niryuu/sni-each-converted huggingface dataset:
Paragraph: Zika virus (ZIKV) infection in pregnant women can lead to fetal deaths and malformations. We have previously reported that ZIKV envelope protein domain III (EDIII) is a subunit vaccine candidate with cross-neutralization activity; however, like many other subunit vaccines, its efficacy is limited. To improve the efficacy of this subunit vaccine, we identified a nonneutralizing epitope on ZIKV EDIII surrounding residue 375, which is buried in the full-length envelope protein but becomes exposed in recombinant EDIII. We then shielded this epitope with an engineered glycan probe. Compared to the wild-type EDIII, the mutant EDIII induced significantly stronger neutralizing antibodies in three mouse strains and also demonstrated significantly improved efficacy by fully protecting mice, particularly pregnant mice and their fetuses, against high-dose lethal ZIKV challenge. Moreover, the mutant EDIII immune sera significantly enhanced the passive protective efficacy by fully protecting mice against lethal ZIKV challenge; this passive protection was positively associated with neutralizing antibody titers. We further showed that the enhanced efficacy of the mutant EDIII was due to the shielding of the immunodominant nonneutralizing epitope surrounding residue 375, which led to immune refocusing on the neutralizing epitopes. Taken together, the results of this study reveal that an intrinsic limitation of subunit vaccines is their artificially exposed immunodominant nonneutralizing epitopes, which can be overcome through glycan shielding. Additionally, the mutant ZIKV protein generated in this study is a promising subunit vaccine candidate with high efficacy in preventing ZIKV infections in mice. IMPORTANCE Viral subunit vaccines generally show low efficacy. In this study, we revealed an intrinsic limitation of subunit vaccine designs: artificially exposed surfaces of subunit vaccines contain epitopes unfavorable for vaccine efficacy. More specifically, we identified an epitope on Zika virus (ZIKV) envelope protein domain III (EDIII) that is buried in the full-length envelope protein but becomes exposed in recombinant EDIII. We further shielded this epitope with a glycan, and the resulting mutant EDIII vaccine demonstrated significantly enhanced efficacy over the wild-type EDIII vaccine in protecting animal models from ZIKV infections. Therefore, the intrinsic limitation of subunit vaccines can be overcome through shielding these artificially exposed unfavorable epitopes. The engineered EDIII vaccine generated in this study is a promising vaccine candidate that can be further developed to battle ZIKV infections. 
 Title: Rational Design of Zika Virus Subunit Vaccine with Enhanced Efficacy
Output: True
Paragraph: Background: Campylobacter jejuni is commonly found in the gastrointestinal tract of many food-animals including sheep without causing visible clinical symptoms of disease. However, C. jejuni has been implicated in ovine abortion cases worldwide. Specifically, in the USA, the C. jejuni sheep abortion (SA) clone has been increasingly associated with sheep abortion. In vivo studies in sheep (the natural host) are needed to better characterize the virulence potential and pathogenesis of this clone. Results: Pregnant ewes intravenously (IV) or orally inoculated with ovine or bovine abortion-associated C. jejuni SA clones exhibited partial or complete uterine prolapse with retained placenta, and abortion or stillbirth, whereas delivery of healthy lambs occurred in pregnant ewes inoculated with C. jejuni 81-176 or in the uninfected group. In sheep inoculated with the SA clone, histopathological lesions including suppurative necrotizing placentitis and/or endometritis coincided with: 1) increased apoptotic death of trophoblasts, 2) increased expression of the host genes (e.g. genes encoding interleukin IL-6 and IL-15) related to cellular necrosis and pro-inflammatory responses in uterus, and 3) decreased expression of the genes encoding GATA binding protein 6, chordin, and insulin-like 3 (INSL3) that account for embryonic development in uterus. Immunohistochemistry revealed localization of bacterial antigens in trophoblasts lining the chorioallantoic membrane of ewes inoculated with the C. jejuni SA clone. Conclusions: The results showed that C. jejuni SA clones are capable of causing abortion or stillbirth in experimentally infected sheep. Furthermore, down-or up-regulation of specific genes in the uterus of infected pregnant ewes might implicate host genes in facilitating the disease progression. Since the C. jejuni SA strains share genotypic similarities with clones that have been isolated from human clinical cases of gastroenteritis, these strains might represent a potential public health risk. 
 Title: Insights into potential pathogenesis mechanisms associated with Campylobacter jejuni-induced abortion in ewes
Output: True
Paragraph: To combat the threat of many emerging infectious diseases, DNA immunization offers a unique and powerful approach to the production of high-quality monoclonal antibodies (mAbs) against various pathogens. Compared with traditional protein-based immunization approaches, DNA immunization is efficient for testing novel immunogen designs, does not require the production or purification of proteins from a pathogen or the use of recombinant protein technology and is effective at generating mAbs against conformation-sensitive targets. Although significant progress in the use of DNA immunization to generate mAbs has been made over the last two decades, the literature does not contain an updated summary of this experience. The current review provides a comprehensive analysis of the literature, including our own work, describing the use of DNA immunization to produce highly functional mAbs, in particular, those against emerging infectious diseases. Critical factors such as immunogen design, delivery approach, immunization schedule, use of immune modulators and the role of final boost immunization are discussed in detail. 
 Title: DNA immunization as a technology platform for monoclonal antibody induction
Output: True
Paragraph: Rhinoviruses (RVs) and respiratory enteroviruses (EVs) are leading causes of upper respiratory tract infections and among the most frequent infectious agents in humans worldwide. Both are classified in the Enterovirus genus within the Picornaviridae family and they have been assigned to seven distinct species, RV-A, B, C and EV-A, B, C, D. As viral infections of public health significance, they represent an important financial burden on health systems worldwide. However, the lack of efficient antiviral treatment or vaccines against these highly prevalent pathogens prevents an effective management of RV-related diseases. Current advances in molecular diagnostic techniques have revealed the presence of RV in the lower respiratory tract and its role in lower airway diseases is increasingly reported. In addition to an established etiological role in the common cold, these viruses demonstrate an unexpected capacity to spread to other body sites under certain conditions. Some of these viruses have received particular attention recently, such as EV-D68 that caused a large outbreak of respiratory illness in 2014, respiratory EVs from species C, or viruses within the newly-discovered RV-C species. This review provides an update of the latest findings on clinical and fundamental aspects of RV and respiratory EV, including a summary of basic knowledge of their biology. 
 Title: viruses Rhinoviruses and Respiratory Enteroviruses: Not as Simple as ABC
Output: True
Paragraph: Mice that are transgenic (Tg) for T cell receptor (TCR) expression are used extensively to analyze longitudinal T cell responses during effector and memory phases of the T cell response. Generation of TCR Tg mice generally requires T cell stimulation and cloning in vitro prior to amplification, processes which introduce biases into selection of the TCR that is ultimately chosen for TCR Tg mouse generation. Here we describe an alternative approach that involves no T cell stimulation or propagation in vitro. We generated mice that were transgenic for a TCR responding to a CD4 T cell epitope (epitope M133) that is immunodominant in mice infected with a neurotropic coronavirus, the JHM strain of mouse hepatitis virus. The CD4 T cell response to epitope M133 is of particular interest because it may be pathogenic, protective or regulatory, depending upon the physiological setting. We applied an iterative process in which we identified a TCR-β chain expressed by all mice that were examined ('public sequence'). This TCR-β chain was introduced into bone marrow cells with a lentivirus vector, generating TCR-β retrogenic mice. A TCR-α chain that paired with this TCR-β was then identified and used to generate a second set of TCR (α/β) retrogenic mice. After demonstrating that these cells were functional and responded to epitope M133, these TCR chains were used to generate an epitope M133-specific TCR Tg mouse. This method should be generally useful for engineering TCR Tg mice without introduction of bias caused by in vitro manipulation and propagation. 
 Title: Development of transgenic mice expressing a coronavirus-specific public CD4 T cell receptor
Output: False
Paragraph: Murine norovirus (MNV) is a recently discovered mouse pathogen. Unlike the fastidious human noroviruses that cause the overwhelming majority of non-bacterial gastroenteritis worldwide, MNV readily infects cells in culture. Its replication in primary murine macrophages and dendritic cells and their derived cell lines allows the study of norovirus cell entry for the first time. In this study we determined the role of pH during MNV-1 infection since the low pH environment of endosomes often triggers uncoating of viruses. We demonstrated that MNV-1 viral titers by plaque assay and expression of the non-structural protein VPg by immunofluorescence were not affected by pH in cultured and primary macrophages and dendritic cells in the presence of two known endosome acidification inhibitors, bafilomycin A1 and chloroquine. These data indicate that MNV-1 enters permissive cells in a pH-independent manner. 
 Title: Murine Norovirus-1 entry into permissive macrophages and dendritic cells is pH-independent
Output: False
Paragraph: In the last decade, advances in cancer therapy have led to improved survival in children and adolescents with malignant disorders. As cure rates improve, treatmentrelated toxicity, especially infections, accounts for a greater proportion of morbidity and mortality. Pediatric hematology and oncology patients are often highly susceptible to infection. Those with medical devices, such as indwelling central catheters, and those with intermittent or chronic neutropenia are particularly at high risk of healthcare-associated infections (HAIs) such as central line-associated bloodstream infections (CLABSI), Clostridium difficile infections (CDIs), ventilator-associated pneumonia (VAP), catheter-associated urinary tract infections (CAUTI), and respiratory viral infections. In the past, infectious complications of therapy for oncological and hematological disorders were regarded as largely unavoidable. It is now recognized that many, although not all, of the most common infections in this population are preventable. Collaborative quality improvement efforts have led to effective strategies to reduce rates of HAI and improved outcomes in these populations. 
 Title: Healthcare-Associated Infections in Pediatric Hematology-Oncology
Output: False
Paragraph: Degenerative joint disease (DJD) associated-pain is a clinically relevant and common condition affecting domesticated cats and other species including humans. Identification of the neurobiological signature of pain is well developed in rodent pain models, however such information is lacking from animals or humans with naturally occurring painful conditions. In this study, identification of housekeeping genes (HKG) for neuronal tissue and expression levels of genes considered associated with chronic pain in rodent models were explored in cats with naturally occurring osteoarthritic pain. Fourteen adult cats were evaluatedseven without clinical signs of osteoarthritic pain, and seven with hind limb radiographic DJD and pain. Expression of an investigator-selected set of pain signaling genes (including ASIC3, ATF3, COX2, CX3CL1, NAV1.7, NAV1.8, NAV1.9, NGF, NK1R, TNFα, TRKA) in lumbar spinal cord dorsal horn and lumbar dorsal root ganglia tissues from clinically healthy cats and cats with DJD were studied using quantitative RT-PCR (qPCR). HKG identified as the most stable across all tissue samples were many of the ribosomal protein genes, such as RPL30 and RPS19. qPCR results showed ATF3 and CX3CL1 up-regulated in DJD-affected dorsal root ganglia compared to clinically healthy controls. In spinal cord, CX3CL1 was up-regulated and NGF was down-regulated when DJD-affected samples were compared to healthy samples. Further work is needed to understand the neurobiology of pain in naturally occurring disease and what rodent models are predictive of these changes in more heterogeneous populations such as domestic cats. 
 Title: Characterization of gene expression in naturally occurring feline degenerative joint disease-associated pain
Output: False
Paragraph: Most RNA viruses lack the mechanisms to recognize and correct mutations that arise during genome replication, resulting in quasispecies diversity that is required for pathogenesis and adaptation. However, it is not known how viruses encoding large viral RNA genomes such as the Coronaviridae (26 to 32 kb) balance the requirements for genome stability and quasispecies diversity. Further, the limits of replication infidelity during replication of large RNA genomes and how decreased fidelity impacts virus fitness over time are not known. Our previous work demonstrated that genetic inactivation of the coronavirus exoribonuclease (ExoN) in nonstructural protein 14 (nsp14) of murine hepatitis virus results in a 15-fold decrease in replication fidelity. However, it is not known whether nsp14-ExoN is required for replication fidelity of all coronaviruses, nor the impact of decreased fidelity on genome diversity and fitness during replication and passage. We report here the engineering and recovery of nsp14-ExoN mutant viruses of severe acute respiratory syndrome coronavirus (SARS-CoV) that have stable growth defects and demonstrate a 21-fold increase in mutation frequency during replication in culture. Analysis of complete genome sequences from SARS-ExoN mutant viral clones revealed unique mutation sets in every genome examined from the same round of replication and a total of 100 unique mutations across the genome. Using novel bioinformatic tools and deep sequencing across the full-length genome following 10 population passages in vitro, we demonstrate retention of ExoN mutations and continued increased diversity and mutational load compared to wild-type SARS-CoV. The results define a novel genetic and bioinformatics model for introduction and identification of multi-allelic mutations in replication competent viruses that will be powerful tools for testing the effects of decreased fidelity and increased quasispecies diversity on viral replication, pathogenesis, and evolution. 
 Title: Infidelity of SARS-CoV Nsp14-Exonuclease Mutant Virus Replication Is Revealed by Complete Genome Sequencing
Output: False
Paragraph: The gold standard for diagnosis of 2019 novel coronavirus (2019-nCoV) infection is the new coronavirus nucleic acid in swabs, sputum, secretions from the lower respiratory tract or blood. However, due to the quite low sensitivity, short of supply and a relatively long period of new coronavirus nucleic acid kits, suspected cases with false-negative results remain a severe problem. Besides, a long incubation period (3-7 days, up to 14 days) and superior transmission capacity of new viruses contribute to the fast spread of 2019-nCoV. Under the circumstances, computed tomography imaging is not only useful for the detection, location of lesions but also helpful in the evaluation of the dynamic changes of patients with 2019-nCoV. A 47-year-old man had a history of cough, sputum production, sore throat and throbbing headache for 3 days without fever. He has been living in Chengdu, Sichuan province, for a long time. However, his mother had traveled to Wuhan a week ago and was diagnosed with the new coronavirus after she got back home. He has referred to the emergency department of our institution on 2 February 2020. General physical examination showed that moist rales were audible over both lungs, and the body temperature was 36.7 C, and other results were unremarkable. The laboratory tests showed that white blood cell count kept in the normal range (5.11 Â 109/l), and the differential count showed decreased lymphocyte (16.8%, normal range 20-50%) and increased C-reactive protein (22.50 mg/l; normal range <5 mg/l). Chest computed tomography (CT) (2 February 2020) showed that there were ground-glass opacities, consolidation or both in bilateral lungs ( Figure 1A ). Considering the contact history with his mother and the CT features, a real-time fluorescence polymerase chain reaction of the patient's throat Figure 1. Chest CT images in a 47-year-old man. (A) CT images show that there are ground-glass opacities, consolidation or both in bilateral lungs, and 'halo sign' is visible in the basal segment of the lower lobe of the right lung. (B) The extent and density of lesions are significantly decreased. (C and D) At the third time of reexamination, CT scan shows multiple patchy ground-glass opacities, consolidation in bilateral lungs and the new lesions are in different locations. 
 Title: Author(s) QJM
Output: True
Paragraph: RNA engineering for nanotechnology and medical applications is an exciting emerging research field. RNA has intrinsically defined features on the nanometre scale and is a particularly interesting candidate for such applications due to its amazing diversity, flexibility and versatility in structure and function. Specifically, the current use of siRNA to silence target genes involved in disease has generated much excitement in the scientific community. The intrinsic ability to sequence-specifically downregulate gene expression in a temporally-and spatially controlled fashion has led to heightened interest and rapid development of siRNA-based therapeutics. Although methods for gene silencing have been achieved with high efficacy and specificity in vitro, the effective delivery of nucleic acids to specific cells in vivo has been a hurdle for RNA therapeutics. This article covers different RNA-based approaches for diagnosis, prevention and treatment of human disease, with a focus on the latest developments of non-viral carriers of siRNA for delivery in vivo. The applications and challenges of siRNA therapy, as well as potential solutions to these problems, the approaches for using phi29 pRNA-based vectors as polyvalent vehicles for specific delivery of siRNA, ribozymes, drugs or other therapeutic agents to specific cells for therapy will also be addressed. 
 Title: Engineering RNA for Targeted siRNA Delivery and Medical Application ☆
Output: False
Paragraph: Herbal plants, plant preparations and phytoconstituents have proved useful in attenuating infectious conditions and were the only remedies available, till the advent of antibiotics (many being of plant origin themselves). Among infectious diseases, viral diseases in particular, remain the leading cause of death in humans globally. A variety of phytoconstituents derived from medicinal herbs have been extensively studied for antiviral activity. Based on this rationale, an online search was performed, which helped to identify a large number of plant species harboring antiviral molecules. These herbal sources have been reported individually or in combinations across a large number of citations studied. Activities against rabies virus, Human immunodeficiency virus, Chandipura virus, Japanese Encephalitis Virus, Enterovirus, Influenza A/H1N1 and other influenza viruses were discovered during the literature search. This review includes all such plant species exhibiting antiviral properties. The review also encompasses composition and methodologies of preparing various antiviral formulations around the globe. An elaborate section on the formulations filed for patent registration, along with non-patented formulations, has also been included in this article. To conclude, herbal sources provide researchers enormous scope to explore and bring out viable alternatives against viral diseases, considering non-availability of suitable drug candidates and increasing resistance to existing drug molecules for many emerging and re-emerging viral diseases. 
 Title: Herbal plants and plant preparations as remedial approach for viral diseases
Output: True
Paragraph: Porcine epidemic diarrhea virus (PEDV) has caused extensive economic losses to pig producers in many countries. It was recently introduced, for the first time, into North America and outbreaks have occurred again in multiple countries within Europe as well. To assess the properties of various diagnostic assays for the detection of PEDV infection, multiple panels of porcine sera have been shared and tested for the presence of antibodies against PEDV in an inter-laboratory ring trial. Different laboratories have used a variety of "in house" ELISAs and also one commercial assay. The sensitivity and specificity of each assay has been estimated using a Bayesian analysis applied to the ring trial results obtained with the different assays in the absence of a gold standard. Although different characteristics were found, it can be concluded that each of the assays used can detect infection of pigs at a herd level by either the early European strains of PEDV or the recently circulating strains (INDEL and non-INDEL). However, not all the assays seem suitable for demonstrating freedom from disease in a country. The results from individual animals, especially when the infection has occurred within an experimental situation, show more variation. 
 Title: Inter-laboratory study to characterize the detection of serum antibodies against porcine epidemic diarrhoea virus
Output: False
Paragraph: Background-The genome annotations of rhesus (Macaca mulatta) and cynomolgus (Macaca fascicularis) macaques, two of the most common nonhuman primate animal models, are limited. Methods-We analyzed large-scale macaque RNA-based next-generation sequencing (RNAseq) data to identify un-annotated macaque transcripts. Results-For both macaque species, we uncovered thousands of novel isoforms for annotated genes and thousands of un-annotated intergenic transcripts enriched with non-coding RNAs. We also identified thousands of transcript sequences which are partially or completely 'missing' from current macaque genome assemblies. We showed that many newly identified transcripts were differentially expressed during SIV infection of rhesus macaques or during Ebola virus infection of cynomolgus macaques. Conclusions-For two important macaque species, we uncovered thousands of novel isoforms and un-annotated intergenic transcripts including coding and non-coding RNAs, polyadenylated and non-polyadenylated transcripts. This resource will greatly improve future macaque studies, as demonstrated by their applications in infectious disease studies. 
 Title: Assessment and improvement of Indian-origin rhesus macaque and Mauritian-origin cynomolgus macaque genome annotations using deep transcriptome sequencing data
Output: False
Paragraph: All over the world, children and adults are severely affected by acute gastroenteritis, caused by one of the emerging enteric pathogens, rotavirus C (RVC). At present, no extensive surveillance program is running for RVC in India, and its prevalence is largely unknown except cases of local outbreaks. Here, we intended to detect the presence of RVC in diarrheic children visiting or admitted to hospitals in Haldwani (state of Uttarakhand, India), a city located in the foothills of the Himalayas. During 2010-2013, we screened 119 samples for RVC by an RVC VP6 gene-specific RT-PCR. Of these, 38 (31.93%) were found positive, which is higher than the incidence rates reported so far from India. The phylogenetic analysis of the derived nucleotide sequences from one of the human RVC (HuRVC) isolates, designated as HuRVC/H28/2013/India, showed that the study isolate belongs to genotype I2, P2 and E2 for RVC structural genes 6 and 4 (VP6, and VP4) and non-structural gene 4 (NSP4), respectively. Furthermore, the VP6 gene of HuRVC/H28/2013/India shows the highest similarity to a recently-reported human-like porcine RVC (PoRVC/ASM140/2013/India, KT932963) from India suggesting zoonotic transmission. We also report a full-length NSP4 gene sequence of human RVC from India. Under the One-health platforms there is a need to launch combined human and animal RVC surveillance programs for a better understanding of the epidemiology of RVC infections and for implementing control strategies. 
 Title: Species C Rotaviruses in Children with Diarrhea in India: A Potentially Neglected Cause of Acute Gastroenteritis
Output: True
Paragraph: Objective: To present the frequency and spectrum of viral infections in primary immunodeficient children. Methods: The data was obtained from the Kuwait National Primary Immunodeficiency Disorders (PIDs) Registry during the period of 2004-2018. Results: A total of 274 PID children were registered in KNPIDR during the study period with predominance of immunodeficiencies affecting cellular and humoral immunity, followed by combined immunodeficiencies with associated syndromic features and diseases of immune dysregulation. Overall infectious complications affected 82.4% of the patients, and viral infections affected 31.7% of the registered patients. Forty-five patients (16.4%) developed viral infections caused by at least 2 organisms, among those 20 patients were affected by three or more viral infections. There was a statistically significant association between viral infections and PID category. However, there was no statistically significant association between viral infections and gender or the patients' onset age. There was a total of 170 viral infections during the study period and the causes of these infections were predominated by CMV (22.2%), adenovirus (11.7%), EBV (11.1%), and enteroviruses (7.4%). CMV and parainfluenza infections were more common in the group of immunodeficiencies affecting cellular and humoral immunity while EBV and human papilloma virus (HPV) were more common in the immune dysregulation group and combined immunodeficiencies with associated syndromic features, respectively. The most common presentation was viremia (28.8%) followed by pneumonia (28.2%) and skin infections (17.6%). The most common causes of viremia were CMV followed by adenovirus and EBV, while the most common organisms causing pneumonia were CMV followed by rhinovirus and parainfluenza. There were 80 deaths among the registered patients, 10% were caused by viral infections. Conclusions: Viral infections are common in PIDs and result into a wide-range of clinical manifestations causing significant morbidity and mortality. 
 Title: Spectrum of Viral Infections Among Primary Immunodeficient Children: Report From a National Registry
Output: False
Paragraph: Porcine epidemic diarrhea virus (PEDV) Isobaric tags for relative and absolute quantitation (iTRAQ) Proteomics Pathway analysis The re-emerging porcine epidemic diarrhea virus (PEDV) variant related diarrhea has been documented in China since late 2010 and now with global distribution. Currently, a virulent PEDV CH/YNKM-8/2013 and a CV777 vaccine strain-like AH-M have been successfully isolated from the clinical samples. To dissect out the underlying pathogenic mechanism of virulent PEDV and clarify the differences between virulent and CV777 vaccine strainlike PEDV infections, we performed an iTRAQ-based comparative quantitative proteomic study of Vero cells infected with both PEDV strains. A total of 661 and 474 differentially expressed proteins were identified upon virulent and CV777 vaccine strain-like isolates infection, respectively. Ingenuity Pathway Analysis was employed to investigate the canonical pathways and functional networks involved in both PEDV infections. Comprehensive studies have revealed that the PEDV virulent strain suppressed protein synthesis of Vero cells through down-regulating mTOR as well as its downstream targets 4EBP1 and p70S6K activities, which were validated by immunoblotting. In addition, the virulent strain could activate NF-κB pathway more intensively than the CV777 vaccine strain-like isolate, and elicit stronger inflammatory cascades as well. These data might provide new insights for elucidating the specific pathogenesis of PEDV infection, and pave the way for the development of effective therapeutic strategies. Biological significance: Porcine epidemic diarrhea is now worldwide distributed and causing huge economic losses to swine industry. The immunomodulation and pathogenesis between PEDV and host, as well as the difference between virulent and attenuated strains of PEDV infections are still largely unknown. In this study, we presented for the first application of proteomic analysis to compare whole cellular protein alterations induced by virulent and CV777 vaccine strain-like PEDV infections, which might contribute to understand the pathogenesis of PEDV and anti-viral strategy development. 
 Title: iTRAQ-based comparative proteomic analysis of Vero cells infected with virulent and CV777 vaccine strain-like strains of porcine epidemic diarrhea virus
Output: True
Paragraph: Southeast Asia will likely be the epicenter of the next infl uenza pandemic. To determine whether health system resources in Thailand are suffi cient to contain an emerging pandemic, we mapped health system resources in 76 provinces. We used 3 prepandemic scenarios of clustered cases and determined resource needs, availability, and gaps. We extended this analysis to a scenario of a modest pandemic and assumed that the same standards of clinical care would be required. We found that gaps exist in many resource categories, even under scenarios in which few cases occur. Such gaps are likely to be profound if a severe pandemic occurs. These gaps exist in infrastructure, personnel and materials, and surveillance capacity. Policy makers must determine whether such resource gaps can realistically be closed, ideally before a pandemic occurs. Alternatively, explicit assumptions must be made regarding allocation of scarce resources, standards of care, and priority setting during a pandemic. 
 Title: Capacity of Thailand to Contain an Emerging Infl uenza Pandemic
Output: True
Paragraph: Induction of effective cytotoxic T lymphocyte (CTL) and/or a specific antibody against conserved viral proteins may be essential to the development of a safe and effective severe acute respiratory syndrome coronavirus (SARS-Cov) vaccine. DNA vaccination represents a new strategy for induction of humoral and cellular immune response. To determine the ability of SARS-Cov nucleoprotein (N protein) to induce antiviral immunity, in this report, we established a stable C2C12 line expressing SARS-Cov N protein, which was used as a target for specific CTL assay. We also expressed recombinant N proteins in Escherichia coli and prepared N protein-specific polyclonal antibodies. C3H/He mice were immunized with N protein-expressible pcDN-fn vector by intramuscular injections. We found that the DNA vaccination induced both N protein-specific antibody and specific CTL activity to the target. When C3H/He mice were immunized by three separate injections, high antibody titre (1:3200-1:6400, average titre is 1:4580) and high CTL activity (67.4 ± 8.4% (E:T = 25:1), 69.6 ± 6.7% (E:T = 50:1) and 71.8 ± 6.2% (E:T = 100:1)) were observed. In the case of two vaccine injections, CTL activity was also high (56.6 ± 12.7% (E:T = 25:1), 57.4 ± 11.7% (E:T = 50:1) and 63.0 ± 6.3% (E:T = 100:1)). However, antibody titres were much lower (1:200-1:3200, average titre is 1:980). Our results suggest that SARS-Cov nucleocapsid gene might be a candidate gene for SARS DNA vaccination. 
 Title: Induction of SARS-nucleoprotein-specific immune response by use of DNA vaccine
Output: False
Paragraph: Ten potential reference genes were compared for their use in experiments investigating cellular mRNA expression of virus infected cells. Human cell lines were infected with Cytomegalovirus, Human Herpesvirus-6, Camelpox virus, SARS coronavirus or Yellow fever virus. The expression levels of these genes and the viral replication were determined by real-time PCR. Genes were ranked by the BestKeeper tool, the GeNorm tool and by criteria we reported previously. Ranking lists of the genes tested were tool dependent. However, over all, β-actin is an unsuitable as reference gene, whereas TATA-Box binding protein and peptidyl-prolyl-isomerase A are stable reference genes for expression studies in virus infected cells. 
 Title: Virology Journal Reference gene selection for quantitative real-time PCR analysis in virus infected cells: SARS corona virus, Yellow fever virus, Human Herpesvirus-6, Camelpox virus and Cytomegalovirus infections
Output: True
Paragraph: Influenza A viruses continue to emerge and re-emerge, causing outbreaks, epidemics and occasionally pandemics. While the influenza vaccines licensed for public use are generally effective against seasonal influenza, issues arise with production, immunogenicity, and efficacy in the case of vaccines against pandemic and emerging influenza viruses, and highly pathogenic avian influenza virus in particular. Thus, there is need of improved influenza vaccines and vaccination strategies. This review discusses advances in alternative influenza vaccines, touching briefly on licensed vaccines and vaccine antigens; then reviewing recombinant subunit vaccines, virus-like particle vaccines and DNA vaccines, with the main focus on virus-vectored vaccine approaches. 
 Title: Experimental vaccines against potentially pandemic and highly pathogenic avian influenza viruses
Output: True
Paragraph: The worldwide outbreak of severe acute respiratory syndrome (SARS) in 2003 had caused a high rate of mortality. Main protease (M pro ) of SARS-associated coronavirus (SARS-CoV) is an important target to discover pharmaceutical compounds for the therapy of this life-threatening disease. During the course of screening new anti-SARS agents, we have identified that a series of unsymmetrical aromatic disulfides inhibited SARS-CoV M pro significantly for the first time. Herein, 40 novel unsymmetrical aromatic disulfides were synthesized chemically and their biological activities were evaluated in vitro against SARS-CoV M pro . These novel compounds displayed excellent IC 50 data in the range of 0.516e5.954 mM. Preliminary studies indicated that these disulfides are reversible and mpetitive inhibitors. A possible binding mode was generated via molecular docking simulation and a comparative field analysis (CoMFA) model was constructed to understand the structure-activity relationships. The present research therefore has provided some meaningful guidance to design and identify anti-SARS drugs with totally new chemical structures. 
 Title: Discovery of unsymmetrical aromatic disulfides as novel inhibitors of SARS-CoV main protease: Chemical synthesis, biological evaluation, molecular docking and 3D-QSAR study
Output: True
Paragraph: In recent years, the incidence of severe infectious diseases has increased, and the number of emerging infectious diseases continues to increase. The Chinese government and military forces have paid a great deal of attention to infectious disease prevention and control, and using military-civilian cooperation, they have successfully prevented numerous severe epidemic situations, such as severe acute respiratory syndrome (SARS), influenza A (H1N1), avian influenza H5N1 and H7N9, and Ebola hemorrhagic fever, while actively maintained public health, economic development, and national construction. This paper focuses on the mechanisms of the military-cooperative emergency response to infectious diseases-the joint working mechanism, the information-sharing mechanism, the research collaboration mechanism, and the joint disposal mechanism-and presents a sorted summary of the practices and experiences of cooperative emergency responses to infectious diseases. In the future, the Chinese military and the civilian sector will further strengthen the cooperative joint command system and emergency rescue force and will reinforce their collaborative information-sharing platform and technical equipment system to further improve military-civilian collaborative emergency infectious diseases disposal, advance the level of infectious disease prevention and control, and maintain public health. 
 Title: Military-civilian cooperative emergency response to infectious disease prevention and control in China
Output: True
Paragraph: The cattle industry is one of the most important Brazilian agribusiness sectors and is a strong contributor to the national economy. Annually about 44.6 million calves are bred, which makes the optimal management of these animals extremely important. Several diseases can affect the initial stages of the bovine production chain, being the bovine respiratory syncytial virus (BRSV) one of the most relevant pathogens. This study aimed to characterize the epidemiology of BRSV infection in dairy cattle herds of São Paulo State, Brazil, using serological and risk factors analyses. For that, 1243 blood samples were collected of animals from 26 farms and a questionnaire about possible risk factors for BRSV prevalence was performed. The obtained blood sera were analyzed using virus neutralization test (VNT). Results: VNT results showed high BRSV prevalence in dairy cattle herds, reaching 79.5% of seropositivity. The BRSV seroprevalence among studied farms ranged from 40 to 100%. The analysis of risk factors indicated that the age group and the occurrence of coinfection with bovine herpesvirus 1 (BoHV-1) and bovine viral diarrhea virus 1 (BVDV-1) should be associated with a higher prevalence of BRSV, while natural suckling was considered a protective factor. The study showed that adult animals over 1 year old are an important risk factor for the high seroprevalence of BRSV in herds. The high BRSV prevalence associated with BoHV-1 and BVDV-1 suggests that biosecurity measures should be applied in order to reduce viral dissemination. Additionally, the natural suckling may be an important management to protect calves from high BRSV seroprevalence. 
 Title: Bovine respiratory syncytial virus seroprevalence and risk factors in non- vaccinated dairy cattle herds in Brazil
Output: True
Paragraph: Coronaviruses devote more than three quarters of their coding capacity to encode two large polyproteins (1a and 1ab polyproteins), which are proteolytically processed into 15-16 mature, nonstructural replicase proteins (nsp1 to 16). These cleavage products are believed to play essential roles in replication of the giant RNA genome of ∼ 30 kb and transcription of a nested set of 5 to 9 subgenomic RNA species by a unique discontinuous transcription mechanism. In this report, one of these replicase proteins, nsp9 of the coronavirus infectious bronchitis virus (IBV) is systematically studied using both biochemical and reverse genetic approaches. The results showed that substitution mutation of a conserved Gly (G98) residue in the C-terminal α-helix domain with an Asp greatly destabilized the IBV nsp9 homodimer and abolished its RNA-binding activity. Introduction of the same mutation into an infectious IBV clone system showed that the mutation totally abolishes the transcription of subgenomic RNA and no infectious virus could be recovered. Mutation of a semi-conserved Ile (I95) residue in the same region showed moderately destabilizing effect on the IBV nsp9 homodimer but minimal effect on its RNA-binding activity. Introduction of the mutation into the IBV infectious clone system showed recovery of a mutant virus with severe growth defects, supporting that dimerization is critical for the function of this replicase protein. Meanwhile, mutations of some positively charged residues in the β-barrel regions of the IBV nsp9 protein significantly reduced its RNA-binding activity, but with no obvious effect on dimerization of the protein. Introduction of these mutations into the viral genome showed only mild to moderate effects on the growth and infectivity of the rescued mutant viruses. 
 Title: Formation of stable homodimer via the C-terminal α-helical domain of coronavirus nonstructural protein 9 is critical for its function in viral replication
Output: False
Paragraph: Interferon inducible transmembrane protein (IFITM) family genes have been implicated in several cellular processes such as the homotypic cell adhesion functions of IFNs and cellular anti-proliferative activities. We previously showed that the IFITM3 single nucleotide polymorphisms (SNPs) associated with susceptibility to ulcerative colitis (UC). The present study aimed to investigate whether the polymorphisms in the IFITM1 gene are associated with susceptibility to UC. We also evaluated the expression levels in the putative functional promoter polymorphisms to determine the change of their activity. Gene expression profiles in the tissues obtained from human digestive tracts by RT-PCR, and the possible variation sites and SNPs of IFITM1 were identified by direct sequencing method. Genotype analysis in the IFITM1 SNPs was performed by high resolution melting and TaqMan probe analysis, and the haplotype frequencies of IFITM1 SNPs for multiple loci were estimated using the expectation maximization (EM) algorithm. The expression levels in the putative functional promoter polymorphisms were evaluated by performing a luciferase reporter assay. We identified two SNPs and two variation sites, g.-1920G>A (rs77537847), g.-1547delA (novel) and g.-416C>G (rs11246062) in the promoter region, and g.364delA (rs200576757) in intron 1. The genotype and allele frequencies of the g.-1920G>A polymorphism of IFITM1 gene in the UC patients were significantly different from those of the healthy controls (P = 0.002 and 0.042, respectively). These results suggest that the g.-1920G>A polymorphism in IFITM1 may be associated with susceptibility to UC. 
 Title: Identification of the polymorphisms in IFITM1 gene and their association in a Korean population with ulcerative colitis
Output: False
Paragraph: Sore throat is common in primary healthcare. Aetiological studies have focused on the presence of a limited number of pathogens. The aim of the present study was to investigate the presence of a wide range of bacteria and viruses, including Fusobacterium necrophorum, in patients with pharyngotonsillitis and in asymptomatic controls. A prospective case control study was performed in primary healthcare in Kronoberg County, Sweden. Patients (n = 220) aged 15 to 45 years with a suspected acute pharyngotonsillitis, and controls (n = 128), were included. Nasopharyngeal and throat swabs were analysed for β-hemolytic streptococci, F. necrophorum, Mycoplasma pneumoniae, and Chlamydophila pneumoniae, and 13 respiratory viruses. Serum samples were analysed for antibodies to Epstein-Barr virus. The patient history and symptoms, including Centor score, were analysed in relation to pathogens. In 155/220 (70.5%) of the patients, as compared to 26/128 (20.3%) of the controls (p <0.001), at least one microorganism was found. Group A streptococci, F. necrophorum, and influenza B virus were the three most common findings, and all significantly more common in patients than in controls (p <0.001, p 0.001, and p 0.002, respectively). Patients with F. necrophorum only (n = 14) displayed a lower Centor score than patients with Group A streptococcus only (n = 46), but a higher score than patients with influenza B, other viruses, or no potential pathogen (Kruskal-Wallis p <0.001). A pathogen was detected in 70% of the patients, displaying a wide range of pathogens contributing to the aetiology of pharyngotonsillitis. This study supports F. necrophorum as one of the pathogens to be considered in the aetiology of pharyngotonsillitis. Clinical Microbiology and Infection 
 Title: The aetiology of pharyngotonsillitis in adolescents and adults - Fusobacterium necrophorum is commonly found
Output: True
Paragraph: Background: The aim of this study was to detect the associations between bovine herpesvirus 1 (BHV-1) status of a herd and respiratory disease (BRD) occurrence and reproductive performance in pregnant heifers and cows. The association between management-related factors and higher BRD occurrence was also estimated. Methods: Serum samples, collected from cows and youngstock from 103 dairy cattle herds, were analyzed for antibodies against BHV-1, bovine respiratory syncytial virus (BRSV), bovine viral diarrhoea virus (BVDV), and Mycoplasma bovis. A questionnaire was used to collect data concerning herd management factors and reproductive performance, as well as the occurrence of clinical signs of respiratory disease in the last two years, as evaluated by the veterinarian or farm manager. Multiple correspondence analysis (MCA) and logistic regression analysis were performed to identify and quantify the risk factors. Results: A low to moderate prevalence (1-49%) of BRSV antibodies among youngstock was associated with a high occurrence of respiratory disease (OR = 6.2, p = 0.010) in cows and in-calf heifers. Employees of the farm may participate in the spread of such disease. Larger herd size, loose-housing of cows, housing youngstock separately from cows until pregnancy, and purchasing new animals were factors possibly related to a high occurrence of respiratory disease symptoms in pregnant heifers and cows. The highest risk of abortions (> 1.3%) and increased insemination index (number of inseminations per pregnancy) (> 1.9) occurred in herds with a moderate prevalence of BHV-1 antibodies (1-49%) in cows. Conclusions: BHV-1 was not associated with acute respiratory disease in adult dairy cattle, however was significantly related to reproductive performance. BRSV possesses the main role in respiratory disease complex in adult dairy cattle. 
 Title: Association of herd BRSV and BHV-1 seroprevalence with respiratory disease and reproductive performance in adult dairy cattle
Output: True
Paragraph: Emerging infectious diseases arising from livestock and wildlife pose serious threats to global human health, as shown by a series of continuous outbreaks involving highly pathogenic influenza, SARS, Ebola and MERS. The risk of pandemics and bioterrorism threats is ever present and growing, but our ability to combat them is limited by the lack of available vaccines, therapeutics and rapid diagnostics. The use of high bio-containment facilities, such as the CSIRO Australian Animal Health Laboratory, plays a key role studying these dangerous pathogens and facilitates the development of countermeasures. To combat diseases like MERS, we must take a holistic approach that involves the development of early biomarkers of infection, a suite of treatment options (vaccines, anti-viral drugs and antibody therapeutics) and appropriate animal models to test the safety and efficacy of candidate treatments. 
 Title: Overview of the CSIRO Australian Animal Health Laboratory
Output: True