bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prospective, Randomized, Parallel-Group, Open-Label Study to Evaluate the Efficacy and Safety of IMU-838, in Combination with Oseltamivir, in Adults with Coronavirus-19 – The IONIC Trial Protocol
Authors: Sharma Kavi , Berry Lisa , Vryonis Evangelos , Ali Asad , Lara Beatriz , Noufaily Angela , Parsons Nick , Bradley Christopher James , Haley Becky , Maria Tabuso , Arasaradnam Ramesh 
Published: July 2021

ABSTRACTBackgroundGlobally there is a scarcity of effective treatments for SARS-CoV-2 infections (causing COVID 19). Repurposing existing medications may offer the best hope for treating COVID 19 patients to curb the pandemic. IMU-838 is a dihydroorotate dehydrogenase (DHODH) inhibitor, which is an effective mechanism for antiviral effects against respiratory viruses. When used synergistically with Oseltamivir, therapeutic effects have been observed against influenza and SARS-CoV-2 in rodents.(13) The IONIC trial is a randomized control trial that will investigate whether time to clinical improvement in COVID 19 patients is improved following a 14 day course of IMU-838 + Oseltamivir versus Oseltamivir alone.MethodsIONIC trial is an open label study in which participants will be randomised 1:1 in two parallel arms; the intervention arm (IMU-838 + Oseltamivir) and control arm (Oseltamivir only). The primary outcome is time-to-clinical improvement; defined as the time from randomisation to: a 2-point improvement on WHO ordinal scale; discharge from hospital, or death (whichever occurs first). The study is sponsored by UHCW NHS Trust and funded by LifeArc.DiscussionThe IONIC Protocol describes an overarching trial design to provide reliable evidence on the efficacy of IMU-838 (vidofludimus calcium) when delivered in combination with an antiviral therapy (Oseltamivir) [IONIC Intervention] for confirmed or suspected COVID-19 infection in adult patients receiving usual standard of care.Trial RegistrationThe trial was registered with EudraCT (2020-001805-21) on 09.04.2020 and ISRCTN on 23.09.2020 (ISRCTN53038326) and Clinicaltrials.gov on 17.08.2020 (NCT04516915)Strengths and LimitationsThis study is the first to recruit participants in the trial exploring the effectiveness of IMU-838 in COVID-19. In addition, we believe it is the only trial exploring the effectiveness of IMU-838 in combination with Oseltamivir (Tamiflu) in patients with moderate to severe COVID-19. However, to make the trial design flexible due to the on-going pandemic the trial is un-blinded.
Gut bacterial tyrosine decarboxylase gene abundance associates with disease duration, medication exposure, and gastrointestinal symptoms in a longitudinal cohort of Parkinson’s disease patients
Authors: van Kessel Sebastiaan P. , Auvinen Petri , Scheperjans Filip , Aidy Sahar El 
Published: July 2021

AbstractGut microbiota influences the clinical response of a wide variety of orally administered drugs. However, the underlying mechanisms by which drug-microbiota interactions occur are still obscure. Previously, we reported that tyrosine decarboxylating (TDC) bacteria may restrict the levels of levodopa reaching the circulation in patients with Parkinson’s disease (PD). We observed a significant positive association between disease duration and the abundance of the bacterial tdc-gene. The question arises whether increased exposure to anti-PD medication could affect the abundance of bacterial TDC, to ultimately impact drug efficacy. To this end, we investigated the potential association between anti-PD drug exposure and bacterial tdc-gene abundance over a time period of two years in a longitudinal cohort of PD patients and healthy controls. Our data reveal significant associations between tdc-gene abundance, anti-PD medication, and gastrointestinal symptoms and warrants further research on the effect of anti-PD medication on microbial changes and gastrointestinal-function.
Inequalities in access to healthcare by local policy model among newly arrived refugees: evidence from population-based studies in two German states
Authors: Wenner Judith , Biddle Louise , Gottlieb Nora , Bozorgmehr Kayvan 
Published: July 2021

AbstractBackgroundAccess to healthcare is restricted for newly arriving asylum seekers and refugees (ASR) in many receiving countries, which may lead to inequalities in health. In Germany, regular access and full entitlement to healthcare (equivalent to statutory health insurance, SHI) is only granted after a waiting time of 18 months. During this time of restricted entitlements, local authorities implement different access models to regulate asylum seekers’ access to healthcare: the electronic health card (EHC) or the healthcare voucher (HV). This paper examines inequalities in access to healthcare by comparing healthcare utilization by ASR under the terms of different local models (i.e., regular access equivalent to SHI, EHC, and HV).MethodsWe used data from three population-based, cross-sectional surveys among newly arrived ASR (N=863) and analyzed six outcome measures: specialist and general practitioner (GP) utilization, unmet needs for specialist and GP services, emergency department use and avoidable hospitalization. Using logistic regression, we calculated odds ratios (OR) and 95% confidence intervals for all outcome measures, while considering need by adjusting for socio-demographic characteristics and health-related covariates.ResultsCompared to ASR with regular access, ASR under the HV model showed lower needs-adjusted odds of specialist utilization (OR=0.41 [0.24-0.66]) and a tendency towards lower GP (OR=0.61 [0.33-1.16]) and emergency department utilization (OR=0.74 [0.48-1.14]). ASR under the EHC model showed a tendency toward higher specialist unmet needs (OR= 1.89 [0.98-3.64]) and avoidable hospitalizations (OR=1.69 [0.87-3.30]) compared to ASR with regular access. A comparison between EHC and HV showed higher odds for specialist utilization under the EHC model as compared to the HV model (OR=2.39 [1.03-5.52]).ConclusionASR using the HV are disadvantaged in their access to healthcare compared to ASR having either an EHC or regular access. Given equal need, they use specialist (and partly also GP) services less. The identified inequalities constitute inequities in access to healthcare that could be reduced by policy change from HV to the EHC model during the initial 18 months waiting time, or by granting ASR regular healthcare access upon arrival. Minor differences in unmet needs, emergency department use and avoidable hospitalization between the models deserve further exploration in future studies.
Child Suicide Rates During the COVID-19 pandemic in England
Authors: Odd David , Williams Tom , Appleby Louis , Gunnell David , Luyt Karen 
Published: July 2021

AbstractBackgroundThere is concern about the impact of COVID-19, and the control measures to prevent the spread, on children’s mental health. The aim of this work was to identify if there had been a rise of childhood suicide during the COVID pandemic; using data from England’s National Child Mortality Database (NCMD).MethodChild suicide rates between April to December 2020 were compared with those in 2019 using negative binomial regression models, and characteristics compared. In a subset (1st January to 17th May 2020) further characteristics and possible contributing factors were obtained.ResultsA total of 193 likely childhood deaths by suicide were reported. There was no evidence overall suicide deaths were higher in 2020 than 2019 (RR 1.09 (0.80-1.48), p=0.584) but weak evidence that the rate in the first lockdown period (April to May 2020) was higher than the corresponding period in 2019 (RR 1.56 (0.86-2.81), p=0.144). Characteristics of individuals were similar between periods. Restriction to education and other activities, disruption to care and support services, tensions at home and isolation appeared to be contributing factors.LimitationsAs child suicides are fortunately rare, the analysis is based on small numbers of deaths with limited statistical power to detect anything but major increases in incidence.ConclusionWe found no consistent evidence that child suicide deaths increased during the COVID-19 pandemic although there was a concerning signal they may have increased during the first UK lockdown. A similar peak was not seen during the following months, or the second lockdown.
Vaccination with BNT162b2 reduces transmission of SARS-CoV-2 to household contacts in Israel
Authors: Prunas Ottavia , Warren Joshua L. , Crawford Forrest W. , Gazit Sivan , Patalon Tal , Weinberger Daniel M. , Pitzer Virginia E. 
Published: July 2021

AbstractThe individual-level effectiveness of vaccines against clinical disease caused by SARS-CoV-2 is well-established. However, few studies have directly examined the effect of COVID-19 vaccines on transmission. We quantified the effectiveness of vaccination with BNT162b2 (Pfizer-BioNTech mRNA-based vaccine) against household transmission of SARS-CoV-2 in Israel. We fit two time-to-event models – a mechanistic transmission model and a regression model – to estimate vaccine effectiveness against susceptibility to infection and infectiousness given infection in household settings. Vaccine effectiveness against susceptibility to infection was 80-88%. For breakthrough infections among vaccinated individuals, the vaccine effectiveness against infectiousness was 41-79%. The overall vaccine effectiveness against transmission was 88.5%. Vaccination provides substantial protection against susceptibility to infection and slightly lower protection against infectiousness given infection, thereby reducing transmission of SARS-CoV-2 to household contacts.One-Sentence SummaryVaccination reduced both the rate of infection with SARS-CoV-2 and transmission to household contacts in Israel.
Epidemiology and Clinical Characteristics in Individuals with Confirmed SARS-CoV-2 Infection During the Early COVID-19 Pandemic in Saudi Arabia
Authors: Alhamlan Fatimah S. , Almaghrabi Reem S. , Devol Edward B. , Alotaibi Anwar B. , Alageel Saleh M. , Obeid Dalia A. , Alraddadi Basem M. , Althawadi Sahar I. , Mutabagani Maysoon S. , Al-Qahtani Ahmed A. 
Published: July 2021

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the catastrophic coronavirus disease 2019 (COVID-19) global pandemic. This study aimed to provide epidemiologic and clinical characteristics of patients with confirmed COVID-19 in Saudi Arabia and to determine whether characteristic profiles differ between patients who are symptomatic vs. asymptomatic for the disease. The first 492 consecutive patients diagnosed with SARS-CoV-2 infection at King Faisal Specialist Hospital and Research Centre in Saudi Arabia between March and September 2020 were included in this study. An electronic case report form developed using REDCap was used to collect data for each patient, including demographic characteristics, virus exposure (travel history, and human and animal contact), vaccination history, comorbidities, signs and symptoms, laboratory and radiographic reports, cardiac workup, medications, treatment regimens, and patient outcome. This patient cohort was 54% male, with 20.4% aged more than 60 years, 19.9% aged 31 to 40 years, and 17% aged 41 to 50 years. Most patients (79.2%) were symptomatic. Variables that significantly differed between symptomatic and asymptomatic patients were age, blood oxygen saturation percentage, hemoglobin level, lymphocyte count, neutrophil to lymphocyte (NTL) ratio, alanine aminotransferase (ALT) level, and aspartate aminotransferase (AST) level. Asymptomatic patients were mostly younger, with lower body mass index and ALT and AST levels but higher lymphocyte counts, NTL ratio, and CD4, CD8, natural killer cell, IgG, and IgM levels. The median incubation period reported for this cohort was 16 day, with upper and lower 95% quartiles of 27 and 10 days, respectively. Factors associated with increased risk of mortality were age (older than 42 years) and comorbidities, including specifically diabetes mellitus and hypertension. Patients who were not given an antiviral regimen were associated with better prognosis than patients who received an antiviral regimen (HR, 0.07; 95% CI, 0.011-0.25). Similar to countries worldwide, Saudi Arabia has explored treatment options to save the lives of patients during the COVID-19 pandemic. Our analyses will inform clinicians as well as policy makers to adopt the best strategies for SARS-CoV-2 infection management and treatment options.
Epidemiology of Atrial Fibrillation in theAll of UsResearch Program
Authors: Alonso Alvaro , Alam Aniqa B. , Kamel Hooman , Subbian Vignesh , Qian Jun , Boerwinkle Eric , Cicek Mine , Clark Cheryl R. , Cohn Elizabeth G. , Gebo Kelly A. , Loperena-Cortes Roxana , Mayo Kelsey R. , Mockrin Stephen , Ohno-Machado Lucila , Schully Sheri D. , Ramirez Andrea H. , Greenland Philip 
Published: July 2021

ABSTRACTBackgroundThe prevalence, incidence and risk factors of atrial fibrillation (AF) in a large, geographically and ethnically diverse cohort in the United States have not been fully described.MethodsWe analyzed data from 173,099 participants of theAll of UsResearch Program recruited in the period 2017-2019, with 92,318 of them having electronic health records (EHR) data available, and 35,483 having completed a medical history survey. Presence of AF at baseline was identified from self-report and EHR records. Incident AF was obtained from EHR. Demographic, anthropometric and clinical risk factors were obtained from questionnaires, baseline physical measurements and EHR.ResultsAt enrollment, mean age was 52 years old (range 18-89). Females and males accounted for 61% and 39% respectively. Non-Hispanic Whites accounted for 67% of participants, with non-Hispanic Blacks, non-Hispanic Asians and Hispanics accounting for 26%, 4% and 3% of participants, respectively. Among 92,318 participants with available EHR data, 3,885 (4.2%) had AF at the time of study enrollment, while the corresponding figure among 35,483 with medical history data was 2,084 (5.9%). During a median follow-up of 16 months, 354 new cases of AF were identified among 88,433 eligible participants. Individuals who were older, male, non-Hispanic white, had higher body mass index, or a prior history of heart failure or coronary heart disease had higher prevalence and incidence of AF.ConclusionThe epidemiology of AF in theAll of UsResearch Program is similar to that reported in smaller studies with careful phenotyping, highlighting the value of this new resource for the study of AF and, potentially, other cardiovascular diseases.
Digitizing ECG image: new fully automated method and open-source software code
Authors: Fortune Julian D. , Coppa Natalie E. , Haq Kazi T. , Patel Hetal , Tereshchenko Larisa G. 
Published: July 2021

AbstractBackgroundWe aimed to develop and validate an automated, open-source code ECG-digitizing tool and assess agreements of ECG measurements across three types of median beats, comprised of digitally recorded, simultaneous and asynchronous ECG leads and digitized asynchronous ECG leads.MethodsWe used the data of clinical studies participants (n=230; mean age 30±15 y; 25% female; 52% had the cardiovascular disease) with available both digitally recorded and printed on paper and then scanned ECGs, split into development (n=150) and validation (n=80) datasets. The agreement between ECG and VCG measurements on the digitally recorded time-coherent median beat, representative asynchronous digitized, and digitally recorded beats was assessed by Bland-Altman analysis.ResultsAgreement between digitally recorded and digitized representative beat was high [area spatial ventricular gradient (SVG) elevation bias 2.5(95% limits of agreement [LOA] -7.9-13.0)°; precision 96.8%; inter-class correlation [ICC] 0.988; Lin’s concordance coefficient ρc0.97(95% confidence interval [CI] 0.95-0.98)]. Agreement between digitally recorded asynchronous and time-coherent median beats was moderate for area-based VCG metrics (spatial QRS-T angle bias 1.4(95%LOA -33.2-30.3)°; precision 94.8%; ICC 0.95; Lin’s concordance coefficient ρc0.90(95%CI 0.82-0.95)], but poor for peak-based VCG metrics of global electrical heterogeneity.ConclusionsWe developed and validated an open-source software tool for paper-ECG digitization. Asynchronous ECG leads are the primary source of disagreement in measurements on digitally recorded and digitized ECGs.
The minor allele of the CREBRF rs373863828 p.R457Q coding variant is associated with reduced levels of myostatin in males: Implications for body composition
Authors: Lee Kate , Vakili Sanaz , Burden Hannah J. , Adams Shannon , Smith Greg C. , Kulatea Braydon , Wright-McNaughton Morag , Sword Danielle , Watene-O’Sullivan Conor , Atiola Robert D. , Paul Ryan G. , Plank Lindsay D. , Wilcox Phillip , Kallingappa Prasanna , Merriman Tony R. , Krebs Jeremy D. , Hall Rosemary M. , Murphy Rinki , Merry Troy L. , Shepherd Peter R. 
Published: July 2021

ABSTRACTThe minor allele (A) of the rs373863828 variant (p.Arg457Gln) in CREBRF is restricted to indigenous peoples of the Pacific islands (including New Zealand Māori and peoples of Polynesia), with a frequency up to 25% in these populations. This allele associates with a large increase in body mass index (BMI) but with significantly lower risk of type-2 diabetes (T2D). It is unclear whether the increased BMI is driven by increased adiposity or by increased lean mass. Hence, we undertook body composition analysis using DXA in 189 young men of Māori and Pacific descent living in Aotearoa New Zealand. The rs373863828 A allele was associated with a trend toward increased relative lean mass although this was not statistically significant (p=0.06). Notably though this allele was associated with significantly lower circulating levels of the muscle inhibitory hormone myostatin (p<0.05). This was further investigated in two Arg458Gln knockin mouse models on FVB/Nj and C57Bl/6j backgrounds. Supporting the human data, significant increases in relative lean mass were observed in male knockin mice. This was more significant in older mice (p<0.01) where it was associated with increased grip strength (p<0.01) and lower levels of myostatin (p <0.05). Overall these results provide new evidence that the rs373863828 A-allele is associated with a reduction of myostatin levels which likely contributes to increased lean muscle mass component of BMI, at least in males.
Mutational landscape of high-grade B-cell lymphoma with MYC-, BCL2 and/or BCL6 rearrangements characterized by whole-exome sequencing
Authors: Künstner Axel , Witte Hanno M. , Riedl Jörg , Bernard Veronica , Stölting Stephanie , Merz Hartmut , Olschewski Vito , Peter Wolfgang , Ketzer Julius , Busch Yannik , Trojok Peter , Bubnoff Nikolas von , Busch Hauke , Feller Alfred C. , Gebauer Niklas 
Published: July 2021

AbstractHigh-grade B-cell lymphoma accompanied with MYC and BCL2 and/or BCL6 rearrangements (HGBL-DH/TH) poses a cytogenetically-defined provisional entity among aggressive B-cell lymphomas that is traditionally associated with unfavorable prognosis.To better understand the mutational and molecular landscape of HGBL-DH/TH we here performed whole-exome sequencing and deep panel next-generation-sequencing (NGS) of 47 clinically annotated cases. Oncogenic drivers, mutational signatures and perturbed pathways were compared with data from follicular lymphoma (FL), diffuse large-B-cell lymphoma (DLBCL) and Burkitt lymphoma (BL).We find an accumulation of oncogenic mutations in NOTCH, IL6/JAK/STAT and NFκB signaling pathways and delineate the mutational relationship within the continuum between FL/DLBCL, HGBL-DH/TH and BL. Further, we provide evidence of a molecular divergence between BCL2 and BCL6 rearranged HGBL-DH. Beyond a significant congruency with the C3/EZB DLBCL cluster in BCL2 rearranged cases on an exome-wide level, we observe an enrichment of the SBS6 mutation signature in BCL6 rearranged cases. Differential gene set enrichment and subsequent network propagation analysis according to cytogenetically defined subgroups revealed an impairment of TP53 and MYC pathway signaling in BCL2 rearranged cases, whereas BCL6 rearranged cases lacked this enrichment, but instead exhibited showed impairment of E2F targets. Intriguingly, HGBL-TH displayed intermediate mutational features in all three aspects.This study elucidates a recurrent pattern of mutational events driving FL into MYC-driven BCL2 rearranged HGBL, unveiling the mutational pathogenesis of this provisional entity. Through this refinement of the molecular taxonomy for aggressive, germinal-center derived B-cell lymphomas, this calls into question the current WHO classification system, especially regarding the status of MYC/BCL6 rearranged HGBL.
Fifty Ways to Tag your Pubtypes: Multi-Tagger, a Set of Probabilistic Publication Type and Study Design Taggers to Support Biomedical Indexing and Evidence-Based Medicine
Authors: Cohen Aaron M. , Schneider Jodi , Fu Yuanxi , McDonagh Marian S. , Das Prerna , Holt Arthur W. , Smalheiser Neil R. 
Published: July 2021

AbstractObjectiveIndexing articles according to publication types (PTs) and study designs can be a great aid to filtering literature for information retrieval, especially for evidence syntheses. In this study, 50 automated machine learning based probabilistic PT and study design taggers were built and applied to all articles in PubMed.Materials and MethodsPubMed article metadata from 1987-2014 were used as training data, with 2015 used for recalibration. The set of articles indexed with a particular study design MeSH term or PT tag was used as positive training sets. For each PT, the rest of the literature from the same time period was used as its negative training set. Multiple features based on each article title, abstract and metadata were used in training the models. Taggers were evaluated on PubMed articles from 2016 and 2019. A manual analysis was also performed.ResultsOf the 50 predictive models that we created, 44 of these achieved an AUC of ∼0.90 or greater, with many having performance above 0.95. Of the clinically related study designs, the best performing was SYSTEMATIC_REVIEW with an AUC of 0.998; the lowest performing was RANDOM_ALLOCATION, with an AUC of 0.823.DiscussionThis work demonstrates that is feasible to build a large set of probabilistic publication type and study design taggers with high accuracy and ranking performance. Automated tagging permits users to identify qualifying articles as soon as they are published, and allows consistent criteria to be applied across different bibliographic databases. Probabilistic predictive scores are more flexible than binary yes/no predictions, since thresholds can be tailored for specific uses such as high recall literature search, user-adjustable retrieval size, and quality improvement of manually annotated databases.ConclusionThe PT predictive probability scores for all PubMed articles are freely downloadable at http://arrowsmith.psych.uic.edu/evidence_based_medicine/mt_download.html for incorporation into user tools and workflows. Users can also perform PubMed queries at our Anne O’Tate value-added PubMed search engine http://arrowsmith.psych.uic.edu/cgi-bin/arrowsmith_uic/AnneOTate.cgi and filter retrieved articles according to both NLM-annotated and model-predicted publication types and study designs.