niryuu/sni-each-converted huggingface dataset:
Paragraph: Background: Bronchiolitis obliterans organizing pneumonia (BOOP) is a type of diffuse interstitial lung disease characterized by the pathology of fibroblastic plugs in the lumens of the respiratory bronchioles, alveolar ducts, and alveoli. The occurrence of BOOP in human immunodeficiency virus (HIV)-infected patients has rarely been described, and there have been no clinical case reports in Korea. Case presentation: A 24-year-old female who had been diagnosed with HIV ten years prior was admitted due to a 1-year history of cough and sputum production and a 3-day history of fever. She had poor adherence to anti-retroviral therapy (ART) due to gastrointestinal troubles. At the time of admission, her CD4 T-cell count was 5 cells/mm 3 . A high resolution computed tomography (CT) scan showed tiny centrilobular nodules with a tree-in-bud pattern in both lungs. Bacterial culture, Pneumocystis jirovecii polymerase chain reaction (PCR), Aspergillus galactomannan antigen (Ag) assay, and respiratory virus PCR were negative. Rapid chest x-ray improvement was seen after a 7-day treatment with anti-tuberculosis medication, ceftriaxone, and clarithromycin. Miliary tuberculosis seemed unlikely considering the rapid radiologic improvement and negative tuberculosis PCR results. Due to the unknown etiology, we performed video-assisted thoracoscopic surgery (VATS) to determine the cause of the diffuse lung infiltration. Pathologic findings were consistent with BOOP, while tissue acid-fast bacilli (AFB) stain and tuberculosis PCR results were negative. Tuberculosis medication and intravenous ceftriaxone were discontinued, while treatment with clarithromycin monotherapy was sustained. Five months after discharge, the patient was asymptomatic with a normal chest x-ray and as her adherence to ART improved, her CD4 T-cell count rose to 181 cells/mm 3 . Clarithromycin was discontinued at that time and the patient is currently receiving regular outpatient follow-up. Conclusion: This case suggests that macrolides are a potential treatment option in HIV-infected patients with mild BOOP. In cases that are otherwise unexplained or unresponsive to treatment, BOOP should be taken into consideration and surgical biopsy performed to confirm a diagnosis of BOOP. 
 Title: A case of bronchiolitis obliterans organizing pneumonia in an HIV-infected Korean patient successfully treated with clarithromycin
Output: True
Paragraph: For epidemic control, rapid identification and characterization of the responsible unknown agent are crucial. To address this critical question, a method was developed for virus discovery based on a flexible nested-PCR subtraction hybridization. As a positive control, we used hepatitis C virus as a hypothetical unrecognized virus and "discover" it in the sample. Using template-switching universal long-PCR to produce large quantities of cDNA, our nested-PCR-based subtractive hybridization coupled with a single-strand deletion technology removed most of the common cDNA. Following subtraction hybridization, a cDNA library was constructed and displayed by differential reverse dot blot hybridization. This new genomic subtraction hybridization method will be ideally suited to identify rapidly any previously unrecognized viral agent. Published by Elsevier B.V. 
 Title: Rapid approach to identify an unrecognized viral agent
Output: False
Paragraph: Rabies is one of the most deadly infectious diseases, with a case-fatality rate approaching 100%. The disease is established on all continents apart from Antarctica; most cases are reported in Africa and Asia, with thousands of deaths recorded annually. However, the estimated annual fi gure of almost 60 000 human rabies fatalities is probably an underestimate. Almost all cases of human rabies result from bites from infected dogs. Therefore, the most cost-eff ective approach to elimination of the global burden of human rabies is to control canine rabies rather than expansion of the availability of human prophylaxis. Mass vaccination campaigns with parenteral vaccines, and advances in oral vaccines for wildlife, have allowed the elimination of rabies in terrestrial carnivores in several countries worldwide. The subsequent reduction in cases of human rabies in such regions advocates the multidisciplinary One Health approach to rabies control through the mass vaccination of dogs and control of canine populations. 
 Title: Current status of rabies and prospects for elimination
Output: False
Paragraph: This paper proposes an ethical framework for evaluating biosafety risks of gain-of-function (GOF) experiments that create novel strains of influenza expected to be virulent and transmissible in humans, so-called potential pandemic pathogens (PPP). Such research raises ethical concerns because of the risk that accidental release from a laboratory could lead to extensive or even global spread of a virulent pathogen. Biomedical research ethics has focused largely on human subjects research, while biosafety concerns about accidental infections, seen largely as a problem of occupational health, have been ignored. GOF/PPP research is an example of a small but important class of research where biosafety risks threaten public health, well beyond the small number of persons conducting the research. We argue that bioethical principles that ordinarily apply only to human subjects research should also apply to research that threatens public health, even if, as in GOF/PPP studies, the research involves no human subjects. Specifically we highlight the Nuremberg Code's requirements of "fruitful results for the good of society, unprocurable by other methods," and proportionality of risk and humanitarian benefit, as broad ethical principles that recur in later documents on research ethics and should also apply to certain types of research not involving human subjects. We address several potential objections to this view, and conclude with recommendations for bringing these ethical considerations into policy development. 
 Title: The Ethics of Biosafety Considerations in Gain-of-Function Research Resulting in the Creation of Potential Pandemic Pathogens
Output: True
Paragraph: Recombinant proteins are traditionally limited to linear configuration. Herein, we report in vivo protein topology engineering using highly efficient, mechanically interlocking SpyX modules named AXB and BXA. SpyX modules are protein domains composed of p53dim (X), SpyTag (A), and SpyCatcher (B). The p53dim guides the intertwining of the two nascent protein chains followed by autocatalytic isopeptide bond formation between SpyTag and SpyCatcher to fulfill the interlocking, leading to a variety of backbone topologies. Direct expression of AXB or BXA produces protein catenanes with distinct ring sizes. Recombinant proteins containing SpyX modules are obtained either as mechanically interlocked obligate dimers if the protein of interest is fused to the N-or C-terminus of SpyX modules, or as star proteins if the protein is fused to both N-and C-termini. As examples, cellular syntheses of dimers of (GB1) 2 (where GB1 stands for immunoglobulin-binding domain B1 of streptococcal protein G) and of four-arm elastin-like star proteins were demonstrated. Comparison of the catenation efficiencies in different constructs reveals that BXA is generally much more effective than AXB, which is rationalized by the arrangement of three domains in space. Mechanical interlocking induces considerable stability enhancement. Both AXB and BXA have a melting point ∼20°C higher than the linear controls and the BXA catenane has a melting point~2°C higher than the cyclic control BX'A. Notably, four-arm elastin-like star proteins demonstrate remarkable tolerance against trypsin digestion. The SpyX modules provide a convenient and versatile approach to construct unconventional protein topologies via the "assembly-reaction" synergy, which opens a new horizon in protein science for stability enhancement and function reinforcement via topology engineering. 
 Title: Topology Engineering of Proteins in Vivo Using Genetically Encoded, Mechanically Interlocking SpyX Modules for Enhanced Stability
Output: True
Paragraph: During viral and bacterial infections, the innate immune system recognizes various types of pathogen-associated molecular patterns (PAMPs), such as nucleic acids, via a series of membrane-bound or cytosolic pattern-recognition receptors. These include Toll-like receptors (TLRs), RIG-I-like receptors (RLRs), AIM2-like receptors (ALRs), and cytosolic DNA sensors. The binding of PAMPs to these receptors triggers the production of type I interferon (IFN) and inflammatory cytokines. Type I IFN induces the expression of interferon stimulated genes (ISGs), which protect surrounding cells from infection. Some ISGs are nucleic acids-binding proteins that bind viral nucleic acids and suppress their replication. As nucleic acids are essential components that store and transmit genetic information in every species, infectious pathogens have developed systems to escape from the host nucleic acid recognition system. Host cells also have their own nucleic acids that are frequently released to the extracellular milieu or the cytoplasm during cell death or stress responses, which, if able to bind pattern-recognition receptors, would induce autoimmunity and inflammation. Therefore, host cells have acquired mechanisms to protect themselves from contact with their own nucleic acids. In this review, we describe recent research progress into the nucleic acid recognition mechanism and the molecular bases of discrimination between self and non-self-nucleic acids. 
 Title: Discrimination Between Self and Non-Self-Nucleic Acids by the Innate Immune System
Output: True
Paragraph: The thiol-disulfide oxidoreductase thioredoxin-1 (Trx1) is known to be secreted by leukocytes and to exhibit cytokine-like properties. Extracellular effects of Trx1 require a functional active site, suggesting a redox-based mechanism of action. However, specific cell surface proteins and pathways coupling extracellular Trx1 redox activity to cellular responses have not been identified so far. Using a mechanism-based kinetic trapping technique to identify disulfide exchange interactions on the intact surface of living lymphocytes, we found that Trx1 catalytically interacts with a single principal target protein. This target protein was identified as the tumor necrosis factor receptor superfamily member 8 (TNFRSF8/CD30). We demonstrate that the redox interaction is highly specific for both Trx1 and CD30 and that the redox state of CD30 determines its ability to engage the cognate ligand and transduce signals. Furthermore, we confirm that Trx1 affects CD30dependent changes in lymphocyte effector function. Thus, we conclude that receptor-ligand signaling interactions can be selectively regulated by an extracellular redox catalyst. 
 Title: Selective redox regulation of cytokine receptor signaling by extracellular thioredoxin-1
Output: False
Paragraph: The nucleocapsid protein gene of transmissible gastroenteritis virus, 1 149 bp in length, was amplified by RT-PCR from isolated strain HB06 and cloned into pMD18-T. Sequence comparison with other transmissible gastroenteritis virus (TGEV) strains selected from the Gene Bank revealed that the homology of N gene complete sequence shares more than 97% in nucleotide. N gene was cloned into BamHI and EcoRI multiple cloning sites of the prokaryotic expression vector pET 20 b, and named pETN. After being induced by isopropyl-b-D-thiogalactopyranoside (IPTG), the recombinant nucleocapsid protein was expressed. The result of SDS-PAGE and Western-blot showed that the recombinant nucleocapsid protein was 47 kDa and had strong positive reactions with TGEV-specific antibody. 
 Title: Cloning and expression of nucleocapsid protein gene of TGEV HB06 strain
Output: False
Paragraph: Human herpesvirus type 6B (HHV-6B) is a strong inducer of IFN-alpha and has the capacity to promote Th1 responses and block Th2 responses in vitro. In this study we addressed whether inactivated HHV-6B can also induce IFN lambda responses and to what extent interferons alpha and lambda affect Th1/Th2 polarization. We show that inactivated HHV-6B induced IFN-lambda1 (IL-29) but not IFN-lambda2 (IL-28A) responses in plasmacytoid DC and that this induction was mediated through TLR9. We have previously shown that HHV-6B promotes Th1 responses and blocks Th2 responses in both humans and mice. We now show that neutralization of IFN-alpha but not IFN-lambda1 blocked the HHV-6B-induced enhancement of Th1 responses in MLR, but did not affect the HHV-6-induced dampening of Th2 responses. Similarly, blockage of TLR9 counteracted HHV-6Bs effects on the Th1/Th2 balance. In addition, IFN-alpha but not IFN-lambda1 promoted IFN-gamma production and blocked IL-5 and IL-13 production in purified CD4+ T-cells. The lack of effect of IFN-lambda1 correlated with the absence of the IFN-lambda receptor IL-28Ralfa chain on the cell surface of both resting and activated CD4+ T-cells. We conclude that inactivated HHV-6B is a strong inducer of IFN-lambda1 in plasmacytoid DC and that this induction is TLR9dependent. However, human CD4+ T-cells do not express the IFN-lambda receptor and are refractory to IFN-lambda1 treatment. The HHV-6B-induced alterations in the Th1/Th2 balance are instead mediated mainly through TLR9 and IFNalpha. Citation: Nordströ m I, Eriksson K (2012) HHV-6B Induces IFN-Lambda1 Responses in Cord Plasmacytoid Dendritic Cells through TLR9. PLoS ONE 7(6): e38683. 
 Title: HHV-6B Induces IFN-Lambda1 Responses in Cord Plasmacytoid Dendritic Cells through TLR9
Output: False
Paragraph: Porcine aminopeptidase N (pAPN) is a cellular membrane protein and a functional receptor for porcine coronaviruses. Here, we describe the heterologous expression of pAPN without signal peptide in BL21(DE3)pLysS host cells. The Escherichia coli (E. coli) harboring the recombinant construct was efficiently induced to express the pAPN protein at a high level. The most optimal expression profile for pAPN expression was investigated. By inoculating a rabbit with the purified pAPN, a high tittered specific antibody was achieved. Biologically, the antibody reacted with either pAPN-expressing E. coli or native pAPN on the surface of swine testis cells. The pAPN and its specific antibody blocked transmissible gastroenteritis coronavirus infection in vitro. Furthermore, the localization of pAPN on the small intestine of swine was analyzed by immunohistochemistry. 
 Title: Expression and functional analysis of porcine aminopeptidase N produced in prokaryotic expression system
Output: True
Paragraph: Interferon lambdas (IFN-λs; IFNL1-4) modulate immunity in the context of infections and autoimmune diseases, through a network of induced genes. IFN-λs act by binding to the heterodimeric IFN-λ receptor (IFNLR), activating a STAT phosphorylationdependent signaling cascade. Thereby hundreds of IFN-stimulated genes are induced, which modulate various immune functions via complex forward and feedback loops. When compared to the well-characterized IFN-α signaling cascade, three important differences have been discovered. First, the IFNLR is not ubiquitously expressed: in particular, immune cells show significant variation in the expression levels of and susceptibilities to IFN-λs. Second, the binding affinities of individual IFN-λs to the IFNLR varies greatly and are generally lower compared to the binding affinities of IFN-α to its receptor. Finally, genetic variation in the form of a series of single-nucleotide polymorphisms (SNPs) linked to genes involved in the IFN-λ signaling cascade has been described and associated with the clinical course and treatment outcomes of hepatitis B and C virus infection. The clinical impact of IFN-λ signaling and the SNP variations may, however, reach far beyond viral hepatitis. Recent publications show important roles for IFN-λs in a broad range of viral infections such as human T-cell leukemia type-1 virus, rotaviruses, and influenza virus. IFN-λ also potentially modulates the course of bacterial colonization and infections as shown for Staphylococcus aureus and Mycobacterium tuberculosis. Although the immunological processes involved in controlling viral and bacterial infections are distinct, IFN-λs may interfere at various levels: as an innate immune cytokine with direct antiviral effects; or as a modulator of IFN-α-induced signaling via the suppressor of cytokine signaling 1 and the ubiquitin-specific peptidase 18 inhibitory feedback loops. In addition, the modulation of adaptive immune functions via macrophage and dendritic cell polarization, and subsequent priming, activation, and proliferation of pathogen-specific T-and B-cells may also be important elements associated with infectious disease outcomes. This review summarizes the emerging details of the IFN-λ immunobiology in the context of the host immune response and viral and bacterial infections. 
 Title: interferon Lambda: Modulating immunity in infectious Diseases
Output: True
Paragraph: Viral infections are a major global health problem, representing a significant cause of mortality with an unfavorable continuously amplified socio-economic impact. The increased drug resistance and constant viral replication have been the trigger for important studies regarding the use of nanotechnology in antiviral therapies. Nanomaterials offer unique physico-chemical properties that have linked benefits for drug delivery as ideal tools for viral treatment. Currently, different types of nanomaterials namely nanoparticles, liposomes, nanospheres, nanogels, nanosuspensions and nanoemulsions were studied either in vitro or in vivo for drug delivery of antiviral agents with prospects to be translated in clinical practice. This review highlights the drug delivery nanosystems incorporating the major antiviral classes and their transport across specific barriers at cellular and intracellular level. Important reflections on nanomedicines currently approved or undergoing investigations for the treatment of viral infections are also discussed. Finally, the authors present an overview on the requirements for the design of antiviral nanotherapeutics. 
 Title: pharmaceutics Nanomaterials Designed for Antiviral Drug Delivery Transport across Biological Barriers
Output: False
Paragraph: The frequency, social, and economic impacts of natural disasters show exponential increases in recent decades. Cities and countries around the world have begun to realize that these events are no longer "hundred year" storms, but repeat within a few years. As urbanisation continues throughout this century, more and more people and more economic activity will be concentrated in at-risk areas; especially as new arrivals in cities throughout Asia and Africa are likely to be concentrated in the highest risk districts, much as they often are in North America and Europe today. This article reviews recent growth of natural disasters and considers how a systems approach can improve approaches to mitigation and adaptation of these risks and to recovery from such events. 
 Title: A systems approach to natural disaster resilience
Output: False
Paragraph: Introduction: Accurate and timely prediction for endemic infectious diseases is vital for public health agencies to plan and carry out any control methods at an early stage of disease outbreaks. Climatic variables has been identified as important predictors in models for infectious disease forecasts. Various approaches have been proposed in the literature to produce accurate and timely predictions and potentially improve public health response. Methods: We assessed how the machine learning LASSO method may be useful in providing useful forecasts for different pathogens in countries with different climates. Separate LASSO models were constructed for different disease/country/forecast window with different model complexity by including different sets of predictors to assess the importance of different predictors under various conditions. Results: There was a more apparent cyclicity for both climatic variables and incidence in regions further away from the equator. For most diseases, predictions made beyond 4 weeks ahead were increasingly discrepant from the actual scenario. Prediction models were more accurate in capturing the outbreak but less sensitive to predict the outbreak size. In different situations, climatic variables have different levels of importance in prediction accuracy. Conclusions: For LASSO models used for prediction, including different sets of predictors has varying effect in different situations. Short term predictions generally perform better than longer term predictions, suggesting public health agencies may need the capacity to respond at short-notice to early warnings. 
 Title: The utility of LASSO-based models for real time forecasts of endemic infectious diseases: A cross country comparison
Output: False
Paragraph: In 2002 the US-based Association for Veterinary Epidemiology and Preventive Medicine (AVEPM) co-organized a symposium in St. Louis, Missouri, to honour the lifetime achievements of Calvin W. Schwabe, who had served as professor of epidemiology in both the medical and veterinary schools of the University of California, Davis until his retirement in 1991. 1 At the symposium, Schwabe gave a keynote address summarizing his ideas about how veterinary medicine should relate to other disciplines-particularly human medicine-and the wider world. Arguing against the compartmentalization of medicine by species, into human and veterinary strands, he used the opportunity to restate his longstanding arguments for a philosophy of One Medicine (OM), which sees veterinary medicine as a close collaborative partner with human medicine, working together towards the broader endeavours of healthcare and furthering knowledge in the life sciences. 2 He claimed that this positioning reflected and recognized the contributions that veterinary medicine made to a range of other fields, including comparative zoology, parasitology, epidemiology, human public health, agriculture CHAPTER 6 
 Title: Humans, Other Animals and 'One Health' in the Early Twenty-First Century
Output: True
Paragraph: Background: Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most important pathogens in the swine industry and causes important economic losses. No effective antiviral drugs against it are commercially available. We recently reported that the culture supernatant of Actinobacillus pleuropneumoniae, the porcine pleuropneumonia causative agent, has an antiviral activity in vitro against PRRSV in SJPL cells. Objectives of this study were (i) to identify the mechanism behind the antiviral activity displayed by A. pleuropneumoniae and (ii) to characterize the active molecules present in the bacterial culture supernatant. Methods: Antibody microarray analysis was used in order to point out cellular pathways modulated by the A. pleuropneumoniae supernatant. Subsequent, flow cytometry analysis and cell cycle inhibitors were used to confirm antibody microarray data and to link them to the antiviral activity of the A. pleuropneumoniae supernatant. Finally, A. pleuropneumoniae supernatant characterization was partially achieved using mass spectrometry. Results: Using antibody microarray, we observed modulations in G2/M-phase cell cycle regulation pathway when SJPL cells were treated with A. pleuropneumoniae culture supernatant. These modulations were confirmed by a cell cycle arrest at the G2/M-phase when cells were treated with the A. pleuropneumoniae culture supernatant. Furthermore, two G2/M-phase cell cycle inhibitors demonstrated the ability to inhibit PRRSV infection, indicating a potential key role for PRRSV infection. Finally, mass spectrometry lead to identify two molecules (m/z 515.2 and m/z 663.6) present only in the culture supernatant. Conclusions: We demonstrated for the first time that A. pleuropneumoniae is able to disrupt SJPL cell cycle resulting in inhibitory activity against PRRSV. Furthermore, two putative molecules were identified from the culture supernatant. This study highlighted the cell cycle importance for PRRSV and will allow the development of new prophylactic or therapeutic approaches against PRRSV. 
 Title: Actinobacillus pleuropneumoniae induces SJPL cell cycle arrest in G2/M-phase and inhibits porcine reproductive and respiratory syndrome virus replication
Output: False
Paragraph: Viroporins are viral proteins with ion channel (IC) activity that play an important role in several processes, including virus replication and pathogenesis. While many coronaviruses (CoVs) encode two viroporins, severe acute respiratory syndrome CoV (SARS-CoV) encodes three: proteins 3a, E, and 8a. Additionally, proteins 3a and E have a PDZ-binding motif (PBM), which can potentially bind over 400 cellular proteins which contain a PDZ domain, making them potentially important for the control of cell function. In the present work, a comparative study of the functional motifs included within the SARS-CoV viroporins was performed, mostly focusing on the roles of the IC and PBM of E and 3a proteins. Our results showed that the full-length E and 3a proteins were required for maximal SARS-CoV replication and virulence, whereas viroporin 8a had only a minor impact on these activities. A virus missing both the E and 3a proteins was not viable, whereas the presence of either protein with a functional PBM restored virus viability. E protein IC activity and the presence of its PBM were necessary for virulence in mice. In contrast, the presence or absence of the homologous motifs in protein 3a did not influence virus pathogenicity. Therefore, dominance of the IC and PBM of protein E over those of protein 3a was demonstrated in the induction of pathogenesis in mice. Aguilella VM, Sola I, Enjuanes L. 2018. Role of severe acute respiratory syndrome coronavirus viroporins E, 3a, and 8a in replication and pathogenesis. mBio 9:e02325-17. https://doi . 
 Title: Role of Severe Acute Respiratory Syndrome Coronavirus Viroporins E, 3a, and 8a in Replication and Pathogenesis
Output: True
Paragraph: SARS-coronavirus (SARS-CoV) replication and transcription are mediated by a replication/transcription complex (RTC) of which virus-encoded, non-structural proteins (nsps) are the primary constituents. The 16 SARS-CoV nsps are produced by autoprocessing of two large precursor polyproteins. The RTC is believed to be associated with characteristic virus-induced double-membrane structures in the cytoplasm of SARS-CoV-infected cells. To investigate the link between these structures and viral RNA synthesis, and to dissect RTC organization and function, we isolated active RTCs from infected cells and used them to develop the first robust assay for their in vitro activity. The synthesis of genomic RNA and all eight subgenomic mRNAs was faithfully reproduced by the RTC in this in vitro system. Mainly positive-strand RNAs were synthesized and protein synthesis was not required for RTC activity in vitro. All RTC activity, enzymatic and putative membrane-spanning nsps, and viral RNA cosedimented with heavy membrane structures. Furthermore, the pelleted RTC required the addition of a cytoplasmic host factor for reconstitution of its in vitro activity. Newly synthesized subgenomic RNA appeared to be released, while genomic RNA remained predominantly associated with the RTC-containing fraction. RTC activity was destroyed by detergent treatment, suggesting an important role for membranes. The RTC appeared to be protected by membranes, as newly synthesized viral RNA and several replicase/transcriptase subunits were protease-and nucleaseresistant and became susceptible to degradation only upon addition of a non-ionic detergent. Our data establish a vital functional dependence of SARS-CoV RNA synthesis on virus-induced membrane structures. 
 Title: SARS-Coronavirus Replication/Transcription Complexes Are Membrane-Protected and Need a Host Factor for Activity In Vitro
Output: True
Paragraph: Acute respiratory distress syndrome (ARDS) is a life-threatening noncardiogenic circulatory disorder of the lungs associated with critical illnesses such as sepsis, trauma, and immune and collagen vascular disease. Its mortality rate is marginally improved with the best supportive care. The demise occurs due to progressive pulmonary hypoxia and multi-organ dysfunction syndrome (MODS) with severe inflammation. Complement activation is a part of immune response against pathogen or insult in which membrane attack complex (MAC) is formed and eliminates microbes. If complement regulatory protein such as endothelial CD59 is underexpressed, MAC may also cause pulmonary vascular injury to the innocent bystander endothelial cell of host and provokes endotheliopathy that causes inflammation and pulmonary vascular microthrombosis, leading to ARDS. 
 Title: Acute Respiratory Distress Syndrome as an Organ Phenotype of Vascular Microthrombotic Disease: Based on Hemostatic Theory and Endothelial Molecular Pathogenesis
Output: True
Paragraph: Among the many medical applications of systems biology, we contend that infectious disease is one of the most important and tractable targets. We take the view that the complexity of the immune system is an inevitable consequence of its evolution, and this complexity has frustrated reductionist efforts to develop host-directed therapies for infection. However, since hosts vary widely in susceptibility and tolerance to infection, host-directed therapies are likely to be effective, by altering the biology of a susceptible host to induce a response more similar to a host who survives. Such therapies should exert minimal selection pressure on organisms, thus greatly decreasing the probability of pathogen resistance developing. A systems medicine approach to infection has the potential to provide new solutions to old problems: to identify host traits that are potentially amenable to therapeutic intervention, and the host immune factors that could be targeted by hostdirected therapies. Furthermore, undiscovered sub-groups with different responses to treatment are almost certain to exist among patients presenting with life-threatening infection, since this population is markedly clinically heterogeneous. A major driving force behind high-throughput clinical phenotyping studies is the aspiration that these subgroups, hitherto opaque to observation, may be observed in the data generated by new technologies. Subgroups of patients are unlikely to be staticserial clinical and biological phenotyping may reveal different trajectories through the pathophysiology of disease, in which different therapeutic approaches are required. We suggest there are two major goals for systems biology in infection medicine: (1) to identify subgroups of patients that share treatable features; and, (2) to integrate high-throughput data from clinical and in vitro sources in order to predict tractable therapeutic targets with the potential to alter disease trajectories for individual patients. Addresses 
 Title: Treatable traits and therapeutic targets: Goals for systems biology in infectious disease
Output: True
Paragraph: Background During each winter the hospital quality of care (QoC) in pediatric wards decreases due to a surge in pediatric infectious diseases leading to overcrowded units. Bed occupancy rates often surpass the good hospital bed management threshold of 85%, which can result in poor conditions in the workplace. This study explores how QoCscores could be improved by investing in additional beds and/or better vaccination programs against vaccine-preventable infectious diseases. Methods The Cobb-Douglas model was selected to define the improvement in QoC (%) as a function of two strategies (rotavirus vaccination coverage [%] and addition of extra hospital beds [% of existing beds]), allowing improvementisocurves to be produced. Subsequently, budget minimization was applied to determine the combination of the two strategies needed to reach a given QoC improvement at the lowest cost. Data from Jessa Hospital (Hasselt, Belgium) were chosen as an example. The annual population in the catchment area to be vaccinated was 7000 children; the winter period was 90 days with 34 pediatric beds available. Rotavirus vaccination cost per course was €118.26 and the daily cost of a pediatric bed was €436.53. The target QoC increase was fixed at 50%. The model was first built with baseline parameter values. Results The model predicted that a combination of 64% vaccine coverage and 39% extra hospital beds (& 13 extra beds) in winter would improve QoC-scores by 50% for the minimum budget allocation. Conclusion The model allows determination of the most efficient allocation of the healthcare budget between rotavirus vaccination and bed expansion for improving QoCscores during the annual epidemic winter seasons. 
 Title: Improving the Hospital Quality of Care during Winter Periods by Optimizing Budget Allocation Between Rotavirus Vaccination and Bed Expansion
Output: True
Paragraph: Most significant change in the evolution of the influenza virus is the rapid growth of the Concentrated Animal Feeding Operations (CAFOs) on a global scale. These industrial agricultural operations have the potential of housing thousands of animals in a relatively small area. Emerging Infectious Diseases (EIDs) event can be considered as a shift in the pathogen-host-environment interplay characteristics described by Engering et al. (2013) . These changes in the host-environment and the disease ecology are key to creating novel transmission patterns and selection of novel pathogens with a modification of genetic traits. With the development of CAFOs throughout the world, the need for training of animal caretakers to observe, identify, treat, vaccinate and cull if necessary is important to safeguard public health. The best defense against another pandemic of Emerging Infectious Diseases (EIDs) is the constant monitoring of the livestock and handlers of CAFOs and the live animal markets. These are the most likely epicenter of the next pandemic. 
 Title: Interaction of the role of Concentrated Animal Feeding Operations (CAFOs) in Emerging Infectious Diseases (EIDS)
Output: True
Paragraph: A loop-mediated isothermal amplification (LAMP) assay was developed for the detection of herpes simplex virus 1 (HSV-1). The specificity of the assay was tested using DNA extracted from HSV-1-infected rabbit corneal epithelium cultures, HSV-2 grown on Vero cell line, cytomegalovirus (CMV) (AD-169), varicella zoster virus (VZV) (Oka-vaccine), adenovirus, Aspergillus flavus and Staphylococcus aureus. The specificity of LAMP was confirmed by bidirectional sequencing of the amplicons. The sensitivity of the LAMP assay was tested using different concentrations of HSV-1 DNA. To evaluate the application of the LAMP assay in clinical diagnosis, we tested vitreous samples from 20 patients with suspected viral retinitis using LAMP and real-time PCR for HSV-1. The LAMP primers amplified only HSV-1 DNA; no LAMP products were detected with the DNAs of HSV-2, CMV, VZV, adenovirus A. flavus and S. aureus. The sequences of the positive HSV-1 LAMP products perfectly (99-100%) matched the HSV-1 sequences deposited in the GenBank database. LAMP is as sensitive as real-time PCR, with the lowest detection limit being 10 copies/lL of HSV-1 DNA. Of the 20 patients with suspected viral retinitis, four tested positive for HSV-1 using real-time PCR and LAMP. A 100% concordance was observed across the two methods. The LAMP assay is a rapid, highly specific and sensitive method for the diagnosis of retinitis caused by HSV-1. 
 Title: Loop-mediated isothermal amplification assay for the diagnosis of retinitis caused by herpes simplex virus-1
Output: True
Paragraph: Theoretically, there are several ways of preventing the common cold: quarantine, immunisation (or vaccination); early treatment of effected individuals; or physical barriers to reduce transmission. All these methods can be dismissed after considering the epidemiology of the common cold, apart from the last. Evidence for effectiveness for physical barriers (which include masks to reduce aerosol transmission; handwashing; and gloves and gowns) come from a variety of empirical studies. The chance of bias for these studies is variable, but we can conclude that all of these barrier methods have important potential for preventing transmission of the common cold, although some methods will not be acceptable to the community currently. 
 Title: Common Cold 211 Interventions to prevent transmission of the common cold
Output: True
Paragraph: Objective: To analyse the clinical features of COVID-19 parturients, and to compare anaesthetic regimen and clinical outcomes in parturients with or without COVID-19 undergoing cesarean delivery. Methods: Data were extracted from the electronic medical record of 3 medical institutions in Hubei Province, China, from June 1, 2019 to March 20, 2020 according to inclusion and exclusion criteria. After propensity score matching with demographics, the clinical and laboratory characteristics of parturients with or without COVID-19 were analysed. The anaesthetic regimen and clinical outcomes of themselves and their infants were compared in these two groups of parturients. Results: A total of 1,588 patients without SARS-CoV-2 infection undergoing cesarean delivery were retrospectively included. After achieving a balanced cohort through propensity score matching, 89 patients (COVID-19 group), who were diagnosed with COVID-19 by SARS-CoV-2 nucleic acid test and CT scan matched with 173 patients without COVID-19 (Control group). The SARS-CoV-2 infected parturients in the early stages of COVID-19 outbreak was much more than during the later stage. The main clinical characteristics of parturients with COVID-19 were fever (34.8%), cough (33.7%), an increased plasma CRP (52.8%) and a decreased lymphocyte counting (33.7%). A high rate of emergency and a high incidence of anaesthesia-related complications, such as pharyngalgia, multiple puncture, intraoperative hypotension, nausea, vomiting, vertigo and chills in the COVID-19 parturients. In addition, the parturients with COVID-19 had a long duration of operation and hospital stay, and an increased intraoperative oxytocin utilization and postoperative oxygen therapy. The newborns from the SARS-CoV-2 infected mothers, who received general anaesthesia, had a high risk of Apgar score ≤ 8 at 1 and 5 minutes after delivery and a higher rate of neonatal intensive care unit (NICU) admission. Conclusions: Anaesthesia-related complications occur more frequently in the COVID-19 parturients and their newborns have a high risk of distress. 
 Title: Anaesthetic managment and clinical outcomes of parturients with COVID-19: a multicentre, retrospective, propensity score matched cohort study Short Title: Obstetric anaesthesia for parturients with COVID-19
Output: True
Paragraph: as well as sporadic cases in industrialized countries. The life cycle of HEV is still poorly understood and the lack of efficient cell culture systems and animal models are the principal limitations for a detailed study of the viral replication cycle. Here we exhaustively examine all possible intraviral protein-protein interactions (PPIs) of HEV by systematic Yeast two-hybrid (Y2H) and LuMPIS screens, providing a basis for studying the function of these proteins in the viral replication cycle. Key PPIs correlate with the already published HEV 3D structure. Furthermore, we report 20 novel PPIs including the homodimerization of the RNA dependent RNA polymerase (RdRp), the self-interaction of the papain like protease, and ORF3 interactions with the papain-like protease and putative replicase components: RdRp, methylase and helicase. Furthermore, we determined the dissociation constant (K d ) of ORF3 interactions with the viral helicase, papain-like protease and methylase, which suggest a regulatory function for ORF3 in orchestrating the formation of the replicase complex. These interactions may represent new targets for antiviral drugs. Hepatitis E virus (HEV) is the causative pathogen of Hepatitis E disease, a major form of acute viral hepatitis worldwide. Four different genotypes are known in various geographical regions 1 : genotype 1 (Asia), genotype 2 (Africa and Mexico), genotype 3 (Europe and North America) and genotype 4 (Asia). The global burden of genotype 1 and 2 infections is substantial and the number of infections is estimated at 20 million per year, leading to 70,000 deaths and 3,000 stillbirths 2 . The Hepatitis E virus is a single strand plus RNA virus belonging to the family Hepeviridae. Approximately 7,200 nucleotides encode for three open reading frames (Fig. 1 ). ORF1 is a nonstructural, functional poly-protein with several defined functions 3,4 . The first functional domain encodes a methyltransferase (Met), which is required for capping the 5′ end of the HEV RNA. Next, ORF1 contains a so-called Y domain which shows significant similarities to sequences of Rubella virus and Beet necrotic yellow vein virus but whose function in the viral context remains unknown. Further downstream ORF1 contains a papain-like cysteine protease (Plp) domain. The functionality of the protease domain was often questioned but recently the processing of the ORF1 poly-protein and ORF2 capsid protein by the Plp protease has been confirmed 5 . Next, a hypervariable (V) proline-rich region is located between the putative protease domain and the subsequent so-called X domain (X). For the proline-rich domain an important role in the fine tuning of viral replication through protein-protein interactions (PPIs) has been postulated 6 . The above mentioned X domain is also known as macro-domain or ADP-Ribose binding domain and has been exclusively associated with viral protease domains in other viruses. Towards the 3′ end, ORF1 encodes for the well characterized helicase 
 Title: The Hepatitis E virus intraviral interactome
Output: False
Paragraph: The current standard care therapy for hepatitis C virus (HCV) infection consists of two regimes, namely interferon-based and interferon-free treatments. The treatment through the combination of ribavirin and pegylated interferon is expensive, only mildly effective, and is associated with severe side effects. In 2011, two direct-acting antiviral (DAA) drugs, boceprevir and telaprevir, were licensed that have shown enhanced sustained virologic response (SVR) in phase III clinical trial, however, these interferon-free treatments are more sensitive to HCV genotype 1 infection. The variable nature of HCV, and the limited number of inhibitors developed thus aim in expanding the repertoire of available drug targets, resulting in targeting the virus assembly therapeutically. (isolatek3a) and HCV genotype 4a (GT4) (isolateED43). Furthermore, we conducted a quantitative structure-activity relationship and docking interaction study. The drug NB-DNJ formed the highest number of hydrogen bond interactions with both modeled p7 proteins with high interaction energy, followed by BIT225. A flavonoid screen demonstrated that Epigallocatechin gallate (EGCG), nobiletin, and quercetin, have more binding modes in GT3 than in GT4. Thus, the predicted p7 protein molecule of HCV from GT3 and GT4 provides a general avenue to target structure-based antiviral compounds. We hypothesize that the inhibitors of viral p7 identified in this screen may be a new class of potent agents, but further confirmation in vitro and in vivo is essential. This structure-guided drug design for both GT3 and GT4 can lead to the identification of drug-like natural compounds, confirming p7 as a new target in the rapidly increasing era of HCV. Computational Docking Study of HCVp7 Ion Channel from Genotype 3 and 4 PLOS ONE | 
 Title: Computational Docking Study of p7 Ion Channel from HCV Genotype 3 and Genotype 4 and Its Interaction with Natural Compounds
Output: False
Paragraph: We replaced the HIV-1 nucleocapsid (NC) domain with different N-coding sequences to test SARS-CoV nucleocapsid (N) self-interaction capacity, and determined the capabilities of each chimera to direct viruslike particle (VLP) assembly. Analysis results indicate that the replacement of NC with the carboxyl-terminal half of the SARS-CoV N resulted in the production of wild type (wt)-level virus-like particles (VLPs) with the density of a wt HIV-1 particle. When co-expressed with SARS-CoV N, chimeras containing the N carboxyl-terminal half sequence efficiently packaged N. However, the same was not true for the chimera bearing the N amino-terminal half sequence, despite its production of substantial amounts of VLPs. According to further analysis, HIV-1 NC replacement with N residues 2-213, 215-421, or 234-421 resulted in efficient VLP production at levels comparable to that of wt HIV-1, but replacement with residues 215-359, 302-421, 2-168, or 2-86 failed to restore VLP production to wildtype levels. The results suggest that the domain conferring the ability to direct VLP assembly and release in SARS-CoV N is largely contained between residues 168 and 421. 
 Title: Severe acute respiratory syndrome coronavirus nucleocapsid protein confers ability to efficiently produce virus-like particles when substituted for the human immunodeficiency virus nucleocapsid domain
Output: False
Paragraph: The spike (S) protein of severe acute respiratory syndrome (SARS) coronavirus (CoV), a type I transmembrane envelope glycoprotein, consists of S1 and S2 domains responsible for virus binding and fusion, respectively. The S1 contains a receptor-binding domain (RBD) that can specifically bind to angiotensin-converting enzyme 2 (ACE2), the receptor on target cells. Here we show that a recombinant fusion protein (designated RBD-Fc) containing 193-amino acid RBD (residues 318-510) and a human IgG1 Fc fragment can induce highly potent antibody responses in the immunized rabbits. The antibodies recognized RBD on S1 domain and completely inhibited SARS-CoV infection at a serum dilution of 1:10,240. Rabbit antisera effectively blocked binding of S1, which contains RBD, to ACE2. This suggests that RBD can induce highly potent neutralizing antibody responses and has potential to be developed as an effective and safe subunit vaccine for prevention of SARS. 
 Title: Receptor-binding domain of SARS-CoV spike protein induces highly potent neutralizing antibodies: implication for developing subunit vaccine
Output: False
Paragraph: Flos Trollii, the flowers of Trollius chinensis Bunge, has been widely used in Chinese and Mongolian medicine for its efficacy of heat-clearing and detoxification. This drug has both medicinal and edible applications, and has led to various pharmacognosy, natural product chemistry, and pharmacology studies. As a result, its chemical constituents and bioactivities have been well-characterized in recent years. Nevertheless, a couple of critical issues, such as the major effective components, are still unresolved. The present review summarizes research progress on this drug regarding the constituents and bioactivities based on investigations in these laboratories and the results reported in recent publications. In addition, the pending issues are discussed and constructive suggestions for further investigation are proposed. 
 Title: Chinese Journal of Natural Medicines Investigation on Flos Trollii: Constituents and bioactivities
Output: False
Paragraph: The interferon-induced transmembrane protein 3 (IFITM3) is a widely expressed potent antiviral effector of the host innate immune system. It restricts a diverse group of pathogenic, enveloped viruses, by interfering with endosomal fusion. In this report, the swine IFITM3 (sIFITM3) gene was cloned. It shares the functionally conserved CD225 domain and multiple critical amino acid residues (Y19, F74, F77, R86 and Y98) with its human ortholog, which are essential for antiviral activity. Ectopic expression of sIFITM3 significantly inhibited non-enveloped foot-and-mouth disease virus (FMDV) infection in BHK-21 cells. Furthermore, sIFITM3 blocked FMDV infection at early steps in the virus life cycle by disrupting viral attachment to the host cell surface. Importantly, inoculation of 2-day-old suckling mice with a plasmid expressing sIFITM3 conferred protection against lethal challenge with FMDV. These results suggest that sIFITM3 is a promising antiviral agent and that can safeguard the host from infection with FMDV. 
 Title: Swine interferon-induced transmembrane protein, sIFITM3, inhibits foot-and-mouth disease virus infection in vitro and in vivo
Output: True