT scan, fever, cough, dyspnea, diarrhea, myalgia, rhinorrhea, abnormalities at lung auscultation, temperature, heart rate, blood pressure, respiratory rate, oxygen saturation, and oxygen needed. The main findings of the presented work are that 1) LDCT scans can depict the typical features of SARS-CoV-2 pneumonia with limited irradiation; and 2) the COVID19-LDCT score is correlated with the NEWS used routinely to assess disease severity and patient prognosis. doi = 10.1371/journal.pone.0241407 id = cord-001011-vjxmrmfc author = Lei, Daoxiong title = Hepatic Deficiency of COP9 Signalosome Subunit 8 Induces Ubiquitin-Proteasome System Impairment and Bim-Mediated Apoptosis in Murine Livers date = 2013-07-01 keywords = Bax; Bcl2; Bim; Csn8 summary = doi = 10.1371/journal.pone.0067793 id = cord-310396-jitao9k0 author = Lei, Yu title = MAVS-Mediated Apoptosis and Its Inhibition by Viral Proteins date = 2009-03-07 keywords = Fig; IFN; MAVS; SARS; cell summary = The mitochondrial antiviral signaling adaptor, MAVS (IPS-1, VISA or Cardif) is critical for host defenses to viral infection by inducing type-1 interferons (IFN-I), however its role in virus-induced apoptotic responses has not been elucidated. A functional screen identifies the hepatitis C virus NS3/4A and the Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) nonstructural protein (NSP15) as inhibitors of MAVS-induced apoptosis, possibly as a method of immune evasion. Currently, there are no reports of viral proteins targeting MAVS for inhibition of virus-induced cell death responses. In this report, we describe a novel function of MAVS in mediating virus-induced apoptosis, and identify viral proteins as inhibitors of this response. In addition, the involvement of proteins on IFN axis in virusinduced host cell apoptosis has been implicated in another previous report, in which MAVS has been shown to be critical for reovirus-triggered caspase-3/7 activation in HEK293T cells [46] , however, the study did not evaluate whether MAVS mediates virus-induced apoptosis and what roles type 1 IFNs play in MAVS-mediated apoptosis. doi = 10.1371/journal.pone.0005466 id = cord-297835-ukrz8tlv author = Leith, Douglas J. title = Measurement-based evaluation of Google/Apple Exposure Notification API for proximity detection in a light-rail tram date = 2020-09-30 keywords = API; GAEN; Google summary = title: Measurement-based evaluation of Google/Apple Exposure Notification API for proximity detection in a light-rail tram Contact tracing apps based on the Google/Apple Exposure Notification (GAEN) API [4] are currently being rolled out across Europe, with apps already deployed in Italy, Switzerland and Germany. We observe that changing the people holding a pair of handsets, with the location of the handsets otherwise remaining unchanged, can cause variations of ±10dB in the attenuation level reported by the GAEN API. To provide baseline data on the radio propagation environment we also used the standard Android Bluetooth LE scanner API to collect measurements of RSSI as the distance was varied between two Google Pixel 2 handsets placed at a height of approximately 0.5m (about the same height as the tram seating) in the centre aisle of the tram carriage. doi = 10.1371/journal.pone.0239943 id = cord-001129-gi2kswai author = Lemos de Matos, Ana title = Positive Evolutionary Selection On the RIG-I-Like Receptor Genes in Mammals date = 2013-11-27 keywords = LGP2; MDA5; figure; rig summary = Because viruses are responsible for a great number of severe and lethal diseases, together with the important role that RLRs play in mammalian innate immune system, we expect that RIG-I, MDA5 and LGP2 genes may have been under intense selective pressures in all mammals. Evidence for positive selection on mammalian orthologous for RIG-I ( Figure S7 ), MDA5 ( Figure S8 ) and LGP2 ( Figure S9 ) genes was detected using PAML package [54, 55] site-specific models M1a versus M2a and M7 versus M8. (C) Positively-selected codons are exhibited in the table and numbered according to the mammalian LGP2 deduced protein sequences alignment ( Figure S6 downstream RIG-I and MDA5 signaling, which implies functional constraints, the observed variability across species can be perceived as a great structural plasticity for mammalian CARDs. The helicase domain in the RLR family is generally described as exhibiting affinity for dsRNA [78] . doi = 10.1371/journal.pone.0081864 id = cord-291104-6chpmgry author = Leung, Danny T. M. title = Osteopontin Fragments with Intact Thrombin-Sensitive Site Circulate in Cervical Cancer Patients date = 2016-08-05 keywords = ELISA; Fig; OPN summary = The possibility that the target epitope recognized by the antibody probe in these assays was absent from the circulating OPN due to protein truncation was supported by gel fractionation of the OPN found in patients'' plasma: 60–64 kDa fragments were found instead of the presumably full-length OPN (68 kDa) seen in healthy people. Similar results were found when the serum of these individuals was examined: the cancer patients (424 +/-121 ng/ mL) had significantly (P = 0.0002) higher levels of OPN than healthy subjects (314 +/-98 ng/ mL) (Fig 5B) , the assay sensitivity and specificity being 18% and 97%, respectively. The finding that the mAb 446 inhibition ELISA and the commercial OPN kit could not detect elevated OPN levels in the cancer patients suggested the possibility that the OPN present could be fragmented i.e. the target sites for the antibodies used in these assays could be missing, whereas, by virtue of the design of the mAb 659-based assay, the thrombin-sensitive site must be present. doi = 10.1371/journal.pone.0160412 id = cord-354052-x4ckzw64 author = Li, Chunhua title = Manipulation of the Porcine Epidemic Diarrhea Virus Genome Using Targeted RNA Recombination date = 2013-08-02 keywords = GFP; ORF3; PEDV summary = We have established a reverse genetics system for PEDV based on targeted RNA recombination that allows the modification of the 3′-end of the viral genome, which encodes the structural proteins and the ORF3 protein. All mPEDV infected cells stained positive both with the polyclonal MHV serum and with the monoclonal antibody directed against the PEDV nucleocapsid protein confirming the purity and the identity of the chimeric virus. Donor RNAs transcribed from the pPEDV and pPEDV-DORF3 transfer vectors were electroporated into mPEDV-infected L cells after which we were able to recover and purify the r-wtPEDV and PEDV-DORF3 viruses in VERO cells. Thus, the PEDV-DORF3/GFP and PEDV-DORF3/RLuc virus were preincubated with dilutions of serum obtained from an experimentally PEDV-infected pig and control serum, and the mixtures were subsequently added to VERO cells and incubated after which the GFP and Renilla luciferase expression was recorded at 9 and 6 hours p.i., respectively (Fig. 5D) . doi = 10.1371/journal.pone.0069997 id = cord-011798-uss38ped author = Li, Guowei title = Intellectual capital and the efficiency of SMEs in the transition economy China; Do financial resources strengthen the routes? date = 2020-07-02 keywords = capital; financial; intellectual; resource summary = Despite the bourgeoning literature, studies have not yet unleashed the influence of each dimension of intellectual capital; human capital, structural capital and customer capital on SMEs'' efficiency with financial resources as a moderator. A survey method was used and collected evidence from 264 Chinese SMEs. The findings exhibit that human capital directly enhances SMEs'' efficiency but the presence of financial resources as a moderator weakens the influence. This research recommends that owners and managers of SMEs need to use their financial resources complementary with structural and customer capital while human capital should be used exclusively. Studies have also discussed the role of intellectual capital (IC) (human capital, customer capital and structural capital) in firm competitive advantage and performance in emerging and developed economies [12, 13] Also, studies have assessed the direct and indirect influence of IC on performance [14] [15] [16] . doi = 10.1371/journal.pone.0235462 id = cord-278018-3qemb0x3 author = Li, Li title = Identification of M.tuberculosis-Specific Th1 Cells Expressing CD69 Generated in vivo in Pleural Fluid Cells from Patients with Tuberculous Pleurisy date = 2011-08-22 keywords = CD4; CD69; IFN summary = In the present study, we found that without any stimulation, CD4(+) T cells in pleural fluid cells (PFCs) from patients with TBP expressed significantly higher levels of CD69 than PBMCs from patients with tuberculosis (TB) or healthy donors. The phenotypic and functional analysis of CD69-expressing cells strongly suggested that CD69 could be a useful marker for the identification or enrichment of antigen specific Th1 cells at local sites following MTB infection. However, following stimulation with MTB-specific peptides of ESAT-6/CFP-10, CD4 + CD69 + T cells from the same patients expressed high levels of IFN-c, IL-2 and TNF-a (data not shown). However, following stimulation with MTB-specific peptides of ESAT-6/ CFP-10, CD4 + CD69 + T cells from the same patients with tuberculous pleurisy expressed high levels of IFN-c, IL-2 and TNF-a, indicating that the response was MTB-specific. doi = 10.1371/journal.pone.0023700 id = cord-273764-itu39mln author = Li, Taisheng title = Long-Term Persistence of Robust Antibody and Cytotoxic T Cell Responses in Recovered Patients Infected with SARS Coronavirus date = 2006-12-20 keywords = CTL; SARS summary = In this report, we have sequentially monitored 30 recovered patients over a two-year period to characterize temporal changes in SARS-CoV-specific antibody responses as well as cytotoxic T cell (CTL) responses. As show in Fig. 1 , recovered patients clearly experienced two distinct phases of cell restoration in the peripheral blood; an initial rapid phase for all the cell populations studied in the first 3 months after the onset of symptoms followed by a significant slower phase during the subsequent months. To study the sequential changes in CTL responses against SARS-CoV, we used ELISPOT-based technique to quantify the number of INF-c releasing cells in the peripheral blood against peptide pools covering the entire N protein derived from the Urbani strain [3] . We have shown for the first time that recovered patients have persistent and robust binding as well as neutralizing antibody and CTL responses throughout the study period with a moderate decline one year after the onset of symptoms. doi = 10.1371/journal.pone.0000024 id = cord-284016-zb6cv8ik author = Li, Wei title = Activation of Interleukin-32 Pro-Inflammatory Pathway in Response to Influenza A Virus Infection date = 2008-04-16 keywords = COX-2; Fig; IL-32; PGE summary = Expression of IL-32 in influenza A virus infected A549 human lung epithelial cells was blocked by either selective COX-2 inhibitor NS398 or Aspirin, a known anti-inflammatory drug, indicating IL-32 was induced through COX-2 in the inflammatory cascade. It has been reported that influenza virus can activate the expression of COX-2 in cell culture systems [26] and that dsRNA can induce the production of COX-2, followed by PGE 2 release [5] . To identify the viral components which play important roles in IV-stimulated pro-inflammatory factors COX-2 and IL-32 expression, we screened all ten proteins of influenza virus: HA, NA, NP, NS1, NS2, M1, M2, PA, PB1, PB2 and poly(IC) (to mimic viral replicative intermediate dsRNA) by luciferase assays. Both influenza A virus infection and poly(IC)+IFN-c treatment in A549 human lung epithelial cells were able to induce COX-2/ IL-32 mRNA and protein expression as well as PGE 2 and IL-32 accumulation in the cell culture supernatants. doi = 10.1371/journal.pone.0001985 id = cord-001383-hww0watl author = Li, Wenchao title = Self-Assembly and Release of Peste des Petits Ruminants Virus-Like Particles in an Insect Cell-Baculovirus System and Their Immunogenicity in Mice and Goats date = 2014-08-12 keywords = PPRV; USA summary = title: Self-Assembly and Release of Peste des Petits Ruminants Virus-Like Particles in an Insect Cell-Baculovirus System and Their Immunogenicity in Mice and Goats For many viral diseases, vaccination with virus-like particles (VLPs) has shown considerable promise as a prophylactic approach; however, the processes of assembly and release of peste des petits ruminants virus (PPRV) VLPs are not well characterized, and their immunogenicity in the host is unknown. In this study, we found that the major structural genes of PPRV can be efficiently expressed in recombinant baculovirus-infected Sf21 insect cells and that these genes can then support the production of PPRV VLPs. The expression of M protein was necessary and sufficient for the formation of VLPs (data not shown); the additional expression of the H or F glycoproteins allowed formation of budding particles with the typical morphology and size of PPRV and related paramyxoviruses. doi = 10.1371/journal.pone.0104791 id = cord-264880-0tmd9knh author = Li, Zhao title = Picoliter Well Array Chip-Based Digital Recombinase Polymerase Amplification for Absolute Quantification of Nucleic Acids date = 2016-04-13 keywords = PCR; PWA; RPA; chip; dna summary = We developed a picoliter well array (PWA) chip with 27,000 consistently sized picoliter reactions (314 pL) for isothermal DNA quantification using digital RPA (dRPA) at 39°C. To avoid thermal cycling, different isothermal amplification methods have been developed that rapidly amplify nucleic acids to detectable levels at a single temperature [42, 43] , such as loop-mediated amplification (LAMP) [44] , rolling circle amplification (RCA) [45] , helicasedependent amplification (HDA) [46] , nucleic acid sequence-based amplification (NASBA) [47] , recombinase polymerase amplification (RPA) [48] , transcription-mediated amplification (TMA) [49] , multiple displacement amplification (MDA) [50] , and strand-displacement amplification (SDA) [51] . Finally, we sealed the PWA chip in a homemade copper chamber filled with oil and successfully performed real-time dRPA on an isothermal incubation setup for the absolute quantification of serial dilutions of a Listeria monocytogenes gDNA stock solution. doi = 10.1371/journal.pone.0153359 id = cord-308480-t2vukbwp author = Liang, Zhongjie title = Molecular Basis of NDM-1, a New Antibiotic Resistance Determinant date = 2011-08-24 keywords = NDM-1; antibiotic; figure summary = In addition, the detailed analysis indicates that the more flexible and hydrophobic loop1, together with the evolution of more positive-charged loop2 leads to NDM-1 positive strain more potent and extensive in antibiotics resistance compared with other MBLs. Furthermore, through biological experiments, we revealed the molecular basis for antibiotics catalysis of NDM-1 on the enzymatic level. Taking two typical antibiotics, imipenem and carbapenem as example, the docked complex structures revealed that although the antibiotics adopted diverse conformations in the active site, the lactam motifs were positioned in the same orientation by coordinating with zinc ions tightly ( Figure 2C ), which suggested that the catalytic mechanisms were highly conserved among B1 subclass enzymes, as shown in Figure 3 . To gain the structural insight into the mechanism of the potent hydrolysis of NDM-1, the intermolecular interactions of three models of NDM-1, VIM-2 and FEZ-1 in complex with antibiotics meropenem were compared and analyzed in details ( Figure 4A -C). doi = 10.1371/journal.pone.0023606 id = cord-000266-xwfptmmv author = Liao, Qiuyan title = Situational Awareness and Health Protective Responses to Pandemic Influenza A (H1N1) in Hong Kong: A Cross-Sectional Study date = 2010-10-12 keywords = H1N1; Hong; Kong; self; worry summary = METHODOLOGY: Data from cross-sectional telephone interviews of 1,001 Hong Kong adults in June, 2009 were tested against theory and data-derived hypothesized associations between trust in (formal/informal) information, understanding, self-efficacy, perceived susceptibility and worry, and hand hygiene and social distancing using Structural Equation Modelling with multigroup comparisons. We report on a theoretical model that incorporated elements of influenza causal knowledge, perceived self-efficacy and also social and affective influences ( Figure 1 ) because these latter variables have been less frequently studied in combination, but have theoretical and logical support for their potential importance in the context of RIDs. We tested this model against data collected in the early phase of the influenza A/H1N1 pandemic (Table S1 ) to examine how levels of trust in formal and informal sources of risk/prevention information associated with hand washing and social distancing. doi = 10.1371/journal.pone.0013350 id = cord-000336-57es391o author = Liao, Qiuyan title = Factors Affecting Intention to Receive and Self-Reported Receipt of 2009 Pandemic (H1N1) Vaccine in Hong Kong: A Longitudinal Study date = 2011-03-11 keywords = Hong; Kong; TPB; vaccination summary = Greater perceived vaccine benefits (β = 0.15), less concerns regarding vaccine side-effects (β = −0.20), greater adherence to social norms of vaccination (β = 0.39), anticipated higher regret if not vaccinated (β = 0.47), perceived higher self-efficacy for vaccination (β = 0.12) and history of seasonal influenza vaccination (β = 0.12) were associated with higher intention to receive the pH1N1 vaccine, which in turn predicted self-reported vaccination uptake (β = 0.30). The model proposed that attitudes towards vaccination (perceived benefits of pH1N1 vaccination and concerns regarding possible adverse effects of pH1N1 vaccination), perceived social pressures from significant others and other people around regarding pH1N1 vaccination (social norms regarding pH1N1 vaccination), perceived self-efficacy in taking vaccination (perceived self-efficacy), anticipated regret for not taking the pH1N1 vaccination (anticipated regret) and seasonal influenza vaccination history would predict vaccination intention, which in turn predicts vaccination planning and future vaccination uptake; anticipated regret and perceived self-efficacy could also predict vaccination status directly; finally, vaccination planning was proposed to bridge the intention-behavior gap and predict vaccination status directly ( Figure 3 ). doi = 10.1371/journal.pone.0017713 id = cord-333413-8buawes0 author = Liebing, J. title = Health status of free-ranging ring-necked pheasant chicks (Phasianus colchicus) in North-Western Germany date = 2020-06-16 keywords = Germany; Mycoplasma; PCR; chick; pheasant; sample summary = Being a typical ground-breeding bird of the agricultural landscape in Germany, the pheasant has experienced a strong and persistent population decline with a hitherto unexplained cause. In the present study, 62 free-ranging pheasant chicks were caught within a two-year period in three federal states of Germany; Lower Saxony, North Rhine-Westphalia and Schleswig-Holstein. Pheasant chick deaths may often have been triggered by poor nutritional status, probably in association with inflammatory changes in various tissues and organs as well as bacterial and parasitic pathogens. In 2014 and 2015, the Institute for Terrestrial and Aquatic Wildlife Research (ITAW), University of Veterinary Medicine Hannover, Foundation, Hannover and the Wildlife Research Institute, State Office for Nature, Environment and Consumer Protection of North Rhine-Westphalia caught free-living Ring-necked Pheasant chicks from Lower Saxony (Cuxhaven, Grafschaft Bentheim, Emsland, Osnabrück, Vechta), North Rhine-Westphalia (Coesfeld, Warendorf) and Schleswig-Holstein (Dithmarschen) to assess the health state by means of pathological, microbiological, virological, parasitological and toxicological investigations. doi = 10.1371/journal.pone.0234044 id = cord-001537-i34vmfpp author = Lima, Francisco Esmaile de Sales title = Genomic Characterization of Novel Circular ssDNA Viruses from Insectivorous Bats in Southern Brazil date = 2015-02-17 keywords = Circoviridae; Cyclovirus; dna; sequence summary = The predicted protein sequences encoded by ORF2 (cap) and ORF1 (rep) of BatCV I-VI genomes were used for phylogenetic analysis with representative and recently discovered circoviruses/cycloviruses; Pepper golden mosaic virus was used as outgroup, as they are somewhat related to other members in the Circoviridae family (Fig. 3A, 3B and 3C ). The phylogenetic analysis constructed based on the alignments of the complete REP and CAP protein confirms that BatCV POA/II and VI cluster into the genus Cyclovirus along with the Chinese cycloviruses sequences clade detected in bat feces [18] and sharing less than 65% of identity at the CAP/REP amino acid level. BatCV POA I and V had a low amino acid identity with CAP (<20%) and REP (<10%) sequences of two other sequences detected in bat feces in this study with known circoviruses/cycloviruses (Table 2) . doi = 10.1371/journal.pone.0118070 id = cord-334218-bkjfy66e author = Lin, Jung-Da title = Impact of Mated Female Nonproductive Days in Breeding Herd after Porcine Epidemic Diarrhea Virus Outbreak date = 2016-01-15 keywords = January; PEDV summary = title: Impact of Mated Female Nonproductive Days in Breeding Herd after Porcine Epidemic Diarrhea Virus Outbreak The objectives of the present study were to investigate the effects between a 1-year period before and after PEDV outbreak on a sow''s reproductive traits on a commercial pig farm in Taiwan. The average number of mated females, average parity of farrowed sows, number of matings, number of farrowings, FR, RR, number of abortions, LMFY, percentage of sows mated by 7 days after weaning, WFSI, FI, NPDs, replacement rates of sows and sow culling rates of preand post-PEDV outbreak periods were compared using a Mann-Whitney test. In the present study, we compared the productivity index of gilts and sows between 1 year pre-and post-PEDV outbreak in a Taiwanese breeding herd. Impact of porcine epidemic diarrhea virus infection at different periods of pregnancy on subsequent reproductive performance in gilts and sows doi = 10.1371/journal.pone.0147316 id = cord-301180-ndiwmnv0 author = Lin, Min-Hsuan title = Nullbasic, a Potent Anti-HIV Tat Mutant, Induces CRM1-Dependent Disruption of HIV Rev Trafficking date = 2012-12-10 keywords = Fig; Nullbasic; Rev summary = Importantly, treatment of Myc-Rev and Nullbasic-mCherry expressing cells with LMB resulted in the complete restoration of Myc-Rev nucleolar accumulation (Fig. 3, row 6) , suggesting that Nullbasic requires functional CRM1 to mislocalize Rev most likely by an indirect interaction. While expression of Nullbasic-mCherry alone had no apparent effect on the nucleolar localization of either protein (Fig. 6 , rows 2 and 5), coexpression of Nullbasic-mCherry with Myc-Rev induced relocalization of C23 but not fibrillarin from the nucleolus to the nucleoplasm, in a manner concomitant with the redistribution of Myc-Rev (Fig. 6, rows 3 and 6 , respectively). CRM1 is a cellular receptor that recognizes and binds to the leucine-rich NES domain of Rev, an interaction which facilitates the egress of Rev/viral mRNA complexes through nuclear pores [3, 4, 42] and is readily visualized in cells as a colocalization in the nucleolus (Fig. 3, row 2 ). doi = 10.1371/journal.pone.0051466 id = cord-001123-n2e4s7bu author = Lin, Yue-Zhi title = The Soluble Form of the EIAV Receptor Encoded by an Alternative Splicing Variant Inhibits EIAV Infection of Target Cells date = 2013-11-22 keywords = EIAV; ELR1; ELR1-IN; GFP summary = doi = 10.1371/journal.pone.0079299 id = cord-256326-3ebcuzd6 author = Liotta, Giuseppe title = Is social connectedness a risk factor for the spreading of COVID-19 among older adults? The Italian paradox date = 2020-05-21 keywords = Italy; covid-19 summary = We analyzed several variables to test this hypothesis, such as the percentage of infected patients aged >80 years, available nursing home beds, COVID-19 incidence rate, and the number of days from when the number of positive tests exceeded 50 (epidemic maturity). While there is a very clear association between the case fatality rate and age demographics (Italy has the second oldest population worldwide and has the highest ageing index in Europe [4] with a value of 168.9), we wanted to test the hypothesis that the supposed closeness between younger and older generations in Italian families may have played a major role in the pandemic spread. Additionally, we explored the relationship between the proportion of infected patients aged >80 years and social connectedness indicators, such as the percentage of family comprising one members and household size [5] . doi = 10.1371/journal.pone.0233329 id = cord-001199-9khx93c0 author = Liu, Fengchen title = Effect of the One-Child Policy on Influenza Transmission in China: A Stochastic Transmission Model date = 2014-02-06 keywords = China; child; policy summary = Changes in household structure and the proportion of children in the population as a result of the one-child policy could have more effects on the AR, and the difference in AR could be as high as 60% under a scenario of very high immunity loss rate per year ( Figures 5(A) ). For each parameter set, we simulated the influenza trajectories under two demographic control policies, and then computed the difference in average annual attack rates over 10 years (2015 to 2024) between two policies. For each parameter set, we simulated the influenza trajectories under two demographic control policies, and then computed the difference in average annual attack rates over 10 years (2015 to 2024) between two policies. For each parameter set, we simulated the influenza trajectories under two demographic control policies, and then computed the difference in average secondary attack rates over 10 years (2015 to 2024) between two policies. doi = 10.1371/journal.pone.0084961 id = cord-292537-9ra4r6v6 author = Liu, Fenglin title = Predicting and analyzing the COVID-19 epidemic in China: Based on SEIRD, LSTM and GWR models date = 2020-08-27 keywords = COVID-19; China; Hubei; Wuhan summary = For the study of infectious diseases like COVID-19, SARS, and Ebola, most of the literature used descriptive research or model methods to assess indicators and analyze the effect of interventions, such as combining migration data to evaluate the potential infection rate [18, 19] , understanding the impact of factors like environmental temperature and vaccines that might be potentially linked to the diseases [20, 21] , using basic and time-varying reproduction number (R 0 & R t ) to estimate changeable transmission dynamics of epidemic conditions [22] [23] [24] [25] [26] [27] , calculating and predicting the fatal risk to display any stage of outbreak [28] [29] [30] , or providing suggestions and interventions from risk management and other related aspects based on the results of modeling tools or historical lessons [31] [32] [33] [34] [35] [36] [37] [38] [39] . doi = 10.1371/journal.pone.0238280 id = cord-317058-anvmj4li author = Liu, Xinkui title = Analysis of clinical features and early warning signs in patients with severe COVID-19: A retrospective cohort study date = 2020-06-26 keywords = covid-19; severe summary = doi = 10.1371/journal.pone.0235459 id = cord-000574-7eflwyxk author = Liu, Yanli title = Effects of a Non-Conservative Sequence on the Properties of β-glucuronidase from Aspergillus terreus Li-20 date = 2012-02-07 keywords = TIM summary = The non-conservative N-terminal domain of the protein phosphatase1 (PP1), with 1-8 residues deleted, showed higher sensitivity to three substrates and influenced the structure and properties of PP1 [10] , whereas the truncation of the Cterminal region improved the thermal stability of endo-bglucanase from Bacillus subtilis JA18 [11] . The TIM barrel domain, which is one of the most common catalytic domains, is adopted by about 10% of the enzymes; thus, sequence modification inside or outside the domain to improve the enzymatic property and determine the catalytic mechanism was reported in many studies. In the present research, Atgus and the partial sequence [Atgus(-3t)] without Cterminal non-conservative sequence behind the TIM barrel domain were amplified in order to investigate effects of nonconservative sequence on enzymatic property. Based on the same hydrolyzing mode, relatively higher thermal stability, and especially the enhanced affinity and catalytic efficiency for GL, deletion of the non-conservative sequence behind the TIM barrel domain was a successful evolution of AtGUS. doi = 10.1371/journal.pone.0030998 id = cord-001363-irysq6pf author = Liu, Zhenjiang title = SELDI-TOF-MS Proteomic Profiling of Serum, Urine, and Amniotic Fluid in Neural Tube Defects date = 2014-07-23 keywords = NTD; SELDI; TOF summary = Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) is a breakthrough in clinical proteomics, and can detect different protein expression patterns of body fluid and tissue specimens between patients and healthy subjects, and its rapid development provides an alternative tool to search for biomarkers. The purpose of this pilot study was to preliminarily explore the differential protein expression pattern between NTD case mothers and normal control mothers using SELDI-TOF-MS protein profiling and Classification and Regression Tree (CART) analysis, in order to differentiate pregnancies complicated by the presence of an NTD-affected fetus from healthy controls. Analysis of amniotic fluid samples from mothers of NTDaffected fetuses and normal control mothers revealed two major, differentially expressed proteins at 14700 and 13776 Da used in the classification pattern to generate 3 terminal nodes (Fig. 7) . However, when we analyzed the data, we found that only four protein/peptide biomarkers, 4188, 6451, 11744 and 23425 Da, were detected in all serum, urine and amniotic fluid samples. doi = 10.1371/journal.pone.0103276 id = cord-267644-guzn0peq author = Livadiotis, George title = Statistical analysis of the impact of environmental temperature on the exponential growth rate of cases infected by COVID-19 date = 2020-05-29 keywords = ffi; italian summary = We perform a statistical analysis for understanding the effect of the environmental temperature on the exponential growth rate of the cases infected by COVID-19 for US and Italian regions. In particular, we analyze the datasets of regional infected cases, derive the growth rates for regions characterized by a readable exponential growth phase in their evolution spread curve and plot them against the environmental temperatures averaged within the same regions, derive the relationship between temperature and growth rate, and evaluate its statistical confidence. The results clearly support the first reported statistically significant relationship of negative correlation between the average environmental temperature and exponential growth rates of the infected cases. First, we derive the exponential growth rates of the infected cases characterizing each examined region of US and Italy; then, we plot these values against the environmental temperatures of each region, and perform the corresponding statistical analysis. doi = 10.1371/journal.pone.0233875 id = cord-351098-x729wpp7 author = Long, Rachel B. title = Characterizing trends in human-wildlife conflicts in the American Midwest using wildlife rehabilitation records date = 2020-09-11 keywords = admission; case; wildlife summary = The purpose of this study was to examine the value of wildlife rehabilitation facility admissions records for informing understanding of local human-wildlife conflicts and wildlife disease trends by 1) identifying the top reasons for admission to this facility, 2) examining how occurrences as measured by admitted cases may fluctuate monthly and across taxa, and 3) analyzing trends in commonly admitted disease cases. To examine how human-wildlife conflict as measured by admissions to this facility may vary seasonally and across taxonomic groups, we assessed changes in mean cases admitted per month via Chi-squared tests. We further examined the top four identified specific causes of admission to the wildlife rehabilitation facility: orphaned, dog attacks, cat attacks, and vehicle strikes. Our study demonstrates the value of wildlife rehabilitation records for characterizing local human-wildlife conflicts and potentially select disease trends, as well as how occurrences may fluctuate seasonally and impact taxa differently. doi = 10.1371/journal.pone.0238805 id = cord-277548-hgmmtew3 author = Lou, Emil title = Perspectives of cancer patients and their health during the COVID-19 pandemic date = 2020-10-30 keywords = COVID-19; cancer summary = doi = 10.1371/journal.pone.0241741 id = cord-276763-x3dqi0ym author = Lowery-North, Douglas W. title = Measuring Social Contacts in the Emergency Department date = 2013-08-21 keywords = RFID; contact; staff summary = doi = 10.1371/journal.pone.0070854 id = cord-284275-bqo203pf author = Lu, Roujian title = Characterization of Human Coronavirus Etiology in Chinese Adults with Acute Upper Respiratory Tract Infection by Real-Time RT-PCR Assays date = 2012-06-15 keywords = HKU1; PCR; URTI summary = title: Characterization of Human Coronavirus Etiology in Chinese Adults with Acute Upper Respiratory Tract Infection by Real-Time RT-PCR Assays The etiology and clinical impact of HCoVs in Chinese adults with acute upper respiratory tract infection (URTI) needs to be characterized systematically by molecular detection with excellent sensitivity. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we detected 4 non-SARS related HCoV species by real-time RT-PCR in 981 nasopharyngeal swabs collected from March 2009 to February 2011. Respiratory syncytial virus (RSV), human parainfluenza virus (PIV) and HBoV were detected in very low rate (less than 1%) among adult patients with URTI. CONCLUSIONS/SIGNIFICANCE: All 4 non-SARS-associated HCoVs were more frequently detected by real-time RT-PCR assay in adults with URTI in Beijing and HCoV-229E led to the most prevalent infection. In our retrospective study, a 16.0% detection rate for HCoVs infection was found in adults with URTI; 229E was the most common infection (9.8% of all cases), followed by OC43 (4.3%), HKU1 (1.6%) and NL63 (1.1%). doi = 10.1371/journal.pone.0038638 id = cord-289873-6hivjqof author = Lu, Rui title = Patients with mild and general COVID-19 should be negative for at least 3 consecutive nucleic acid tests before discharged date = 2020-10-02 keywords = COVID-19 summary = The median time from the onset of COVID-19 to the occurrence of two consecutive negative nucleic acid tests of these patients was 21 days. Thus, we suggested that the patient should be negative for at least 3 consecutive nucleic acid tests before discharge, and the test time should be no earlier than the 23rd day since the onset of the disease. According to the latest COVID-19 clinical diagnosis and treatment guideline [3] , patients who meet the following four criteria can be discharged: (1) the body temperature has returned to normal for more than 3 days; (2) the respiratory symptoms have improved significantly; (3) the pulmonary imaging examination shows that the acute exudative lesions have improved significantly, (4) two consecutive negative nucleic acid test for respiratory specimens such as sputum and nasopharyngeal swabs (sampling interval at least 24 hours). The median time from the onset of COVID-19 to the occurrence of two consecutive negative nucleic acid tests in 845 patients with COVID-19 was 21 days (range: 1-56 days). doi = 10.1371/journal.pone.0240081 id = cord-000408-pt3b4yc7 author = Lu, Sydney X. title = Ceacam1 Separates Graft-versus-Host-Disease from Graft-versus-Tumor Activity after Experimental Allogeneic Bone Marrow Transplantation date = 2011-07-06 keywords = BMT; Ceacam1; GVHD summary = The accelerated early mortality of Ceacam1 2/2 allo-BMT recipients, together with increased accumulation of donor T cells in GI tract and mesenteric lymph nodes, but decreased numbers peripheral lymph nodes ( Figure 3C ), led us to ask whether Ceacam1 had differential effects in regulating GVHD target organ damage for various target organs and tissues. We analyzed donor WT and Ceacam1 2/2 alloactivated splenic T cells on day 14 after allo-BMT for trafficking molecules, and found that Ceacam1 2/2 CD8 + CD44 + CD62L 2 effector T cells expressed higher levels of integrin b 7 subunit and the gut homing integrin a 4 b 7 ( Figure 5A) , which is important for intestinal GVHD [31, 32, 33] . Ceacam12/2 CD4 effector T cells had similar integrin b 7 subunit expression, yet also accumulated in greater numbers in the gut ( Figure 3A) , suggesting that regulation of target organ damage by Ceacam1 is very likely to involve multiple additional mechanisms beyond trafficking molecule expression. doi = 10.1371/journal.pone.0021611 id = cord-319190-esjfhztp author = Lu, Xi title = In Vitro Activity of Sodium New Houttuyfonate Alone and in Combination with Oxacillin or Netilmicin against Methicillin-Resistant Staphylococcus aureus date = 2013-07-02 keywords = MRSA; SNH; Staphylococcus summary = title: In Vitro Activity of Sodium New Houttuyfonate Alone and in Combination with Oxacillin or Netilmicin against Methicillin-Resistant Staphylococcus aureus In synergy studies, the combinations of SNH-oxacillin, SNH-cephalothin, SNH-meropenem and SNH-netilmicin showed synergistic effects against 12 MRSA strains with median fractional inhibitory concentration (FIC) indices of 0.38, 0.38, 0.25 and 0.38 in checkerboard assays. Combinations of sub-MIC levels of SNH and oxacillin or netilmicin significantly improved the in vitro antibacterial activity against MRSA compared with either drug alone. In this study, we examined the in vitro activity of SNH and its potential for synergy when combined with antibiotics against a collection of hospital-associated MRSA (HA-MRSA) isolates recovered from various clinical samples in recent years. This study evaluated activity of SNH against MRSA and its potential for synergistic effect when combined with antibiotics. SNH in combination with OXA exhibited synergistic effect for all the five MRSA strains tested in time-kill analysis. doi = 10.1371/journal.pone.0068053 id = cord-309194-jtouafgd author = Lu, Xiao title = Lung ultrasound score in establishing the timing of intubation in COVID-19 interstitial pneumonia: A preliminary retrospective observational study date = 2020-09-03 keywords = COVID-19; LUS; patient summary = PURPOSE: To investigate the role of lung ultrasound score (LUS) in assessing intubation timing for patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia. Lung ultrasound was performed on days 1, 2, 3, 5, and 7 after patients were admitted to the ICU; if the patient was intubated, LUS determination was performed before intubation within 24 h (T1) and on days 1, 2, 5, and 7 after intubation (T2, T3, T4, and T5, respectively).The goal of this study was to evaluate the severity of lung aeration loss in intubated and non-intubated patients with SARS-CoV-2 pneumonia by ultrasound at different time points within one week. Few studies have addressed the timing of intubation for patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia due to the high mortality of patients treated with invasive ventilation. The patient''s gender, age, body mass index (BMI index), sequential organ failure assessment (SOFA score), and 28-day mortality rate were recorded; and the evolution of respiratory parameters between the two groups on time point T1 (lung ultrasound performed before intubation within 24 h) were also recorded. doi = 10.1371/journal.pone.0238679 id = cord-252838-av7ducrk author = Lucchi, Naomi W. title = Real-Time Fluorescence Loop Mediated Isothermal Amplification for the Diagnosis of Malaria date = 2010-10-29 keywords = PCR; dna summary = doi = 10.1371/journal.pone.0013733 id = cord-312033-iarl77n0 author = López Barreda, Rodrigo title = Poverty, quality of life and psychological wellbeing in adults with congenital heart disease in Chile date = 2020-10-08 keywords = CHD; life; patient; quality summary = The objective of this study was to assess the quality of life and psychological wellbeing of adults with congenital heart disease (CHD) in Chile, and to identify other associated factors. They completed a questionnaire, which included a quality of life assessment tool (the Medical Outcome Study 36-Item Short Form Health Survey), a number of psychological scales (the General Health Questionnaire, the Basic Psychological Needs Scales and the Beck Hopelessness Scale), a socioeconomic survey, and some clinical data. The primary aim of this study was to assess the QoL and psychological wellbeing of a population of adults suffering from CHD in Chile. Poverty, quality of life and psychological wellbeing in adults with congenital heart disease in Chile Poverty, quality of life and psychological wellbeing in adults with congenital heart disease in Chile general population [5, 11, 38] . doi = 10.1371/journal.pone.0240383 id = cord-296487-m4xba78g author = MacIntyre, Chandini Raina title = Health system capacity in Sydney, Australia in the event of a biological attack with smallpox date = 2019-06-14 keywords = Sydney; case; contact summary = doi = 10.1371/journal.pone.0217704 id = cord-000180-howix091 author = MacLeod, Iain J. title = Binding of Herpes Simplex Virus Type-1 Virions Leads to the Induction of Intracellular Signalling in the Absence of Virus Entry date = 2010-03-05 keywords = PCR; Virus; cell; hsv-1 summary = By taking advantage of the entry-defective phenotype of glycoprotein-deficient HSV-1 virus particles, the results presented here show that binding of virions to cellular receptors on the plasma membrane is sufficient to stimulate a change in cellular gene expression. As induction of the NF-kB reporter construct occurred within one hour of inoculation with DgH virions and peaked at around two-and-a-half hours post-inoculation, then the transcripts previHFFs were stimulated with 1000 particles/cell of DgB, DgD or DgH HSV-1 for six hours and a cDNA microarray corresponding to targets of 19 signalling pathways was used to detect changes in cellular gene expression when compared to mock-infected. Real-time PCR confirmed that changes in transcription associated with the NF-kB, JAK/STAT, JAK/Src and PI3K pathways were modulated as a result of virion binding, all of which required gD on the envelope surface To demonstrate that signalling occurred at physiologically relevant multiplicities of infection, HFFs were inoculated with either 1000, 100, 10 or 1 particles per cell of entry-defective HSV-1. doi = 10.1371/journal.pone.0009560 id = cord-337067-j8ebslif author = Mades, Andreas title = Role of Human Sec63 in Modulating the Steady-State Levels of Multi-Spanning Membrane Proteins date = 2012-11-15 keywords = Fig; HBV.S; Sec63; cell; protein summary = The overexpression of Sec63 reduces the steady-state levels of viral and cellular multi-spanning membrane proteins in a cotranslational mode, while soluble and single-spanning ER reporters are not affected. The specific action of Sec63 is further sustained by our observations that the up-regulation of either Sec62 or two other ER proteins with lumenal J domains, like ERdj1 and ERdj4, does not compromise the steady-state level of a multi-spanning membrane reporter. Similar results were obtained with cell lysates prepared with the denaturing detergent SDS (Fig. 1B) , indicating that the observed down-regulation of HBV.S by excess Sec63 was not merely due to changes in the solubility profile. To analyze whether an up-regulation of these ERdj proteins might also affect the level of a multi-spanning membrane protein, FLAG-tagged versions of ERdj1 and ERdj4 were cotransfected with HBV.S. FLAG-specific Western blotting confirmed the ectopic expression of ERdj1 and ERdj4 in 63 and 25 kDa forms, respectively, consistent with their theoretical molecular masses (Fig. 9) . doi = 10.1371/journal.pone.0049243 id = cord-287784-f7usy52w author = Maestre, Ana M. title = Equine Torovirus (BEV) Induces Caspase-Mediated Apoptosis in Infected Cells date = 2011-06-15 keywords = BEV; Derm; MRC-5; cell summary = Based on this finding, we analyzed several apoptotic markers, and observed protein synthesis inhibition, rRNA and DNA degradation, nuclear fragmentation, caspase-mediated cleavage of PARP and eIF4GI, and PKR and eIF2α phosphorylation, all these processes taking place after peak virus production. We did not observe any CPE on the cells treated with UV-inactivated virus (data not shown), and neither of the two caspase substrates was processed in these cells (Fig. 5B) , suggesting that BEV apoptosis triggering is dependent upon viral replication. As a whole, these results indicate that although both cell death receptor and mitochondrial pathways are implicated in the BEV induction of apoptosis, the mitochondrial pathway could be secondarily activated by caspase-8-mediated cleavage of Bid. To further ascertain the involvement of the mitochondrial pathway in BEV-induced apoptosis we analyzed the cellular distribution of cytochrome c at different times postinfection. doi = 10.1371/journal.pone.0020972 id = cord-317244-4su5on6s author = Maganga, Gael D. title = Identification of an Unclassified Paramyxovirus in Coleura afra: A Potential Case of Host Specificity date = 2014-12-31 keywords = PCR; RNA; bat; virus summary = In the present study, among 985 bats belonging to 6 species sampled in the Belinga caves of Gabon, RNA of an unclassified paramyxovirus (Belinga bat virus, BelPV) was discovered in 14 African sheath-tailed bats (Coleura afra), one of which exhibited several hemorrhagic lesions at necropsy, and viral sequence was obtained in two animals. To further investigate the presence of the virus in bat populations, a strain-specific real-time RT-PCR assay (primers: GB09-478-F, 59-GGCGGCTCTTAAAAGT-GAATG-39; GB09-478-R, 59-GCGGGGTCAAATTGGTCAT-39; probe: GB09-478-P, 59-TCCAGCACAAACATATCCGAGAAGGCTAG-39) was designed within the initial PCR fragment and was used to test total RNA extracted from mixed liver and spleen samples from each of all the other bat species. In order to determine the organ distribution of this virus in infected bats, total RNA was extracted from heart, liver, spleen, kidney, lung, intestine and brain samples from all 14 real-time RT-PCR-positive bats, as described previously, and screened, using the same strain-specific real-time RT-PCR assay shown above. doi = 10.1371/journal.pone.0115588 id = cord-295352-b8kztgt8 author = Maksimowski, Nicholas title = Kidney ACE2 expression: Implications for chronic kidney disease date = 2020-10-30 keywords = ACE2; Fig summary = Angiotensin-converting enzyme 2 (ACE2) has been implicated in the pathogenesis of chronic kidney disease (CKD) and is a membrane receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for coronavirus disease (COVID-19), whereas transmembrane protease, serine 2 (TMPRSS2) is involved in viral attachment. Sex, age, body mass index (BMI), and CKD are clinical risk factors for COVID-19 severity, but the relationships between kidney ACE2 and TMPRSS2 expression and these clinical variables are unknown. Tubulointerstitial and glomerular median-centered log2 mRNA expression of ACE2 or TMPRSS2 from renal biopsy samples were compared in CKD and HLD, as well as in male and female subgroups. Mean values for ACE2 mRNA expression in both the tubulointerstitial and glomerular compartments were similar in all of the disease categories represented in the CKD cohort (S1 Fig) . doi = 10.1371/journal.pone.0241534 id = cord-001083-vy1nxax2 author = Malagnac, Fabienne title = Rab-GDI Complex Dissociation Factor Expressed through Translational Frameshifting in Filamentous Ascomycetes date = 2013-09-19 keywords = Fig; IBV; PaYIP3 summary = doi = 10.1371/journal.pone.0073772 id = cord-333650-4towah1t author = Malmo, Jostein title = Cytokine Profiles in Human Metapneumovirus Infected Children: Identification of Genes Involved in the Antiviral Response and Pathogenesis date = 2016-05-12 keywords = IFN; TNF summary = Overall, our data point to cytokines, particularly inflammasome-associated, that might be important in hMPV mediated lung disease and the antiviral response in children with severe infection. To determine the presence of antiviral cytokines in children infected with hMPV and controls, we initially investigated the expression of type I, II and III IFNs. Fig 1A shows that only A2 infected children had slightly elevated mRNA levels of the type I IFN-β compared to the controls. Fig 2 shows the mRNA expression of A) IκBα, a repressor gene induced by NF-κB activation [19] , B) IL-1β, C) IL-18 and D) NLRP3 in hMPV infected children and controls. A previous study comparing the expression of several inflammatory cytokines in hMPV, RSV and influenza virus, detected elevated levels of TNF-α, IL-6 and IL-1β protein in nasal washes from infants with RTI [9] . doi = 10.1371/journal.pone.0155484 id = cord-340027-6l55rcfm author = Mamode Khan, Naushad title = Studying the trend of the novel coronavirus series in Mauritius and its implications date = 2020-07-10 keywords = Mauritius; case; covid-19 summary = This paper proposes an integer-valued time series model to analyze the series of COVID-19 cases in Mauritius wherein the corresponding innovation term accommodates for covariate specification. Based on the proposed COM-Poisson mixture models, we could predict the number of COVID-19 cases in Mauritius. The paper therefore proposes an integer-valued auto-regressive model (INAR(1)) with Conway-Maxwell Poisson (COM-Poisson) mixed innovation terms that can accommodate for covariate, random effect and serial auto-correlation specifications. The organization of the paper is as follows: In Section 2, material in terms of time series of COVID-19 in Mauritius and proposed methods principally the INAR(1) Process and the COM-Poisson mixture innovations have been provided. The results of this research revealed that several factors, the most significant being confinement measure, and least one being climatic conditions, affect the number of COVID-19 cases in Mauritius. doi = 10.1371/journal.pone.0235730 id = cord-348499-7ll7sd3o author = Manderstedt, Eric title = Genetic variation in the C-type lectin receptor CLEC4M in type 1 von Willebrand Disease patients date = 2018-02-01 keywords = VWD; VWF; clec4 summary = von Willebrand factor (VWF) levels in healthy individuals and in patients with type 1 von Willebrand disease (VWD) are influenced by genetic variation in several genes, e.g. VWF, ABO, STXBP5 and CLEC4M. Additional studies of STXBP5 and STX2 [8] and CLEC4M [9, 10] have confirmed that single nucleotide variants (SNVs) in these genes are associated with the variation observed for plasma levels of VWF. CLEC4M also binds to VWF [9] and variants in this gene contribute to the variation in the VWF level observed both in normal individuals [4] and in type 1 VWD patients [9, 10] . The present study aimed to screen comprehensively for genetic variation in the CLEC4M gene in individuals from 106 unrelated type 1 VWD families by re-sequencing the gene region (excluding exon 4) and genotyping the polymorphic neck region (exon 4) of the gene. doi = 10.1371/journal.pone.0192024 id = cord-349476-iac9fak3 author = Mao, Liang title = Evaluating the Combined Effectiveness of Influenza Control Strategies and Human Preventive Behavior date = 2011-10-17 keywords = figure; individual; strategy summary = The simulation outcomes suggest that weaker control strategies could suffice to contain influenza epidemics, because individuals voluntarily adopt preventive behavior, rendering these weaker strategies more effective than would otherwise have been expected. Health policy makers are recommended to review current control strategies and comprehend preventive behavior patterns of local populations before making decisions on influenza containment. The control of influenza primarily involves applying health resources to affected people, known as control strategies, for example, medical treatment for infected individuals, closure of affected workplaces/schools, and travel restriction to affected communities [4] . Results from the influenza-only model indicate the effectiveness of control strategies without individual preventive behavior. Meanwhile, outcomes from the dual-diffusion model show the combined effectiveness of both control strategies and individual preventive behavior. These two modeled effectiveness are compared to a baseline epidemic scenario, which represents a worst situation of no control strategies and no preventive behavior. This research estimates the combined effectiveness of both control strategies and individual preventive behavior. doi = 10.1371/journal.pone.0024706 id = cord-001421-6t5puo6p author = Marfà, Santiago title = Lack of a 5.9 kDa Peptide C-Terminal Fragment of Fibrinogen α Chain Precedes Fibrosis Progression in Patients with Liver Disease date = 2014-10-02 keywords = HCV; patient summary = The serum proteomic profile and routine liver and renal function tests were initially analyzed in a training set of 10 HCV-RNA recurrent LT patients 6 months post LT that showed a fibrosis stage F$1 at 1 year after LT. HVPG was assessed in 53 of these patients and the average value was of 5.560.8 mm Hg. All the serum samples showed a quite similar expression pattern and coincidences included both the different peptide fragments detected and the signal intensity of these fragments (Data S4). All serum samples included in the test set showed an intensity m/z 5905 peak well below the values found in both healthy subjects and non recurrent HCV patients. In conclusion, we identified a 5.9 kDa C-terminal fragment of the fibrinogen a chain as a serum biomarker of early fibrogenic processes in patients with liver disease. In conclusion, we identified a 5.9 kDa C-terminal fragment of the fibrinogen a chain as a serum biomarker of early fibrogenic processes in patients with liver disease. doi = 10.1371/journal.pone.0109254 id = cord-343135-m0pdixw5 author = Marguet, Christophe title = In Very Young Infants Severity of Acute Bronchiolitis Depends On Carried Viruses date = 2009-02-25 keywords = RSV summary = BACKGROUND: RT amplification reaction has revealed that various single viruses or viral co-infections caused acute bronchiolitis in infants, and RV appeared to have a growing involvement in early respiratory diseases. Because remaining controversial, the objective was to determine prospectively the respective role of RSV, RV, hMPV and co-infections on the severity of acute bronchiolitis in very young infants. METHODS AND PRINCIPAL FINDINGS: 209 infants (median age: 2.4 months) were enrolled in a prospective study of infants <1 year old, hospitalized for a first episode of bronchiolitis during the winter epidemic season and with no high risk for severe disease. The aim of this prospective study was to assess the clinical severity and viral etiology in infants hospitalized with a first episode of acute bronchiolitis during the epidemic season. In this study, the clinical severity of dual RSV/RV infection was comparable to that observed with RSV, but differed in a shorter duration of hospitalization in the coinfected infants. doi = 10.1371/journal.pone.0004596 id = cord-012461-v8d91fdo author = Marnissi, Boutheina title = Generation of ssDNA aptamers as diagnostic tool for Newcastle avian virus date = 2020-08-13 keywords = ELAA; NDV; PCR; SELEX; dna summary = doi = 10.1371/journal.pone.0237253 id = cord-260432-imslfm4l author = Marshall, Jenika D. title = THP-1 macrophage cholesterol efflux is impaired by palmitoleate through Akt activation date = 2020-05-21 keywords = Akt; FFA; LPL; THP-1 summary = Thus, we hypothesized that one or more specific fatty acids that exist within the total FFA component of lipoprotein hydrolysis products that are generated by LPL impair cholesterol efflux through the activation of Akt. To test this hypothesis, using THP-1 macrophages, we examined the activation of Akt in response to various FFA mixtures that contain the concentrations of FFA species that we previously reported to be found within LPL hydrolysis products from total lipoproteins [16] . Lastly, we examined the molecular species of phosphoinositides (PIPx) of THP-1 macrophages treated with palmitoleate, to determine if there were changes to select PIPx species that may contribute to a preferential activation of Akt. We previously showed using antibody arrays that the hydrolysis products liberated by LPL from total lipoproteins (ρ<1.21 g/ml), as well as the reconstituted total FFA component matching that liberated by LPL at a physiological concentration of 0.68 mM, significantly increased the phosphorylation of Akt after 30 minutes within THP-1 macrophages [16] . doi = 10.1371/journal.pone.0233180 id = cord-288502-qqg41daz author = Martini, Katharina title = Patterns of organizing pneumonia and microinfarcts as surrogate for endothelial disruption and microangiopathic thromboembolic events in patients with coronavirus disease 2019 date = 2020-10-05 keywords = COVID-19 summary = BACKGROUND: To evaluate chest-computed-tomography (CT) scans in coronavirus-disease-2019 (COVID-19) patients for signs of organizing pneumonia (OP) and microinfarction as surrogate for microscopic thromboembolic events. 21.1% of COVID-19 patients suspected with PE showed subpleural wedge-shaped consolidation resembling infarct pneumonia, while only 13.2% showed visible filling defects of the pulmonary artery branches on CT-PA. However, patients with suspected PE showed a higher prevalence of lung changes, resembling patterns of infarct pneumonia or OP and CT-signs of pulmonary-artery hypertension. Therefore, the purpose of the study was to investigate possible typical parenchymal lung changes resembling patterns of infarct pneumonia or OP as surrogate for microscopic thromboembolic events in COVID-19 patients. Our hypothesis is further strengthened by the higher presence of CT signs for pulmonary artery hypertension and right heart failure in patients undergoing CT-PA or with CT patterns resembling infarct pneumonia. However, our COVID-19 cohort showed lung changes resembling those of infarct pneumonia and OP as well as CT-signs of pulmonary-artery hypertension. doi = 10.1371/journal.pone.0240078 id = cord-003404-eqgc8v7y author = May, Win Lai title = Impact of glucose-6-phosphate dehydrogenase deficiency on dengue infection in Myanmar children date = 2019-01-02 keywords = G6PD; Myanmar; dengue; patient summary = doi = 10.1371/journal.pone.0209204 id = cord-341097-c96hm610 author = Mayer, Craig S. title = Analysis of data dictionary formats of HIV clinical trials date = 2020-10-05 keywords = CDISC; Data; HIV; study summary = To facilitate aggregation across studies, we defined three types of data dictionary (data element, forms, and permissible values) and created a simple information model for each type. The presented study is limited to data dictionary analysis, although the motivation is to later analyze a large body of past HIV data elements to inform data-driven consensus on CDEs. This study is part of a larger research project titled ''Identification of Research Common Data Elements in HIV/AIDS using data science methods'' [12] . We use the term Forms Data Dictionary (or forms dictionary in shorter form) to refer to a data dictionary that provides a full list of titles and descriptions of all Case Report Forms (CRFs) used in the study (or other relevant metadata for data element grouping). Use of categorical data elements in research is extremely common and, as stated earlier, most studies would be expected to provide a permissible value dictionary. doi = 10.1371/journal.pone.0240047 id = cord-332922-2qjae0x7 author = Mbuvha, Rendani title = Bayesian inference of COVID-19 spreading rates in South Africa date = 2020-08-05 keywords = SEIR; SIR; model summary = In this work, we perform Bayesian parameter inference using Markov Chain Monte Carlo (MCMC) methods on the Susceptible-Infected-Recovered (SIR) and Susceptible-Exposed-Infected-Recovered (SEIR) epidemiological models with time-varying spreading rates for South Africa. The results find two change points in the spreading rate of COVID-19 in South Africa as inferred from the confirmed cases. The second change point coincides with the start of a state-led mass screening and testing programme which has highlighted community-level disease spread that was not well represented in the initial largely traveller based and private laboratory dominated testing data. In this work we combine Bayesian inference with the compartmental SEIR and SIR models to infer time varying spreading rates that allow for quantification of the impact of government interventions in South Africa. SIR and SEIR model parameter inference was performed using confirmed cases data up to and including 20 April 2020 and MCMC samplers described in the methodology section. doi = 10.1371/journal.pone.0237126 id = cord-273343-als886fe author = McClenahan, Shasta D. title = Discovery of a Bovine Enterovirus in Alpaca date = 2013-08-12 keywords = PCR; virus summary = A cytopathic virus was isolated using Madin-Darby bovine kidney (MDBK) cells from lung tissue of alpaca that died of a severe respiratory infection. To identify the virus, the infected cell culture supernatant was enriched for virus particles and a generic, PCR-based method was used to amplify potential viral sequences. The new alpaca virus sequence was most similar to recently designated Enterovirus species F, previously bovine enterovirus (BEVs), viruses that are globally prevalent in cattle, although they appear not to cause significant disease. Analysis of the full polyprotein and the individual capsid, 2A protease, 3C protease, and polymerase proteins of the alpaca-infecting virus relative to sequences of other representative enteroviruses from bovine EV-E (BEV-A serotypes 1-4) and EV-F (BEV-B serotypes 1-4), and sequences from three unclassified EV-F viruses [16] , two from bovine sources (AY724744 and AY724745) [20] , and one from a capped langur (JX538037) [21] , possum, porcine (PEV), and human (HEV) hosts. doi = 10.1371/journal.pone.0068777 id = cord-346089-u31n0qxa author = McDade, Thomas W. title = High seroprevalence for SARS-CoV-2 among household members of essential workers detected using a dried blood spot assay date = 2020-08-14 keywords = SARS; dbs summary = title: High seroprevalence for SARS-CoV-2 among household members of essential workers detected using a dried blood spot assay To address this problem we developed a serological test for SARS-CoV-2 IgG antibodies that requires only a single drop of finger stick capillary whole blood, collected in the home and dried on filter paper (dried blood spot, DBS). Serological testing for SARS-CoV-2 IgG antibodies in DBS samples can facilitate seroprevalence assessment in community settings to address epidemiological questions, monitor duration of antibody responses, and assess if antibodies against the spike protein correlate with protection from reinfection. In addition, we demonstrate the feasibility and utility of quantifying SARS-CoV-2 antibodies in self-collected DBS with results from a community-based sample enriched with health care workers. We have validated a DBS assay to facilitate large-scale serological testing of SARS-CoV-2 IgG antibodies, and results from our feasibility study document a high rate of household transmission. doi = 10.1371/journal.pone.0237833 id = cord-315531-2gc2dc46 author = McGarvey, Peter B. title = Systems Integration of Biodefense Omics Data for Analysis of Pathogen-Host Interactions and Identification of Potential Targets date = 2009-09-25 keywords = Bacillus; MPD; Proteomics; datum; protein summary = (1) The identification of a hypothetical protein with differential gene and protein expressions in two host systems (mouse macrophage and human HeLa cells) infected by different bacterial (Bacillus anthracis and Salmonella typhimurium) and viral (orthopox) pathogens suggesting that this protein can be prioritized for additional analysis and functional characterization. The centers have generated a heterogeneous set of experimental data using various technologies loosely defined as proteomic, but encompassing genomic, structural, immunology and protein interaction technologies, as well as more standard cell and molecular biology techniques used to validate potential targets identified via high-throughput methods. Here we describe in detail a protein-centric approach for systems integration of such a large and heterogeneous set of data from the NIAID Biodefense Proteomics program, and present scientific case studies to illustrate its application to facilitate the basic understanding of pathogen-host interactions and for the identification of potential candidates for therapeutic or diagnostic targets. doi = 10.1371/journal.pone.0007162 id = cord-001387-2g9dc5z4 author = McIntyre, K. Marie title = A Quantitative Prioritisation of Human and Domestic Animal Pathogens in Europe date = 2014-08-19 keywords = animal; index; pathogen summary = By coupling the H-index method with the EID2, the primary aim of this study was to establish priority lists of human and domestic animal pathogens (including zoonoses) present in Europe. Its potential as a quantitative One Health indicator (i.e. a single measure applicable to both human and animal diseases) was investigated by comparing scores for human-only, zoonotic, and animal-only pathogen groups, including emerging status as this would likely drive research impact. We investigated its value as a proxy for animal disease impact by comparing domestic animal pathogen H-indices with other measures of impact including presence on the OIE list [10] , and inclusion in DISCONTOOLS [11] . The study establishes priority lists of human and domestic animal pathogens (including zoonoses) present in Europe, using the H-index as a proxy measure for impact. doi = 10.1371/journal.pone.0103529 id = cord-319921-uxtydu60 author = Meli, Marina L. title = Feline Leukemia Virus and Other Pathogens as Important Threats to the Survival of the Critically Endangered Iberian Lynx (Lynx pardinus) date = 2009-03-09 keywords = FeLV; Lynx; PCR; feline; iberian summary = METHODOLOGY/ PRINCIPAL FINDINGS: We systematically analyzed the prevalence and importance of seven viral, one protozoan (Cytauxzoon felis), and several bacterial (e.g., hemotropic mycoplasma) infections in 77 of approximately 200 remaining free-ranging Iberian lynxes of the Doñana and Sierra Morena areas, in Southern Spain, between 2003 and 2007. Furthermore, the presence of feline leukemia virus (FeLV) provirus was recently reported in six samples originating from both the Doñ ana and Sierra Morena areas in southern Spain between 1994 and 2003 [29] . Thus, in the present study, we report on the prevalence of the aforementioned pathogens and we describe a dramatic FeLV epidemic, which most likely led to the death of 6 Iberian lynxes within a 6-months period in 2007, its possible origin, and its relationship to other infectious agents. However, endogenous FeLV sequences related to those of domestic cats are apparently not present in Iberian lynxes: only 5 of the 77 lynxes tested displayed weak signals by quantitative realtime PCR, which is not compatible with presence of enFeLV sequences. doi = 10.1371/journal.pone.0004744 id = cord-002141-9mxi4dzi author = Memczak, Henry title = Anti-Hemagglutinin Antibody Derived Lead Peptides for Inhibitors of Influenza Virus Binding date = 2016-07-14 keywords = Aichi; Fig; H3N2; bind; peptide summary = title: Anti-Hemagglutinin Antibody Derived Lead Peptides for Inhibitors of Influenza Virus Binding We used complementary experimental and theoretical approaches to select HA binding VH-CDR peptides and to improve their potential to inhibit binding, and finally, infection of cells by influenza A virus. Contribution to the total binding free energy change of every amino acid of PeB GF binding to HA of Aichi H3N2 obtained by MD-simulations is shown in Fig 2B. Our aim was to obtain peptide inhibitors that recognize the conserved region of the sialic acid binding pocket of HA with a broader specificity to cover several influenza virus strains. The three CDRs of the VH-chain of antibody HC19 against hemagglutinin of influenza virus Aichi H3N2 were used as templates to design peptides being a potential inhibitor of virus binding to host cells. As a consequence, the hemagglutination inhibition efficiency may not necessarily be stronger against Aichi H3N2, even though the peptide was derived from an antibody binding to this influenza strain. doi = 10.1371/journal.pone.0159074 id = cord-001958-2gt3fwpy author = Meseda, Clement A. title = Percutaneous Vaccination as an Effective Method of Delivery of MVA and MVA-Vectored Vaccines date = 2016-02-19 keywords = Ankara; MVA; mouse; virus summary = Our data suggest that MVA administered by percutaneous inoculation, elicited vaccinia-specific antibody responses, and protected mice from lethal vaccinia virus challenge, at levels comparable to or better than subcutaneous or intramuscular inoculation. In the work described here, we demonstrate in mouse models that percutaneous inoculation of MVA elicited protective immune responses against lethal intranasal challenge with the Western Reserve (WR) strain of vaccinia virus, and at low doses of MVA, lower morbidity was recorded in mice that were vaccinated via the percutaneous route than in those immunized via the intramuscular or subcutaneous routes. In a preliminary experiment to investigate the utility of the percutaneous route for the delivery of MVA, we observed that MVA delivered by tail scarification, while statistically insignificant (p = 0.298), elicited a higher vaccinia-specific IgG response and protection in mice than the same dose (10 6 pfu) delivered by the intramuscular route (S1 Fig) . doi = 10.1371/journal.pone.0149364 id = cord-286065-x0g67pnb author = Metzgar, David title = The IRIDICA BAC BSI Assay: Rapid, Sensitive and Culture-Independent Identification of Bacteria and Candida in Blood date = 2016-07-06 keywords = Assay; BAC; BSI; IRIDICA; PCR summary = We describe the analytical characteristics of the IRIDICA BAC BSI Assay and compare its pre-clinical performance to current standard-of-care methods in a collection of prospectively collected blood specimens from patients with symptoms of sepsis. During the clinical sample study, performed following the sterility and personal protective equipment recommendations of the manufacturer, 61 negative controls were tested and yielded no Other reportable organisms excluding potential contaminants (n = 550) 0 0 0 207 A These 11 culture-negative, IRIDICA BAC BSI Assay-positive detections were supported by later organism-specific ID data which identified the same species as agents of infection (as noted on the subjects'' charts). The broad-spectrum nature of the IRIDICA BAC BSI Assay primers, paired with a signal analysis method capable of sensitive and specific detection and identification of one or more species signatures in samples with high background levels of human DNA, make it uniquely suited as a molecular test for bacterial and Candida DNA in blood samples. doi = 10.1371/journal.pone.0158186 id = cord-289285-aof7xy13 author = Michaelis, Martin title = Glycyrrhizin Exerts Antioxidative Effects in H5N1 Influenza A Virus-Infected Cells and Inhibits Virus Replication and Pro-Inflammatory Gene Expression date = 2011-05-17 keywords = Germany; H5N1; figure; influenza summary = title: Glycyrrhizin Exerts Antioxidative Effects in H5N1 Influenza A Virus-Infected Cells and Inhibits Virus Replication and Pro-Inflammatory Gene Expression Here, the effects of an approved parenteral glycyrrhizin preparation (Stronger Neo-Minophafen C) were investigated on highly pathogenic influenza A H5N1 virus replication, H5N1-induced apoptosis, and H5N1-induced pro-inflammatory responses in lung epithelial (A549) cells. The mechanism by which glycyrrhizin interferes with H5N1 replication and H5N1-induced pro-inflammatory gene expression includes inhibition of H5N1-induced formation of reactive oxygen species and (in turn) reduced activation of NFκB, JNK, and p38, redox-sensitive signalling events known to be relevant for influenza A virus replication. Glycyrrhizin 200 mg/ml (the maximum tested concentration) did not affect A549 cell viability (data not shown) but clearly decreased CPE formation in A549 cells infected with the H5N1 influenza strain A/Thailand/1(Kan-1)/04 at MOIs of 0.01, 0.1 or 1 ( Figure 1A ). Here, we show that glycyrrhizin inhibits the replication of highly pathogenic H5N1 influenza A virus, H5N1-induced apoptosis, and H5N1-induced expression of pro-inflammatory cytokines in lung-derived A549 cells. doi = 10.1371/journal.pone.0019705 id = cord-291417-p49ukyhx author = Mikulska, Malgorzata title = Tocilizumab and steroid treatment in patients with COVID-19 pneumonia date = 2020-08-20 keywords = COVID-19; SOC; patient; treatment summary = METHODS: This observational single-center study included patients with COVID-19 pneumonia who were not intubated and received either standard of care (SOC, controls) or SOC plus early (within 3 days from hospital admission) anti-inflammatory treatment. This observational single-center study included patients with COVID-19 pneumonia who were not intubated and received either standard of care (SOC, controls) or SOC plus early (within 3 days from hospital admission) anti-inflammatory treatment. We hypothesized that outcomes such as no need for intubation and survival of patients with severe COVID-19 pneumonia in whom tocilizumab and/or methylprednisolone were administered in addition to standard of care (SOC) could be better than in those who received only SOC. In this observational study in non-intubated patients with mainly severe COVID-19 pneumonia, the early addition of tocilizumab and/or methylprednisolone to SOC resulted in adjusted failure-free survival of 86.5% and 80.8% at day 14 and 30, which was, respectively, 10.7% and 16.7% higher than in SOC patients. doi = 10.1371/journal.pone.0237831 id = cord-327199-ggomuomb author = Moerdyk-Schauwecker, Megan title = Cellular Proteins Associated with the Interior and Exterior of Vesicular Stomatitis Virus Virions date = 2014-08-08 keywords = RNP; VSV; protein; virion; virus summary = In another example, the presence of host complement control proteins such as CD46, CD55 and CD59 in the viral envelope has been shown to protect against antibody dependent complement mediated virus lysis in several viruses including human T cell leukemia/ lymphoma virus type I [16] , human cytomegalovirus [16] , hepatitis C virus [17] , HIV-1 [18, 19] , extracellular enveloped vaccinia virus [20] , simian virus 5 [21] and mumps virus [21] . As discussed in the previous section, proteins not associated with the interior of the virion, including proteins embedded in the host derived viral envelope, can be identified by their absence in ProK treated samples or by a size shift upon ProK treatment. While many of the proteins identified in VSV virions appear to be associated with viral assembly, budding or the host-derived viral envelope, they may also have additional functions that affect virus replication. doi = 10.1371/journal.pone.0104688 id = cord-001253-3jnkki5z author = Mohammad, Fahim title = Advantages and Limitations of Anticipating Laboratory Test Results from Regression- and Tree-Based Rules Derived from Electronic Health-Record Data date = 2014-04-14 keywords = PPV; result; test summary = doi = 10.1371/journal.pone.0092199 id = cord-345717-ktajrf7d author = Monagin, Corina title = Serologic and behavioral risk survey of workers with wildlife contact in China date = 2018-04-03 keywords = China; SARS; animal; risk summary = We report on a study conducted in Guangdong Province, China, to characterize behaviors and perceptions associated with transmission of pathogens with pandemic potential in highly exposed human populations at the animal-human interface. The present study focuses on the potential for zoonotic viral transfer through contact with wildlife in Guangdong prefectures in China, and seeks to augment our understanding and identification of risky populations, occupations, and behaviors, as well as the perceptions of risk at these interfaces. We performed a serological survey and concurrent behavioral questionnaire of individuals with wildlife contact in Guangdong Province, China, in order to better characterize occupations and community-level behavioral risks that contribute to zoonotic transmission of various wildlife pathogens with pandemic potential. We targeted high-risk individuals, defined as individuals with high levels of exposure to wildlife (wild animal blood or bodily fluids)-primarily hunters, persons working in wet markets and restaurants that butcher wild game, who could be followed over a period of time. doi = 10.1371/journal.pone.0194647 id = cord-000642-mkwpuav6 author = Moreira, Rebeca title = Transcriptomics of In Vitro Immune-Stimulated Hemocytes from the Manila Clam Ruditapes philippinarum Using High-Throughput Sequencing date = 2012-04-19 keywords = Ruditapes; immune; philippinarum; protein; sequence summary = title: Transcriptomics of In Vitro Immune-Stimulated Hemocytes from the Manila Clam Ruditapes philippinarum Using High-Throughput Sequencing The 35 most frequently found contigs included a large number of immune-related genes, and a more detailed analysis showed the presence of putative members of several immune pathways and processes like the apoptosis, the toll like signaling pathway and the complement cascade. The discovery of new immune sequences was very productive and resulted in a large variety of contigs that may play a role in the defense mechanisms of Ruditapes philippinarum. Moreover, a few transcripts encoded by genes putatively involved in the clam immune response against Perkinsus olseni have been reported by cDNA library sequencing [18] . philippinarum transcriptome and another four bivalve species sequences were analyzed by comparative genomics (Crassostrea gigas of the family Ostreidae, Bathymodiolus azoricus and Mytilus galloprovincialis of the family Mytilidae and Laternula elliptica of the family Laternulidae). doi = 10.1371/journal.pone.0035009 id = cord-002560-pue5q5wp author = Moreno, Paloma S. title = Characterisation of the canine faecal virome in healthy dogs and dogs with acute diarrhoea using shotgun metagenomics date = 2017-06-01 keywords = PCR; canine; dog; sample summary = Recently, due to the advent of molecular enrichment protocols, high throughput sequencing and new metagenomic analytical methods we are now able to explore, identify and characterise viruses from different biological and environmental samples with a greater capacity [2, [5] [6] [7] [8] [9] [10] [11] In studies of human faeces, the virome has been shown to include viruses that infect eukaryotic organisms and viruses that infect prokaryotes (bacteriophages) [2, 5, [12] [13] [14] [15] [16] [17] [18] . Another eukaryotic viral family found in one healthy dog sample was Parvoviridae, genetic analysis of the 3 contigs/singletons showed a coverage of approximately 3.5% of the complete genome of canine parvovirus reference sequence (NC_001539), or 9.3% of the polyprotetin Ns1-Ns2. Nucleic acids from a single faecal sample from a dog with acute diarrhoea (DD1), which had 18 contigs/singletons of canine astrovirus (after tBLASTx analysis) was used to determine the complete genome sequence. doi = 10.1371/journal.pone.0178433 id = cord-295201-u2dola34 author = Morimoto, Konosuke title = The Burden and Etiology of Community-Onset Pneumonia in the Aging Japanese Population: A Multicenter Prospective Study date = 2015-03-30 keywords = Japan; pneumonia summary = doi = 10.1371/journal.pone.0122247 id = cord-328633-c31xsyeo author = Moser, Michael J. title = Thermostable DNA Polymerase from a Viral Metagenome Is a Potent RT-PCR Enzyme date = 2012-06-04 keywords = MS2; PCR; Pol; RNA; dna summary = Most RT-PCR protocols rely on two DNA polymerase (Pol) enzymes; a retroviral reverse transcriptase (RT) to copy RNA into cDNA and a thermostable DNA Pol to amplify the target sequence. Despite their wide use and general reliability, existing twoenzyme RT-PCR systems have several documented performance problems attributed to deficiencies inherent in retroviral RTs: 1) poor reagent stability, 2) low fidelity, 3) frequent rearrangements during cDNA synthesis, 4) secondary enzymatic activities (i.e. RNase H and strand switching), 5) bias for specific primers and templates, and 6) inhibition of PCR Pol enzymes [3, 4, 5, 6, 7] . We describe the discovery and biochemical attributes of one of these, 3173 Pol, its inherent RT activity and its incorporation into a single-enzyme PyroScriptH 2X RT-PCR Master Mix. The sensitivity, specificity and overall performance of this mix were compared to available one-and two-enzyme systems using a control MS2 RNA bacteriophage template, the clinically-relevant influenza A RNA and commonly used reference mRNA transcripts. doi = 10.1371/journal.pone.0038371 id = cord-341880-wxliz485 author = Mottaleb, Khondoker Abdul title = COVID-19 induced economic loss and ensuring food security for vulnerable groups: Policy implications from Bangladesh date = 2020-10-16 keywords = Bangladesh; COVID-19; daily; wage summary = This study examines the food security and welfare impacts of the COVID-19 induced lockdown on daily wage workers both in the farm and nonfarm sectors in Bangladesh. Then, applying simple econometric estimation processes, this study estimates the minimum compensation packages for the daily wage-based farm and nonfarm households of Bangladesh that ensure their minimum food security during the lockdown. The estimation suggests a common minimum support at US $ 1 per daily wage-based household in Bangladesh to ensure minimum food security during COVID-19 induced lockdown time. Using information of more than 50,000 respondents from the HIES 2016-17 dataset, this study, firstly quantified the economic loss due to the COVID-19 induced lockdown and suggested the minimum support package to ensure food security of the daily wage-based workers in Bangladesh. doi = 10.1371/journal.pone.0240709 id = cord-337585-kpghvb6u author = Moustaqim-Barrette, Amina title = Accessing Take-Home Naloxone in British Columbia and the role of community pharmacies: Results from the analysis of administrative data date = 2020-09-11 keywords = THN; kit summary = Individuals not personally at risk of overdose had higher odds of collecting naloxone at a pharmacy site, compared to other community sites (including harm reduction supply distribution sites, peer led organizations, drop-in centers, and supportive housing sites) (Adjusted Odds Ratio (AOR): 2.69; 95% CI: 2.50–2.90). While those at highest risk of overdose may preferentially access naloxone through community sites, naloxone distribution through pharmacies has allowed the BC THN program to expand dramatically, increasing naloxone availability through longer opening hours on evenings and weekends. While analyses from the BCCDC shows that the BC THN program, combined with other harm reduction interventions, has averted thousands of opioid overdose deaths [20, 21] , there is still relatively little data in the published literature examining community reach and barriers to access of naloxone distribution programs in Canada. After evaluating data from 2018, our analysis also finds that individuals at risk of opioid overdose were significantly less likely to collect a naloxone kit at a pharmacy site compared to community-based sites. doi = 10.1371/journal.pone.0238618 id = cord-335404-s48psqth author = Mukandavire, Zindoga title = Quantifying early COVID-19 outbreak transmission in South Africa and exploring vaccine efficacy scenarios date = 2020-07-24 keywords = Africa; COVID-19; South summary = We used a mathematical model to fit to the observed cases of COVID-19 in South Africa to estimate the basic reproductive number and critical vaccination coverage to control the disease for different hypothetical vaccine efficacy scenarios. Early model estimates show that COVID-19 outbreak in South Africa had a basic reproductive number of 2.95 (95% credible interval [CrI] 2.83–3.33). Here, we adapt a susceptible-exposed-infected-removed (SEIR) compartmental model to quantify early transmissibility of COVID-19 in South Africa and explore the potential utility of a vaccine in containing the disease. Following a similar approach in [37] , we use a Markov Chain Monte Carlo (MCMC) within a Bayesian framework (in R FME package [38] ) to fit the model to the cumulative data of confirmed COVID-19 cases in South Africa and estimate the magnitude of the epidemic using the basic reproductive number and quantify required vaccines'' attributes to stem similar outbreaks. doi = 10.1371/journal.pone.0236003 id = cord-294592-zwvr57a0 author = Mukherjee, Moumita title = Global cataloguing of variations in untranslated regions of viral genome and prediction of key host RNA binding protein-microRNA interactions modulating genome stability in SARS-CoV-2 date = 2020-08-11 keywords = RNA; SARS; UTR; viral summary = doi = 10.1371/journal.pone.0237559 id = cord-001707-piyo00yg author = Murray, Jillian title = Determining the Provincial and National Burden of Influenza-Associated Severe Acute Respiratory Illness in South Africa Using a Rapid Assessment Methodology date = 2015-07-08 keywords = HIV; sari summary = doi = 10.1371/journal.pone.0132078 id = cord-294023-knaxr7t0 author = Murri, Rita title = Social media as a tool for scientific updating at the time of COVID pandemic: Results from a national survey in Italy date = 2020-09-03 keywords = COVID-19 summary = title: Social media as a tool for scientific updating at the time of COVID pandemic: Results from a national survey in Italy Seventy percent (n = 261) of respondents reported that their use of social media to find medical information increased during the current pandemic (Fig 1) . In terms of COVID-19 medical practice, information coming from social media were considered "enough" or "much" or "very much" useful by 82.9% (n = 306) of the sample. To the question "During the last week, do you think that information shared on social media had an impact on your clinical practice for patients with COVID?" 28.7% (n = 106) answered "enough" and 47.1% (n = 174) "much" or "very much". Our survey shows that, at the time of COVID pandemic, many clinicians react to their urgent need for updates by seeking information through unconventional sources instead of academic journals publications. doi = 10.1371/journal.pone.0238414 id = cord-001964-iy6qzq58 author = Muñoz-González, Sara title = Classical Swine Fever Virus vs. Classical Swine Fever Virus: The Superinfection Exclusion Phenomenon in Experimentally Infected Wild Boar date = 2016-02-26 keywords = CSFV; IFN; Margarita; RNA summary = The wild boars persistently infected with CSFV were protected from superinfection by the virulent CSFV Margarita strain, as evidenced by the absence of clinical signs and the absence of Margarita RNA detection in serum, swabs and tissue samples. Additionally, in PBMCs, a well-known target for CSFV viral replication, only the primary infecting virus RNA (Cat01 strain) could be detected, even after the isolation in ST cells, demonstrating SIE at the tissue level in vivo. Interestingly, the RNA of the vaccinal C-strain was undetectable by specific RT-PCR [8] in any of the samples analysed after vaccination, including blood, nasal and rectal swabs, or organs throughout the experiment, suggesting a phenomenon of homologous interference, also known as superinfection exclusion (SIE), between the high viral load generated by the primary persistent infection and the CSFV vaccine strain. doi = 10.1371/journal.pone.0149469 id = cord-333208-tibtngy8 author = Muñoz-Moreno, Raquel title = Antiviral Role of IFITM Proteins in African Swine Fever Virus Infection date = 2016-04-26 keywords = ASFV; Fig; IFITM2; IFN; Vero summary = The interferon-induced transmembrane (IFITM) protein family is a group of antiviral restriction factors that impair flexibility and inhibit membrane fusion at the plasma or the endosomal membrane, restricting viral progression at entry. The role of IFITM2 in the inhibition of ASFV in Vero cells could be related to impaired endocytosis-mediated viral entry and alterations in the cholesterol efflux, suggesting that IFITM2 is acting at the late endosome, preventing the decapsidation stage of ASFV. Thus, our goal in the current work was to test whether the IFITM family of proteins affected early entry steps of ASFV infection in Vero cell cultures using the cell-adapted Ba71V isolate. Confocal microscopy experiments revealed that, IFITM1 was mainly distributed at the plasma membrane and to a lesser extent in perinuclear compartments, resembling endosomal structures (Fig 3C, lower left panel) , while endogenous IFITM1 was barely detected in Vero cells containing the empty vector (Fig 3C, upper left panel) . doi = 10.1371/journal.pone.0154366 id = cord-002398-0a3okta0 author = Myllykoski, Matti title = Structural aspects of nucleotide ligand binding by a bacterial 2H phosphoesterase date = 2017-01-31 keywords = -AMP; Fig; RNA summary = doi = 10.1371/journal.pone.0170355 id = cord-289555-1z4vbldd author = Mühldorfer, Kristin title = Diseases and Causes of Death in European Bats: Dynamics in Disease Susceptibility and Infection Rates date = 2011-12-28 keywords = Germany; bat; european; specie summary = Comparative analysis of pathological findings and microbiological results show that microbial agents indeed have an impact on bats succumbing to infectious diseases, with fatal bacterial, viral and parasitic infections found in at least 12% of the bats investigated. The clear seasonal and individual variations in disease prevalence and infection rates indicate that maternity colonies are more susceptible to infectious agents, underlining the possible important role of host physiology, immunity and roosting behavior as risk factors for infection of bats. In this study, we provide new data on infectious diseases in European bat species, considering factors likely to affect the susceptibility of bats to infectious agents including effects of seasonality, individual and species-specific heterogeneities, and possible intra-and inter-species transmission dynamics. Comparative bacteriologic and histo-pathologic analysis identified 22 different bacterial species that were clearly associated with pathological lesions and/or systemic infection, found in 17% (n = 73) of bats investigated bacteriologically ( Table 5) . doi = 10.1371/journal.pone.0029773 id = cord-272445-0xauff51 author = Naaber, Paul title = Evaluation of SARS-CoV-2 IgG antibody response in PCR positive patients: Comparison of nine tests in relation to clinical data date = 2020-10-27 keywords = SARS; covid-19 summary = title: Evaluation of SARS-CoV-2 IgG antibody response in PCR positive patients: Comparison of nine tests in relation to clinical data The specificity and sensitivity of SARS-CoV-2 antibody tests are known to vary and very few studies have addressed the performance of these tests in COVID-19 patient groups at different time points. We here compared the sensitivity and specificity of seven commercial (SNIBE, Epitope, Euroimmun, Roche, Abbott, DiaSorin, Biosensor) and two in-house LIPS assays (LIPS N and LIPS S-RBD) IgG/total Ab tests in serum samples from 97 COVID-19 patients and 100 controls, and correlated the results with the patients'' clinical data and the time-point the test was performed. Our study aimed to compare the performance characteristics of seven commercial and two in-house IgG/total Ab tests, which analyze the reactivity to several target proteins, and to correlate the results with the patients'' clinical data (with different symptoms score and age), and time from disease onset. doi = 10.1371/journal.pone.0237548 id = cord-000720-5b936n3g author = Nannyonga, Betty title = The Dynamics, Causes and Possible Prevention of Hepatitis E Outbreaks date = 2012-07-24 keywords = Hepatitis summary = The models designed are fit to data from the Kitgum outbreak, to estimate the basic reproduction number and to relate them to the level of contamination of the environment. Susceptible individuals without bore hole access become infected with the Hepatitis E virus at a rate bc, where b is the transmission rate of HEV from the contaminated environment c, to the human. To estimate model parameters and determine the critical level of control needed to eradicate the epidemic, the model described by the equations in (7) is fit to the data collected during the Kitgum outbreak ( Figure 1 ) During the invasion phase of HEV, the prevalence is approximately Under the above assumption, equations (7) are rewritten to incorporate the malaria dynamics in equation (11) where j is a parameter that models change the increase (or decrease) in susceptibility to Hepatitis E of malaria infected individuals [12] . doi = 10.1371/journal.pone.0041135 id = cord-001983-zo9yngfc author = Napp, S. title = Understanding Spatio-Temporal Variability in the Reproduction Ratio of the Bluetongue (BTV-1) Epidemic in Southern Spain (Andalusia) in 2007 Using Epidemic Trees date = 2016-03-10 keywords = Andalusia; BTV; BTV-1 summary = doi = 10.1371/journal.pone.0151151 id = cord-000143-2xvd5ogf author = Napthine, Sawsan title = Expression of the VP2 Protein of Murine Norovirus by a Translation Termination-Reinitiation Strategy date = 2009-12-22 keywords = AUG; MNV; ORF; RNA summary = In this process, following translation of an upstream open reading frame (ORF) and termination at the stop codon, a proportion of 40S subunits remain associated with the mRNA and reinitiate at the AUG of a downstream ORF, which is typically in close proximity. Recent studies of termination-reinitiation in the expression of the orthomyxovirus influenza BM2 protein have revealed a requirement for a shorter stretch of mRNA (45 nt) upstream of the stop-start window, but nevertheless, the RNA contains a similar TURBS Motif 1 [19] . Whilst in principle, reinitiation of translation of the MNV 49.7 VP2fluc ORF, following termination, could occur at the next available AUG, this is located 54 amino acids from the natural stop-start signal and initiation here would produce a substantially shorter product that would have been detectable by SDS-PAGE. doi = 10.1371/journal.pone.0008390 id = cord-002705-ntokyoai author = Nasir, Nazrila Hairin title = Effectiveness of a fluid chart in outpatient management of suspected dengue fever: A pilot study date = 2017-10-04 keywords = dengue; fluid; study summary = However, there have been no published studies looking at self-care intervention measures to improve oral fluid intake among patients suspected of dengue fever. OBJECTIVE: To assess the feasibility and effectiveness of using a fluid chart to improve oral fluid intake in patients with suspected dengue fever in a primary care setting. To assess the feasibility and effectiveness of using a fluid chart to improve oral fluid intake in patients with suspected dengue fever in a primary care setting. A non-randomized controlled study was conducted in Taiwan comparing the effects of oral rehydration with intravenous fluid replacement in adult patients with non-shock dengue haemorrhagic fever [7] . Most importantly, there have been no published studies looking at self-care intervention measures to improve oral fluid intake among patients suspected of dengue fever. Thus, this pilot randomized controlled study aimed to assess the feasibility of using a fluid chart to improve oral fluid intake in patients with suspected dengue fever in a primary care setting. doi = 10.1371/journal.pone.0183544 id = cord-000721-leedutqo author = Nawaz, Sameena title = Human Bocaviruses Are Not Significantly Associated with Gastroenteritis: Results of Retesting Archive DNA from a Case Control Study in the UK date = 2012-07-24 keywords = case; control summary = Human bocavirus (HBoV)s, which are associated with respiratory infections, have also frequently been detected in stool samples in cases of gastroenteritis, and a tentative association between HBoVs, and in particular type-2 HBoVs, and gastroenteritis has previously been made. The aim of this study was to determine the role of HBoVs in gastroenteritis, using archived DNA samples from the case-control Infectious Intestinal Disease Study (IID). In the genotype-specific assays 106 of the 324 HBoV-positive samples were genotyped, with HBoV-1 predominantly found in controls whilst HBoV-2 was more frequently associated with cases of gastroenteritis (p<0.01). The prevalence of HBoV-2 in children in the UK was significantly lower than that reported in a study in Australia, in which HBoV-2 was detected in 17.2% and 8.1% of the cases and controls, respectively [22] . Human bocavirus in children hospitalized for acute gastroenteritis: a case-control study doi = 10.1371/journal.pone.0041346 id = cord-307036-n44yml79 author = Ng, Oi-Wing title = Substitution at Aspartic Acid 1128 in the SARS Coronavirus Spike Glycoprotein Mediates Escape from a S2 Domain-Targeting Neutralizing Monoclonal Antibody date = 2014-07-14 keywords = D1128A; N1056; SARS summary = Next, to determine if mAb 1A9 exhibits cross-neutralizing activity, S-pseudotyped virus particles, or S-pps, carrying the human SARS-CoV S or the various RBD-modified chimeric S of civet SARS-CoV SZ3 strain and bat SL-CoV Rp3 and Rf1 strains were generated and used to infect CHO-ACE2 cells in the absence or presence of different concentrations (100, 150 and 200 mg/ml) of mAb 1A9. Wild-type S, substitution S mutants, namely D1128A, N1056K, and that containing both D1128A and N1056K, were then expressed in 293 FT cells and Western Blot analysis was performed to determine the effects of these mutations on the binding of the S protein to mAb 1A9. (A) S-pp expressing S protein of humans SARS-CoV HKU39849, civet SARS-CoV SZ3, bat SL-CoV Rp3 and Rf1 and (B) S-pp containing wild-type or mutant D1128A, N1056K or D1128A/ N1056K S were generated and used to infect CHO-ACE2 cells at equal amount (as quantitated using P24 ELISA). doi = 10.1371/journal.pone.0102415 id = cord-001601-tsuz3j40 author = Ngan, Luong Thi My title = Antiviral Activity and Possible Mechanism of Action of Constituents Identified in Paeonia lactiflora Root toward Human Rhinoviruses date = 2015-04-10 keywords = HRV; HRV-4; MRC5; PGG summary = An assessment was made of the antiviral activities and mechanisms of action of paeonol (PA) and 1,2,3,4,6-penta-O-galloyl-β-D-glucopyranose (PGG) from Paeonia lactiflora root toward HRV-2 and HRV-4 in MRC5 cells using a tetrazolium method and real-time quantitative reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay. These findings suggest that PGG and PA may block or reduce the entry of the viruses into the cells to protect the cells from the virus destruction and abate virus replication, which may play an important role in interfering with expressions of rhinovirus receptors (intercellular adhesion molecule-1 and low-density lipoprotein receptor), inflammatory cytokines (interleukin (IL)-6, IL-8, tumor necrosis factor, interferon beta, and IL-1β), and Toll-like receptor, which resulted in diminishing symptoms induced by HRV. In the presence of 100 μg/mL PA or 20 μg/mL PGG in MRC5 cell cultures infected with HRV-2, the RNA replication levels were reduced by 30.1 and 14.3 fold, respectively, compared to the levels in the cell cultures without the compounds (Fig 4A) . doi = 10.1371/journal.pone.0121629 id = cord-000176-z76vjkxg author = Nguyen, Jack T. title = Triple Combination of Amantadine, Ribavirin, and Oseltamivir Is Highly Active and Synergistic against Drug Resistant Influenza Virus Strains In Vitro date = 2010-02-22 keywords = H1N1; TCAD; oseltamivir summary = Our data show that the triple combination was highly synergistic against drug-resistant viruses, and the synergy of the triple combination was significantly greater than the synergy of any double combination tested (P<0.05), including the combination of two NAIs. Surprisingly, amantadine and oseltamivir contributed to the antiviral activity of the TCAD regimen against amantadineand oseltamivir-resistant viruses, respectively, at concentrations where they had no activity as single agents, and at concentrations that were clinically achievable. In an earlier study, we explored the in vitro antiviral activity and synergy of single, double, and triple combinations of amantadine, ribavirin and oseltamivir against a panel of influenza A viruses that were susceptible to these drugs [10] . Statistical analysis of the variability across all replicates from the six experiments for each virus revealed that amantadine made a significant contribution to the synergy of the TCAD regimen at concentrations 0.1 mg/mL and 0.32 mg/mL and above against CA05 and CA10, respectively, compared to the double combination of ribavirin/oseltamivir carboxylate without amantadine ( Figure 1B ). doi = 10.1371/journal.pone.0009332 id = cord-282668-bs634hti author = Niang, Mbayame Ndiaye title = Respiratory viruses in patients with influenza-like illness in Senegal: Focus on human respiratory adenoviruses date = 2017-03-22 keywords = ILI; Senegal; infection; respiratory summary = In the present study, we investigate the epidemiologic and viral molecular features of HAdVs circulating in Senegal after 4 consecutive years of sentinel surveillance of influenza-like Illness cases. In the present study, we investigate the epidemiologic and viral molecular features of HAdVs circulating in Senegal after 4 consecutive years of sentinel surveillance of influenzalike Illness cases. From January 2012 to December 2015 we collected specimens (nasal-pharyngeal and oral-pharyngeal swabs) and surveillance data for influenza and other viral respiratory pathogens from outpatients presenting with influenza-like-illness (ILI) at different sentinel sites in Senegal. So the circulation of such HAdV genome types in Senegal emphasizes the need to reinforce HAdV surveillance, especially in hospitalized patients, by including HAdV genome detection and genotyping in the documentation of severe respiratory infections. Molecular epidemiology of human adenovirus isolated from children hospitalized with acute respiratory infection in São Paulo, Brazil doi = 10.1371/journal.pone.0174287 id = cord-000322-8ctsa9sd author = Ninove, Laetitia title = RNA and DNA Bacteriophages as Molecular Diagnosis Controls in Clinical Virology: A Comprehensive Study of More than 45,000 Routine PCR Tests date = 2011-02-09 keywords = MS2; PCR; RNA summary = doi = 10.1371/journal.pone.0016142 id = cord-001432-d4zavkcn author = Nishida, Yoriko title = Antibody-Validated Proteins in Inflamed Islets of Fulminant Type 1 Diabetes Profiled by Laser-Capture Microdissection Followed by Mass Spectrometry date = 2014-10-16 keywords = FT1DM; cell; islet summary = PROCEDURES: Proteins expressed in the islets of enterovirus-associated fulminant type 1 diabetes (FT1DM) with extensive insulitis were identified by laser-capture microdissection mass spectrometry using formalin-fixed paraffin-embedded pancreatic tissues. Migratory activity-related proteins, including plastin-2 (LCP1), moesin (MSN), lamin-B1 (LMNB1), Ras GTPase-activating-like protein (IQGAP1) and others, were identified in CD8(+) T cells and CD68(+) macrophages infiltrated to inflamed FT1DM islets. Proteins involved in successive signaling in innate/adaptive immunity were identified, including SAM domain and HD domain-containing protein 1 (SAMHD1), Ras GTPase-activating-like protein (IQGAP1), proteasome activator complex subunit 1 (PSME1), HLA class I histocompatibility antigen (HLA-C), and signal transducer and activator of transcription 1-alpha/beta (STAT1). Actin-related protein 3 (ACTR3) was over-expressed in the cytoplasm and nucleus of MNCs infiltrated to the islets in FT1DM-affected pancreas tissue. Signal transducer and activator of transcription 1-alpha/beta (STAT1) was highly expressed in islet endocrine cells and MNCs in FT1DM tissue ( Figure 2Q, R) . doi = 10.1371/journal.pone.0107664 id = cord-352447-bc1pf272 author = Nishida, Yu title = Novel prognostic biomarkers of pouchitis after ileal pouch-anal anastomosis for ulcerative colitis: Neutrophil-to-lymphocyte ratio date = 2020-10-26 keywords = IPAA; NLR summary = Despite conflicting results, the development of pouchitis in patients with UC, as reported in several studies, has been linked to various factors, including primary sclerosing cholangitis [2, 4] , other extraintestinal manifestations of inflammatory bowel disease [4, 8, 9] , young age at UC diagnosis [4] , preoperative terminal ileal inflammation [10, 11] , extensive colonic disease [10], presence of interleukin-1 receptor antagonist gene allele 2 [12] , total steroid dose of > 10000 mg [13] , use of infliximab [14] , neutrophil percentage of > 65% [13] , and presence of perinuclear antineutrophil cytoplasmic antibodies [15, 16] . Therefore, our study aimed to evaluate the clinical utility of the NLR for predicting the development of pouchitis after IPAA in patients with UC. Third, we were unable to evaluate the reported pouchitis predictive factors, such as extraintestinal manifestations of inflammatory bowel disease, preoperative terminal ileal inflammation, the presence of interleukin-1 receptor antagonist gene allele 2, total steroid dose of >10000 mg, or presence of perinuclear antineutrophil cytoplasmic antibodies owing to the retrospective design of the study. doi = 10.1371/journal.pone.0241322 id = cord-263453-7v4y02j6 author = Nishiura, Hiroshi title = Early Epidemiological Assessment of the Virulence of Emerging Infectious Diseases: A Case Study of an Influenza Pandemic date = 2009-08-31 keywords = Canada; USA summary = We first examine the approach by analyzing an outbreak of severe acute respiratory syndrome in Hong Kong (2003) with known unbiased cCFR estimate, and then investigate published epidemiological datasets of novel swine-origin influenza A (H1N1) virus infection in the USA and Canada (2009). Nevertheless, a much-used crude estimate of the cCFR, i.e. the ratio of the cumulative number of deaths to cases at calendar time t, tends to yield a biased (and mostly underestimated) cCFR due to the time-delay from onset to death [8] ; similar estimates of such a biased cCFR for severe acute respiratory syndrome (SARS) have shown how such estimates can vary substantially as an epidemic progresses, stabilizing only in the later stages of the outbreak [8, 9] . doi:10.1371/journal.pone.0006852.g003 Figure 6 shows the time course of biased cCFR estimates in the USA and Canada based on the reporting date of confirmed cases and deaths to the World Health Organization. doi = 10.1371/journal.pone.0006852 id = cord-001748-7e8px4vx author = Nobach, Daniel title = Shedding of Infectious Borna Disease Virus-1 in Living Bicolored White-Toothed Shrews date = 2015-08-27 keywords = Borna; RNA; shrew; virus summary = The bicolored white-toothed shrew (Crocidura leucodon) has recently been identified as reservoir of the neurotropic Borna disease virus 1 (BoDV-1). In animals caught in 2013 (group 1: female #2, male #5, female #6), after an adaption phase of one month, samples of saliva, lacrimal fluid, skin surface, urine and excrements from the BoDV-1-infected shrews were taken weekly over a period of 4 weeks as necessary veterinary care. The five other shrews did not exhibit any evidence for BoDV-1-infection, neither infectious virus nor viral RNA was detected at any time point investigated. Current data from living shrews provide reliable evidence that natural BoDV-1-infection in these animals is indeed clinically inconspicuous over a long time period as already previously assumed [15, 18] despite persistent infection with shedding of infectious virus via various sites. Distribution of Borna Disease Virus Antigen and RNA in Tissues of naturally infected Bicolored White-Toothed Shrews, Crocidura leucodon, supporting their role as Reservoir Host Species doi = 10.1371/journal.pone.0137018 id = cord-306466-y4yg42p8 author = Nofal, Ahmed Maged title = Who complies with COVID-19 transmission mitigation behavioral guidelines? date = 2020-10-08 keywords = behavioral; covid-19; guideline; transmission summary = Particularly, we examine if major personality traits (i.e. conscientiousness, agreeableness, openness to experience, extraversion, and emotional stability) [12] , yield differences in the tendency of people to comply with 21 implemented COVID-19 transmission mitigation behavioral guidelines (see S1 Appendix). However, there has been no work examining the influence of personality traits, such as the big five (i.e. conscientiousness, agreeableness, openness to experience, extraversion, and emotional stability) on the tendency of people to comply with COVID-19 transmission mitigation behavioral guidelines. Connecting literatures of emotional responses to COVID-19 messages, and personalized/tailored communication, we believe that this research not only supports prior work in highlighting the importance of pro-social messages, but also the importance of knowing the specific personality traits that may make individuals less likely to comply with COVID-19 transmission mitigation behavioral guidelines. First, drawing from research on persuasive mass communication [e.g., 19] , we aim to demonstrate if personality traits, specifically, conscientiousness, agreeableness, openness to experience, extraversion, and emotional stability, relate to the tendency of people to comply with COVID-19 transmission mitigation behavioral guidelines. doi = 10.1371/journal.pone.0240396 id = cord-339327-4422s317 author = Norris, Susan L. title = An evaluation of emergency guidelines issued by the World Health Organization in response to four infectious disease outbreaks date = 2018-05-30 keywords = IQR; guideline summary = For guidelines, the methods for development were incompletely reported; WHO''s quality assurance process was rarely used; systematic or other evidence reviews were infrequently referenced; external peer review was not performed; and they scored poorly with AGREE II, particularly for rigour of development and editorial independence. For guidelines, the methods for development were incompletely reported; WHO''s quality assurance process was rarely used; systematic or other evidence reviews were infrequently referenced; external peer review was not performed; and they scored poorly with AGREE II, particularly for rigour of development and editorial independence. WHO quality standards dictate that guidelines must address a critical public health problem, use transparent and explicit processes minimizing potential sources of bias such as conflicts of interest, include diverse perspectives in the guideline development group, reflect the current state of the evidence, and provide a clear link between the evidence and recommendations taking into consideration the balance of benefits and harms of interventions and other important considerations [2] . doi = 10.1371/journal.pone.0198125 id = cord-257217-f9sdt7ax author = Nunes, Marta C. title = Clinical Epidemiology of Bocavirus, Rhinovirus, Two Polyomaviruses and Four Coronaviruses in HIV-Infected and HIV-Uninfected South African Children date = 2014-02-03 keywords = HIV; LRTI; PCR summary = We aimed to determine the prevalence and clinical characteristics of human bocavirus (hBoV), human rhinovirus (hRV), polyomavirus-WU (WUPyV) and –KI (KIPyV) and human coronaviruses (CoV)-OC43, -NL63, -HKU1 and -229E among children hospitalized with lower respiratory tract infections (LRTI). METHODS: Multiplex real-time reverse-transcriptase polymerase chain reaction was undertaken on archived nasopharyngeal aspirates from HIV-infected and –uninfected children (<2 years age) hospitalized for LRTI, who had been previously investigated for respiratory syncytial virus, human metapneumovirus, parainfluenza I–III, adenovirus and influenza A/B. The aim of this study was to identify the prevalence of hBoV, hRV, WUPyV, KIPyV, CoV-OC43, CoV-NL63, CoV-HKU1 and CoV-229E among HIV-infected and -uninfected children who were hospitalized for LRTI using real-time reverse transcriptase-polymerase chain reaction (RT-PCR). Very few viral aetiology studies have been conducted in Africa: in a Mozambican study of virus-associated acute respiratory infections (ARI) in infants with an estimated 3-5% HIV prevalence, the most frequently detected viruses were hRV (26%), influenza (15%) and adenovirus (14%) [27] . doi = 10.1371/journal.pone.0086448 id = cord-003024-17f1evh3 author = Nunes, Márcio Roberto Teixeira title = Revalidation and genetic characterization of new members of Group C (Orthobunyavirus genus, Peribunyaviridae family) isolated in the Americas date = 2018-05-24 keywords = Group summary = doi = 10.1371/journal.pone.0197294 id = cord-263464-fdosch11 author = Nuvey, Francis Sena title = Evaluation of the sentinel surveillance system for influenza-like illnesses in the Greater Accra region, Ghana, 2018 date = 2019-03-14 keywords = Ghana; ILI; influenza summary = We evaluated the ILI surveillance system in the Greater Accra region, Ghana, to assess the system''s attributes and its performance on set objectives. In collaboration with the Ghana Health Service (GHS) and the Ministry of Defense (MOD), it currently operates sentinel surveillance for influenza in 27 sites across all regions in Ghana with support from the U.S. Naval Medical Research Unit No. 3 (NAMRU-3), Centers for Disease Control and Prevention (CDC) and WHO [8] . We found that data on patients meeting the ILI case definition (S2 Table) from the sentinel sites are collected together with nasopharyngeal or oropharyngeal specimen. Our study provides evidence, that the ILI sentinel surveillance system in the Greater Accra Region (GAR), Ghana, is only partially meeting its objectives because it did not have thresholds for alerting the health system and does not perform antiviral resistance testing. doi = 10.1371/journal.pone.0213627 id = cord-329468-vjsurl60 author = Okino, Cintia Hiromi title = Early immune responses and development of pathogenesis of avian infectious bronchitis viruses with different virulence profiles date = 2017-02-15 keywords = Fig; IBV; group summary = This study compared the expression profile of genes related to immune responses in tracheal samples after challenge with two Brazilian field isolates (A and B) of IBV from the same genotype, associating these responses with viral replication and with pathological changes in trachea and kidney. Cell-mediated immune (CMI) related genes presented also lower levels of expression in tracheal samples from birds challenged with B isolate at 1dpi. This differential pattern of early immune responses developed after challenge with IBV B isolate, related to the downregulation of TLR7, leading to insufficient pro-inflammatory response and lower CMI responses, seem to have an association with a most severe renal lesion and an enhanced capability of replication of this isolate in chicken. In this study, we found a suppressive effect on expression of some early innate and adaptive cell-mediated immune genes in the primary site of virus replication (trachea) from chickens infected with one of the tested IBV isolates (B). doi = 10.1371/journal.pone.0172275 id = cord-002222-rgqwm3vb author = Olarte-Castillo, Ximena A. title = Divergent Sapovirus Strains and Infection Prevalence in Wild Carnivores in the Serengeti Ecosystem: A Long-Term Study date = 2016-09-23 keywords = RNA; Serengeti; african; infection; sapovirus summary = By screening a large number of predominantly fecal samples (n = 631) obtained from five carnivore species in the Serengeti ecosystem, East Africa, sapovirus RNA was detected in the spotted hyena (Crocuta crocuta, family Hyaenidae), African lion (Panthera leo, family Felidae), and bat-eared fox (Otocyon megalotis, family Canidae), but not in golden or silver-backed jackals (Canis aureus and C. Long-term monitoring of sapovirus in a population of individually known spotted hyenas from 2001 to 2012 revealed: i) a relatively high overall infection prevalence (34.8%); ii) the circulation of several genetically diverse variants; iii) large fluctuations in infection prevalence across years, indicative of outbreaks; iv) no significant difference in the likelihood of infection between animals in different age categories. A total of 20 partial RdRp gene sequences (16 from spotted hyenas, 3 from African lions and 1 from bat-eared foxes) were obtained and used for the phylogenetic analysis, together with publically available sequence data from 25 representatives of all sapovirus genogroups, divergent unclassified sapoviruses, and other genera in the Caliciviridae family, including Norovirus and Vesivirus. doi = 10.1371/journal.pone.0163548 id = cord-340627-xyvzgkxl author = Ornaghi, Sara title = Performance of an extended triage questionnaire to detect suspected cases of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection in obstetric patients: Experience from two large teaching hospitals in Lombardy, Northern Italy date = 2020-09-15 keywords = PCR; SARS summary = title: Performance of an extended triage questionnaire to detect suspected cases of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection in obstetric patients: Experience from two large teaching hospitals in Lombardy, Northern Italy Initially, a targeted SARS-CoV-2 screening approach triggered by a positive questionnaire and based on RT-PCR testing of nasopharyngeal swabs was used in women with hospital admission after accessing the Emergency Department. On April 8 th , we changed our policy and started testing all women for SARS-CoV-2 infection independent of the type of hospital admission and the questionnaire result, in agreement with a disposition of the Lombardy Region Health Care Authority. Our study investigated the accuracy of a comprehensive questionnaire thoroughly assessing obstetric patients upon hospital admission to identify cases suspected for SARS-CoV-2 infection. Our data show that thorough assessment of obstetric patients upon hospital admission by means of an exhaustive questionnaire is feasible and effective in discriminating women at low risk of SARS-CoV-2 infection in the context of both a targeted and a universal screening doi = 10.1371/journal.pone.0239173 id = cord-277306-r8jki3x4 author = Osborne, Christina title = Alphacoronaviruses in New World Bats: Prevalence, Persistence, Phylogeny, and Potential for Interaction with Humans date = 2011-05-12 keywords = Colorado; RNA; World; bat summary = doi = 10.1371/journal.pone.0019156 id = cord-001359-c1uom5f7 author = Oslund, Karen L. title = Synergistic Up-Regulation of CXCL10 by Virus and IFN γ in Human Airway Epithelial Cells date = 2014-07-17 keywords = CXCL10; IFN; IFNAR summary = In this study, we demonstrate the synergistic stimulation of CXCL10 mRNA and protein, a key chemokine responsible for the early immune response to viral infection, following treatment of airway epithelial cells with IFN γ and influenza virus. Therefore, we conclude that IFN γ and dsRNA act in concert to potentiate CXCL10 expression in airway epithelial cells via an NFκB-dependent but IFNAR-STAT independent pathway and it is at least partly regulated at the transcriptional level. In this study, we demonstrate synergistic induction of CXCL10 in well differentiated primary human bronchial epithelial (HBE) cells following influenza virus infection and the treatment with IFN c. As shown in Fig. 1A , well differentiated HBE cells demonstrated significant synergistic induction of CXCL10 mRNA following infection with the MEM influenza virus and treatment with IFN c. These results demonstrate that influenza virus in combination with IFN c synergistically induce CXCL10 mRNA and protein production from primary human airway epithelial cells. doi = 10.1371/journal.pone.0100978 id = cord-312002-4qhvljpv author = Pacheco-Barrios, Kevin title = COVID-19 pandemic and Farr’s law: A global comparison and prediction of outbreak acceleration and deceleration rates date = 2020-09-17 keywords = Farr; June; covid-19 summary = However, a 150-year old epidemics law promulgated by William Farr might be useful as a simple arithmetical model (percent increase [R1] and acceleration [R2] of new cases and deaths) to provide a first sight of the epidemic behavior and to detect regions with high predicted dynamics. In this study, we will model COVID-19 current data (until April 10, 2020) of new confirmed cases and deaths, from 210 countries as to test the assumptions of the 1840 Farr''s law, to describe the epidemic dynamics, and also to make predictions to identify areas with high dynamic and suggest preparation and actions of health system in those regions. doi = 10.1371/journal.pone.0239175 id = cord-001460-eo2bxxbq author = Padhi, Siladitya title = Atomistic Detailed Mechanism and Weak Cation-Conducting Activity of HIV-1 Vpu Revealed by Free Energy Calculations date = 2014-11-13 keywords = Vpu; channel; ion summary = doi = 10.1371/journal.pone.0112983 id = cord-013333-7jx4t0ol author = Palloni, Alberto title = Impacts of the 1918 flu on survivors' nutritional status: A double quasi-natural experiment date = 2020-10-20 keywords = earthquake; effect; exposure; flu; height; severity summary = doi = 10.1371/journal.pone.0232805 id = cord-310947-aqau2n7q author = Pan, Ji''An title = Genome-Wide Analysis of Protein-Protein Interactions and Involvement of Viral Proteins in SARS-CoV Replication date = 2008-10-01 keywords = Fig; RNA; SARS; interaction; protein summary = In this study, we adopted a mammalian two-hybrid system to screen the genome-wide intraviral protein-protein interactions of SARS coronavirus (SARS-CoV) and therefrom revealed a number of novel interactions which could be partly confirmed by in vitro biochemical assays. Using a SARS-CoV replicon expressing a luciferase reporter under the control of a transcription regulating sequence, it has been shown that several viral proteins (N, X and SUD domains of nsp3, and nsp12) provided in trans stimulated the replicon reporter activity, indicating that these proteins may regulate coronavirus replication and transcription. However, the viral protein interaction maps have been generated until now only for a limited number of viruses, including T7 bacteriophage [1] , vaccinia virus [2] , potato virus A [3] , pea seed-borne mosaic virus [3] , wheat steak mosaic virus [4] , hepatitis C virus [5, 6] , porcine teschovirus [7] , Kaposi sarcoma-associated herpesvirus [8] , and very recently severe acute respiratory syndrome coronavirus (SARS-CoV) [9, 10] . doi = 10.1371/journal.pone.0003299 id = cord-003270-vu9b5a14 author = Panahi, Heidar Ali title = A comprehensive in silico analysis for identification of therapeutic epitopes in HPV16, 18, 31 and 45 oncoproteins date = 2018-10-24 keywords = HLA; IEDB; MHC summary = In the first step, MHC-I and II binding, MHC-I processing, MHC-I population coverage and MHC-I immunogenicity prediction analyses, and in the second step, MHC-I and II protein-peptide docking, epitope conservation, and cross-reactivity with host antigens'' analyses were carried out successively by different tools. For the first step, MHC-I and II binding, MHC-I processing, MHC-I population coverage and MHC-I immunogenicity prediction analyses, and for the second step, MHC-I and II protein-peptide docking, epitope conservation, and cross-reactivity with host antigens analyses were considered. In this study, the binding ability of the first step selected peptides to human and mouse MHC molecules, was analyzed by CABS-dock (http://biocomp.chem.uw.edu.pl/CABSdock/) server. In cancer immunotherapy, the CTL-mediated responses play the central role in eradication of malignant cells, and the binding of epitopes to MHC-I molecules is an essential step for antigen presentation to CTLs. Thus, in this study, predicted epitopes were primarily selected by their MHC-I binding and processing scores. doi = 10.1371/journal.pone.0205933 id = cord-279259-eu80ccm6 author = Pandey, Aseem title = Impact of Preexisting Adenovirus Vector Immunity on Immunogenicity and Protection Conferred with an Adenovirus-Based H5N1 Influenza Vaccine date = 2012-03-14 keywords = CD8 summary = The immunogenicity and protection results suggest that low levels of vector immunity (<520 virus-neutralization titer) induced by priming mice with up to 10(7) plaque forming units (p.f.u.) of HAd-WT did not adversely impact the protective efficacy of the vaccine. Furthermore, high levels of vector immunity (approximately 1500 virus-neutralization titer) induced by priming mice with 10(8) p.f.u. of HAd-WT were overcome by either increasing the vaccine dose or using alternate routes of vaccination. To determine the level of vector immunity that can be tolerated without significantly affecting the vaccine efficacy, we primed groups of mice with varying doses of wild type (WT) HAd5 via intranasal (i.n.) or intramuscular (i.m.) route of inoculation to generate different levels of HAd5-neutralizing antibody titers. Further increase in the level of vector-specific neutralizing antibody titer to 3040 by i.m. priming with HAd5 only provided partial protection even in the groups receiving a high vaccine dose. doi = 10.1371/journal.pone.0033428 id = cord-270408-4qqyb8sd author = Pane, Masdalina title = Causes of Mortality for Indonesian Hajj Pilgrims: Comparison between Routine Death Certificate and Verbal Autopsy Findings date = 2013-08-21 keywords = Hajj; death; indonesian summary = title: Causes of Mortality for Indonesian Hajj Pilgrims: Comparison between Routine Death Certificate and Verbal Autopsy Findings This study presents the patterns and causes of death for Indonesian pilgrims, and compares routine death certificates to verbal autopsy findings. In the last two decades, the mortality rate of Indonesian pilgrims, excluding years in which disasters such as stampedes occurred, fluctuated between 200-380 deaths per 100,000 persons during the ten-week Hajj period [5] . The cause of death based on this verbal autopsy method was then recorded in the database and compared to that reported by the hospital or flight doctor death certificate. A greater proportion of deaths were attributed to cardiovascular disease by the flight doctor or hospital death certificate (66%) compared to the cause of death ascertained using the verbal autopsy method (49%, p<0.001). Based on both the death certificates and verbal autopsy categories, cardiovascular disease was the leading cause of Indonesian pilgrim mortality in 2008. doi = 10.1371/journal.pone.0073243 id = cord-316703-8kxx3034 author = Parera, Mariona title = Canine Hepacivirus NS3 Serine Protease Can Cleave the Human Adaptor Proteins MAVS and TRIF date = 2012-08-01 keywords = CHV; HCV; ns3/4a summary = The aim of this study was to investigate whether the NS3/4A serine protease of CHV specifically cleaves human mitochondrial antiviral signaling protein (MAVS) and Toll-IL-1 receptor domain-containing adaptor inducing interferon-beta (TRIF). The target specificity for the MAVS and TRIF cleavage sites was tested by coexpressing them with CHV or HCV NS3/4A protease constructs. coli cells coexpressing the lambda cI repressor with either MAVS or TRIF cleavage site and a CHV NS3/4A construct, lambda phage replicated up to 2,000-fold more efficiently than in cells expressing a CHV protease variant that included a substitution in catalytic residue S139 ( Fig. 3A and 3B). In this study, we tested the ability of CHV NS3/4A protease to specifically cleave the human adaptor proteins MAVS and TRIF. Canine orthologs of human MAVS and TRIF differ in sequence at the cleavage site processed by HCV NS3/4A protease; therefore, they were not tested in this study. doi = 10.1371/journal.pone.0042481 id = cord-261410-kb91eagd author = Park, Ji Young title = Clinical Features and Courses of Adenovirus Pneumonia in Healthy Young Adults during an Outbreak among Korean Military Personnel date = 2017-01-23 keywords = hadv; patient; pneumonia summary = The clinical features of respiratory adenoviral infection among military personnel were described previously; however, HAdV pneumonia in immunocompetent individuals and risk factors of disease progression to severe pneumonia or acute respiratory failure have not been well studied. All military trainees or active duty members, but not officers, were eligible for enrollment if they were !18 years old and had been admitted to the study hospital for pneumonia, defined by acute respiratory symptoms (fever, cough, sputum, dyspnea, and pleuritic chest pain) and pulmonary infiltrates on chest X-rays or computed tomography (CT) scans. Most HAdV pneumonia patients were basic military trainees or personnel who had recently completed training; active duty service personnel were not usually affected, even during outbreak peaks. Our results show that an outbreak of HAdV pneumonia occurred in Korean military training centers and indicate that emergent-type HAdV-55 infections might have caused the outbreak. doi = 10.1371/journal.pone.0170592 id = cord-001254-y2knt8g0 author = Parkhomenko, Taisiya A. title = Comparison of DNA-Hydrolyzing Antibodies from the Cerebrospinal Fluid and Serum of Patients with Multiple Sclerosis date = 2014-04-15 keywords = Abs; CSF; dna summary = Here we have shown, for the first time, that average concentration of total proteins (132-fold), total IgGs (194-fold) and anti-DNA antibodies (200-fold) in the sera is significantly higher than that in the cerebrospinal fluid (CSF) of fifteen MS patients. We present first evidence showing that IgGs from CSF not only bind but efficiently hydrolyze DNA and that average specific DNase activity of homogeneous antibodies from CSF is unpredictably ∼49-fold higher than that from the sera of the same MS patients. Finally, the relative concentration of total anti-DNA Abs correlated with the relative specific IgG DNase activity better in the sera (CC = +0.51; columns 6 and 12) than in CSF (CC = + 0.11; columns 5 and 11) (Tables 2 and 3 ). doi = 10.1371/journal.pone.0093001 id = cord-311531-wezrs7gc author = Parčina, Marijo title = Multicenter evaluation of the QIAstat Respiratory Panel—A new rapid highly multiplexed PCR based assay for diagnosis of acute respiratory tract infections date = 2020-03-12 keywords = Allplex; QIAstat summary = The QIAstat Respiratory Panel(®) assay (QIAstat RP) is a multiplexed in vitro diagnostics test for the rapid simultaneous detection of 21 pathogens directly from respiratory samples, including human mastadenovirus A-G, primate bocaparvovirus 1+2, human coronavirus (HKU1, NL63, OC43, 229E), human metapneumovirus A/B, rhinovirus/enterovirus, influenza A virus (no subtype, subtype H1, H1N1/2009, H3), influenza B virus, human respirovirus 1+3, human orthorubulavirus 2+4, human orthopneumovirus, Bordetella pertussis, Chlamydia pneumoniae, Mycoplasma pneumoniae and Legionella pneumophila. The FilmArray RP is a multiplex sample-to-answer PCR panel that tests for 20 viral and bacterial pathogens on nasopharyngeal swabs in UTM at a time. Before resolution by discrepancy testing, QIAstat RP and FilmArray RP agreed on the detection of 376 pathogens in the 445 samples (Table 3) . After resolution by discrepancy testing on the Allplex RP, a total of 402 pathogen results were considered as true positive (Table 4) , of which QIAstat RP detected 394, for an overall PPA of 98.0% (95%CI 96.0%-99.1%). doi = 10.1371/journal.pone.0230183 id = cord-048477-ze511t38 author = Patel, Mahomed S. title = General Practice and Pandemic Influenza: A Framework for Planning and Comparison of Plans in Five Countries date = 2008-05-28 keywords = Canada; general; health; plan; practice summary = The framework identifies four functional domains: clinical care for influenza and other needs, public health responsibilities, the internal environment and the macro-environment of general practice. Although there is little evidence linking specific preparedness activities to effective system-wide responses to pandemic influenza [5, 6] , change management theories point to a need for dynamic partnerships between general practices and other ambulatory care services, hospitals and public health departments [10] . We aimed to develop a framework that will facilitate systematic planning for the general practice response to pandemic influenza and used it to appraise coverage of key elements in publicly available pandemic plans from Australia, England, USA, New Zealand and Canada. This calls for coordination across general practices and other ambulatory care services to ensure primary health care needs within the community are effectively monitored and addressed; with hospitals to avoid/delay hospitalisation and facilitate early discharge; and with public health units to share responsibilities for contact tracing, monitoring and treating people in home isolation or quarantine, dispensing of anti-viral medications, and participation in mass immunisations against pandemic strains of the virus (when these become available). doi = 10.1371/journal.pone.0002269 id = cord-348055-azlb1zy1 author = Patel, Mira C. title = Enterovirus D-68 Infection, Prophylaxis, and Vaccination in a Novel Permissive Animal Model, the Cotton Rat (Sigmodon hispidus) date = 2016-11-04 keywords = D68; Fig; VANBT summary = To determine effect of the EV-D68 infection on the induction of an inflammatory response, we focused on the lung tissue and measured the expression of cotton rat mRNA for several chemokines, Type I and Type II interferons (IFNs), cytokines, and select IFN-inducible genes following VANBT infection. As there are no current animal models for EV-D68 and information regarding relevant disease-related outcomes from human cases is limited, we herein characterized EV-D68 infection in cotton rats by measuring viral load and vRNA (negative or total) in either nose or lung tissues until 4 days p.i., assessing mRNA expression of various chemokines, IFNs, and proinflammatory cytokines, and lung histology. Although the replication cycle of VANBT appeared to be short-lived, its profile of viral titer in the nose over time (showing clear virus eclipse at 4 h, rising quickly and reaching a peak by 10 h p.i.), and their differences with the output virus obtained after infection with different strains demonstrate that VANBT replicates in upper respiratory tract of cotton rats. doi = 10.1371/journal.pone.0166336 id = cord-335245-1eksm537 author = Pattyn, Els title = HyperISGylation of Old World Monkey ISG15 in Human Cells date = 2008-06-18 keywords = IFN; cell; figure; isg15 summary = Western blot analysis visualized more efficient conjugation of OWmISG15 relative to HuISG15 in human (Hu), monkey and mouse (Mo) cell-lines. Western blot analysis on total cell lysates containing b-ME confirmed ISGylation of UbcH10, H13 and H17 with AgmISG15 but not with HuISG15, as seen by a 15 kDa shift upon staining with anti-V5 Ab detecting the ectopic expressed UbcH proteins (Figure 3a ,b and Figure S2a ). Previous studies using Western blot analysis in HekT cells revealed Hu or MoISG15 conjugation to substrates such as UbcH13 only upon co-transfection of at least UbE1L -and generally also UbcH/M8or upon IFN stimulation. The effect of mutating HuISG15 residues situated near the predicted UbE1L interface and the different allelic variants on conjugation to UbcH proteins is shown in Figure 5a and S3a. As shown in Figure 5c , mutation of D133N and QIT31-33KIA in the HuISG15 N89D variant further enhanced its ISGylation in human HekT cells. doi = 10.1371/journal.pone.0002427 id = cord-270683-982eqtog author = Pavel, Shaikh Terkis Islam title = Isolation and characterization of severe acute respiratory syndrome coronavirus 2 in Turkey date = 2020-09-16 keywords = Fig; SARS; Turkey; Vero summary = doi = 10.1371/journal.pone.0238614 id = cord-303490-rixuuytu author = Pazos, Michael A. title = Estrogen Mediates Innate and Adaptive Immune Alterations to Influenza Infection in Pregnant Mice date = 2012-07-05 keywords = CD8; cell; figure; infection summary = These data suggest that despite significant morbidity associated with fetal gestation, pregnant mice have an impaired ability to control influenza virus infection in both lethal and nonlethal models. We did not observe any significant differences in the absolute number of cells infiltrating lung tissue during infection with X31 in pregnant ( Figure 5A ) or E2-treated mice (data not shown). In order to determine whether emigration from the lung was impaired, we investigated the number of dendritic cells in the draining mediastinal lymph node at key time points of infection and found no significant differences between pregnant mice and their non-pregnant controls ( Figure 5B ), or between E2-pelleted mice and their placebo controls (data not shown). We found strongly reduced levels of CD86 expression on CD11c+ cells at critical early time points after infection in both pregnancy ( Figure 5C ) and estrogen-treatment ( Figure 5D ), suggesting a deficiency in proper DC maturation. doi = 10.1371/journal.pone.0040502 id = cord-013356-y6vceq2x author = Peace, Angela title = Orchard layout and plant traits influence fruit yield more strongly than pollinator behaviour and density in a dioecious crop date = 2020-10-23 keywords = ffl; flower summary = The predictive model provides strategies for improving crop management, such as choosing cultivars which have their peak bloom on the same day, increasing the number of flowers with approximately 70% female flowers in the orchard, and placing enough hives to maintain more than 6 bees per 1000 flowers to optimize yield. We expected that male-female kiwifruit flower ratio and pollinator density will influence fruit yield, along with various parameters of pollinator behavior. The model explicitly tracks pollinators (parameterized here based on data from honey bees), with varying pollen loads as they preferentially visit male and female flowers, as well as A major model output measure is the predicted yield, which is defined as the number of female flowers per ha that became fully pollinated fruit. The model includes preference parameters for pollinators to remain on the type of flower they are visiting, based again on data from honey bee observations. doi = 10.1371/journal.pone.0231120 id = cord-335880-m8gecsf0 author = Peci, Adriana title = Epidemiology of Enterovirus D68 in Ontario date = 2015-11-23 keywords = D68; Ontario summary = In response to CDC reports, Public Health Ontario Laboratories (PHOL) launched an investigation of patients being tested for enterovirus D-68 (EV-D68) in Ontario, Canada. In order to better understand the epidemiology of this virus, surveillance for EV-D68 should include testing of symptomatic individuals from all treatment settings and patient age groups, with collection and analysis of comprehensive clinical and epidemiological data. Data for this study included specimens submitted for EV-D68 testing at PHOL from patients who presented with respiratory symptoms in different health care settings across Ontario, from September 1, 2014 to October 31, 2014. Percent positivity and descriptions of EV-D68 cases by timing of specimen collection, age, sex, setting, symptoms and local health unit of residence were analysed at the patient level. Bivariate and multivariate logistic regression analyses were performed at the patient level to compare cases and controls in terms of age, sex, settings, symptoms and timing of specimen collection. doi = 10.1371/journal.pone.0142841 id = cord-337795-khqx4t4q author = Pellecchia, Umberto title = Social Consequences of Ebola Containment Measures in Liberia date = 2015-12-09 keywords = Ebola; Liberia; Monrovia; quarantine summary = INTRODUCTION: In the Ebola Virus Disease (EVD) outbreak in Liberia, two major emergency disease-control measures were cremation of bodies and enforcement of quarantine for asymptomatic individuals suspected of being in contact with a positive case. To address these questions, this study was conducted to assess Liberian community perspectives on State-imposed Ebola public health and outbreak containment measures implemented in 2014 and 2015. The grids were organized according to three main themes: 1) general social perception of the epidemic and community''s reactions; 2) funerary and burial practices before and during the epidemic, and opinions on cremation; and 3) health-seeking behaviours and perception of quarantine. Forced quarantine of asymptomatic contacts of positive cases was the main State-imposed measure that transformed social perceptions and practices. Cremation of bodies and forced quarantine, as ways to quickly reduce transmission of Ebola outbreak for the benefit of the larger public, produced social dynamics of resistance in the same population that they wished to protect. doi = 10.1371/journal.pone.0143036 id = cord-318845-w7q5o8wc author = Pendell, Dustin L. title = Economic Assessment of FMDv Releases from the National Bio and Agro Defense Facility date = 2015-06-26 keywords = FMD; States; U.S.; United summary = This study evaluates the economic consequences of hypothetical foot-and-mouth disease releases from the future National Bio and Agro Defense Facility in Manhattan, Kansas. To assess the economic impacts of unintentional FMDv releases from NBAF, we follow [4, 7, [21] [22] to link supply shocks from an animal disease spread model with a multi-commodity, multi-market partial equilibrium model. To determine the total economic impact for a scenario, the changes in producer returns to capital and management and consumer welfare, government indemnification and non-indemnification expenditures, and the costs to the non-agricultural regional sector were summed together. Because the duration of the FMD outbreaks and number of animals culled and vaccinated are similar to the aerosol scenarios, the total economic impacts of the transference release scenarios are similar to impacts of an aerosol release, including the distribution of impacts by production types across time. doi = 10.1371/journal.pone.0129134 id = cord-003712-mafz21no author = Perez Vidakovics, Maria Laura A. title = Junín virus induces autophagy in human A549 cells date = 2019-06-19 keywords = Fig; JUNV; LC3; a549; cell summary = We found that JUNV infection induces an increment of the LC3-II/LC3-I ratio, an accumulation of punctate pattern in RFP-LC3-transfected cells and the colocalisation of viral nucleoprotein and LC3 protein, suggesting autophagosome formation. Either with the early autophagy inhibitor (3-MA) or the late inhibitor (BAF), the treatment pre or post-infection resulted in reduced expression of N and lower viral titre as compared to JUNV-infected cells that received no treatment (NT) (Fig 4B-4D) . In parallel, experiments performed adding Rap post-infection resulted in a similar increase in viral yields of JUNV, which indicates that the activation of autophagy benefits both viral entry/uncoating and later steps as assembling and viral budding (Fig 4) . When compared to control cells, an increase in the number of mCherry puncta following rapamycin treatment was observed, indicating promoted autophagy and fusion between autophagosomes and acidic compartments (Fig 5C) . doi = 10.1371/journal.pone.0218730 id = cord-000837-rdpsxb4n author = Perez-Pepe, Marcelo title = BUHO: A MATLAB Script for the Study of Stress Granules and Processing Bodies by High-Throughput Image Analysis date = 2012-12-20 keywords = BUHO; cell; figure summary = title: BUHO: A MATLAB Script for the Study of Stress Granules and Processing Bodies by High-Throughput Image Analysis Stress granules (SGs) and processing bodies (PBs) belong to a novel family of cellular structures collectively known as mRNA silencing foci that harbour repressed mRNAs and their associated proteins. To assess the suitability of BUHO for the analysis of additional cell structures, we investigated several examples of cytoplasmic foci stained with different strategies, including SGs and PBs in mammalian and insect cells, and synapses and Smaug 1-mRNA silencing foci (S-foci) in primary neurons. Moreover, as expected given that SGs and PBs are morphologically similar, we found that prototype SGs were useful to identify PBs. To test the performance of BUHO in analyzing distances between objects, we focused on the presence of synaptic mRNA silencing foci at the synapse surroundings. With minor modifications, we have successfully applied it for processing images of different magnification and resolution of synapses, SGs, PBs and similar foci in mammalian and Drosophila cell lines as well as in primary cultured neurons. doi = 10.1371/journal.pone.0051495 id = cord-349217-vpih1wvs author = Petropoulos, Fotios title = Forecasting the novel coronavirus COVID-19 date = 2020-03-31 keywords = case; forecast summary = Assuming that the data used is reliable and that the future will continue to follow the past pattern of the disease, our forecasts suggest a continuing increase in the confirmed COVID-19 cases with sizable associated uncertainty. While all three data patterns show an exponential increase, the trends of both the confirmed cases and the deaths were reduced in the mid of February; a second exponential increase is observed in late February and March as a result of the increased number of cases in South Korea, Iran, and Europe. The mean estimate (point forecast) for the confirmed cases ten-days-ahead was 209 thousand with the 90% prediction intervals ranging from about 38 to 534 thousand cases. However, the estimated uncertainty by splitting the data is considerably lower, possibly since the confirmed cases outside Mainland China have significantly increased only recently. doi = 10.1371/journal.pone.0231236 id = cord-000866-dr2uow4m author = Picard-Jean, Frédéric title = The Immunosuppressive Agent Mizoribine Monophosphate Is an Inhibitor of the Human RNA Capping Enzyme date = 2013-01-17 keywords = GMP; GTase; HCE; MZP; RNA summary = doi = 10.1371/journal.pone.0054621 id = cord-280386-a8qr7nl6 author = Pires, Sara M. title = Aetiology-Specific Estimates of the Global and Regional Incidence and Mortality of Diarrhoeal Diseases Commonly Transmitted through Food date = 2015-12-03 keywords = disease; estimate summary = The objective of this study is to provide estimates of the global and regional incidence and mortality of diarrhoeal diseases caused by nine pathogens that are commonly transmitted through foods. METHODS AND FINDINGS: We abstracted data from systematic reviews and, depending on the overall mortality rates of the country, applied either a national incidence estimate approach or a modified Child Health Epidemiology Reference Group (CHERG) approach to estimate the aetiology-specific incidence and mortality of diarrhoeal diseases, by age and region. To identify and prioritize targeted interventions to reduce the public health impact of foodborne diseases, public health policy makers and other stakeholders need aetiology-specific regional and global estimates of the incidence and mortality of diarrhoeal diseases caused by pathogens that are commonly transmitted through foods. While approach 1 analysed national incidence and mortality of disease by pathogens commonly transmitted through foods estimated primarily by correcting surveillance data to account for underreporting and under-diagnosis, approach 2 relied on systematic reviews of studies identifying causative agents in patients with diarrhoea. doi = 10.1371/journal.pone.0142927 id = cord-000224-2lz03oqb author = Porter, Kristen A. title = Class II Transactivator (CIITA) Enhances Cytoplasmic Processing of HIV-1 Pr55Gag date = 2010-06-24 keywords = CIITA; Gag; HLA; MHC summary = METHODOLOGY/PRINCIPAL FINDINGS: Here we demonstrate that both stable and transient expression of CIITA in HIV producer cells does not induce HLA-DR-associated intracellular retention of Gag, but does increase the infectivity of virions. We hypothesized that recapitulating endogenous expression of the entire class II antigen presentation pathway in producer cells via expression of CIITA would restore infectious virus release and provide a more physiologically relevant model for HIV-1 assembly studies. Virus release, both infectious and particle titers) were reduced when cells were transfected with either HLA-DR or other components of the MHC class II antigen presentation pathway ( Figure S2 ), confirming a correlation between Gag retention and reduced virus titers in the presence of HLA-DR, as previously demonstrated [8] . Together, these data suggest CIITA has two effects on the HIV replicative cycle in producer cells, both of which are independent of the MHC II antigen processing pathway; i) it does not induce HLA-DR, mediated intracellular retention of Gag and ii) it increases the infectivity of HIV virions. doi = 10.1371/journal.pone.0011304 id = cord-002935-jq1xumrh author = Postnikova, Elena title = Testing therapeutics in cell-based assays: Factors that influence the apparent potency of drugs date = 2018-03-22 keywords = EBOV; Ebola; MOI; Vero summary = doi = 10.1371/journal.pone.0194880 id = cord-303331-xolksoy3 author = Pourghasemi, Hamid Reza title = Assessment of the outbreak risk, mapping and infection behavior of COVID-19: Application of the autoregressive integrated-moving average (ARIMA) and polynomial models date = 2020-07-28 keywords = Fars; Iran; SVM; covid-19 summary = A geographic information system (GIS)-based machine learning algorithm (MLA), support vector machine (SVM), was used for the assessment of the outbreak risk of COVID-19 in Fars Province, Iran whereas the daily observations of infected cases were tested in the—polynomial and the autoregressive integrated moving average (ARIMA) models to examine the patterns of virus infestation in the province and in Iran. The aims of the present study were to analyze the risk factors of coronavirus outbreak and test the SVM model for mapping areas with a high risk of human infection with the virus in Fars Province, Iran. Accordingly, in this research, we selected sixteen most relevant effective factors for the outbreak risk mapping of COVID-19 in Fars Province of Iran, which includes minimum temperature of coldest month (MTCM), maximum temperature of warmest month (MTWM), precipitation in wettest month (PWM), precipitation of driest month (PDM), distance from roads, distance from mosques, distance from hospitals, distance from fuel stations, human footprint, density of cities, distance from bus doi = 10.1371/journal.pone.0236238 id = cord-000321-ee7q7jhv author = Powell, Michael L. title = Further Characterisation of the Translational Termination-Reinitiation Signal of the Influenza B Virus Segment 7 RNA date = 2011-02-08 keywords = 18S; AUG; BM2; TURBS; figure summary = The features identified in caliciviral TURBS suggest a model for termination-reinitiation in which post-termination 40S subunits are tethered to the mRNA through interactions between the mRNA (through motif 1) and 18S rRNA, initiation factors are recruited and the AUG restart codon located, processes which may require precise RNA folding (involving motif 2) within the TURBS. Analysis of primary and secondary structural features of the BM2 signal has revealed that it contains a short TURBS (of 45 nt) which is largely single-stranded, with motif 1 likely to be located in the apical loop of a metastable stem-loop structure when the ribosome is positioned at the termination codon of the upstream ORF [11] . Importantly, mutation of the motif 1 homologue such that it was fully complementary to yeast 18S rRNA led to a significant (p,0.01) increase in BM2fluc synthesis relative to the wild-type BM2 reporter ( Figure 4C ), supporting the view that mRNA:rRNA base pairing is a key determinant in BM2 ORF expression. doi = 10.1371/journal.pone.0016822 id = cord-254117-2ttwaegh author = Priest, Patricia C. title = Thermal Image Scanning for Influenza Border Screening: Results of an Airport Screening Study date = 2011-01-05 keywords = ITIS; influenza; traveller summary = The prediction by ITIS of tympanic temperature (37.8°C and 37.5°C) and of influenza infection was assessed using Receiver Operating Characteristic (ROC) curves and estimated sensitivity, specificity and positive predictive value (PPV). This evaluation of thermal image scanning was carried out as part of a larger study to measure the prevalence of seasonal influenza infection in arriving airline travellers and the effectiveness of a screening questionnaire for detecting those with influenza infection. To assess the utility of fever as a screening test for influenza infection (MT-PCR result), sensitivity, specificity, and population PPV for influenza were estimated for each tympanic temperature threshold, and the ITIS threshold used above. The greatest potential for the use of ITIS to screen incoming or departing travellers for infectious diseases such as a pandemic strain of influenza would be as the first stage of screening; that is, to identify and select out a high risk group for further assessment, for example by questionnaire, body core temperature measurement, and/or respiratory sample collection. doi = 10.1371/journal.pone.0014490 id = cord-342133-khrljehj author = Principi, Nicola title = Bocavirus Infection in Otherwise Healthy Children with Respiratory Disease date = 2015-08-12 keywords = child; infection; respiratory; viral summary = To evaluate the role of human bocavirus (hBoV) as a causative agent of respiratory disease, the importance of the viral load in respiratory disease type and severity and the pathogenicity of the different hBoV species, we studied all hBoV-positive nasopharyngeal samples collected from children who attended an emergency room for a respiratory tract infection during three winters (2009–2010, 2011–2012, and 2013–2014). To evaluate the circulation of the different hBoV types and the possible relationships between viral load, virus genetic characteristics, and the severity of infection, nasopharyngeal swabs were collected from otherwise healthy children attending the emergency room of the Fondazione IRCCS Ca'' Granda Ospedale Maggiore Policlinico, University of Milan, Italy, due to a respiratory tract infection arising between November 1 and March 31 during 3 winters (2009-2010, 2011-2012, and 2013-2014) . Single detection of human bocavirus 1 with a high viral load in severe respiratory tract infections in previously healthy children doi = 10.1371/journal.pone.0135640 id = cord-000736-6f8vyziv author = Pripuzova, Natalia title = Development of Real-Time PCR Array for Simultaneous Detection of Eight Human Blood-Borne Viral Pathogens date = 2012-08-17 keywords = HBV; HIV-1; PCR; RNA summary = FINDINGS: We developed a real-time PCR array capable of simultaneously detecting eight human viral pathogens: human immunodeficiency virus types 1 and 2 (HIV-1 and -2), hepatitis B virus (HBV), hepatitis C virus (HCV), human T-cell leukemia virus-1 and -2 (HTLV-1 and -2), vaccinia virus (VACV) and West Nile virus (WNV). The analytical sensitivity of each primer set was determined in the single virus testing using FDA/CBER panels (kindly provided by Dr. Stephen Kerby, FDA/CBER) consisting of various amounts of the viruses (0-1,000 genome copies/ml) spiked into the ''''normal'''' human plasma. The results of sensitivity testing of the real-time PCR array primer sets specific for HIV-1, HIV-2, HBV, HCV, and WNV the with FDA/CBER analytical plasma panels. Tm and C(t) values obtained with primer sets specific for HIV-1, HCV, or HBV in testing of 17 human clinical samples in the format of PCR array targeting eight different viruses. doi = 10.1371/journal.pone.0043246 id = cord-319845-oob2ktnz author = Proença-Modena, José Luiz title = Detection of Human Bocavirus mRNA in Respiratory Secretions Correlates with High Viral Load and Concurrent Diarrhea date = 2011-06-20 keywords = ARI; HBoV; PCR; VP1 summary = Therefore, in order to test whether active viral replication of human bocavirus is associated with respiratory diseases and to understand the clinical impact of this virus in patients with these diseases, we performed a 3-year retrospective hospital-based study of HBoV in outpatients and inpatients with symptoms of Acute Respiratory Infections (ARI) in Brazil. This article reports a cross-sectional study of HBoV in ARI patients from Ribeirão Preto, Brazil, in which the shedding of VP1 mRNA in respiratory secretions was used as surrogate marker for active HBoV replication, to look for correlations with viral load, and presence of particular clinical manifestations and simultaneous detection of other respiratory viruses. The results of this cross-sectional study of HBoV in ARI patients from Ribeirão Preto, Brazil, indicate that shedding of VP1 mRNA in respiratory secretions, as a marker of HBoV replication, correlates positively with high viral load, presence of diarrhea, and lack of co-infection by other respiratory viruses. doi = 10.1371/journal.pone.0021083 id = cord-278224-sq7tokbx author = Protopopova, Alexandra title = Behavioral predictors of subsequent respiratory illness signs in dogs admitted to an animal shelter date = 2019-10-23 keywords = curiosity; day; dog; shelter summary = doi = 10.1371/journal.pone.0224252 id = cord-291756-ejh1r8h4 author = Pérez-Fuentes, María del Carmen title = Threat of COVID-19 and emotional state during quarantine: Positive and negative affect as mediators in a cross-sectional study of the Spanish population date = 2020-06-25 keywords = COVID-19; negative; threat summary = title: Threat of COVID-19 and emotional state during quarantine: Positive and negative affect as mediators in a cross-sectional study of the Spanish population AIMS: The objective of this study was therefore to analyze the effect of exceptionally stressful situations, such as the current health risk, on the cognitive and emotive state of the individual, that is, perceived threat and emotional state on affect and mood. RESULTS: The results showed that the perception of threat from COVID-19 was related positively to negative affect and emotional signs, that is, sadness-depression, anxiety and anger-hostility. The starting hypothesis was that perception of threat in the exceptional state of health emergency caused by COVID-19, affects one''s emotional situation (Model 1), and this, in turn, affects perception of risk (Model 2), in which positive and negative affect balances act as mediators in these relationships (Fig 1) . doi = 10.1371/journal.pone.0235305 id = cord-000689-8lvzab4i author = Qi, Yilin title = The Acute Environment, Rather than T Cell Subset Pre-Commitment, Regulates Expression of the Human T Cell Cytokine Amphiregulin date = 2012-06-14 keywords = CD4; cell summary = doi = 10.1371/journal.pone.0039072 id = cord-295559-yc8q62z8 author = Qian, Zhaohui title = Role of the Spike Glycoprotein of Human Middle East Respiratory Syndrome Coronavirus (MERS-CoV) in Virus Entry and Syncytia Formation date = 2013-10-03 keywords = MERS; SARS; Vero summary = Coronavirus S proteins are Class I viral fusion proteins like the HIV envelope (env), influenza hemagglutinin (HA) and paramyxovirus fusion (F) glycoproteins [17] , which typically require protease cleavage between the S1 and S2 domains ( Figure 1A ) to permit conformational changes in S2, activated by receptor binding and/or low pH, that mediate membrane fusion leading to virus entry and syncytia formation [3, 17, 18] . In addition to entry by endocytosis, we showed that, like SARS-CoV [21, 22] , MERS pseudovirions could enter susceptible Vero E6 cells at the plasma membrane if virions were first bound to cell surface receptors at 4°C at neutral pH in the presence of NH 4 Cl to inhibit acidification of endosomes, and also treated briefly at room temperature with trypsin to cleave the viral S protein. doi = 10.1371/journal.pone.0076469 id = cord-281665-6n7aq4k9 author = Qiu, Sangsang title = Is Tuberculosis Treatment Really Free in China? A Study Comparing Two Areas with Different Management Models date = 2015-05-20 keywords = China; ZJG summary = This study describes the economic burden on patients with tuberculosis; identifies related factors by comparing two areas with different management models; and provides policy recommendation for tuberculosis control reform in China. Based on the multivariable linear regression analysis, factors related to the total out-of-pocket costs were study site, age, number of clinical visits, residence, diagnosis delay, hospitalization, intake of liver protective drugs and use of the second-line drugs. This study describes the economic burden on patients with tuberculosis, identifies related factors by comparing two areas with different management models, and provides a policy recommendation for the tuberculosis control system in China. Significant factors related to the total out-of-pocket costs were study setting (t = -3.10, P = 0.002), age (t = -4.04, P < 0.001), number of clinical visits (t = 4.46, P < 0.001), residence (t = 3.19, P = 0.002), diagnosis delay (t = 3.47, P = 0.001), hospitalization (t = 15.04, P < 0.001), intake of liver protective drugs (t = 2.78, P = 0.006) and intake of second-line drugs (t = 2.87, P = 0.004) ( Table 5) . doi = 10.1371/journal.pone.0126770 id = cord-351990-aham72b9 author = Radin, Jennifer M. title = Epidemiology of Pathogen-Specific Respiratory Infections among Three US Populations date = 2014-12-30 keywords = FRI; influenza; respiratory summary = METHODS: Febrile respiratory illness (FRI) and severe acute respiratory infection (SARI) surveillance was conducted from October 2011 through March 2013 among three US populations: civilians near the US–Mexico border, Department of Defense (DoD) beneficiaries, and military recruits. Recruits with rhinovirus had higher percentages of pneumonia, cough, shortness of breath, congestion, cough, less fever and longer time to seeking care and were more likely to be male compared to those in the no/unknown pathogen group. This study aimed to describe characteristics associated with specific respiratory pathogens, as well as the etiology, seasonality, and coinfection rates among three US populations: military recruits, Department of Defense (DoD) beneficiaries, and civilians living near the US-Mexico border. Additionally, the following demographic and clinical signs and symptoms were collected from each FRI and SARI case: sex, age, study population, month of illness, pneumonia, sore throat, cough, nausea, shortness of breath, congestion, pink eye, body ache, headache, temperature, number of days of symptoms before seeking care, and date of seeking care. doi = 10.1371/journal.pone.0114871 id = cord-000410-av8b8g8c author = Radoshitzky, Sheli R. title = Machupo Virus Glycoprotein Determinants for Human Transferrin Receptor 1 Binding and Cell Entry date = 2011-07-07 keywords = Fig; MACV; gp1 summary = doi = 10.1371/journal.pone.0021398 id = cord-352222-zq9o66i4 author = Rajatonirina, Soatiana title = Outcome Risk Factors during Respiratory Infections in a Paediatric Ward in Antananarivo, Madagascar 2010–2012 date = 2013-09-12 keywords = child; infection; respiratory summary = BACKGROUND: Acute respiratory infections are a leading cause of infectious disease-related morbidity, hospitalisation and mortality among children worldwide, and particularly in developing countries. MATERIALS AND METHODS: We conducted a prospective study in a paediatric ward in Antananarivo from November 2010 to July 2012 including patients under 5 years old suffering from respiratory infections. CONCLUSION: Co-mordidity, low-income and age under 6 months increase the risk of severe outcome for children infected by numerous respiratory pathogens. Our study aimed to evaluate the risk factors associated with the evolution and outcome of respiratory illnesses in patients aged under 5 years old hospitalised in one of the four main public hospitals in Antananarivo. In our study, Streptococcus pneumoniae was the most common bacterial pathogen as in other studies of hospitalised patients with acute respiratory illness, and Haemophilus influenzae type B was the next most frequent [16] [17] [18] [19] . doi = 10.1371/journal.pone.0072839 id = cord-000609-dpcgl6ig author = Raju, Sammeta V. title = Suppression of Adenosine-Activated Chloride Transport by Ethanol in Airway Epithelia date = 2012-03-19 keywords = CFTR; Calu-3 summary = Here, air-liquid interface cultures of Calu-3 epithelial cells were basolaterally exposed to physiologically relevant concentrations of ethanol (0, 25, 50 and 100 mM) for 24 hours and adenosine-stimulated ion transport was measured by Ussing chamber. These results imply that ethanol exposure dysregulates CFTR-mediated chloride transport in airways by suppression of adenosine-A(2B)AR-cAMP signaling pathway, which might contribute to alcohol-associated lung infections. The current report directly measured the adenosineinduced chloride secretion of airway epithelia under the exposure of physiologically relevant concentrations of alcohol and found that ethanol attenuates epithelial CFTR-mediated chloride transport by modulating cellular cAMP levels. To explore if ethanol affects adenosine-activated ion transport function of airway epithelium, we employed air-liquid interface cultures of Calu-3 cells, a system widely used to investigate airway epithelial electrophysiological properties [27, 28] . These results not only confirm that ethanol modulates adenosine-cAMP signaling but also suggest that phosphodiesterase inhibitors may be useful as the potential therapeutic agents for improving the airway epithelial ion transport and mucociliary clearance in alcoholic patients. doi = 10.1371/journal.pone.0032112 id = cord-000050-tfcerilc author = Rao, Srinivas title = Multivalent HA DNA Vaccination Protects against Highly Pathogenic H5N1 Avian Influenza Infection in Chickens and Mice date = 2008-06-18 keywords = H5N1; dna; vaccine; virus summary = METHODOLOGY / PRINCIPAL FINDINGS: The ability of DNA vaccines encoding hemagglutinin (HA) proteins from different HPAI H5N1 serotypes was evaluated for its ability to elicit neutralizing antibodies and to protect against homologous and heterologous HPAI H5N1 strain challenge in mice and chickens after DNA immunization by needle and syringe or with a pressure injection device. After optimization of injection conditions, alternative multivalent DNA vaccine regimens were analyzed and compared for magnitude and breadth of neutralizing antibodies, as well as protective efficacy after challenge in mouse and chicken models of HPAI H5N1 infection. The ability of chickens to generate specific antibodies was assessed with three strains that showed broad cross protection in mouse studies (A/Vietnam/1203/2004, A/Anhui/ 1/2005 and A/Indonesia/05/2005), administered individually or in combination, by different injection methods. doi = 10.1371/journal.pone.0002432 id = cord-001455-n7quwr4s author = Rapin, Noreen title = Activation of Innate Immune-Response Genes in Little Brown Bats (Myotis lucifugus) Infected with the Fungus Pseudogymnoascus destructans date = 2014-11-12 keywords = PCR; bat; infection summary = title: Activation of Innate Immune-Response Genes in Little Brown Bats (Myotis lucifugus) Infected with the Fungus Pseudogymnoascus destructans Using tissue samples collected at the termination of an experiment to explore the pathogenesis of White Nose Syndrome in Little Brown Bats, we determined if hibernating bats infected with the fungus Pseudogymnoascus destructans could respond to infection by activating genes responsible for innate immune and stress responses. We found that bats responded to infection with a significant increase in lungs of transcripts for Cathelicidin (an anti-microbial peptide) as well as the immune modulators tumor necrosis factor alpha and interleukins 10 and 23. We used samples collected during the experiment to address the question: Can hibernating bats respond to infection by activating genes responsible for innate immune and stress responses? We determined levels of transcripts for several immune and stress response genes (Table 1) in lungs from infected and control bats. doi = 10.1371/journal.pone.0112285 id = cord-346586-fxxceffl author = Razanajatovo, Norosoa Harline title = Epidemiology of severe acute respiratory infections from hospital-based surveillance in Madagascar, November 2010 to July 2013 date = 2018-11-21 keywords = Madagascar; RSV; SARI summary = CONCLUSION: The frequency of influenza viruses detected among SARI patients aged 65 years and more highlights the need for health authorities to develop strategies to reduce morbidity amongst at-risk population through vaccine recommendation. The frequency of influenza viruses detected among SARI patients aged 65 years and more highlights the need for health authorities to develop strategies to reduce morbidity amongst at-risk population through vaccine recommendation. Following the A/H1N1/2009 influenza pandemic that was associated with a high morbidity and an increased risk of mortality among particular groups [13] , a number of countries have strengthened vigilance for the surveillance of severe diseases and deaths in order to rapidly detect new viruses and to provide information in assessing the impact on the population and having operational preparedness plans. A meta-analysis of data from Africa reported that the incidence of RSV in lower acute respiratory infections that required hospitalization ranged from 10-18 per 1000 person year for infants and 3-9 per 1000 person year for children under 5 years of age [26] . doi = 10.1371/journal.pone.0205124 id = cord-272655-qeojdpez author = Remolina, Yuly Andrea title = Viral Infection in Adults with Severe Acute Respiratory Infection in Colombia date = 2015-11-17 keywords = Influenza; patient; viral summary = OBJECTIVES: To identify the viral aetiology in adult patients with severe acute respiratory infection (SARI) admitted to sentinel surveillance institutions in Bogotá in 2012. DESIGN: A cross-sectional study was conducted in which microarray molecular techniques for viral identification were used on nasopharyngeal samples of adult patients submitted to the surveillance system, and further descriptions of clinical features and relevant clinical outcomes, such as mortality, need for critical care, use of mechanical ventilation and hospital stay, were obtained. Under this initiative, countries have developed surveillance systems by following cases of influenza-like illness and severe acute respiratory infections (SARIs), which are clinically diagnosed among patients with fever, coughing or sore throat, difficulty breathing and the need for hospitalization [3] . In our study, viruses were identified as the most frequent causal agents of SARI requiring hospitalization in 2012, with most cases showing a high rate of viral co-infection, a high degree of morbidity, prolonged hospital stays and frequent needs for ICU management and mechanical ventilation. doi = 10.1371/journal.pone.0143152 id = cord-277409-q5wx313k author = Resende, Lucilene Aparecida title = Impact of LbSapSal Vaccine in Canine Immunological and Parasitological Features before and after Leishmania chagasi-Challenge date = 2016-08-24 keywords = Control; IFN; Leishmania summary = doi = 10.1371/journal.pone.0161169 id = cord-002939-6a3ga6v9 author = Ribeiro, Ana Freitas title = Severe influenza A(H1N1)pdm09 in pregnant women and neonatal outcomes, State of Sao Paulo, Brazil, 2009 date = 2018-03-26 keywords = influenza; pregnant; woman summary = doi = 10.1371/journal.pone.0194392 id = cord-315343-ywgoqlxj author = Ribeiro, Haroldo V. title = City size and the spreading of COVID-19 in Brazil date = 2020-09-23 keywords = COVID-19; case; city summary = Our results indicate small towns are proportionally more affected by COVID-19 during the initial spread of the disease, such that the cumulative numbers of cases and deaths per capita initially decrease with population size. However, during the long-term course of the pandemic, this urban advantage vanishes and large cities start to exhibit higher incidence of cases and deaths, such that every 1% rise in population is associated with a 0.14% increase in the number of fatalities per capita after about four months since the first two daily deaths. Investigating whether this behavior generalizes to other places and how different quantities such as the number of cases and deaths scale with city size are thus important elements for a better understanding of the spreading of COVID-19 in urban areas. To test for an increasing urban advantage for the treatment of COVID-19 during the initial spread of the disease, we investigate the scaling relation between the number of hospital intensive care unit (ICU) beds and city population. doi = 10.1371/journal.pone.0239699 id = cord-314908-kp2jznwb author = Roczniewska, Marta title = I believe I can craft! introducing Job Crafting Self-Efficacy Scale (JCSES) date = 2020-08-10 keywords = JCSE; Study; craft; job; table summary = To better predict these behaviors, we introduce the concept of job crafting self-efficacy (JCSE) and define it as an individual''s beliefs about their capability to modify the demands and resources of their job to better fit their needs. In this project we integrate Social Cognitive Theory and the Job Demands-Resources model [6, 7] to introduce the concept of job crafting self-efficacy (JCSE). Based on the assumptions of Social Cognitive Theory, we also expect that these specific beliefs predict matching job-crafting behaviors, for example, individuals who feel self-efficacious with respect to increasing challenging job demands are more likely to start new projects or learn about new developments at work and try them out. doi = 10.1371/journal.pone.0237250 id = cord-270647-vn4kirrx author = Romero-Espinoza, Jose A. title = Virome and bacteriome characterization of children with pneumonia and asthma in Mexico City during winter seasons 2014 and 2015 date = 2018-02-15 keywords = asthma; respiratory; virus summary = OBJECTIVES: To describe the virome and bacteriome present in the upper respiratory tract of hospitalized children with a clinical diagnosis of asthma and pneumonia during an acute exacerbation and an acute respiratory illness ARI episode respectively. Both groups differ with respect to the associated virus and bacteria: while asthma exacerbations have been associated to a specific rhinovirus infection, pneumonia can be related to a wide range of bacterial, fungal and viral agents, with a high prevalence of Respiratory Syncytial Virus (RSV) [2, 7] . Here we describe the virome and bacteriome present in the Upper Respiratory Tract of hospitalized children clinically diagnosed with asthma and pneumonia, during an acute exacerbation and an ARI episode respectively, at the National Institute of Respiratory Diseases (INER, Mexico City) during 2014 and 2015 winter seasons. Prevalence of respiratory viral infection in children hospitalized for acute lower respiratory tract diseases, and association of rhinovirus and influenza virus with asthma exacerbations doi = 10.1371/journal.pone.0192878 id = cord-275395-w2u7fq1g author = Romero-Severson, Ethan Obie title = Change in global transmission rates of COVID-19 through May 6 2020 date = 2020-08-06 keywords = COVID-19; country; model summary = doi = 10.1371/journal.pone.0236776 id = cord-266799-t7lqlv41 author = Rotejanaprasert, Chawarat title = Preliminary estimation of temporal and spatiotemporal dynamic measures of COVID-19 transmission in Thailand date = 2020-09-24 keywords = Thailand; covid-19 summary = This study thus aims to estimate and compare disease dynamic measures in several dimensions that can be augmented with epidemiological summary statistics to monitor the COVID-19 situation for each location and time at different stages of the epidemic. The data in this study were from confirmed COVID-19 cases in 77 provinces of Thailand from January 12 th 2020 through June 30 th 2020 provided in the daily reports of the Department of Disease Control, Thai Ministry of Public Health (MOPH). During the early stage of an epidemic curve caused by emerging diseases, the exponential growth (EG) rate, denoted by r, can be related to the initial reproduction rate and can be described as the change in number of new cases per time unit [15] . We wanted to provide information that could be used to help design effective control strategies for the current COVID-19 situation in Thailand after the disease has spread to different provinces across the country much of which was from cluster outbreaks originating from several super spreader events. doi = 10.1371/journal.pone.0239645 id = cord-002602-2qvyhjlp author = Roy, Amrita title = Solution conformations of Zika NS2B-NS3pro and its inhibition by natural products from edible plants date = 2017-07-10 keywords = Fig; NMR; NS2B; NS3pro; Zika summary = Subsequently with selective isotope-labeling using NMR spectroscopy, we demonstrated that C-terminal residues (R73-K100) of NS2B is highly disordered without any stable tertiary and secondary structures in the Zika NS2B-NS3pro complex in the free state. Therefore, our results suggest that in the Zika NS2B-NS3pro complex, NS2B has a portion of residues undergo μs-ms dynamics which made their NMR peaks too broad to be detectable; while the rest of NS2B is highly disordered and lacks tight tertiary packing, which results in a narrowly-dispersed HSQC spectrum (S2B Fig) . Together with recent reports on the crystal structures of Zika NS2B-NS3pro complexes in both open and closed conformations [34, 43] , our current results reveal that in solution the NS2B residues over Arg73-Lys100 are highly disordered in the open conformation. Unfortunately, as previously observed on Dengue-2 NS2B-NS3pro complexes [21, 30, 43] , our linked Zika complex also underwent significant μs-ms dynamics, thus making its NMR signals too broad to be detected (Fig 1A and 1B) . doi = 10.1371/journal.pone.0180632 id = cord-268816-nth3o6ot author = Roy, Satyaki title = Factors affecting COVID-19 infected and death rates inform lockdown-related policymaking date = 2020-10-23 keywords = covid-19; death; feature; lockdown summary = The features in the order shown under "Feature name" are: GDP, inter-state distance based on lat-long coordinates, gender, ethnicity, quality of health care facility, number of homeless people, total infected and death, population density, airport passenger traffic, age group, days for infection and death to peak, number of people tested for COVID-19, days elapsed between first reported infection and the imposition of lockdown measures at a given state. Unless otherwise stated, the feature set comprises GDP, gender, ethnicity, health care, homeless, lockdown type, population density, airport activity, and age groups, whereas the output labels consist of infected and death scores on a scale of 0-6. Although proposing a machine learning algorithm that works best on COVID-19 data is not the purpose of this study, it is worth reporting that decision tree classifier (DT) slightly outperforms the other algorithms for both cases of infected and death scores. doi = 10.1371/journal.pone.0241165 id = cord-000581-ewx5xhrb author = Rudge, James W. title = Health System Resource Gaps and Associated Mortality from Pandemic Influenza across Six Asian Territories date = 2012-02-21 keywords = Taiwan; figure; resource summary = This study was conducted as part of the AsiaFluCap project (www.asiaflucap.org), the overall aim of which is to conduct health systems analyses to support capacity development for responding to pandemic influenza across six countries and territories in Asia, specifically: Cambodia, Indonesia, Lao PDR, Taiwan, Thailand and Vietnam. Estimating resource needs, gaps, and associated mortality In our baseline scenario, resource gaps were estimated assuming that 12% of ''''general'''' hospital resources (beds, ventilators and human resources) are available for care of pandemic influenza cases, with the remaining 88% required for maintaining essential healthcare services, as in a previous pilot study for Thailand [20] , and based on previous reports [25] [26] . Figure 1 presents the geographical distribution of estimated resource gaps across provinces (or districts in the case of Indonesia) in each study country for the modeled pandemic influenza scenario, under our baseline assumptions and point estimates for parameter values. doi = 10.1371/journal.pone.0031800 id = cord-346067-zly8p0y7 author = Ruiz-Irastorza, Guillermo title = Second week methyl-prednisolone pulses improve prognosis in patients with severe coronavirus disease 2019 pneumonia: An observational comparative study using routine care data date = 2020-09-22 keywords = COVID-19 summary = title: Second week methyl-prednisolone pulses improve prognosis in patients with severe coronavirus disease 2019 pneumonia: An observational comparative study using routine care data Our therapeutic protocol was updated on April 3 rd 2020, including the recommendation of MP for patients with COVID-19 pneumonia with altered/worsening inflammatory parameters (lymphopenia, thrombocytopenia, rising ferritin, D-dimers and or C-reactive protein) and clinical deterioration, particularly those showing impending respiratory failure with decreasing SpO2/FiO2 values. Other independent predictors of death included a previous diagnosis of arterial hypertension, the use of non-pulse glucocorticoids, a high-risk CURB65 category and SpO2/FiO2 at week 2 ( Table 2 ). Glucocorticoid use, however, should not be indiscriminate, but rather restricted to patients with laboratory evidence of inflammation and progressing respiratory compromise, and best used as short-course pulse therapy (125-250 mg/d of methyl-prednisolone during 3 days) administered during the second week after the onset of symptoms, where the hyperinflammatory reaction takes usually place. doi = 10.1371/journal.pone.0239401 id = cord-347317-qcghtkk0 author = Russo, Lucia title = Tracing day-zero and forecasting the COVID-19 outbreak in Lombardy, Italy: A compartmental modelling and numerical optimization approach date = 2020-10-30 keywords = Lombardy; March; case; number summary = For the estimation of the day-zero of the outbreak in Lombardy, as well as of the "effective" per-day transmission rate for which no clinical data are available, we have used the proposed SEIIRD simulator to fit the numbers of new daily cases from February 21 to the 8th of March. Among the perplexing problems that mathematical models face when they are used to estimate epidemiological parameters and to forecast the evolution of the outbreak, two stand out: (a) the uncertainty regarding the day-zero of the outbreak, the knowledge of which is crucial to assess the stage and dynamics of the epidemic, especially during the first growth period, and (b) the uncertainty that characterizes the actual number of the asymptomatic infected cases in the total population (see e.g. doi = 10.1371/journal.pone.0240649 id = cord-339026-eu11larc author = Ryals, Renee C. title = The effects of PEGylation on LNP based mRNA delivery to the eye date = 2020-10-29 keywords = DSPC; LNP; peg; rpe summary = Similar injections of LNP delivered cre mRNA into Ai9 mice revealed cell-specific protein expression in the retinal pigment epithelium (RPE), confirmed by fundus photography and immunohistochemistry of whole globe cross-sections. Thus far, these particles successfully transfect RPE, Müller cells, the optic nerve head and the trabecular meshwork based on route of administration which can expand the utility of LNP-mediated gene therapies for the eye. Most intriguingly, these particles successfully transfect RPE, Müller glia, the optic nerve head and the trabecular meshwork based on route of administration which can expand the utility of LNP-mediated gene therapies for the eye. Since the subretinal injection places the LNPs in close proximity to the RPE, we utilized this method to understand how PEGylation and size may impact intracellular delivery ( In general, for all particles, luciferase activity in the eye was measurable at 4 hours post-injection, increased to a maximum level at 24 hours post-injection and decreased by 48 hours post-injection (Figs 2B and 3B). doi = 10.1371/journal.pone.0241006 id = cord-001207-yjaiybwf author = Sachsenröder, Jana title = The General Composition of the Faecal Virome of Pigs Depends on Age, but Not on Feeding with a Probiotic Bacterium date = 2014-02-19 keywords = NCIMB; sample; virus summary = faecium) NCIMB 10415 on the pig faecal virome composition was analysed in a pig feeding trial with sows and their piglets, which received either the probiotic bacterium or not. RESULTS: From 8 pooled faecal samples derived from the feeding trial, DNA and RNA virus particles were prepared and subjected to process-controlled Next Generation Sequencing resulting in 390,650 sequence reads. However, it is not known so far, whether probiotic bacteria can also influence the general composition of the faecal virome, e.g. by changing the composition of the bacterial community, which represents the host population for bacteriophages, or by direct interactions with specific viruses. Faecal samples from sows and their piglets experimentally fed with or without the probiotic bacterium were analyzed using a process-controlled deep sequencing method. As the detection rate of the bacteriophages is -besides technical factors -also dependent on the amount of viruses initially present in the analyzed sample, improved deep sequencing methods enabling quantitative analyses should be developed in future for comparative virome investigations. doi = 10.1371/journal.pone.0088888 id = cord-000588-3wok0n21 author = Sainz, Juan title = Dectin-1 and DC-SIGN Polymorphisms Associated with Invasive Pulmonary Aspergillosis Infection date = 2012-02-27 keywords = CCL2; Dectin-1; IPA; SIGN summary = The present study was designed to investigate whether the presence of single nucleotide polymorphisms (SNPs) within DC-SIGN, Dectin-1, Dectin-2, CCL2 and CCR2 genes influence the risk of developing Invasive Pulmonary Aspergillosis (IPA). In addition, healthy individuals with this latter genotype showed a significantly decreased level of Dectin-1 mRNA expression compared to C-allele carriers, suggesting a role of the Dectin-1 (rs7309123) polymorphism in determining the levels of Dectin-1 and, consequently, the level of susceptibility to IPA infection. Based on these observations, the objective of the present study was to investigate the role of tagging and potentially functional single-nucleotide polymorphisms (SNPs) located within the DC-SIGN, Dectin-1, Dectin-2, MCP-1/CCL2 and CCR2 genes on IPA susceptibility. Of note is that two SNPs showing genetic interaction in this model were not significantly associated with an increased risk of IPA infection in the univariate analysis (CCR2 rs3918358 and Dectin-2 rs7134303 ). doi = 10.1371/journal.pone.0032273 id = cord-010369-x9z8dg6a author = Saito, Kyoko title = Comparative characterization of flavivirus production in two cell lines: Human hepatoma-derived Huh7.5.1-8 and African green monkey kidney-derived Vero date = 2020-04-24 keywords = Fig; Huh7.5.1; JEV; Vero summary = doi = 10.1371/journal.pone.0232274 id = cord-001781-afg1nmib author = Saksena, Sumeet title = Evidence for the Convergence Model: The Emergence of Highly Pathogenic Avian Influenza (H5N1) in Viet Nam date = 2015-09-23 keywords = CTI; H5N1; HPAI; Nam; risk summary = We developed and tested a model of the emergence of highly pathogenic avian influenza (HPAI) H5N1 based on suspected convergence factors that are mainly associated with land-use change. The results presented here highlight three main findings: 1) when relevant risk factors are taken into account, urbanization is generally not a significant independent risk factor; but in peri-urban landscapes emergence factors converge, including higher levels of chicken densities, duck and geese flock size diversities, and fraction of land under rice or aquaculture; 2) high land-use diversity landscapes, a variable not previously considered in spatial studies of HPAI H5N1, are at significantly greater risk for HPAI H5N1 outbreaks; as are 3) landscapes where intensive and extensive forms of poultry production are co-located. Hence diseases associated with rice production are likely to peak in peri-urban areas given other risk factors such as land-use diversity, CTI, and distance to infrastructure. doi = 10.1371/journal.pone.0138138 id = cord-048471-7jszm1nd author = Salim, Omar title = Functional Analysis of the 5′ Genomic Sequence of a Bovine Norovirus date = 2008-05-14 keywords = RNA; protein summary = doi = 10.1371/journal.pone.0002169 id = cord-350398-w75flrwv author = Sampath, Rangarajan title = Comprehensive Biothreat Cluster Identification by PCR/Electrospray-Ionization Mass Spectrometry date = 2012-06-29 keywords = PCR; PLEX; biothreat summary = Coupling biothreat cluster-specific PCR to electrospray ionization mass spectrometry simultaneously provides the breadth of coverage, discrimination of near neighbors, and an extremely low false positive rate due to the requirement that an amplicon with a precise base composition of a biothreat agent be detected by mass spectrometry. In addition to detecting the threat organisms, the biothreat assay described here also detects virulence factors associated with three of the agents: Bacillus anthracis (pXO1 and pXO2), Yersinia pestis (pla and caf), and Vibrio cholera (ctx1). PCR primers were designed to conserved regions within the selected target genes such that the targeted threat agent was clearly identified and differentiated from its near-neighbor species ( Table 1) . In the biothreat assay, the Francisella biocluster is identified by two genus-specific primer pairs targeting the asd (BCT2328) and galE (BCT2332) genes ( Table 1) . doi = 10.1371/journal.pone.0036528 id = cord-313506-6bb4q7nv author = Sano, Akiko title = Physiological Level Production of Antigen-Specific Human Immunoglobulin in Cloned Transchromosomic Cattle date = 2013-10-24 keywords = DT40; HAC; PCR summary = We previously showed that transchromosomic (Tc) cattle carrying a human artificial chromosome (HAC) comprising the entire unrearranged human immunoglobulin heavy-chain (hIGH) and kappa-chain (hIGK) germline loci (named as κHAC) are capable of producing functional hpAbs when both of the bovine immunoglobulin mu heavy-chains, bIGHM and bIGHML1, are homozygously inactivated (double knockouts or DKO). Therefore, in an effort to improve B cell development and hIgG production in Tc cattle, we sought to enhance pre-BCR function by engineering a new HAC into which, in addition to the hIGH, hIGK and hIGL chromosome loci that carry the entire human immunoglobulin gene repertoire, the human VpreB (hVPREB1) and λ5 (hIGLL1) genomic loci from human chromosome 22 (hChr22) was incorporated, and part of CH and TM domains, CH2-TM, of hIGHM gene, was replaced by the corresponding bovine gene sequence (bovinization of the CH2-TM domains of hIGHM). doi: 10.1371/journal.pone.0078119.g002 DT40 colonies were screened with genomic PCR (data not shown) for the correctly modified hChr2, and clone K53 was identified and selected for the final HAC construction ( Figure 5 ). doi = 10.1371/journal.pone.0078119 id = cord-001605-8p06bpt1 author = Sapmak, Ariya title = The pbrB Gene Encodes a Laccase Required for DHN-Melanin Synthesis in Conidia of Talaromyces (Penicillium) marneffei date = 2015-04-13 keywords = DHN; Fig summary = title: The pbrB Gene Encodes a Laccase Required for DHN-Melanin Synthesis in Conidia of Talaromyces (Penicillium) marneffei marneffei genome encodes a number of laccases and this study describes the characterization of one of these, pbrB, during growth and development. The pbrB gene is required for the synthesis of DHN-melanin in conidia and when deleted results in brown pigmented conidia, in contrast to the green conidia of the wild type. marneffei MCO participates in conidial DHN-melanin synthesis, we combined 55 fungal MCO sequences and performed alignments using CLUSTALW (http://www.genome.jp/ tools/clustalw/). marneffei PbrB, this clade comprises of characterized laccases functioning in conidial DHN-melanin synthesis. Talaromyces (Penicillium) marneffei pbrB Gene Cytoplasmic protein extracts from the wild type and ΔpbrB mutant cultured in brain heart infusion broth at 37°C for 3 days were capable of catalyzing L-DOPA (data not shown). doi = 10.1371/journal.pone.0122728 id = cord-276577-06boh550 author = Schanzer, Dena L. title = Estimating Sensitivity of Laboratory Testing for Influenza in Canada through Modelling date = 2009-08-18 keywords = RVDSS; influenza; test summary = doi = 10.1371/journal.pone.0006681 id = cord-348243-e5tdb08v author = Schermer, Bernhard title = Rapid SARS-CoV-2 testing in primary material based on a novel multiplex RT-LAMP assay date = 2020-11-02 keywords = LAMP; RNA; SARS summary = METHODS: To avoid these obstacles, we tested PCR-independent methods for the detection of SARS-CoV-2 RNA from primary material (nasopharyngeal swabs) including reverse transcription loop-mediated isothermal amplification (RT-LAMP) and specific high-sensitivity enzymatic reporter unlocking (SHERLOCK). To allow for the comparison of different nucleic acid detection methods for SARS-CoV-2 we collected redundant material from nasopharyngeal swabs obtained for qPCR testing in clinical routine due to suspected COVID-19. We first tested two recently described assays for SARS-CoV-2 detection on isolated RNA from patient samples. In summary, our multiplex RT-LAMP protocol is a simple and sensitive way to detect SARS-CoV-2 RNA from clinical samples. Currently, a test based on our multiplexed RT-LAMP assay would-in contrast to a good specificity-most likely miss to identify those infected patients with very low amounts of viral RNA in the nose or throat and would not yet reach the sensitivity of the gold-standard qPCR assays. doi = 10.1371/journal.pone.0238612 id = cord-330749-xt4aa2ur author = Schilling, Stefan title = Isolation Facilities for Highly Infectious Diseases in Europe – A Cross-Sectional Analysis in 16 Countries date = 2014-10-28 keywords = HID; european; facility summary = The term highly infectious diseases (HID) defines mostly viral and bacterial infections that (i) are easily transmissible from person to person; (ii) cause a life-threatening clinical illness with no or few treatment options; and (iii) pose a threat for both health care workers and the public, thus requiring specific infection control measures and public health planning [1] . Despite such efforts, no pooled data on isolation facilities resources, such as infrastructure design, technical equipment, capacity and access to intensive care, do exist. The study presented was performed by the European Network for Highly Infectious Diseases, EuroNHID, and set up to compare the operational management, resources, and technical equipment among isolation facilities with recommendations published. Infection control management of patients with suspected highly infectious diseases in emergency departments: data from a survey in 41 facilities in 14 European countries doi = 10.1371/journal.pone.0100401 id = cord-272878-6f0q661e author = Schnepf, Nathalie title = High Burden of Non-Influenza Viruses in Influenza-Like Illness in the Early Weeks of H1N1v Epidemic in France date = 2011-08-17 keywords = ILI; SLS; respiratory summary = doi = 10.1371/journal.pone.0023514 id = cord-299509-7xjdryoq author = Scholte, Florine E. M. title = Characterization of Synthetic Chikungunya Viruses Based on the Consensus Sequence of Recent E1-226V Isolates date = 2013-08-01 keywords = CHIKV; Fig; ITA07-RA1; LS3; LS3-GFP; RNA; Vero summary = doi = 10.1371/journal.pone.0071047 id = cord-002973-bkr4ndl2 author = Seifi, Morteza title = Accurate prediction of functional, structural, and stability changes in PITX2 mutations using in silico bioinformatics algorithms date = 2018-04-17 keywords = PITX2; Rieger; protein; variant summary = doi = 10.1371/journal.pone.0195971 id = cord-000833-m6abyuvx author = Sekiguchi, Satoshi title = Immunization with a Recombinant Vaccinia Virus That Encodes Nonstructural Proteins of the Hepatitis C Virus Suppresses Viral Protein Levels in Mouse Liver date = 2012-12-17 keywords = CD8; CN2; HCV; N25 summary = The HCV core protein was expressed consistently in the liver after polyinosinic acid–polycytidylic acid injection, and these mice showed chronic hepatitis C-related pathological findings (hepatocyte abnormalities, accumulation of glycogen, steatosis), liver fibrosis, and hepatocellular carcinoma. These observations, in addition to the modified histology activity index (HAI) scores, indicated that expression of HCV proteins caused chronic hepatitis in the CN2-29 (+/2) /MxCre (+/2) mice because a weak, though persistent, immune response followed an initial bout of acute hepatitis ( Figure S1 ). To determine whether activation of the host immune response caused the reduction with HCV protein levels in the livers of CN2-29 (+/2) /MxCre (+/2) mice, we used a highly attenuated VV strain, LC16m8, to generate three rVVs [12] . To determine whether rVV-N25 treatment induced the same effect in other strains of HCV transgenic mice, we analyzed RzCN5-15 (+/2) /MxCre (+/2) mice, which express all HCV proteins; in these mice, chronic hepatitis was resolved within 28 days of immunization with rVV-N25. doi = 10.1371/journal.pone.0051656 id = cord-322533-adqqm0n9 author = Sha, Dexuan title = Spatiotemporal analysis of medical resource deficiencies in the U.S. under COVID-19 pandemic date = 2020-10-14 keywords = CCS; ICU; MRDI; U.S. summary = The study duration was mainly from February 15, 2020 to May 1, 2020 in the U.S. Multiple data sources were used to extract local population, hospital beds, critical care staff, COVID-19 confirmed case numbers, and hospitalization data at county level. Then, we developed two medical resource deficiency indices that measured the local medical burden based on the number of accumulated active confirmed cases normalized by local maximum potential medical resources, and the number of hospitalized patients that can be supported per ICU bed per critical care staff, respectively. In this report, three fundamental elements or features, i.e. ventilators, ICU beds, and critical care staff (CCS) were identified as medical resources to plan for or manage a COVID-19 pandemic, and it would be wise to consider the interconnections among these factors in a spatiotemporal data analysis framework. doi = 10.1371/journal.pone.0240348 id = cord-001021-nag4at49 author = Shaheen, Hussam H. title = A Dual-Mode Surface Display System for the Maturation and Production of Monoclonal Antibodies in Glyco-Engineered Pichia pastoris date = 2013-07-10 keywords = Pichia; figure; pcsk9 summary = doi = 10.1371/journal.pone.0070190 id = cord-000366-u4649rtx author = Shan, Tongling title = Genomic Characterization and High Prevalence of Bocaviruses in Swine date = 2011-04-15 keywords = bocavirus; human; porcine summary = Using random PCR amplification followed by plasmid subcloning and DNA sequencing, we detected bocavirus related sequences in 9 out of 17 porcine stool samples. Using primer walking, we sequenced the nearly complete genomes of two highly divergent bocaviruses we provisionally named porcine bocavirus 1 isolate H18 (PBoV1-H18) and porcine bocavirus 2 isolate A6 (PBoV2-A6) which differed by 51.8% in their NS1 protein. Presently, the bocavirus genus contains eight members: bovine parvovirus, canine minute virus (CnMV), human bocavirus 1-4 (HBoV1-4), a gorilla bocavirus and a partially sequenced chimpanzee bocavirus [1, 6, 7] . In 2009, a porcine bocalike virus (PBo-likeV) was reported in swine feces with postweaning multisystemic wasting syndrome in Sweden and 1854 bp of its partial genome sequenced [27] . Finally, partial genome sequences of 2.4 Kb from another clade of porcine bocaviruses labeled 6V and 7V where also identified yielding three major bocavirus groups in swine (PBo-likeV, PBoV1/PBoV2, and 6V/7V). doi = 10.1371/journal.pone.0017292 id = cord-305303-82n96ukr author = Shapira, Assaf title = Removal of Hepatitis C Virus-Infected Cells by a Zymogenized Bacterial Toxin date = 2012-02-16 keywords = HCV; MazF; Tet; USA; cell; ns3 summary = As shown in Figure 2 , similar numbers of surviving colonies were observed when the cells were transfected with the plasmids encoding mCherry-NS3 activated MazF or the red fluorescent protein alone, suggesting that expression of NS3-activable ribonuclease in naïve HEK293 T-REx cells (that do not express NS3) cause minimal toxicity, if any. The ER membrane-targeted zymoxin colocalizes with NS3 protease in vivo Previously we described a HEK293 cell line which inducibly expresses (by addition of tetracycline) a fusion between EGFP and the coding sequence of the full length NS3 (including the helicase domain) followed by NS4A from HCV 1a genotype [10] . When infection reached ,50% (about 50% of the cultured cells showed expression of the HCV-core protein, as detected by immuno-staining and fluorescence microscopy), the mixed culture and a culture of uninfected cells were treated with NS3 activated MazF or uncleavable-MazF encoding adenoviruses at MOI of ,3. doi = 10.1371/journal.pone.0032320 id = cord-335272-jypxi99z author = Sharma, Anupam Joya title = A cross-sectional study of psychological wellbeing of Indian adults during the Covid-19 lockdown: Different strokes for different folks date = 2020-09-03 keywords = AJS; LGBT; covid-19; indian; lockdown summary = Moreover, both qualitative and quantitative study findings suggested that greater frequency of calling family members during lockdown could strengthen social relationships and increase social empathy. In response, our study of Indian adults unpacks how social factors such as sexual orientation, relationship status, and residence in high-infection areas, could be linked with several psychological outcomes during the lockdown. Next, we fitted separate multivariable linear regression models to estimate the association of the independent variables (sexual orientation, relationship status, high-risk group, and living in a state with high number of cases) with psychological outcomes (anxiety, depressive symptoms, Internet addiction and pornography consumption) adjusted for the sociodemographic covariates-age, gender, annual income, educational qualification, place of residence-and for individual personal resources (optimism and resilience). Our quantitative and qualitative findings both suggest that LGBT adults, compared to the heterosexuals, are at a higher risk of developing anxiety, depressive symptoms, and using pornography during the lockdown. doi = 10.1371/journal.pone.0238761 id = cord-322446-ddv86eoy author = Sharma, Kulbhushan title = SARS-CoV 9b Protein Diffuses into Nucleus, Undergoes Active Crm1 Mediated Nucleocytoplasmic Export and Triggers Apoptosis When Retained in the Nucleus date = 2011-05-27 keywords = Fig; LMB; NES; SARS; cell summary = We found that an export signal deficient SARS-CoV 9b protein induces apoptosis in transiently transfected cells and showed elevated caspase-3 activity. Analysis of 9b-YFP localization showed that in addition to the extranuclear region, some amount of 9b was also present within the nucleus similar to the SARS-CoV infected cells (Fig. S1 , panel (i), (ii) and (iii)). Panel (ii) shows that even in in-vitro transport assay, SARS-CoV 9b protein localizes in both cytoplasm as well as nucleus. As shown in panel (v), the SARS-CoV 9b protein was able to enter the nucleus even in the presence of WGA showing that its entry is independent of active transport pathway. The SARS-CoV 9b protein triggers caspase 3 mediated apoptosis when retained in the nucleus of mammalian cells While performing pulse-chase assays, we found that a significant number of Vero E6 cells, in which nuclear export of 9b has been inhibited (either by treating with LMB or using NES deficient 9b), were showing caspase 3 dependent apoptosis. doi = 10.1371/journal.pone.0019436 id = cord-339392-2ocz784l author = Sharma, Kulbhushan title = Influenza A Virus Nucleoprotein Exploits Hsp40 to Inhibit PKR Activation date = 2011-06-15 keywords = Hsp40; IAV; PKR summary = BACKGROUND: Double-stranded RNA dependent protein kinase (PKR) is a key regulator of the anti-viral innate immune response in mammalian cells. In case of influenza A virus (IAV) infection, P58(IPK) is known to dissociate from Hsp40 and inhibit PKR activation. PRINCIPAL FINDINGS: Human heat shock 40 protein (Hsp40) was identified as an interacting partner of Influenza A virus nucleoprotein (IAV NP) using a yeast two-hybrid screen. It is known that under stress conditions the expression level of Hsp40 is enhanced and its cellular localization changes from cytoplasmic to nuclear [38] , however its distribution in influenza virus infected cells was not studied. Taken together, these results suggest that during IAV infection, NP induces the dissociation of the P58 IPK -Hsp40 complex leading to an inhibition of PKR activation and downregulation of eIF2a phosphorylation. In case of influenza virus infection, viral NS1 protein is known to bind directly to PKR and inhibit its activation [20, 21] . doi = 10.1371/journal.pone.0020215 id = cord-353410-tbmtg88k author = Sharma, Shreela V. title = Using a rapid assessment methodology to identify and address immediate needs among low-income households with children during COVID-19 date = 2020-10-01 keywords = Bites; COVID-19; family summary = Due to COVID-19-related school closures, states were under "shelter in place" orders, and Brighter Bites administered a rapid assessment survey to identify social needs among their families. While overall results of the qualitative thematic analysis for the n = 1048 participants are presented elsewhere (Sharma et al., under review) , a qualitative analysis of participant responses in the high-risk group revealed four major themes presented in Table 2 : fear of contracting COVID-19, disruption of employment status, financial hardship, and exacerbated food insecurity. Conducting a COVID-19 rapid response survey was a purposeful decision on part of Brighter Bites to identify those with highest need during this time of crisis and develop a framework to immediately address a variety of social needs among those in the "high risk" category. doi = 10.1371/journal.pone.0240009 id = cord-274241-biqbsggu author = Shaw, Timothy I. title = Transcriptome Sequencing and Annotation for the Jamaican Fruit Bat (Artibeus jamaicensis) date = 2012-11-15 keywords = TCRV; bat; blast; gene; human; jamaican summary = Annotated genes are involved in a broad range of activities ranging from cellular metabolism to genome regulation through ncRNAs. Reciprocal BLAST best hits yielded 8,785 sequences that are orthologous to mouse, rat, cattle, horse and human. Species tree analysis of sequences from 2,378 loci was used to achieve 95% bootstrap support for the placement of bat as sister to the clade containing horse, dog, and cattle. Through substitution rate estimation between bat and human, 32 genes were identified with evidence for positive selection. To address some of these deficiencies, we have performed transcriptome sequencing and analysis of spleen, lung, kidney and poly-IC-stimulated primary kidney cells to identify genes of interest for assessing the host response to TCRV infection. There were 20,145 contigs that mapped to Pteropus alecto, Australian flying fruit bat, and 18,359 that overlapped between genomic and transcriptome sequences for all three datasets ( Figure 5 ). doi = 10.1371/journal.pone.0048472 id = cord-000375-fvfl0bn1 author = Shen, Ching-I title = The Infection of Chicken Tracheal Epithelial Cells with a H6N1 Avian Influenza Virus date = 2011-05-06 keywords = MAA; MAL; cell summary = This result clearly elucidates the receptor distribution for the avian influenza virus among chicken tracheal epithelial cells and illustrates a primary cell model for evaluating the cell tropisms of respiratory viruses in poultry. In contrast to the finding for MAA/MAL-I, abundant SNA signals were mainly restricted to the mucin + cells (ratio of SNA + /mucin + cells, 0.8560.09, n = 368) ( Fig. 2A) , indicating that the goblet cells expressed SAa2-6Gal terminal glycan. To determine whether a single basal cells can express both SAa2-3Gal and SAa2-6Gal, CTE cells were triple-stained with K14 primary antibody (Cy5-2u Ab, purple), FITC-conjugated MAA (green) and biotin-labeled SNA (detected by Cy3-Streptovidin, red) (Figs. In humans, by contrast, both ciliated and goblet cells can be labeled with MAA/MAL-I and SNA [19, 20] , indicating that these two epithelial cells have both types of influenza viral receptors. doi = 10.1371/journal.pone.0018894 id = cord-004068-d66lwylf author = Shimoda, Tomoko title = Effect of thermal control of dry fomites on regulating the survival of human pathogenic bacteria responsible for nosocomial infections date = 2019-12-27 keywords = ATCC summary = A specialized handrail device fitted with a heater, which was maintained at normal human body core temperature, successfully prohibited the prolonged survival of bacteria [Enterococcus faecalis (ATCC), E. Furthermore, we propose that fomites warmed to human body core temperature may help to control bacterial survival in dry environments, and that such a strategy may prohibit the emergence of human pathogenic bacteria in hospital environments, eventually reducing the need for antibiotics as well as disinfectants. A heatmap generated with the high-resolution infrared sensor showed that in contrast to the stainless steel pipe without the heater, the surface temperature on the heated pipe was maintained at body core temperature (Fig 5A) , indicating that it is an effective tool to monitor the influence of temperature on bacterial survival on a dry surface. Taken together, we concluded that the handrail device warmed to human body core temperature prohibited the prolonged survival of some bacteria and a yeast-like fungus responsible for nosocomial infections on a dry surface. doi = 10.1371/journal.pone.0226952 id = cord-295536-dbpt4dhr author = Shook, Natalie J. title = Disease avoidance in the time of COVID-19: The behavioral immune system is associated with concern and preventative health behaviors date = 2020-08-20 keywords = BIS; COVID-19; health summary = This study examined whether individual differences in BIS reactivity (germ aversion, pathogen disgust sensitivity) were associated with concern about COVID-19 and engagement in recommended preventative health behaviors (social distancing, handwashing, cleaning/disinfecting, avoiding touching face, wearing facemasks). Germ aversion and pathogen disgust sensitivity were the two variables most consistently associated with COVID-19 concern and preventative health behaviors, while accounting for demographic, health, and psychosocial covariates. In general, younger age, higher income, more populated location of residence, more recent illness, better perceived health, having/had COVID-19, greater religiosity, greater extraversion, greater conscientiousness, greater perceived infectability, greater germ aversion, and greater pathogen disgust sensitivity were associated with engaging in most (at least three) of the preventative health behaviors more frequently. When demographic, health, social, personality, and BIS variables were considered simultaneously, greater germ aversion and pathogen disgust sensitivity were most consistently associated with COVID-19 concern and preventative behaviors. doi = 10.1371/journal.pone.0238015 id = cord-000715-zl1s82yi author = Shulman, Lester M. title = Evaluation of Four Different Systems for Extraction of RNA from Stool Suspensions Using MS-2 Coliphage as an Exogenous Control for RT-PCR Inhibition date = 2012-07-16 keywords = MS2; PCR; RNA summary = These samples were selected from among archived stool samples previously tested for enterovirus and MS2 after extraction by QIAamp Viral RNA Mini Kit. A sufficient number of samples with high, intermediate, and low levels of inhibitors were chosen for re-analysis to enable comparison between extraction procedures at each of these levels of inhibition. Analysis of variance ( Fig. 3 , part 2), indicated that there was no significant difference (paired t-test, P.0.05) between the inhibition of rRT-PCR of the MS2 external control and the added enterovirus (P.0.05) for protocols A, C, and D. Stool suspensions (N = 185) prepared for routine analysis of clinical stool samples sent to the Central Virology Laboratory (CVL) at Chaim Sheba Medical Center in Israel were used to evaluate the efficiency of four different RNA extraction systems in excluding inhibitors of rRT-PCR. doi = 10.1371/journal.pone.0039455 id = cord-273594-vmbhok1u author = Sichelstiel, Anke title = Targeting IL-1β and IL-17A Driven Inflammation during Influenza-Induced Exacerbations of Chronic Lung Inflammation date = 2014-06-11 keywords = COPD; IL-17A; LPS; figure summary = doi = 10.1371/journal.pone.0098440 id = cord-313107-6cfenpxm author = Singh, Anirudh K. title = Evaluation of pooled sample analysis strategy in expediting case detection in areas with emerging outbreaks of COVID-19: A pilot study date = 2020-09-22 keywords = PCR; pool; sample summary = In this context, a pooled sample testing strategy was evaluated in the setting of emerging disease outbreak in 3 central Indian districts to assess if the cost of the test and turn-around time could be reduced without compromising its diagnostic characteristics and thus lead to early containment of the outbreak. At the reported point prevalence of 4.8% in this study, the negative predictive value of qRT-PCR on pooled samples was around 96% suggesting that the adoption of this strategy as an effective screening tool for COVID-19 needs to be carefully evaluated. We hypothesized that testing of pooled respiratory samples, collected from potentially infected individuals, could lead to faster laboratory confirmation and quicker containment of the emerging infection in these districts and, thus, undertook this study to evaluate the diagnostic concordance between the strategies of pooled vs. doi = 10.1371/journal.pone.0239492 id = cord-329727-h47q76y8 author = Sisó-Almirall, Antoni title = Prognostic factors in Spanish COVID-19 patients: A case series from Barcelona date = 2020-08-21 keywords = COVID-19; ICU; patient summary = CONCLUSION: Determining the clinical, biological and radiological characteristics of patients with suspected COVID-19 infection will be key to early treatment and isolation and the tracing of contacts. Therefore, this study aimed to describe the clinical, biological and radiological manifestations, the evolution, treatments and mortality rate of patients with COVID-19 infection in the population of Barcelona city and determine the most important predictors of a poor prognosis. Signs and symptoms, the main available haematological and biochemical data and the results of imaging tests were recorded, as were comorbidities, the evolution, the hospitalization rate, intensive care unit (ICU) admission and the treatments received. This study summarizes the clinical, biological and radiological characteristics, evolution and prognostic factors of patients with COVID-19 disease in primary and community healthcare. https://doi.org/10.1371/journal.pone.0237960.t002 In bold, statistically significant independent predictive factors associated with hospitalization, death or ICU admission (logistic multivariate regression adjusted for age and sex). doi = 10.1371/journal.pone.0237960 id = cord-001186-jkg7qkj6 author = Skowronski, Danuta M. title = Randomized Controlled Ferret Study to Assess the Direct Impact of 2008–09 Trivalent Inactivated Influenza Vaccine on A(H1N1)pdm09 Disease Risk date = 2014-01-27 keywords = Ch+5; H1N1; TIV; Table summary = During spring-summer 2009, several observational studies from Canada reported that prior receipt of the 2008-09 trivalent inactivated influenza vaccine (TIV) was associated with increased risk of medically-attended, laboratory-confirmed A(H1N1)pdm09 illness, with estimated risk or odds ratios of 1.4-2.5 compared to those unvaccinated [1] . Protein microarray results were consistent with ELISA but in addition showed vaccine-induced HA1 antibody to the seasonal H1 antigen, for which values were significantly higher in vaccinated animals relative to pre-immunization and compared to placebo from day 28, most pronounced from day 49 after the first TIV dose (i.e. three weeks after two-dose vaccine series completion) ( Figure 2 ). Lower neutralizing antibody to A(H1N1)pdm09 even at Ch+14 among vaccinated versus placebo ferrets, although not statistically significant, is consistent with human immunogenicity trials showing blunting of pandemic H1N1 vaccine-induced responses in association with prior seasonal vaccine receipt [53] [54] [55] [56] . doi = 10.1371/journal.pone.0086555 id = cord-333853-p2kbjwpy author = Smee, Donald F. title = Therapy and Long-Term Prophylaxis of Vaccinia Virus Respiratory Infections in Mice with an Adenovirus-Vectored Interferon Alpha (mDEF201) date = 2011-10-13 keywords = infection; pfu; virus summary = title: Therapy and Long-Term Prophylaxis of Vaccinia Virus Respiratory Infections in Mice with an Adenovirus-Vectored Interferon Alpha (mDEF201) An adenovirus 5 vector encoding for mouse interferon alpha, subtype 5 (mDEF201) was evaluated for efficacy against lethal vaccinia virus (WR strain) respiratory infections in mice. Lung virus titers were significantly (>100-fold) lower than in the placebo group, and the other infection parameters in mDEF201 treated mice were nearly at baseline. Ad5-vectored mouse interferon (mDEF201) resulted in sustained IFN levels [16] , that completely protected mice from a lethal Western equine encephalitis virus infection when given intramuscularly at 10 7 plaque forming units (PFU)/ mouse up to 7 days prior to virus challenge [16] . The extent of inhibition of lung Intranasal treatments with mDEF201 (10 7 PFU/mouse) were given one time only on the indicated day prior to virus exposure. doi = 10.1371/journal.pone.0026330 id = cord-340195-425rd7ul author = Smith, Kristine M. title = Zoonotic Viruses Associated with Illegally Imported Wildlife Products date = 2012-01-10 keywords = NHP; SFV; States; United summary = Initial findings from samples collected at several international airports identified parts originating from nonhuman primate (NHP) and rodent species, including baboon, chimpanzee, mangabey, guenon, green monkey, cane rat and rat. These results are the first demonstration that illegal bushmeat importation into the United States could act as a conduit for pathogen spread, and suggest that implementation of disease surveillance of the wildlife trade will help facilitate prevention of disease emergence. Our study is the first to establish surveillance for zoonotic viruses in wild animal products illegally imported into the United States in an effort to prevent the transmission of infectious agents from these shipments. To date, four groups of HTLV viruses found in humans are believed to have originated from corresponding STLV strains in NHP species (including mangabeys, baboons, and chimpanzees) via multiple transmission events [35] . In summary, our study establishes initial surveillance methodology to detect and identify zoonotic pathogens and species of origin of wildlife products entering the United States. doi = 10.1371/journal.pone.0029505 id = cord-256837-100ir651 author = Smith, Steven B. title = Identification of Common Biological Pathways and Drug Targets Across Multiple Respiratory Viruses Based on Human Host Gene Expression Analysis date = 2012-03-14 keywords = Parkin; RSV; TNF; figure; gene; pathway; virus summary = Several recent studies have generated multiple mRNA microarray gene expression datasets derived from experiments involving the infection of human cell-lines or animal models with one or more of the major respiratory viruses [21] [22] [23] . Through a systematic analysis of these respiratory virus-human host gene expression datasets, we determined common sets of genes and pathways involved in host responses to viral infections. A total of seven different respiratory viruses were analyzed, represented by fifteen unique Gene Expression Omnibus (GEO) datasets (indicated by GEO Series or GSE accession numbers), nine different human cell types, and seven different array platforms for a total of 28 unique comparisons. This assumption is based on the occurrence of genes that are differentially expressed in infection models for at least five of the seven respiratory viruses, have involvement in a number of relevant pathways related to host immune response, and encode for known drug targets. doi = 10.1371/journal.pone.0033174 id = cord-339920-dr5bvpm0 author = Soberman, Roy J. title = CD200R1 Supports HSV-1 Viral Replication and Licenses Pro-Inflammatory Signaling Functions of TLR2 date = 2012-10-17 keywords = CD200R1; IL-6; TLR2; cd200; hsv-1 summary = We generated CD200R1(−/−) mice and employed them to explore both the role of CD200R1 in regulating macrophage signaling via TLR2 as well as the host response to an in vivo, TLR2-dependent model, herpes simplex virus 1 (HSV-1) infection. CD200R1 2/2 macrophages showed a marked decrease in the generation of both IL-6 and CCL5 (Rantes) in response to stimulation by both Pam 2 CSK 4 and HSV-1, whereas no difference was observed in the generation of any cytokine/chemokine in response to the TLR4 ligand bacterial lipopolysaccharide (LPS). These results indicated that CD200R1 directly controls the inducible surface expression of TLR2 either directly or secondary to decreased viral replication and that it may play a role in the amplification of HSV-1 infection. The lack of difference in brain leukocyte scores, and in CCL2 (MCP-1), CCL5 (Rantes), and IL-6 levels indicated that CD200R1 2/2 mice had equivalent or modestly reduced brain inflammation, rather than an enhanced, inflammatory response to HSV-1 infection compared to CD200R1 +/+ mice (see above). doi = 10.1371/journal.pone.0047740 id = cord-353245-es7b1rs0 author = Song, Deping title = Molecular Characterization and Phylogenetic Analysis of Porcine Epidemic Diarrhea Viruses Associated with Outbreaks of Severe Diarrhea in Piglets in Jiangxi, China 2013 date = 2015-03-19 keywords = JX-1/2013; PEDV summary = Compared to the PEDV CV777 strain, CH/JX-1/2013 and CH/JX-2/2013 had some unique genetic characteristics in the proximal region of the 5''-UTRs. Phylogenetic analysis of the complete genomes and the structural proteins revealed that CH/JX-1/2013 and CH/JX-2/2013 had a close relationship with post-2010 Chinese PEDV strains and US strains identified in 2013. Genetic characteristics were observed between the two groups: 1) compared to genome sequences of the members in G1, four insertions, 20803G, 20810CAGGGTGTCAA20820, 20830G, 21042AAT21044 and two deletions, 20842A, 21097CGTGAT21102, existed in the N-terminal domain (NTD) of the S protein in G 2 members; 2) the three field PEDV strains of JS2008, JS2008new and SD-M together with two attenuated PEDV strains, DR13 and vaccine_KC189944, were clustered into subgroup 1b. Notably, an amino acid substitution was found in the middle of one neutralizing epitope Phylogenetic trees based on the complete genome, aa sequences of structural proteins and ORF3 of PEDV strains. Sequence and phylogenetic analysis of nucleocapsid genes of porcine epidemic diarrhea virus (PEDV) strains in China doi = 10.1371/journal.pone.0120310 id = cord-281124-4nhy35xn author = Soowannayan, Chumporn title = RNA-Binding Domain in the Nucleocapsid Protein of Gill-Associated Nidovirus of Penaeid Shrimp date = 2011-08-03 keywords = GAV; RNA; protein summary = To examine this domain in more detail, the 18 aa peptide (M(11)PVRRPLPPQPPRNARLI(29)) encompassing this sequence was synthesized and found to bind nucleic acids similarly to the full-length N protein in EMSAs. The data indicate a fundamental role for the GAV N protein proline/arginine-rich domain in nucleating genomic ssRNA to form nucleocapsids. In a preliminary attempt to identify an RNA packaging signal in the GAV genome, EMSAs were performed using ssRNAs synthesized to various genome regions including (i) an ORF1b gene 39-region spanning the relative position to the genome packaging signal identified in MHV [28] , (ii) a 39-terminal genome region corresponding in position to the region in the infectious bronchitis virus (IBV) genome reported to contain an RNA binding domain [29] and (iii) the 59-genomic RNA terminus which, in coronaviruses, has also been reported to interact specifically with N protein [30] . doi = 10.1371/journal.pone.0022156 id = cord-342519-tjr6dvtt author = Souza, Thiago Moreno L. title = H1N1pdm Influenza Infection in Hospitalized Cancer Patients: Clinical Evolution and Viral Analysis date = 2010-11-30 keywords = H1N1; H1N1pdm; influenza; patient summary = The aim of the present study was to evaluate the clinical course, duration of viral shedding, H1N1pdm evolution and emergence of antiviral resistance in hospitalized cancer patients with severe H1N1pdm infections during the winter of 2009 in Brazil. Because the analysis of this novel viral infection in cancer patients is an important component of the 2009 pandemics, we conducted a prospective cohort study aimed at evaluating the clinical course of influenza infection, the duration of viral shedding, H1N1pdm evolution and the emergence of antiviral resistance in hospitalized cancer patients with a severe H1N1pdm infection in a reference cancer center during the winter of 2009 in Brazil. Although prolonged influenza A shedding has been observed for a cancer patient infected with the H3N2 seasonal virus [15] , more detailed data on H1N1pdm secretion in severely ill cancer patients are required. doi = 10.1371/journal.pone.0014158 id = cord-337913-eu2gn4bl author = Stojanov, Ana title = Does Perceived Lack of Control Lead to Conspiracy Theory Beliefs? Findings from an online MTurk sample date = 2020-08-17 keywords = belief; conspiracy; control; theory summary = Across six studies conducted online using MTurk samples, we observed no effect of control manipulations on conspiracy theory beliefs, while replicating previously reported correlational evidence of their association. Given the significance and potential consequences of widespread conspiracy beliefs [38, 39] , and the plausible but largely unsubstantiated role of control in their appeal, we here report three studies to test the effects of lack of control on conspiracy theory beliefs using a standard priming paradigm and a validated measure of conspiracy ideation, which reflects the belief that a powerful entity lies behind significant social or political events and that the conventional (official) truth is not the "real" truth. In a recent meta-analysis of experimental manipulations of control on conspiracy beliefs [68] conducted on 45 effect sizes across 23 studies (including those reported here), we found no moderating effect of sample type (MTurk vs. doi = 10.1371/journal.pone.0237771 id = cord-262876-civfvk45 author = Su, Tong title = Knowledge Levels and Training Needs of Disaster Medicine among Health Professionals, Medical Students, and Local Residents in Shanghai, China date = 2013-06-24 keywords = China; disaster; health summary = title: Knowledge Levels and Training Needs of Disaster Medicine among Health Professionals, Medical Students, and Local Residents in Shanghai, China Continuing medical education and public education plans on disaster medicine via media should be practice-oriented, and selectively applied to different populations and take the knowledge levels and training needs into consideration. Three groups of participants in Shanghai, China, were enrolled in this cross-sectional epidemiological study: health professionals, medical students, and community residents. Moreover, the knowledge level was also significantly different among clinicians, public health physicians, nurses, and medical technicians, especially in correctly answering 5 questions (Table S2) . Figure 3 presents the key contents concerning disaster medicine training prioritized by health professionals, medical students, and community residents. Figure 4 presents the most interested contents of disaster medicine training prioritized by health professionals, medical students, and community residents. In this study, we evaluated the current knowledge levels and training needs of disaster medicine among health professionals, medical students, and community residents in Shanghai, China. doi = 10.1371/journal.pone.0067041 id = cord-281815-zvs5qe8x author = Subramanian, Shoba title = Hemoglobin Cleavage Site-Specificity of the Plasmodium falciparum Cysteine Proteases Falcipain-2 and Falcipain-3 date = 2009-04-09 keywords = Leu; Plasmodium; hemoglobin summary = The Plasmodium falciparum cysteine proteases falcipain-2 and falcipain-3 degrade host hemoglobin to provide free amino acids for parasite protein synthesis. Treatment of erythrocytic parasites with cysteine protease inhibitors or disruption of the falcipain-2 gene results in accumulation of undegraded hemoglobin in the food vacuole, confirming a role for this enzyme in hemoglobin hydrolysis [6, 10] . To better characterize the roles of falcipain-2 and falcipain-3, we evaluated activities of these proteases against a library of small peptide substrates, a series of larger peptides spanning the sequences of a and b globin, and intact human hemoglobin. Falcipain-2 and falcipain-3 demonstrated a marked preference for cleavage of small peptide substrates with P 2 Leu, but the enzymes showed less specificity against larger peptides and intact hemoglobin, with hydrolysis at multiple sites. Despite the presence of multiple proteases in the food vacuole, it is noteworthy that treatment of cultured parasites with specific inhibitors of cysteine proteases fully blocked the hydrolysis of hemoglobin, highlighting the key role for the falcipains in this process [22] . doi = 10.1371/journal.pone.0005156 id = cord-000063-tex6bgab author = Sui, Hong-Yan title = Small Interfering RNA Targeting M2 Gene Induces Effective and Long Term Inhibition of Influenza A Virus Replication date = 2009-05-22 keywords = H5N1; MDCK; RNA summary = Using this vector that also expresses enhanced green fluorescence protein (EGFP) as surrogate marker, stable shRNA-expressing cell lines were successfully established and the inhibition efficiencies of rationally designed siRNAs targeting to conserved regions of influenza A virus genome were assessed. It was further demonstrated that no siRNA-resistant viral mutation appeared in siM2 targeting sequence even after the virus was cultured in the shRNA expressing stable cell line for 40 passages. A recent report by Zhou et al [30] also showed that several siRNAs targeting NP and M genes exhibited effective inhibition against influenza A virus replication in cultured MDCK cells and in animal models. Taken together, all the findings about effective RNAi target, lentiviral vector delivery and the establishment of stable shRNA expressing cell lines in our study provide rational information for the development of siRNAs as prophylaxis and therapy for influenza virus infection in humans. doi = 10.1371/journal.pone.0005671 id = cord-285433-ehnu83qe author = Sun, Hongliu title = Detection of Cytomegalovirus Antibodies Using a Biosensor Based on Imaging Ellipsometry date = 2015-08-21 keywords = BIE; CMV; CMV-3A summary = METHODS: An antibody analysis method is reported for the detection and identification of CMV antibodies in serum using a biosensor based on high spatial resolution imaging ellipsometry (BIE). As such, the concentration of CMV antibody in serum was quantitatively detected by BIE and then compared using ELISAs. Silicon wafers were purchased from the General Research Institute for Nonferrous Metals (China). Compared to blank controls areas, the purified CMV antibody and patient serum sample detection areas had markedly thicker films, with the average grayscale value displaying significant increases, while negative control areas did not (Fig 1) . Quantitative detection of CMV antibodies in clinical serum 41 CMV patients (Table A in S2 File) with quantitative results by ELISA were tested with BIE (Fig 4) . Thus, this label-free method may avoid some Detection of CMV antibodies in patient serum using BIE. doi = 10.1371/journal.pone.0136253 id = cord-353866-0r1b44id author = Sun, Hongpeng title = Changes of Adult Population Health Status in China from 2003 to 2008 date = 2011-12-02 keywords = China; chinese; health summary = Stratified analyses revealed significant subpopulation disparities in rate ratios for 2008/2003 in the presence of chronic disease, with greater increases among women, elderly, the Han nationality, unmarried and widow, illiterate, rural, and regions east of China than other groups. This study aimed to describe the male and female adult Chinese population health status in multiple dimensions, including overall morbidity, presence of illness in the last 2 weeks and chronic disease in the last 6 months, and healthy behavior as regards smoking, alcohol consumption, and physical activity, using data from the most recent National Health Services Surveys by the Chinese government in 2003 and 2008. However, overall Chinese adult population health status has not been improved due to short time and small proportion of residents performing frequent exercise; hence it seems that the prevalence and burden of chronic diseases will continue to grow. doi = 10.1371/journal.pone.0028411 id = cord-271660-5sfkhg19 author = Sun, Hsin-Yun title = Impact of introducing fluorescent microscopy on hospital tuberculosis control: A before-after study at a high caseload medical center in Taiwan date = 2020-04-03 keywords = Taiwan; patient summary = METHODS: We measured the impact of switch to fluorescent microscopy on the smear detection rate of culture-confirmed pulmonary TB, timing of respiratory isolation, and total non-isolated infectious person-days in hospital at a high-caseload medical center (approximately 400 TB cases annually) in Taipei. Hospitalized patients had typical presentations of pulmonary TB if they had: (a) a prolonged cough for >3 weeks; (b) clinical suspicion of pulmonary TB based on chest radiography, such as cavitary pulmonary lesions, upper lobe diseases, or miliary lesions; or (c) already received a confirmed diagnosis of pulmonary TB by a positive sputum culture of Mycobacterium tuberculosis, positive acid-fast stain (AFS), or positive TB PCR, before the hospitalization. Our previous survey on age/sex-standardised TB incidence ratio of HCWs (using general population as reference)---the excess TB risk that are attributable to nosocomial TB transmission---in Medical Center A showed a drop of this risk, from 3.11 in 2006 to 1.37 in 2012 [23] , and the decrease in time-to-isolation and total non-isolated infectious patient-days was in parallel in the present study. doi = 10.1371/journal.pone.0230067 id = cord-280471-cqypwi5d author = Sun, Hua-Bao title = The changes of the peripheral CD4+ lymphocytes and inflammatory cytokines in Patients with COVID-19 date = 2020-09-25 keywords = CD4; COVID-19 summary = To investigate the clinical value of changes in the subtypes of peripheral blood lymphocytes and levels of inflammatory cytokines in patients with COVID-19, the total numbers of lymphocytes and CD4+ lymphocytes and the ratio of CD4+/CD8+ lymphocytes were calculated and observed in different groups of patients with COVID-19. Characteristic chest CT imaging patterns, positive nucleic acid detection in nasal and throat swab samples, normal or decreased numbers of peripheral white blood cells, decreased numbers of lymphocytes and increased levels of inflammatory cytokines are the key factors in the diagnosis of COVID-19 [3] . The total number of lymphocytes, the percentages of lymphocyte subtypes and the levels of inflammatory cytokines (TNF-α and IL-6) secreted by CD4+ helper T lymphocytes in the peripheral blood were detected by hematology counter and flow cytometer, respectively. In the COVID-19 patients in the general, severe and critical groups, the numbers of peripheral lymphocytes and CD4+ T lymphocytes and the ratio of CD4+/CD8+ lymphocytes were significantly lower than those in the normal control group. doi = 10.1371/journal.pone.0239532 id = cord-003503-t6cnjwpd author = Sung, Ming-Hua title = Phylogeographic investigation of 2014 porcine epidemic diarrhea virus (PEDV) transmission in Taiwan date = 2019-03-06 keywords = PEDV; Taiwan; virus summary = doi = 10.1371/journal.pone.0213153 id = cord-334955-gnu92up6 author = Sutton, Jeannette title = COVID-19: Retransmission of official communications in an emerging pandemic date = 2020-09-16 keywords = COVID-19; content; message; retransmission summary = In this research, we examine message features shown in prior disasters to increase or decrease message retransmission under imminent threat conditions to develop models of official risk communicators'' messages shared online from February 1, 2020-April 30, 2020. We develop a lexicon of keywords associated with risk communication about the pandemic response, then use automated coding to identify message content and message structural features. They found that actionable and instructive messages and those that included a visual image were highly shared regardless of the time period; however, daily updates in the form of forecasts or current weather conditions involving little uncertainty, as well as message features that increase interaction, such as direct replies and URLs, decreased message passing. Messages that include information sharing decreases retransmission; however, this content increased post emergency declaration by 61%. doi = 10.1371/journal.pone.0238491 id = cord-254000-pbzcupjg author = Suvannachart, Pukkapol title = Repeatability, reproducibility, agreement, and safety of Tono-Pen tip cover for intraocular measurement using latex and polyethylene wrap date = 2020-09-28 keywords = LOA summary = PURPOSE: To evaluate repeatability, reproducibility, and agreement of intraocular pressure measurement with Tono-Pen using Ocufilm and polyethylene wrap tip cover in human eyes. For the right eye, 4 measurements using polyethylene wrap tip cover were done by two examiners (A and B) in random order to assess intra-observer repeatability and inter-observer reproducibility. For the left eye, 4 measurements were done by examiner A using both polyethylene wrap tip cover and Ocufilm in random order to assess intra-observer repeatability and agreement. RESULTS: For examiner A, the repeatability of polyethylene wrap tip cover was -0.34, 95% limits of agreement (LOA) were -3.04 to 2.36, and ICC was 0.93 in the right eyes. For IOP measurement with TP, our previous eye model and study conducted in canine eyes showed good repeatability and agreement between the custom-made polyethylene wrap (PW) tip cover and OF without causing any ocular surface complications [13, 14] . doi = 10.1371/journal.pone.0239875 id = cord-000580-dcid9emx author = Sällman Almén, Markus title = The Dispanins: A Novel Gene Family of Ancient Origin That Contains 14 Human Members date = 2012-02-20 keywords = Dispanins; IFITM; figure; gene summary = We show that the IFITM genes are a subfamily in a larger family of transmembrane (TM) proteins that we call Dispanins, which refers to a common 2TM structure. We mined 36 eukaryotic species, covering all major eukaryotic groups, and found that the IFITMs form a subfamily in a larger novel family that has ten human members in addition to the four IFITM genes. By combining the results of the phylogenetic analysis and BLAST classification, we created a schematic overview of the organisms'' gene repertoire and a schematic picture of the Dispanin family''s evolutionary history, which suggests that the invertebrate Dispanins share more similarity towards the DSPC and D subfamilies than DSPA and B ( Figure 2 ). We provide evidence that the four IFITM genes together with ten additional human genes, known as TUSC5, TMEM233, PRRT2, TMEM90A, DSPC2, TMEM90B, TMEM91, AC023157, AL160276 and AC068580, form a novel gene family that we call the Dispanins, which refers to the 2TM membrane topology that is common to all identified members. doi = 10.1371/journal.pone.0031961 id = cord-336420-1a2u9p4t author = Söderman, Martina title = Frequent Respiratory Viral Infections in Children with Febrile Neutropenia - A Prospective Follow-Up Study date = 2016-06-16 keywords = respiratory; table summary = title: Frequent Respiratory Viral Infections in Children with Febrile Neutropenia A Prospective Follow-Up Study Advances in molecular methods have increased the sensitivity of viral diagnostics tests, with recent studies reporting the detection of respiratory viruses in the nasopharynx in 44-57% of childhood febrile neutropenia episodes using real-time polymerase chain reaction (PCR) [3] [4] [5] 12] . Viral nucleic acids were extracted from the NPA with a MagAttract Virus Mini M48 kit (Qiagen, Sollentuna, Sweden) and analyzed with in-house real-time PCRs for the following 16 viruses: adenovirus (HAdV); bocavirus (HBoV); coronaviruses NL63/OC43/229E/HKU1 (HCoV); enterovirus (EV); influenza virus A, including A(H1N1)pdm09 and B (Flu); metapneumovirus (HMPV); parainfluenza viruses 1-3 (PIV); respiratory syncytial virus (RSV) and rhinovirus (RV) [19] . These results support the theory holding that there is a causal relationship between respiratory viral infections and episodes of febrile neutropenia, but proving this theory will require more longitudinal studies with asymptomatic neutropenic control cohorts. doi = 10.1371/journal.pone.0157398 id = cord-002094-7tewne3a author = Tago, Damian title = The Impact of Farmers’ Strategic Behavior on the Spread of Animal Infectious Diseases date = 2016-06-14 keywords = MRP; disease summary = Incorporating the strategic behavior of farmers in an epidemiologic model reveals that the MRP can trigger premature animal sales by farms at high risk of becoming infected that significantly reduce the efficacy of the policy. The idea behind control strategies such as the MRP and vaccination [7] is that removing infected nodes or immunizing susceptible ones are efficient mechanisms to fight the spread of a disease. If an infectious disease is detected at t = 1, a farmer sufficiently close to the infected zone will face the risk that the restricted zone (RZ) will expand to include his location by the next period (with probability q). In the case of non-vector-borne diseases, i.e. when the transmission channel is restricted to the trade network, the MRP is an effective control strategy. The MRP becomes significantly less efficient when infected nodes that have not been detected spread the disease through both trade and geographic networks. doi = 10.1371/journal.pone.0157450 id = cord-352219-z245sb3s author = Tallam, Aravind title = Gene Regulatory Network Inference of Immunoresponsive Gene 1 (IRG1) Identifies Interferon Regulatory Factor 1 (IRF1) as Its Transcriptional Regulator in Mammalian Macrophages date = 2016-02-12 keywords = CAD; Fig; IRF1; IRG1; LPS; cell summary = Furthermore, using literature information and transcription factor prediction models, we re-constructed raw gene regulatory networks (GRNs) for IRG1 in mouse and human macrophages. We further implemented a contextualization algorithm that relies on genome-wide gene expression data to infer putative cell type-specific gene regulatory interactions in mouse and human macrophages, which allowed us to predict potential transcriptional regulators of IRG1. Among the computationally identified regulators, siRNA-mediated gene silencing of interferon regulatory factor 1 (IRF1) in macrophages significantly decreased the expression of IRG1/CAD at the gene and protein level, which correlated with a reduced production of itaconic acid. Putative transcriptional regulators of IRG1 were hypothesized from the resulting GRN and tested using siRNA-mediated gene silencing experiments in mouse and human macrophages under LPS stimulation. Although the human data were obtained from primary cells, while the mouse analysis was conducted using the macrophage cell line RAW264.7, it is tempting to speculate that the transcriptional machinery inducing IRG1 expression, with the exception of IRF1, is mostly species-specific, as highlighted by the different transcriptional regulators identified in the two species (Table 1) . doi = 10.1371/journal.pone.0149050 id = cord-290120-fd26t8ja author = Tan, Chew Yee title = First molecular detection and complete sequence analysis of porcine circovirus type 3 (PCV3) in Peninsular Malaysia date = 2020-07-24 keywords = Malaysia; ORF2; PCV2; PCV3; porcine summary = title: First molecular detection and complete sequence analysis of porcine circovirus type 3 (PCV3) in Peninsular Malaysia Given that PCV3 is increasingly reported in countries including Thailand and U.S. with whom Malaysia shares trade and geographical relationship; and that PCV3 is associated with several clinical presentations that affect productivity, there is a need to study the presence and molecular characteristics of PCV3 in Malaysian swine farms. Results revealed that PCV3 is present in Peninsular Malaysia at a molecular prevalence of 17.02%, with inguinal lymph nodes and lungs showing the highest molecular detection rates of 81.82% and 71.43% respectively. To test for association between PCV3 molecular detection status and age group, health status, farm standing sow population and distance from neighbouring farms, Chi-square tests were performed with statistical significance level set at p < 0.05. PCV3 infection susceptibility has been suggested to be associated with the age of wild boar, with juvenile animals showing statistically lower detection rates, unlike reports described in domestic pigs [37, 48] . doi = 10.1371/journal.pone.0235832 id = cord-301811-ykpiorgo author = Tanaka, Takuma title = Estimation of the percentages of undiagnosed patients of the novel coronavirus (SARS-CoV-2) infection in Hokkaido, Japan by using birth-death process with recursive full tracing date = 2020-10-28 keywords = Hokkaido; SARS; patient summary = title: Estimation of the percentages of undiagnosed patients of the novel coronavirus (SARS-CoV-2) infection in Hokkaido, Japan by using birth-death process with recursive full tracing We estimated the numbers of undiagnosed symptomatic patients and the lower bound of the number of total infected individuals per diagnosed patient before and after the declaration of the state of emergency in Hokkaido, Japan. The present analysis uses the distributions of the cluster size and patients'' time from onset to diagnosis, which are released by the health officials, to estimate the model parameters. At the same time, the nodes in the connected component containing the diagnosed node are also removed from the network, which corresponds to the contact tracing of the infected individuals (Fig 2, gray open circles) . In this paper, we have formulated a model to describe the spreading of infection and the quarantine of infected individuals, and estimated the number of undiagnosed symptomatic and asymptomatic COVID-19 patients in Hokkaido. doi = 10.1371/journal.pone.0241170 id = cord-048492-4z38v9rg author = Tang, Julian W. title = Seasonality of Influenza A(H3N2) Virus: A Hong Kong Perspective (1997–2006) date = 2008-07-23 keywords = A(H3N2 summary = In this study, an analysis is presented of 281 Hong Kong influenza A(H3N2) hemagglutinin (HA) and neuraminidase (NA) full-length, dated sequences collected over 10 years (1997-2006) to assist the ongoing efforts to elucidate the underlying basis for the seasonality of influenza A(H3N2). One example of such possible viral persistence between influenza seasons was found, with HA and NA sequences from the same viruses (5251Jan02 and 5267Jan03, as indicated in Figures S1 and S2 for the HA and NA phylogenetic trees, respectively), showing a similar clustering pattern for both these genes, separated by at least one year. A similar analysis was recently performed using dated whole genome influenza A(H3N2) sequences from New York, New Zealand and Australia, downloaded from publicly available databases, in an attempt to test two competing hypotheses: whether seasonal influenza A(H3N2) viruses continuously ''migrate'' around the world, particularly between Northern and Southern hemispheres; or whether the virus remains ''latent'' in one location and reactivates each year to produce the familiar pattern of influenza seasonality [19] . doi = 10.1371/journal.pone.0002768 id = cord-263684-3535k3op author = Tang, Julian W. title = Different Types of Door-Opening Motions as Contributing Factors to Containment Failures in Hospital Isolation Rooms date = 2013-06-24 keywords = door; figure; isolation; room summary = Using colored food dye as a tracer, the qualitative effects of door-opening motions on the dissemination of potentially contaminated air into and out of a single isolation room were visualized and filmed using Reynolds-number-equivalent, small-scale, water-tank models fitted with programmable door-opening and moving human figure motions. This study is part of a longer-term project that aims to demonstrate the effects of door-opening motions using a variety of doors, with and without the passage of a human figure, on the movement of potentially contaminated air into and out of an isolation room, using both a small-scale, Reynolds-number-equivalent model in water, and a full-scale model in air. In the small-scale water-tank models used in these experiments, the compartment outside the isolation room, into or from which The series of 4 snapshots with each dooropening, manikin movement scenario were taken with respect to the following events, rather than at specific times: food dye movement due to door-opening motions alone then with any initial manikin movement -manikin interaction and any entrainment food dye -final food dye movements once the manikin had come to rest at its destination position. doi = 10.1371/journal.pone.0066663 id = cord-337630-ojhk5opy author = Tasic, Velibor title = Clinical and Functional Characterization of URAT1 Variants date = 2011-12-16 keywords = SLC22A12; SLC2A9; hypouricaemia; renal; urat1 summary = reported that mutations in gene SLC22A12 encoding the URAT1 transporter were responsible for most cases of idiopathic renal hypouricaemia [3] . It is noteworthy that reports of idiopathic renal hypouricaemia secondary to mutations in uric acid transporters URAT1 and GLUT9 were initially reported from Japan, Korea and China [23] . Since the hypouricaemia was associated with an elevated FE urate , we undertook mutational analysis of SLC22A12 which revealed a heterozygous missense mutation, leading to amino acid change R434C. SLC22A12 encodes the protein URAT1 and loss of function mutations are responsible for majority of patients with idiopathic renal hypouricaemia. reported a W258X homozygous mutation in a 7 year old child, whose mother and brother were also heterozygous for W258X and had mild hypouricaemia and abnormally high FE urate , whilst his father who was also heterozygous for W258X, had a normal serum uric acid level of 4.6 mg/dL [23] . doi = 10.1371/journal.pone.0028641 id = cord-312493-wbhji81g author = Tay, Ee Laine title = Exploring a Proposed WHO Method to Determine Thresholds for Seasonal Influenza Surveillance date = 2013-10-11 keywords = ILI; MMDS; influenza summary = For all datasets, including the composite datasets, we aligned data on the median week of peak influenza or ILI activity and assigned three threshold levels: seasonal threshold, determined by inspection; and two intensity thresholds termed average and alert thresholds, determined by calculations of means, medians, confidence intervals (CI) and percentiles. Comparison of thresholds revealed variations in defining the start of a season but good agreement in describing the end and intensity of influenza seasons, except in hospital admissions data after the pandemic year of 2009. Four independent surveillance data sources were used: (i) the Victorian GPSS, (ii) sentinel data from the Melbourne Medical Deputising Service (MMDS), (iii) routine laboratoryconfirmed influenza (LAB data) from the Victorian Infectious Diseases Reference Laboratory (VIDRL) and the (iv) Victoria Admitted Episode Dataset (VAED) for hospital admissions. Comparison of thresholds derived from different datasets revealed variations in defining the start of a season but relatively good agreement in describing the end and intensity of influenza seasons, except in the hospital data after the pandemic year. doi = 10.1371/journal.pone.0077244 id = cord-330110-pamxy4av author = Teissier, Elodie title = Mechanism of Inhibition of Enveloped Virus Membrane Fusion by the Antiviral Drug Arbidol date = 2011-01-25 keywords = Arb; DMPC; HCV; figure; fusion; membrane summary = Interestingly, apparent binding affinities between lipids and tryptophan residues are comparable with those of Arb IC50 of the hepatitis C virus (HCV) membrane fusion. By combining surface plasmon resonance, fluorescence and NMR spectroscopy approaches, we showed that Arb directly interacts with the phospholipid membrane interface, with an affinity in the micromolar range, comparable to the concentration inhibiting HCVpp membrane fusion by 50% (IC50). Altogether our results demonstrate that Arb interacts with the polar head of phospholipid membranes and protein motifs enriched in aromatic residues, suggesting that the inhibitory activity of Arb on HCV entry and fusion could involve both types of interactions. Conversely, Arb inhibition of HCVpp membrane fusion, as assessed by a in vitro model system where the only proteins present are the viral glycoproteins, could merely reflect the interaction of Arb on lipids and/or on motifs present in HCV glycoproteins of any genotype. doi = 10.1371/journal.pone.0015874 id = cord-002624-59nznqsd author = Ti, Jinfeng title = Identification of one B-cell epitope from NS1 protein of duck Tembusu virus with monoclonal antibodies date = 2017-07-26 keywords = TMUV; ns1 summary = title: Identification of one B-cell epitope from NS1 protein of duck Tembusu virus with monoclonal antibodies This study describes the identification of one linear B-cell epitope on TMUV NS1 protein with monoclonal antibody (mAb) 3G2 by indirect enzyme-linked immunosorbent assay (ELISA). In this study, one linear B-cell epitope was identified and characterized with one monoclonal antibody against TMUV NS1 protein. To screen the antigenic epitope of TMUV NS1 mAb, 35 short peptide fusion proteins were successfully expressed in prokaryotic expression system and purified. A pane of 16-AA polypeptides of NS1 protein was expressed and one 16-AA polypeptide NS1-27 was screened and identified by 3G2 mAb. In order to accurately map the B-cell epitope, a set of truncated fusion oligopeptides of NS1-27 were expressed. The B-cell epitope of TMUV NS1 protein could apply into the development of detection methods to investigate whether the detected antibody was a result of inactivated vaccine immunization or live virus infection. doi = 10.1371/journal.pone.0181177 id = cord-302189-3xab3yxc author = Tillmann, Ramona Liza title = Sensitive Commercial NASBA Assay for the Detection of Respiratory Syncytial Virus in Clinical Specimen date = 2007-12-26 keywords = PCR; RSV summary = Thereby, NASBA turned out to be the most sensitive method with a total number of 80 RSV positive samples out of a cohort of 251 nasopharyngeal washings from patients suffering from clinical symptoms, followed by the inhouse RT-PCR (62/251) and ELISA (52/251). Despite an increasing number of newly detected respiratory pathogen the human Respiratory syncytial virus (RSV) remains the single most prevalent etiologic agent in pediatric viral respiratory tract infection [1, 2, 3] . In relation to the positive test results obtained with the NucliSENSH EasyQ NASBA, the relative sensitivity of the RT-PCR was 77,5% compared to 65% obtained with the NOWH RSV ELISA. The results showed that from the three tested methods for molecular diagnosis of RSV the NucliSENSH EasyQ NASBA (bioMerieux, Nürtingen, Germany) detected the most RSV positive samples in a cohort of 251 nasopharyngeal samples of pediatric patients hospitalized with respiratory disease. doi = 10.1371/journal.pone.0001357 id = cord-260728-4w23kwzu author = Timmermans, Ans title = Human Sentinel Surveillance of Influenza and Other Respiratory Viral Pathogens in Border Areas of Western Cambodia date = 2016-03-30 keywords = Cambodia; PCR; Table; influenza summary = Real-time reverse transcriptase (rRT) PCR for influenza was performed on combined nasal and throat specimens followed by viral culture, antigenic analysis, antiviral susceptibility testing and full genome sequencing for phylogenetic analysis. Between May 2010 and December 2012, we collected specimens and surveillance data for influenza and other viral respiratory pathogens from a subset of outpatients presenting with influenza-like-illness (ILI) at four sentinel sites-located in five health centers and hospitals in Battambang, Oddar Meanchey, Pailin and Banteay Meanchey provinces in Cambodia (Fig 1) . A subset of 164 culture-negative specimens (collected between May 2010 and April 2012), where we found a higher proportion (5.6%) of non-polio enteroviruses in children less than 5 years old as compared with previous studies (1%) in Cambodia [2] , were tested for enterovirus and rhinovirus by two separate nested RT-PCR methods adapted from Coiras et al., 2004 and Singh et al., 2002 [29,30] , one for simultaneous detection of pan-enteroviruses and rhinoviruses, and the other specific for enterovirus 71 (EV71). doi = 10.1371/journal.pone.0152529 id = cord-001219-517gka4h author = Timpka, Toomas title = Intentions to Perform Non-Pharmaceutical Protective Behaviors during Influenza Outbreaks in Sweden: A Cross-Sectional Study following a Mass Vaccination Campaign date = 2014-03-07 keywords = AUC; influenza; intention; outbreak summary = We administered a cross-sectional telephone survey to a representative sample (n = 443) of the Swedish adult population to examine whether self-reported intentions to improve personal hygiene and increase social distancing during influenza outbreaks could be explained by trust in official information, self-reported health (SF-8), sociodemographic factors, and determinants postulated in protection motivation theory, namely threat appraisal and coping appraisal. A hypothetical explanatory model was constructed to inform the analysis of the main research question; i.e. to what extent selfreported intentions to perform protective behaviors during influenza outbreaks can be explained by perceptions of threat and the ability to cope as outlined in the PMT, self-assessments of health status, trust in official information, and sociodemiographic factors. doi = 10.1371/journal.pone.0091060 id = cord-000166-36bfeoqv author = Tracht, Samantha M. title = Mathematical Modeling of the Effectiveness of Facemasks in Reducing the Spread of Novel Influenza A (H1N1) date = 2010-02-10 keywords = H1N1; N95; mask summary = We construct and analyze a mathematical model for a population in which some people wear facemasks during the pandemic and quantify impact of these masks on the spread of influenza. The results show that if N95 respirators are only 20% effective in reducing susceptibility and infectivity, only 10% of the population would have to wear them to reduce the number of influenza A (H1N1) cases by 20%. With the implementation of N95 respirators Table 3 exhibits a reduction in the cumulative number of cases of almost 200,000, or a 19% decrease, when 10% of the population wears masks and they are 20% effective. With 10% of the population wearing N95 respirators with effectiveness at 20% in reducing both susceptibility and infectivity there is a 19% reduction in the cumulative number of cases. Even at 50% effectiveness in reducing both susceptibility and infectivity and with 50% of the population wearing surgical masks only a 6% reduction in the number of cumulative cases is seen. doi = 10.1371/journal.pone.0009018 id = cord-273175-bao8xxe2 author = Tran, Viet-Thi title = COVID-19–related perceptions, context and attitudes of adults with chronic conditions: Results from a cross-sectional survey nested in the ComPaRe e-cohort date = 2020-08-06 keywords = COVID-19; patient; risk summary = doi = 10.1371/journal.pone.0237296 id = cord-331652-oc5s1if2 author = Trudeau, Michaela P. title = Comparison of Thermal and Non-Thermal Processing of Swine Feed and the Use of Selected Feed Additives on Inactivation of Porcine Epidemic Diarrhea Virus (PEDV) date = 2016-06-24 keywords = PEDV; feed; virus summary = title: Comparison of Thermal and Non-Thermal Processing of Swine Feed and the Use of Selected Feed Additives on Inactivation of Porcine Epidemic Diarrhea Virus (PEDV) Feed samples were spiked with PEDV and then heated to 120–145°C for up to 30 min or irradiated at 0–50 kGy. Another set of feed samples spiked with PEDV and mixed with Ultracid P (Nutriad), Activate DA (Novus International), KEM-GEST (Kemin Agrifood), Acid Booster (Agri-Nutrition), sugar or salt was incubated at room temperature (~25°C) for up to 21 days. Therefore, the objective of this study was to determine if thermal and non-thermal methods of microbial inactivation, as well as the use of selected feed additives, are effective in reducing the survival of PEDV in experimentally contaminated swine feed. The PEDV showed a high thermal resistance in the dry feed samples and it was completely inactivated (3.0 log reduction) at each of the tested temperatures within 30 min. doi = 10.1371/journal.pone.0158128 id = cord-318614-518giv0m author = Tsai, Jih-Jin title = A fully automated sample-to-answer PCR system for easy and sensitive detection of dengue virus in human serum and mosquitos date = 2019-07-10 keywords = DENV; PCR; pockit summary = A pan-dengue virus (DENV) RT-iiPCR, targeting the 5'' untranslated region, was validated previously on the semi-automated POCKIT combo system (involving separate devices for nucleic acid extraction and PCR amplification/detection) to offer performance comparable to a laboratory real-time PCR. CONCLUSIONS/SIGNIFICANCE: With performance comparable to a previously validated system, the fully-automated PCR system allows applications of the pan-DENV reagent as a useful tool near points of need to facilitate easy, fast and effective detection of dengue virus and help mitigate versatile public health challenges in the control and management of dengue disease. Testing with the pan-DENV RT-iiPCR, the analytical and clinical performance of the fully automatic POCKIT Central system was comparable to those of the semi-automatic POCKI combo system, which was validated previously to offer performances equivalent to the CDC DENV1-4 real-time RT-PCR for the detection of DENV in human serum [7, 24, 26] . doi = 10.1371/journal.pone.0218139 id = cord-001090-qg2r691d author = Twin, Jimmy title = The Potential of Metatranscriptomics for Identifying Screening Targets for Bacterial Vaginosis date = 2013-09-27 keywords = Prevotella; RNA; dna summary = doi = 10.1371/journal.pone.0076892 id = cord-001603-vlv8x8l8 author = Ul-Haq, Zaheer title = 3D Structure Prediction of Human β1-Adrenergic Receptor via Threading-Based Homology Modeling for Implications in Structure-Based Drug Designing date = 2015-04-10 keywords = Fig; Surflex; model summary = doi = 10.1371/journal.pone.0122223 id = cord-000008-3dgjv0x1 author = Vali, Bahareh title = HIV-Specific T-Cells Accumulate in the Liver in HCV/HIV Co-Infection date = 2008-10-20 keywords = HCV; HIV summary = In response to stimulation with HIV peptide pool, untreated co-infected individuals showed significantly higher frequencies of intra-hepatic CD4 + T-cells producing IFN-c, compared to HCV mono-infected [0.1660.05% vs 0.0260.01%, p,0.05], and HAART-treated co-infected individuals [0.1660.05% vs 0.0360.05%, p,0.05] (Figure 2a ). Therapy naïve co-infected subjects had greater IFN-c producing CD8 + T-cells in response to HIV peptides compared to HCV mono-infected individuals [1.3960.37% vs 0.0260.0%, p,0.05], and HAART was associated with a significant reduction in the frequencies of these cells [1.3960.37% vs 0.3060.26%, p,0.05] (figure 2b). The tetramer cytokine response pattern was shown to be different in the liver compared to blood of the same individual, with diminished intra-hepatic tetramer-specific IFN-c responses and an increase in both CD107a and TNF-a responses, with the majority of SL9 tetramer positive cells expressing these two markers. Therapy naïve co-infected individuals demonstrated a higher frequency of intra-hepatic CD8 + T-cells that produce TNF-a in response to both HCV and HIV antigen stimulation compared to HCV mono-infected individuals. doi = 10.1371/journal.pone.0003454 id = cord-310061-nro623aa author = Valitutto, Marc T. title = Detection of novel coronaviruses in bats in Myanmar date = 2020-04-09 keywords = Myanmar; SARS; bat; sample summary = Historically, bats have been linked to highly pathogenic viruses that pose a serious threat to human health, including the coronaviruses responsible for severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), the hemorrhagic ebola and Marburg filoviruses, and paramyxoviruses such as Nipah virus [10, 11, [13] [14] [15] [16] [17] [18] . The 2002-2003 SARS epidemic, the emergence of MERS in people in 2012, and the ongoing COVID-19 pandemic have prompted substantial interest in detecting coronaviruses of bat origin due to public health concern and their pandemic potential [10, [13] [14] [15] [16] [17] [18] . In addition to human-associated CoVs, bats are also hosts of coronaviruses that infect production animals, and have been implicated in the emergence and origin of swine acute diarrhea syndrome (SADS), transmissible gastroenteritis virus (TGEV) in pigs, and porcine epidemic diarrhea (PED), which can cause considerable losses [23] [24] [25] [26] . doi = 10.1371/journal.pone.0230802 id = cord-255576-738khdwv author = Van Duyne, Rachel title = Localization and Sub-Cellular Shuttling of HTLV-1 Tax with the miRNA Machinery date = 2012-07-10 keywords = Drosha; HTLV-1; RNA; cell; figure; tax summary = We have previously shown that Tax interacts directly with the cellular Rb (Retinoblastoma) protein and targets Rb for degradation via the proteasome pathway, resulting in a decrease in Rb protein expression in HTLV-1 infected cells and a dysregulation of the cell cycle [47] . Collectively, these data indicate that the Drosha in Tax-containing and HTLV-1 infected cells is mostly functionally inactive and the functional suppression of Drosha is dependent on its interaction with a small region of the N-terminus of Tax. We have shown above that Drosha is downregulated, degraded, and mostly inactive in HTLV-1 infected cells, however, it was not clear what effect this dysregulation of Drosha would have on viral replication. Collectively, these data indicate that proteins, such as IKK-b, among others, may directly be regulated by the Tax/Drosha interaction in HTLV infected cells. doi = 10.1371/journal.pone.0040662 id = cord-295781-b831y105 author = VanLeuven, James T. title = Lung epithelial cells have virus-specific and shared gene expression responses to infection by diverse respiratory viruses date = 2017-06-02 keywords = IFN; MHV; PR8 summary = doi = 10.1371/journal.pone.0178408 id = cord-001071-bjx5td52 author = Vanhems, Philippe title = Estimating Potential Infection Transmission Routes in Hospital Wards Using Wearable Proximity Sensors date = 2013-09-11 keywords = RFID; contact; number summary = doi = 10.1371/journal.pone.0073970 id = cord-323185-n0rubc72 author = Varshney, Bhavna title = SARS Coronavirus 3b Accessory Protein Modulates Transcriptional Activity of RUNX1b date = 2012-01-12 keywords = ERK; IL2; SARS; runx1 summary = Chromatin immunoprecipitaion (ChIP) and reporter gene assays in 3b expressing jurkat cells showed recruitment of 3b on the RUNX1 binding element that led to an increase in RUNX1b transactivation potential on the IL2 promoter. In this study, we confirmed the putative interaction of 3b and RUNX1b and observed in vivo recruitment of 3b on the RUNX1 binding element on the IL2 promoter in transiently transfected human T, jurkat cells. We next determined the positive effect of 3b-RUNX1b interaction on the expression of RUNX1b regulated chemokine MIP-1a, reported to be upregulated in SARS-CoV infected monocyte derived dendritic cells. To investigate whether 3b-RUNX1b interaction leads to the recruitment of 3b on RUNX1 binding elements on the endogenous IL2 promoter, ChIP assays were performed in RUNX1b/CBFb endogenously expressing jurkat cells that are abortively infected by SARS-CoV. To investigate the effect of SARS-CoV 3b protein on the RUNX1b transcriptional activity, reporter gene assays were performed using the mouse IL2 promoter. doi = 10.1371/journal.pone.0029542 id = cord-340937-6mpob1nx author = Varshney, Mohit title = Initial psychological impact of COVID-19 and its correlates in Indian Community: An online (FEEL-COVID) survey date = 2020-05-29 keywords = India; covid-19; impact summary = The survey collected data on socio-demographic and clinical variables related to COVID-19 (based on the current knowledge); along with measuring psychological impact with the help of Impact of Event–revised (IES-R) scale. The survey collected data on socio-demographic and clinical variables related to COVID-19 (based on the current knowledge); along with measuring psychological impact with the help of Impact of Eventrevised (IES-R) scale. The current study investigated the initial psychological impact of COVID-19 outbreak in Indian population. Despite the limitations, this study provides the first cross-sectional data on actual level of psychological impact among Indian community; and how mental health of people is affected during a pandemic of this nature. Our survey is one of the first mental health related data from India, during the initial phase of COVID-19 pandemic and indicated that a significant proportion of them have had a psychological impact during the crisis. doi = 10.1371/journal.pone.0233874 id = cord-290446-43h1r4pm author = Vazquez, Leonardo title = Comprehensive structural analysis of designed incomplete polypeptide chains of the replicase nonstructural protein 1 from the severe acute respiratory syndrome coronavirus date = 2017-07-27 keywords = Fig; NMR; construct; nsp1; nsp1(13 summary = This spacer provided a reasonably dynamic loop, according to our NMR data, which included narrow chemical shift dispersion (S2A Fig As depicted in Fig 1A, we designed the nsp1 constructs so as to avoid truncating their secondary-structure elements. The full-length nsp1 fusion protein has only a few missing peaks, indicating a well-folded 3D domain, which causes a wide dispersion of chemical shifts and allows straightforward identification of backbone HN signals. The SSP indicates the propensity ranging from -1 to 1 to adopt backbone conformations typical for extended β-strands or helical structures, respectively, according to the effect of these conformations on the chemical shifts of backbone atoms, [39] [40] [41] As shown in Fig 7, with the SSP algorithm it was possible to define very well the secondarystructure elements of the folded globular domain of nsp1 (orange bars in the uppermost graph). doi = 10.1371/journal.pone.0182132 id = cord-000666-je9t4i6q author = Verbist, Katherine C. title = IL-15 Participates in the Respiratory Innate Immune Response to Influenza Virus Infection date = 2012-05-18 keywords = CD8; IL-15; figure summary = ( Figure 2E) ; however, these animals seemed to regain control of viral replication by day 4 p.i., which perhaps corresponds with the early entry of cells of the adaptive immune response as anti-influenza specific CD8 T cells are first detectable in the lung airways by d6 post infection by flow cytometry ( [34] and data not shown). We observed significant reductions in the numbers of NK cells in the lung airways of influenza-infected animals in which IL-15 was blocked at time points associated with their arrival at the site of infection, and failure of these cell populations to accumulate had implications in early viral control (Figure 2) . doi:10.1371/journal.pone.0037539.g002 frequencies, numbers, CD122 expression, and BrdU incorporation were specific to the lung airways (the sight of treatment), as NK cells isolated from spleens were similar in control and IL-15ctreated animals ( Figure 3C and data not shown). doi = 10.1371/journal.pone.0037539 id = cord-048360-n9sih438 author = Villard, Viviane title = Rapid Identification of Malaria Vaccine Candidates Based on α-Helical Coiled Coil Protein Motif date = 2007-07-25 keywords = antibody; figure; peptide; protein; table summary = To identify malaria antigens for vaccine development, we selected α-helical coiled coil domains of proteins predicted to be present in the parasite erythrocytic stage. Here, we focus on the Pf parasite erythrocytic stage, a target of protective antibodies and describe a straightforward, rapid procedure based on bioinformatic analysis of a-helical coiled-coil motifs and peptide synthesis. With regard to the structural features and cellular location prediction of the proteins corresponding to the peptides selected for ADCI assays ( Table 1) , 15 of the proteins contain a pentapeptide conforming to the PEXEL consensus [19, 20; 21, 22] , but that none of these have a position within the amino acid sequence that conforms to the location of known active PEXEL motifs (see Materials and Methods and membrane segments, and none of them has a GPI anchor. In conclusion, an approach combining a genome-wide search by bioinformatics of a-helical coiled coil protein motifs and chemical synthesis can lead to the rapid identification and development of new malaria vaccine candidates. doi = 10.1371/journal.pone.0000645 id = cord-000912-6l6c7jpq author = Vitelli, Alessandra title = Vaccination to Conserved Influenza Antigens in Mice Using a Novel Simian Adenovirus Vector, PanAd3, Derived from the Bonobo Pan paniscus date = 2013-03-11 keywords = cell summary = doi = 10.1371/journal.pone.0055435 id = cord-000742-0r4z1zea author = Vittecoq, Marion title = High Influenza A Virus Infection Rates in Mallards Bred for Hunting in the Camargue, South of France date = 2012-08-27 keywords = AIV; Camargue; H10N7; mallard summary = We conducted a 2-year study in the Camargue (Southern France) to investigate the influence of hand-reared Mallard releases on avian influenza virus dynamics in surrounding wildlife. Our results indicate that the potential role of hand-reared Mallards in influenza virus epizootics must be taken into account given the likely risk of viral exchange between game bird facilities and wild habitats, owing to duck rearing conditions. However, to our knowledge no study ever aimed at investigating the potential role of hand-reared Mallards released for hunting in the epidemiology of AIV, despite the very large number of ducks being released in the wild annually. Our results highlighted that: i) GBF represent an epidemiological compartment into which important AIV outbreaks can occur; ii) a significant proportion of Mallards wintering in the Camargue are infected by LPAIV, including H5 strains that are known to be able to evolve to HPAIV in domestic birds [30] . doi = 10.1371/journal.pone.0043974 id = cord-000359-y0m1utug author = Walpita, Pramila title = Vaccine Potential of Nipah Virus-Like Particles date = 2011-04-06 keywords = Nipah; VLP; virus summary = doi = 10.1371/journal.pone.0018437 id = cord-336441-m6pur6td author = Wang, Changjian title = Features and drivers for energy-related carbon emissions in mega city: The case of Guangzhou, China based on an extended LMDI model date = 2019-02-11 keywords = China; Guangzhou; LMDI summary = title: Features and drivers for energy-related carbon emissions in mega city: The case of Guangzhou, China based on an extended LMDI model Based on the apparent energy consumption data, a systematic and comprehensive city-level total carbon accounting approach was established and applied in Guangzhou, China. g. Stochastic impacts by regression on population, affluence, and technology (STIRPAT) model) are the most commonly applied methods for the scientific evaluation and quantitative analysis of factors influencing city-level carbon emissions, especially the Logarithmic Mean Divisia Index (LMDI) method based on the IDA framework. [51] performed a multi-sectoral decomposition analysis of city-level greenhouse gas emissions in Tianjin from 2001 to 2009, including the agricultural, industrial, transportation, commercial and other sectors, and the results showed that economic growth was the most important driver for emissions increments while energy efficiency was primarily responsible for emissions reductions. doi = 10.1371/journal.pone.0210430 id = cord-356132-1nisyl5r author = Wang, Huiyao title = The psychological distress and coping styles in the early stages of the 2019 coronavirus disease (COVID-19) epidemic in the general mainland Chinese population: A web-based survey date = 2020-05-14 keywords = covid-19; psychological summary = The population with younger age (F = 102.04), unmarried (t = 15.28), with history of visiting Wuhan in the past month (t = -40.86), with history of epidemics occurring in the community (t = -10.25), more concern with media reports (F = 21.84), perceived more impacts of the epidemic outbreak (changes over living situations, F = 331.71; emotional control, F = 1863.07; epidemic-related dreams, F = 1642.78) and negative coping style (t = 37.41) had higher level of psychological distress. The general mainland Chinese population with unmarried, history of visiting Wuhan in the past month, perceived more impacts of the epidemic and negative coping style had higher level of psychological distress in the early stages of COVID-19 epidemic. Unmarried, history of visiting Wuhan, more serious changes over living situations, more difficult of emotional control, higher frequency of epidemic-related dreams, and negative coping style in the general population showed higher level of psychological distress. doi = 10.1371/journal.pone.0233410 id = cord-354547-eomm1sl5 author = Wang, Jibin title = Interaction of the Coronavirus Infectious Bronchitis Virus Membrane Protein with β-Actin and Its Implication in Virion Assembly and Budding date = 2009-03-16 keywords = Fig; IBV; protein summary = title: Interaction of the Coronavirus Infectious Bronchitis Virus Membrane Protein with β-Actin and Its Implication in Virion Assembly and Budding In this study, we report that interaction between coronavirus membrane protein (M) and actin with functional implication in facilitating virion assembly and budding. Similarly, analysis of cells expressing the M protein either on its own or together with the Myc-tagged actin by Western blot with anti-M polyclonal antibodies showed the detection of the full-length glycosylated (two upper bands) and unglycosylated (25 kDa) forms of the M protein (Fig. 2, lanes 5 and 6) . In cells transfected with both wild type and MD5 constructs with or without IBV infection, detection of similar amounts of M protein was observed (Fig. 5b, top two panels, lanes 1 and 2) , suggesting that both constructs were expressed at similar efficiencies. doi = 10.1371/journal.pone.0004908 id = cord-281161-u896icp9 author = Wang, Jing title = The Adjuvanticity of an O. volvulus-Derived rOv-ASP-1 Protein in Mice Using Sequential Vaccinations and in Non-Human Primates date = 2012-05-17 keywords = ASP-1; SARS; adjuvant; mouse; rOv summary = We previously reported that the Onchocerca volvulus recombinant protein rOv-ASP-1 can induce activation and maturation of naïve human DCs and therefore could be used as an innate adjuvant to promote balanced Th1 and Th2 responses to bystander vaccine antigens in mice. As shown in Table 2 , similar IgG1 and IgG2a humoral immune responses against the influenza viruses were induced in the mice vaccinated previously with rRBD plus rOv-ASP-1 adjuvant and those administered with PBS only. As shown in Table 3 , all of the NHPs vaccinated with rRBD protein plus 50 mg (n = 2), 100 mg rOv-ASP-1 (n = 2) or 500 mg CpG (n = 1) as the adjuvant developed RBDspecific IgG antibody response with increasing antibody level after each boost. Secondly, using two concentration of the rOv-ASP-1 adjuvant, 50 or 100 mg, and rRBD as the vaccine antigen, we were able to induce after three immunizations high titers of neutralizing antibodies (1:3,500-1:6,392) that much exceed what is needed for protection against SARS-CoV infection in vivo (.1:500) [56] . doi = 10.1371/journal.pone.0037019 id = cord-355874-nz6eqcdb author = Wang, Le title = A GeXP-Based Assay for Simultaneous Detection of Multiple Viruses in Hospitalized Children with Community Acquired Pneumonia date = 2016-09-14 keywords = CAP; PCR summary = title: A GeXP-Based Assay for Simultaneous Detection of Multiple Viruses in Hospitalized Children with Community Acquired Pneumonia In this study, we used the GeXP-based assay for simultaneous detection of 20 types/subtypes of viruses in 1699 nasopharyngeal specimens collected from hospitalized children with CAP. To evaluate the sensitivity of the GeXP assay, nucleic acid from all 20 target viruses and the internal control pcDNA3.1 (+) DNA were mixed to make the template pool. In the present study, we applied multiplex RT-PCR together with automated capillary electrophoresis, namely the GeXP-based assay, to detect virus in 1699 nasopharyngeal specimens from hospitalized children with CAP. We showed that the GeXP-based assay had high sensitivity and specificity for simultaneous detection of multiple viruses, and about 65% of cases tested were positive for virus. The development of a GeXP-based multiplex reverse transcription-PCR assay for simultaneous detection of sixteen human respiratory virus types/ subtypes doi = 10.1371/journal.pone.0162411 id = cord-000140-5kapn32k author = Wang, Pei-Gang title = Efficient Assembly and Secretion of Recombinant Subviral Particles of the Four Dengue Serotypes Using Native prM and E Proteins date = 2009-12-15 keywords = dv1; figure summary = METHODOLOGY/PRINCIPAL FINDINGS: We have used a codon optimization strategy to obtain an efficient expression of native viral proteins and production of recombinant subviral particles (RSPs) for all four dengue virus (DV) serotypes. Pulse chase experiment showed that 8 hours are required for the secretion of DV1 RSPs. We have used HeLa-prME to develop a semi-quantitative assay and screened a human siRNA library targeting genes involved in membrane trafficking. Our data demonstrate that newly synthesized proteins need 8 hours to be translocated through the secretory pathway and released into the supernatant as mature RSPs. To further characterize secreted DV1 RSPs, we performed sucrose gradient fractionation on RSPs concentrated from supernatant of HeLa-prME cells. To identify host factors that could either enhance or reduce production of DV RSPs, we first developed a quantitative assay to relatively quantify levels of secreted particles in supernatant of HeLa-prME cells. doi = 10.1371/journal.pone.0008325 id = cord-324410-be2ith3z author = Wang, Qi title = Accurate Reproduction of 161 Small-Molecule Complex Crystal Structures using the EUDOC Program: Expanding the Use of EUDOC to Supramolecular Chemistry date = 2007-06-13 keywords = EUDOC; crystal; structure summary = These results demonstrate the significant influence of crystal packing on small molecule complexation and suggest that EUDOC is able to predict small-molecule complexes and that it is useful for the design of new materials, molecular sensors, and multimeric inhibitors of protein-protein interactions. To expand the application of the EUDOC program to supramolecular chemistry, we tested its ability to reproduce the crystal structures of small-molecule guest-host complexes. Herein we report the results of our docking studies with 161 selected crystal structures of small-molecule guest-host complexes using the EUDOC program. These results show that the program is able to reproduce all 161 crystal structures and that the average interaction energy of these small-molecule complexes (250.1 kcal/mol) is nearly half of that of the 153 small molecule-bound protein complexes we studied in previous tests (2108.5 kcal/mol). The results also demonstrate the significant influence of crystal packing on small-molecule complex crystal structures and suggest that the EUDOC program is able to predict 3D structures of small-molecule guest-host complexes with reasonable reliability. doi = 10.1371/journal.pone.0000531 id = cord-296691-cg463fbn author = Wang, Ren title = De novo Sequence Assembly and Characterization of Lycoris aurea Transcriptome Using GS FLX Titanium Platform of 454 Pyrosequencing date = 2013-04-09 keywords = Amaryllidaceae; Lycoris; alkaloid; sequence summary = title: De novo Sequence Assembly and Characterization of Lycoris aurea Transcriptome Using GS FLX Titanium Platform of 454 Pyrosequencing Based on our sequence analysis and published literatures, many putative genes involved in Amaryllidaceae alkaloids synthesis, including PAL, TYDC OMT, NMT, P450, and other potentially important candidate genes, were identified for the first time in this Lycoris. They have played significant roles in functional genomics research for discovery of novel genes together with identifying different protein groups (e.g. proteins with signal peptides) other than the whole genome [27] [28] [29] , developing SSRs and SNPs markers [30] [31] [32] [33] [34] , allowing large-scale expression analysis [35] , improving genome annotation [36] , and elucidating phylogenetic relationships [37] . Hence, determination of the genetic pathways and specific genes involved in Amaryllidaceae alkaloids biosynthesis and some other aspects of Lycoris could be beneficial for humans and enrich our knowledge and understanding of functional genomics and biological research. doi = 10.1371/journal.pone.0060449 id = cord-296435-6dergkha author = Wang, Tiehua title = Thrombocytopenia Is Associated with Acute Respiratory Distress Syndrome Mortality: An International Study date = 2014-04-14 keywords = ARDS; Beijing; Boston; ICU summary = doi = 10.1371/journal.pone.0094124 id = cord-265138-i5m3ax7g author = Wang, Xi-Ling title = Model Selection in Time Series Studies of Influenza-Associated Mortality date = 2012-06-20 keywords = GCV; Poisson; influenza summary = METHODS: We assessed four model selection criteria: quasi Akaike information criterion (QAIC), quasi Bayesian information criterion (QBIC), partial autocorrelation functions of residuals (PACF), and generalized cross-validation (GCV), by separately applying them to select the Poisson model best fitted to the mortality datasets that were simulated under the different assumptions of seasonal confounding. CONCLUSIONS: GCV criterion is recommended for selection of Poisson models to estimate influenza-associated mortality and morbidity burden with proper adjustment for confounding. Four model selection criteria were considered in this study: quasi Akaike information criterion (QAIC), quasi Bayesian information criterion (QBIC), partial autocorrelation functions of residuals (PACF), and generalized cross-validation (GCV). Two recent studies in Canada and Hong Kong have demonstrated the estimates of influenza-associated hospitalization derived from Poisson regression models reasonably matched the numbers of patients with laboratory confirmed influenza infections [17, 29] . doi = 10.1371/journal.pone.0039423 id = cord-267189-xq70rn1j author = Wang, Xinyu title = Co-Circulation of Canine Coronavirus I and IIa/b with High Prevalence and Genetic Diversity in Heilongjiang Province, Northeast China date = 2016-01-15 keywords = CCoV; China; strain summary = To trace the evolution of canine coronavirus (CCoV), 201 stool samples from diarrheic dogs in northeast China were subjected to reverse transcription-polymerase chain reactions (RT-PCRs) targeting the partial M and S genes of CCoV, followed by an epidemiological analysis. Our data provide evidence that CCoV-I, CCoV-IIa, and CCoV-IIb strains co-circulate in the diarrhoetic dogs in northeast China, high co-infection rates with CaKV and CPV-2 were observed, and the CCoV-II strains exhibited high prevalence and genetic diversity. A phylogenetic analysis using partial S gene sequences demonstrated that the 26 CCoV-IIa strains were closely related to three reference strains, 5281 (Japan), TN-449 (USA), and 1086-IIa (Brazil), and differed genetically from reference strains from China and other countries (Fig 2A) . This result demonstrated that vaccination for other canine viruses did not effect CCoV infections in the dog population in Heilongjiang province, northeast China. doi = 10.1371/journal.pone.0146975 id = cord-002043-z1b7pj3s author = Wang, Xue-Yang title = Comparative Transcriptome Analysis of Bombyx mori (Lepidoptera) Larval Midgut Response to BmNPV in Susceptible and Near-Isogenic Resistant Strains date = 2016-05-11 keywords = BC9; BmNPV; Bombyx; Fig; P50; infection summary = obtained numerous differentially expressed genes (DEGs) involved in metabolism, immunity, and inflammatory responses in Microtus fortis following infection with Schistosoma japonicum based on comparative transcriptome analysis [20] . reported that several genes related to physical barriers, immune response, proteolytic/metabolic enzymes, heat-shock proteins, and hormonal signaling were possibly involved in silkworm resistance against Bombyx mori cytoplasmic polyhedrosis virus (BmCPV) infection; although these genes might be induced by the virus in order to increase infectivity [21] . After BmNPV infection, the expression levels of 4 genes were down-regulation in BC9 and A35 (resistant strain) (Fig 6) , which was consistent with the transcriptome data. Based on their role in apoptosis activation, hosts need to increase the expression level of these genes to promote apoptosis when exposed to a virus; this supposition explains the up-regulation of genes involved in apoptosis in the transcriptome following BmNPV infection. doi = 10.1371/journal.pone.0155341 id = cord-001343-3euy4u9k author = Wang, Yadong title = A Multi-Method Approach to Curriculum Development for In-Service Training in China’s Newly Established Health Emergency Response Offices date = 2014-06-27 keywords = China; Health; hero summary = In recognition of the national need for an in-service program to target the''''level four'''' health staff as defined by WADEM, i.e.''h ealth workers who played lead roles in disaster health management'''' [20] , China''s Ministry of Health (MoH) commissioned the Capital Medical University in 2010 to develop and implement a competency-based curriculum to help strengthen the performance of the new cadre of HERO staff. We assessed tasks, roles and responsibilities, and training needs of HERO staff through face-to-face interviews of eleven experienced key informants; they included health emergency experts from the government, the military and the academic sector, and senior staff of HEROs. We also explored their awareness of existing training activities and the associated relative strengths and weaknesses, their preferences on modes of curriculum delivery and the optimal duration of in-service training. doi = 10.1371/journal.pone.0100892 id = cord-000851-uylgyhs8 author = Wang, Zhenya title = Inhibitory Influence of Enterococcus faecium on the Propagation of Swine Influenza A Virus In Vitro date = 2013-01-07 keywords = Fig; MDBK summary = faecium caused a modified cellular expression of selected mediators of defence in 3D4-cells: while the expression of TNF-α, TLR-3 and IL-6 were decreased in the SwIV-infected and probiotic treated cells, IL-10 was found to be increased. The results from quantitative RT-PCR shown in Fig. 5 reveal a decreased expression of these mediators when compared to the non-treated samples (SwIV-infected 3D4/21-cells without E. faecium effectively protects host cells from swine influenza virus infection and are in support of the above author''s hypothesis, that probiotics are not only useful to inhibit enteric viruses, but may also have potential for the control of respiratory viruses. faecium before SwIV-infection and a 1 h treatment after completion of virus infection also led to a 2-3 log-unit loss of virus titer, the probiotic must alter host cell factors which apparently results in an inhibition of influenza virus multiplication. faecium in SwIV-infected 3D4/21 cells, the reduced inflammatory response caused by some cytokines at the cellular level may contribute to the antiviral effect of the probiotic. doi = 10.1371/journal.pone.0053043 id = cord-354000-jxqskt4k author = Warren, Cody J. title = The Antiviral Restriction Factors IFITM1, 2 and 3 Do Not Inhibit Infection of Human Papillomavirus, Cytomegalovirus and Adenovirus date = 2014-05-14 keywords = HPV; IFN; dna; ifitm1 summary = Here, we demonstrate that IFN-α or -β treatment of keratinocytes substantially decreases human papillomavirus 16 (HPV16) infection while robustly inducing IFITM1, 2 and 3 expression. IFITM protein expression induced by type I IFN inhibits infection of many RNA viruses [22] [23] [24] [25] [26] [27] [28] [29] [30] . Therefore, we analyzed induction of IFITM1, 2 and 3 expression by IFN-b treatment in human keratinocytes, the natural host cells for HPV. To determine the effect of IFITMs on HPV16 entry, HeLa cells stably expressing c-Myc-tagged IFITM1, 2 or 3 or with vector alone ( Fig. 2A-B) were infected with HPV16-LucF. Using various epithelial cell lines and primary keratinocytes expressing IFITMs, we show that HPV infection is surprisingly enhanced by IFITM1 and IFITM3 overexpression (Fig. 2) . Taken together, our results suggest that HPV and other DNA viruses may have evolved to avoid IFITM1, 2 and 3 restriction during entry into host cells. doi = 10.1371/journal.pone.0096579 id = cord-001599-pfdnmzx2 author = Wee, Yin Shen title = Age-Related Onset of Obesity Corresponds with Metabolic Dysregulation and Altered Microglia Morphology in Mice Deficient for Ifitm Proteins date = 2015-04-09 keywords = Fig; Ifitm; IfitmDel; Poly summary = Analysis of the gene expression profiles in the hypothalamus of IfitmDel animals, compared to WT, demonstrated an altered ratio of Pomc and Npy neuropeptide expression, which likely impairs the satiation response of the IfitmDel animal leading to an increased eating behavior. As we maintain these animals as homozygous deletion lines, over time we have observed a pronounced enhanced weight gain and an obesity phenotype (e.g., [21] [22] [23] ) in older IfitmDel mice compared to C57BL/6 controls. In this report we quantify the obesity phenotype and link this to altered leptin/neuropeptide signaling, and demonstrate abnormal microglia morphology in the IfitmDel animal. Based upon the previously described findings that the absence of the Ifitm proteins can alter cellular induction pathways following type I interferon treatment, we tested whether or not the IfitmDel animals would have an altered response, compared to WT, to chronic Poly I:C treatment. doi = 10.1371/journal.pone.0123218 id = cord-308764-9z4qcoqz author = Wei, Lin title = Transcriptome Analysis of Houttuynia cordata Thunb. by Illumina Paired-End RNA Sequencing and SSR Marker Discovery date = 2014-01-02 keywords = Houttuynia; Illumina; SSR; cordata summary = cordata to generate an enormous transcriptome sequence dataset for gene discovery and molecular marker development. cordata; 43 (86%) produced fragments of expected size, suggesting that the unigenes were suitable for specific primer design and of high quality, and the SSR marker could be widely used in marker-assisted selection and molecular breeding of H. cordata and used Illumina paired-end sequencing technology to generate a large-scale EST database and develop a set of SSR markers. For further assessment of the assembly quality and development of new molecular markers, all 63,954 unigenes generated in this study were used to mine potential microsatellites, which were defined as di-to hexa-nucleotide SSRs with a minimum of four repetitions for all motifs. Here, the N50 length of the unigenes was 1,051 bp and the average length was 679 bp, which suggests that the relatively short reads from Illumina paired-end sequencing for this non-model organism have been effectively and accurately assembled. doi = 10.1371/journal.pone.0084105 id = cord-048446-gaemgm0t author = White, Laura Forsberg title = Transmissibility of the Influenza Virus in the 1918 Pandemic date = 2008-01-30 keywords = estimate; number summary = doi = 10.1371/journal.pone.0001498 id = cord-002889-fie121ns author = White, Michael title = Development of improved therapeutic mesothelin-based vaccines for pancreatic cancer date = 2018-02-23 keywords = MVA; cell; mesothelin; panc02 summary = Human and mouse mesothelin share sequence similarity, expression patterns, and biochemical characteristics, [7] , and the homeostatic function of mesothelin in mammals is unknown: the gene can be deleted without apparent effect in mice PLOS C57Bl6 mice and thus can be grown in syngeneic mice to allow for study of an anti-tumor immune response in an immunocompetent mouse model. In order to create a putative therapeutic anti-mesothelin vaccine, we inserted the mouse mesothelin gene into the poxvirus MVA genome under a viral promoter so that mesothelin would be expressed in any cells infected with the recombinant virus. To determine whether the viruses expressing mesothelin protein were able to induce an immune response in mice, we first attempted to measure anti-mesothelin antibody in vaccinated mouse sera. In comparison, there were very few spots (1-3) in response to stimulation with Lewis Lung cells that do not express mouse mesothelin, and mice vaccinated with MVA, MVAmeso and MVAmesoA35Del viruses all had good responses to restimulation with vaccinia virus (124, 147, and 148 spots respectively). doi = 10.1371/journal.pone.0193131 id = cord-299953-sasfvcun author = Whitehead, Ashley B. R. title = Burden of exposure to infectious bursal disease virus, infectious bronchitis virus, Newcastle disease virus, Mycoplasma gallisepticum, and intestinal parasites in introduced broiler chickens on the Galapagos date = 2018-09-24 keywords = Cruz; Galapagos; Santa summary = The objective of the study reported here was to measure the burden of exposure to infectious bursal disease virus (IBDV), infectious bronchitis virus (IBV), Newcastle disease virus (NDV), Mycoplasma gallisepticum (MG), and intestinal parasites in a sample of broiler chickens on 13 farms on Santa Cruz Island and San Cristobal Island in July 2017. Study results are relevant because (i) they provide new baseline data on the burden of exposure to avian pathogens in broiler farms, (ii) justify the need to verify standard operating procedures in hatcheries that supply (non-vaccinated) day-old chicks to the Galapagos and (iii) to implement enhanced biosecurity standards on broiler chicken farms to mitigate risk of disease transmission between broilers, backyard poultry, and wild birds on the Galapagos. doi = 10.1371/journal.pone.0203658 id = cord-253436-dz84icdc author = Wille, Michelle title = High Prevalence and Putative Lineage Maintenance of Avian Coronaviruses in Scandinavian Waterfowl date = 2016-03-03 keywords = Scaup; sequence summary = In this study we screened 764 samples from 22 avian species of the orders Anseriformes and Charadriiformes in Sweden collected in 2006/2007 for CoV, with an overall CoV prevalence of 18.7%, which is higher than many other wild bird surveys. Coronavirus sequences from Mallards in this study were highly similar to CoV sequences from the sample species and location in 2011, suggesting long-term maintenance in this population. Despite few studies, small samples sizes and differences in prevalence, what is clear, is that in the Northern Hemisphere waterfowl species, especially dabbling and diving ducks are important in the epidemiology of avian CoVs. It is interesting to note that these patterns are very similar to those found in low pathogenic influenza A viruses: high prevalence in waterfowl and gulls in the Northern Hemisphere [30] , and little host species and temporal structuring within waterfowl derived viruses in the conserved polymerase genes (such as PB2, PB1) [31] . doi = 10.1371/journal.pone.0150198 id = cord-338594-wft7yy6j author = Winkler, Michael title = Rhesus macaque IFITM3 gene polymorphisms and SIV infection date = 2017-03-03 keywords = HIV-1; IFITM3; SIV; polymorphism summary = In particular, polymorphisms of the human IFITM3 gene have been shown to affect disease severity and progression in influenza A virus (FLUAV) and human immunodeficiency virus (HIV) infection, respectively. Employing previously characterized samples from two cohorts of SIV-infected rhesus macaques, we investigated the relationship between these rhIFITM3 polymorphisms and both AIDS-free survival time and virus load. Polymorphisms in several immune-relevant gene loci such as MHC or KIR are associated with the transmission and course of disease in SIV infected rhesus macaques and HIV-1 infected humans [36, 37] . Immune-related IFITM proteins have been established as important antiviral effectors of the interferon response, and a polymorphism in the human IFITM3 gene has been found to be associated with disease severity and progression in FLUAV and HIV-1 infection [27, 33] . Notably, all polymorphism in the coding region were silent and strong evidence for an association of rhIFITM3 polymorphisms with disease progression and viral load in SIV infected animals was not obtained. doi = 10.1371/journal.pone.0172847 id = cord-312817-gskbu0oh author = Witte, Carmel title = Spatiotemporal network structure among “friends of friends” reveals contagious disease process date = 2020-08-06 keywords = bird; friend; network summary = These results provide empirical evidence that at least some avian mycobacteriosis infections are transmitted between birds, and provide new methods for detecting contagious processes in large-scale global network structures with indirect contacts, even when transmission pathways, timing of cases, or etiologic agents are unknown. Thus, the population represents a group of birds for which 1) a near-complete social network could be assembled from housing records that tracked dynamic movement over time, and 2) avian mycobacteriosis disease status could be determined for any bird that died. Although disease clustering among friends of friends could represent a contagious process, there is a possibility that some of the association could be explained by homophily, i.e., that connected birds could be more alike than the general bird population in terms of species, behavior, susceptibility, enclosure characteristics, etc. For this test, we evaluated disease clustering between a subject and its friends of friends from different enclosures that could not have transmitted infection based on the timing of the contact. doi = 10.1371/journal.pone.0237168 id = cord-351387-i0zamkpd author = Witte, Katrin title = The Pelargonium sidoides Extract EPs 7630 Drives the Innate Immune Defense by Activating Selected MAP Kinase Pathways in Human Monocytes date = 2015-09-25 keywords = IL-10; IL-6; Pelargonium; TNF summary = In summary, we demonstrate that EPs 7630 activates human monocytes, induces MAP kinase-dependent pro-inflammatory cytokines in these cells, and specifically modulates their production capacity of mediators known to lead to an increase of acute phase protein production in the liver, neutrophil generation in the bone marrow, and the generation of adaptive Th17 and Th22 cells. In the first setting, PBMCs were stimulated with EPs 7630 (3 and 30 μg/ml), Escherichia coli 0127:B8 lipopolysaccharide (TLR4 ligand; 100 ng/ml; Sigma-Aldrich), polyinosinic-polycytidylic acid [poly (I:C); 10 μg/ml; Sigma-Aldrich], a cytokine mixture of IL-1β, IL-2 and IL-12 (10 ng/ml each; R&D systems), anti-CD3 (Orthoclone; Cilag) and anti-CD28 (R&D systems) monoclonal antibodies (1 μg/ml each), or were left without specific treatment (0.1% ethanol as solvent control) for 4 and 24 h, before cell culture supernatant was recovered for ELISA cytokine production analysis. Our data show that EPs 7630 strongly and dose-dependently induced the production of the pro-inflammatory cytokines TNF-α and IL-6 in human blood immune cells. doi = 10.1371/journal.pone.0138075 id = cord-000269-v4jochbe author = Wittekindt, Nicola E. title = Nodeomics: Pathogen Detection in Vertebrate Lymph Nodes Using Meta-Transcriptomics date = 2010-10-18 keywords = Acinetobacter; Helicobacter; RNA; dna summary = cDNA libraries from five individuals and two pools of samples were prepared from retropharyngeal lymph node RNA enriched for polyadenylated RNA and sequenced using Roche-454 Life Sciences technology. Representatives of all bacterial phyla were detected in the seven libraries based on protein-coding transcripts indicating that viable microbiota were present in lymph nodes. Based on detection of both rRNA and protein-coding transcripts, we identified two new proteobacterial species; a Helicobacter closely related to Helicobacter cetorum in the Helicobacter pylori/Helicobacter acinonychis complex and an Acinetobacter related to Acinetobacter schindleri. The microbial community of mule deer lymph nodes Detection of protein-coding and ribosomal RNA transcripts provides strong support for the presence of viable and replicating microorganisms. As an alternative approach to identifying bacterial microorganisms present in lymph node tissue, we utilized amplicon DNA library sequencing technology. doi = 10.1371/journal.pone.0013432 id = cord-292777-oztmw8jo author = Wong, Michelle title = Microbial Translocation Contribute to Febrile Episodes in Adults with Chemotherapy-Induced Neutropenia date = 2013-07-16 keywords = FUO; concentration; endotoxin summary = In this study we sought to determine the contribution of microbial translocation to febrile episodes with no attributable microbiological cause (Fever of Unknown Origin, FUO) in an adult febrile neutropaenic cohort. In this study we thus sought to determine the contribution of microbial translocation to FUO episodes in an adult febrile neutropaenic cohort using endotoxin and sCD14 concentrations in the plasma as markers for microbial translocation. In this cohort of iatrogenic neutropaenic adults, we found elevated plasma levels of endotoxin and sCD14 in febrile neutropaenic episodes where no other microbiological findings have been documented, implicating microbial translocation as a potential contributor towards their febrile status. Adding to the field, we have, in our study, in addition to measuring plasma endotoxin concentrations, also measured the host receptor for LPS, sCD14 in an attempt to determine the contribution of microbial translocation to fever as a clinical outcome. doi = 10.1371/journal.pone.0068056 id = cord-336615-jfnj6l41 author = Wong, Sarah Sze Wah title = In Vitro and In Vivo Activity of a Novel Antifungal Small Molecule against Candida Infections date = 2014-01-22 keywords = Candida; SM21 summary = We screened a library of 50,240 small molecules for inhibitors of yeast-to-hypha transition, a major virulence attribute of Candida albicans. Further examination of the in vitro antifungal and anti-biofilm properties of these compounds, using a range of Candida spp., led to the discovery of SM21, a highly potent antifungal molecule (minimum inhibitory concentration (MIC) 0.2 – 1.6 µg/ml). In vitro, SM21 was toxic to fungi but not to various human cell lines or bacterial species and was active against Candida isolates that are resistant to existing antifungal agents. Second, the increased incidence of invasive candidiasis caused by non-albicans Candida (NAC) species, such as Candida glabrata, Candida tropicalis, Candida krusei or Candida parapsilosis, has been a major concern [13, 14] , because these infections are often associated with higher mortality and antifungal resistance than those caused by C. The antifungal activity of small molecules was assessed by disk diffusion and broth dilution assays (see below) using four groups of Candida isolates. doi = 10.1371/journal.pone.0085836 id = cord-001620-yy5gq0ki author = Woo, Hye-Min title = Isolation of Single-Stranded DNA Aptamers That Distinguish Influenza Virus Hemagglutinin Subtype H1 from H5 date = 2015-04-22 keywords = Fig; GST; H1-HA1 summary = These results indicate that the selected aptamers that distinguish H1-HA1 from H5-HA1 can be developed as unique probes for the detection of the H1 subtype of influenza virus. Subtype H5 is known as highly pathogenic in protein (GST-H5-HA1) was incubated with 100 μL of glutathione agarose beads in 100 μL of binding buffer (50 mM Tris/HCl; pH 8.0, 150 mM NaCl, 1.5 mM MgCl 2 , 2 mM DTT, and 1% [w/v] BSA) for 30 min at room temperature with occasional shaking. To select specific ssDNA aptamers that can distinguish H1-HA1 from H5-HA1, counter-SELEX was performed with an ssDNA library of 88-mers containing a randomized sequence region of 45 nucleotides in the center, followed by lambda exonuclease digestion, as shown in Fig 1A. To confirm that the selected aptamers were bound to the sialic acid-binding region of HA1, we performed a flow cytometry analysis (Fig 7) . doi = 10.1371/journal.pone.0125060 id = cord-002890-g7aje88u author = Wood, Paul L. title = Lipidomic analysis of immune activation in equine leptospirosis and Leptospira-vaccinated horses date = 2018-02-23 keywords = DAG; Leptospira; horse; serum summary = In this study, we undertook a lipidomics approach to determine if there are any differences in the serum lipid profiles of horses naturally infected with pathogenic Leptospira spp. Utilizing a high-resolution mass spectrometry serum lipidomics analytical platform, we demonstrate that cyclic phosphatidic acids, diacylglycerols, and hydroperoxide oxidation products of choline plasmalogens are elevated in the serum of naturally infected as well as vaccinated horses. In this study, we asked if differences in host''s responses to live, multiplying Leptospira versus killed leptospires, present in the vaccine, are reflected in the serum lipidome of these two groups of horses. Our results show that serum levels of cyclic phosphatidic acids (cPA), diacylglycerols, and hydroperoxide oxidation products of choline plasmalogens were elevated in both vaccinated and naturally infected horses. Our data indicate that the immune response induced by vaccination has a more dramatic effect than leptospiral infection on sphingomyelin synthesis in horses. doi = 10.1371/journal.pone.0193424 id = cord-335859-k37jivp6 author = Wu, Daphne C. title = Predictors of self-reported symptoms and testing for COVID-19 in Canada using a nationally representative survey date = 2020-10-21 keywords = COVID; SARS summary = To understand the socio-demographic predictors of COVID symptoms, we conducted a logistic regression analysis where the outcome was self-reported symptoms suggestive of COVID infection which we defined in this study as the respondent reporting himself/herself and/or at least one member of the household having had a combination of fever (with or without hallucinations) and any of i) difficulty breathing/shortness of breath or ii) dry cough so severe that it disrupts sleep or iii) a loss of a sense of smell in the past month; and the explanatory variables were gender (male, female, or other), education level (high school and under, or some college/ university and higher), province, age, ethnicity (Indigenous, English and other European, or others), visible minority (defined as persons, other than Aboriginal peoples, who are nonwhite in race or colour) [6] , and number of household members. doi = 10.1371/journal.pone.0240778 id = cord-003377-9vkhptas author = Wu, Tong title = The live poultry trade and the spread of highly pathogenic avian influenza: Regional differences between Europe, West Africa, and Southeast Asia date = 2018-12-19 keywords = ECOWAS; H5N1; Model summary = title: The live poultry trade and the spread of highly pathogenic avian influenza: Regional differences between Europe, West Africa, and Southeast Asia We focus on the role played by the live poultry trade in the spread of H5N1 across three regions widely infected by the disease, which also correspond to three major trade blocs: the European Union (EU), the Economic Community of West African States (ECOWAS), and the Association of Southeast Asian Nations (ASEAN). The indicator for wild bird habitat used in this study was the set of "Important Bird and Biodiversity Areas" (IBAs) for "migratory and congregatory waterbirds" identified by BirdLife The live poultry trade poses different avian influenza risks in different regions of the world Table 1 . Our first specification (Model 1) included a number of factors related to disease risk but excluded both live poultry imports and biosecurity measures. doi = 10.1371/journal.pone.0208197 id = cord-340387-ohkjheat author = Wynne, James W. title = Purification and Characterisation of Immunoglobulins from the Australian Black Flying Fox (Pteropus alecto) Using Anti-Fab Affinity Chromatography Reveals the Low Abundance of IgA date = 2013-01-07 keywords = Fig; Protein; SDS summary = title: Purification and Characterisation of Immunoglobulins from the Australian Black Flying Fox (Pteropus alecto) Using Anti-Fab Affinity Chromatography Reveals the Low Abundance of IgA To further understand the antibody response of bats, the present study purified and characterised the major immunoglobulin classes from healthy black flying foxes, Pteropus alecto. Considering that in other mammalian species, immunoglobulins IgG, IgM and IgA are present in relatively high abundance in serum and tissues, we anticipated that bats would possess a similar immunoglobulin profile. IgG-depleted samples were fractionated by affinity chromatography on immobilised anti-Fab-specific antibodies adopting the same procedure as that described for immobilised Protein A and G except that the binding and washing buffer consisted of 0.3 M NaCl in 50 mM phosphate buffer, pH 7.4. Two major bands were detected by reducing SDS-PAGE in the eluate from both serum and plasma samples; a 66-70 kDa band representative of IgM H , and a 25 kDa band representative of immunoglobulin light chain ( Fig. 3A and 3B ). doi = 10.1371/journal.pone.0052930 id = cord-309471-lr68epyb author = Xia, Jingya title = Virus-Specific Immune Memory at Peripheral Sites of Herpes Simplex Virus Type 2 (HSV-2) Infection in Guinea Pigs date = 2014-12-08 keywords = ASC; HSV; hsv-2; specific summary = Memory B cells were detected primarily in the spleen and to a lesser extent in bone marrow but not in the genital tract or neural tissues suggesting that the HSV-specific antibody-secreting cells present at peripheral sites of HSV-2 infection represented persisting populations of plasma cells. The presence of memory B cells in the culture is therefore detected as a TLR-agonist-induced increase in the number of antigen-specific, ASCs. To test for the presence of memory B cells at peripheral tissues, we stimulated lymphocyte populations isolated from bone marrow, spleen, vagina/cervix, or spinal cord/sensory ganglia of previously infected guinea pigs with a combination of LPS and CpG oligonucleotides and quantified HSV-specific ASC by ELISPOT. On day 7 post infection, HSV-specific, IFN-c-secreting T cells from the spleen, vagina/cervix, and lumbosacral ganglia and the adjacent spinal cord were quantified using a pair Peripheral Tissue-Resident Immune Memory to HSV-2 of previously described anti-guinea pig IFN-c -specific monoclonal antibodies [27] in an IFN-c ELISPOT assay. doi = 10.1371/journal.pone.0114652 id = cord-299491-8rfm0jxh author = Xiao, Shenglan title = Role of fomites in SARS transmission during the largest hospital outbreak in Hong Kong date = 2017-07-20 keywords = File; SARS summary = Like many other respiratory viruses, the SARS-CoV is suspected to spread from an infected person to the susceptible via three basic transmission routes, i.e., the long-range airborne, close contact and fomite routes [14] [15] [16] , as shown in Fig 1. Several studies have proposed probable evidence for the airborne spread of the SARS-CoV based on the consistencies between bio-aerosol concentration distributions and reported attack rates [19] [20] [21] , but no mechanism-based investigations exist for the fomite route. To investigate the role the fomite route plays in SARS-CoV transmission, we conducted a detailed modelling study of the largest hospital outbreak in Hong Kong [20] , in which the distribution of reported attack rates of inpatients showed a statistically significant spatial pattern. A multi-agent model ( Fig 2) was developed to simulate the possible spread of the viruses from the index patient to the susceptible by air flow and surface touching, and to calculate the possible exposure doses and infection risks for each hypothesis. doi = 10.1371/journal.pone.0181558 id = cord-298131-zolwjl9u author = Xiao, Shuqi title = Understanding PRRSV Infection in Porcine Lung Based on Genome-Wide Transcriptome Response Identified by Deep Sequencing date = 2010-06-29 keywords = IFN; PRRSV; figure; gene; infection summary = Upregulation expression of virus-induced pro-inflammatory cytokines, chemokines, adhesion molecules and inflammatory enzymes and inflammatory cells, antibodies, complement activation were likely to result in the development of inflammatory responses during N-PRRSV infection processes. To investigate the regulation of the host response to the N-PRRSV virus, we considered the global gene expression profiles in lungs using Solexa/Illumina''s DGE system, a tag-based transcriptome sequencing method. From the data presented in the paper, a model for the relationship between pulmonary gene expression profiles and infection pathology can be surmised in Figure 7 , N-PRRSV virus replicates and spreads by subverting host innate immune response and hijacking host lipid metabolism as well as inducing an antiapoptotic and anti-inflammatory state, as indicated by suppression expression of SPI IFN, IFN-a, down-regulation expression of proapoptotic genes for BAK, APR-1, SARP3, high levels expression of genes involved in lipid metabolism, such as APOE, LDLB, PIK3C3, anti-apoptotic genes for MCL1, BCL2A1, CHFR, ADM, NFKB, IL10, and anti-inflammatory molecule PGE2 as well as CD163. doi = 10.1371/journal.pone.0011377 id = cord-000267-xroo7z7g author = Xiao, Xiaodong title = Human Anti-Plague Monoclonal Antibodies Protect Mice from Yersinia pestis in a Bubonic Plague Model date = 2010-10-13 keywords = anti summary = doi = 10.1371/journal.pone.0013047 id = cord-316853-vaea6siv author = Xie, Nanzhen title = Prevalence of depressive symptoms among nurses in China: A systematic review and meta-analysis date = 2020-07-07 keywords = chinese; nurse; prevalence summary = Therefore, the primary aim of this study is to quantitatively assess the prevalence of depressive symptoms in nurses from Chinese mainland and its primary related influencing factors by systematic review and meta-analysis. The following information was extracted from all included studies: title, year of publication, province, sample size, number of positive cases, diagnostic methods and other potential factors that may affect the prevalence of depressive symptoms in nurses and that was provided in the studies. In addition, subgroup analysis was performed based on other potential sources of heterogeneity, such as province, regions (Northwest, Southwest, Northeast, South, Central, East and North China), severity of depressive symptoms, department, gender, age, job title, marriage, education background, shift work and hospital grade (if available). doi = 10.1371/journal.pone.0235448 id = cord-350842-4m82l5t8 author = Xing, Jun title = Study of the mental health status of medical personnel dealing with new coronavirus pneumonia date = 2020-05-19 keywords = COVID-19; medical; personnel summary = Factors affecting the mental health and status of medical personnel based on their significance from high to low are: the degree of suspicion that they were infected when the novel coronavirusrelated symptoms occurred, the level of concern whether they and their family members have been infected, age, whether they have supported in affected areas in Hubei Province, designated hospitals, and other places for the novel coronavirus, and whether family members support them working on the front line (p < 0.05). The results of this study have shown that the factors affecting the mental health status of medical personnel based on the significance from high to low are: the degree of suspicion that they were infected when the novel coronavirus-related symptoms occurred, the level of concern whether they and their family members have been infected, age, whether they have supported in affected areas in Hubei Province, designated hospitals, and other places for the novel coronavirus, and whether their family members support them working on the front line. doi = 10.1371/journal.pone.0233145 id = cord-000460-h3owwjao author = Xiong, Jing title = Leukocyte- and Platelet-Derived Microvesicle Interactions following In Vitro and In Vivo Activation of Toll-Like Receptor 4 by Lipopolysaccharide date = 2011-09-26 keywords = LPS; TLR4; platelet summary = However, with LPS stimulation numbers of platelets staining positive for both plateletand leukocyte-specific antigens increased in blood derived from WT but not dTLR4 mice. Alternatively, comparable activation of leukocyte as well as platelet result in formation of cell-derived microvesicles (MV) which may contribute to increased thrombogenic propensity of the blood, pro-inflammatory immune processes and thus cardiovascular risk [15, 16, 17, 18, 19, 20, 21, 22] . Therefore, the present study was designed to test the hypothesis that acute exposure to a sentinel dose of LPS would induce MV production and exchange of specific proteins/ receptors between platelets and leukocytes via TLR4 activation. The acute effects of LPS on platelet and leukocyte activation were most likely mediated through activation of TLR4 as platelet positive leukocyte antigen was not observed in blood from dTLR4 mice. Platelet-leukocyte interactions require TLR4 signaling as the dual antigen positivity of platelets was observed in blood derived from wild type but not dTLR4 mice. doi = 10.1371/journal.pone.0025504 id = cord-330079-pdaowkop author = Xu, Lin title = Surveillance and Genome Analysis of Human Bocavirus in Patients with Respiratory Infection in Guangzhou, China date = 2012-09-11 keywords = HBoV; PCR; respiratory summary = To investigate the epidemiological and genetic variation of HBoV in Guangzhou, South China, we screened 3460 throat swab samples from 1686 children and 1774 adults with acute respiratory infection symptoms for HBoV between March 2010 and February 2011, and analyzed the complete genome sequence of 2 HBoV strains. In our current study, we screened throat swab specimens from patients with acute respiratory tract infection symptoms for HBoV and other common respiratory viruses over a 12-month period using polymerase chain reaction (PCR) methods, and in addition, the molecular phylogeny and complete genome sequences of 2 HBoV strains were also analyzed. Of the 3460 samples collected from patients with respiratory tract infection symptoms and signs enrolled in the study during the period between March 2010 and February 2011, detection for 7 viruses, namely, Influenza, PIV, RSV, HMPV, HCoV, AdV and HBoV, showed that 1275 (36.8%) were found positive for one single virus and 112 (3.2%) were infected by more than one virus. doi = 10.1371/journal.pone.0044876 id = cord-280482-o887a7q9 author = Xu, Suming title = Transgenic Mice Expressing MCP-1 by the Urothelium Demonstrate Bladder Hypersensitivity, Pelvic Pain and Voiding Dysfunction: A Multidisciplinary Approach to the Study of Chronic Pelvic Pain Research Network Animal Model Study date = 2016-09-29 keywords = BPS; LPS; MCP-1; URO summary = doi = 10.1371/journal.pone.0163829 id = cord-293072-giakcaki author = Xu, Wan-Xiang title = A simpler and more cost-effective peptide biosynthetic method using the truncated GST as carrier for epitope mapping date = 2017-10-12 keywords = BCE; Fig; dna; peptide summary = The protocol involves the following core steps: (i) design of plus and minus strands of DNA fragments encoding overlapping 8/18mer peptides; (ii) chemical synthesis of the designed DNA fragments; (iii) development of r-clones using pXXGST-3 vector expressing each 8/18mer peptide fused with truncated GST188 protein; (iv) screening r-clones by running the cell pellets from each induced clone on SDS-PAGE gel followed by sequencing of inserted DNA fragments for each verified r-clone; and (v) Western blotting with either monoclonal antibodies or polyclonal antibodies. doi = 10.1371/journal.pone.0186097 id = cord-000341-d3a06n3f author = Xu, Wanghui title = Screening of Random Peptide Library of Hemagglutinin from Pandemic 2009 A(H1N1) Influenza Virus Reveals Unexpected Antigenically Important Regions date = 2011-03-18 keywords = Fig; HA1; HA2 summary = doi = 10.1371/journal.pone.0018016 id = cord-331885-8zmuhebu author = Xu, Xiuyan title = Risk factor analysis combined with deep learning in the risk assessment of overseas investment of enterprises date = 2020-10-02 keywords = assessment; investment; risk summary = To evaluate the overseas investment risks of enterprises and expand the application and development of deep learning methods in risk assessment, 15 national clusters are utilized as samples to analyze and discuss the overseas investment risk indicators of enterprises. Second, the Deep Neural Network (DNN) is introduced; a risk evaluation model is constructed for enterprise overseas investment. The results show that the major source of overseas investment risks includes basic resources, political systems, economic and financial development, and environmental protection. To build a risk assessment model for overseas investment of enterprises and evaluate investment risks scientifically and effectively, the Deep Neural Network (DNN) based on deep learning is introduced, which is an innovation. The above analysis suggests that a country''s infrastructure, health care conditions, economic development level, environmental protection conditions, and political system are the key components that affect its risks of enterprise overseas investment [29, 30] . doi = 10.1371/journal.pone.0239635 id = cord-352200-i05h8csb author = Xu, Yi title = Transcriptome and Comparative Gene Expression Analysis of Sogatella furcifera (Horváth) in Response to Southern Rice Black-Streaked Dwarf Virus date = 2012-04-27 keywords = RNA; SRBSDV; WBPH; gene; virus summary = title: Transcriptome and Comparative Gene Expression Analysis of Sogatella furcifera (Horváth) in Response to Southern Rice Black-Streaked Dwarf Virus METHODOLOGY/PRINCIPAL FINDINGS: By de novo transcriptome assembling and massive parallel pyrosequencing, we constructed two transcriptomes of WBPH and profiled the alternation of gene expression in response to SRBSDV infection in transcriptional level. As a whole, 81388 distinct unigenes have been identified and the results indicated that SRBSDV infection can potentially perturb primary metabolism and the ubiquitin-proteasome pathway of WBPH and activate immune regulatory systems, such as RNA interfering, autophagy and antimicrobial peptide production. However, some unigenes were obtained only from viruliferous or non-viruliferous samples (data not shown) and we believe these differences may be caused by distinctions that arise from long-term ecological adaptation to virus infection. In addition, GO analysis also showed a similar distribution of gene functions for non-viruliferous and viruliferous WBPH (Figure 4 ), indicating that the number of genes expressed in each GO category was not significantly affected by SRBSDV infection. doi = 10.1371/journal.pone.0036238 id = cord-262748-v4xue7ha author = Xu, Yongtao title = Identification of Peptide Inhibitors of Enveloped Viruses Using Support Vector Machine date = 2015-12-04 keywords = SVM; peptide; protein; virus summary = Here we developed a support vector machine model using sequence-based statistical scores of self-derived peptide inhibitors as input features to correlate with their activities. The predictive support vector machine model for selfderived peptides of envelope proteins would be useful in development of antiviral peptide inhibitors targeting the virus fusion process. In view of the important role of E proteins in virus fusion process and common mechanism of action of self-derived peptides, we developed a SVM model to predict the antiviral activities of self-derived peptides using sequence-based statistical scores as input features. Because similar sequences are often associated with similar structure and function, the sequence-based property AVPalign would account for the activities of the self-derived peptide inhibitors which regulate the virus fusion by mimicking the binding to E proteins. The prominent performance of EAPscoring model indicates the sequence-based stability feature of self-derived peptides may reflect their potential of binding to E proteins so as to regulate the virus entry process. doi = 10.1371/journal.pone.0144171 id = cord-000723-wo20st5w author = Xu, Zhenqiang title = Molecular and Microscopic Analysis of Bacteria and Viruses in Exhaled Breath Collected Using a Simple Impaction and Condensing Method date = 2012-07-25 keywords = EBC; breath; collection; exhale summary = doi = 10.1371/journal.pone.0041137 id = cord-000813-gagakqw4 author = Xue, Mei title = Identification of a Conserved B-cell Epitope on Reticuloendotheliosis Virus Envelope Protein by Screening a Phage-displayed Random Peptide Library date = 2012-11-21 keywords = A9E8; GST; REV; epitope summary = doi = 10.1371/journal.pone.0049842 id = cord-352511-gkm7i62s author = Yamada, Yoshiyuki title = Acquisition of Cell–Cell Fusion Activity by Amino Acid Substitutions in Spike Protein Determines the Infectivity of a Coronavirus in Cultured Cells date = 2009-07-02 keywords = Fig; IBV; Vero summary = title: Acquisition of Cell–Cell Fusion Activity by Amino Acid Substitutions in Spike Protein Determines the Infectivity of a Coronavirus in Cultured Cells Here we report that acquisition of the cell–cell fusion activity by amino acid mutations in the S protein determines the infectivity of IBV in cultured cells. This study demonstrates that acquisition of the cell–cell fusion activity in S protein determines the selection and/or adaptation of a coronavirus from chicken embryo to cultured cells of human and animal origins. In this study, we report that acquisition of the cell-cell fusion activity by point mutations in the spike (S) protein of avian coronavirus infectious bronchitis virus (IBV) plays a critical role in adaptation and/or selection of a variant that infects cultured cells. Sequence comparison of two S protein constructs, S(EP3) and S(CK), cloned from EP3 and CK-adapted IBV strains, respectively, showed amino acid substitutions at 31 positions (Fig. 1a) . doi = 10.1371/journal.pone.0006130 id = cord-276898-ia80cy8j author = Yamanaka, Atsushi title = Imported Case of Acute Respiratory Tract Infection Associated with a Member of Species Nelson Bay Orthoreovirus date = 2014-03-25 keywords = Bali/2007; Bay; Miyazaki; Nelson summary = Miyazaki-Bali/2007, a strain of the species of Nelson Bay orthoreovirus, was isolated from the patient''s throat swab using Vero cells, in which syncytium formation was observed. Here, we report an imported case of an RTI associated with an orthoreovirus, which is classified to the species of Nelson Bay orthoreovirus, in a patient who returned to Japan from Bali, Indonesia in November 2007. Interestingly, S1segment of Miyazaki-Bali/2007 showed 94% homology to that of Kampar virus originated in Malaysia, while it did 48-59% homology to those of the other orthoreoviruses in the genus of Nelson Bay orthoreovirus. S2-segment of Miyazaki-Bali/2007 had the highest homology with being approximately 92-94% in nucleotide sequences to those of HK23629/07, HK46886/09, and HK50842/10, which also seem to have originated in Indonesia [6, 20] , while it showed 83-90% homology to those of Kampar, Melaka, Pulau, Sikamat, and Nelson Bay viruses. doi = 10.1371/journal.pone.0092777 id = cord-000374-gt2pwc9b author = Yang, Albert C. title = Clustering Heart Rate Dynamics Is Associated with β-Adrenergic Receptor Polymorphisms: Analysis by Information-Based Similarity Index date = 2011-05-04 keywords = -ar; HRV; IBS; heart summary = With these considerations in mind, in the present study, we introduce a bottom-up genotype-phenotype analysis to investigate the association between genetic polymorphisms and autonomic control of heart rate dynamics, using three common polymorphisms in genes encoding b-adrenergic receptor (b-AR) as an example. The analyses of the present study were two-fold: 1) a nonrandomness index [17] derived from the IBS method was applied to quantify the nonlinear aspect of HRV according to b-AR genotype and to test the correlation of this index with standard HRV indices; and 2) using agglomerative hierarchical cluster analysis, we unsupervisedly categorized these subjects into clusters based on pairwise dissimilarity among heart rate dynamics, and then we investigated the association of these clustering patterns with b-AR gene polymorphisms. The data presented in this study demonstrate a significant association of a common b 2 -AR polymorphism, Arg16Gly, with the non-randomness index, a nonlinear HRV measure derived from the IBS method. doi = 10.1371/journal.pone.0019232 id = cord-269453-30l6rzgo author = Yang, Po title = Feasibility study of mitigation and suppression strategies for controlling COVID-19 outbreaks in London and Wuhan date = 2020-08-06 keywords = COVID-19; London; Wuhan summary = doi = 10.1371/journal.pone.0236857 id = cord-355259-779czzzx author = Yang, Xiaoyun title = A Beneficiary Role for Neuraminidase in Influenza Virus Penetration through the Respiratory Mucus date = 2014-10-15 keywords = Fig; SIV; mucus; virus summary = Swine influenza virus (SIV) has a strong tropism for pig respiratory mucosa, which consists of a mucus layer, epithelium, basement membrane and lamina propria. The microscopic diffusion of SIV particles in the mucus was analyzed by single particle tracking (SPT), and the macroscopic penetration of SIV through mucus was studied by a virus in-capsule-mucus penetration system, followed by visualizing the translocation of the virions with time by immunofluorescence staining. These findings clearly show that the neuraminidase helps SIV move through the mucus, which is important for the virus to reach and infect epithelial cells and eventually become shed into the lumen of the respiratory tract. To this purpose, we applied swine influenza virus to a model we previously set up using porcine respiratory mucus, pseudorabies virus (PRV) and single particle tracking (SPT) [20] . This does not only confirm the beneficial effect of neuraminidase on releasing SIV from respiratory mucus, but also highlights bidirectional synergistic interactions between influenza virus and bacterial infections. doi = 10.1371/journal.pone.0110026 id = cord-262832-5iejckwx author = Yen, Muh-Yong title = Taipei''s Use of a Multi-Channel Mass Risk Communication Program to Rapidly Reverse an Epidemic of Highly Communicable Disease date = 2009-11-23 keywords = AHC; City; Keelung; Taipei summary = In launching countermeasures to bring the AHC outbreak under control, the Taipei Department of Health was also able to test its system and fine-tune its public health response for future EIDs. To evaluate the effectiveness of these intervention measures, daily surveillance was conducted to analyze the incidence rate and temporal-spatial distribution of new AHC cases. This risk communication program focused on communicating directly to the public through three routes: (1) schools delivered a Taipei Department of Health letter signed by the mayor (that detailed AHC information and prevention methods) for students to take home to their parents, (2) the mayor held a press conference to discuss the epidemic and offer guidance to citizens for preventing the spread of the disease, and (3) over 2.2 million short message services (SMS) messages, a communication tool for exchanging short text messages between mobile telephonic devices, were delivered to all Taipei mobile phone numbers. doi = 10.1371/journal.pone.0007962 id = cord-316287-4i1grvlr author = Yim, Sung Sun title = Rapid Isolation of Antibody from a Synthetic Human Antibody Library by Repeated Fluorescence-Activated Cell Sorting (FACS) date = 2014-10-10 keywords = FACS; antibody; cell summary = During the cultivation for regeneration of sorted cells, differential growth rates among various clones (particularly non-specific clones) due to unregulated protein expression and differing cell viability can decrease the library screening efficiency, resulting in more rounds of sorting (longer duration) to isolate the potential antibody candidate [12] . The whole FACS screening rounds of the synthetic human antibody library against each viral antigen could be done in one day, and these results show that repeated FACS screening without regeneration of the sorted cells can be a rapid and efficient method to isolate potential antibody candidates in case of urgent requirements. For the FACS screening of a human synthetic antibody (scFv) library, three fluorescent antigen probes were chemically synthesized: (i) FITC-CRDNWHGSNRPW as an N1 epitope of H1N1 influenza virus [13] ; (ii) FITC-NSTTFHQALLDPRVRGLYF-PAGG as a PreS2 epitope of HBV [14] ; and (iii) FITC-PVTNVRGDLQVLAQK as a VP1 epitope of FMDV [15] . doi = 10.1371/journal.pone.0108225 id = cord-001761-yvd1n42f author = Yoshimura, Takeo title = Controlled Microwave Heating Accelerates Rolling Circle Amplification date = 2015-09-08 keywords = RCA; dna summary = Analysis of the temperature profiles of each RCA component subjected to microwave heating revealed the selectivity heating of buffer components compared with primers, template DNA, dNTP, and RNase-free water. To determine the component of RCA by microwave selectivity heating, we measured the temperatures of the five components (circularized template with primers, dNTPs, ThermoPol Buffer, Bst-LF, and RNase-free water) of the RCA and MW-RCA mixtures for 10 min from 13°C to 60°C. To reveal the effect of the selectivity heating in MW-RCA, we compared the efficiency of DNA amplification in the RCA and MW-RCA reactions mixtures containing a 4-fold excess concentration of each RCA component (dNTP, template-primers, Bst-LF, Tris-HCl, KCl, (NH 4 ) 2 SO 4 , and MgSO 4 ). We performed MW-RCA reactions containing a four-fold higher concentration of each RCA component [dNTP, template-primers, Bst DNA polymerase-LF, Tris-HCl, KCl, (NH 4 ) 2 SO 4 , and MgSO 4 ] to identify a link between microwave selective heating and DNA amplification. doi = 10.1371/journal.pone.0136532 id = cord-001099-jirkkkvy author = Yousuf, Mohammad A. title = Caveolin-1 Associated Adenovirus Entry into Human Corneal Cells date = 2013-10-11 keywords = D37; HAdV; Src; cell; entry; figure summary = Collectively, these experiments indicate for the first time that HAdV-D37 uses a lipid raft mediated caveolin-1 associated pathway for entry into corneal cells, and connects the processes of viral entry with downstream proinflammatory cell signaling. Initial binding is followed by a secondary interaction between the arginine-glycine-aspartic acid (RGD) motif in the viral capsid penton base and cellular integrins α v β 3 , α v β 5, and α V β 1 [42] [43] [44] [45] This secondary interaction is thought to induce a host cell signaling cascade resulting in clathrin mediated endocytosis [46] [47] [48] , and possibly, activation of the rab5 dependent classical endosomal pathway [49] . Herein, we show that HAdV-D37, an etiologic agent of epidemic keratoconjunctivitis, enters primary human corneal fibroblasts predominantly via lipid rafts and caveolae, suggesting both redundancy and cell specificity in mechanisms of adenoviral entry. To further examine the role of lipid raft microdomains in HAdV-D37 entry, we treated corneal cells with both Cy3-labeled virus and 488-CTXB, and tracked their cellular localization over time ( Figure 1C ). doi = 10.1371/journal.pone.0077462 id = cord-002901-u4ybz8ds author = Yu, Chanki title = Acral melanoma detection using a convolutional neural network for dermoscopy images date = 2018-03-07 keywords = CNN; image; melanoma summary = We applied a convolutional neural network to dermoscopy images of acral melanoma and benign nevi on the hands and feet and evaluated its usefulness for the early diagnosis of these conditions. To perform the 2-fold cross validation, we split them into two mutually exclusive subsets: half of the total image dataset was selected for training and the rest for testing, and we calculated the accuracy of diagnosis comparing it with the dermatologist''s and non-expert''s evaluation. CONCLUSION: Although further data analysis is necessary to improve their accuracy, convolutional neural networks would be helpful to detect acral melanoma from dermoscopy images of the hands and feet. In the result of group B by the training of group A images, CNN also showed a higher diagnostic accuracy (80.23%) than that of the non-expert (62.71%) but was similar to that of the expert (81.64%). doi = 10.1371/journal.pone.0193321 id = cord-328206-iylw1bvw author = Yu, Daojun title = Simultaneous Detection and Differentiation of Human Papillomavirus Genotypes 6, 11, 16 and 18 by AllGlo Quadruplex Quantitative PCR date = 2012-11-09 keywords = HPV; PCR; dna summary = In this study, applying novel AllGlo fluorescent probes, we established a quadruplex quantitative PCR method to simultaneously detect and differentiate HPV 6, 11, 16 and 18 in a single tube. So AllGlo quadruplex quantitative PCR has the advantages of relatively high throughput, good reproducibility, high sensitivity, high specificity, it is easy for designing the probes and primers of multiplex qPCR and can increase the detection throughput. Two aliquots were used for the detection of HPV6-11 and HPV16-18 mixed types by TaqMan uniplex probe fluorescence quantitative PCR (Guangzhou Da''an Diagnostic Co., Ltd., China). Single-tube AllGlo probe quadruplex fluorescence qPCR could simultaneously type HPV 6, 11, 16, and 18 and quantitatively detect the viral load of each HPV at the same time. Single-tube AllGlo probe quadruplex fluorescence qPCR could simultaneously type HPV 6, 11, 16, and 18 and quantitatively detect the viral load of each HPV at the same time. doi = 10.1371/journal.pone.0048972 id = cord-309621-6jj19xpr author = Yu, Pin title = Comparative pathology of rhesus macaque and common marmoset animal models with Middle East respiratory syndrome coronavirus date = 2017-02-24 keywords = East; Fig; MERS; Middle summary = The main histopathological findings in the lungs of rhesus macaques and common marmosets were varying degrees of pulmonary lesions, including pneumonia, pulmonary oedema, haemorrhage, degeneration and necrosis of the pneumocytes and bronchial epithelial cells, and inflammatory cell infiltration. Although there have been several studies in animal models on the pathogenic mechanisms of MERS-CoV infection, little is known about the comparative pathology and inflammatory cell response in rhesus macaques or common marmosets infected with this virus. Pathological findings in the rhesus macaque tissues HE stained tissues from rhesus macaques experimentally infected with MERS-CoV demonstrate that MERS-CoV induces lesions that are primarily observed in the lungs, with varying degrees of inflammation, interstitial pneumonia (Fig 1A) , pulmonary oedema (Fig 1B) , haemorrhaging, degeneration and necrosis of pneumocytes and bronchial epithelial cells (Fig 1C) , and the infiltration of inflammatory cells. Using immunohistochemical techniques and an ISH analysis, we confirmed that MERS-CoV protein and viral RNA were distributed in the lungs of rhesus macaques and common marmosets and that they were primarily located in the pneumocytes and inflammatory cells. doi = 10.1371/journal.pone.0172093 id = cord-290833-m0wodqr3 author = Yuan, Lvfeng title = Synthetic surfactin analogues have improved anti-PEDV properties date = 2019-04-11 keywords = PEDV; SLP5; surfactin summary = In this study, 10 surfactin analogues were obtained by chemical synthesis and evaluated to determine their anti-PEDV activities, hemolytic activities, and critical micelle concentrations. The production of designer surfactins, made by changing the number and composition of amino acids and fatty acids has proven to be an effective strategy for screening large numbers of lipopeptides for biological activity, but most current research focuses on their anticancer [4] , antimicrobial [5] and insulin delivery [6] properties but not on their antiviral potential. Time of addition assays were performed to determine whether the SLP5 exerts its anti-PEDV effect at the same stage during infection as surfactin. As expected for a normal component of the cell membrane, DEPE did not affect PEDV replication at any stage, while SLP5 and surfactin exhibited antiviral activity at specific stages. SLP5 also has two fewer hydrophobic amino acids than surfactin, this reduces the cost of synthesis while having little effect on antiviral activity. doi = 10.1371/journal.pone.0215227 id = cord-001162-z8cbbit3 author = Yun, Heather C. title = Pandemic Influenza Virus 2009 H1N1 and Adenovirus in a High Risk Population of Young Adults: Epidemiology, Comparison of Clinical Presentations, and Coinfection date = 2014-01-08 keywords = H1N1; adenovirus; respiratory summary = title: Pandemic Influenza Virus 2009 H1N1 and Adenovirus in a High Risk Population of Young Adults: Epidemiology, Comparison of Clinical Presentations, and Coinfection While coinfections with viral pathogens including 2009 H1N1 have been described in patients with respiratory infections, few prospective studies have related these to clinical presentation and outcomes in adults since molecular diagnostics became available, and none in the setting of high background rates of adenovirus. [12] [13] [14] [15] [16] [17] We sought to describe the epidemiology of 2009 H1N1 and adenovirus in a basic training population, and to correlate differences in clinical presentations and outcomes with each respective pathogen and in coinfections. Subject enrollment was variable throughout the study period, depending on rates of clinical illness within the training population, as well as availability of study personnel to enroll trainees, and given that 2009 H1N1 influenza virus PCR was done as part of clinical care, there could have been some differences in those who enrolled vs. doi = 10.1371/journal.pone.0085094 id = cord-002848-w6q1x1zs author = Zhang, Ailian title = Immunostimulatory activity of water-extractable polysaccharides from Cistanche deserticola as a plant adjuvant in vitro and in vivo date = 2018-01-23 keywords = OVA; WPCD summary = doi = 10.1371/journal.pone.0191356 id = cord-001368-ymp1pj3r author = Zhang, Chao title = Recombinant Scorpine Produced Using SUMO Fusion Partner in Escherichia coli Has the Activities against Clinically Isolated Bacteria and Inhibits the Plasmodium falciparum Parasitemia In Vitro date = 2014-07-28 keywords = SUMO; Scorpine summary = title: Recombinant Scorpine Produced Using SUMO Fusion Partner in Escherichia coli Has the Activities against Clinically Isolated Bacteria and Inhibits the Plasmodium falciparum Parasitemia In Vitro Scorpions are a rich source of antimicrobial peptides: (1) androctonin isolated from the hemolymph of Androctonus australis, shows marked sequence similarity to tachyplesins, polyphemusins and gomesin [3, 4] ; (2) hadrurin from the venom of Hadrurus aztecus, which is hemolytic [5] ; (3) opistoporin-1, which possesses hemolytic activity, and opistoporin-2, both from the venom of the South African scorpion Opistophtalmus carinatus [6] ; (4) scorpine, which is the subject of this study, arising from the venom of Pandinus imperator, was shown to have anti-bacterial and anti-plasmodial activity in vitro [7] , and has shown a potent toxic effect on sexual and asexual stages of Plasmodium berghei and Plasmodium falciparum, respectively, and also a strong inhibition of dengue 2 virus (DENV-2) infection [8] . doi = 10.1371/journal.pone.0103456 id = cord-339157-wj47xeqj author = Zhang, Chao title = Involvement of the renin-angiotensin system in the progression of severe hand-foot-and-mouth disease date = 2018-05-23 keywords = Ang; HFMD summary = RESULTS: The concentrations of Ang II and NA in serum of the HFMD patients with mild or severe symptoms were significantly higher than that in healthy controls. According to the "diagnosis and treatment guideline on hand-foot-and-mouth disease (2010)", patients younger than 60 months with severe symptoms including meningitis, pulmonary edema, and mild cases without any nervous system lesions or pulmonary edema were included in this study. The concentrations of Ang II and NA in serum of the HFMD patients with mild or severe symptoms were significantly higher than that in healthy controls (P<0.001). The concentrations of Ang II and NA in serum of the HFMD patients with mild or severe symptoms were significantly higher than that in healthy controls (P<0.001). In the present study, we found that the concentrations of Ang II and NA were increased in serum of HFMD cases with mild or severe symptoms. doi = 10.1371/journal.pone.0197861 id = cord-335505-s013j5ex author = Zhang, Chen title = Viral Etiology and Clinical Profiles of Children with Severe Acute Respiratory Infections in China date = 2013-08-22 keywords = SARI; respiratory summary = BACKGROUND: No comprehensive analysis is available on the viral etiology and clinical characterization among children with severe acute respiratory infection (SARI) in China during 2009 H1N1 pandemic and post-pandemic period. The RVP Fast assay simultaneously detects the following viruses: respiratory syncytial virus (RSV); influenza(IFV) A (H1, H3, and H5) and B viruses; parainfluenza viruse (PIV) 1, 2, 3, and 4; human metapneumovirus (hMPV); adenovirus(ADV); piconavirus(PIC) which includes enterovirus (EV) and rhinovirus (RV); human coronaviruse(HCoV) NL63, HKU1, 229E, and OC43; and human bocavirus(BoCA). To find the reason that causes severe infection, we performed complete comparison between VSARI patients and the SARI, including clinical signs, number of viral target, gender, and age(Table 3, Figure 2B ). To find the association between virus infection and clinical signs in SARI, binary logistic regression was performed between 4 commonly diagnosed respiratory abnormality, including anhelation, respiratory failure, heart failure and pleural effusion, and the viral target detected by xTAG® RVP FAST. doi = 10.1371/journal.pone.0072606 id = cord-279421-rxocrgfu author = Zhang, Dan title = Clinical Evaluation of a Single-Tube Multiple RT-PCR Assay for the Detection of 13 Common Virus Types/Subtypes Associated with Acute Respiratory Infection date = 2016-04-04 keywords = assay; respiratory; tube summary = title: Clinical Evaluation of a Single-Tube Multiple RT-PCR Assay for the Detection of 13 Common Virus Types/Subtypes Associated with Acute Respiratory Infection In the present study, an improved single-tube multiplex reverse transcription PCR assay for simultaneous detection of 13 respiratory viruses was evaluated and compared with a previously reported two-tube assay as the reference method using clinical nasopharyngeal aspirates samples. In conclusion, our results demonstrates the one-tube assay revealed significant improvements over the two-tube assay in terms of the better sensitivity, more accurate quality control, less nonspecific amplification, more cost-effective and shorter turn-around time and will be a valuable tool for routine surveillance of respiratory virus infection in China. In the present study, we adopted the two-tube assay as a reference, and have been progressively optimized and substantially improved the performance of simultaneous detection of thirteen respiratory viruses types/subtypes, the most frequently detected viral agents of respiratory tract infections documented by Beijing Monitoring Network for Pneumonia between 2012-2014 (unpublished data), in a single-tube assay while maintaining excellent sensitivity and specificity. doi = 10.1371/journal.pone.0152702 id = cord-000077-d441jam3 author = Zhang, Hao-Jie title = The Y271 and I274 Amino Acids in Reverse Transcriptase of Human Immunodeficiency Virus-1 Are Critical to Protein Stability date = 2009-07-03 keywords = Fig; HIV-1; I274A summary = Reverse transcriptase (RT) of human immunodeficiency virus (HIV)-1 plays a key role in initiating viral replication and is an important target for developing anti-HIV drugs. Our native gel analysis indicated that the mutations at 271 and 274 amino acids might cause conformational changes, leading to the formation of higher order oligomers instead of dimers, resulting in increased protein instability and susceptibility to viral protease. As shown in Fig. 3A , similar levels of Pr160 gag-pol , Gag protein (Pr55 Gag ) and capsid protein p24 (CA p24) were found in cells transfected with the wild type or mutant constructs, indicating that the expression and stability of RT precursor protein were not affected by the mutations. To study if the RTs in the viral particles of Y271A and I274A mutants were degraded by proteolysis that made them undetectable, pseudoviruses of wild type and mutants were generated in the presence or absence of indinavir, a highly specific inhibitor of HIV-1 protease. doi = 10.1371/journal.pone.0006108 id = cord-344782-ond1ziu5 author = Zhang, Jing title = Identification of a novel nidovirus as a potential cause of large scale mortalities in the endangered Bellinger River snapping turtle (Myuchelys georgesi) date = 2018-10-24 keywords = PCR; RNA; River; sequence; virus summary = Nucleic acid sequencing of the virus isolate has identified the entire genome and indicates that this is a novel nidovirus that has a low level of nucleotide similarity to recognised nidoviruses. Following the detection of the novel virus, in November 2015 (about 6 months after the cessation of the outbreak) an intensive survey of the parts of the river where affected turtles had been detected [2] was undertaken by groups of biologists and ecologists and samples collected from a wide range of aquatic species and some terrestrial animals (n = 360) to establish the size of the remaining population and whether any other animals were carrying this virus. BRV, as a novel nidovirus, was isolated from tissues of diseased animals, very high levels of viral RNA were detected in tissues with marked pathological changes and in situ hybridisation assays demonstrated the presence of specific viral RNA in lesions in kidneys and eye tissue-two of the main affected organs. doi = 10.1371/journal.pone.0205209 id = cord-000413-h2e6h076 author = Zhang, Jingyu title = A Conformation-Sensitive Monoclonal Antibody against the A2 Domain of von Willebrand Factor Reduces Its Proteolysis by ADAMTS13 date = 2011-07-11 keywords = ADAMTS13; VWF summary = To investigate whether murine monoclonal antibodies (mAbs) against human VWF affect the susceptibility of VWF to proteolysis by ADAMTS13 in vitro, eight mAbs to different domains of human VWF were used to evaluate the effects on VWF cleavage by ADAMTS13 under fluid shear stress and static/denaturing conditions. The results indicate that mAb SZ34 inhibited proteolytic cleavage of VWF by ADAMTS13 in a concentration-dependent manner under fluid shear stress, but not under static/denaturing conditions. We showed that the decreased amount of the high and intermediate molecular weight multimers were dramatically reduced by mAb SZ34 in a concentration-dependent manner under shear stress (Figure 2 ), further confirming the role of SZ34 in decreasing the susceptibility of VWF to proteolytic cleavage by ADAMTS13 under physiologically relevant conditions. doi = 10.1371/journal.pone.0022157 id = cord-350443-ca5avyjf author = Zhang, Lei title = Trends in Notifiable Infectious Diseases in China: Implications for Surveillance and Population Health Policy date = 2012-02-16 keywords = China; HIV; chinese; disease summary = This study reviews trends in notifiable infectious diseases in China, in their historical context, discusses the current epidemiological state of these infections and their implications for disease surveillance and public health interventions. The total number of diagnosed and death cases were estimated by multiplying morbidity and mortality rates by the overall Chinese population in the study years. In 2008, the three most frequently reported disease types included viral hepatitis (38.3%), bacterial infections (33.3%) and STIs and HIV (9.8%), which account for 5.4, 4.8 and 1.4 million diagnosed cases respectively during the period 2005-2008 (Table 1) . Second, the rapid rise in the number of notified cases of STIs, especially HIV infection, and viral hepatitis in China is associated with growth of the sex industry, increasingly frequent risky sexual behaviours and an increasing number of sexual partners in the general Chinese population. doi = 10.1371/journal.pone.0031076 id = cord-339796-gccnvh0z author = Zhang, Si Min title = Membrane-Active Sequences within gp41 Membrane Proximal External Region (MPER) Modulate MPER-Containing Peptidyl Fusion Inhibitor Activity and the Biosynthesis of HIV-1 Structural Proteins date = 2015-07-31 keywords = Env; Fig; Gag; HIV-1; MPER; trp summary = The MPER in the human immunodeficiency virus type I (HIV-1) envelope protein (Env) interacts with the lipid bilayers through a cluster of tryptophan (Trp) residues and a C-terminal cholesterol-interacting motif. We found that elimination of the membrane-active elements in MPER peptides, namely, penta Trp→alanine (Ala) substitutions and the disruption of the C-terminal cholesterol-interacting motif through deletion inhibited the anti-viral effect against the pseudotyped HIV-1. The secondary structure study revealed that the penta-Trp→Ala substitutions also increased the helical content in the MPER sequence, which prompted us to study the biological relevance of such mutations in pre-fusion Env. We observed that Ala mutations of Trp664, Trp668 and Trp670 in MPER moderately lowered the intracellular and intraviral contents of Env while significantly elevating the content of another viral structural protein, p55/Gag and its derivative p24/capsid. Here we describe the roles of the Trp residues in the membrane-active MPER sequence in anti-HIV fusion inhibitor design and a surprising role in the biosynthesis of viral structural proteins. doi = 10.1371/journal.pone.0134851 id = cord-001910-6zfz2ns5 author = Zhang, Xianming title = Abdominal Muscle Activity during Mechanical Ventilation Increases Lung Injury in Severe Acute Respiratory Distress Syndrome date = 2016-01-08 keywords = ARDS; BIPAP summary = title: Abdominal Muscle Activity during Mechanical Ventilation Increases Lung Injury in Severe Acute Respiratory Distress Syndrome The purpose of this study was to test the hypothesis that abdominal muscle activity during mechanically ventilation increases lung injury in severe ARDS. Therefore, we hypothesized that abdominal muscle activity during mechanically ventilation increases lung injury in severe acute respiratory distress syndrome. In an oleic acid-induced model of experimental ARDS in beagles, our findings suggested that abdominal muscle activity during mechanically ventilation increases lung injury in severe acute respiratory distress syndrome. In an oleic acid-induced ARDS model, our study showed that BIPAP AP had lower mRNA expression of IL-6 and IL-8 in lung tissues and less total cumulative histopathological lung injury scores compared with BIPAP SB group. doi = 10.1371/journal.pone.0145694 id = cord-000539-uh3q65we author = Zhang, Yi title = Acute Respiratory Distress Syndrome Induced by a Swine 2009 H1N1 Variant in Mice date = 2012-01-03 keywords = ARDS; H1N1; mouse; virus summary = BACKGROUND: Acute respiratory distress syndrome (ARDS) induced by pandemic 2009 H1N1 influenza virus has been widely reported and was considered the main cause of death in critically ill patients with 2009 H1N1 infection. Mice infected with SD/09 virus showed typical ARDS symptoms characterized by 60% lethality on days 8–10 post-inoculation, highly edematous lungs, inflammatory cellular infiltration, alveolar and interstitial edema, lung hemorrhage, progressive and severe hypoxemia, and elevated levels of proinflammatory cytokines and chemokines. In the present mouse model, the number of leukocytes observed in the BALF of virus-infected mice significantly increased compared with the control mice on day 8 p.i. Different counts in BALF showed that the proportion of neutrophils dramatically increased. doi = 10.1371/journal.pone.0029347 id = cord-001126-uqr00nzd author = Zhang, Zhicheng title = Synonymous Codon Usage in TTSuV2: Analysis and Comparison with TTSuV1 date = 2013-11-26 keywords = codon; usage summary = In addition, hierarchical cluster analysis of 41 TTSuV2 isolates based on relative synonymous codon usage (RSCU) values suggested that there was no association between geographic distribution and codon bias of TTSuV2 sequences. To explore whether the evolution of codon usage bias in TTSuV2 CDS had been driven by mutation pressure alone or whether translation selection from its host has also contributed, we first compared the correlation between general nucleotide composition (A%, T%, G%, C%, GC%) and nucleotide composition at the third codon position (A 3S %, T 3S %, G 3S %, C 3S %, GC 3S %) using the Spearman''s rank correlation analysis method (Table 4) . These results further support the conclusion that composition constraints under mutational bias is an important factor determining synonymous codon usage pattern in TTSuV2, and but that other factors, such as natural selection, contributed. doi = 10.1371/journal.pone.0081469 id = cord-314651-e4uaw5fy author = Zhao, Guangyu title = Multi-Organ Damage in Human Dipeptidyl Peptidase 4 Transgenic Mice Infected with Middle East Respiratory Syndrome-Coronavirus date = 2015-12-23 keywords = East; Fig; MERS; Middle summary = After intranasal inoculation with MERS-CoV, the mice rapidly developed severe pneumonia and multi-organ damage, with viral replication being detected in the lungs on day 5 and in the lungs, kidneys and brains on day 9 post-infection. To assess viral replication and histopathologic damage following MERS-CoV infection, mice were euthanized with overdose inhalational carbon dioxide, and tissues included lungs, kidneys, livers, spleens, intestines and brains were harvested on indicated time points. Although a transgenic mouse model expressing human DPP4 was also established, and its immune response was studied after infection with MERS-CoV [16] , the transgenic mice in the study died on day 6 with only progressive pneumonia and mild perivascular cuffing in brain, and no neurological disorder or other multi-organ damage was observed. doi = 10.1371/journal.pone.0145561 id = cord-000434-ff2zadol author = Zhao, Rongmao title = Identification of a Highly Conserved H1 Subtype-Specific Epitope with Diagnostic Potential in the Hemagglutinin Protein of Influenza A Virus date = 2011-08-19 keywords = ELISA; IAV; P31 summary = The highly conserved H1 subtype-specific immunodominant epitope may form the basis for developing novel assays for sero-diagnosis and active surveillance against H1N1 IAVs. Influenza A viruses (IAVs), members of the Orthomyxoviridae family, are highly contagious to a variety of avian and mammalian species. To confirm that these antibodies can recognize the HA antigen, the reactivity of the anti-peptide sera were evaluated by Western blot and ELISA against the purified HA0 protein of H1N1pdm virus. The sensitivity and specificity of peptide-ELISA versus HI test was 96.5% and 74.4%, respectively, indicating the potential of the peptide-ELISA method in detecting antibody against H1-subtype IAVs. In the present study, we identified immunodominant linear B cell epitopes on the H1N1pdm virus HA protein by a peptide scanning approach using H1N1pdm patients sera. To screen the H1-subtype specific epitopes, a set of 50 peptides spanning the amino acid sequences of the HA protein ectodomain of pandemic A/H1N1 2009 (H1N1pdm) influenza virus strain A/ California/04/2009 were synthesized. doi = 10.1371/journal.pone.0023374 id = cord-267605-efb10j3u author = Zheng, Li-Zhen title = Steroid-Associated Hip Joint Collapse in Bipedal Emus date = 2013-10-21 keywords = MPS; MRI; SAON; femoral; figure summary = The combination of pulsed LPS and MPS developed in the current study was safe and effective to induce SAON and deterioration of subchondral bone in bipedal emus with subsequent femoral head collapse, a typical clinical feature observed in patients under pulsed steroid treatment. Accordingly, the aim of the current study was to establish a SAON model in bipedal emus, with potentials to bone structural deterioration with subsequent femoral head collapse, a condition seen in SAON patients attributed to similar biomechanics or loading ratio imposed onto the hip joint [23, 24] . Using a combined pulsed LPS and MPS induction protocol previously established for SAON quadrupedal rabbits [11, 13] , the present study established a SAON model in bipedal emus characterized with subchondral bone deterioration and hip joint collapse, an experimental model mimicking human ON often developed at hip joint with femoral head collapse. doi = 10.1371/journal.pone.0076797 id = cord-252739-1manzf3l author = Zheng, Yueming title = Hexachlorophene Is a Potent KCNQ1/KCNE1 Potassium Channel Activator Which Rescues LQTs Mutants date = 2012-12-12 keywords = HCP; KCNQ1 summary = The voltage-gated KCNQ1 potassium channel is expressed in cardiac tissues, and coassembly of KCNQ1 with an auxiliary KCNE1 subunit mediates a slowly activating current that accelerates the repolarization of action potential in cardiomyocytes. Mutations of KCNQ1 genes that result in reduction or loss of channel activity cause prolongation of repolarization during action potential, thereby causing long QT syndrome (LQTs). Small molecule activators of KCNQ1/KCNE1 are useful both for understanding the mechanism of the complex activity and for developing therapeutics for LQTs. In this study we report that hexachlorophene (HCP), the active component of the topical anti-infective prescription drug pHisoHex, is a KCNQ1/KCNE1 activator. Consistent with previous reports, the effects of KCNE1 on KCNQ1 include increase in overall current amplitude, slowing of the activation and deactivation kinetics, and removal of inactivation (Fig. 4A) . The common phenotype of these mutants is reduction of IKs current, which are commonly thought to be mediated by the KCNQ1/KCNE1 complex [2, 3] , as a result of decrease in either channel activity or trafficking efficiency. doi = 10.1371/journal.pone.0051820 id = cord-000326-a18rch1f author = Zhou, Jun-Wei title = Apolipoprotein M Gene (APOM) Polymorphism Modifies Metabolic and Disease Traits in Type 2 Diabetes date = 2011-02-24 keywords = APOM; Kong; SNP summary = This study aimed at substantiating the associations of the apolipoproein M gene (APOM) with type 2 diabetes (T2D) as well as with metabolic traits in Hong Kong Chinese. Several additional lines of evidence also indicated the possible involvement of APOM in the development of diabetes and metabolic disturbances: 1) the human APOM gene is located within a high susceptibility region (6q21-q23) to type 2 diabetes (T2D) in genome-wide linkage analyses [6] . 2) SNP rs805296 (T-778C) in APOM promoter has been associated with the levels of plasma total cholesterol (TC) and fasting plasma glucose (FPG) in non-diabetic participants, 3) SNP rs805296 has also been associated with the susceptibility to T2D and coronary artery disease among the Northern Chinese [7, 8] . While our results did not support an association between APOM and T2D susceptibility in Hong Kong Chinese, subgroup analyses found SNP as well as haplotype associations between APOM and metabolic traits in T2D. doi = 10.1371/journal.pone.0017324 id = cord-327534-f2wvh6la author = Zhou, Peng title = IRF7 in the Australian Black Flying Fox, Pteropus alecto: Evidence for a Unique Expression Pattern and Functional Conservation date = 2014-08-06 keywords = IFN; IRF3; IRF7; bat; figure summary = To explore the role of bat IRF7 in the regulation of the IFN response, we performed sequence and functional analysis of IRF7 from the pteropid bat, Pteropus alecto. Regions containing putative IRF3 or IRF7 binding sites were identified from 2221 to 270 bp from the ATG of the bat IFN-b gene by comparison with human IFN promoters and cloned into the pGL4.1 expression vector (Promega). Analysis of the putative bat IRF7 promoter region around 1000 bp upstream of the start site of the ORF resulted in the identification of two IFN stimulated response elements (ISREs) and one nuclear factor kappa B (NF-kB) binding site. Our results demonstrate that even with a significant difference in its MyD88 binding region, bat IRF7 is still capable of inducing IFN-a transcription via MyD88 ( Figure 5 ). doi = 10.1371/journal.pone.0103875 id = cord-263276-keyu60in author = Zhou, Weimin title = Prevalence of Herpes and Respiratory Viruses in Induced Sputum among Hospitalized Children with Non Typical Bacterial Community-Acquired Pneumonia date = 2013-11-18 keywords = CMV; RSV; cap summary = METHODS: Induced sputum (IS) samples were collected from 354 hospitalised patients (infants, n = 205; children, n = 149) with respiratory illness (CAP or non-CAP) admitted to Wenling Hospital of China. The present study was undertaken to describe the profiles of HHVs and other respiratory viruses associated with hospital-based CAP and non-CAP among infants and young children in a rural area of China using comprehensive and sensitive molecular diagnostic techniques. In this study, the viral prevalence in sputum specimens of childhood with non typical bacterial CAP was investigated using sensitive molecular diagnostic methods for HHVs and 15 respiratory viruses, and viruses were detected in 99.6% of the children. In summary, our study on the prevalence of HHVs and other respiratory viruses in infants and young children with CAP identified a detectable virus in more than 99.6% of case participants, in which CMV, HHV-6, EBV, RSV and HBoV were clearly predominant (.25%) and contributed significantly to the spectrum of CAP in a rural area of China. doi = 10.1371/journal.pone.0079477 id = cord-340718-amfs4zay author = Zhu, Gengping title = Potential Geographic Distribution of the Novel Avian-Origin Influenza A (H7N9) Virus date = 2014-04-01 keywords = China; H7N9 summary = CONCLUSIONS/SIGNIFICANCE: Central-eastern China appears to represent an area of high risk for H7N9 spread, but suitable areas were distributed more spottily in the north and only along the coast in the south; highly suitable areas also were identified in western Taiwan. Since the first case was reported, researchers focused on improving diagnosis, understanding location of origin, and methods of cure; however, little is known about the geographic potential of H7N9 or environmental correlates of its transmission, except Butler [3] and He and Chen [4] , who presented ideas based on lessons from the previous avian influenza threat (i.e. H5N1), and Shi [5] and Fang [6] , who mapped the spread potential of H7N9 using spatial regression method. Effective and predictive risk maps can provide a useful means by which to design targeted surveillance efforts [3] [4] [5] [6] , and ecological niche modeling approaches are offering novel views of the geography of potential for disease transmission [9, 18] . doi = 10.1371/journal.pone.0093390 id = cord-327257-doygrgrc author = Zhu, Jocelyn title = Deep transfer learning artificial intelligence accurately stages COVID-19 lung disease severity on portable chest radiographs date = 2020-07-28 keywords = CXR; covid-19 summary = title: Deep transfer learning artificial intelligence accurately stages COVID-19 lung disease severity on portable chest radiographs This study employed deep-learning convolutional neural networks to stage lung disease severity of Coronavirus Disease 2019 (COVID-19) infection on portable chest x-ray (CXR) with radiologist score of disease severity as ground truth. Deep-learning convolutional neural network (CNN) was used to predict lung disease severity scores. In conclusion, deep-learning CNN accurately stages disease severity on portable chest x-ray of COVID-19 lung infection. This study tested the hypothesis that deep-learning convolutional neural networks accurately stage disease severity on portable chest x-rays using radiologists'' severity scores as ground truths associated with COVID-19 lung infection. Deep-learning AI, specifically a convolutional neural network, is well suited to extract information from CXR and stage disease severity by training using chest radiologist determination of disease severity scores. In conclusion, deep-learning convolutional neural networks accurately stage lung disease severity on portable chest x-rays associated with COVID-19 lung infection. doi = 10.1371/journal.pone.0236621 id = cord-351868-w4d45fue author = Zuwała, Kaja title = The Nucleocapsid Protein of Human Coronavirus NL63 date = 2015-02-20 keywords = CTD; NL63; NTD; TTT summary = Surprisingly, analysis of the subcellular localization of the N protein of HCoV-NL63 revealed that, differently than homologous proteins from other coronaviral species except for SARS-CoV, it is not present in the nucleus of infected or transfected cells. In order to test subcellular localization of the N protein in LLC-MK2 cells, the maxFP-Green-N/NL63-N encoding RNA was prepared based on the original plasmid. For EMSA assay 10 μg of RNA or DNA corresponding in sequence to the N-NL63 gene (prepared in the same manner as for the transfection of eukaryotic cells) was incubated in buffered solution (5 mM Tris, 50 mM NaCl, pH8.0) with 10 μg of the NTD or CTD for 30 minutes at room temperature. The constructs of NTD and CTD used in this study were designed based on literature data, HCoV-NL63 N protein amino acid sequence alignment with known homologs and on the comparative analysis of currently available crystal structures of these homologs. doi = 10.1371/journal.pone.0117833 id = cord-254025-j1l0mder author = de Melo, Andreia C. title = Cancer inpatients with COVID-19: A report from the Brazilian National Cancer Institute date = 2020-10-26 keywords = COVID-19; patient summary = According to the univariate analysis COVID-19-specific mortality was significantly associated with age over 75 years (P = .002), metastatic cancer (p <0.001), two or more sites of metastases (P < .001), the presence of lung (P < .001) or bone metastases (P = .001), non-curative treatment or best supportive care intent (P < .001), higher C-reactive protein levels (P = .002), admission due to COVID-19 (P = .009), and antibiotics use (P = .02). As shown in Table 3 , mortality related to COVID-19 was significantly associated to older age (P < .001 for patients between 60 to 74 years and P = .002 for patients aged 75 years or older), metastatic cancer (P < .001), two or more sites of metastases (P < .001), the presence of lung (P < .001) or bone metastases (P = .001), non-curative treatment or best supportive care intent (P < .001), higher C-reactive protein levels (P = .002), admission due to COVID-19 (P = .009), and antibiotics use (P = .02). doi = 10.1371/journal.pone.0241261 id = cord-011496-r8e19t0c author = de Rooij, Doret title = Development of a competency profile for professionals involved in infectious disease preparedness and response in the air transport public health sector date = 2020-05-21 keywords = Health; airport; competency; disease; profile summary = doi = 10.1371/journal.pone.0233360 id = cord-342476-0rupk21u author = van Rijn, Anneloes L. title = The respiratory virome and exacerbations in patients with chronic obstructive pulmonary disease date = 2019-10-24 keywords = COPD; PCR; exacerbation; respiratory summary = The sensitivity, specificity and predictive values of mNGS were calculated based on 24 PCR positive and 1120 PCR negative target results of 88 samples and the normalized read counts (Table 5 ). The following markers were tested for potential associations with clinical severity of exacerbation (exacerbation severity, self-reported exacerbation severity), length of exacerbation and a decrease/increase in FEV 1 (control visit compared to baseline): mNGS pathogen positive versus negative exacerbation (qPCR targets), the number of normalized reads (log, cutoff of �5normalized reads) for the different target viruses (species level). The Shannon diversity scores for bacteriophages (normalized reads, cut-off of �5normalized reads) were comparable for COPD exacerbations of viral aetiology in PCR positive versus negative patients (Fig 5) . In this study, the respiratory virome in patients with COPD exacerbations was analysed with both mNGS and qPCR, and combined with clinical data. doi = 10.1371/journal.pone.0223952 id = cord-305900-ht7hb2rc author = van den Brand, Judith M. A. title = Comparison of Temporal and Spatial Dynamics of Seasonal H3N2, Pandemic H1N1 and Highly Pathogenic Avian Influenza H5N1 Virus Infections in Ferrets date = 2012-08-08 keywords = H3N2; H5N1; dpi; figure; table summary = Therefore, we inoculated ferrets with seasonal H3N2, pandemic H1N1 (pH1N1), and highly pathogenic avian H5N1 influenza virus and performed detailed virological and pathological analyses at time points from 0.5 to 14 days post inoculation (dpi), as well as describing clinical signs and hematological parameters. To this end, we inoculated ferrets with either seasonal human H3N2, pH1N1, or HPAI H5N1 virus, and performed detailed virological and pathological analyses at time points from 0.5 to 14 dpi, as well as measuring virus excretion, clinical signs, and hematological parameters. Comparable with the pattern of antigen expression in the respiratory tissues, high virus titers were seen in the nasal concha from 0.5 to 4 dpi with a peak on 1 dpi (Figure 3) . However, in the current study, we found very little H3N2 infection (based on virus antigen expression) in any cell types of the ferret lower respiratory tract ( Figure 3 ). doi = 10.1371/journal.pone.0042343 id = cord-323433-9km824uh author = van den Wijngaard, Cees C. title = Syndromic Surveillance for Local Outbreaks of Lower-Respiratory Infections: Would It Work? date = 2010-04-29 keywords = LRI; Legionnaires; cluster summary = We evaluated how many LRI-clusters were detected in 1999–2006 and assessed likely causes for the cluster-signals by looking for significantly higher proportions of specific hospital discharge diagnoses (e.g. Legionnaires disease) and overlap with regional influenza elevations. Furthermore, since comparatively few new clusters per year were observed that would prompt investigation, syndromic hospital-surveillance could be a valuable tool for detection of local LRI-outbreaks. Geographic analysis methods -such as space-time scan statistics -may further increase the sensitivity of syndromic surveillance for detection of local outbreaks or of regional differences in regular seasonal epidemic diseases [2, 6] . The objective of this study was to evaluate to what extent syndromic surveillance detects local outbreaks of lower-respiratory infections (LRIs) without swamping true signals by false alarms. Of these, 6 belonged to influenza and/ or RSV related clusters (Figure 2a When repeating the weekly analyses with restricted time or spatial windows, both Legionnaires'' disease outbreaks were still detected with the same timeliness. doi = 10.1371/journal.pone.0010406 id = cord-048483-umvrwgaw author = van der Sande, Marianne title = Professional and Home-Made Face Masks Reduce Exposure to Respiratory Infections among the General Population date = 2008-07-09 keywords = mask; protection; wear summary = doi = 10.1371/journal.pone.0002618 id = cord-309043-dlmx12vt author = von Brunn, Albrecht title = Analysis of Intraviral Protein-Protein Interactions of the SARS Coronavirus ORFeome date = 2007-05-23 keywords = RNA; SARS; interaction; protein; y2h summary = The severe acute respiratory syndrome coronavirus (SARS-CoV) genome is predicted to encode 14 functional open reading frames, leading to the expression of up to 30 structural and non-structural protein products. There are reports that a number of MHV and SARS-CoV replicase proteins colocalize and eventually interact in cytoplasmic membrane bound complexes, in which viral RNA synthesis occurs [18, 19] . We therefore cloned the SARS-CoV ORFeome by recombinatorial cloning (GATEWAY technology) and performed a genome-wide analysis for viral protein interactions by yeast-two-hybrid (Y2H) matrix screen. To systematically study the subcellular localization of viral proteins within eukaryotic HeLa cells the SARS-CoV ORFs were transfected in eukaryotic vectors with either N-or C-terminal Flag tags and detected with an anti-Flag antibody. In this study we report the cloning of the complete ORFeome of SARS-CoV and the results of a matrix-based yeast two-hybrid screen of pairwise viral protein-protein interactions. doi = 10.1371/journal.pone.0000459