niryuu/sni-each-converted huggingface dataset:
Linear motifs are short, evolutionarily plastic components of regulatory proteins and provide low-affinity interaction interfaces. These compact modules play central roles in mediating every aspect of the regulatory functionality of the cell. They are particularly prominent in mediating cell signaling, controlling protein turnover and directing protein localization. Given their importance, our understanding of motifs is surprisingly limited, largely as a result of the difficulty of discovery, both experimentally and computationally. The Eukaryotic Linear Motif (ELM) resource at http:// elm.eu.org provides the biological community with a comprehensive database of known experimentally validated motifs, and an exploratory tool to discover putative linear motifs in user-submitted protein sequences. The current update of the ELM database comprises 1800 annotated motif instances representing 170 distinct functional classes, including approximately 500 novel instances and 24 novel classes. Several older motif class entries have been also revisited, improving annotation and adding novel instances. Furthermore, addition of full-text search capabilities, an enhanced interface and simplified batch download has improved the overall accessibility of the ELM data. The motif discovery portion of the ELM resource has added conservation, and structural attributes have been incorporated to aid users to discriminate biologically relevant motifs from stochastically occurring non-functional instances. Figure 5 . Schema of the ELM resource and data life cycle. Annotated ELM classes, and instances thereof, can be searched by database query. Via sequence search by the motif detection pipeline, annotated ELM classes yield putative instances in query sequences. By adding experimental evidence and references, these putative instances become candidate instances for annotation, and, with further curation, ultimately become fully annotated instances.
Output: ELM-the database of eukaryotic linear motifs
Zika virus has been declared as a public health emergency of international concern. The Center for Disease Control and Prevention has issued guidelines reminding healthcare workers about the importance of taking steps to prevent the spread of Zika virus, how to test and isolate patients suspected of carrying the Zika virus, and how to protect themselves from infection. Therefore, it is of utmost importance for healthcare professionals to be fully aware of Zika virus preparedness, and response measures should an outbreak occur in Malaysia in order to quickly and efficiently contain the outbreak, ensure the safety of individual or healthcare personnel safety, as well as to prevent further spreading of the disease. This research aims to show how prepared Malaysian healthcare professionals are against Zika virus and how well can they respond during an outbreak. In total, 504 healthcare professionals (128 general practitioners, 215 community pharmacists, 161 nurses) from private health clinics were the target population of the four states of Malaysia where Zika cases suspected. The sample size of each category was calculated by using a formula for estimating the population proportion. An additional 10% of the calculated sample size was added to compensate the non-response rate. The Center For Disease Control and Prevention and World Health Organisation provided a checklist to assess how prepared healthcare professionals are for an Zika outbreak. This checklist was modified to a questionnaire in order to assess health care professionals' preparedness and response to the Zika outbreak. Community pharmacists are still lacking in their preparedness and perceived response to the Zika outbreak compared to the general practitioners in the private sector. Hence community pharmacists should attend training given by the Ministry of Health Malaysia as a continuing education, which may help them to respond during a Zika outbreak.
Output: microorganisms Zika Outbreak Emergency Preparedness and Response of Malaysian Private Healthcare Professionals: Are They Ready?
Community-acquired respiratory viruses (CARVs) are a frequent cause of disease in solid organ transplant (SOT) recipients. Lower respiratory tract infections with CARVs can be associated with significant morbidity and even mortality in this population. This article reviews the clinical manifestations of CARVs infections and summarizes the evidence-based recommendations on the preventive and therapeutic strategies to decrease the burden of these viral infections in SOT recipients. with influenza-like symptoms during the influenza season while waiting for microbiological confirmation The efficacy of ribavirin (aerosolized or oral) for the treatment of RSV infection in SOT recipients has not been determined
Output: Influenza and other respiratory virus infections in solid organ transplant recipients Hot topics
Banyangvirus in the family of Phenuiviridae. In vitro and in vivo studies of GTV demonstrated that it was able to infect animal and human cell lines and could cause pathological lesions in mice. Glycoproteins (GP, including Gn and Gc) on the surface of Guertu virus (GTV) could bind to receptors on host cells and induce protective immunity in the host, but knowledge is now lacking on the information of B cell epitopes (BCEs) present on GTV-GP protein. The aim of this study was to identify all BCEs on Gn of the GTV DXM strain using rabbit pAbs against GTV-Gn. Seven fine BCEs and two antigenic peptides (APs) from nine reactive 16mer-peptides were identified, which are E Gn six of mapped BCEs were recognized by the IgG-positive sheep serum obtained from sheep GTV-infected naturally. Multiple sequence alignments (MSA) based on each mapped BCE motif identified that the most of identified BCEs and APs are highly conserved among 10 SFTSV strains from different countries and lineages that share relatively close evolutionary relationships with GTV. The fine epitope mapping of the GTV-Gn would provide basic data with which to explore the GTV-Gn antigen structure and pathogenic mechanisms, and it could lay the foundation for the design and development of a GTV multi-epitope peptide vaccine and detection antigen. Fig 1. Schematic of epitope mapping strategy. (a) The black band indicates the full-length sequence of GTV-Gn, and the gray bands indicate three of truncated Gn1, Gn2 and Gn3 segments. Schematic of epitope mapping strategy involves 56 overlapping 16mer-peptides spanning Gn1 (b), Gn2 (c) and Gn3 sequences (d).
Output: Fine epitope mapping of glycoprotein Gn in Guertu virus
J o u r n a l P r e -p r o o f 2 (Lanjuan Li); yidayang65@zju.edu.cn (Yida Yang) Highlight  COVID-19 has be a great threat to world health.  We aim to investigate clinical features of patients with abnormal imaging findings.  Those with abnormal images have more obvious clinical and laboratory features.  Combing clinical data with imaging score can predict severe/critical type. Purpose: To investigate the epidemiological, clinical characteristics of COVID-19 patients with abnormal imaging findings. Jan 17 to Feb 8 underwent CT or x-ray were enrolled. Epidemiological, clinical data were analyzed between those with abnormal or normal imaging findings. Results: Excluding 72 patients with normal images, 230 of 573 patients affected more than two lobes. The median radiograph score was 2.0 and there's negative correlation between the score and oxygenation index (ρ=-0.657, P<0.001). Patients with abnormal images were older (46.65±13.82), with higher rate of coexisting condition(28.8%), lower rate of exposure history and longer time between onset and confirmation(5d) than non-pneumonia patients(all P<0.05). Higher rate of fever, cough, expectoration, and headache, lower lymphocytes, albumin, serum sodium levels and higher total bilirubin, creatine kinase, lactate dehydrogenase and C-reactive J o u r n a l P r e -p r o o f 3 protein levels and lower oxygenation index were observed in pneumonia patients (all P<0.05). Muscle ache, shortness of breath, nausea and vomiting, lower lymphocytes levels and higher serum creatinine and radiograph score at admission were predictive factors for severe/critical subtype. Patients with abnormal images have more obvious clinical manifestations and laboratory changes. Combing clinical features and radiograph score can effectively predict severe/critical type.
Output: Journal Pre-proof Epidemiological, clinical characteristics of cases of SARS-CoV-2 infection with abnormal imaging findings clinical characteristics of cases of SARS-CoV-2 infection with abnormal imaging findings Epidemiological, clinical characteristics of cases of SARS-CoV-2 infection with abnormal imaging findings
We describe a systematic, high-throughput approach to identify proteins involved in functional adenovirus (Ad)-host interactions in vitro and in vivo. We were particularly interested in identifying cellular proteins that interact with fiber knob, which is the moiety within the Ad capsid responsible for high-affinity attachment of virus to cellular receptors. We used recombinant fiber knob domains from members of group C and B Ads to purify virus interacting proteins from cell membrane lysates and from human and mouse plasma. Using tandem mass spectrometry, we identified a number of candidate Ad-interacting proteins, including functional cellular receptors and previously unknown interacting partners such as complement component C4-binding protein and other blood proteins that presumably are involved in Ad infection after intravenous virus application. The ability of these proteins to bind to Ad was further confirmed using in vitro protein binding assays as well as infection competition assays. The approach of using a structural protein can be universally applied for a variety of viral and nonviral pathogens and can reveal host cell factors critical in viral infection, immune evasion, and tissue specificity. This information is also a prerequisite to assess in vivo safety and efficacy of Ad-based gene transfer vectors.
Output: Adenovirus-Host Protein Interactions 141 141 Identifying Functional Adenovirus-Host Interactions Using Tandem Mass Spectrometry
The wide variability in prevalence of childhood asthma across Asia Pacific is well documented, but less is known about its trends in mortality and hospitalization. Objectives: To examine pediatric asthma mortality and hospitalization trends of selected countries across Asia Pacific, and also patterns of asthma drug utilization. Materials and Methods: Mortality and population data were sourced from the World Health Organization's mortality database. Data on hospitalization were obtained by direct inquiry and from government and scientific publications. Drug use for asthma was expressed as a controller-to-reliever (C:R) ratio (ie, units of inhaled corticosteroids/units of short-acting ␤-agonists, sold in each country). Time-series regression analyses were used to examine temporal patterns and study association between deaths, hospitalizations, and drug use. Results: Japan showed a decreasing trend in pediatric asthma mortality whereas an increase was observed in Thailand. Hospitalizations decreased in Australia and Singapore but increased in Taiwan, Republic of China. C:R ratios increased significantly across the countries. Conclusions: Mixed trends in pediatric asthma mortality and hospitalization rates were observed, which coincided with a uniform increase in C:R ratios. This may reflect importance of other aspects of asthma management besides pharmacotherapy.
Output: Pediatric Asthma Mortality and Hospitalization Trends Across Asia Pacific Relationship With Asthma Drug Utilization Patterns
Vaccines represent the discovery of utmost importance for global health, due to both prophylactic action to prevent infections and therapeutic intervention in neoplastic diseases. Despite this, current vaccination strategies need to be refined to successfully generate robust protective antigen-specific memory immune responses. To address this issue, one possibility is to exploit the high efficiency of dendritic cells (DCs) as antigen-presenting cells for T cell priming. DCs functional plasticity allows shaping the outcome of immune responses to achieve the required type of immunity. Therefore, the choice of adjuvants to guide and sustain DCs maturation, the design of multifaceted vehicles, and the choice of surface molecules to specifically target DCs represent the key issues currently explored in both preclinical and clinical settings. Here, we review advances in DCs-based vaccination approaches, which exploit direct in vivo DCs targeting and activation options. We also discuss the recent findings for efficient antitumor DCs-based vaccinations and combination strategies to reduce the immune tolerance promoted by the tumor microenvironment. FiGURe 1 | Dendritic cells (DCs) readapted taxonomy. Newly identified populations of blood human DCs are shown. DC1 subset is clearly distinct by the expression of CLEC9A, and it is specialized in cross-presentation of ags. DC2 and DC3 constitute the conventional DCs pool, even though they appear to be phenotypically slightly different and, upon stimulation with TLR ligands, their diversity emerges. DC4 is a population characterized by an upregulated Type I Interferon pathway for antiviral responses. DC5 has emerged as a new population whose specific functions are still unexplored. DC6 corresponds to the classic plasmacytoid DCs. These advances in the fine characterization of DCs in humans may shed light on the best subset to be targeted to incentivize the desired immune response.
Output: Dendritic Cells in the Cross Hair for the Generation of Tailored vaccines
Despite being simple eukaryotic organisms, the yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe have been widely used as a model to study human pathologies and the replication of human, animal, and plant viruses, as well as the function of individual viral proteins. The complete genome of S. cerevisiae was the first of eukaryotic origin to be sequenced and contains about 6,000 genes. More than 75% of the genes have an assigned function, while more than 40% share conserved sequences with known or predicted human genes. This strong homology has allowed the function of human orthologs to be unveiled starting from the data obtained in yeast. RNA plant viruses were the first to be studied in yeast. In this paper, we focus on the use of the yeast model to study the function of the proteins of human immunodeficiency virus type 1 (HIV-1) and the search for its cellular partners. This human retrovirus is the cause of AIDS. The WHO estimates that there are 33.4 million people worldwide living with HIV/AIDS, with 2.7 million new HIV infections per year and 2.0 million annual deaths due to AIDS. Current therapy is able to control the disease but there is no permanent cure or a vaccine. By using yeast, it is possible to dissect the function of some HIV-1 proteins and discover new cellular factors common to this simple cell and humans that may become potential therapeutic targets, leading to a long-lasting treatment for AIDS.
Output: Yeast and the AIDS Virus: The Odd Couple
Endou proteins belong to the Eukaryotic EndoU ribonuclease family of enzymes that present high sequence homology with the founding member XendoU domain. The enzymatic activity and threedimensional structure of some Endou proteins have been previously reported. However, their molecular structure and gene expression patterns during embryogenesis remain to be elucidated. Therefore, we took zebrafish (Danio rerio) endouC as the model to study molecular structure and gene expression dynamics at different developmental stages. Zebrafish endouC cDNA contains 930 base pairs encoding 309 amino acid residues, sharing 27%, 27%, 27%, and 25% identity with that of human, mouse, chicken and frog, respectively. A phylogenetic tree showed that zebrafish EndouA was clustered with vertebrate Endou groups, while zebrafish EndouB and EndouC were found to belong to a unique monophyletic group. Furthermore, the endouC transcript was detected in one-cell embryos, suggesting that it is a maternal gene. While the endouC transcript was only weakly present at early developmental stages, its expression was greatly increased in embryos from 18 to 48 h post-fertilization (hpf) and then decreased after 72 hpf. Finally, endouC was ubiquitously expressed throughout the whole embryo during early embryogenesis, but its expression was enriched in brain, eyes and fin buds from 24 to 96 hpf.
Output: Embryonic expression patterns of Eukaryotic EndoU ribonuclease family gene endouC in zebrafish
Surveillance for zoonotic diseases among wildlife is a research and public health challenge. The inherent limitations posed by the requisite human-animal interactions are often undefined and underappreciated. The national surveillance system for animal rabies in the United States was examined as a model system; reporting of animal rabies is legally mandated, each case of rabies is laboratory confirmed, and data have been consistently collected for more than 50 years. Factors influencing the monthly counts of animal rabies tests reported during 1992-2001 were assessed by univariate and multivariable regression methods. The suitability of passively collected surveillance data for determining the presence or absence of the raccoon-associated variant of rabies within states and within individual counties was assessed by determining critical threshold values from the regression analyses. The size of the human population and total expenditures within a county accounted for 72% and 67%, respectively, of the variance in testing. The annual median number of rabies tests performed was seven for counties without rabies, 22 for counties with non-raccoon rabies, and 34 for counties with raccoon rabies. Active www.elsevier.com/locate/prevetmed Preventive Veterinary Medicine 78 (2007) 246-261 surveillance may be required in locales with sparse human populations when a high degree of confidence in the status of rabies is required. #
Output: Animal-based national surveillance for zoonotic disease: Quality, limitations, and implications of a model system for monitoring rabies
For decades, cationic polymer nanoparticles have been investigated for nucleic acid delivery. Despite promising in vitro transfection results, most formulations have failed to translate into the clinic due to significant in vivo toxicity -especially when delivered intravenously. To address this significant problem, we investigated the detailed mechanisms that govern the complex in vivo systemic toxicity response to common polymeric nanoparticles. We determined that the toxicity response is material dependent. For branched polyethylenimine (bPEI) nanoparticles -toxicity is a function of multiple pathophysiological responses -triggering of innate immune sensors, induction of hepatic toxicity, and significant alteration of hematological properties. In contrast, for chitosan-based nanoparticles -systemic toxicity is primarily driven through innate immune activation. We further identified that modification of primary amines to secondary and tertiary amines using the small molecule imidazole-aceticacid (IAA) ameliorates in vivo toxicity from both nanocarriers by different, material-specific mechanisms related to Toll-like receptor 4 activation (for bPEI) and complement activation driven neutrophil infiltration (for chitosan), respectively. Our results provide a detailed roadmap for evaluating in vivo toxicity of nanocarriers and identifies potential opportunities to reduce toxicity for eventual clinical translation.
Output: Modification of primary amines to higher order amines reduces in vivo hematological and immunotoxicity of cationic nanocarriers through TLR4 and complement pathways
The primary objective of this randomized controlled trial was to determine whether anti-IL-10 egg yolk antibodies fed upon arrival to a calf ranch would lower the prevalence of Cryptosporidium parvum shedding in naturally challenged preweaned dairy calves. The secondary objectives included measuring the effect of anti-IL-10 antibodies on calf health, performance, and shedding of less common diarrheal pathogens. A total of 133 calves, enrolled at 24 to 72 h of age, received a daily dose of 0.96 g of egg yolk powder with anti-IL-10 antibodies (MAB, n = 71) or without anti-IL-10 antibodies (MEP, n = 62) split between 2 feedings for the first 11 d on feed at a calf ranch. Daily health evaluations were completed for 15 d after arrival and on d 56. Digital weights were collected at enrollment and d 56, and hipometer weights were collected at enrollment and d 7 and 56. Packed cell volume and serum total protein concentration were measured at enrollment and on d 7 and 14. Fecal pH was measured at enrollment and on d 5 and 14, and fecal pathogen (C. parvum, coronavirus, rotavirus, and Salmonella spp.) shedding was assessed at d 5 and 14. Continuous outcomes were compared between groups using a Student's t-test or Wilcoxon rank sum test. Fecal pathogen shedding at d 14, respiratory disease at d 56, and antibiotic usage were compared using relative risk (RR) and chi-squared test. Fecal pH (median and interquartile range) on d 14 was 6.65 (6.39-6.99) and 6.52 (5.97-6.81) for MAB and MEP, respectively. On d 56, the risk of respiratory disease was lower for MAB compared with MEP (RR = 0.40; confidence interval = 0.16-0.99). The risk for antibiotic treatment was lower for MAB-compared with MEP-treated calves (RR = 0.38; confidence interval = 0.17-0.88). The risk of shedding rotavirus was higher in MAB (RR = 1.38; confidence interval = 1.10-1.81) calves. After multivariable analyses, hipometer weights (least squares means ± standard error) were 1.7 ± 0.8 kg greater on d 56 in MAB compared with MEP; however, ADG was 0.04 ± 0.02 kg/d lower in MAB calves. Total health score, diarrhea days, average respiratory score, packed cell volume, and serum total protein were not affected by feeding anti-IL-10 egg antibodies. In summary, feeding anti-IL-10 antibodies was associated with increased fecal pH, reduced risk of respiratory disease later in the preweaning period, and decreased antibiotic usage despite higher rotavirus infection. These findings might be associated with improved mucosal immunity, enhanced host defenses, or reduced susceptibility and warrant further investigation.
Output: Health benefits of orally administered anti-IL-10 antibody in milk-fed dairy calves
General medical training programs are aimed at promoting competency in general practice skills with a holistic perspective of patient-centered medicine for the new generation of physicians. The faculty development program was implemented to promote learning and application of the six core competencies established by the Accreditation Council for Graduate Medical Education. This article describes the implementation and outcome of the current faculty development program. Additional assessment tools of the faculty development program are recommended to evaluate different perspectives of outcome. Our experience suggests that OSTEs are a realistic and well-received approach for faculty development that merits further investigation. According to the clinical instructors' response, our faculty development program effectively increased familiarity with various teaching and assessment skills needed to teach PGY 1 residents and ACGME competencies, and these clinical instructors also then subsequently applied these skills.
Output: Faculty development program for general medicine in Taiwan: Past, present, and future
As the infection of 2019-nCoV coronavirus is quickly developing into a global pneumonia epidemic, careful analysis of its transmission and cellular mechanisms is sorely needed. In this report, we re-analyzed the computational approaches and findings presented in two recent manuscripts by Ji et al. (https://doi.org/10.1002/jmv.25682) and by Pradhan et al. (https://doi.Global protein sequence alignment of the full-length coronavirus spike proteins was performed by MUSCLE 17 and visualized by SeaView 18 . We use C-I-TASSER 5 to create structural models of the full-length spike protein. Here, C-I-TASSER is an extended pipeline of I-TASSER 19 and utilizes the deep convolutional neuralnetwork based contact-maps 20 to guide the Monte Carlo fragment assembly simulations. Since the RBD domain of spike exhibits different conformations relative to the remaining portion of . CC-BY 4.0
Output: Protein structure and sequence re-analysis of 2019-nCoV genome does not indicate snakes as its intermediate host or the unique similarity between its spike protein insertions and HIV-1
Primary chick kidney cells were infected with avian infectious bronchitis virus (IBV) and examined by electron microscopy. Virus particles entered the cells by viropexis and distinction could be made between engulfment by cell processes (phagoeytosis) and entry by mieropinocytosis in coated transport vesicles. Virus maturation occurred by budding into either the cisternae of the endoplasmie reticulum or cytoplasmic vacuoles, and evidence was obtained to suggest that the viral surface projections could be attached during the budding process. Late in infection large numbers of virus particles were present, mainly in cytoplasmic vacuoles, and the majority were released by cell lysis. Release by fusion of vacuoles with the plasma membrane was also observed, and individual virions could be transported from the endoplasmic retieulum to the surface within coated vesieles.
Output: Morphoflenesis of Avian Infectious Bronchitis Virus in Primary Ehiek Kidney Eeiis
The search for new immunobiologicals against canine visceral leishmaniasis (CVL) has intensified in the last decade. However, it still remains to be elucidated that mechanisms of the innate immune response in situ after immunization (a.i.). The aim of this study was to investigate the kinetics of cell migration in the skin dogs with distinct antigenic compounds of the LBSap vaccine. Our major findings indicated that saponin adjuvant alone or combined with Leishmania braziliensis antigen induced strong local acute inflammatory reaction. However, these reactions not progressed to ulcerated lesions. Overall, the cell profile found in Sap and LBSap was composed of neutrophils, lymphocytes and eosinophils. There was also increased production of iNOS in Sap and LBSap groups. Thus, we can conclude that dogs immunized by LBSap and the saponin adjuvant elicited a potential innate-immune activations status compatible with effective control of the resistance to infection by Leishmania and contributing to a better understanding of the innate-immunity events induced by the LBSap vaccine.
Output: Kinetics of cell migration to the dermis and hypodermis in dogs vaccinated with antigenic compounds of Leishmania braziliensis plus saponin
Coronaviruses (CoVs) are important human pathogens with significant zoonotic potential. Progress has been made toward identifying potential vaccine candidates for highly pathogenic human CoVs, including use of attenuated viruses that lack the CoV envelope (E) protein or express E mutants. However, no approved vaccines or anti-viral therapeutics exist. CoVs assemble by budding into the lumen of the early Golgi prior to exocytosis. The small CoV E protein plays roles in assembly, virion release, and pathogenesis. CoV E has a single hydrophobic domain (HD), is targeted to Golgi membranes, and has cation channel activity in vitro. The E protein from the avian infectious bronchitis virus (IBV) has dramatic effects on the secretory system, which requires residues in the HD. Mutation of the HD of IBV E during infection results in impaired growth kinetics, impaired release of infectious virions, accumulation of IBV S protein on the plasma membrane when compared IBV WT infected cells, and aberrant cleavage of IBV S on the surface of virions. We previously reported the formation of two distinct oligomeric pools of IBV E in transfected and infected cells. Disruption of the secretory pathway by IBV E correlates with a form that is likely monomeric, suggesting that the effects on the secretory pathway are independent of E ion channel activity. Here, we present evidence suggesting that the monomeric form of IBV E correlates with a rise in the pH of the Golgi lumen. We demonstrate that infection with IBV induces neutralization of Golgi luminal pH, promoting a model in which IBV E alters the secretory pathway through interaction with host cells factors, protecting IBV spike protein (S) from premature cleavage and leading to the efficient release of infectious virus from the cells.
Output: The Infectious Bronchitis Virus Coronavirus Envelope Protein Alters Golgi pH to Protect Spike Protein and Promote Release of Infectious Virus
This work describes the application of thermophilic microorganisms for obtaining 6-halogenated purine nucleosides. Biosynthesis of 6-chloropurine-2 0 -deoxyriboside and 6-chloropurine riboside was achieved by Geobacillus stearothermophilus CECT 43 with a conversion of 90% and 68%, respectively. Furthermore, the selected microorganism was satisfactorily stabilized by immobilization in an agarose matrix. This biocatalyst can be reused at least 70 times without significant loss of activity, obtaining 379 mg/L of 6chloropurine-2 0 -deoxyriboside. The obtained compounds can be used as antiviral agents.
Output: Universidad Nacional de La Plata
Infiltration and runoff from manured agricultural fields can result in livestock pathogens reaching groundwater and surface waters. Here, we measured the effectiveness of glass wool filters to simultaneously concentrate enteric viruses and bacteria of bovine origin from water. The recovery efficiencies were determined for bovine viral diarrhea virus types 1 and 2, bovine rotavirus group A, bovine coronavirus, poliovirus Sabin III, toxigenic Escherichia coli ,and Campylobacter jejuni seeded into water with three different turbidity levels (0.5, 215, and 447 NTU). Twenty liters of dechlorinated tap water (pH 7) were seeded with the test organisms, and then passed through a glass wool filter using a peristaltic pump (flow rate = 1 liter min -1 ). Retained organisms were eluted from the filters by passing beef extract-glycine buffer (pH 9.5) in the direction opposite of sample flow. Recovered organisms were enumerated by qPCR except for C. jejuni, which was quantified by culture. Mean recovery efficiencies ranged from 55 to 33 % for the bacteria and 58 to 16 % for the viruses. Using bootstrapping techniques combined with Analysis of Variance, recovery efficiencies were found to differ among the pathogen types tested at the two lowest turbidity levels; however, for a given pathogen type turbidity did not affect recovery except for C. jejuni. Glass wool filtration is a cost-effective method for concentrating several waterborne pathogens of bovine origin simultaneously, although recovery may be low for some specific taxa such as bovine viral diarrhea virus 1.
Output: Simultaneous Concentration of Bovine Viruses and Agricultural Zoonotic Bacteria from Water Using Sodocalcic Glass Wool Filters
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 .
Output: Title: Spatial variability in the risk of death from COVID-19 in Italy, 2020
Pertussis, commonly referred to as "whooping cough," is a highly contagious acute respiratory infection that has exhibited cyclical outbreaks throughout the last century. Although vaccines have provided some immunity, many populations, including infants and pregnant women, remain at risk for serious illness. Through the use of the novel "Identify, Isolate, Inform" (3I) tool, emergency department (ED) providers can readily recognize key symptoms of the disease and risk factors for exposure, thus curbing its transmission through early initiation of antimicrobial therapy and post-exposure prophylaxis. The three classic stages of pertussis include an initial catarrhal stage, characterized by nonspecific upper respiratory infection symptoms, which may advance to the paroxysmal stage, revealing the distinctive "whooping cough." This cough can persist for weeks to months leading into the convalescent stage. Household contacts of patients with suspected pertussis or other asymptomatic, high-risk populations (infants, pregnant women in their third trimester, and childcare workers) may benefit from post-exposure prophylactic therapy. The Pertussis 3I tool can also alert healthcare professionals to the proper respiratory droplet precautions during contact with a symptomatic patient, as well as isolation practices until antimicrobial treatment is in progress. ED personnel should then inform local public health departments of any suspected cases. All of these actions will ultimately aid public health in controlling the incidence of pertussis cases, thus ensuring the protection of the general public from this re-emerging respiratory illness. [West J Emerg Med. 2019;20(2)191-197.] 
Output: Pertussis: The Identify, Isolate, Inform Tool Applied to a Re-emerging Respiratory Illness
Human and bovine respiratory syncytial viruses (HRSV and BRSV) are two closely related, worldwide prevalent viruses that are the leading cause of severe airway disease in children and calves, respectively. Efficacy of commercial bovine vaccines needs improvement and no human vaccine is licensed yet. We reported that nasal vaccination with the HRSV nucleoprotein produced as recombinant ringshaped nanoparticles (N SRS ) protects mice against a viral challenge with HRSV. The aim of this work was to evaluate this new vaccine that uses a conserved viral antigen, in calves, natural hosts for BRSV. Calves, free of colostral or natural anti-BRSV antibodies, were vaccinated with N SRS either intramuscularly, or both intramuscularly and intranasally using Montanide TM ISA71 and IMS4132 as adjuvants and challenged with BRSV. All vaccinated calves developed anti-N antibodies in blood and nasal secretions and N-specific cellular immunity in local lymph nodes. Clinical monitoring post-challenge demonstrated moderate respiratory pathology with local lung tissue consolidations for the non-vaccinated calves that were significantly reduced in the vaccinated calves. Vaccinated calves had lower viral loads than the nonvaccinated control calves. Thus N SRS vaccination in calves provided cross-protective immunity against BRSV infection without adverse inflammatory reaction. (S. Riffault). 1 Contributed equally to the work. more than 60% of the epizootic respiratory diseases observed in dairy herds and up to 70% in beef herds [2] . Mortality caused by BRSV infections ranges generally between 0.5% and 3% but can reach up to 20% in some outbreaks [3] . The control of BRSV infections is a high priority for animal health and farming organizations, not only for economic reasons, but also due to the impact on animal welfare. Several commercial BRSV vaccines, including modified-live virus and inactivated single fraction are available for use in cattle. Their efficacy needs improvement in terms of duration of protection, clinical and virological protection. Even though the commercial bovine vaccines probably have reduced the prevalence of infection, BRSV continues to circulate in cattle populations. No commercial vaccine is available against HRSV, a pathogen of major importance in infants. HRSV induced-bronchiolitis is the most common cause of infant hospitalization in industrialized countries and is a suspected risk factor of recurrent wheeze and asthma in later life [4] . The main reason for the lack of human 0264-410X/$ -see front matter
Output: A new subunit vaccine based on nucleoprotein nanoparticles confers partial clinical and virological protection in calves against bovine respiratory syncytial virus
between the virion and the host cell. We focused on using synthetic peptides for developing antibodies against SARS-CoV, which aimed to block viral invasion by eliciting an immune response specific to the native SARS-CoV S protein. Methods: Six peptide sequences corresponding to the surface regions of SARS-CoV S protein were designed and investigated by use of combined bioinformatics and structural analysis. These synthetic peptides were used to immunize both rabbits and monkeys. Antisera collected 1 week after the second immunization were analyzed by ELISA and tested for antibody specificity against SARS-CoV by immunofluorescent confocal microscopy. Conclusions: Synthetic peptides can elicit specific antibodies to SARS-CoV. The study provides insights for the future development of SARS vaccine via the synthetic-peptide-based approach.
Output: Synthetic Peptide Studies on the Severe Acute Respiratory Syndrome (SARS) Coronavirus Spike Glycoprotein: Perspective for SARS Vaccine Development
In an influenza pandemic, the benefit of vaccines and antiviral medications will be constrained by limitations on supplies and effectiveness. Non-pharmaceutical public health interventions will therefore be vital in curtailing disease spread. However, the most comprehensive assessments of the literature to date recognize the generally poor quality of evidence on which to base non-pharmaceutical pandemic planning decisions. In light of the need to prepare for a possible pandemic despite concerns about the poor quality of the literature, combining available evidence with expert opinion about the relative merits of non-pharmaceutical interventions for pandemic influenza may lead to a more informed and widely accepted set of recommendations. We evaluated the evidence base for non-pharmaceutical public health interventions. Then, based on the collective evidence, we identified a set of recommendations for and against interventions that are specific to both the setting in which an intervention may be used and the pandemic phase, and which can be used by policymakers to prepare for a pandemic until scientific evidence can definitively respond to planners' needs. Methods: Building on reviews of past pandemics and recent historical inquiries, we evaluated the relative merits of nonpharmaceutical interventions by combining available evidence from the literature with qualitative and quantitative expert opinion. Specifically, we reviewed the recent scientific literature regarding the prevention of human-to-human transmission of pandemic influenza, convened a meeting of experts from multiple disciplines, and elicited expert recommendation about the use of non-pharmaceutical public health interventions in a variety of settings (healthcare facilities; community-based institutions; private households) and pandemic phases (no pandemic; no US pandemic; early localized US pandemic; advanced US pandemic).
Output: BMC Public Health Non-pharmaceutical public health interventions for pandemic influenza: an evaluation of the evidence base
Hepatitis C virus (HCV) RNA replication requires viral nonstructural proteins as well as cellular factors. Recently, a cellular protein, synaptotagmin-binding, cytoplasmic RNA-interacting protein (SYNCRIP), also known as NSAP1, was found to bind HCV RNA and enhance HCV IRES-dependent translation. We investigate whether this protein is also involved in the HCV RNA replication. We found that SYNCRIP was associated with detergent-resistant membrane fractions and colocalized with newly-synthesized HCV RNA. Knock-down of SYNCRIP by siRNA significantly decreased the amount of HCV RNA in the cells containing a subgenomic replicon or a full-length viral RNA. Lastly, an in vitro replication assay after immunodepletion of SYNCRIP showed that SYNCRIP was directly involved in HCV RNA replication. These findings indicate that SYNCRIP has dual functions, participating in both RNA replication and translation in HCV life cycle.
Output: SYNCRIP (synaptotagmin-binding, cytoplasmic RNA-interacting protein) is a host factor involved in hepatitis C virus RNA replication
Acute cough is a major symptom of viral respiratory tract infection and causes excessive morbidity in human populations across the world. A wide variety of viruses play a role in the development of cough after acute infection and all of these manifest a similar clinical picture across different age groups. Despite the large disease burden surprisingly little is known about the mechanism of acute cough following viral infection. Both in vitro and in vivo experiments show that increased production of neuropeptides and leukotrienes mediate cough after viral infection, along with altered expression of neural receptors. Increased airway mucus production is also likely to play a significant role. This work is reviewed in this article. Following the recent development of a mouse model for rhinovirus infection and the establishment of experimental models of rhinovirus challenge in human subjects with both asthma and COPD the field is expanding to translate in vitro research into clinical studies and hopefully eventually into clinical practice. Developing a clearer understanding of the mechanisms underlying virus induced cough may lead to more specific and effective therapies.
Output: Cough and viruses in airways disease: Mechanisms
Motivation: An important aspect of infectious disease research involves understanding the differences and commonalities in the infection mechanisms underlying various diseases. Systems biology-based approaches study infectious diseases by analyzing the interactions between the host species and the pathogen organisms. This work aims to combine the knowledge from experimental studies of hostpathogen interactions in several diseases to build stronger predictive models. Our approach is based on a formalism from machine learning called 'multitask learning', which considers the problem of building models across tasks that are related to each other. A 'task' in our scenario is the set of host-pathogen protein interactions involved in one disease. To integrate interactions from several tasks (i.e. diseases), our method exploits the similarity in the infection process across the diseases. In particular, we use the biological hypothesis that similar pathogens target the same critical biological processes in the host, in defining a common structure across the tasks. Results: Our current work on host-pathogen protein interaction prediction focuses on human as the host, and four bacterial species as pathogens. The multitask learning technique we develop uses a taskbased regularization approach. We find that the resulting optimization problem is a difference of convex (DC) functions. To optimize, we implement a Convex-Concave procedure-based algorithm. We compare our integrative approach to baseline methods that build models on a single host-pathogen protein interaction dataset. Our results show that our approach outperforms the baselines on the training data. We further analyze the protein interaction predictions generated by the models, and find some interesting insights.
Output: Multitask learning for host-pathogen protein interactions
A mammalian orthoreovirus (MRV) strain was isolated from a pup with fatal diarrhea, which had a concurrent infection by canine parvovirus type 2. The reovirus isolate showed an atypical hemagglutination pattern and a retarded electrophoretic mobility of the S1 segment, which is characteristic of MRV type 3 (MRV-3). Assignment of the isolated virus to MRV-3 was confirmed by type-specific RT-PCR assays, targeting the S1 gene, and by subsequent sequence analysis of the PCR product. By phylogeny based on the S1 gene of several MRVs, the isolate fell into lineage E, along with the murine strain T3C9/61 and the bovine strains T3C18/61 and T3C31/59. Conversely, L1 sequences were found to segregate regardless of the viral type. A total of 110 fecal samples, 56 nasal and 31 ocular swabs from dogs with diarrhea or nasal/ocular discharge were tested by a nested-PCR assay specific for reoviruses, and no sample was found to contain MRV RNA, a finding that is apparently in contrast with the seroprevalence (25.77%) observed in dogs. #
Output: Virological and molecular characterization of a mammalian orthoreovirus type 3 strain isolated from a dog in Italy
Massive aggregations of macrophages are frequently detected in afflicted lungs of patients with severe acute respiratory syndrome-associated coronavirus (SARS-CoV) infection. In vitro, ectopic expression of transcription factors, in particular CCAAT/enhancer-binding protein alpha (C/EBP␣) and C/EBP␤, can convert B cells into functional macrophages. However, little is known about the specific ligands responsible for such phenotype conversion. Here, we investigated whether spike protein of SARS-CoV can act as a ligand to trigger the conversion of B cells to macrophages. We transduced SARS-CoV spike proteindisplayed recombinant baculovirus (SSDRB), vAtEpGS688, into peripheral B cells and B lymphoma cells. Cell surface expression of CD19 or Mac-1 (CD11b) was determined by flow cytometry. SSDRB-mediated changes in gene expression profiles of B lymphoma cells were analyzed by microarray. In this report, we showed that spike protein of SARS virus could induce phenotypic conversion of human B cells, either from peripheral blood or B lymphoma cells, to macrophage-like cells that were steadily losing the B-cell marker CD19 and in turn expressing the macrophage-specific marker Mac-1. Furthermore, we found that SSDRB enhanced the expression of CD86, hypoxia-inducible factor-1␣ (HIF1␣), suppressor of cytokine signaling (SOCS or STAT-induced STAT inhibitor)-3, C/EBP␤, insulin-like growth factor-binding protein 3 (IGFBP3), Krüpple-like factor (KLF)-5, and CD54, without marked influence on C/EBP␣ or PU.1 expression in transduced cells. Prolonged exposure to hypoxia could also induce macrophage-like conversion of B cells. These macrophage-like cells were defective in phagocytosis of red fluorescent beads. In conclusion, our results suggest that conversion of B cells to macrophage-like cells, similar to a pathophysiological response, could be mediated by a devastating viral ligand, in particular spike protein of SARS virus, or in combination with severe local hypoxia, which is a condition often observed in afflicted lungs of SARS patients.
Output: SARS spike protein induces phenotypic conversion of human B cells to macrophage-like cells