niryuu/sni-each-converted huggingface dataset:
Paragraph: In this two-part series of reviews, we have invited experts in their fields to contribute articles on the status of vaccine research and development for emerging pathogens. This topic has been brought into sharp focus in recent years following significant outbreaks of viral diseases such as those causing severe acute respiratory syndrome and Middle East respiratory syndrome, as well as devastating outbreaks of diseases caused by the Ebola, Marburg, Zika and Lassa fever viruses, to name only a few examples. Additionally, bacterial infections leading to bubonic and pneumonic plague, most notably in Madagascar in 2018, as well as malaria in many tropical countries, melioidosis in south east Asia and tularaemia in northern Europe and North America, have incurred significant morbidity and mortality. In this review series, the life cycle of these pathogens and the epidemiology of disease have been reviewed in the context of potential points of intervention for the prevention of human infection. Many of the emerging pathogens are zoonoses and, as such, there is scope for intervention at the animal/insect/environmental reservoir. Other pathogens covered in this review series are considered to be re-emerging, such as multi-drug resistant tuberculosis. 
 Title: Vaccines for emerging pathogens: from research to the clinic
Output: True
Paragraph: Two studies of H5N1 avian influenza viruses that had been genetically engineered to render them transmissible between ferrets have proved highly controversial. Divergent opinions exist about the importance of these studies of influenza transmission and about potential 'dual use' research implications. No consensus has developed yet about how to balance these concerns. After not recommending immediate full publication of earlier, less complete versions of the studies, the United States National Science Advisory Board for Biosecurity subsequently recommended full publication of more complete manuscripts; however, controversy about this and similar research remains. 
 Title: Engineering H5N1 avian influenza viruses to study human adaptation
Output: False
Paragraph: One word can be used to best describe the theme of each day that has transpired since the onset of the COVID-19 pandemic: uncertainty. Urologic surgical residents around the nation are faced with the unknown when they walk through the doors of the hospital each day. While experience has taught us navigational strategies to handle these circumstances, the COVID-19 pandemic has undoubtedly brought new meaning to this concept. Priorities have quickly transitioned from closely following our previously developed academic curriculum and enhancing our surgical skills, to limiting physician-patient encounters and ensuring the safety and health of our team. Normalcy within our professional and personal lives is completely lost. Yet, as health care providers, we must and will forge on. We review the techniques and guidelines that our institution has implemented in order to allow us to do just that. We believe that our leadership, both at an enterprise and program level, has taken the necessary and early measures to prepare our residency cohort for the uncertain future and challenges posed by COVID-19. This plan emphasizes social and professional distancing, allows residents and faculty to stay current on academic topics, and provides reasonable opportunities for personal wellness, all while emphasizing safety and rationalization. Most importantly, however, we have continued to provide our patients with exceptional urologic care at 2 adult hospitals and 1 children's hospital in the Greater Akron, Ohio area. While we understand each residency program has a unique curriculum with a different number of residents that cover a range of different hospitals, we hope to provide insight into our personal experience. We believe that this method of organization allows a residency program to continue to grow professionally, socially, academically, and personally during the uncertainty that is COVID-19. This framework could serve as an immediate action plan for future pandemics and natural disasters, especially for residency programs that cover multiple hospitals and health care settings. 
 Title: Editorial Cleveland Clinic Akron General Urology Residency Program's COVID-19 Experience
Output: True
Paragraph: Background: The Middle East respiratory syndrome (MERS) associated coronavirus has been imported via travelers into multiple countries around the world. In order to support risk assessment practice, the present study aimed to devise a novel statistical model to quantify the country-level risk of experiencing an importation of MERS case. Methods: We analyzed the arrival time of each reported MERS importation around the world, i.e., the date on which imported cases entered a specific country, which was modeled as a dependent variable in our analysis. We also used openly accessible data including the airline transportation network to parameterize a hazard-based risk prediction model. The hazard was assumed to follow an inverse function of the effective distance (i.e., the minimum effective length of a path from origin to destination), which was calculated from the airline transportation data, from Saudi Arabia to each country. Both country-specific religion and the incidence data of MERS in Saudi Arabia were used to improve our model prediction. Results: Our estimates of the risk of MERS importation appeared to be right skewed, which facilitated the visual identification of countries at highest risk of MERS importations in the right tail of the distribution. The simplest model that relied solely on the effective distance yielded the best predictive performance (Area under the curve (AUC) = 0. 943) with 100 % sensitivity and 79.6 % specificity. Out of the 30 countries estimated to be at highest risk of MERS case importation, 17 countries (56.7 %) have already reported at least one importation of MERS. Although model fit measured by Akaike Information Criterion (AIC) was improved by including country-specific religion (i.e. Muslim majority country), the predictive performance as measured by AUC was not improved after accounting for this covariate. Conclusions: Our relatively simple statistical model based on the effective distance derived from the airline transportation network data was found to help predicting the risk of importing MERS at the country level. The successful application of the effective distance model to predict MERS importations, particularly when computationally intensive large-scale transmission models may not be immediately applicable could have been benefited from the particularly low transmissibility of the MERS coronavirus. 
 Title: Predicting the international spread of Middle East respiratory syndrome (MERS)
Output: True
Paragraph: Viral replicase recruitment and long-range RNA interactions are essential for RNA virus replication, yet the mechanism of their interplay remains elusive. Flaviviruses include numerous important human pathogens, e.g., dengue virus (DENV) and Zika virus (ZIKV). Here, we revealed a highly conserved, conformation-tunable cis-acting element named 5 0 -UAR-flanking stem (UFS) in the flavivirus genomic 5 0 terminus. We demonstrated that the UFS was critical for efficient NS5 recruitment and viral RNA synthesis in different flaviviruses. Interestingly, stabilization of the DENV UFS impaired both genome cyclization and vRNA replication. Moreover, the UFS unwound in response to genome cyclization, leading to the decreased affinity of NS5 for the viral 5 0 end. Thus, we propose that the UFS is switched by genome cyclization to regulate dynamic RdRp binding for vRNA replication. This study demonstrates that the UFS enables communication between flavivirus genome cyclization and RdRp recruitment, highlighting the presence of switch-like mechanisms among RNA viruses. 
 Title: Viral RNA switch mediates the dynamic control of flavivirus replicase recruitment by genome cyclization
Output: False
Paragraph: The rapid improvements in DNA synthesis technology hold the potential to revolutionize biosciences in the near future. Traditional genetic engineering methods are template dependent and make extensive but laborious use of site-directed mutagenesis to explore the impact of small variations on an existing sequence ''theme.'' De novo gene and genome synthesis frees the investigator from the restrictions of the pre-existing template and allows for the rational design of any conceivable new sequence theme. Viruses, being among the simplest replicating entities, have been at the forefront of the advancing biosciences since the dawn of molecular biology. Viral genomes, especially those of RNA viruses, are relatively short, often less than 10,000 bases long, making them amenable to whole genome synthesis with the currently available technology. For this reason viruses are once again poised to lead the way in the budding field of synthetic biology-for better or worse. 
 Title: Putting Synthesis into Biology: A Viral View of Genetic Engineering through De Novo Gene and Genome Synthesis
Output: True
Paragraph: These authors contributed equally to this work White powder, yield 49%, m. p. >300 o C; 1 H-NMR (DMSO-D 6 ) δ H 6.95 (1H, br, s, H10), 7.49-7.95 (5H, m. H15-H16), 8.58 (2H, s, H2 and H11), 12.41 (1H, s, H1); 13 C-NMR (DMSO-d 6 ) 121.9 (C15 ). QTOF-MS m/z calcd for C 12 H 9 KN 5 OS M+K + 310.39 found 310.33. 7 General procedure for the N-alkylation of acetamide-thioguanine The synthesis of 17 and 20 followed the general procedure for N-alkylation Salvatore et al., 2002 4 . Briefly, 138.23 mg of 4 Å Molecular Sieves (MS) was suspended into 3 mL of DMF. Cessium hydroxide monohydrate (CsOH.H 2 O) (140 µL) was added into the mixture and then stirred up for 10 minutes at the room temperature. The stirring was continued while adding N-(6-mercapto-9H-purin-2-yl)acetamide (MH022; 0.5 mmol) into the mixture for 30 minutes at the same temperature. Lastly, cyclopentyl bromide (0.6 mmol) was added into the mixture and the stirring was continued while monitoring the reaction's progress using TLC with CHCl 3 : acetone (3:1) as a solvent. After the reaction completed, the mixture was diluted with 70 mL of water and then extracted using 3 x 70 mL of EtO-Ac. The organic phase was collected, washed with 3 x 70 mL of water and then dried over anhydrous magnesium sulfate. This organic phase was then evaporated in vacuo and purified using PLC to afford the product as a white off powder. (15) White powder; yield 86%; m.p 154-156 o C; ʋ max / cm -1 (KBr) 3211 (NH), 1585 (C=O); 1 H-NMR (DMSO-D 6 ) δ H 1.73 (4H, m, H12 and H13), 2.19 (3H, s,H19), 2.26 (4H, m, H11 and H14), 2.65 (1H. m, H10), 8.03 (1H, s, H2), 12.85 (1H, br, s, H16); δ C 24.0 (MS m/z calcd for C 12 H 16 N 5 OS M+H + 278.35 found 278.13. White powder, yield 64%, m. p. >300 o C; 1 H-NMR (DMSO-D 6 ) δ H 1.09 (3H, t, H17), 1.19 (3H, t, H19), 2.55 (2H, q, H18), 3.29 (2H, q, H16), 8.61 (1H, s, H2), 11.97 (1H, br, s, H1); 13 C-NMR (DMSO-d 6 ) 8. 
 Title: Supporting Information Thioguanine-based DENV-2 NS2B/NS3 protease inhibitors: Virtual screening, synthesis, biological evaluation and molecular modelling
Output: True
Paragraph: There is an urgent need to develop new innovative therapies for the control of cancer. Antigenspecific immunotherapy and the employment of proteasome inhibitors have emerged as two potentially plausible approaches for the control of cancer. In the current study, we explored the combination of the DNA vaccine encoding calreticulin (CRT) linked to human papillomavirus type 16 E7 antigen (CRT/E7) with the proteasome inhibitor, bortezomib, for their ability to generate E7-specific immune responses and antitumor effects in vaccinated mice. We found that the combination of treatment with bortezomib and CRT/E7(detox) DNA generated more potent E7-specific CD8+ T cell immune responses and better therapeutic effects against TC-1 tumors in tumor-bearing mice compared to monotherapy. Furthermore, we found that treatment with bortezomib led to increased apoptosis of TC-1 tumor cells and could render the TC-1 tumor cells more susceptible to lysis by E7-specific CD8+ T cells. Our data have significant implications for future clinical translation. Keywords Bortezomib . DNAvaccine . Calreticulin (CRT) . E7 . Human papillomavirus (HPV) Advanced-stage cancers are difficult to control using conventional therapies such as chemotherapy, surgery, and radiation. Therefore, new innovative therapies are urgently required in order to combat the high mortality and morbidity associated with cancers. Antigen-specific immunotherapy has emerged as an attractive approach for the treatment of cancers since it has the ability to specifically eradicate systemic tumors and control metastases without damaging normal cells. DNA vaccination has become a potentially promising approach for antigen-specific immunotherapy due to its safety, J Mol Med (2008) 86:899-908  
 Title: Treatment with proteasome inhibitor bortezomib enhances antigen-specific CD8+ T-cell-mediated antitumor immunity induced by DNA vaccination
Output: True
Paragraph: Chlamydophila pneumoniae (CPn) is a common respiratory pathogen that causes a chronic and persistent airway infection. The elderly display an increased susceptibility and severity to this infection. However, the underlying mechanisms are not well understood. Dendritic cells (DCs) are the initiators and regulators of immune responses. Therefore, we investigated the role of DCs in the age-associated increased CPn infection in vitro in humans. Though the expression of activation markers was comparable between the two age groups, DCs from aged subjects secreted enhanced levels of proinflammatory mediators such as TNF-and CXCL-10 in response to CPn. In contrast, the secretion of IL-10 and innate interferons, IFN-and IFN-, was severely impaired in DCs from aged donors. The increased activation of DCs from aged subjects to CPn also resulted in enhanced proliferation of CD4 and CD8 T cells in a DC-T coculture. Furthermore, T cells primed with CPn-stimulated DCs from aged subjects secreted increased levels of IFN-and reduced levels of IL-10 compared to DCs obtained from young subjects. In summary, DCs from the elderly displayed enhanced inflammatory response to CPn which may result in airway remodeling and increase the susceptibility of the elderly to respiratory diseases such as asthma. 
 Title: Dendritic Cells from Aged Subjects Display Enhanced Inflammatory Responses to Chlamydophila pneumoniae
Output: True
Paragraph: In this study, a pathogenic avian infectious bronchitis virus (IBV) QX-type strain YN was successfully rescued by vaccinia virus based reverse genetic technology. Ten fragments contiguously spanning the complete IBV genome were amplified and cloned into the vaccinia virus genome by homologous recombination. The full-length genomic cDNA was transcribed in vitro, and its transcript was transfected into BHK-21/N cells that could stably express IBV N protein. At 48 h post transfection, the culture medium was harvested and inoculated into 10-dayold specific-pathogen-free embryonated chicken eggs to replicate the rescued virus. This strategy was chosen to facilitate the rescue procedure and to ensure that the recombinant rYN virus will not require any cell culture adaptations. After only one in ovo passage, the recombinant YN virus (rYN) was successfully recovered and confirmed to possess the introduced silent marker mutation in its genome. Biological characteristics of rYN such as the EID 50 , TCID 50 , replication in ovo, and replication kinetcs in vitro were tested and all were similar to its parental strain YN. Our findings demonstrate the successful construction of highly-pathogenic QX-type IBV using a modified rescue procedure, allowing for future studies of the molecular biology and pathogenicity of IBV field strains. 
 Title: Successful establishment of a reverse genetic system for QX-type infectious bronchitis virus and technical improvement of the rescue procedure
Output: True
Paragraph: Much progress has been made in understanding the role of structural and accessory proteins in the pathogenesis of severe acute respiratory syndrome coronavirus (SARS-CoV) infections. The SARS epidemic also brought new attention to the proteins translated from ORF1a and ORF1b of the input genome RNA, also known as the replicase/transcriptase gene. Evidence for change within the ORF1ab coding sequence during the SARS epidemic, as well as evidence from studies with other coronaviruses, indicates that it is likely that the ORF1ab proteins play roles in virus pathogenesis distinct from or in addition to functions directly involved in viral replication. Recent reverse genetic studies have confirmed that proteins of ORF1ab may be involved in cellular signaling and modification of cellular gene expression, as well as virulence by mechanisms yet to be determined. Thus, the evolution of the ORF1ab proteins may be determined as much by issues of host range and virulence as they are by specific requirements for intracellular replication. 
 Title: SARS coronavirus replicase proteins in pathogenesis
Output: False
Paragraph: Context: The 2-1-1 helpline is a social services innovation that has spread rapidly throughout the U.S. Policy diffusion theory suggests that policymakers seek to reduce uncertainty by anticipating the effects of a proposed innovation through tools such as cost-benefıt analyses. Few policy diffusion studies have examined use of information, such as cost-benefıt analyses, in the diffusion process. The purpose of this study is to examine how cost-benefıt analyses were used during the rapid diffusion of 2-1-1 across states. The paper also describes components of 2-1-1 cost-benefıt analyses. Evidence acquisition: In 2011, cost-benefıt analyses of 2-1-1 and substantive citations of them were identifıed through scholarly key word searches using Academic Search Premier and Web of Science, general Internet searches using Google search terms, and communications with academicians and 2-1-1 practitioners through personal contact and e-mail discussion groups. To be included in this study, documents had to be related to 2-1-1 helplines, present information about their costs and benefıts, and be formal documents. The documents were catalogued and analyzed for costbenefıt analyses or references to analyses, and stated purpose. Evidence synthesis: Of the 19 documents that met eligibility inclusion criteria, nine were original cost-benefıt analyses and ten referenced analyses conducted for other jurisdictions. The diffusion of2-1-1 helplinesin the U.S.hasbeen influenced by interjurisdictionalexchange of cost-benefıt analyses, in both the creation of original analyses and/or the referencing of previous work. (Am J Prev Med 2012;43(6S5):S497-S505) Am J Prev Med 2012;43(6S5):S497-S505 S497 S498 Shank / Am J Prev Med 2012;43(6S5):S497-S505 www.ajpmonline.org S502 Shank / Am J Prev Med 2012;43(6S5):S497-S505 www.ajpmonline.org 
 Title: A Review of the Role of Cost-Benefit Analyses in 2-1-1 Diffusion
Output: True
Paragraph: Faecal samples were taken from cats living in multi-cat households with endemic feline coronavirus (FCoV) infection. Total RNA was extracted from faecal suspensions and FCoV RNA was quantified using a real-time reverse transcriptase-polymerase chain reaction (RT-PCR) assay. The real-time RT-PCR threshold cycle (C T ) values were consistently high suggesting that the samples contained very little viral RNA. However, experiments in which RNA extracted from FCoV-infected cell culture supernatants was combined with RNA extracted from faecal suspensions revealed the presence of faecal factors that significantly inhibited the reverse transcription reaction. Consequently, three methods of RNA extraction were investigated and RNA dilution was undertaken to investigate whether the effects of the faecal inhibitors could be reduced. Our results show that using the QIAgen RNA mini kit for RNA extraction and dilution of the RNA samples helps to reduce the inhibitory effects. However, because the extent of the inhibitory effects varied between faecal samples, accurate quantification proved difficult. We, therefore, conclude that although real-time RT-PCR provides an excellent method for detecting the presence of viral shedding, quantification of FCoV RNA in faecal material has to take into account the possible effects of RT-PCR inhibitors. It is, therefore, essential that all new assays, and the methods of sample preparation, are carefully evaluated before being used in a clinical setting. 
 Title: Evaluation of real-time RT-PCR for the quantification of FCoV shedding in the faeces of domestic cats
Output: False
Paragraph: Polymorphism of angiotensin converting enzyme (ACE) gene is reported to be associated with ischemic heart disease, hypertrophic cardiomyopathy, and idiopathic dilated cardiomyopathy. In this study, we investigated the relationship between Kawasaki disease and insertion/deletion polymorphism of ACE gene. Fifty five Kawasaki disease patients and 43 healthy children were enrolled. ACE genotype was evaluated from each of the subjects' DNA fragments through polymerase chain reaction (PCR). Frequencies of ACE genotypes (DD, ID, II) were 12.7%, 60.0%, 27.3% in Kawasaki group, and 41.9%, 30.2%, 27.9% in control group respectively, indicating low rate of DD and high rate of ID genotype among Kawasaki patients (p<0.01). Comparing allelic (I, D) frequencies, I allele was more prevalent in Kawasaki group than in control group (57.3% vs. 43.0%, p<0.05). In Kawasaki group, both genotype and allelic frequencies were not statistically different between those with coronary dilatations and those without. ACE gene I/D polymorphism is thought to be associated with Kawasaki disease but not with the development of coronary dilatations. 
 Title: Address for correspondence Insertion/Deletion Polymorphism of Angiotensin Converting Enzyme Gene in Kawasaki Disease
Output: False
Paragraph: Arboviruses are often maintained in complex cycles involving vertebrates such as mammals or birds and blood-feeding mosquitoes. However, the role of wildlife hosts in their emergence or re-emergence in human populations has received little attention. The recent emergence of Zika virus in America, and previous occurrences of chikungunya and dengue, forces us to confront a potential new disease-emergence phenomenon. Using a spatial data mining framework to identify potential biotic interactions, based on the degree of co-occurrence between different species, we identified those mammal species with the highest potential for establishing mammal-vector interactions, considering as principal vector Aedes aegypti. Seven of the top ten identified mammal species with highest potential were bats, with two of them having previously been confirmed as positive hosts for dengue in Mexico. We hope that this will raise interest of Mexican public health authorities and academic institutions to assess the role of wild hosts in the maintenance and spread of arboviruses. 
 Title: Predicting the Potential Role of Non-human Hosts in Zika Virus Maintenance
Output: True
Paragraph: Feline coronavirus (FCoV) is endemic in feral cat populations and cat colonies, frequently preceding outbreaks of fatal feline infectious peritonitis (FIP). FCoV exhibits 2 biotypes: the pathogenic disease and a benign infection with feline enteric coronavirus (FECV). Uncertainty remains regarding whether genetically distinctive avirulent and virulent forms coexist or whether an avirulent form mutates in vivo, causing FIP. To resolve these alternative hypotheses, we isolated viral sequences from FCoV-infected clinically healthy and sick cats (8 FIP cases and 48 FECV-asymptomatic animals); 735 sequences from 4 gene segments were generated and subjected to phylogenetic analyses. Viral sequences from healthy cats were distinct from sick cats on the basis of genetic distances observed in the membrane and nonstructural protein 7b genes. These data demonstrate distinctive circulating virulent and avirulent strains in natural populations. In addition, 5 membrane protein amino acid residues with functional potential differentiated healthy cats from cats with FIP. These findings may have potential as diagnostic markers for virulent FIP-associated FCoV. 
 Title: Genetics and Pathogenesis of Feline Infectious Peritonitis Virus
Output: False
Paragraph: † These authors contributed equally to this work. One sentence summary: The anti-arrhythmic drug amiodarone, and one of its active metabolites interfere with the early steps of Ebola virus life cycle by blocking the fusion step between the viral envelope and the endosomal membrane. Ebola virus disease (EVD) is one of the most lethal transmissible infections characterized by a high fatality rate, and a treatment has not been developed yet. Recently, it has been shown that cationic amphiphiles, among them the antiarrhythmic drug amiodarone, inhibit filovirus infection. In the present work, we investigated how amiodarone interferes with Ebola virus infection. Wild-type Sudan ebolavirus and recombinant vesicular stomatitis virus, pseudotyped with the Zaire ebolavirus glycoprotein, were used to gain further insight into the ability of amiodarone to affect Ebola virus infection. We show that amiodarone decreases Ebola virus infection at concentrations close to those found in the sera of patients treated for arrhythmias. The drug acts by interfering with the fusion of the viral envelope with the endosomal membrane. We also show that MDEA, the main amiodarone metabolite, contributes to the antiviral activity. Finally, studies with amiodarone analogues indicate that the antiviral activity is correlated with drug ability to accumulate into and interfere with the endocytic pathway. Considering that it is well tolerated, especially in the acute setting, amiodarone appears to deserve consideration for clinical use in EVD. 
 Title: Amiodarone and metabolite MDEA inhibit Ebola virus infection by interfering with the viral entry process
Output: False
Paragraph: | Lysosomes are membrane-bound organelles with roles in processes involved in degrading and recycling cellular waste, cellular signalling and energy metabolism. Defects in genes encoding lysosomal proteins cause lysosomal storage disorders, in which enzyme replacement therapy has proved successful. Growing evidence also implicates roles for lysosomal dysfunction in more common diseases including inflammatory and autoimmune disorders, neurodegenerative diseases, cancer and metabolic disorders. With a focus on lysosomal dysfunction in autoimmune disorders and neurodegenerative diseases -including lupus, rheumatoid arthritis, multiple sclerosis, Alzheimer disease and Parkinson disease -this Review critically analyses progress and opportunities for therapeutically targeting lysosomal proteins and processes, particularly with small molecules and peptide drugs. 
 Title: Lysosomes as a therapeutic target
Output: False
Paragraph: BALB/c male mice were mated with either Swiss-Webster or MF1 females to produce first generation cross-bred offspring. Hybridoma cell lines, from the fusion of P3-NS1-Ag4/1 myeloma cells with spleen cells sensitised to the porcine coronavirus causing transmissible gastroenteritis, were injected intraperitoneally into these mice to produce ascitic fluid containing monoclonal antibodies. Mice of 11 weeks of age weighing between 26 and 34 g were used. The volume of ascites produced by mice injected with four of the five hybrid cell lines tested was greater in the cross-bred offspring than in the BALB/c parent. The fifth cell line gave comparable volumes in the MF1 cross-breed and BALB/c parent but a lesser volume in the Swiss-Webster cross-breed. The antibody titres of the ascites as determined by virus neutralisation, radioimmune and indirect immune fluorescence assays, did not differ significantly between mouse types. The ability to use all offspring from a litter of cross-bred mice, irrespective of sex, and the increased volume of ascitic fluid formed in each mouse, permits fewer animals to be used for the production of ascites in these strains, thereby offering considerable economic and ethical advantages over the use of BALB/c mice. 
 Title: Comparison of ascites production for monoclonal antibodies in BALB/c and BALB/c-derived cross-bred mice
Output: True
Paragraph: Human adenoviral (HAd) vectors have demonstrated great potential as vaccine vectors. Preclinical and clinical studies have demonstrated the feasibility of vector design, robust antigen expression and protective immunity using this system. However, clinical use of adenoviral vectors for vaccine purposes is anticipated to be limited by vector immunity that is either preexisting or develops rapidly following the first inoculation with adenoviral vectors. Vector immunity inactivates the vector particles and rapidly removes the transduced cells, thereby limiting the duration of transgene expression. Due to strong vector immunity, subsequent use of the same vector is usually less efficient. In order to circumvent this limitation, nonhuman adenoviral vectors have been proposed as alternative vectors. In addition to eluding HAd immunity, these vectors possess most of the attractive features of HAd vectors. Several replication-competent or replication-defective nonhuman adenoviral vectors have been developed and investigated for their potential as vaccine delivery vectors. Here, we review recent advances in the design and characterization of various nonhuman adenoviral vectors, and discuss their potential applications for human and animal vaccination. 
 Title: Development of nonhuman adenoviruses as vaccine vectors
Output: False
Paragraph: We assessed the alterations of viral gene expression occurring during persistent infections by cloning fulllength transcripts of measles virus (MV) genes from brain autopsies of two subacute sclerosing panencephalitis patients and one measles inclusion body encephalitis (MIBE) patient. The sequence of these MV genes revealed that, most likely, almost 2% of the nucleotides were mutated during persistence, and 35% of these differences resulted in amino acid changes. One of these nucleotide substitutions and one deletion resulted in alteration of the reading frames of two fusion genes, as confirmed by in vitro translation of synthetic mRNAs. One cluster of mutations was exceptional; in the matrix gene of the MIBE case, 50% of the U residues were changed to C, which might result from a highly biased copying event exclusively affecting this gene. We propose that the cluster of mutations in the MIBE case, and other combinations of mutations in other cases, favored propagation of MV infections in brain cells by conferring a selective advantage to the mutated genomes. c c c Figure 3. Sequences of the M Genes of Cases A, 8, and C in Comparison with Other M Gene Sequences 
 Title: Biased Hypermutation and Other Genetic Changes in Defective Measles Viruses in Human Brain Infections
Output: False
Paragraph: The burden of unsafe drinking water is responsible for millions of deaths each year. To relieve this burden, we are in search of an inexpensive material that can adsorb pathogens from drinking water. In this pursuit, we have studied the natural carbohydrate, chitosan. To impart virus removal features, chitosan has been functionalized with a quaternary amine to form quaternized chitosan N-[(2-hydroxyl-3-trimethylammonium) propyl] chitosan (HTCC). HTCC can be electrospun into nanofibers with the non-ionogenic polyvinyl alcohol (PVA), creating a high surface area mat. High surface area is a major requirement for effective adsorption processes. HTCC is antiviral and antimicrobial, making it a good material for water purification. However, HTCC dissolves in water. We have explored the parameters to crosslink the nanofibers with glutaraldehyde. We have imparted water stability so there is a maximum of 30% swelling of the fibers after 6 h in water. The water stable fibers retain their ability to adsorb virus, as shown for an enveloped and nonenveloped virus. HTCC now has the potential to be incorporated into a microfiltration membrane that can remove viruses. This could create an inexpensive, low pressure filtration membrane for drinking water purification. 
 Title: Virus adsorption of water-stable quaternized chitosan nanofibers
Output: False
Paragraph: Category A arenaviruses as defined by the National Institute of Allergy and Infectious Diseases (NIAID) are human pathogens that could be weaponized by bioterrorists. Many of these deadly viruses require biosafety level-4 (BSL-4) containment for all laboratory work, which limits traditional laboratory high-throughput screening (HTS) for identification of small molecule inhibitors. For those reasons, a related BSL-2 New World arenavirus, Tacaribe virus, 67-78% identical to Junín virus at the amino acid level, was used in a HTS campaign where approximately 400,000 small molecule compounds were screened in a Tacaribe virus-induced cytopathic effect (CPE) assay. Compounds identified in this screen showed antiviral activity and specificity against not only Tacaribe virus, but also the Category A New World arenaviruses (Junín, Machupo, and Guanarito). Drug resistant variants were isolated, suggesting that these compounds act through inhibition of a viral protein, the viral glycoprotein (GP2), and not through cellular toxicity mechanisms. A lead compound, ST-294, has been chosen for drug development. This potent and selective compound, with good bioavailability, demonstrated protective anti-viral efficacy in a Tacaribe mouse challenge model. This series of compounds represent a new class of inhibitors that may warrant further development for potential inclusion in a strategic stockpile. 
 Title: Identification and characterization of potent small molecule inhibitor of hemorrhagic fever New World arenaviruses
Output: True
Paragraph: The emergence of the highly pathogenic SARS coronavirus (SARS-CoV) has reignited interest in coronavirus biology and pathogenesis. An emerging theme in coronavirus pathogenesis is that the interaction between specific viral genes and the host immune system, specifically the innate immune system, functions as a key determinant in regulating virulence and disease outcomes. Using SARS-CoV as a model, we will review the current knowledge of the interplay between coronavirus infection and the host innate immune system in vivo, and then discuss the mechanisms by which specific gene products antagonize the host innate immune response in cell culture models. Our data suggests that the SARS-CoV uses specific strategies to evade and antagonize the sensing and signaling arms of the interferon pathway. We summarize by identifying future points of consideration that will contribute greatly to our understanding of the molecular mechanisms governing coronavirus pathogenesis and virulence, and the development of severe disease in humans and animals. 
 Title: SARS coronavirus and innate immunity
Output: True
Paragraph: Bamboo mosaic virus (BaMV) has a positive-sense single-stranded RNA genome with a 5′ cap and a 3′ poly (A) tail. To characterize polyadenylation activity in the BaMV replicase complex, we performed the in vitro polyadenylation with various BaMV templates. We conducted a polyadenylation activity assay for BaMV RNA by using a partially purified BaMV replicase complex. The results showed that approximately 200 adenylates at the 3′ end of the RNA were generated on the endogenous RNA templates. Specific fractions derived from uninfected Nicotiana benthamiana plants enhanced the polyadenylation activity, implying that host factors are involved in polyadenylation. Furthermore, polyadenylation can be detected in newly synthesized plus-strand RNA in vitro when using the exogenous BaMV minus-strand minigenome. For polyadenylation on the exogenous plus-strand minigenome, the 3′ end requires at least 4A to reach 22% polyadenylation activity. The results indicate that the BaMV replicase complex recognizes the 3′ end of BaMV for polyadenylation. 
 Title: Characterization of the polyadenylation activity in a replicase complex from Bamboo mosaic virus-infected Nicotiana benthamiana plants
Output: False
Paragraph: Cryptococcus gattii is a pathogenic environmental yeast that is considered to be emerging in different areas of the world including the Mediterranean Basin. Exposure to infection might be more likely in animals than in human beings, given their closer relationship with the natural habitat of the yeast, vegetation and soil. Thus, animals, and especially pets, can act as indicators of the presence of this yeast in a determined area. Domestic ferrets (Mustela putorius furo) have become common pets in the past 10-20 years. Their natural behavior of sniffing around and going inside narrow spaces makes them prone to contact with decaying organic matter and soil, the substrate for Cryptococcus species. This study describes two cases of cryptococcosis in ferrets in the Iberian Peninsula and Balearic Islands and documents a relationship of ferret cryptococcosis with environmental isolates in the same locations. Here, we emphasize the importance of how an adequate identification and environmental search of the yeast leads to a better understanding of the epidemiology of cryptococcosis and suggests ferrets may act as sentinels for this fungal disease. 
 Title: Ferrets as Sentinels of the Presence of Pathogenic Cryptococcus Species in the Mediterranean Environment
Output: True
Paragraph: Background: Up to date, there have been no studies to evaluate pilgrims' knowledge, attitude and practices regarding MERS-CoV during the annual Hajj pilgrimage in order to see whether there is a need for these aspects to be improved. Methods: A cross-sectional survey study was conducted with a convenience sampling. Participants were pilgrims, aged over 18, and able to speak Arabic or English. A self-administered structured questionnaire was distributed during Hajj season in Mecca. Descriptive and multiple linear regression analysis were used in data analysis. Results: Two hundred and fifty-seven participants completed the study, 80% of whom were female, and the median (IQR) age was 35 (24.5e43.5) years. Pilgrims had moderately correct knowledge and accurate attitudes about MERS-CoV with median scores of 5 (IQR 4e7) and 6 (IQR: 5e7) respectively. Educational level and employment status were significantly associated with knowledge whereas gender and age were significantly associated with attitude and practices respectively (P < 0.05). The correlation between knowledge, attitude and practices was significant (correlation coefficient: 0.207; P < 0.05). Better knowledge was found to be a predictor for positive practice. Conclusions: These findings will provide insight when designing future interventions to promote specific messages to enhance knowledge, change attitude and improve practice regarding MERS-CoV. 
 Title: "Your Health Essential for Your Hajj": Muslim pilgrims' knowledge, attitudes and practices regarding Middle East respiratory syndrome coronavirus (MERS-CoV) during Hajj season
Output: False
Paragraph: Background: The novel influenza A pandemic virus (H1N1pdm) caused considerable morbidity and mortality worldwide in 2009. The aim of the present study was to evaluate the clinical course, duration of viral shedding, H1N1pdm evolution and emergence of antiviral resistance in hospitalized cancer patients with severe H1N1pdm infections during the winter of 2009 in Brazil. We performed a prospective single-center cohort study in a cancer center in Rio de Janeiro, Brazil. Hospitalized patients with cancer and a confirmed diagnosis of influenza A H1N1pdm were evaluated. The main outcome measures in this study were in-hospital mortality, duration of viral shedding, viral persistence and both functional and molecular analyses of H1N1pdm susceptibility to oseltamivir. Results: A total of 44 hospitalized patients with suspected influenza-like illness were screened. A total of 24 had diagnosed H1N1pdm infections. The overall hospital mortality in our cohort was 21%. Thirteen (54%) patients required intensive care. The median age of the studied cohort was 14.5 years (3-69 years). Eighteen (75%) patients had received chemotherapy in the previous month, and 14 were neutropenic at the onset of influenza. A total of 10 patients were evaluated for their duration of viral shedding, and 5 (50%) displayed prolonged viral shedding (median 23, range = 11-63 days); however, this was not associated with the emergence of a resistant H1N1pdm virus. Viral evolution was observed in sequentially collected samples. Conclusions: Prolonged influenza A H1N1pdm shedding was observed in cancer patients. However, oseltamivir resistance was not detected. Taken together, our data suggest that severely ill cancer patients may constitute a pandemic virus reservoir with major implications for viral propagation. 
 Title: H1N1pdm Influenza Infection in Hospitalized Cancer Patients: Clinical Evolution and Viral Analysis
Output: False
Paragraph: More than 100 years of research has now been conducted into the prevention, control and elimination of rabies with safe and highly efficacious vaccines developed for use in human and animal populations. Domestic dogs are a major reservoir for rabies, and although considerable advances have been made towards the elimination and control of canine rabies in many parts of the world, the disease continues to kill tens of thousands of people every year in Africa and Asia. Policy efforts are now being directed towards a global target of zero human deaths from dog-mediated rabies by 2030 and the global elimination of canine rabies. Here we demonstrate how research provides a cause for optimism as to the feasibility of these goals through strategies based around mass dog vaccination. We summarize some of the pragmatic insights generated from rabies epidemiology and dog ecology research that can improve the design of dog vaccination strategies in low-and middleincome countries and which should encourage implementation without further delay. We also highlight the need for realism in reaching the feasible, although technically more difficult and longer-term goal of global elimination of canine rabies. Finally, we discuss how research on rabies has broader relevance to the control and elimination of a suite of diseases of current concern to human and animal health, providing an exemplar of the value of a 'One Health' approach. 
 Title: Rabies elimination research: juxtaposing optimism, pragmatism and realism
Output: True
Paragraph: Cytotoxic CD8+ T-cell immunosurveillance for intracellular pathogens, such as viruses, is controlled by classical major histocompatibility complex (MHC) class Ia molecules, and ideally, these antiviral T-cell populations are defined by the specific peptide and restricting MHC allele. Surprisingly, despite the utility of the cat in modeling human viral immunity, little is known about the Feline Leukocyte Antigen class I complex (FLAI). Only a few coding sequences with uncertain locus origin and expression patterns have been reported. Of 19 class I genes, 3 loci -FLAI-E, -H and -K -are predicted to encode classical molecules, and our objective was to evaluate their status by analyzing polymorphisms and tissue expression. Using locus-specific, PCR-based genotyping, we amplified 33 FLAI-E, -H, and -K alleles from 12 cats of various breeds, identifying, for the first time, alleles across 3 distinct loci in a feline species. Alleles shared the expected polymorphic and invariant sites in the 1/ 2 domains, and full-length cDNA clones possessed all characteristic class Ia exons. Alleles could be assigned to a specific locus with reasonable confidence, although there was evidence of potentially confounding interlocus recombination between FLAI-E and -K. Only FLAI-E, -H and -K-origin alleles were amplified from cDNAs of multiple tissue types. We also defined hypervariable regions across these genes, which permitted the assignment of names to both novel and established alleles. As predicted, FLAI-E, -H, and -K fulfill the major criteria of class Ia genes. These data represent a necessary prerequisite for studying epitope-specific antiviral CD8+ T-cell responses in cats. 
 Title: Polymorphisms and Tissue Expression of the Feline Leukocyte Antigen Class I Loci FLAI-E, -H and -K
Output: True
Paragraph: Pathological, immunocytochemical and microbiological findings in 32 cases of calf pneumonia associated with Haemophilus somnus infection are described. The majority of cases were "found dead" or died after a sudden onset pneumonia of less than 24h duration. Lesions of exudative bronchopneumonia were present and the cases could be divided into two main groups on the basis ofhistopathological and immunocytochemical features. In group A, cases were dominated by necrotizing bronchiolitis, degeneration and necrosis of airway and alveolar exudates, severe alveolitis with accumulations of degenerate basophilic cells, interstitial inflammatory changes and the widespread distribution ofH. somnus antigen in airways and alveoli. In Group B, necrotizing and degenerative changes were much less extensive and less severe and the overall appearance was of suppurative bronchopneumonia with H. somnus antigen much less widespread within the lungs. Alveolar oedema, hyaline membrane formation and alveolar epithelial hyperplasia were present in caudodorsal lung areas of several calves. No major differences were seen between the histopathology of lungs where H. somnus was' the sole isolate and that of lungs where H. somnus was isolated along with other bacterial pathogens. 
 Title: Pathological, Immunocytochemlcal and Microbiological Findings in Calf Pneumonias associated with Haernophilus sornnus infection
Output: False
Paragraph: Natural human exhalation flows such as coughing, sneezing and breathing can be considered as 'jet-like' airflows in the sense that they are produced from a single source in a single exhalation effort, with a relatively symmetrical, conical geometry. Although coughing and sneezing have garnered much attention as potential, explosive sources of infectious aerosols, these are relatively rare events during daily life, whereas breathing is necessary for life and is performed continuously. Real-time shadowgraph imaging was used to visualise and capture high-speed images of healthy volunteers sneezing and breathing (through the nose -nasally, and through the mouth -orally). Six volunteers, who were able to respond to the pepper sneeze stimulus, were recruited for the sneezing experiments (2 women: 27.566.36 years; 4 men: 29.25610.53 years). The maximum visible distance over which the sneeze plumes (or puffs) travelled was 0.6 m, the maximum sneeze velocity derived from these measured distances was 4.5 m/s. The maximum 2-dimensional (2-D) area of dissemination of these sneezes was 0.2 m 2 . The corresponding derived parameter, the maximum 2-D area expansion rate of these sneezes was 2 m 2 /s. For nasal breathing, the maximum propagation distance and derived velocity were 0.6 m and 1.4 m/s, respectively. The maximum 2-D area of dissemination and derived expansion rate were 0.11 m 2 and 0.16 m 2 /s, respectively. Similarly, for mouth breathing, the maximum propagation distance and derived velocity were 0.8 m and 1.3 m/ s, respectively. The maximum 2-D area of dissemination and derived expansion rate were 0.18 m 2 and 0.17 m 2 /s, respectively. Surprisingly, a comparison of the maximum exit velocities of sneezing reported here with those obtained from coughing (published previously) demonstrated that they are relatively similar, and not extremely high. This is in contrast with some earlier estimates of sneeze velocities, and some reasons for this difference are discussed. 
 Title: Airflow Dynamics of Human Jets: Sneezing and Breathing -Potential Sources of Infectious Aerosols
Output: True