niryuu/sni-each-converted huggingface dataset:
Variation in temperature and R 0 amongst Canadian sites 2 Table S1 . Basic characteristics of sites used in this study 4 Figure S1 . The locations of sites used in the study 5 Figure S2 . Model-estimated R 0 and DD > 0°C using observed daily temperature 5 Figure S3 . Climate classification tree for the sites 6 Figure S4. Daily normal of ANUSPLIN daily maximum temperatures for each cluster 6 Model sensitivity analysis 7 Table S2. The parameters used in sensitivity analysis 9 Fig S5. Local sensitivity analysis 10 Fig S6. Results of global sensitivity analysis 11 Validation of climate model output 11 Table S3 . Basic information about RCM simulations 13 Figure S7 . Mean DD > 0°C for each cluster using observed and model temperature 14 Figure S8. Mean R 0 for each cluster using observed and climate model temperature 14 Mapping R 0 15 Figure S9. Plots of model-estimated R 0 values plotted against DD > 0°C 16 References 17
Output: Supplemental Material Estimated Effects of Projected Climate Change on the B asic Reproductive Number of the Lyme Disease Vector Ixodes scapularis
Viral pathogens often generate strong CD4 + T cell responses that are best known for their ability to help B cell and CD8 + T cell responses. However, recent studies reveal additional roles for CD4 + T cells, some of which are independent of other lymphocytes, and indicate that memory cells are more effective in most functions than naïve CD4 T cells. Here, we review the full spectrum of antiviral functions of CD4 + T cells, including their helper activities, innate immune induction, and direct anti-viral roles, and suggest how these functions are integrated to provide highly protective responses against viral pathogens.
Output: Expanding roles for CD4 + T cells in immunity to viruses NIH Public Access
The nucleocapsid (N) protein is the most abundant protein of porcine reproductive and respiratory syndrome virus (PRRSV). It has been shown to be multiphosphorylated. However, the phosphorylation sites are still unknown. In this study, we used liquid chromatography tandem mass spectrometry (LC-MS/MS) to analyze the phosphorylation sites of N protein expressed in Sf9 cells. The results showed that N protein contains two phosphorylation sites. Since N protein can regulate IL-10, which may facilitate PRRSV replication, we constructed four plasmids (pCA-XH-GD, pCA-A105, pCA-A120 and pCA-A105-120) and transfected them into Pig alveolar macrophages (PAMs,3D4/2). The qPCR results showed that mutations at residues 105 and 120 were associated with down-regulation of the IL-10 mRNA level, potentially decreasing the viral growth ability. Then, we mutated the phosphorylation sites (S105A and S120A) and rescued three mutated viruses, namely, A105, A120 and A105-120. Compared with wild-type virus titers, the titers of the mutated viruses at 48 hpi were significantly decreased. The Nsp(non-structural protein) 9 qPCR results were consistent with the multistep growth kinetics results. The infected PAMs (primary PAMs) results were similar with Marc-145.The findings indicated that the mutations impaired the viral replication ability. The confocal microscopy results suggested that mutations to residues 105 and 120 did not affect N protein distribution. Whether the mutations affected other functions of N protein and what the underlying mechanisms are need further investigation. In conclusion, our results show that residues 105 and 120 are phosphorylation sites and are important for N protein function and for viral replication ability.
Output: Serine 105 and 120 are important phosphorylation sites for porcine reproductive and respiratory syndrome virus N protein function
Human Ebola virus causes severe hemorrhagic fever disease with high mortality and there is no vaccine or treatment. Antibodies in survivors occur early, are sustained, and can delay infection when transferred into nonhuman primates. Monoclonal antibodies (mAbs) from survivors exhibit potent neutralizing activity in vitro and are protective in rodents. To better understand targets and mechanisms of neutralization, we investigated a panel of mAbs shown previously to react with the envelope glycoprotein (GP). While one nonneutralizing mAb recognized a GP epitope in the nonessential mucin-like domain, the rest were specific for GP1, were neutralizing, and could be further distinguished by reactivity with secreted GP. We show that survivor antibodies, human KZ52 and monkey JP3K11, were specific for conformation-dependent epitopes comprising residues in GP1 and GP2 and that neutralization occurred by two distinct mechanisms; KZ52 inhibited cathepsin cleavage of GP whereas JP3K11 recognized the cleaved, fusion-active form of GP. Published by Elsevier Inc.
Output: Antibody-mediated neutralization of Ebola virus can occur by two distinct mechanisms
Cryptosporidiosis of calves is caused by the enteroprotozoan Cryptosporidium spp. The disease results in intense diarrhea of calves associated with substantial economic losses in dairy farming worldwide. The aim of this study was to determine calf, herd, and within-herd Cryptosporidium prevalence and identify Cryptosporidium species and subtypes in calves with diarrhea in intensive dairy herds in central Argentina. A total of 1073 fecal samples were collected from 54 randomly selected dairy herds. Cryptosporidium-oocysts were isolated and concentrated from fecal samples using formol-ether and detected by light microscopy with the modified Ziehl-Neelsen technique. Overall prevalence of oocyst-excreting calves was found to be 25.5% (274/ 1073) (95% C.I. 22.9; 28.1%). Of the herds studied, 89% (48/54) included at least one infected calf, whereas within-herd prevalence ranged from the absence of infection to 57% (20/35). A highly significant association was found between the presence of diarrhea and C. parvum infection (χ 2 = 55.89, p < 0.001). For species determination, genomic DNA isolated from oocystpositive fecal samples was subjected to PCR-RFLP of the 18S rRNA gene resulting exclusively in Cryptosporidium parvum identification. C. parvum isolates of calves displaying diarrhea and high rate of excretion of oocysts were subtyped by PCR amplification and direct sequencing of the 60 kDa glycoprotein (GP60) gene. Altogether five GP60 subtypes, designated IIaA18G1R1, IIaA20G1R1, IIaA21G1R1, IIaA22G1R1, and IIaA24G1R1 were identified. Interestingly, IIaA18G1R1 and IIaA20G1R1 were predominant in calves with diarrhea and high infection intensity. Notably, IIaA24G1R1 represents a novel, previously unrecognized C. parvum subtype. The subtype IIaA18G1R1, frequently found in this study, is strongly implicated in zoonotic transmission. These results suggest that calves might be an important source for human cryptosporidiosis in Argentina.
Output: Prevalence of Cryptosporidium parvum in dairy calves and GP60 subtyping of diarrheic calves in central Argentina
Intestinal parasitic infections (IPIs) remain a widespread public health concern causing severe implications in both developed and developing countries. Globally, numerous studies have been carried out ranging from various communities to schoolchildren as well as indigenous communities. The infections are commonly caused by helminths (e.g. Ascaris lumbricoides, Trichuris trichiura and hookworm) and protozoa (e.g. Blastocystis hominis, Cryptosporidium sp., Entamoeba histolytica and Giardia duodenalis). Poor sanitation and poverty are some of the factors associated with IPIs. With the ever-increasing impact of IPIs, newer detection approaches have been developed and studied. The efficacy of diagnostic method is crucial to give an accurate identification of these parasites. Recent developments of diagnostic tools such as serology-and molecular-based assays are assisting the conventional method of microscopy in detecting and further confirming current or past infections and the specific species of parasites. Ongoing investigations in parasitic infections using these advanced tools will provide useful information that will enable the evaluation of the effectiveness of the current control program and thus, assist future planning for improved strategies in eradicating these parasitic infections.
Output: Advancements in Parasite Diagnosis and Challenges in the Management of Parasitic Infections: A Mini Review
Background: Insect-borne diseases could induce severe symptoms in human and clinical signs in animals, such as febrility, erythra, arthralgia and hemorrhagic fever, and cause significant economic losses and pose public health threat all over the world. The significant advantages of Luminex xMAP technology are high-throughput, high parallel and automation. This study aimed to establish a liquid bead array based on Luminex xMAP technology that was able to simultaneously detect multiple insect-borne pathogens. Methods: Specific probes and primers to detect the nucleic acid of 10 insect-borne pathogens were designed. Probes were coupled with fluorescent carboxylated microspheres. The parameters of the system were optimized, including ratio of forward/reverse primers (1:2), hybridization temperature (50°C) and duration (30 min) and quantity of PCR product (2 μl). The sensitivity and specificity of the system were also evaluated. Moreover mixed nucleic acid of 10 insect-borne pathogens, including Bluetongue virus, Epizootic hemorrhagic disease virus of deer, Coxiella burnetii, African swine fever virus, West Nile fever virus, Borrelia burgdorferi, vesicular stomatitis virus, Rift Valley fever virus, Ebola virus and Schmalenberg's disease virus, and 3000 clinical samples were tested for practicability. Results: The optimized detection system showed high sensitivity, specificity and reproducibility. Each probe showed specific fluorescence signal intensity without any cross-hybridization for the other insect-borne pathogens tested, which included dengue virus, tick-borne encephalitis virus, Japanese encephalitis virus, Xinjiang hemorrhagic fever virus, spotted fever group rickettsiae, ehrlichiae and chikungunya virus. The limit of detection was 10 copies of target gene. Insect-borne pathogens were successfully detected among the 3000 clinical samples, and the results were consistent with those obtained using gold-standard assays or commercial nucleic acid detection kits. Conclusions: This optimized liquid array detection system was high-throughput and highly specific and sensitive in screening of the insect-borne pathogens. It was promising in detection of these pathogens for molecular epidemiological studies.
Output: Establishment and optimization of a liquid bead array for the simultaneous detection of ten insect-borne pathogens
In December 2019, a cluster of patients with emerging pneumonia of unknown etiology were discovered in Wuhan city, China. Laboratory examination identified a novel coronavirus which was tentatively named as 2019 novel coronavirus (2019-nCoV) by the World Health Organization (WHO) in January 2020. The WHO has more recently formally named the 2019-nCoV as coronavirus Diseases 2019 (COVID-19). Within one month, the novel coronavirus rapidly spread across the whole of China through droplet transmission and contact transmission, and the reported number of confirmed COVID-19 cases demonstrated a rising trend. Radiological examinations, especially computed tomography CT, were confirmed as effective methods for the screening and diagnosis of infected cases. Reports stated that many radiologists and technologists were being infected when examining patients with COVID-19. In order to clarify the imaging features of COVID-19 and reduce the infection risk of medical personnel in radiology departments, we summarized the experience on radiological examinations and infection prevention for COVID-19, aiming to guide virus prevention, diagnosis and control within radiology departments.
Output: Journal Pre-proof Experience on radiological examinations and infection prevention for COVID-19 in radiology department Experience on radiological examinations and infection prevention for COVID-19 in radiology department Corresponding authors
Porcine epidemic diarrhea virus (PEDV), being highly virulent and contagious in piglets, has caused significant damage to the pork industries of many countries worldwide. There are no commercial drugs targeting coronaviruses (CoVs), and few studies on anti-PEDV inhibitors. The coronavirus 3C-like protease (3CL pro ) has a conserved structure and catalytic mechanism and plays a key role during viral polyprotein processing, thus serving as an appealing antiviral drug target. Here, we report the anti-PEDV effect of the broad-spectrum inhibitor GC376 (targeting 3Cpro or 3CL pro of viruses in the picornavirus-like supercluster). GC376 was highly effective against the PEDV 3CL pro and exerted similar inhibitory effects on two PEDV strains. Furthermore, the structure of the PEDV 3CL pro in complex with GC376 was determined at 1.65 Å. We elucidated structural details and analyzed the differences between GC376 binding with the PEDV 3CL pro and GC376 binding with the transmissible gastroenteritis virus (TGEV) 3CL pro . Finally, we explored the substrate specificity of PEDV 3CL pro at the P2 site and analyzed the effects of Leu group modification in GC376 on inhibiting PEDV infection. This study helps us to understand better the PEDV 3CL pro substrate specificity, providing information on the optimization of GC376 for development as an antiviral therapeutic against coronaviruses.
Output: Structural Basis for Inhibiting Porcine Epidemic Diarrhea Virus Replication with the 3C-Like Protease Inhibitor GC376
ADAR1 isoforms are adenosine deaminases that edit and destabilize double-stranded RNA reducing its immunostimulatory activities. Mutation of ADAR1 leads to a severe neurodevelopmental and inflammatory disease of children, Aicardi-Goutié res syndrome. In mice, Adar1 mutations are embryonic lethal but are rescued by mutation of the Mda5 or Mavs genes, which function in IFN induction. However, the specific IFN regulated proteins responsible for the pathogenic effects of ADAR1 mutation are unknown. We show that the cell-lethal phenotype of ADAR1 deletion in human lung adenocarcinoma A549 cells is rescued by CRISPR/Cas9 mutagenesis of the RNASEL gene or by expression of the RNase L antagonist, murine coronavirus NS2 accessory protein. Our result demonstrate that ablation of RNase L activity promotes survival of ADAR1 deficient cells even in the presence of MDA5 and MAVS, suggesting that the RNase L system is the primary sensor pathway for endogenous dsRNA that leads to cell death.
Output: Ribonuclease L mediates the cell-lethal phenotype of double-stranded RNA editing enzyme ADAR1 deficiency in a human cell line
The chicken Harderian gland (HG) plays an important role in adaptive immune responses upon ocular exposure to avian pathogens such as avian influenza (AI). To determine the role of HGs in generating immunity, chickens were immunized ocularly with an adenovirus (Ad5) vector expressing the AI hemagglutinin H5 gene. The Ad5-H5 vector induced H5 transgene expression and induced H5-and Ad5-specific IgA and IgG spot-forming cells (SFCs) in the HGs. The IgA and IgG SFC peaked on day 9 for Ad5 and day 11 for the H5 protein. In addition, Ad5-and H5-specific antibodies were induced in serum. IgA in chicken tears was predominantly dimeric, while in serum monomeric IgA was most abundant. Analysis of HG mRNA confirmed expression of the polymeric immunoglobulin receptor (pIgR). These data demonstrated the importance of HGs to generate mucosal and systemic immunity to AI following ocular Ad5-H5 administration to chickens.
Output: Induction of mucosal immunity in the avian Harderian gland with a replication-deficient Ad5 vector expressing avian influenza H5 hemagglutinin
After decades of low personal risk for contracting lethal diseases, physicians are suddenly facing the possibility of a substantial increase in occupational risk during an influenza pandemic. If they are not confronted before the onset of an influenza pandemic, feelings of unease and fear or ignorance about physicians' professional obligations could profoundly hinder individual physicians in fulfilling their professional duties. Such feelings could therefore undermine institutional and societal preparations. In their review published in Critical Care, Anantham and coworkers outline the ethical framework that forms the basis of the professional obligations of physicians who respond to health care emergencies, such as an influenza pandemic.
Output: Pandemic influenza: are we prepared to face our obligations?
Newly available data sets present an exciting opportunity to investigate how human population movement contributes to the spread of infectious diseases across large geographical distances. It is now possible to construct realistic models of infectious disease dynamics for the purposes of understanding global-scale epidemics. Nevertheless, a remaining unanswered question is how best to leverage the new data to parameterize models of movement, and whether one's choice of movement model impacts modeled disease outcomes. We adapt three well-studied models of infectious disease dynamics, the SIR model; the SIS model; and the Ross-Macdonald model, to incorporate either of two candidate movement models. We describe the effect that the choice of movement model has on each disease model's results, finding that in all cases there are parameter regimes where choosing one movement model instead of another has a profound impact on epidemiological outcomes. We further demonstrate the importance of choosing an appropriate movement model using the applied case of malaria transmission and importation on Bioko Island, Equatorial Guinea, finding that one model produces intelligible predictions of R 0 while the other produces nonsensical results. Mathematical modeling | Infectious disease dynamics | Human population movement | Malaria DT Citron developed the project and carried out the analysis. DL Smith provided guidance and context for the project. CA Guerra provided the data for building the Bioko Island model. SL Wu, JM Henry, HM Sánchez C, and D Dolgert discussed and reviewed the analysis.
Output: Comparing Metapopulation Dynamics of Infectious Diseases under Di erent Models of Human Movement
microRNAs (miRNAs) represent a newly identified class of nonprotein-coding *22 nt small RNA that plays important roles in multiple biological processes by degrading targeted mRNA or repressing mRNA translation. This study observed the morphology of swine testicular tissue at different developmental stages (including 1-day old, 1-7 month old) by Hematoxylin-eosin staining. We also examined the expression of miR-499 and its target genes (CYLC1, DMRT1, QKI, XRN2, ZNF313) in samples of tissue slices using quantitative reversetranscription polymerase chain reaction, which showed that miR-499 had a significant negative correlation with QKI gene. Then, the proteins of QKI gene expression were determined by western blot, which were consistent with results of quantitative polymerase chain reaction (qPCR) detection. Therefore, the luciferase reporter gene system was used to verify correlation between miR-499 and QKI gene. Activity of luciferase was significantly lower in miR-499 co-transfected with pmiR-RB-REPORT-QKI-WT group than the miR-499 co-transfected with pmiR-RB-REPORT-QKI-mut/si groups, indicating that target sequence of miR-499 existed in 3¢UTR of QKI gene. Furthermore, the expressions of miR-499 and QKI were detected in testicular cells that were transfected with miR-499, miR-499 negative control and untreated. The results showed that the diameter of convoluted seminiferous tubule growth increased with age. Significantly different expressions of miR-499 and its target genes were found in swine testicular tissue at different developmental stages ( p < 0.05), overexpressing miR-499 analysis, suggesting that miR-499 was negatively correlated to the expression of QKI ( p < 0.05). In conclusion, QKI is a target gene of miR-499.
Output: Differential Expression of miR-499 and Validation of Predicted Target Genes in the Testicular Tissue of Swine at Different Developmental Stages
One contribution of 15 to a theme issue 'Modelling infectious disease outbreaks in humans, animals and plants: approaches and important themes'. Subject Areas: computational biology, ecology, environmental science, health and disease and epidemiology Lassa fever (LF) is a zoonotic disease that is widespread in West Africa and involves animal-to-human and human-to-human transmission. Animal-tohuman transmission occurs upon exposure to rodent excreta and secretions, i.e. urine and saliva, and human-to-human transmission occurs via the bodily fluids of an infected person. To elucidate the seasonal drivers of LF epidemics, we employed a mathematical model to analyse the datasets of human infection, rodent population dynamics and climatological variations and capture the underlying transmission dynamics. The surveillance-based incidence data of human cases in Nigeria were explored, and moreover, a mathematical model was used for describing the transmission dynamics of LF in rodent populations. While quantifying the case fatality risk and the rate of exposure of humans to animals, we explicitly estimated the corresponding contact rate of humans with infected rodents, accounting for the seasonal population dynamics of rodents. Our findings reveal that seasonal migratory dynamics of rodents play a key role in regulating the cyclical pattern of LF epidemics. The estimated timing of high exposure of humans to animals coincides with the time shortly after the start of the dry season and can be associated with the breeding season of rodents in Nigeria. This article is part of the theme issue 'Modelling infectious disease outbreaks in humans, animals and plants: approaches and important themes'. This issue is linked with the subsequent theme issue 'Modelling infectious disease outbreaks in humans, animals and plants: epidemic forecasting and control'.
Output: Quantifying the seasonal drivers of transmission for Lassa fever in Nigeria
The recently reported Middle East respiratory syndrome coronavirus (MERS-CoV) is phylogenetically closely related to the bat coronaviruses (BatCoVs) HKU4 and HKU5. However, the evolutionary pathway of MERS-CoV is still unclear. A receptor binding domain (RBD) in the MERS-CoV envelope-embedded spike protein specifically engages human CD26 (hCD26) to initiate viral entry. The high sequence identity in the viral spike protein prompted us to investigate if HKU4 and HKU5 can recognize hCD26 for cell entry. We found that HKU4-RBD, but not HKU5-RBD, binds to hCD26, and pseudotyped viruses embedding HKU4 spike can infect cells via hCD26 recognition. The structure of the HKU4-RBD/hCD26 complex revealed a hCD26-binding mode similar overall to that observed for MERS-RBD. HKU4-RBD, however, is less adapted to hCD26 than MERS-RBD, explaining its lower affinity for receptor binding. Our findings support a bat origin for MERS-CoV and indicate the need for surveillance of HKU4-related viruses in bats.
Output: Article Bat Origins of MERS-CoV Supported by Bat Coronavirus HKU4 Usage of Human Receptor CD26
which may together contribute to the alleviated lung injury and the attenuation of the virulence of H5N1 virus in mice. Keywords Highly pathogenic H5N1 AIV · PA-X · ALI · Pathogenesis · Mice Abstract PA-X is a novel discovered accessory protein encoded by the PA mRNA. Our previous study demonstrated that PA-X decreases the virulence of a highly pathogenic H5N1 strain A/Chicken/Jiangsu/k0402/2010 in mice. However, the underlying mechanism of virulence attenuation associated with PA-X is still unknown. In this study, we compared two PA-X-deficient mutant viruses and the parental virus in terms of induction of pathology and manipulation of host response in the mouse lung, stimulation of cell death and PA nuclear accumulation. We first found that down-regulated PA-X expression markedly aggravated the acute lung injury of the infected mice early on day 1 post-infection (p.i.). We then determined that loss of PA-X expression induced higher levels of cytokines, chemokines and complement-derived peptides (C3a and C5a) in the lung, especially at early time point's p.i. In addition, in vitro assays showed that the PA-X-deficient viruses enhanced cell death and increased expression of reactive oxygen species (ROS) in mammalian cells. Moreover, we also found that PA nuclear accumulation of the PA-X-null viruses accelerated in MDCK cells. These results demonstrate that PA-X decreases the level of complement components, ROS, cell death and inflammatory response,
Output: PA-X-associated early alleviation of the acute lung injury contributes to the attenuation of a highly pathogenic H5N1 avian influenza virus in mice
Dendrolimus punctatus cypovirus (DpCPV), belonging to the genus Cypovirus within the family Reoviridae, is considered the most destructive pest of pine forests worldwide. DpCPV has a genome consisting of 10 linear double-stranded RNA segments. To establish a reverse genetics system, we cloned cDNAs encoding the 10 genomic segments of DpCPV into three reverse genetics vectors in which each segment was transcribed under the control of a T7 RNA polymerase promoter and terminator tagged with a hepatitis delta virus ribozyme sequence. We also constructed a vp80-knockout Autographa californica multiple nucleopolyhedrovirus bacmid to express a T7 RNA polymerase codon-optimized for Sf9 cells. Following transfection of Sf9 cells with the three vectors and the bacmid, occlusion bodies (OBs) with the typical morphology of cypovirus polyhedra were observed by optical microscopy. The rescue system was verified by incorporation of a HindIII restriction enzyme site null mutant of the 9th genomic segment. Furthermore, when we co-transfected Sf9 cells with the reverse genetics vectors, the bacmid, and an additional vector bearing an egfp gene flanked with the 5 and 3 untranslated regions of the 10th genomic segment, aggregated green fluorescence co-localizing with the OBs was observed. The rescued OBs were able to infect Spodopetra exigua larvae, although their infectivity was significantly lower than that of wild-type DpCPV. This reverse genetics system for DpCPV could be used to explore viral replication and pathogenesis and to facilitate the development of novel bio-insecticides and expression systems for exogenous proteins.
Output: A Reverse Genetics System for Cypovirus Based on a Bacmid Expressing T7 RNA Polymerase
Background: Cost-benefit evaluation of measures against respiratory disease in cattle requires accounting with the associated production losses. Investigations of naturally occurring respiratory infections in a herd setting are an opportunity for accurate estimates of the consequences. This article presents estimates based on individual monitoring of weight and concentrate intake of several hundred bulls previous to, during and after a respiratory infection outbreak with bovine respiratory syncytial virus (BRSV) as the main pathogen. The aim of the study was to analyse the association between exposure to BRSV, weight gain and feed conversion rate, quantify any change in these parameters, and estimate the duration of the change in production. A comparison of growth curves for the bulls that were present during the outbreak revealed that bulls with severe clinical signs had a clear and consistent trend of poorer growth rate than those with milder or no signs. The weight/age-ratio was 0.04-0.10 lower in the severely affected bulls, and evident throughout the study period of 8 months. A comparison of growth rates between apparently healthy bulls being present during the outbreak and a comparable group of bulls exactly 1 year later (n = 377) showed a reduced growth rate of 111 g/day in the first group. The difference amounted to 23 extra days needed to reach the reference weight. Feed conversion was also reduced by 79 g weight gain/kilogram concentrate consumed in the outbreak year. Conclusion: This study indicates significant negative effects on performance of animals that develop severe clinical signs in the acute stage, and that the growth and production is negatively affected many months after apparent recovery. In addition, the performance of apparently healthy animals that are exposed during an outbreak are severely negatively affected. The duration of this decrease in production in animals after recovery, or animals that have not shown disease at all, has not previously been documented. These losses will easily be underestimated, but contribute significantly to the costs for the producer. The findings emphasize the importance of BRSV infection for profitability and animal welfare in cattle husbandry. The study also illustrates that utilising intra-herd comparison of health and production parameters is a productive approach to estimate consequences of an outbreak.
Output: Bovine respiratory syncytial virus outbreak reduced bulls' weight gain and feed conversion for eight months in a Norwegian beef herd
Recommended treatment of chronic hepatitis B with interferon-α and/or nucleos(t)ide analogues does not lead to a satisfactory result. Induction of HBV-specific T cells by therapeutic vaccination or immunotherapies may be an innovative strategy to overcome virus persistence. Vaccination with commercially available HBV vaccines in patients did not result in effective control of HBV infection, suggesting that new formulations of therapeutic vaccines are needed. The woodchuck (Marmota monax) is a useful preclinical model for developing the new therapeutic approaches in chronic hepadnaviral infections. Several innovative approaches combining antiviral treatments with nucleos(t)ide analogues, DNA vaccines, and protein vaccines were tested in the woodchuck model. In this paper we summarize the available data concerning therapeutic immunization and gene therapy using recombinant viral vectors approaches in woodchucks, which show encouraging results. In addition, we present potential innovations in immunomodulatory strategies to be evaluated in this animal model.
Output: Therapeutic Vaccination in Chronic Hepatitis B: Preclinical Studies in the Woodchuck
Effects of 3,3'-iminodipropionitrile on acquisition andperformance of spatial tasks in rats. NEUROTOXICOL TERATOL 16(6) 583-591, 1994.--3,3 '-Iminodipropionitrile (IDPN) has been reported to disrupt learning and memory in rats (24). The present work addressed the effects of IDPN on tasks requiring the use of spatial information. Separate groups of male rats were dosed with IDPN (IP, in 1 ml/kg saline) for 3 consecutive days and tested in the following procedures: (a) step-through passive avoidance conditioning (0, 100, 150, and 200 mg/kg/ day); (b) Morris water maze (MWM) acquisition and retention (0, 125, 150, 175, and 200 mg/kg/day); (c) radial arm maze (RAM) acquisition (0, 100, 200, and 400 mg/kg/day); (d) RAM steady-state performance (0, 200, and 400 mg/kg/day); (e) repeated acquisition in the RAM (0, and 200 mg/kg/day). The vestibular toxicity of IDPN resulted in alterations in spontaneous behavior or swimming deficits in 5 of 8 rats treated with 175 mg/kg/day and in all the animals dosed with 200 or 400 nag/ kg/day. IDPN increased step-through PA latencies at 200 mg/kg/day but not at lower doses. In the MWM, no performance deficits were observed at the dose levels preserving the swimming ability of the animals. In both the acquisition and the steady-state RAM tasks, IDPN (400 mg/kg/day) induced an increase in both choice errors and perseverative errors. In the RAM repeated acquisition paradigm, IDPN (200 mg/kg/day) induced performance deficits that included a decreased rate of within-session reduction in errors. The present data show that IDPN disrupts performance of tasks requiring spatial learning and memory and indicate that these deficits can be in part caused by an acquisition deficit.
Output: Effects of 3,3 '-Iminodipropionitrile on Acquisitionand Performance of Spatial Tasks in Rats
Background: Suicide is a grave public health issue that is responsible for a high mortality rate among individuals aged 15-44 years. Attitudes toward suicide among medical staff members have been associated with appropriate therapeutic responses to suicidal individuals. The aim of this study was to examine the effects of parental rearing on attitudes toward suicide among Japanese medical college students. Methods: We examined the association between parental bonding and attitudes toward suicide in 160 medical college students in Japan. The Parental Bonding Instrument was used to assess the attitudes and behaviors of parents. The attitudes toward suicide were evaluated using the Japanese version of the Attitudes Toward Suicide questionnaire. Results: The mean age of the subjects was 25.2±4.0 years old. The majority of the participants in our study agreed that anyone could commit suicide (88.8%) and that suicide is preventable (86.3%). After adjusting for age and sex, multivariate regression analysis revealed that maternal care approached a statistically significant association with the "right to suicide" attitude. Under the same conditions, maternal care was shown to be significantly associated with the "common occurrence" attitude. No other significant relationships were observed between parental bonding and attitudes toward suicide. This study suggests that a higher level of maternal care ensures that children think that suicide occurs less commonly. The promotion of best practices for suicide prevention among medical students is needed. Child rearing support might be associated with suicide prevention.
Output: Neuropsychiatric Disease and Treatment Neuropsychiatric Disease and Treatment Dovepress Parental bonding and attitudes toward suicide among medical college students in Japan
Current technologies with next generation sequencing have revolutionized metagenomics analysis of clinical samples. To achieve the non-selective amplification and recovery of low abundance genetic sequences, a simplified Sequence-Independent, Single-Primer Amplification (SISPA) technique in combination with MiSeq platform was applied to target negative-and positive-sense single-stranded RNA viral sequences. This method allowed successful sequence assembly of full or near full length avian influenza virus (AIV), infectious bronchitis virus (IBV), and Newcastle disease virus (NDV) viral genome. Moreover, SISPA analysis applied to unknown clinical cases of mixed viral infections produced genome assemblies comprising 98% NDV and 99% of IBV genomes. Complete or near complete virus genome sequence was obtained with titers at or above 10 4.5 EID 50 / ml (50% embryo infectious dose), and virus identification could be detected with titers at or above 10 3 EID 50 / ml. Taken together, these studies demonstrate a simple template enrichment protocol for rapid detection and accurate characterization of avian RNA viruses.
Output: Use of Sequence-Independent, Single-Primer-Amplification (SISPA) for rapid detection, identification, and characterization of avian RNA viruses
Dengue fever (DF) is one of the world's emerging infectious diseases. The steady increase in European tourists, as well as soldiers serving on peacekeeping duties, in endemic areas, coupled with the present resurgence of dengue, raises the risk of exposure for a large number of European travellers. Significant numbers of travellers have, in fact, developed DF. There is a risk of dengue haemorrhagic fever (DHF) in travellers who revisit the same place, and they have the potential not only to acquire, but also to spread, the dengue viral infection. Of concern is the potential for a dengue outbreak in a previously dengue-free country through imported cases. Another major concern is the potential area of dengue transmission, due to spread of its vectors through sizeable parts of southern Europe. In addition to the risk of haemorrhagic fever in returning tourists, the introduction of DF by returning travellers, whether they have symptoms or are unaffected by signs and symptoms of the disease, poses a threat to health systems in Europe.
Output: Dengue fever in travellers: A challenge for European physicians
The constitutional isomers and tautomers of oxadiazolones, as well as their mono-and disulfur analogues, were calculated at the B3LYP/aug-cc-pVDZ level. Four groups of 30 molecules each were considered: oxadiazolone, oxadiazolthione, thiadiazolone, and thiadiazolthione isomers. The compounds were categorized into six groups according to permutations of three heteroatoms in the five-membered ring. Additionally, each of the constitutional isomer was considered to have five tautomers conserving stable five-membered ring: two NH tautomers, two rotameric OH (or SH) forms and one CH 2 tautomer. It appeared that the largest difference between oxadiazolone O and S analogues is produced by the kind of chalcogen atom in the ring, which is strained when the O atom is in the ring while much less strained when the S-atom, of much larger van der Waals radius, is built into the ring. The external chalcogen is only modifying the general energetic factors. The comparison of energetics of analogous groups of molecules with thiadiazole and oxadiazole rings is done in details as well as differences resulting from different external chalcogen atoms are discussed as well. The presence of water surrounding was mimicked with the IEF-PCM implicit water model which did not change general isomer relative stability picture, but for some special cases indicated an extra stability of the forms with external OH or SH groups. The aromaticity monitored by the structural HOMA aromaticity index shows that the systems are not additionally stabilized by pi-electron delocalization. The fair linear correlation between the aromaticity indices of oxadiazolones and oxadiazolthiones shows that the pi-electron system in the studied systems is not sensitive to change of the external chalcogen group.
Output: On constitutional isomers and tautomers of oxadiazolones and their mono- and disulfur analogues (C 2 H 2 N 2 XY; X, Y = S, O)
Background: Whilst numerous studies have investigated nurses' compliance with hand hygiene and use of alcohol-based hand rub (ABHR), limited attention has been paid to these issues in allied health staff. Reports have linked infections to breaches in infection control in the radiography unit (RU). With advances in medical imaging, a higher proportion of patients come into contact with RU staff increasing the need for good hand hygiene compliance. This study aimed to evaluate effectiveness on compliance of an intervention to improve awareness of hand hygiene in the RU of a district hospital. Methods: A quasi-experimental study design including questionnaires assessing knowledge and attitudes of hand hygiene and direct observation of participants was used to evaluate an educational programme on hand hygiene of the RU of a large district hospital. All healthcare workers (HCW), comprising 76 radiographers, 17 nurses, and nine healthcare assistants (HCA), agreed to participate in the study. Of these, 85 completed the initial and 76 the posttest anonymous questionnaire. The hand hygiene compliance of all 102 HCW was observed over a 3-week period prior to and after the intervention. The 2-month intervention consisted of talks on hand hygiene and benefits of ABHR, provision of visual aids, wall-mounted ABHR dispensers, and personal bottles of ABHR. Results: Before the intervention, overall hand hygiene compliance was low (28.9 %). Post-intervention, compliance with hand hygiene increased to 51.4 %. This improvement was significant for radiographers and HCA. Additionally, knowledge and attitudes improved in particular, understanding that ABHR can largely replace handwashing and there is a need to perform hand hygiene after environmental contact. The increased use of ABHR allowed HCW to feel they had enough time to perform hand hygiene. Conclusions: The educational intervention led to increased awareness of hand hygiene opportunities and better acceptance of ABHR use. The reduced time needed to perform hand rubbing and improved access to dispensers resulted in fewer missed opportunities. Although radiographers and other allied HCW make frequent contact with patients, these may be mistakenly construed as irrelevant with respect to healthcare associated infections. Stronger emphasis on hand hygiene compliance of these staff may help reduce infection risk.
Output: A quasi-experimental study to determine the effects of a multifaceted educational intervention on hand hygiene compliance in a radiography unit
Background: Drainage systems and its role in sanitation related outbreaks are evident but still occluded once it has been installed. This current review evaluates if drainage systems can cause infections and thus be of clinical concern. Method: A review of the literature was analyzed. Papers, guidelines, and quality management systems have been considered. Results: Adequate sanitation is fundamental and a prerequisite for safe life and productivity. In contrast, malfunctioning sanitation has been reported to cause outbreaks all over the world. In areas with no sanitation, diarrheal mortality is high and has been shown to decrease by 36% after interventions to improve sanitation. Often, infections are faeces associated and when present in wastewater and sewage sludge poses a high risk of infection upon exposure. Hence, there are working safety guidelines and in industries where infection reduction is essential strict quality assurance systems, i.e. HACCP (hazard analysis critical control points) and GMP (Good Manufacturing Practice) must be complied. Healthcare has recently taken interest in the HACCP system in their efforts to reduce healthcare associated infections as a response to increasing number of ineffective antibiotics and the threat of mortality rate like the pre-antibiotic era. The last few years have called for immediate action to contain the emergence of increasing resistant microorganisms. Resistance is obtained as a result of overuse and misuse of antibiotics in both healthcare and agriculture. Also, by the discharge of antibiotics from manufacturers, healthcare and society. One mechanism of development of novel resistant pathogens has been shown to be by effortless sharing of genetic mobile elements coding for resistance from microbes in the environment to human microbes. These pathogens have been sampled from the drainage systems. These were noticed owing to their possession of an unusual antibiotic resistance profile linking them to the outbreak. Often the cause of sanitation related outbreaks is due to inadequate sanitation and maintenance. However, in general these infections probably go unnoticed. Conclusion: Drainage systems and its maintenance, if neglected, could pose a threat in both community and healthcare causing infections as well as emergence of multi-resistant bacteria that could cause unpredictable clinical manifestations.
Output: Drainage systems, an occluded source of sanitation related outbreaks
Endoplasmic reticulum (ER) stress can be activated by various pathological and physiological conditions including the unfolded protein response (UPR) to restore homeostasis. The UPR signaling pathways initiated by double-stranded RNA-activated protein kinase (PKR) like ER kinase (PERK), inositol requiring enzyme 1 α (IRE1α), and activating transcription factor 6 (ATF6) are vital for tumor growth, aggressiveness, microenvironment remodeling, and resistance to cancer therapeutics. This review focuses on the role of ER stress and activity of UPR signaling pathways involved in tumor formation and uncontrolled cell proliferation during various cancers and viral malignancies.
Output: Virus and tumor microenvironment induced ER stress and unfolded protein response: from complexity to therapeutics
This chapter seeks to survey many of the common pathological entities identified in the lungs at autopsy and the potential role of pulmonary disease in formulating an opinion regarding the cause of death. Appreciation of pulmonary pathology in the medicolegal context is important as it frequently contributes to the immediate or underlying mechanisms of death. The primacy of the lungs in breathing and their coordinated function with the cardiovascular system means that pulmonary failure can rapidly compromise tissue oxygenation and body chemistry, leading to an alteration in blood pH, hypoxic damage to downstream tissues and ultimately multiorgan failure and death. Moreover, given that the lungs have direct contact with the environment through inhalation and receive approximately 50% of the cardiac output with each beat of the heart, they may be adversely affected by hazardous agents from the outside world or other pathologic processes not primarily located in the lungs. The range of topics discussed herein is limited by design to deaths due to disease and largely foregoes discussion of more forensically relevant issues relating to toxicology or trauma. Furthermore, the content and format of this chapter is not intended to be encyclopedic, but rather attempts to highlight selected issues regarding pulmonary disease of potential relevance to surgical or forensic pathologists who perform medicolegal postmortem examinations.
Output: Sudden Death from Pulmonary Causes
Genome Detective is a web-based, user-friendly software application to quickly and accurately assemble all known virus genomes from next generation sequencing datasets. This application allows the identification of phylogenetic clusters and genotypes from assembled genomes in FASTA format. Since its release in 2019, we have produced a number of typing tools for emergent viruses that have caused large outbreaks, such as Zika and Yellow Fever Virus in Brazil. Here, we present The Genome Detective Coronavirus Typing Tool that can accurately identify the novel severe acute respiratory syndrome (SARS) related coronavirus (SARS-CoV-2) sequences isolated in China and around the world. The tool can accept up to 2,000 sequences per submission and the analysis of a new whole genome sequence will take approximately one minute. The tool has been tested and validated with hundreds of whole genomes from ten coronavirus species, and correctly classified all of the SARS-related coronavirus (SARSr-CoV) and all of the available public data for SARS-CoV-2. The tool also allows tracking of new viral mutations as the outbreak expands globally, which may help to accelerate the development of novel diagnostics, drugs and vaccines to stop the COVID-19 disease.
Output: Genome Detective Coronavirus Typing Tool for rapid identification and characterization of novel coronavirus genomes
RNA is produced from the majority of human genomic sequences, although only a relatively small portion of these transcripts has known functions. Diverse RNA species interact with RNA, DNA, proteins, lipids, and metabolites to form intricate molecular networks. In this review, we attempt to delineate diverse RNA functions by interaction types between RNA and other macromolecules. Through such interactions RNAs participate in essentially every major molecular function and process, including information flow and storage, environment sensing, signal transduction, and gene regulation at transcriptional and posttranscriptional levels. Through such interactions, RNAs promote or inhibit diverse biological processes, and act as catalyzer or quencher to modulate the pace of these progresses. Alterations and personal variations of these interactions are mechanistically coupled with disease etiology and phenotypical variations for clinical use. Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Output: RNA: interactions drive functionalities