bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mortality due to SARS COV-2 And its Associated Factors in East Shewa Zone Treatment Centers, Ethiopia, 2022: A retrospective cross-sectional study
Authors: Hassen Jemal , Getinet Tewodros , Botore Abera , Bekele Mesfin , Bekele Bayissa , Jalata Firaol , Abebe Wake , Sisay Mekdes , Getahun Asnakech , Ligidi Tadesse 
Published: November 2022

AbstractBackgroundCoronavirus disease (COVID-19) is an infectious disease that is caused by the SARS-CoV-2virus. The objective of this study was to determine SARS COV-2 Mortality and its associated factors in East Shewa Zone Treatment centers, Oromia, Ethiopia, 2022. The study of these types of viral infection will add new insight into the most common causes of mortality in SARS-CoV-2infection and the most common co-morbidities associated with the disease in the East Shewa Zone.MethodsThe study was conducted on patients who were admitted to Adama Hospital medical college and Modjo Primary Hospital for SARS-COV 2 treatment. Data used for the study were collected from March 2020-April 2022 GC. The study population was SARS-COV 2 patients who come to Adama Hospital and Medical College and Modjo Primary Hospital for treatment. All eligible SARS-CoV-2 patients’ data were collected from Both Adama and Modjo treatment center SARS-CoV-2 accession registration book and medical record card.ResultA total of 409 patient data were collected from which 199 were from Adama Hospital and Medical College and 210 samples were collected from Modjo Primary Hospital Treatment center. The study design was a retrospective Cross-sectional study. The most affected age group in terms of mortality was the age group between 60-69 years old which suffers a 45.28% death rate. The major sign symptoms identified include cough (80.4%), Shortness of breath (66.7%) followed by fever (43.2%). SARS-CoV-2 Comorbidity was detected in 152 (37.2%) patients. Pneumonia was identified as the major comorbid disease to be recorded with 89(21.8%) cases. Other major comorbidities include Hypertension (16.9%) and Diabetes Mellites (13.9%). The least identified comorbidities were anemia (0.2%), Rectal cancer (0.2%), breast cancer (0.5%), and Chronic liver disease.ConclusionNearly one in four (22.7%) SARS-COV 2 patients admitted for treatment to Adama Hospital and Medical College and Modjo Primary Hospital did not make their way out of treatment Hospitals alive. Pneumonia was identified as the major comorbid disease to be recorded with 89(21.8%) cases
Non-COVID-19 mortality in France, April 2020 - June 2022: reduction compared to pre-pandemic mortality patterns, relative increase during the Omicron period, and the importance of detecting SARS-CoV-2 infections
Authors: Goldstein Edward 
Published: November 2022

AbstractAimsWe compared the number of non-COVID-19 deaths between April 2020 and June 2022 to the expected number of deaths based on the patterns observed in the five years prior to the pandemic in France with the aims of (a) estimating the reduction in non-COVID-19 mortality, particularly due to reduction in the circulation of other respiratory viruses during the pandemic; (b) examining the degree to which SARS-CoV-2 infection was detected and characterized as a cause of death during different periods of the pandemic.MethodsUsing a previously developed regression model, we expressed weekly mortality rates in the 5-year period prior to the pandemic as a combination of influenza-associated mortality rates and baseline and a linear trend for the rates of non-influenza mortality. Estimates for the baseline and trend for non-influenza mortality together with estimates of influenza-related mortality prior to the pandemic were used to estimate expected mortality during the pandemic period.ResultsThe number of recorded non-COVID-19 deaths between week 15, 2020 and week 26, 2022 in France was less than the expected number of deaths by 49,623 (95% CI (20364,78837)). Additionally, rates of non-COVID-19 mortality increased during the later part of the study period, with the difference between the number of non-COVID-19 deaths and the expected number of deaths during the last 52 weeks of the study period being greater than the corresponding difference for the first 52 weeks of the study period by 28,954 (24979,32918) deaths.ConclusionsOur results suggest (a) the effectiveness of mitigation measures during the pandemic for reducing the rates of non-COVID-19 mortality, particularly mortality related to circulation of other respiratory viruses, including influenza (that was responsible for an annual average of 15,334 (12593,18077) deaths between 2015-2019 in France); (b) detection of a high proportion of SARS-CoV-2 infections leading to deaths in France, and characterization of those infections as the underlying cause of death. Additionally, while the increase in non-COVID-19 mortality during the later part of the study period is partly related to the temporal increase in the circulation of other respiratory viruses, there was an increase, particularly during the period of the circulation of the Omicron variant, in the proportion of hospitalizations with a SARS-CoV-2 infection in France that were coded as hospitalizations with COVID-19 (rather than COVID-19 hospitalizations), suggesting an increasing proportion of SARS-COV-2-associated deaths not being coded as COVID-19 deaths. All of this suggests the importance of timely detection of infections with SARS-CoV-2, particularly the Omicron variant (for which manifestations of disease complications are different compared to the earlier variants), and of providing the necessary treatment to patients to avoid progression to fatal outcomes.
POIROT: A powerful test for parent-of-origin effects in unrelated samples leveraging multiple phenotypes
Authors: Head S. Taylor , Leslie Elizabeth J. , Cutler David J. , Epstein Michael P. 
Published: November 2022

ABSTRACTMotivationThere is widespread interest in identifying genetic variants that exhibit parent-of-origin effects (POEs) wherein the effect of an allele on phenotype expression depends on its parental origin. POEs can arise from different phenomena including genomic imprinting and have been documented for many complex traits. Traditional tests for POEs require family data to determine parental origins of transmitted alleles. As most genome-wide association studies (GWAS) instead sample unrelated individuals (where allelic parental origin is unknown), the study of POEs in such datasets requires sophisticated statistical methods that exploit genetic patterns we anticipate observing when POEs exist. We propose a method to improve discovery of POE variants in large-scale GWAS samples that leverages potential pleiotropy among multiple correlated traits often collected in such studies. Our method compares the phenotypic covariance matrix of heterozygotes to homozygotes based on a Robust Omnibus Test. We refer to our method as the Parent of Origin Inference using Robust Omnibus Test (POIROT) of multiple quantitative traits.ResultsThrough simulation studies, we compared POIROT to a competing univariate variance-based method which considers separate analysis of each phenotype. We observed POIROT to be well-calibrated with improved power to detect POEs compared to univariate methods. POIROT is robust to non-normality of phenotypes and can easily adjust for population stratification and other confounders. Finally, we applied POIROT to a GWAS of quantitative anthropometric measures at birth. We identified two loci of suggestive significance for follow-up investigation.
H3K4 di- and trimethylation modulate the stability of RNA polymerase II pausing
Authors: Hu Shibin , Song Aixia , Peng Linna , Tang Nan , Qiao Zhibin , Wang Zhenning , Chen Fei Xavier 
Published: November 2022

SUMMARYModifications of histones are intricately linked with the regulation of gene expression, with demonstrated roles in various physiological processes and disease pathogenesis. Methylation of histone H3 lysine 4 (H3K4), implemented by the COMPASS family, is enriched at promoters and associated cis-regulatory elements, with H3K4 trimethylation (H3K4me3) considered a hallmark of active gene promoters. However, the relative roles of deposition and removal of H3K4 methylation, as well as the extent to which these events contribute to transcriptional regulation have so far remained unclear. Here, through rapid depletion of the transcription regulator SPT5 or either of two shared subunits of COMPASS family members, we reveal a dynamic turnover of H3K4me3 mediated by the KDM5 family of histone demethylases. Loss of H3K4me3 following COMPASS disruption does not impair the recruitment of TFIID and initiating RNA polymerase II (Pol II). Instead, H3K4me3 loss leads to reductions in the paused form of Pol II on chromatin while inducing the relative enrichment of the Integrator-PP2A (INTAC) termination complex, leading to reduced levels of elongating polymerases, thus revealing how H3K4me3 dynamics can regulate Pol II pausing to sustain or attenuate transcription.
Reducing the foreign body response on human cochlear implants and their materialsin vivowith photografted zwitterionic hydrogel coatings
Authors: Horne Ryan , Ben-Shlomo Nir , Jensen Megan , Ellerman Morgan , Escudero Caleb , Hua Rong , Bennion Douglas , Guymon C Allan , Hansen Marlan R. 
Published: November 2022

AbstractThe foreign body response to implanted materials often complicates the functionality of sensitive biomedical devices. For cochlear implants, this response can reduce device performance, battery life and preservation of residual acoustic hearing. As a permanent and passive solution to the foreign body response, this work investigates ultra-low-fouling poly(carboxybetaine methacrylate) (pCBMA) thin film hydrogels that are simultaneously photo-grafted and photo-polymerized onto polydimethylsiloxane (PDMS). The cellular anti-fouling properties of these coatings are robustly maintained even after six-months subcutaneous incubation and over a broad range of cross-linker compositions. On pCBMA-coated PDMS sheets implanted subcutaneously, capsule thickness and inflammation are reduced significantly in comparison to uncoated PDMS or coatings of polymerized poly(ethylene glycol dimethacrylate) (pPEGDMA) or poly(hydroxyethyl methacrylate) (pHEMA). Further, capsule thickness is reduced over a wide range of pCBMA cross-linker compositions. On cochlear implant electrode arrays implanted subcutaneously for one year, the coating bridges over the exposed platinum electrodes and dramatically reduces the capsule thickness over the entire implant. Coated cochlear implant electrode arrays could therefore lead to persistent improved performance and reduced risk of residual hearing loss. More generally, thein vivoanti-fibrotic properties of pCBMA coatings also demonstrate potential to mitigate the fibrotic response on a variety of sensing/stimulating implants.Graphical Abstract
Time to run: Late rather than early exercise training in mice remodels the gut microbiome and reduces atherosclerosis development
Authors: Schönke Milena , Ying Zhixiong , Kovynev Artemiy , het Panhuis Wietse In , Binnendijk Anne , van der Poel Sabine , Pronk Amanda C.M. , Streefland Trea C.M , Hoekstra Menno , Kooijman Sander , Rensen Patrick C.N. 
Published: November 2022

AbstractThe metabolic and inflammatory processes that are implicated in the development of cardiovascular diseases are under control of the biological clock. While skeletal muscle function exhibits circadian rhythms, it is unclear to what extent the beneficial health effects of exercise are restricted to unique time windows. We aimed to study whether the timing of exercise training differentially modulates the development of atherosclerosis and elucidate underlying mechanisms. We endurance-trained atherosclerosis-prone female APOE*3-Leiden.CETP mice fed a Western-type diet, a well-established human-like model for cardiometabolic diseases, for one hour five times a week for four weeks either in their early or in their late active phase on a treadmill. We monitored metabolic parameters, the development of atherosclerotic lesions in the aortic root and assessed the composition of the gut microbiota. Late, but not early, exercise training reduced fat mass by 19% and the size of early-stage atherosclerotic lesions by as much as 29% compared to sedentary animals. No correlation between cholesterol exposure and lesion size was evident, as no differences in plasma lipid levels were observed, but circulating levels of the pro-inflammatory markers ICAM-1 and VCAM-1 were reduced with late exercise. Strikingly, we observed a time-of-day-dependent effect of exercise training on the composition of the gut microbiota as only late training increased the abundance of gut bacteria producing short-chain fatty acids with proposed anti-inflammatory properties. Together, these findings indicate that timing is a critical factor to the beneficial anti-atherosclerotic effects of exercise with a great potential to further optimize training recommendations for patients.
Despite impaired binocular function, binocular disparity integration across the visual field is spared in normal aging and glaucoma
Authors: Maiello Guido , Kwon MiYoung 
Published: November 2022

AbstractObjectiveTo examine how binocularly asymmetric glaucomatous visual field damage affects processing of binocular disparity across the visual field.DesignCase–control study.Participants and ControlsA sample of 18 patients with primary open-angle glaucoma, 16 age-matched controls, and 13 young controls.MethodsParticipants underwent standard clinical assessments of binocular visual acuity, binocular contrast sensitivity, stereoacuity, and perimetry. We employed a previously validated psychophysical procedure to measure how sensitivity to binocular disparity varied across spatial frequencies and visual field sectors, i.e. with full-field stimuli spanning the central 21° of the visual field, and with stimuli restricted to annular regions spanning 0°-3°, 3°-9° or 9°-21°.Main Outcome MeasuresWe verified the presence of binocularly asymmetric glaucomatous visual field damage by comparing—between the two eyes— the mean deviation values obtained from the Humphrey Field Analyzer (HFA) 24-2 test. To assess the spatial-frequency tuning of disparity sensitivity across the visual field of patients and controls, we fit disparity sensitivity data to log-parabola models and compared fitted model parameters. Lastly, we employed disparity sensitivity measurements from restricted visual field conditions to model different possible scenarios regarding how disparity information is combined across visual field sectors. We adjudicated between the potential mechanisms by comparing model predictions to the observed patterns of disparity sensitivity with full-field stimuli.ResultsThe interocular difference in HFA 24-2 mean deviation was greater in glaucoma patients compared to both young and age-matched controls (ps=.01). Across participant groups foveal regions preferentially processed disparities at finer spatial scales, whereas periphery regions were tuned for coarser scales (p<.001). Disparity sensitivity also decreased from the fovea to the periphery (p<.001) and across participant groups (ps<.01). Finally, similar to controls, glaucoma patients exhibited near-optimal disparity integration, specifically at low spatial frequencies (p<.001).ConclusionsContrary to the conventional view that glaucoma spares central vision, we find that glaucomatous damage causes a widespread loss of disparity sensitivity across both foveal and peripheral regions. Despite these losses, cortical integration mechanisms appear to be well preserved, suggesting that glaucoma patients make the best possible use of their remaining binocular function.
A performance evaluation of neural network features and functions settings on the model accuracy
Authors: Bozděch Michal 
Published: November 2022

AbstractNot only in sports is a neural network the most used type of artificial intelligence. With software development, anyone can create a neural network model, but little is known about how to prepare the data and how to set up the model algorithms to their maximum performance. For these reasons, this study aims to determine whether features or function settings have a greater effect on model accuracy. An initial feature dataset (n= 18882) was obtained from publicly available sources. Each of the six different feature settings consisted of 96 models. A total of 384 models were created, in which their testing accuracy and the percentage difference between the training and testing phases were further analyzed. No statistically significant differences were found between the accuracy of the function’s settings, but statistically significant differences were confirmed between the feature settings. The study found that feature settings, especially the reduction of the number of outputs, are a more important factor in increasing the model accuracy, than function settings. Although the literature focuses more on the function setting and sets feature setting is taken rather as a type of how to improve the model.
Structure-Kinetic Relationship for Drug Design Revealed by PLS Model with Retrosynthesis-Based Pre-trained Molecular Representation and Molecular Dynamics Simulation
Authors: Zhou Feng , Yin Shiqiu , Xiao Yi , Lin Zaiyun , Fu Weiqiang , Zhang Yingsheng J. 
Published: November 2022

ABSTRACTDrug design based on their molecular kinetic properties is growing in application. Pre-trained molecular representation based on retrosynthesis prediction model (PMRRP) was trained from 501 inhibitors of 55 proteins and successfully predicted the koffvalues of 38 inhibitors for HSP90 protein from an independent dataset. Our PMRRP molecular representation outperforms others such as GEM, MPG, and common molecular descriptors from RDKit. Furthermore, we optimized the accelerated molecular dynamics to calculate relative retention times for 128 inhibitors of HSP90. We observed high correlation between the simulated, predicted, and experimental -log(koff) scores. Combining machine learning (ML) and molecular dynamics (MD) simulation help design a drug with specific selectivity to the target of interest. Protein-ligand interaction fingerprints (IFPs) derived from accelerated MD further expedite the design of new drugs with the desired kinetic properties. To further validate our koffML model, from the set of potential HSP90 inhibitors obtained by similarity search of commercial databases, we identified two novel molecules with better predicted koffvalues and longer simulated retention time than the reference molecules. The IFPs of the novel molecules with the newly discovered interacting residues along the dissociation pathways of HSP90 shed light on the nature of the selectivity of HSP90 protein. We believe the ML model described here is transferable to predict koffof other proteins and enhance the kinetics-based drug design endeavor.
The importance of vaccinated individuals to population-level evolution of pathogens
Authors: Gutierrez Maria A. , Gog Julia R. 
Published: November 2022

AbstractVirus evolution shapes the epidemiological patterns of infectious disease, particularly via evasion of population immunity. At the individual level, host immunity itself may drive viral evolution towards antigenic escape. Using compartmental SIR-style models with imperfect vaccination, we allow the probability of immune escape to differ in vaccinated and unvaccinated hosts. As the relative contribution to selection in these different hosts varies, the overall effect of vaccination on the antigenic escape pressure at the population level changes.We find that this relative contribution to escape is important for understanding the effects of vaccination on the escape pressure and we draw out some fairly general patterns. If vaccinated hosts do not contribute much more than unvaccinated hosts to the escape pressure, then increasing vaccination always reduces the overall escape pressure. In contrast, if vaccinated hosts contribute significantly more than unvaccinated hosts to the population level escape pressure, then the escape pressure is maximised for intermediate vaccination levels. Past studies find only that the escape pressure is maximal for intermediate levels with fixed extreme assumptions about this relative contribution. Here we show that this result does not hold across the range of plausible assumptions for the relative contribution to escape from vaccinated and unvaccinated hosts.We also find that these results depend on the vaccine efficacy against transmission, particularly through the partial protection against infection. This work highlights the potential value of understanding better how the contribution to antigenic escape pressure depends on individual host immunity.
A systematic review exploring the association between the human gut microbiota and brain connectivity in health and disease
Authors: Mulder Danique , Aarts Esther , Vasquez Alejandro Arias , Bloemendaal Mirjam 
Published: November 2022

1AbstractA body of pre-clinical evidence shows how the gut microbiota influence brain functioning, including brain connectivity. A growing number of studies have investigated the association between the gut microbiota and brain connectivity in humans. Linking brain connectivity measures to the gut microbiota can provide important mechanistic insights into the bi-directional gut-brain communication. In this systematic review, we therefore synthesized the available literature assessing this association, evaluating the degree of consistency in microbiota-connectivity associations. Following the PRISMA guidelines, a PubMed search was conducted, including studies published up to September 1, 2022. We identified 16 studies that met the inclusion criteria. Several bacterial genera, includingPrevotella,Bacteroides,RuminococcusandBlautiawere most consistently reported in association with brain connectivity. Additionally, the salience (specifically the insula and anterior cingulate cortex), default mode and frontoparietal networks were most frequently associated with the gut microbiota, both in terms of microbial diversity and composition. Altogether, based on our synthesis, there is evidence for an association between the gut microbiota and brain connectivity. However, the specificity of the signal is yet unclear as most findings were poorly replicated across studies. The current studies show substantial inter-study heterogeneity in methodology and reporting, limiting the robustness and reproducibility of the findings and emphasizing the need to harmonize methodological approaches. To enhance comparability and replicability, future research should focus on further standardizing processing pipelines and employ data-driven multivariate analysis strategy.