bluuebunny/crossref_metadata_2025_split huggingface dataset:
Side effects of Covishield vaccine among frontline healthcare workers of a tertiary health care center
Authors: Dhungana Durga , Regmi Yukta Narayan , Shrestha Deependra , Thapa Krishna , Pun Chandra Bahadur , Upadhayaya Tirthalal , Hirachan Gopi 
Published: June 2022

AbstractObjectivesCOVID disease started in the late 2019 and within a short time became a pandemic disease. With the increasing morbidity and mortality all over the world and the therapeutics not doing wonders, scientists were in the attempt to develop vaccines as a mitigating measure. With continuous efforts and developments, different vaccines were developed and rolled out gradually in different countries. Concerns were notable for occurrence of side effects. Hence this study was done to assess the side effects following Covishield vaccination in Nepal at the initial stage.MethodsThis was a cross-sectional study done via snowball sampling method among healthcare workers at a tertiary medical college hospital in Pokhara, Nepal after obtaining ethical consent from the institutional review committee of the concerned hospital. The proforma was sent via online means through different social media platforms and also printed forms were also given to the respondents. A total of 139 respondents were obtained after removing duplications. The data were entered into SPSS and analyzed using descriptive and inferential statistics. P-value ≤ 0.05 was considered statistically significant.ResultsMajority (64.7%) were female healthcare workers. More than half (52.3%) used pre-medication in an attempt to avoid the side effects of vaccine. Most (90.6%) reported at least one side effect-local or systemic to the first dose and approximately three-quarter (74.3%) reported side effect to the second dose. Common side effects were pain at injection site, muscle pain, headache, fatigue and weakness. Most of the side effects were higher with the first dose as compared to the second dose.ConclusionSide effects are common with Covishield vaccination, significantly more with the first dose as compared to the second dose. Female gender, younger age and past covid infection were associated with slightly more occurrence of side effects; however were not found to be statistically significant.
Statistical Analysis Plan for the Bedside Ultrasound Conducted in Kids with distal upper Limb fractures in the Emergency Department (BUCKLED) trial
Authors: Jones Philip M , Keijzers Gerben , Byrnes Joshua , Ware Robert S , Snelling Peter J 
Published: June 2022

AbstractBackgroundThe Bedside Ultrasound Conducted in Kids with distal upper Limb fractures in the Emergency Department (BUCKLED) trial is a multicentre, randomised, open-label, non-inferiority study comparing point-of-care ultrasound to x-ray as the initial imaging modality in children with clinically non-angulated distal forearm injuries.ObjectiveThe purpose of this document is to minimise bias by defining and making publicly available our analysis approach prior to completing the study and reviewing or analysing the trial data.MethodsWe developed a statistical analysis plan (SAP) for reporting and analysing the BUCKLED trial including our approach to expected protocol deviations, withdrawals, missing data, and loss to follow up. Study methods are described using a previously published study protocol. Broad statistical analysis principles are outlined. Primary and secondary trial outcomes are described, along with appropriate methods for statistical comparison.ResultsThis report pre-specifies the SAP for the primary outcome of upper limb function at 4 weeks, using an intention-to-treat analysis with a hypothesis of non-inferiority. Results of a per-protocol analysis will also be reported. Subgroup analyses will include diagnostic category and age category and secondary outcomes will include cost, quality of life, satisfaction, pain, adverse events, rates of imaging, Emergency Department length of stay, treatment time and diagnostic accuracy. Methods of statistical comparison are outlined.ConclusionThis report describes the SAP for the BUCKLED trial, to minimise analysis bias and ensure transparency and internal validity for the findings of this randomised controlled trial.
The association of child marriage with morbidities and mortality among children under 5 years in Afghanistan: Findings from a national survey
Authors: Dadras Omid , Hazratzai Mohammadsediq , Dadras Fateme 
Published: June 2022

AbstractBackgroundThere is still a gap in knowledge of the impact that child marriage could have on the mortality and morbidity of children in Afghanistan. This study used the data from the latest Afghanistan demographic health survey conducted in 2015 (ADHS) to address this gap and advance the current knowledge.MethodsA secondary analysis of the 2015 ADHS, including the births in the past 5 years to ever-married women aged 15-24 years old, was carried out. Logistic regression analyses were employed to examine the association of child marriage (<18y) with morbidities (diarrhea, acute respiratory infection, and fever in the last 2 weeks), mortality (neonatal, infant, child), and size at birth among the children under 5 born to women aged 15-24 years, before and after adjusting for the effect of sociodemographic and structural inequalities.ResultsApproximately two-thirds of births in the past 5 years belong to 15-24 years old mothers who married at ages <18. The majority of them were born to mothers residing in rural areas (75.67%) with no education (51.68%) from poor households (39.39%). As compared to the births to women married at ages ≥18, there was a significantly higher likelihood of neonatal mortality among births to women married at ages <18 (crude OR = 2.30, 95% CI: 1.52-3.49 & adjusted OR = 1.94, 95% CI: 1.25-3.01) and higher infant mortality among the births to the women married at ages ≤14y (crude OR = 1.94, 95% CI: 1.06-3.53). However, it disappeared for neonatal mortality after adjustment for adequacy of antenatal care (ANC) and infant mortality after adjustment for sociodemographic inequalities.ConclusionAlthough the births to women married as a child (<18) were more likely to die at an early age, this association disappeared after adjustment for the adequacy of ANC. Given the unavoidable practice of child marriage in Afghanistan, this finding emphasizes the importance of providing adequate ANC for young brides to prevent child mortality. In addition, strong global advocacy is required to empower and support young Afghan women in negotiating their reproductive and maternity rights with their partners by reducing social and gender-based inequalities.
Immunosuppression as a hub for SARS-CoV-2 mutational drift
Authors: Shapira Guy , Patalon Tal , Gazit Sivan , Shomron Noam 
Published: June 2022

AbstractNewly emerging SARS-CoV-2 variants of concern (VOCs) play a major role in the persistence of the coronavirus disease 2019 (COVID-19) pandemic. While these VOCs are characterized by extraordinary evolutionary leaps and evasion from previously acquired immunity, their origins remain mostly unknown. In this study, we paired electronic health records of individuals infected with SARS-CoV-2 to viral whole-genome sequences, to assess effects of host clinical parameters and immunity on the intra-host evolution of SARS-CoV-2. We found small, albeit significant differences in SARS-CoV-2 intra-host diversity, which depended on host parameters such as vaccination status and smoking. Viral genomes showed a significant difference in the early course of disease in only one of 31 immunosuppressed patients, a recently vaccinated woman aged in her 70s. We highlight the unusually mutated viral genome obtained from this woman, which harbored near-complete truncating of the accessory protein ORF3a. Our findings suggest only minor influence of host parameters on the SARS-CoV-2 intra-host evolutionary rate and trajectory, with even the majority of immunosuppressed persons carrying fairly unremarkable viral genomes. We hypothesize that major evolutionary steps, such as those observed in VOCs, are rare occurrences, even among immunodeficient hosts.HighlightsIntra-host viral diversity is modestly affected by host clinical parameters, such as vaccination status and smoking.The emergence and fixation of high-impact SARS-CoV-2 mutations in immunosuppressed hosts are rare, and not exclusive to patients with prolonged viral shedding.We identified a rare stop-gain mutation, leading to near-complete truncating of ORF3a, in an immunosuppressed woman recently vaccinated against COVID-19.
American Covid: An Econometric Analysis of Variants
Authors: McIntosh James 
Published: June 2022

AbstractCovid-19 time series data on new cases from the United States for the period January 20, 2020 to February 7, 2022 is analyzed using a distributed lag econometric model applied to the Wild Type, Alpha, and Delta variants to determine the relative efficacy of vaccines and previous infection induced immunity. The results from this study confirm, for the most part, what others have found using large cross section samples: vaccines are effective in dealing with all three variants, more so with Delta. Infection induced immunity is always greater than or equal that delivered by a vaccination and is largest for the Delta variant. However, in the Delta case previous non-Delta infections had no prophylactic value in preventing new Delta infections.
HEALTHCARE UTILISATION IN PATIENTS WITH LONG-TERM CONDITIONS DURING THE COVID-19 PANDEMIC: A POPULATION BASED STUDY ACROSS GREATER MANCHESTER, UK
Authors: Sammut-Powell Camilla , Williams Richard , Sperrin Matthew , Thomas Owain , Peek Niels , Grant Stuart W. 
Published: June 2022

ABSTRACTBackgroundThe COVID-19 pandemic has placed an unprecedented demand on global healthcare resources. Data on whole population healthcare utilisation (HCU) across both primary and secondary care during the COVID-19 pandemic are lacking.AimTo describe primary and secondary HCU stratified by LTCs and deprivation, during the first 19 months of COVID-19 pandemic across a large urban area in the United Kingdom.MethodsObservational HCU data between 30th-December-2019 and 1st-August-2021 were extracted from the Greater Manchester Care Record. Primary care HCU (incident prescribing and recording of healthcare information) and secondary care HCU (planned and unplanned admissions) were assessed.ResultsThe first national lockdown was associated with reductions in all primary HCU measures, ranging from 24.7% (24.0% to 25.5%) for incident prescribing to 84.9% (84.2% to 85.5%) for cholesterol monitoring. Secondary HCU also dropped significantly for planned (47% (42.9% to 51.5%)) and unplanned admissions (35.0% (28.3% to 41.6%)). Only secondary care had significant reductions in HCU during the second national lockdown. Primary HCU measures had not recovered to pre-pandemic levels by the end of the study. The secondary admission rate ratio between multi-morbid patients and those without LTCs increased during the first lockdown by a factor of 2.4 (2.0 to 2.9;p<0.001) for planned admissions and by 1.3 (1.1 to 1.5;p=0.006) for unplanned admissions. No significant changes in this ratio were observed in primary HCU. Different patterns in secondary care HCU were observed by LTC group.ConclusionMajor changes in primary and secondary HCU have been observed during the COVID-19 pandemic. Secondary HCU reduced more in those without LTCs and the ratio of utilisation between the most and least deprived increased for the majority of HCU measures. Overall primary HCU measures and secondary care HCU for some LTC groups had not returned to pre-pandemic levels by the end of the study.
Tau and α-synuclein shape microtubule organization and microtubule-dependent transport in neuronal dendrites
Authors: Rierola Marina , Trushina Nataliya I. , Monteiro-Abreu Nanci , Conze Christian , Holtmannspötter Michael , Kurre Rainer , Holzer Max , Arendt Thomas , Heinisch Jürgen J. , Brandt Roland , Bakota Lidia 
Published: June 2022

SummaryTau and α-synuclein are major players in neurodegenerative diseases, but their physiological role, particularly in dendrites, is poorly understood. Here we show that, surprisingly, lack of tau protein induces the development of a more elaborate dendritic arbor of hippocampal pyramidal cells in organotypic tissue. Using high-speed volumetric lattice light-sheet microscopy and single particle tracking, we found a more directional KIF1A-mediated transport in dendrites of Tau KO cells. Increased transport processivity correlated with longer and straighter dendritic microtubules as revealed by three-dimensional super-resolution microscopy of cultured hippocampal neurons. Unbiased mass spectrometric analysis of tissue showed highly increased expression of α-synuclein in Tau KO hippocampi. Overexpression of α-synuclein mimicked the transport characteristics observed in Tau KO cells. Our data indicate that tau and α-synuclein shape microtubule-dependent transport in neuronal dendrites, thereby promoting dendritic arborization during maturation. Furthermore, the data demonstrate that transport efficiency and length and straightness of microtubules are correlated.
Saturation genome editing of DDX3X clarifies pathogenicity of germline and somatic variation
Authors: Radford E.J. , Tan H.K. , Andersson M.H.L. , Stephenson J.D , Gardner E.J. , Ironfield H. , Waters A.J. , Gitterman D. , Lindsay S. , Abascal F. , Martincorena I. , Kolesnik A. , Ng-Cordell E. , Firth H.V. , Baker K. , Perry J.R.B. , Adams D.J. , Gerety S.S. , Hurles M.E. 
Published: June 2022

AbstractLoss-of-function ofDDX3Xis a leading cause of neurodevelopmental disorders (NDD) in females.DDX3Xis also a somatically mutated cancer driver gene proposed to have tumour promoting and suppressing effects. We performed saturation genome editing ofDDX3X,testingin vitrothe functional impact of 12,776 nucleotide variants. We identified 3,432 functionally abnormal variants, in three distinct classes. We trained a machine learning classifier to identify functionally abnormal variants of NDD-relevance. This classifier has at least 97% sensitivity and 99% specificity to detect variants pathogenic for NDD, substantially out-performingin silicopredictors, and resolving up to 93% of variants of uncertain significance. Moreover, functionally-abnormal variants could account for almost all of the excess nonsynonymousDDX3Xsomatic mutations seen inDDX3X- driven cancers. Systematic maps of variant effects generated in experimentally tractable cell types have the potential to transform clinical interpretation of both germline and somatic disease-associated variation.
Synaptic proteomics reveal distinct molecular signatures of cognitive change andC9ORF72repeat expansion in the human ALS cortex
Authors: Laszlo Zsofia I. , Hindley Nicole , Sanchez Avila Anna , Kline Rachel A. , Eaton Samantha L. , Lamont Douglas J. , Smith Colin , Spires-Jones Tara L. , Wishart Thomas M. , Henstridge Christopher M. 
Published: June 2022

AbstractThe two major hypotheses of Amyotrophic Lateral Sclerosis (ALS) pathogenesis (dying-forward and dying-back) have synapses at their core. Furthermore, increasing evidence suggests synaptic dysfunction is a central and possibly triggering factor in ALS. Despite this, we still know very little about the molecular profile of an ALS synapse. To address this gap, we designed a synaptic proteomics experiment to perform an unbiased assessment of the synaptic proteome in the ALS brain. We isolated synaptoneurosomes from fresh-frozen post-mortem human cortex (11 controls and 18 ALS) and stratified the ALS group based on cognitive profile (Edinburgh Cognitive and Behavioural ALS Screen (ECAS score)) and presence of aC9ORF72hexanucleotide repeat expansion (C9ORF72-RE). This allowed us to assess regional differences and the impact of phenotype and genotype on the synaptic proteome, using Tandem Mass Tagging-based proteomics. We identified over 6000 proteins in our synaptoneurosomes and using robust bioinformatics analysis we validated the strong enrichment of synapses. We found more than 30 ALS-associated proteins at the synapse, including TDP-43, FUS, SOD1 and C9ORF72. We identified almost 500 proteins with altered expression levels in ALS synapses, with region-specific changes highlighting proteins and pathways with intriguing links to neurophysiology and pathology. Stratifying the ALS cohort by cognitive status revealed almost 150 specific alterations in cognitively impaired ALS synapses, highlighting novel synaptic proteins that may underlie the synaptic vulnerability in these patients. Stratifying byC9ORF72-RE status revealed 330 protein alterations in theC9ORF72-RE+ve group, with KEGG pathway analysis highlighting strong enrichment for postsynaptic dysfunction, related to glutamatergic receptor signalling. We have validated some of these changes by western blot and at a single synapse level using array tomography imaging. In summary, we have generated the first unbiased map of the human ALS synaptic proteome, revealing novel insight into this key compartment in ALS pathophysiology and highlighting the influence of cognitive decline andC9ORF72-RE on synaptic composition.
Exploring the knowledge and acceptance of reputed Authorship Criteria: A Pilot Study among medical researchers in India
Authors: Bansal Bhavik 
Published: June 2022

AbstractObjectivesTo determine knowledge and acceptance of authorship criteria among residents, PhD scholars and faculty involved in medical research in India.DesignA cross sectional survey was performed via Google forms (a web based platform).ResultsA total of 117 participants responded to the survey, of whom 66 (56%) were faculty/professors, 23 (20%) residents and 28 (24%) PhD scholars. 33% respondents had faced conflicts with their guide, 58% respondents have offered honorary authorship sometime in their careers. Only half of the respondents were aware of the ICMJE guidelines for authorship.ConclusionsGift Authorship and ‘pressure to publish’ are largely prevalent in bio medical research in India. Journals requiring author-contribution declarations, overlooking the number of publications as the sole source of offering academic promotions among others are possible solutions to curb this problem.
Radiographic Assessment of Lung Edema (RALE) Scores are Highly Reproducible and Prognostic of Clinical Outcomes for Inpatients with COVID-19
Authors: Al-Yousif Nameer , Komanduri Saketram , Qurashi Hafiz , Korzhuk Anatoliy , Lawal Halimat O. , Abourizk Nicholas , Schaefer Caitlin , Mitchell Kevin J. , Dietz Catherine M. , Hughes Ellen K. , Brandt Clara S. , Fitzgerald Georgia M. , Joyce Robin , Chaudhry Asmaa S. , Kotok Daniel , Rivera Jose D. , Kim Andrew I. , Shettigar Shruti , Lavina Allen , Girard Christine E. , Gillenwater Samantha R. , Hadeh Anas , Bain William , Shah Faraaz A. , Bittner Matthew , Lu Michael , Prendergast Niall , Evankovich John , Golubykh Konstantin , Ramesh Navitha , Jacobs Jana J. , Kessinger Cathy , Methé Barbara , Lee Janet S. , Morris Alison , McVerry Bryan J. , Kitsios Georgios D. 
Published: June 2022

AbstractINTRODUCTIONChest imaging is necessary for diagnosis of COVID-19 pneumonia, but current risk stratification tools do not consider radiographic severity. We quantified radiographic heterogeneity among inpatients with COVID-19 with the Radiographic Assessment of Lung Edema (RALE) score on Chest X-rays (CXRs).METHODSWe performed independent RALE scoring by ≥2 reviewers on baseline CXRs from 425 inpatients with COVID-19 (discovery dataset), we recorded clinical variables and outcomes, and measured plasma host-response biomarkers and SARS-CoV-2 RNA load from subjects with available biospecimens.RESULTSWe found excellent inter-rater agreement for RALE scores (intraclass correlation co-efficient=0.93). The required level of respiratory support at the time of baseline CXRs (supplemental oxygen or non-invasive ventilation [n=178]; invasive-mechanical ventilation [n=234], extracorporeal membrane oxygenation [n=13]) was significantly associated with RALE scores (median [interquartile range]: 20.0[14.1-26.7], 26.0[20.5-34.0] and 44.5[34.5-48.0], respectively, p<0.0001). Among invasively-ventilated patients, RALE scores were significantly associated with worse respiratory mechanics (plateau and driving pressure) and gas exchange metrics (PaO2/FiO2 and ventilatory ratio), as well as higher plasma levels of IL-6, sRAGE and TNFR1 levels (p<0.05). RALE scores were independently associated with 90-day survival in a multivariate Cox proportional hazards model (adjusted hazard ratio 1.04[1.02-1.07], p=0.002). We validated significant associations of RALE scores with baseline severity and mortality in an independent dataset of 415 COVID-19 inpatients.CONCLUSIONReproducible assessment of radiographic severity revealed significant associations with clinical and physiologic severity, host-response biomarkers and clinical outcome in COVID-19 pneumonia. Incorporation of radiographic severity assessments may provide prognostic and treatment allocation guidance in patients hospitalized with COVID-19.
Disentangling the common genetic architecture and causality of rheumatoid arthritis and systemic lupus erythematosus with COVID-19 outcomes: genome-wide cross trait analysis and bi-directional Mendelian randomization study
Authors: Yao Minhao , Huang Xin , Guo Yunshan , Zhao Jie V. , Liu Zhonghua 
Published: June 2022

AbstractCOVID-19 may cause a dysregulation of the immune system and has complex relationships with multiple autoimmune diseases, including rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). However, little is known about their common genetic architecture. We analysed summary-level genetic data from the latest COVID-19 host genetics consortium and consortia on RA and SLE to examine the shared genetic etiology and causal relationship between COVID-19 and RA/SLE. The cross-trait meta-analysis identified 46, 47, and 19 shared genetic loci for severe COVID-19, COVID-19 hospitalization, and SARS-CoV-2 infection with RA, and 19, 24, and 11 shared loci with SLE, respectively. Shared genes were significantly enriched in the spleen, lung, whole blood, and small intestine, and involved in immune function, inflammation and coagulation process. Co-localization analysis identified eight shared loci in TYK2, IKZF3, COL11A2, PSORS1C1, MANEAL and COG6 genes for COVID-19 with RA, and four in CRHR1, FUT2 and NXPE3 genes for COVID-19 with SLE. Bi-directional Mendelian randomization analysis suggested RA is associated with a higher risk of COVID-19 hospitalization, and COVID-19 is not related to RA or SLE. Our novel findings improved the understanding of the common genetic aetiology shared by COVID-19, RA and SLE, and suggested an increased risk of COVID-19 hospitalization in people with higher genetic liability to RA.