niryuu/sni-each-converted huggingface dataset:
Paragraph: We report the synthesis of a series of novel 2 0 -deoxy-2 0 ,2 0 -difluoro-5-halouridines and their corresponding phosphoramidate ProTides. All compounds were evaluated for antiviral activity and for cellular toxicity. Interestingly, 2 0 -deoxy-2 0 ,2 0 -difluoro-5-iodo-and -5-bromo-uridines showed selective activity against feline herpes virus replication in cell culture due to a specific recognition (activation) by the virus-encoded thymidine kinase. Crown 
 Title: Design, synthesis and biological evaluation of 2 0 -deoxy-2 0 ,2 0 -difluoro- 5-halouridine phosphoramidate ProTides
Output: False
Paragraph: Background. Precision public health is a novel set of methods to target disease prevention and mitigation interventions to highrisk subpopulations. We applied a precision public health strategy to syndromic surveillance for severe acute respiratory infection (SARI) in Uganda by combining spatiotemporal analytics with genomic sequencing to detect and characterize viral respiratory pathogens with epidemic potential. Methods. Using a national surveillance network we identified patients with unexplained, influenza-negative SARI from 2010 to 2015. Spatiotemporal analyses were performed retrospectively to identify clusters of unexplained SARI. Within clusters, respiratory viruses were detected and characterized in naso-and oropharyngeal swab samples using a novel oligonucleotide probe capture (VirCapSeq-VERT) and high-throughput sequencing platform. Linkage to conventional epidemiologic strategies further characterized transmission dynamics of identified pathogens. Results. Among 2901 unexplained SARI cases, 9 clusters were detected, accounting for 301 (10.4%) cases. Clusters were more likely to occur in urban areas and during biannual rainy seasons. Within detected clusters, we identified an unrecognized outbreak of measles-associated SARI; sequence analysis implicated cocirculation of endemic genotype B3 and genotype D4 likely imported from England. We also detected a likely nosocomial SARI cluster associated with a novel picobirnavirus most closely related to swine and dromedary viruses. Conclusions. Using a precision approach to public health surveillance, we detected and characterized the genomics of vaccine-preventable and zoonotic respiratory viruses associated with clusters of severe respiratory infections in Uganda. Future studies are needed to assess the feasibility, scalability, and impact of applying similar approaches during real-time public health surveillance in low-income settings. 
 Title: Clinical Infectious Diseases Precision Surveillance for Viral Respiratory Pathogens: Virome Capture Sequencing for the Detection and Genomic Characterization of Severe Acute Respiratory Infection in Uganda
Output: False
Paragraph: Bovine coronavirus (BCoV) is an economically signifi cant cause of enteric and respiratory diseases in cattle throughout the world. BCoV is a known cause of neonatal calf diarrhea, winter dysentery in adult cattle, and respiratory disorders in cattle of all ages. In this chapter, we describe a simple and effi cient protocol for total nucleic acids extraction to be used in conventional RT-PCR assay. This is a technique used routinely in our virology laboratory to detect BCoV from stool and nasopharyngeal samples of cattle. 
 Title: Detection of Bovine Coronavirus by Conventional Reverse Transcription Polymerase Chain Reaction
Output: True
Paragraph: In recent years, many studies have drawn attention to the important role of collective awareness and human behaviour during epidemic outbreaks. A number of modelling efforts have investigated the interaction between the disease transmission dynamics and human behaviour change mediated by news coverage and by information spreading in the population. Yet, given the scarcity of data on public awareness during an epidemic, few studies have relied on empirical data. Here, we use fine-grained, geo-referenced data from three online sources -Wikipedia, the GDELT Project and the Internet Archive -to quantify population-scale information seeking about the 2016 Zika virus epidemic in the U.S., explicitly linking such behavioural signal to epidemiological data. Geolocalized Wikipedia pageview data reveal that visiting patterns of Zika-related pages in Wikipedia were highly synchronized across the United States and largely explained by exposure to national television broadcast. Contrary to the assumption of some theoretical models, news volume and Wikipedia visiting patterns were not significantly correlated with the magnitude or the extent of the epidemic. Attention to Zika, in terms of Zika-related Wikipedia pageviews, was high at the beginning of the outbreak, when public health agencies raised an international alert and triggered 1 All rights reserved. No reuse allowed without permission. The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. . https://doi.org/10.1101/346411 doi: bioRxiv preprint media coverage, but subsequently exhibited an activity profile that suggests nonlinear dependencies and memory effects in the relation between information seeking, media pressure, and disease dynamics. This calls for a new and more general modelling framework to describe the interaction between media exposure, public awareness and disease dynamics during epidemic outbreaks. 
 Title: The impact of news exposure on collective attention in the United States during the 2016 Zika epidemic
Output: False
Paragraph: Emerging data support a role for antibody Fc-mediated antiviral activity in vaccine efficacy and in the control of HIV-1 replication by broadly neutralizing antibodies. Antibody-mediated virus internalization is an Fc-mediated function that may act at the portal of entry whereby effector cells may be triggered by pre-existing antibodies to prevent HIV-1 acquisition. Understanding the capacity of HIV-1 antibodies in mediating internalization of HIV-1 virions by primary monocytes is critical to understanding their full antiviral potency. Antibody isotypes/subclasses differ in functional profile, with consequences for their antiviral activity. For instance, in the RV144 vaccine trial that achieved partial efficacy, Env IgA correlated with increased risk of HIV-1 infection (i.e. decreased vaccine efficacy), whereas V1-V2 IgG3 correlated with decreased risk of HIV-1 infection (i.e. increased vaccine efficacy). Thus, understanding the different functional attributes of HIV-1 specific IgG1, IgG3 and IgA antibodies will help define the mechanisms of immune protection. Here, we utilized an in vitro flow cytometric method utilizing primary monocytes as phagocytes and infectious HIV-1 virions as targets to determine the capacity of Env IgA (IgA1, IgA2), IgG1 and IgG3 antibodies to mediate HIV-1 infectious virion internalization. Importantly, both broadly neutralizing antibodies (i.e. PG9, 2G12, CH31, VRC01 IgG) and non-broadly neutralizing antibodies (i.e. 7B2 mAb, mucosal HIV-1+ IgG) mediated internalization of HIV-1 virions. Furthermore, we found that Env IgG3 of multiple specificities (i.e. CD4bs, V1-V2 and gp41) mediated increased infectious virion internalization over Env IgG1 of the same specificity, while Env IgA mediated decreased infectious virion internalization compared to IgG1. These data PLOS Pathogens | 
 Title: Antibody-Mediated Internalization of Infectious HIV-1 Virions Differs among Antibody Isotypes and Subclasses
Output: True
Paragraph: Purpose of Review-Interferon-induced transmembrane protein 3 (IFITM3) is a cellular restriction factor that blocks fusion between virus and host membranes. Here, we provide an introduction to IFITM3 and the biochemical regulation underlying its antiviral activity. Further, we analyze and summarize the published literature examining phenotypes of IFITM3 knockout mice upon infections with viral pathogens and discuss the controversial association between single nucleotide polymorphisms (SNPs) in the human IFITM3 gene and severe virus infections. Recent Findings-Recent publications show that IFITM3 knockout mice experience more severe pathologies than wild-type mice in diverse virus infections, including infections with influenza A virus, West Nile virus, Chikungunya virus, Venezuelan equine encephalitis virus, respiratory syncytial virus, and cytomegalovirus. Likewise, numerous studies of humans of Chinese ancestry have associated the IFITM3 SNP rs12252-C with severe influenza virus infections, though examinations of other populations, such as Europeans, in which this SNP is rare, have largely failed to identify an association with severe infections. A second SNP, rs34481144-A, found in the human IFITM3 promoter has also recently been reported to be a risk allele for severe influenza virus infections. Summary-There is significant evidence for a protective role of IFITM3 against virus infections in both mice and humans, though additional work is required to identify the range of pathogens restricted by IFITM3 and the mechanisms by which human SNPs affect IFITM3 levels or functionality. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http:// creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. 
 Title: Antiviral Protection by IFITM3 In Vivo HHS Public Access
Output: False
Paragraph: 2 3 Halim Maaroufi 4 Institut de biologie intégrative et des systèmes (IBIS). Université Laval. Quebec. Canada 5 Halim.maaroufi@ibis.ulaval.ca 6 7 ABSTRACT The novel betacoronavirus (SARS-CoV-2) is highly contagious and can cause 8 serious acute respiratory illness syndromes, often fatal, called covid-19. It is an urgent priority to 9 better understand SARS-CoV-2 infection mechanisms that will help in the development of 10 prophylactic vaccines and therapeutics that are very important to people health and socioeconomic 11 stability around the world. The surface coronavirus spike (S) glycoprotein is considered as a key 12 factor in host specificity because it mediates infection by receptor-recognition and membrane 13 fusion. Here the analysis of CoV-2 S protein revealed in S1subunit a B56-binding LxxIxE-like 14 motif that could recruit the host protein phosphatase 2A (PP2A). This motif is absent in SARS-15 CoV and MERS-CoV. PP2A is a major family of serine/threonine phosphatases in eukaryotic cells. 16 Phosphatases and kinases are big players in the regulation of pro-inflammatory responses during 17 pathogenic infections. Moreover, studies have shown that viruses use multiple strategies to target 18 PP2A in order to manipulate host's antiviral responses. The latest studies have indicated that 19 SARS-CoV-2 is involved in sustained inflammation in the host. Therefore, by controlling acute 20 inflammation; it is possible to eliminate its dangerous effects on the host. Among efforts to fight 21 covid-19, the interaction between LxxIxE-like motif and PP2A-B56-binding pocket could be a 22 target for the development of a bioactive peptide and ligand inhibitors for therapeutic purposes. 23 24 25 
 Title: The Spike Protein S1 Subunit of SARS-CoV-2 Contains an LxxIxE-like Motif that is Known to Recruit the Host PP2A-B56 Phosphatase
Output: False
Paragraph: The basic reproduction number R 0 is one of the most important concepts in modern infectious disease epidemiology. However, for more realistic and more complex models than those assuming homogeneous mixing in the population, other threshold quantities can be defined that are sometimes more useful and easily derived in terms of model parameters. In this paper, we present a model for the spread of a permanently immunizing infection in a population socially structured into households and workplaces/schools, and we propose and discuss a new household-to-household reproduction number R H for it. We show how R H overcomes some of the limitations of a previously proposed threshold parameter, and we highlight its relationship with the effort required to control an epidemic when interventions are targeted at randomly selected households. 
 Title: Threshold parameters for a model of epidemic spread among households and workplaces
Output: True
Paragraph: Since the first imported case of Middle East respiratory syndrome coronavirus (MERS-CoV) infection was reported on May 20, 2015 in Korea, there have been 186 laboratoryconfirmed cases of MERS-CoV infection with 36 fatalities. Ninety-seven percent (181/186) of the cases had exposure to the health care facilities. We are reporting a superspreading event that transmitted MERS-CoV to 81 persons at a hospital emergency room (ER) during the Korean outbreak in 2015. The index case was a 35-yr-old man who had vigorous coughing while staying at the ER for 58 hr. As in severe acute respiratory syndrome outbreaks, superspreading events can cause a large outbreak of MERS in healthcare facilities with severe consequences. All healthcare facilities should establish and implement infection prevention and control measure as well as triage policies and procedures for early detection and isolation of suspected MERS-CoV cases. 
 Title: Middle East Respiratory Syndrome Coronavirus Superspreading Event Involving 81 Persons, Korea 2015
Output: True
Paragraph: Molecular diagnostics of infectious diseases, in particular, nucleic-acid-based methods, are the fastest growing field in clinical laboratory diagnostics. These applications are stepwise replacing or complementing culture-based, biochemical, and immunological assays in microbiology laboratories. The first-generation nucleic acid assays were monoparametric such as conventional tests, determining only a single parameter. Improvements and new approaches in technology now open the possibility for the development of multiparameter assays using microarrays, multiplex nucleic acid amplification techniques, or mass spectrometry, while the introduction of closed-tube systems has resulted in rapid microbial diagnostics with a subsequently reduced contamination risk. Whereas the first assays were focused on the detection and identification of microbial pathogens, these new technologies paved the way for the parallel determination of multiple antibiotic resistance determinants or to perform microbial epidemiology and surveillance on a genetic level. Phenotype-based methods One of the oldest but still very important methods in clinical bacteriology is the detection of human pathogens by direct microscopic examination of the specimen. Many 
 Title: Current applications and future trends of molecular diagnostics in clinical bacteriology
Output: True
Paragraph: Scarlet fever is one of a variety of diseases caused by group A Streptococcus (GAS). During 2011, a scarlet fever epidemic characterized by peak monthly incidence rates 2.9-6.7 times higher than those in 2006-2010 occurred in Beijing, China. During the epidemic, hospital-based enhanced surveillance for scarlet fever and pharyngitis was conducted to determine characteristics of circulating GAS strains. The surveillance identified 3,359 clinical cases of scarlet fever or pharyngitis. GAS was isolated from 647 of the patients; 76.4% of the strains were type emm12, and 17.1% were emm1. Almost all isolates harbored superantigens speC and ssa. All isolates were susceptible to penicillin, and resistance rates were 96.1% to erythromycin, 93.7% to tetracycline, and 79.4% to clindamycin. Because emm12 type GAS is not the predominant type in other countries, wider surveillance for the possible spread of emm12 type GAS from China to other countries is warranted. 
 Title: Group A Streptococcus Strains Circulating during Scarlet Fever Epidemic, Beijing, China, 2011
Output: False
Paragraph: Positive-strand RNA viruses are known to rearrange cellular membranes to facilitate viral genome replication. The biogenesis and three-dimensional organization of these membranes and the link between replication and virus assembly sites is not fully clear. Using electron microscopy, we find Dengue virus (DENV)-induced vesicles, convoluted membranes, and virus particles to be endoplasmic reticulum (ER)-derived, and we detect double-stranded RNA, a presumed marker of RNA replication, inside virusinduced vesicles. Electron tomography (ET) shows DENV-induced membrane structures to be part of one ER-derived network. Furthermore, ET reveals vesicle pores that could enable release of newly synthesized viral RNA and reveals budding of DENV particles on ER membranes directly apposed to vesicle pores. Thus, DENV modifies ER membrane structure to promote replication and efficient encapsidation of the genome into progeny virus. This architecture of DENV replication and assembly sites could explain the coordination of distinct steps of the flavivirus replication cycle. 
 Title: Composition and Three-Dimensional Architecture of the Dengue Virus Replication and Assembly Sites
Output: True
Paragraph: We have identified oleuropein (Ole) and hydroxytyrosol (HT) as a unique class of HIV-1 inhibitors from olive leaf extracts effective against viral fusion and integration. We used molecular docking simulation to study the interactions of Ole and HT with viral targets. We find that Ole and HT bind to the conserved hydrophobic pocket on the surface of the HIV-gp41 fusion domain by hydrogen bonds with Q577 and hydrophobic interactions with I573, G572, and L568 on the gp41 N-terminal heptad repeat peptide N36, interfering with formation of the gp41 fusion-active core. To test and confirm modeling predications, we examined the effect of Ole and HT on HIV-1 fusion complex formation using native polyacrylamide gel electrophoresis and circular dichroism spectroscopy. Ole and HT exhibit dose dependent inhibition on HIV-1 fusion core formation with EC 50 s of 66-58 nM, with no detectable toxicity. Our findings on effects on HIV-1 integrase are reported separately. 
 Title: Discovery of Small-Molecule HIV-1 Fusion and Integrase Inhibitors Oleuropein and Hydroxytyrosol: I. Fusion Inhibition
Output: False
Paragraph: Therapeutic recombinant human catalase (rhCAT) can quench infection-induced reactive oxygen species (ROS), thereby alleviating the associated tissue damage. Although the intranasal route is efficient to deliver native rhCAT to the lung, the therapeutic effect is limited by rapid elimination from the blood. In this study, we modified rhCAT with the active polymer, polyethylene glycol monomethyl ether (PEG)-5000, and analyzed the pharmacokinetics of PEGylated rhCAT in mice. The high tetra-PEGylation ratio was about 60 %, and PEGylation prolonged the half-life of rhCAT in serum (75 vs. 13.5 min for native rhCAT). The protective effects of PEG-rhCAT were investigated in a mouse model of influenza virus A (H1N1)-associated pneumonia. PEG-rhCAT was more effectively delivered than native rhCAT and was associated with higher survival ratio, less extensive lung injuries, reduced ROS levels, and lower viral replication. Collectively, these findings indicate that PEGylation can enhance the therapeutic efficacy of native rhCAT and suggest that PEGylated rhCAT may represent a novel complement therapy for H1N1 influenza-induced pneumonia. 
 Title: PEGylated human catalase elicits potent therapeutic effects on H1N1 influenza-induced pneumonia in mice
Output: False
Paragraph: Human rhinovirus type C is a recently discovered species that has been associated with respiratory tract infections of unusual severity in some cases. However, the precise type of diseases associated with this new human rhinovirus needs to be investigated. In the present report, we used adapted real-time PCR assays to screen different clinical specimens collected from a 14-month-old boy presenting an acute lower respiratory tract disease complicated by a severe pericarditis. RT-PCR identified picornavirus RNA in the bronchoalveolar lavage (BAL) specimen, pericardial fluid, plasma and stools. This supported the existence of a disseminated viral infection that extended to the pericardial space. 5 UTR and VP1 sequence analysis performed directly from the BAL sample allowed genotyping of the virus as a human rhinovirus C. This observation highlights the need for adapted diagnostic tools and the potential for the new rhinovirus species C to cause complications, including pericarditis. 
 Title: Pneumonia and pericarditis in a child with HRV-C infection: A case report
Output: False
Paragraph: During virus entry, the surface glycoprotein of Ebola virus (EBOV) undergoes a complex set of transformations within the endosomal network. Tools to study EBOV entry have been limited to static immunofluorescence or biochemical and functional analysis. In a recent article in mBio, Spence et al. reported a novel, live-cell-imaging method that tracks this transformational journey of EBOV in real time [J. S. Spence, T. B. Krause, E. Mittler, R. K. Jangra, and K. Chandran, mBio 7(1):e01857-15, 2016, http://dx.doi.org/10.1128/mBio.01857-15]. The assay validates known mechanisms of EBOV entry and sheds light on some novel intricacies. Direct evidence supports the hypothesis that fusion is a rare event that starts in maturing early endosomes, is completed in late endosomes, and occurs entirely in Niemann-Pick C1 (NPC1)-positive (NPC1 ؉ ) compartments. The study demonstrated that lipid mixing and productive fusion are temporally decoupled, with different energetic barriers and a protease-dependent step between the two events. Analysis of the mechanism of action of an important class of EBOV neutralizing antibodies, such as KZ52 and ZMapp, provides direct evidence that these antibodies act by inhibiting the membrane fusion. 
 Title: Chasing Ebola through the endosomal labyrinth
Output: False
Paragraph: The present work was conducted to investigate the antioxidant activity and neuroprotective effects of Tripterygium regelii extract (TRE) on H 2 O 2 -induced apoptosis in human dopaminergic cells, SH-SY5Y. TRE possessed considerable amounts of phenolics (282.73 mg tannic acid equivalents/g of extract) and flavonoids (101.43 mg naringin equivalents/g of extract). IC 50 values for reducing power and DPPH radical scavenging activity were 52.51 and 47.83 lg, respectively. The H 2 O 2 scavenging capacity of TRE was found to be 57.68 lM 9 lg -1 min -1 . By examining the effects of TRE on SH-SY5Y cells injured by H 2 O 2 , we found that after incubation of cells with TRE prior to H 2 O 2 exposure, the H 2 O 2 induced cytotoxicity was significantly reversed and the apoptotic features such as change in cellular morphology, nuclear condensation and DNA fragmentation was inhibited. Moreover, TRE was very effective attenuating the disruption of mitochondrial membrane potential and apoptotic cell death induced by H 2 O 2 . TRE extract effectively suppressed the up-regulation of Bax, Caspase-3 and -9, and down-regulation of Bcl-2. Moreover, TRE pretreatment evidently increased the tyrosine hydroxylase (TH) and brain-derived neurotrophic factor (BDNF) in SH-SY5Y cells. These findings demonstrate that TRE protects SH-SY5Y cells against H 2 O 2 -induced injury and antioxidant properties may account for its neuroprotective actions and suggest that TRE might potentially serve as an agent for prevention of neurodegenerative disease associated with oxidative stress. 
 Title: Antioxidant Activity and Protective Effects of Tripterygium regelii Extract on Hydrogen Peroxide-Induced Injury in Human Dopaminergic Cells, SH-SY5Y
Output: True
Paragraph: Objective: Health literacy has become a global issue, and it is important that patients and individuals are able to use information technology to access health information and educational services. The research objective is to develop a Saudi e-health literacy scale (SeHL) for measuring e-health literacy among Saudis suffering from non-communicable diseases (NCD). Methods: Overall, 14 relevant papers in related interdisciplinary fields were reviewed to select the most useful literacy dimensions. From these articles, we extracted the most common dimensions used to measure e-health literacy across the disciplines. Multiple workshops with multidisciplinary team members reviewed and evaluated items for SeHL. Results: Four key aspects of e-health literacy-use of technology/media, information-seeking, usefulness and confidence-were identified and integrated as e-health literacy dimensions. These will be used to measure e-health literacy among Saudi patients with NCDs. A translation from Arabic to English was performed in order to ensure that translation process was accurate. A SeHL scale was developed to measure e-health literacy among Saudi patients. By understanding e-health literacy levels, we will be able to create a patient-education system to be used by patients in Saudi Arabia. Conclusions: As information technology is increasingly used by people of all ages all over the world, e-health literacy has been identified as a key factor in determining health outcomes. To date, no comprehensive scale exists to assess e-health literacy levels among speakers of Arabic, particularly among people with NCD such as diabetes, cardiovascular diseases and hypertension. 
 Title: Saudi Arabia, 5 Prince Sultan Military Medical City, AlSulimaniah, Riyadh 11159, Saudi Arabia, 6 King Faisal Specialist and Research Center
Output: False
Paragraph: Paramyxovirus entry into cells requires fusion of the viral and cell membranes mediated by one of the major virus glycoproteins, the fusion (F) glycoprotein which transits from a metastable pre-fusion conformation to a highly stable post-fusion structure during the membrane fusion process. F protein refolding involves large conformational changes of the protein trimer. One of these changes results in assembly of two heptad repeat sequences (HRA and HRB) from each protomer into a six-helix bundle (6HB) motif. To assist in distinguishing pre-and post-fusion conformations of the Pneumovirinae F proteins, and as extension of previous work , a general strategy was designed to obtain polyclonal and particularly monoclonal antibodies specific of the 6HB motif of the Pneumovirinae fusion protein. The antibodies reported here should assist in the characterization of the structural changes that the F protein of human metapneumovirus or respiratory syncytial virus experiences during the process of membrane fusion. 
 Title: Generation of monoclonal antibodies specific of the postfusion conformation of the Pneumovirinae fusion (F) protein
Output: True
Paragraph: The High-speed Railway (HSR) network in China is the largest in the world, competing intensively with airlines for inter-city travel. Panel data from 2007 to 2013 for 138 routes with HSR-air competition were used to identify the ex-post impacts of the entry of HSR services, the duration of operating HSR services since entry, and the specific impacts of HSR transportation variables such as travel time, frequency, and ticket fares on air passenger flows in China. The findings show that the entry of new HSR services in general leads to a 27% reduction in air travel demand. After two years of operating HSR services, however, the negative impact of HSR services on air passenger flows tends to further increase. The variations of the frequency in the temporal dimension and the travel time in the spatial dimension significantly affect air passenger flows. Neither in the temporal nor spatial dimensions are HSR fares strongly related to air passenger flows in China, due to the government regulation of HSR ticket prices during the period of analysis. The impacts of different transportation variables found in this paper are valuable to consider by operational HSR companies in terms of scheduling and planning of new routes to increase their competitiveness relative to airlines. 
 Title: The implications of high-speed railways on air passenger flows in China
Output: False
Paragraph: The innate immune system detects viruses through molecular sensors that trigger the production of type I interferons (IFN-I) and inflammatory cytokines. Because viruses vary tremendously in size, structure, genomic composition, and tissue tropism, multiple sensors are required to detect their presence in various cell types and tissues. In this review, we summarize current knowledge of the diversity, specificity, and signaling pathways downstream of viral sensors and ask whether two distinct sensors that recognize the same viral component are complementary, compensatory, or simply redundant. We also discuss why viral sensors are differentially distributed in distinct cell types and whether a particular cell type dominates the IFN-I response during viral infection. Finally, we review evidence suggesting that inappropriate signaling through viral sensors may induce autoimmunity. The picture emerging from these studies is that disparate viral sensors in different cell types form a dynamic and integrated molecular network that can be exploited for improving vaccination and therapeutic strategies for infectious and autoimmune diseases. 
 Title: dsRNA sensors and plasmacytoid dendritic cells in host defense and autoimmunity The primary response to viral detection: type I interferons
Output: False
Paragraph: Coronaviruses (CoVs) continuously threaten human health. However, to date, the evolutionary mechanisms that govern CoV strain persistence in human populations have not been fully understood. In this study, we characterized the evolution of the major antigen-spike (S) gene in the most prevalent human coronavirus (HCoV) OC43 using phylogenetic and phylodynamic analysis. Among the five known HCoV-OC43 genotypes (A to E), higher substitution rates and dN/dS values as well as more positive selection sites were detected in the S gene of genotype D, corresponding to the most dominant HCoV epidemic in recent years. Further analysis showed that the majority of substitutions were located in the S1 subunit. Among them, seven positive selection sites were chronologically traced in the temporal evolution routes of genotype D, and six were located around the critical sugar binding region in the N-terminal domain (NTD) of S protein, an important sugar binding domain of CoV. These findings suggest that the genetic drift of the S gene may play an important role in genotype persistence in human populations, providing insights into the mechanisms of HCoV-OC43 adaptive evolution. Coronaviruses (CoVs) are widely found in humans as well as in mammalian and avian species, causing asymptomatic infections or respiratory tract disorders, and gastroenteritis of varying severity 1 . CoVs belong to the genus Coronavirus of family Coronaviridae, and are classified into four genera, Alphacoronavirus (α -CoV), Betacoronavirus (ß-CoV), Gammacoronavirus, and Deltacoronavirus based on phylogenetics and serology 1 . To date, α -CoV [including human CoV (HCoV)-229E and NL63] and ß-CoV [including HCoV-OC43, HKU1, Severe Acute Respiratory Syndrome CoV (SARS-CoV) and Middle East Respiratory Syndrome CoV (MERS-CoV)] are known to infect human beings 1 . Interspecies transmission is a common phenomenon for CoVs that may be responsible for generation of new CoV epidemics during viral evolution 2-5 . For instance, the feline CoV (FCoV) type II, a member of α -CoV, might be generated by a double recombination between FCoV type I and canine CoV 4 . Interestingly, porcine hemagglutinating encephalomyelitis virus, bovine CoV (BCoV) and HCoV-OC43 of ß-CoV are thought to have evolved from the same common ancestor 5 . During evolution, high frequencies of homologous RNA recombination and gene mutations are considered the main forces that push CoVs to adapt to specific hosts. Such events can lead to emergence of new strains or genotypes within a certain species, and even to new species, causing epidemic or zoonotic outbreaks that continuously threaten human health 2,3 . This phenomenon is exemplified by the recent emergence of SARS-CoV and MERS-CoV 6,7 . However, the detailed evolutionary mechanism of interspecies transmission and the persistence of CoVs in specific hosts have yet to be fully elucidated. 
 Title: Genetic drift of human coronavirus OC43 spike gene during adaptive evolution OPEN
Output: False
Paragraph: Infectious bronchitis virus (IBV) causes highly contagious respiratory or urogenital tract diseases in chickens. The Maryland 27(Md27) strain was first isolated in 1976 from diseased chicken flocks in the Delmarva Peninsula region. To understand the genetic diversity and phylogenetic relationship of existing strains with Md27, the complete nucleotide sequence of the 3'end coding region (~7.2 kb) of Md27 was determined and compared with other IBV strains and coronaviruses. It has the same S-3-M-5-N-3' gene order, as is the case of other IBV strains. The spike gene of Md27 exhibits 97% identity with the SE17 strain. There are deletions at the spike gene, non-coding region between M and 5 genes, and at the 3'untranslated region (UTR), which is different from Ark-like strains. Phylogenetic analysis and sequence alignments demonstrate that Md27 is a chimera containing different gene segments that are most closely related to the SE17, Conn and JMK strains. This current study provides evidence for genomic mutations and intergenic recombination that have taken place in the evolution of IBV strain Md27. 
 Title: Complete Nucleotide Analysis of the Structural Genome of the Infectious Bronchitis Virus Strain Md27 Reveals its Mosaic Nature
Output: True
Paragraph: Background: Nonspecific interstitial pneumonia (NSIP) is characterized by interstitial infiltration of T lymphocytes, and subpopulations of these cells may be associated with the progression of fibrosis. However, few studies evaluate the correlation of prognosis with this characteristic. Therefore, we performed morphological and quantitative analyses of T lymphocytes in patients with NSIP and evaluated the relationship between T lymphocytes and prognosis. Methods: Immunohistochemistry was used to detect the presence of CD4+ and CD8+ T lymphocytes in 55 biopsies of patients with NSIP to determine the numbers of these T cell subpopulations in lymphoid follicles as well as in perivascular, interstitial, and peribronchial anatomical compartments. The relationship between CD4+ and CD8+ T lymphocyte populations and prognosis was analyzed. Results: The mean age of 55 patients was 48.9 ± 10.5 years, and 36 (65 %) of patients were women. All patients were followed for a mean duration of 46 ± 25 months. Thirteen (23.6 %) patients died during follow-up. Perivascular CD4+ lymphocyte infiltration (HR, 0.939; 95 % CI, 0.883-0.999; p = 0.048) was an independent risk factor for survival. Perivascular infiltrates of CD4+ T lymphocytes correlated with survival time (r = 0.270, p = 0.046). Patients with improved forced vital capacity survived longer and had higher numbers of CD4+ T lymphocytes that infiltrated perivascular tissue. The densities of CD4+ and CD8+ T lymphocytes infiltrating other tissues were not significantly associated with survival time. Conclusions: Perivascular infiltration of CD4+ T lymphocytes in patients with NSIP correlated with prognosis. The underlying mechanisms are unknown and require further studies. 
 Title: Prognosis of nonspecific interstitial pneumonia correlates with perivascular CD4+ T lymphocyte infiltration of the lung
Output: True
Paragraph: Rotavirus NSP2 is an abundant non-structural RNA-binding protein essential for forming the viral factories that support replication of the double-stranded RNA genome. NSP2 exists as stable doughnut-shaped octamers within the infected cell, representing the tail-to-tail interaction of two tetramers. Extending diagonally across the surface of each octamer are four highly basic grooves that function as binding sites for single-stranded RNA. Between the N and C-terminal domains of each monomer is a deep electropositive cleft containing a catalytic site that hydrolyzes the γ-β phosphoanhydride bond of any NTP. The catalytic site has similarity to those of the histidine triad (HIT) family of nucleotide-binding proteins. Due to the close proximity of the grooves and clefts, we investigated the possibility that the RNA-binding activity of the groove promoted the insertion of the 5′-triphosphate moiety of the RNA into the cleft, and the subsequent hydrolysis of its γ-β phosphoanhydride bond. Our results show that NSP2 hydrolyzes the γP from RNAs and NTPs through Mg 2+dependent activities that proceed with similar reaction velocities, that require the catalytic His225 residue, and that produce a phosphorylated intermediate. Competition assays indicate that although both substrates enter the active site, RNA is the preferred substrate due to its higher affinity for the octamer. The RNA triphosphatase (RTPase) activity of NSP2 may account for the absence of the 5′-terminal γP on the (−) strands of the double-stranded RNA genome segments. This is the first report of a HIT-like protein with a multifunctional catalytic site, capable of accommodating both NTPs and RNAs during γP hydrolysis. 
 Title: Histidine Triad-like Motif of the Rotavirus NSP2 Octamer Mediates both RTPase and NTPase Activities
Output: True
Paragraph: During an epidemic outbreak in a human population, susceptibility to infection can be reduced by raising awareness of the disease. In this paper, we investigate the effects of three forms of awareness (i.e., contact, local, and global) on the spread of a disease in a random network. Connectivity-correlated transmission rates are assumed. By using the mean-field theory and numerical simulation, we show that both local and contact awareness can raise the epidemic thresholds while the global awareness cannot, which mirrors the recent results of Wu et al. The obtained results point out that individual behaviors in the presence of an infectious disease has a great influence on the epidemic dynamics. Our method enriches mean-field analysis in epidemic models. 
 Title: Modeling epidemic spread with awareness and heterogeneous transmission rates in networks
Output: False
Paragraph: The phosphoprotein (P) gene of most Paramyxovirinae encodes several proteins in overlapping frames: P and V, which share a common N-terminus (PNT), and C, which overlaps PNT. Overlapping genes are of particular interest because they encode proteins originated de novo, some of which have unknown structural folds, challenging the notion that nature utilizes only a limited, well-mapped area of fold space. The C proteins cluster in three groups, comprising measles, Nipah, and Sendai virus. We predicted that all C proteins have a similar organization: a variable, disordered N-terminus and a conserved, a-helical Cterminus. We confirmed this predicted organization by biophysically characterizing recombinant C proteins from Tupaia paramyxovirus (measles group) and human parainfluenza virus 1 (Sendai group). We also found that the C of the measles and Nipah groups have statistically significant sequence similarity, indicating a common origin. Although the C of the Sendai group lack sequence similarity with them, we speculate that they also have a common origin, given their similar genomic location and structural organization. Since C is dispensable for viral replication, unlike PNT, we hypothesize that C may have originated de novo by overprinting PNT in the ancestor of Paramyxovirinae. Intriguingly, in measles virus and Nipah virus, PNT encodes STAT1-binding sites that overlap different regions of the C-terminus of C, indicating they have probably originated independently. This arrangement, in which the same genetic region encodes simultaneously a crucial functional motif (a STAT1-binding site) and a highly constrained region (the C-terminus of C), seems paradoxical, since it should severely reduce the ability of the virus to adapt. The fact that it originated twice suggests that it must be balanced by an evolutionary advantage, perhaps from reducing the size of the genetic region vulnerable to mutations. Citation: Lo MK, Søgaard TM, Karlin DG (2014) Evolution and Structural Organization of the C Proteins of Paramyxovirinae. PLoS ONE 9(2): e90003. 
 Title: Evolution and Structural Organization of the C Proteins of Paramyxovirinae
Output: False
Paragraph: During severe acute respiratory syndrome coronavirus (SARS-CoV) infection, the activity of the replication/ transcription complexes (RTC) quickly peaks at 6 hours post infection (h.p.i) and then diminishes significantly in the late post-infection stages. This "down-up-down" regulation of RNA synthesis distinguishes different viral stages: primary translation, genome replication, and finally viron assembly. Regarding the nsp8 as the primase in RNA synthesis, we confirmed that the proteolysis product of the primase (nsp8) contains the globular domain (nsp8C), and indentified the resectioning site that is notably conserved in all the three groups of coronavirus. We subsequently crystallized the complex of SARS-CoV nsp8C and nsp7, and the 3-D structure of this domain revealed its capability to interfuse into the hexadecamer super-complex. This specific proteolysis may indicate one possible mechanism by which coronaviruses to switch from viral infection to genome replication and viral assembly stages. KEYWORDS nsp8, SARS-CoV, RNA primase, viral life cycle * These authors contributed equally to the work 198 
 Title: New nsp8 isoform suggests mechanism for tuning viral RNA synthesis
Output: False
Paragraph: Epidemics of infectious diseases such as SARS, H1N1, and MERS threaten public health, particularly in large cities such as Hong Kong. We constructed a human behavior integrated hierarchical (HiHi) model based on the SIR (Susceptible, Infectious, and Recovered) model, the Wells-Riley equation, and population movement considering both spatial and temporal dimensions. The model considers more than 7 million people, 3 million indoor environments, and 2566 public transport routes in Hong Kong. Smallpox, which could be spread through airborne routes, is studied as an example. The simulation is based on people's daily commutes and indoor human behaviors, which were summarized by mathematical patterns. We found that 59.6%, 18.1%, and 13.4% of patients become infected in their homes, offices, and schools, respectively. If both work stoppage and school closure measures are taken when the number of infected people is greater than 1000, an infectious disease will be effectively controlled after 2 months. The peak number of infected people will be reduced by 25% compared to taking no action, and the time of peak infections will be delayed by about 40 days if 90% of the infected people go to hospital during the infectious period. When ventilation rates in indoor environments increase to five times their default settings, smallpox will be naturally controlled. Residents of Kowloon and the north part of Hong Kong Island have a high risk of infection from airborne infectious diseases. Our HiHi model reduces the calculation time for infection rates to an acceptable level while preserving accuracy. 
 Title: A human behavior integrated hierarchical model of airborne disease transmission in a large city
Output: False
Paragraph: h i g h l i g h t s • We obtained a spatial epidemic model with logistic growth. • Using multiple-scale analysis, we present amplitude equations. • There are different types of stationary patterns. • Reaction diffusion epidemic systems have rich dynamics. Mathematical models are very useful in analyzing the spread and control of infectious diseases which can be used to predict the developing tendency of the infectious disease, determine the key factors and to seek the optimum strategies of disease control. As a result, we investigated the pattern dynamics of a spatial epidemic model with logistic growth. By using amplitude equation, we found that there were different types of stationary patterns including spotted, mixed, and stripe patterns, which mean that spatial motion of individuals can form high density of diseases. The obtained results can be extended in other related fields, such as vegetation patterns in ecosystems. 
 Title: Physica A Dynamics of an epidemic model with spatial diffusion
Output: True
Paragraph: Interferon lambda 4 (IFNλ4) has been recently known and studied for its role in hepatitis C virus (HCV) infection, but its clinical potential is significantly hampered due to its poor expression in vitro. Our study reports the successful production of IFNλ4 from a mammalian cell line through a glycoengineering and structure-based approach. We introduced de novo N-glycosylation of IFNλ4, guided by structural analysis, and produced IFNλ4 variants in Expi293F that displayed improved expression and potency. To preserve the structure and functionality of IFNλ4, the model structure of the IFNλ4 signaling complex was analyzed and the N-glycosylation candidate sites were selected. The receptor binding activity of engineered IFNλ4 variants and their receptormediated signaling pathway were similar to the E. coli version of IFNλ4 (eIFNλ4), while the antiviral activity and induction levels of interferon-stimulated gene (ISG) were all more robust in our variants. Our engineered IFNλ4 variants may be further developed for clinical applications and utilized in basic research to decipher the immunological roles of IFNλ4. Previously, the transient expression of wild-type IFNλ4 in mammalian cells failed to produce significant amounts of recombinant 
 Title: Structure-based glycoengineering of interferon lambda 4 enhances its productivity and anti-viral potency
Output: True
Paragraph: Profiles of antibodies to the nucleocapsid protein of the severe acute respiratory syndrome (SARS)-associated coronavirus in 445 probable SARS patients and 3,749 healthy people or non-SARS patients were analyzed by antigen-capturing enzyme-linked immunosorbent assay. Antinucleocapsid antibodies were elucidated in 17.5% of the probable SARS patients 1 to 7 days after the onset of symptoms and in 80% of the patients 8 to 14 days after the onset. About 90% of the probable SARS patients were positive 15 or more days after illness. Antibody titers increased up to 70 days, and high antibody titers were maintained at least for another 3 months. Of the healthy people and non-SARS patients, only seven (0.187%) were weakly positive. FIG. 1. Development of anti-N protein antibody titers over time in 445 patients who probably had SARS. 228 NOTES CLIN. DIAGN. LAB. IMMUNOL. 
 Title: Profile of Antibodies to the Nucleocapsid Protein of the Severe Acute Respiratory Syndrome (SARS)-Associated Coronavirus in Probable SARS Patients
Output: True
Paragraph: The main protease of coronaviruses and the 3C protease of enteroviruses share a similar active-site architecture and a unique requirement for glutamine in the P1 position of the substrate. Because of their unique specificity and essential role in viral polyprotein processing, these proteases are suitable targets for the development of antiviral drugs. In order to obtain near-equipotent, broad-spectrum antivirals against alphacoronaviruses, betacoronaviruses, and enteroviruses, we pursued a structure-based design of peptidomimetic α-ketoamides as inhibitors of main and 3C proteases. Six crystal structures of protease−inhibitor complexes were determined as part of this study. Compounds synthesized were tested against the recombinant proteases as well as in viral replicons and virus-infected cell cultures; most of them were not cell-toxic. Optimization of the P2 substituent of the αketoamides proved crucial for achieving near-equipotency against the three virus genera. The best near-equipotent inhibitors, 11u (P2 = cyclopentylmethyl) and 11r (P2 = cyclohexylmethyl), display low-micromolar EC 50 values against enteroviruses, alphacoronaviruses, and betacoronaviruses in cell cultures. In Huh7 cells, 11r exhibits three-digit picomolar activity against the Middle East Respiratory Syndrome coronavirus. 
 Title: α-Ketoamides as Broad-Spectrum Inhibitors of Coronavirus and Enterovirus Replication: Structure-Based Design, Synthesis, and Activity Assessment
Output: False