niryuu/sni-each-converted huggingface dataset:
Paragraph: Two well-known antibiotic heterocycles, the 'quinolone' nalidixic acid and the b-lactam penicillin V, active at different levels of the bacterial growth process, have been attached via an ether-ester junction to the p-tert-butylcalix[4]arene lower rim, in alternate position. The resulting hydrophobic molecular drug-organisers were fully characterized, and evaluated over two Gram negative and three Gram positive reference strains, using disk diffusion assays with disks impregnated with solution of title compound in pure DMSO. An interesting activity was observed over Staphylococcus aureus ATCC 25923 with the dissymmetrical podand incorporating one penicillin and one nalidixic ester moieties. 
 Title: Molecular drug-organiser: Synthesis, characterization and biological evaluation of penicillin V and/or nalidixic acid calixarene-based podands
Output: True
Paragraph: This article takes a historical perspective on the changing position of WHO in the global health architecture over the past two decades. From the early 1990s a number of weaknesses within the structure and governance of the World Health Organization were becoming apparent, as a rapidly changing post Cold War world placed more complex demands on the international organizations generally, but significantly so in the field of global health. Towards the end of that decade and during the first half of the next, WHO revitalized and played a crucial role in setting global health priorities. However, over the past decade, the organization has to some extent been bypassed for funding, and it lost some of its authority and its ability to set a global health agenda. The reasons for this decline are complex and multifaceted. Some of the main factors include WHO's inability to reform its core structure, the growing influence of non-governmental actors, a lack of coherence in the positions, priorities and funding decisions between the health ministries and the ministries overseeing development assistance in several donor member states, and the lack of strong leadership of the organization. 
 Title: The World Health Organization and Global Health Governance: post-1990
Output: False
Paragraph: Much of the biology surrounding macrophage functional specificity has arisen through examining inflammation-induced polarising signals, but this also occurs in homeostasis, requiring tissuespecific environmental triggers that influence macrophage phenotype and function. The TAM receptor family of receptor tyrosine kinases (Tyro3, Axl and MerTK) mediates the noninflammatory removal of apoptotic cells by phagocytes through the bridging phosphatidylserinebinding molecules Gas6 or Protein S. We show that one such TAM receptor (Axl) is exclusively expressed on mouse airway macrophages, but not interstitial macrophages and other lung leukocytes, under homeostatic conditions and is constitutively ligated to Gas6. Axl expression is potently induced by GM-CSF expressed in the healthy and inflamed airway, and by type I interferon or TLR3 stimulation on human and mouse macrophages, indicating potential involvement of Axl in apoptotic cell removal under inflammatory conditions. Indeed, an absence of Axl does not cause sterile inflammation in health, but leads to exaggerated lung inflammatory disease upon influenza infection. These data imply that Axl allows specific identification of airway macrophages, and that its expression is critical for macrophage functional compartmentalisation in the airspaces or lung interstitium. We propose that this may be a critical feature to prevent excessive inflammation due to secondary necrosis of apoptotic cells that have not been cleared by efferocytosis. Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms Correspondence: T Hussell (tracy.hussell@manchester.ac.uk; Tel: +44 161 2751537). 
 Title: The Axl receptor tyrosine kinase is a discriminator of macrophage function in the inflamed lung Europe PMC Funders Group Europe PMC Funders Author Manuscripts Europe PMC Funders Author Manuscripts
Output: True
Paragraph: Picornaviruses form replication complexes in association with membranes in structures called replication organelles. Common themes to emerge from studies of picornavirus replication are the need for cholesterol and phosphatidylinositol 4-phosphate (PI4P). In infected cells, type III phosphatidylinositol 4-kinases (PI4KIIIs) generate elevated levels of PI4P, which is then exchanged for cholesterol at replication organelles. For the enteroviruses, replication organelles form at Golgi membranes in a process that utilizes PI4KIIIb. Other picornaviruses, for example the cardioviruses, are believed to initiate replication at the endoplasmic reticulum and subvert PI4KIIIa to generate PI4P. Here we investigated the role of PI4KIII in foot-and-mouth disease virus (FMDV) replication. Our results showed that, in contrast to the enteroviruses and the cardioviruses, FMDV replication does not require PI4KIII (PI4KIIIa and PI4KIIIb), and PI4P levels do not increase in FMDV-infected cells and PI4P is not seen at replication organelles. These results point to a unique requirement towards lipids at the FMDV replication membranes. 
 Title: Foot-and-mouth disease virus replicates independently of phosphatidylinositol 4-phosphate and type III phosphatidylinositol 4-kinases
Output: False
Paragraph: Several studies suggest that the open reading frame 3 (ORF3) gene of porcine epidemic diarrhea virus (PEDV) is related to viral infectivity and pathogenicity, but its function remains unknown. Here, we propose a structure model of the ORF3 protein consisting of four TM domains and forming a tetrameric assembly. ORF3 protein can be detected in PEDV-infected cells and it functions as an ion channel in both Xenopus laevis oocytes and yeast. Mutation analysis showed that Tyr170 in TM4 is important for potassium channel activity. Furthermore, viral production is reduced in infected Vero cells when ORF3 gene is silenced by siRNA. Interestingly, the ORF3 gene from an attenuated PEDV encodes a truncated protein with 49 nucleotide deletions, which lacks the ion channel activity. 
 Title: PEDV ORF3 encodes an ion channel protein and regulates virus production
Output: True
Paragraph: Bats have been proposed as major reservoirs for diverse emerging infectious viral diseases, with rabies being the best known in Europe. However, studies exploring the ecological interaction between lyssaviruses and their natural hosts are scarce. This study completes our active surveillance work on Spanish bat colonies that began in 1992. Herein, we analyzed ecological factors that might affect the infection dynamics observed in those colonies. Between 2001 and 2011, we collected and tested 2,393 blood samples and 45 dead bats from 25 localities and 20 bat species. The results for dead confirmed the presence of EBLV-1 RNA in six species analyzed (for the first time in Myotis capaccinii). Samples positive for European bat lyssavirus-1 (EBLV-1)-neutralizing antibodies were detected in 68% of the localities sampled and in 13 bat species, seven of which were found for the first time (even in Myotis daubentonii, a species to date always linked to EBLV-2). EBLV-1 seroprevalence (20.7%) ranged between 11.1 and 40.2% among bat species and seasonal variation was observed, with significantly higher antibody prevalence in summer (July). EBLV-1 seroprevalence was significantly associated with colony size and species richness. Higher seroprevalence percentages were found in large multispecific colonies, suggesting that intra-and interspecific contacts are major risk factors for EBLV-1 transmission in bat colonies. Although bat-roosting behavior strongly determines EBLV-1 variability, we also found some evidence that bat phylogeny might be involved in batspecies seroprevalence. The results of this study highlight the importance of life history and roost ecology in understanding EBLV-1-prevalence patterns in bat colonies and also provide useful information for public health officials. 
 Title: Ecological Factors Associated with European Bat Lyssavirus Seroprevalence in Spanish Bats
Output: True
Paragraph: Hepatitis C virus (HCV) is a small enveloped virus with a positive stranded RNA genome belonging to the Flaviviridae family. The virion has the unique ability of forming a complex with lipoproteins, which is known as the lipoviroparticle. Lipoprotein components as well as the envelope proteins, E1 and E2, play a key role in virus entry into the hepatocyte. HCV entry is a complex multistep process involving sequential interactions with several cell surface proteins. The virus relies on glycosaminoglycans and possibly the low-density lipoprotein receptors to attach to cells. Furthermore, four specific entry factors are involved in the following steps which lead to virus internalization and fusion in early endosomes. These molecules are the scavenger receptor SRB1, tetraspanin CD81 and two tight junction proteins, Claudin-1 and Occludin. Although they are essential to HCV entry, the precise role of these molecules is not completely understood. Finally, hepatocytes are highly polarized cells and which likely affects the entry process. Our current knowledge on HCV entry is summarized in this review. © Versita Sp. z o.o. 
 Title: Hepatitis C virus entry into the hepatocyte
Output: True
Paragraph: Four truncated porcine aminopeptidase N (pAPN, a cellular receptor for porcine coronaviruses) proteins were expressed in prokaryotic cells. The recognizing of a specific serum against pAPN to these proteins was investigated by enzyme-linked immunosorbent assay (ELISA) and immunoblotting. The binding ability of the proteins to transmissible gastroenteritis virus (TGEV), a porcine coronavirus, was analyzed by ELISA. The inhibitory effect of these proteins to cell infection by TGEV was analyzed using plaque assays. Our data indicate that three truncated pAPNs positively reacted with the specific antiserum and the major binding regions of pAPN were limited in regions 36aa-223aa, 349aa-591aa and 592-963aa. The proteins showed discrepant binding activity to either pAPN antibody or TGE virions. Moreover, the truncated proteins blocked the infection of cells by TGEV to different extent. The results suggest that the major antibody-binding domains of pAPN may associate with the receptor-binding determinants. The role of APN is discussed in the context of virus receptor usage. 
 Title: Binding characterization of determinants in porcine aminopeptidase N, the cellular receptor for transmissible gastroenteritis virus
Output: False
Paragraph: Attenuated measles virus (MV) is one of the most effective and safe vaccines available, making it attractive candidate vector to prevent infectious diseases. Attenuated MV have acquired the ability to use the complement regulator CD46 as a major receptor to mediate virus entry and intercellular fusion. Therefore, attenuated MV strains preferentially infect and destroy a wide variety of cancer cells making them also attractive oncolytic vectors. The use of recombinant MV vector has to comply with various regulatory requirements, particularly relating to the assessment of potential risks for human health and the environment. The present article highlights the main characteristics of MV and recombinant MV vectors used for vaccination and virotherapy and discusses these features from a biosafety point of view. 
 Title: Biosafety considerations for attenuated measles virus vectors used in virotherapy and vaccination
Output: False
Paragraph: Egyptian poultry suffer from frequent respiratory disease outbreaks associated with Infectious Bronchitis Virus (IBV) variant 2 strains (Egy/VarII). Different vaccination programs using imported vaccines have failed to protect the flocks from field challenge. Recent studies confirmed a successful protection using homologous strains as live attenuated vaccines. In this study, a newly developed live attenuated IB-VAR2 vaccine representing the GI-23 Middle East IBV lineage was evaluated in day-old commercial broilers in an IBV-endemic area. A commercial broiler flock was vaccinated with the IB-VAR2 vaccine at day-old age followed by IB-H120 at day 16. The vaccinated flock was monitored on a weekly basis till the slaughter age. The health status and growth performance were monitored, and selected viral pathogen real-time RT-PCR (rRT-PCR) detection was conducted on a weekly basis. Finally, the flock was compared to a nearby farm with only the classical IB-H120 vaccination program. Results showed that the IB-VAR2 vaccine was tolerable in day-old broiler chicks. The IBV virus rRT-PCR detection was limited to the trachea as compared to its nephropathogenic parent virus. Respiratory disease problems and high mortalities were reported in the IB-H120-only vaccinated flock. An exposure to a wild-type Egy/VarII strain was confirmed in both flocks as indicated by partial IBV S1 gene sequence. Even though the IB-VAR2-vaccinated flock performance was better than the flock that received only IB-H120, the IBV ELISA (enzyme-linked immunosorbent assay) and log2 Haemagglutination inhibition (HI) antibody mean titers remained high (3128 ± 2713 and ≥9 log2, respectively) until the 28th day of age. The current study demonstrates the safety and effectiveness of IB-VAR2 as a live attenuated vaccine in day-old commercial broilers. Also, the combination of IB-VAR2 and classical IBV vaccines confers a broader protective immune response against IBV in endemic areas. 
 Title: Field Efficacy of an Attenuated Infectious Bronchitis Variant 2 Virus Vaccine in Commercial Broiler Chickens
Output: True
Paragraph: The massive abundance of studies relating to tropical medicine and health has increased strikingly over the last few decades. In the field of tropical medicine and health, a well-conducted systematic review and meta-analysis (SR/MA) is considered a feasible solution for keeping clinicians abreast of current evidence-based medicine. Understanding of SR/MA steps is of paramount importance for its conduction. It is not easy to be done as there are obstacles that could face the researcher. To solve those hindrances, this methodology study aimed to provide a step-by-step approach mainly for beginners and junior researchers, in the field of tropical medicine and other health care fields, on how to properly conduct a SR/MA, in which all the steps here depicts our experience and expertise combined with the already well-known and accepted international guidance. We suggest that all steps of SR/MA should be done independently by 2-3 reviewers' discussion, to ensure data quality and accuracy. Conclusion: SR/MA steps include the development of research question, forming criteria, search strategy, searching databases, protocol registration, title, abstract, full-text screening, manual searching, extracting data, quality assessment, data checking, statistical analysis, double data checking, and manuscript writing. 
 Title: A step by step guide for conducting a systematic review and meta-analysis with simulation data
Output: True
Paragraph: Monoclonal antibodies to the Quebec isolate of bovine coronavirus were produced and characterized . Monoclonal antibodies to both the E2 and the E3 glycoproteins were found to efficiently neutralize virus in vitro. None of the monoclonal antibodies directed against the El glycoprotein neutralized virus infectivity . Neutralizing monoclonal antibodies to the E2 glycoprotein were all found to immunoprecipitate gpl 90, gpl 00, and their intracellular precursor protein gp170. Neutralizing monoclonal antibodies to the E3 glycoprotein immunoprecipitated gp124 and showed differential reactivity to its precursor proteins gp59 and gpl 18 . These monoclonal antibodies also showed differential reactivity to an apparent degradation product of E3 . Neutralizing monoclonal antibodies to E2 bound to two distinct nonoverlappig antigenic domains as defined by competitive binding assays . Neutralizing monoclonal antibodies to the E3 glycoprotein also bound to two distinct antigenic sites as defined by competitive binding assays plus a third site which overlapped these regions . Other results indicated that one domain on the E3 glycoprotein could be further subdivided into two epitopes . Thus four epitopes could be defined by E3-specific monoclonal antibodies . C 1987 Academic Press, Inc . 
 Title: Monoclonal Antibodies to Bovine Coronavirus : Characteristics and Topographical Mapping of Neutralizing Epitopes on the E2 and E3 Glycoproteins'
Output: False
Paragraph: Hepatitis C Virus (HCV) infects 2% of the world's population and is the leading cause of liver disease and liver transplantation. It poses a serious and growing worldwide public health problem that will only be partially addressed with the introduction of new antiviral therapies. However, these treatments will not prevent re-infection particularly in high risk populations. The introduction of a HCV vaccine has been predicted, using simulation models in a high risk population, to have a significant effect on reducing the incidence of HCV. A vaccine with 50 to 80% efficacy targeted to high-risk intravenous drug users could dramatically reduce HCV incidence in this population. Virus like particles (VLPs) are composed of viral structural proteins which self-assemble into non-infectious particles that lack genetic material and resemble native viruses. Thus, VLPs represent a safe and highly immunogenic vaccine delivery platform able to induce potent adaptive immune responses. Currently, many VLP-based vaccines have entered clinical trials, while licensed VLP vaccines for hepatitis B virus (HBV) and human papilloma virus (HPV) have been in use for many years. The HCV core, E1 and E2 proteins can self-assemble into immunogenic VLPs while inclusion of HCV antigens into heterogenous (chimeric) VLPs is also a promising approach. These VLPs are produced using different expression systems such as bacterial, yeast, mammalian, plant, or insect cells. Here, this paper will review HCV VLP-based vaccines and their immunogenicity in animal models as well as the different expression systems used in their production. 
 Title: Preclinical Development and Production of Virus-Like Particles As Vaccine Candidates for Hepatitis C
Output: True
Paragraph: Atypical" pneumonia was described as a distinct and mild form of community-acquired pneumonia (CAP) already before Mycoplasma pneumoniae had been discovered and recognized as its cause. M. pneumoniae is detected in CAP patients most frequently among school-aged children from 5 to 15 years of age, with a decline after adolescence and tapering off in adulthood. Detection rates by polymerase chain reaction (PCR) or serology in children with CAP admitted to the hospital amount 4-39%. Although the infection is generally mild and self-limiting, patients of every age can develop severe or extrapulmonary disease. Recent studies indicate that high rates of healthy children carry M. pneumoniae in the upper respiratory tract and that current diagnostic PCR or serology cannot discriminate between M. pneumoniae infection and carriage. Further, symptoms and radiologic features are not specific for M. pneumoniae infection. Thus, patients may be unnecessarily treated with antimicrobials against M. pneumoniae. Macrolides are the first-line antibiotics for this entity in children younger than 8 years of age. Overall macrolides are extensively used worldwide, and this has led to the emergence of macrolide-resistant M. pneumoniae, which may be associated with severe clinical features and more extrapulmonary complications. This review focuses on the characteristics of M. pneumoniae infections in children, and exemplifies that simple clinical decision rules may help identifying children at high risk for CAP due to M. pneumoniae. This may aid physicians in prescribing appropriate first-line antibiotics, since current diagnostic tests for M. pneumoniae infection are not reliably predictive. 
 Title: Infection with and Carriage of Mycoplasma pneumoniae in Children
Output: True
Paragraph: Background: Italy is bearing the brunt of the COVID-19 pandemic, as the death toll there has already surpassed that in Wuhan, the city in China where the coronavirus emerged in December 2019. Here we employ statistical methods to assess the severity of COVID-19 pandemic across different regions of Italy. We manually retrieved the daily cumulative numbers of laboratory-confirmed cases and deaths attributed to COVID-19 stratified by region in Italy from March 2, 2020 to March 28, 2020. We estimated both the crude and time-delay adjusted case fatality ratio across five geographic regions of Italy: Northwest, Northeast, Center, South and Island. : The Northwest that includes Lombardy exhibited the highest time-delay-adjusted CFR at 31.4%% [95% credible interval: 30.8, 32.1%] followed by the Northeast (20.3%) [95% CrI: 19.4, 21.1], the Center region (16.5%) [95% CrI: 15.4, 17.7] and the South region (16.8%) [95% CrI: 15.0, 18.7]. The Island region has exhibited the lowest CFR (11.8%) [95% CrI: 9.0, 14.8]. Conclusion: Italy is experiencing one of the highest CFR from the COVID-19 pandemic in the world. Time delay adjusted CFR in all the regions in Italy except the Island region were higher than that estimated for Wuhan, China. The CFR in Northwest Italy is 2.5-fold higher than that in Wuhan. Our finding reflects the need of urgent medical support in the Northwest region and the appropriate planning and supplies procurement in other regions of Italy with . CC-BY-NC-ND 4.0 International license It is made available under a author/funder, who has granted medRxiv a license to display the preprint in perpetuity. is the (which was not peer-reviewed) The copyright holder for this preprint . 
 Title: Title: Spatial variability in the risk of death from COVID-19 in Italy, 2020
Output: False
Paragraph: Ubiquitin-like protease 1 (Ulp1) of Saccharomyces cerevisiae emerges as a fundamental tool to obtain the natural N-terminal target protein by cleavage of the small ubiquitin-related modifier (SUMO) fusion protein. However, the costly commercial Ulp1 and its complicated procedures limit its application in the preparation of the target protein with natural N-terminal sequence. Here, we describe the preparation of bioactive codon-optimized recombinant truncated Ulp1 (Leu403-Lys621) (rtUlp1) of S. cerevisiae in Escherichia coli using only one-step with Ni-NTA affinity chromatograph, and the application of rtUlp1 to cleave the SUMO fusion protein by simply mixing the purified rtUlp1, SUMO fusion protein and DL-Dithiothreitol in Tris-HCl buffer. The optimal expression level of nonfusion protein rtUlp1 accounts for approximately 50 % of the total cellular protein and 36 % of the soluble form by addition of isopropyl b-D-l-thiogalactopyranoside at a final concentration of 0.4 mM at 18°C for 20 h. The purification of target protein rtUlp1 was conducted by Ni-NTA affinity chromatography. The final yield of rtUlp1 was 45 mg/l in flask fermentation with a purity up to 95 %. Furthermore, the high purity of rtUlp1 could effectively cleave the SUMO-tTbRII fusion protein (SUMO gene fused to truncated transforming growth factor-beta receptor type II gene) with the above simplified approach, and the specific activity of the rtUlp1 reached up to 2.8 9 10 4 U/mg, which is comparable to the commercial Ulp1. The preparation and application strategy of the rtUlp1 with commonly available laboratory resources in this study will be convenient to the cleavage of the SUMO fusion protein to obtain the natural N-terminal target protein, which can be implemented in difficult-to-express protein functional analysis. Keywords Ubiquitin-like protease 1 Á Expression Á Nonfusion protein Á Purification Á Escherichia coli Abbreviations Ubiquitin-like protease 1 Ulp2 Ubiquitin-like protease 2 PCR Polymerase chain reaction HRP Horse radish peroxidase IPTG Isopropyl b-D-l-thiogalactopyranoside DTT DL-Dithiothreitol SDS-PAGE SDS-polyacrylamide gel electrophoresis tTbRII Truncated transforming growth factor-beta receptor type II gene 
 Title: A Novel Strategy for the Preparation of Codon-Optimized Truncated Ulp1 and its Simplified Application to Cleavage the SUMO Fusion Protein
Output: False
Paragraph: To exploit a cross passive immunotherapy for enterovirus-induced hand-foot-and-mouth disease (HFMD), the cross antiviral activity of a neutralizing antibody against enterovirus 71 (EV71) and coxsackievirus A16 (CVA16) was investigated in vitro. White Leghorn specific-pathogen-free chickens were immunized with EV71 antigens and a specific isolated immunoglobulin (IgY) was prepared from the chicken egg yolk. IgY was further purified and characterized by SDS-PAGE, ELISA, western blotting and bidirectional immune agar diffusion testing. The antiviral activity and dose-response of the IgY were determined by assessing the cytopathic effect in rhabdomyosarcoma (RD) cells in vitro. It was indicated that the levels of IgY were increased at day 7, peaked at week 7 and were maintained at a higher level for 4 weeks following immunization when compared with the negative control. The results of western blotting and bidirectional immune agar diffusion testing revealed that the IgY had cross-binding properties in EV71 and CVA16 strains through targeting the envelope proteins (VP0, VP1 and VP3) of EV71 and CVA16. Neutralization assay results indicated that the infectivity of EV71 and CVA16 strains in RD cells was cross-blocked by IgY in a dose-dependent manner. To conclude, these findings indicate that IgY has cross antiviral activity against EV71 and CVA16 in vitro, and could potentially be developed as a passive immunotherapy for EV71-and CVA16-induced HFMD. 
 Title: Enterovirus type 71-immunized chicken egg yolk immunoglobulin has cross antiviral activity against coxsackievirus A16 in vitro
Output: True
Paragraph: Drug dosing in critically ill patients is challenging due to the altered drug pharmacokinetics-pharmacodynamics associated with systemic therapies. For many drug therapies, there is potential to use the respiratory system as an alternative route for drug delivery. Aerosol drug delivery can provide many advantages over conventional therapy. Given that respiratory diseases are the commonest causes of critical illness, use of aerosol therapy to provide high local drug concentrations with minimal systemic side effects makes this route an attractive option. To date, limited evidence has restricted its wider application. The efficacy of aerosol drug therapy depends on drug-related factors (particle size, molecular weight), device factors, patient-related factors (airway anatomy, inhalation patterns) and mechanical ventilation-related factors (humidification, airway). This review identifies the relevant factors which require attention for optimization of aerosol drug delivery that can achieve better drug concentrations at the target sites and potentially improve clinical outcomes. 
 Title: Fundamentals of aerosol therapy in critical care
Output: False
Paragraph: In this chapter, we show the presence of tissue-type plasminogen activator (t-PA), urokinase-type plasminogen activator (u-PA), and plasminogen activator inhibitor-1 (PAI-1) in nasal mucosa. It is suggested that t-PA synthesized in mucous cells is promptly secreted and modifies the watery nasal discharge in allergic rhinitis and that u-PA activity may help with the passage of large amounts of rhinorrhea by reducing its viscosity. Furthermore, we clarify the relation between fibrinolytic components and the pathology of allergy, particularly during the development of nasal allergy and nasal tissue changes. Wild-type (WT) mice can develop nasal allergy for ovalbumin (OVA) sensitization, but PAI-1-deficient mice (PAI-T^") cannot. The production of specific immunoglobulins IgGl and IgE in the serum and production of interleukins IL-4 and IL-5 in splenocyte culture supernatant increased significantly in WT-OVA mice. In PAI-l"^" mice, these reactions were absent, and specific IgG2a in serum and interferon-y in splenocyte culture medium increased significantly. Histopathologically, there was marked goblet cell hyperplasia and eosinophil infiltration into the nasal mucosa in WT-OVA mice, but these were absent in PAI-l"^" mice. These results indicate that the immune response in WT-OVA mice can be classified as a dominant Th2 response, which would promote collagen deposition. In contrast, the Th2 response in PAI-l"^" mice was down-regulated and the immune response shifted from Th2-dominant reaction to a Thl-dominant one. Taken together, these findings suggest that PAI-1 plays an important role not only in thrombolysis but also in the immune response. 
 Title: Role of Fibrinolysis in the Nasal System TAKAYUKI SEJIMA AND YOICHI SAKATA^
Output: False
Paragraph: Cyclodextrins (CyDs) currently displays even today the image of a natural macrocyclic compound largely dominant in the formation of inclusion complexes with small hydrophobic molecules. During the past 10 years, advances in this field allowed to achieve more and more sophisticated CyDs derivatives opening a simple access in scale-up quantities to original and better CyD-based gene delivery systems. In addition, possibility to combine covalent and supramolecular approaches offers new venues for the design of tailor-made CyDbased nanovehicles to improve their transfection ability and gene transfer in cells. In this account, we describe our recent progress in the construction of a novel CyD-based G0 (generation number) core dendrimer, scalable to CyD oligomers by a strategy using protonable guanidine tethers and whose concept can be generalized for the assembly of CyD pre-coated dendrimers. The synthetic strategy based on an original Staudinger-Aza-Wittig tandem coupling reaction. We present an outline of the different analytical strategies to characterize CyD-ODN (cyclodextrin-oligodeoxynucleotide) complexes. Among them, Capillary electrophoresis (CE) was used to perfectly characterize our CyD-siRNA and CyD-DNA complexes and shown to be a very attractive method with advantages of low sample consumption, rapid analysis speed, and high efficiency that make this technology a major tool for association constant measurement. Finally, we present the different biological methods that can be used, in vitro, to study gene delivery, and more precisely ones we have performed to evaluate the capability of our original model bis-guanidinium-tetrakis-␤-cyclodextrin dendrimeric tetrapod, to deliver efficiently DNA or siRNA in eukaryotic cells. 
 Title: Interest of designed cyclodextrin-tools in gene delivery ଝ Intérêt des outils cyclodextrines-modèles dans la délivrance de gènes
Output: False
Paragraph: Human coronaviruses (HCoVs) are associated with a variety of clinical presentations in children, but their role in disease remains uncertain. The objective of our prospective study was to investigate HCoVs associations with various clinical presentations in hospitalized children up to 6 years of age. Children hospitalized with acute bronchiolitis (AB), acute gastroenteritis (AGE), or febrile seizures (FS), and children admitted for elective surgical procedures (healthy controls) were included in the study. In patients with AB, AGE, and FS, a nasopharyngeal (NP) swab and blood sample were obtained upon admission and the follow-up visit 14 days later, whereas in children with AGE a stool sample was also acquired upon admission; in healthy controls a NP swab and stool sample were taken upon admission. Amplification of polymerase 1b gene was used to detect HCoVs in the specimens. HCoVs-positive specimens were also examined for the presence of several other viruses. HCoVs were most often detected in children with FS (19/192, 9 .9%, 95% CI: 6-15%), followed by children with AGE (19/218, 8.7%, 95% CI: 5.3-13.3%) and AB (20/308, 6.5%, 95% CI: 4.0-9.8%). The presence of other viruses was a common finding, most frequent in the group of children with AB (19/20, 95%, 95% CI: 75.1-99.8%), followed by FS (10/19, 52.6%, 95% CI: 28.9-75.6%) and AGE (7/19, 36.8%, 95% CI: 16.3-61.6%). In healthy control children HCoVs were detected in 3/156 (1.9%, 95% CI: 0.4-5.5%) NP swabs and 1/150 (0.7%, 95% CI: 0.02-3.3%) stool samples. It seems that an etiological role of HCoVs is most likely in children with FS, considering that they had a higher proportion of positive HCoVs results than patients with AB and those with AGE, and had the highest viral load; however, the co-detection of other viruses was 52.6%. 
 Title: The Role of Human Coronaviruses in Children Hospitalized for Acute Bronchiolitis, Acute Gastroenteritis, and Febrile Seizures: A 2-Year Prospective Study
Output: False
Paragraph: Rapid urbanization combined with climate change necessitates new types of urban services that make best use of science and technology. The Integrated Urban Hydro-Meteorological, Climate and Environmental Services and systems are a new initiative from the World Meteorological Organization (WMO) that seeks to provide science-based integrated urban services supporting safe, healthy and resilient cities. Various cities have already started development and implementation of such Integrated Urban Services and successfully test and use them following specific requirements of local stakeholders. This paper demonstrates the novel concept and approach of Integrated Urban Hydro-Meteorological, Climate and Environmental Services (IUS) from a set of four case study cities: Hong Kong, Toronto, Mexico City and Paris, that use different IUS configurations with good existing practice. These cities represent a range of countries, climates and geophysical settings. The aggregate main joint similarities of the IUS in these cities and synergy of the cities' experience, achievements and research findings are presented, as well as identification of existing gaps in knowledge and further research needs. A list of potential criteria for identifying and classifying IUS demonstration cities is proposed. It will aid future, more detailed analysis of the IUS experience, and selection of additional demonstration cities. Urbanization is an ongoing phenomenon and a growing number of urban settings are particularly vulnerable to weather and climate events, including floods, storms, heat waves, sea-level rise and poor air quality. In addition, urban dwellers are the primary users of energy and resources, and contribute in a significant way to increasing atmospheric greenhouse gasses as well as air pollution. These alterations to the atmosphere from urban to global scales have consequent impacts on human health and the environment. But the urban setting also provides exciting opportunities for scientific advancement in the field of new observations, data assimilation, high resolution coupled modeling and user-specific systems and services for sustainable and climate smart cities. Most (90%) of the disasters affecting urban areas are of a hydro-meteorological nature and these have increased due to climate https://doi. 
 Title: Integrated urban services: Experience from four cities on different continents
Output: True
Paragraph: Cases of progressive multifocal leukoencephalopathy can occur in patients treated with the B cell depleting anti-CD20 antibody, rituximab, highlighting the importance of B cell surveillance of the central nervous system (CNS). The lymphoid chemokine, CXCL13, is critical for B cell recruitment and functional organization of peripheral lymphoid tissues, and CXCL13 levels are often elevated in the inflamed CNS. To more directly investigate the role of CXCL13 in CNS B cell migration, its role in animal models of infectious and inflammatory demyelinating disease was examined. During acute alphavirus encephalitis where viral clearance depends on the local actions of anti-viral antibodies, CXCL13 levels and B cell numbers increased in brain tissue over time. Surprisingly, however, CXCL13-deficient animals showed normal CNS B cell recruitment, unaltered CNS virus replication and clearance, and intact peripheral anti-viral antibody responses. During experimental autoimmune encephalomyelitis (EAE), CNS levels of CXCL13 increased as symptoms emerged and equivalent numbers of B cells were identified among the CNS infiltrates of CXCL13-deficient mice compared to control animals. However, CXCL13-deficient mice did not sustain pathogenic anti-myelin T cell responses, consistent with their known propensity to develop more self-limited EAE. These data show that CXCL13 is dispensable for CNS B cell recruitment in both models. The disease course is unaffected by CXCL13 in a CNS infection paradigm that depends on a pathogen-specific B cell response, while it is heightened and prolonged by CXCL13 when myelin-specific CD4+ T cells drive CNS pathology. Thus, CXCL13 could be a therapeutic target in certain neuroinflammatory diseases, but not by blocking B cell recruitment to the CNS. 
 Title: The lymphoid chemokine, CXCL13, is dispensable for the initial recruitment of B cells to the acutely inflamed central nervous system NIH Public Access
Output: True
Paragraph: Viral 2=,5=-phosphodiesterases (2=,5=-PDEs) help disparate RNA viruses evade the antiviral activity of interferon (IFN) by degrading 2=,5=-oligoadenylate (2-5A) activators of RNase L. A kinase anchoring proteins (AKAPs) bind the regulatory subunits of protein kinase A (PKA) to localize and organize cyclic AMP (cAMP) signaling during diverse physiological processes. Among more than 43 AKAP isoforms, AKAP7 appears to be unique in its homology to viral 2=,5=-PDEs. Here we show that mouse AKAP7 rapidly degrades 2-5A with kinetics similar to that of murine coronavirus (mouse hepatitis virus [MHV]) strain A59 ns2 and human rotavirus strain WA VP3 proteins. To determine whether AKAP7 could substitute for a viral 2=,5=-PDE, we inserted AKAP7 cDNA into an MHV genome with an inactivated ns2 gene. The AKAP7 PDE domain or N-terminally truncated AKAP7 (both lacking a nuclear localization motif), but not full-length AKAP7 or a mutant, AKAP7 H185R , PDE domain restored the infectivity of ns2 mutant MHV in bone marrow macrophages and in livers of infected mice. Interestingly, the AKAP7 PDE domain and N-terminally deleted AKAP7 were present in the cytoplasm (the site of MHV replication), whereas full-length AKAP7 was observed only in nuclei. We suggest the possibility that viral acquisition of the host AKAP7 PDE domain might have occurred during evolution, allowing diverse RNA viruses to antagonize the RNase L pathway. We also reported that the rotavirus VP3 C-terminal domain (VP3-CTD) cleaves 2-5A and that it may rescue ns2 mutant MHV. Here we report that a cellular protein, AKAP7, has an analogous 2=,5=-phosphodiesterase (2=,5=-PDE) domain that is able to restore the growth of chimeric MHV expressing inactive ns2. The proviral effect requires cytoplasmic localization of the AKAP7 PDE domain. We speculate that AKAP7 is the ancestral precursor of viral proteins, such as ns2 and VP3, that degrade 2-5A to evade the antiviral activity of RNase L. RH. 2014 . Murine AKAP7 has a 2=,5=-phosphodiesterase domain that can complement an inactive murine coronavirus ns2 gene. mBio 5(4):e01312-14. 
 Title: Murine AKAP7 Has a 2=,5=-Phosphodiesterase Domain That Can Complement an Inactive Murine Coronavirus ns2 Gene
Output: True
Paragraph: Background The outbreak of severe acute respiratory syndrome in 2003 and the subsequent emergence of the H5N1 virus have highlighted the threat of a global pandemic influenza outbreak. Planning effective public health control measures for such a case will be highly dependent on sound theory-based research on how people perceive the risks involved in such an event. Purpose The present article aims to review theoretical models and concepts underlying current empirical research on pandemic influenza risk perception. Method A review was conducted based on 28 empirical studies from 30 articles which were published between 2003 and 2007. Results Concepts of risk perception mostly seemed more pragmatic than theory-based and were highly heterogeneous, for instance, in terms of conceptualizing risk perception as an exclusively cognitive or as a cognitive and emotional phenomenon or whether the concept was dominated by expectancy or expectancy and value components. Similarly, the majority of studies investigating risk perceptions and protective behaviors were not model-based. Conclusions The current body of knowledge can only provide preliminary insights. Unlike the reviewed studies, which were mostly launched as a rapid response to outbreak situations, future research will have to invest more strongly into theoretical work to provide sounder evidence. 
 Title: Risk Perceptions Related to SARS and Avian Influenza: Theoretical Foundations of Current Empirical Research
Output: False
Paragraph: The Middle East respiratory syndrome-related coronavirus (MERS-CoV) can cause severe disease and has pandemic potential. Therefore, development of antiviral strategies is an important task. The activation of the viral spike protein (S) by host cell proteases is essential for viral infectivity and the responsible enzymes are potential therapeutic targets. The cellular proteases furin, cathepsin L and TMPRSS2 can activate MERS-S and may cleave the S protein at two distinct sites, termed S1/S2 and S2′. Moreover, a potential cathepsin L cleavage site in MERS-S has been reported. However, the relative importance of these sites for MERS-S activation is incompletely understood. Here, we used mutagenic analysis and MERS-S-bearing vectors to study the contribution of specific cleavage sites to S proteindriven entry. We found that an intact S1/S2 site was only required for efficient entry into cells expressing endogenous TMPRSS2. In keeping with a previous study, pre-cleavage at the S1/S2 motif (RSVR) was important although not essential for subsequent MERS-S activation by TMPRSS2, and indirect evidence was obtained that this motif is processed by a protease depending on an intact RXXR motif, most likely furin. In contrast, the S2′ site (RSAR) was required for robust viral entry into all cell lines tested and the integrity of one of the two arginines was sufficient for efficient entry. These findings suggest that cleavage at S2′ is carried out by proteases recognizing a single arginine, most likely TMPRSS2 and cathepsin L. Finally, mutation of the proposed cathepsin L site did not impact viral entry and double mutation of S1/S2 and S2′ site was compatible with cathepsin L-but not TMPRSS2-dependent host cell entry, indicating that cathepsin L can process the S protein at auxiliary sites. Collectively, our results indicate a rigid sequence requirement for S protein activation by TMPRSS2 but not cathepsin L. 
 Title: Functional analysis of potential cleavage sites in the MERS- coronavirus spike protein
Output: True
Paragraph: Griffithsin (GRFT) is a broad-spectrum antiviral protein against several glycosylated viruses. In our previous publication, we have shown that GRFT exerted antiviral activity against Japanese encephalitis virus (JEV) infection. Herein, we further elucidated the mechanism by which GRFT inhibits JEV infection in BHK-21 cells. In vitro experiments using Pull-down assay and Co-immunoprecipitation (CO-IP) assay showed that GRFT binds to the JEV glycosylated viral proteins, specifically the enveloped (E) and premature (prM) glycoproteins. The binding of GRFT to the JEV was competitively inhibited by increasing concentrations of mannose; in turns abolished anti-JEV activity of GRFT. We suggested that, the binding of GRFT to the glycosylated viral proteins may contribute to its anti-JEV activity. Collectively, our data indicated a possible mechanism by which GRFT exerted its anti-JEV activity. This observation suggests GRFT's potentials in the development of therapeutics against JEV or other flavivirus infection. 
 Title: Griffithsin binds to the glycosylated proteins (E and prM) of Japanese encephalitis virus and inhibit its infection
Output: False
Paragraph: Codon usage patterns of viruses reflect a series of evolutionary changes that enable viruses to shape their survival rates and fitness toward the external environment and, most importantly, their hosts. In the present study, we employed multiple codon usage analysis indices to determine genotype specific codon usage patterns of Zika virus (ZIKV) strains from the current outbreak and those reported previously. Several genotype specific and common codon usage traits were noted in ZIKV coding sequences, indicative of independent evolutionary origins from a common ancestor. The overall influence of natural selection was found to be more profound than that of mutation pressure and acting on specific set of viral genes belonging to ZIKV strains of Asian genotype from the recent outbreak. Furthermore, an interplay of codon adaptation and deoptimization have been observed in ZIKV genomes. The collective findings of codon analysis in association with the geographical data of Aedes populations in the Americas suggests that ZIKV have evolved a dynamic set of codon usage patterns in order to maintain a successful replication and transmission chain within multiple hosts and vectors. 
 Title: Zika virus outbreak in the Americas: Is Aedes albopictus an overlooked culprit?
Output: True
Paragraph: Short running head: Sensitive detection of SARS-CoV-2 using double-quencher probe ORCID : 0000-0002-8002-834X (Yosuke Hirotsu) Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerges in Wuhan City, Hubei Province, spreads worldwide, and threats the human life. The detection of SARS-CoV-2 is important for the prevention of the outbreak and management of patients. Real-time reverse-transcription polymerase chain reaction (RT-PCR) assay detected the virus in clinical laboratory. This study utilized primers and single-quencher probes in accordance with the Centers for Disease Control and Prevention (CDC) in the USA and the National Institute of Infectious Diseases (NIID) in Japan. Moreover, we designed the double-quencher probes (YCH assay) according to the oligonucleotide sequence established by NIID. Using these assays, we conducted a one-step real-time RT-PCR with serial DNA positive control to assess the detection sensitivity. The threshold cycle (Ct) value of RT-PCR was relatively low in CDC and YCH assays compared to NIID assay. Serial dilution assay showed that both CDC and YCH assays could detect a low-copy number of DNA positive control. The background fluorescent signal at the baseline was lower in YCH than that of NIID. Double-quencher probes decreased background fluorescent signal and improved detection sensitivity of SARS-CoV-2. 
 Title: Double-Quencher Probes Improved the Detection Sensitivity of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) by One-Step RT-PCR
Output: True
Paragraph: Recycling endosomes maintain plasma membrane homeostasis and are important for cell polarity, migration, and cytokinesis. Yet, the molecular machineries that drive endocytic recycling remain largely unclear. The CORVET complex is a multi-subunit tether required for fusion between early endosomes. Here we show that the CORVET-specific subunits Vps3 and Vps8 also regulate vesicular transport from early to recycling endosomes. Vps3 and Vps8 localise to Rab4-positive recycling vesicles and co-localise with the CHEVI complex on Rab11-positive recycling endosomes. Depletion of Vps3 or Vps8 does not affect transferrin recycling, but delays the delivery of internalised integrins to recycling endosomes and their subsequent return to the plasma membrane. Consequently, Vps3/8 depletion results in defects in integrin-dependent cell adhesion and spreading, focal adhesion formation, and cell migration. These data reveal a role for Vps3 and Vps8 in a specialised recycling pathway important for integrin trafficking. 
 Title: Vps3 and Vps8 control integrin trafficking from early to recycling endosomes and regulate integrin- dependent functions
Output: False