bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploiting Molecular Basis of Age and Gender Differences in Outcomes of SARS-CoV-2 Infections
Authors: Mercatelli Daniele , Pedace Elisabetta , Giorgi Federico M. , Guzzi Pietro Hiram 
Published: May 2021

AbstractMotivationSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (coronavirus disease, 2019; COVID-19) is associated with adverse outcomes in patients. It has been observed that lethality seems to be related to the age of patients. Moreover, it has been demonstrated that ageing causes some modifications at a molecular level.ObjectiveThe study aims to shed out light on a possible link between the increased COVID-19 lethality and the molecular changes that occur in elderly people.MethodsWe considered public datasets on ageing-related genes and their expression at tissue level. We selected interactors that are known to be related to ageing process. Then, we performed a network-based analysis to identify interactors significantly related to both SARS-CoV-2 and ageing. Finally, we investigated changes on the expression level of coding genes at tissue, gender and age level.ResultsWe observed a significant intersection between some SARS-CoV-2 interactors and ageing-related genes suggesting that those genes are particularly affected by COVID-19 infection. Our analysis evidenced that virus infection particularly affects ageing molecular mechanisms centred around proteins EEF2, NPM1, HMGA1, HMGA2, APEX1, CHEK1, PRKDC, and GPX4. We found that HMGA1, and NPM1 have a different expression in lung of males, while HMGA1, APEX1, CHEK1, EEF2, and NPM1 present changes in expression in males due to aging effects.ConclusionOur study generated a mechanistic framework to explaining the correlation between COVID-19 incidence in elderly patients and molecular mechanisms of ageing. This will provide testable hypotheses for future investigation and pharmacological solutions tailored on specific age ranges.
Cohort profile: Actionable Register of Geneva Out- and inpatients with SARS-CoV-2 (ARGOS)
Authors: Genecand Camille , Mongin Denis , Koegler Flora , Lebowitz Dan , Regard Simon , Nehme Mayssam , Braillard Olivia , Grira Marwène , Joubert Dominique , Chopard Pierre , Delaporte Elisabeth , Stirnemann Jerome , Guessous Idris , Tardin Aglaé , Courvoisier Delphine S. 
Published: May 2021

AbstractPurposeThe Actionable Register of Geneva Out- and inpatients with SARS-CoV-2 (ARGOS) is an ongoing prospective cohort created by the Geneva Directorate of Health (GDH). It consists of an operational database compiling all SARS-CoV-2 test results conducted in the Geneva area since late February 2020. This article aims at presenting this comprehensive cohort, in light of some of the varying public health measures in Geneva, Switzerland, since March 2020.ParticipantsAs of June 1st, 2021, the database included 356’868 patients, among which 65’475 had at least one positive test result for SARS-CoV-2. Among all positive patients, 37.6% were contacted only once, 10.6 % had one follow-up call, 8.5% had two, and 27.7% had 3 or more follow-up calls. Participation rate among positive patients is 94%. Data collection is ongoing.Findings to dateARGOS data illustrates the magnitude of COVID-19 pandemic in Geneva, Switzerland, and details a variety of population factors and outcomes. The content of the cohort includes demographic data, comorbidities and risk factors for poor clinical outcome, self-reported COVID-19 symptoms, environmental and socio-economic factors, prospective and retrospective contact tracing data, travel quarantine data, and deaths. The registry has already been used in several publications focusing on symptoms and long COVID, infection fatality rate, and re-infection.Future plansThe data of this large real-world registry provides a valuable resource for various types of research, such as clinical research, epidemiological research or policy assessment as it illustrates the impact of public health policies and overall disease burden of COVID-19.STRENGTHS AND LIMITATIONS OF THIS STUDYARGOS’ main strength consists of its large number of cases, representative of all diagnosed cases on a regional level with the primary aim of assessing all cases.ARGOS involves every individual who performed a SARS-CoV-2 test (PCR or antigenic) and is not limited to hospitalized patients, thus providing a valuable resource to assess the overall disease burden of COVID-19 in a geographically defined population.To mitigate confounding effects and improve data analysis and interpretation, we present the data according to four policy periods.This cohort is multicentric as it includes all tests performed in Geneva’s hospitals (both public and private), private practices and medical centers.Due to operational needs, symptoms and comorbidities are self-reported, which may lead to measurement error or misclassification.
Nursing students’ attitudes, knowledge, and willingness to receive the COVID-19 vaccine: A cross-sectional study
Authors: Jiang Ning , Wei Baojian , Lin Hua , Wang Youjuan , Chai Shouxia , Liu Wei 
Published: May 2021

AbstractAimTo investigate nursing students’ konwledge, attitudes and willingness to receive the COVID-19 vaccine, and the influencing factors.BackgroundVaccination is one of the effective measures to prevent COVID-19, but the vaccination acceptance varies across countries and populations. As reserve nurses, nursing students have both the professionalism of medical personnel and the special characteristics of school students, their attitudes, knowledge, and willingness to receive the COVID-19 vaccine may greatly affect the vaccine acceptance of the population now and in the future. But little research has been done on vaccine acceptance among nursing students.DesignA cross-sectional survey of nursing students was conducted via online questionnaires in March 2021.MethodsDescriptive statistics, independent sample t tests/one-way ANOVA (normal distribution), Mann-Whitney U tests/Kruskal-Wallis H tests (skewness distribution) and multivariate linear regression were performed.ResultsThe score rate of attitude, knowledge and vaccination willingness were 70.07%, 80.70% and 84.38% respectively. Attitude was significantly influenced by family economic conditions and whether a family member had been vaccinated. The main factors influencing knowledge were gender, grade and academic background. In terms of willingness, gender, academic background, visits to risk areas, whether family members were vaccinated, and whether they had side effects were significant influencing factors.ConclusionsThe vaccine acceptance of nursing students was fair. Greater focus needed to be placed on the males, those of younger age, with a science background, and having low grades, as well as on students whose family members had not received the COVID-19 vaccine or had side effects from the vaccine. Targeted intervention strategies were recommended to improve vaccination rates.
External Validation Of A Novel Signature Of Illness In Continuous Cardiorespiratory Monitoring To Detect Early Respiratory Deterioration Of ICU Patients
Authors: Callcut Rachael A. , Xu Yuan , Moorman J Randall , Tsai Christina , Villaroman Andrea , Robles Anamaria J. , Lake Douglas E , Hu Xiao , Clark Matthew T 
Published: May 2021

ABSTRACTThe goal of predictive analytics monitoring is the early detection of patients at high risk of subacute potentially catastrophic illnesses. An excellent example of a targeted illness is respiratory failure leading to urgent unplanned intubation, where early detection might lead to interventions that improve patient outcomes. Previously, we identified signatures of this illness in the continuous cardiorespiratory monitoring data of Intensive Care Unit patients and devised algorithms to identify patients at rising risk. Here, we externally validated three logistic regression models to estimate the risk of emergency intubation developed in Medical and Surgical ICUs at the University of Virginia. We calculated the model outputs for more than 8000 patients in the University of California – San Francisco ICUs, 240 of whom underwent emergency intubation as determined by individual chart review. We found that the AUC of the models exceeded 0.75 in this external population, and that the risk rose appreciably over the 12 hours before the event. We conclude that there are generalizable physiological signatures of impending respiratory failure in the continuous cardiorespiratory monitoring data.
CBX4 regulates long-form thymic stromal lymphopoietin-mediated airway inflammation through SUMOylation in HDM-induced asthma
Authors: Liang Shixiu , Zhou Zicong , Zhou Zili , Liu Jieyi , Dong Hangming , Zou Fei , Zhao Haijin , Yu Changhui , Cai Shaoxi 
Published: May 2021

AbstractRationaleThymic stromal lymphopoietin (TSLP) is present in two distinct isoforms, short-form (sfTSLP) and long-form (lfTSLP). lfTSLP promotes inflammation while sfTSLP inhibits inflammation in allergic asthma. However, little is known about the regulation of lfTSLP and sfTSLP during allergic attack in asthma airway epithelium.Methods and ResultsHere, we report that SUMOylation was enhanced in HDM-induced allergic asthma airway epithelium. Inhibition of SUMOylation significantly alleviated airway Th2 inflammation and lfTSLP expression. Mechanistically, CBX4, a SUMOylation E3 ligase, enhanced lfTSLP, but not sfTSLP, mRNA translation through the RNA binding protein, MEX-3B. MEX-3B promoted lfTSLP translation through binding of its KH domains to the lfTSLP mRNA. Furthermore, CBX4 regulated MEX-3B transcription in HBE through enhancing SUMOylation levels of the transcription factor, TFII-I.ConclusionWe demonstrate an important mechanism whereby CBX4 promotes MEX-3B transcription through enhancing TFII-I SUMOylation, and MEX-3B enhances the expression of lfTSLP through binding to the lfTSLP mRNA and promoting its translation. Our findings uncover a novel target of CBX4 for therapeutic agents to lfTSLP-mediated asthma.
Evolutionary Inference Predicts Novel ACE2 Protein Interactions Relevant to COVID-19 Pathologies
Authors: Varela Austin A. , Cheng Sammy , Werren John H. 
Published: May 2021

AbstractAngiotensin-converting enzyme 2 (ACE2) is the cell receptor that the coronavirus SARS-CoV-2 binds to and uses to enter and infect human cells. COVID-19, the pandemic disease caused by the coronavirus, involves diverse pathologies beyond those of a respiratory disease, including micro-thrombosis (micro-clotting), cytokine storms, and inflammatory responses affecting many organ systems. Longer-term chronic illness can persist for many months, often well after the pathogen is no longer detected. A better understanding of the proteins that ACE2 interacts with can reveal information relevant to these disease manifestations and possible avenues for treatment. We have undertaken an approach to predict candidate ACE2 interacting proteins which uses evolutionary inference to identify a set of mammalian proteins that “coevolve” with ACE2. The approach, called evolutionary rate correlation (ERC), detects proteins that show highly correlated evolutionary rates during mammalian evolution. Such proteins are candidates for biological interactions with the ACE2 receptor. The approach has uncovered a number of key ACE2 protein interactions of potential relevance to COVID-19 pathologies. Some proteins have previously been reported to be associated with severe COVID-19, but are not currently known to interact directly with ACE2, while additional predicted novel ACE2 interactors are of potential relevance to the disease. Using reciprocal rankings of protein ERCs, we have identified strongly interconnected ACE2 associated protein networks relevant to COVID-19 pathologies. ACE2 has clear connections to coagulation pathway proteins, such as Coagulation Factor V and fibrinogen components FGG, FGB, and FGA, the latter possibly mediated through ACE2 connections to Clusterin (which clears misfolded extracellular proteins) and GPR141 (whose functions are relatively unknown). ACE2 also connects to proteins involved in cytokine signaling and immune response (e.g. IFNAR2, XCR1, and TLR8), and to Androgen Receptor (AR). The ERC prescreening approach has also elucidated possible functions for previously uncharacterized proteins and possible new functions for well-characterized ones. Suggestions are made for the validation of ERC predicted ACE2 protein interactions. We propose that ACE2 has novel protein interactions that are disrupted during SARS-CoV-2 infection, contributing to the spectrum of COVID-19 pathologies.
Immunogenic Amino Acid Motifs and Linear Epitopes of COVID-19 mRNA Vaccines
Authors: Wisnewski Adam V , Redlich Carrie A , Kamath Kathy , Abad Queenie-Ann , Smith Richard F , Fazen Louis , Santiago Romero , Liu Jian , Luna Julian Campillo , Martinez Brian , Baum-Jones Elizabeth , Waitz Rebecca , Haynes Winston A , Shon John C 
Published: May 2021

ABSTRACTReverse vaccinology is an evolving approach for improving vaccine effectiveness and minimizing adverse responses by limiting immunizations to critical epitopes. Towards this goal, we sought to identify immunogenic amino acid motifs and linear epitopes of the SARS-CoV-2 spike protein that elicit IgG in COVID-19 mRNA vaccine recipients. Paired pre/post vaccination samples from N=20 healthy adults, and post-vaccine samples from an additional N=13 individuals were used to immunoprecipitate IgG targets expressed by a bacterial display random peptide library, and preferentially recognized peptides were mapped to the spike primary sequence. The data identify several distinct amino acid motifs recognized by vaccine-induced IgG, a subset of those targeted by IgG from natural infection, which may mimic 3-dimensional conformation (mimotopes). Dominant linear epitopes were identified in the C-terminal domains of the S1 and S2 subunits (aa 558-569, 627-638, and 1148-1159) which have been previously associated with SARS-CoV-2 neutralization in vitro and demonstrate identity to bat coronavirus and SARS-CoV, but limited homology to non-pathogenic human coronavirus. The identified COVID-19 mRNA vaccine epitopes should be considered in the context of variants, immune escape and vaccine and therapy design moving forward.
Fear among Syrians: a Proposed Cutoff Score and Validation of the Arabic Fear of COVID-19 Scale- A National Survey
Authors: Mohsen Fatema , Bakkar Batoul , Alsrouji Salma Khadem , Abbas Esraa , Najjar Alma , Marrawi Marah , Latifeh Youssef 
Published: May 2021

AbstractCOVID-19 pandemic has led to psychological health issues one of which is fear. This study validates the Arabic version of the fear of COVID-19 scale and suggests a new cutoff score to measure fear of COVID-19 among the Syrian Population. A total of 3989 participants filled an online survey consisting of socio-demographic information, the fear of COVID-19 scale, the patient health questionnaire 9-item, and the generalized anxiety disorder 7-item. Receiver operating characteristic analysis was used to define cutoff scores for the fear of COVID-19 scale in relation to generalized anxiety disorder 7-item and the patient health questionnaire 9-item. The Cronbach α value of the Arabic fear of COVID-19 scale was 0.896, revealing good stability and internal consistency. The inter-item correlations were between [0.420 – 0.868] and the corrected item-total correlations were between [0.614 – 0.768]. A cutoff point of 17.5 was deduced from analysis. According to the deduced cutoff point, 2111(52.9%) were classified as cases with extreme fear. This cutoff score deduced from this study can be used for screening purposes to identify individuals that may be most vulnerable towards developing extreme fear of COVID-19. Therefore, early preventive and supportive measures can then be delivered.
Engagement with daily testing instead of self-isolating in contacts of confirmed cases of SARS-CoV-2: A qualitative analysis
Authors: Denford Sarah , Martin Alex F. , Love Nicola , Ready Derren , Oliver Isabel , Amlôt Richard , Yardley Lucy , Rubin G. James 
Published: May 2021

AbstractIntroductionIn December 2020 and January 2021 Public Health England (PHE) with NHS Test and Trace conducted a study to explore the feasibility and acceptability of daily testing as an alternative to self-isolation following close contact with a confirmed COVID-19 case. This qualitative paper aims to identify factors influencing uptake among those offered daily testing, and the subsequent impact on behaviour.MethodsWe conducted in-depth interviews with 52 participants who had taken part in the feasibility study. Participants were asked about their experiences of daily testing or self-isolating, their reasons for choosing to test or isolate, and their behaviour during the study period. Data were analysed using inductive thematic analysis.ResultsResults are presented under two main headings: 1) factors influencing acceptance of testing and 2) impact of test results. Participants appeared highly motivated to engage in behaviours that would protect others from the virus. Factors influencing the decision to accept testing included 1) needing to avoid self-isolation 2) concerns about test sensitivity and 3) perceived benefits of detecting infection. Participants who were taking tests reported:1) positive consequences following confirmation of COVID status 2) engaging in essential activities 3) uncertainty and 4) self-isolating whilst testing.ConclusionsThis study has identified a range of factors that appear to influence the decision to engage in daily testing or to self-isolate following close contact with a positive case, many of which could be addressed by clear communications. Covid-19 infection rates and government restrictions influenced experiences, and so further research is needed to explore perceptions of daily testing and behaviour following close contact with a positive case among a wider range of individuals, in the context of lower rates of COVID-19, few government restrictions on general population behaviour and more widespread testing.
Multiple drug arrests reported to the Maine Diversion Alert Program more frequently involved carisoprodol, amitriptyline, or quetiapine
Authors: Siddiqui Maaz , Piserchio John P. , Patel Misha , Park Jino , Foster Michelle , Desrosiers Clare E. , Herbert John , McCall Kenneth L. , Piper Brian J. 
Published: May 2021

ABSTRACTBackgroundMuch of the blame of the increasing death toll by drug overdoses has justifiably been attributed to the United States’ current opioid epidemic. However, nearly 80% of overdoses related to opioids involve another drug substance or alcohol. The objective of this study was to elucidate overrepresentation of drugs in polypharmacy arrests by identifying drugs that were more likely to be found in conjunction with other substances, using the drug arrest data provided by the Maine Diversion Alert Program (DAP).MethodsSingle drug arrest and multiple drug arrest totals reported to the DAP were examined. Drugs involved in the arrests were classified by Drug Enforcement Administration Schedule (I-V or non-controlled prescription) and categorized into five drug families: hallucinogens, opioids, sedatives, stimulants, and miscellaneous. Multiple drug arrest totals were compared to single drug arrest totals to create a Multiple-to-Single Ratio (MSR) specific to each drug family and each drug. Chi-square approximations without Yates correction and two-tailed P values were used to determine statistical significance through GraphPad’s 2×2 contingency tables.ResultsOver three-fifths (63.8%) of all arrests involved a single drug. Opioids accounted for over-half (53.5%) of single arrests, followed by stimulants (27.7%) and hallucinogens (7.7%). Similarly, nearly two-fifths (39.6%) of multiple arrests were opioids, followed by stimulants (30.8%) and miscellaneous (13.0%). Miscellaneous family drugs were recorded with the highest Multiple-to-Single Ratio (1.51), followed by sedatives (1.09), stimulants (0.63), opioids (0.42), and hallucinogens (0.35). Carisoprodol (8.80), amitriptyline (6.34), and quetiapine (4.69) had the highest MSR values and therefore were the three most overrepresented drugs in polysubstance arrests.ConclusionThe abuse of opioids, both alone and in conjunction with another drug, deserves continued surveillance in public health. In addition, common prescription drugs with lesser-known misuse potential, especially carisoprodol, amitriptyline, and quetiapine, require more attention by medical providers for their ability to enhance the effects of other drugs or to compensate for undesired drug effects.
Magnetic Field Mapping and Correction for Moving OP-MEG
Authors: Mellor Stephanie , Tierney Tim M. , O’Neill George C. , Alexander Nicholas , Seymour Robert A. , Holmes Niall , López José D. , Hill Ryan M. , Boto Elena , Rea Molly , Roberts Gillian , Leggett James , Bowtell Richard , Brookes Matthew J. , Maguire Eleanor A. , Walker Matthew C. , Barnes Gareth R. 
Published: May 2021

AbstractBackgroundOptically pumped magnetometers (OPMs) have made moving, wearable magnetoencephalography (MEG) possible. The OPMs typically used for MEG require a low background magnetic field to operate, which is achieved using both passive and active magnetic shielding. However, the background magnetic field is never truly zero Tesla, and so the field at each of the OPMs changes as the participant moves. This leads to position and orientation dependent changes in the measurements, which manifest as low frequency artefacts in MEG data.ObjectiveWe modelled the spatial variation in the magnetic field and used the model to predict the movement artefact found in a dataset.MethodsWe demonstrate a method for modelling this field with a triaxial magnetometer, then showed that we can use the same technique to predict the movement artefact in a real OPM-based MEG (OP-MEG) dataset.ResultsUsing an 86-channel OP-MEG system, we found that this modelling method maximally reduced the power spectral density of the data by 26.2 ± 0.6 dB at 0 Hz, when applied over 5 s non-overlapping windows.ConclusionThe magnetic field inside our state-of-the art magnetically shielded room can be well described by low-order spherical harmonic functions. We achieved a large reduction in movement noise when we applied this model to OP-MEG data.SignificanceReal-time implementation of this method could reduce passive shielding requirements for OP-MEG recording and allow the measurement of low-frequency brain activity during natural participant movement.
Variation in upstream open reading frames contributes to allelic diversity in protein abundance
Authors: Gage Joseph L. , Mali Sujina , McLoughlin Fionn , Khaipho-Burch Merritt , Monier Brandon , Bailey-Serres Julia , Vierstra Richard D. , Buckler Edward S. 
Published: May 2021

AbstractThe 5’ untranslated region (UTR) sequence of eukaryotic mRNAs may contain upstream open reading frames (uORFs), which can regulate translation of the main open reading frame (mORF). The current model of translational regulation by uORFs posits that when a ribosome scans an mRNA and encounters a uORF, translation of that uORF can prevent ribosomes from reaching the mORF and cause decreased mORF translation. In this study, we first observed that rare variants in the 5’ UTR dysregulate protein abundance. Upon further investigation, we found that rare variants near the start codon of uORFs can repress or derepress mORF translation, causing allelic changes in protein abundance. This finding holds for common variants as well, and common variants that modify uORF start codons also contribute disproportionately to metabolic and whole-plant phenotypes, suggesting that translational regulation by uORFs serves an adaptive function. These results provide evidence for the mechanisms by which natural sequence variation modulates gene expression, and ultimately, phenotype.