bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation and clinical implications of the time to a positive results of antigen testing for SARS-CoV-2
Authors: Akashi Yusaku , Kiyasu Yoshihiko , Takeuchi Yuto , Kato Daisuke , Kuwahara Miwa , Muramatsu Shino , Ueda Atsuo , Notake Shigeyuki , Nakamura Koji , Ishikawa Hiroichi , Suzuki Hiromichi 
Published: June 2021

AbstractAntigen tests for severe acute respiratory coronavirus 2 sometimes show positive lines earlier than their specified read time, although the implication of getting the results at earlier time is not well understood. This study aimed to evaluate the clinical utility of an antigen test by evaluating the time period to get positive results and by comparing the test sensitivity with that of a digital immunoassay (DIA) test.We prospectively collected additional nasopharyngeal samples from patients who had already tested positive for SARS-CoV-2 by reverse transcription PCR. The additional swab was used for an antigen test, QuickNavi™-COVID19 Ag, and the time periods to get positive results were measured. The sensitivity of QuickNavi™-COVID19 Ag was also compared with that of a DIA.In 84 of 96 (87.5%) analyzed cases, the results of QuickNavi™-COVID19 Ag were positive. The time to obtain positive results was 15.0 seconds in median (inter quartile range: 12.0-33.3, range 11-736), and was extended in samples with higher cycle thresholds (Ct) (p<0.001). Positive lines appeared within a minute in 85.7% of cases and within 5 minutes in 96.4%. The sensitivities of QuickNavi™-COVID19 Ag and the DIA were 87.5% (95% confident interval [CI]: 79.2%-93.4%) and 88.6% (95%CI: 75.4%- 96.2%), respectively. Their results were concordant in 90.9% of cases, with discrepancies present only in cases with Ct values >32.QuickNavi™-COVID19 Ag immediately showed positive results in most cases, and the time to a positive reaction may have indicated the viral load. In addition, the sensitivity of the test was comparable to the DIA.
Plasma zinc status and hyperinflammatory syndrome in hospitalized COVID-19 patients: an observational study
Authors: Verschelden Gil , Noeparast Maxim , Noparast Maryam , Lauwers Maïlis , Michel Charlotte , Cotton Frédéric , Goyvaerts Cleo , Hites Maya 
Published: June 2021

AbstractDeficiency of the element zinc is associated with cytokine releasing syndrome (CRS) and the related acute respiratory distress syndrome as well as impaired antiviral response. Similar complications associate with severe SARS-CoV-2.We conducted a prospective, single-center, observational study in a tertiary university hospital (CUB-Hopital Erasme, Brussels) to address the zinc status, the association between the plasma zinc concentration, development of CRS, and the clinical outcomes in PCR-confirmed and hospitalized COVID-19 patients. One hundred and thirty-nine eligible patients were included between May 2020 and November 2020 (median age of 65 years [IQR, 54 to 77]).Our cohort’s mean plasma zinc concentration was 56.2 µg/dL (standard deviation [SD], 14.8) compared to 75.7 µg/dL (SD = 18.9 µg/dL) in the retrospective non-COVID-19 control group (N = 1513;P<.001). Markedly, the absolute majority of patients (96%) were zinc deficient (<80 µg/dL).The mean zinc concentration was lower in patients with CRS compared to those without CRS (−5 µg/dL; 95% CI, -10.5 to 0.051;P= 0.048).Among the tested outcomes, zinc concentration is significantly correlated with only the length of hospital stay (rho = -0.19;P= 0.022), but not with mortality or morbidity. As such, our findings do not support the role of zinc as a robust prognostic marker among hospitalized COVID-19 patients who in our cohort presented high prevalence of zinc deficiency. It might be more beneficial to explore the role of zinc as a biomarker for assessing the risk of developing a tissue-damaging CRS and predicting outcomes in patients diagnosed with COVID-19 at the early stage of the disease.
Parental inflammatory bowel disease and autism in the offspring: Triangulating the evidence using four complementary study designs
Authors: Sadik Aws , Dardani Christina , Pagoni Panagiota , Havdahl Alexandra , Stergiakouli Evie , Grove Jakob , Khandaker Golam M. , Sullivan Sarah A. , Zammit Stan , Jones Hannah J. , Smith George Davey , Dalman Christina , Karlsson Håkan , Gardner Renee M. , Rai Dheeraj 
Published: June 2021

ABSTRACTImportanceEvidence linking parental diagnoses of inflammatory bowel disease (IBD) with offspring autism is inconclusive.ObjectiveTo investigate associations between parental diagnoses of IBD and offspring autism and elucidate their underlying aetiology by conducting four complementary studies.Design, Setting and Participants(1) Nationwide population-based cohort study using Swedish registers to examine associations between parental IBD diagnoses and autism diagnoses in offspring, (2) Linkage disequilibrium (LD)-score regression to estimate the genetic correlation between the phenotypes. (3) Polygenic risk score (PRS) analyses in the Avon Longitudinal Study of Parents and Children (ALSPAC) to investigate associations between maternal genetic liability to IBD and autism factor mean score in offspring. (4) Two-sample Mendelian randomization (MR) to assess bidirectional causal links between genetic liability to IBD and autism.ResultsObservational analyses provided evidence of an association between parental IBD diagnoses and offspring autism diagnosis in mutually adjusted models (maternal: OR= 1.32; 95% CI: 1.25 to 1.40; p<0.001; paternal: OR= 1.09; 95% CI: 1.02 to 1.17; p=0.012; n=2 324 227, 52.3% male). PRS analyses in ALSPAC indicated associations between maternal PRS for IBD subtypes and a measure of broad autism phenotype, autism factor mean score, in the offspring (UC: βPRS= 0.02; 95%CI: 0.003 to 0.05; p= 0.02; R2=0.06; Crohn’s: βPRS= 0.03; 95%CI: 0.01 to 0.05; p= 0.004; R2= 0.06; n= 7357, 50.3% male). MR analyses provided evidence of a potential causal effect of genetic liability for IBD, especially ulcerative colitis, on autism (ORMR= 1.03; 95%CI: 1.01 to 1.06). There was little evidence to suggest a causal effect of genetic liability to autism on risk of IBD, or a genetic correlation between the two conditions.Conclusions and relevanceTriangulating evidence from a nationwide register-based cohort study, genetic correlation, polygenic risk score analyses and MR, we found evidence of a potentially causal link between parental, particularly maternal, diagnoses and genetic liability to IBD and offspring autism. Perinatal immune system dysregulation, micronutrient malabsorption and anaemia may be implicated.
Increased risk of death in covid-19 hospital admissions during the second wave as compared to the first epidemic wave. A prospective dynamic cohort study in South London, UK
Authors: Cusinato Martina , Gates Jessica , Jajbhay Danyal , Planche Tim , Ong Yee-Ean 
Published: June 2021

ABSTRACTObjectiveTo assess whether mortality of patients admitted for covid-19 treatment was different in the second UK epidemic wave of covid-19 compared to the first wave accounting for improvements in the standard of care available and differences in the distribution of risk factors between the two waves.DesignSingle-centre, analytical, dynamic cohort study.Participants2,701 adults (≥18 years) with SARS-CoV-2 infection confirmed by polymerase chain reaction (PCR) and/or clinico-radiological diagnosis of covid-19, who required hospital admission to covid-19 specific wards, between January 2020 and March 2021. There were 884 covid-19 admissions during the first wave (before 30 Jun 2020) and 1,817 during the second wave.Outcome measuresin-hospital covid-19 associated mortality, ascertained from clinical records and Medical Certificate Cause of Death.ResultsThe crude mortality rate was 25% lower during the second wave (2.23 and 1.66 deaths per 100 person-days in first and second wave respectively). However, after accounting for age, sex, dexamethasone, oxygen requirements, symptoms at admission and Charlson Comorbidity Index, mortality hazard ratio associated with covid-19 hospital admissions was 1.62 (95% confidence interval 1.26, 2.08) times higher in the second wave compared to the first.ConclusionsAnalysis of covid-19 admissions recorded in St. Georges Hospital, shows a larger second epidemic wave, with a lower crude mortality in hospital admissions. Nevertheless, after accounting for other factors underlying risk of death for covid-19 admissions was higher in the second wave. These findings are temporally and ecologically correlated with an increased circulation of SARS-CoV-2 variant of concern 202012/1 (alpha).
A Survey of Copy Number Variants Associated with Neurodevelopmental Disorders in a Large-Scale, Multi-Ancestry Biobank
Authors: Birnbaum Rebecca , Mahjani Behrang , Loos Ruth J.F. , Sharp Andrew J. 
Published: June 2021

ABSTRACTBACKGROUNDPast clinical genetic studies have identified rare, copy number variants (CNVs) as risk factors for multiple neurodevelopmental disorders (NDD), including autism spectrum disorder and schizophrenia. However, the broad, clinical characterization of these NDD-CNVs in large population cohorts, especially of diverse ancestry, is relatively understudied. We characterized the clinical presentation of NDD-CNVs in the BioMe biobank, comprising ∼25,000 individuals across diverse ancestry, medical and neuropsychiatric clinical presentation, with a mean age of 50.3 years.METHODSIndividuals within the BioMe biobank harboring NDD-CNVs were identified using a consensus of two CNV calling algorithms, based on whole-exome sequencing and genotype array data, followed by a series of novel, in-silico clinical assessments.RESULTSThe overall prevalence of a set of 64 NDD-CNVs was calculated at ∼2.5%, with prevalence varying by locus, corroborating the presence of some relatively, highly-prevalent NDD-CNVs (i.e., 15q11.2 deletion/duplication, 2q13(NPHP1) deletion/duplication). An aggregate set of rare, NDD-CNVs were enriched for congenital disorders (OR=1.8, p-value=0.02) and major depressive disorders (OR=1.3, p-value=0.04) in multi-ancestry analyses, and major depressive-disorder in an African ancestry-stratified group (OR=1.8, p-value=0.01). In a meta-analysis of medical diagnoses (n=195 hierarchically-clustered diagnostic codes), an aggregated set of rare, NDD-CNVs was significantly associated with obstructive sleep apnea (Z-score=3.6 p=3.2×10−4). Further, an aggregated set of rare, NDD-CNVs was associated with increased body mass index (BMI) in a multi-ancestry analysis (Beta=0.14, p-value=0,04), and in Hispanic-stratified analyses (Beta=0.30, p-value=4.2×10−3). For 38 common serum laboratory tests, there was no identified association with an aggregate set of NDD-CNVs.CONCLUSIONThe current analyses elucidated clinical features of individuals harboring NDD-CNVs, in a large-scale, multi-ancestry biobank, identifying enrichments for congenital disorders and major depressive disorder, as well as identifying associations with obesity-related phenotypes, obstructive sleep apnea and increased BMI. Future recall of individuals harboring NDD-CNVs will allow for further clinical assessments beyond the electronic health records (EHR) presently analyzed, including neurocognitive and neuroimaging outcomes.
Pretransplant BK virus-specific T-cell-mediated immunity and serotype specific antibodies may have utility in identifying patients at risk for BK virus associated haemorrhagic cystitis after allogeneic HSCT
Authors: Šťastná-Marková Markéta , Hamšíková Eva , Hainz Petr , Hubáček Petr , Kroutilová Marie , Kryštofová Jitka , Ludvíková Viera , Musil Jan , Pecherková Pavla , Saláková Martina , Šroller Vojtěch , Vydra Jan , Němečková Šárka 
Published: June 2021

ABSTRACTBK polyomavirus (BKV) persists lifelong in the urinary tract with asymptomatic urinary shedding in healthy individuals. In immunocompromised persons after transplantation of hematopoietic stem cells (HSCT) the BKV high-rate replication is associated with haemorrhagic cystitis (HC) with a reported incidence of 17 %. Numerous studies of reconstitution of the immune system after HSCT have established the principal role of T cell effectors in the control of viral replication and reactivation. The value of pretransplant BKV-specific antibodies in transplanted patients for the protection from viral disease was long considered insignificant. We hypothesized that the status of BKV immunity prior to HSCT could provide evidence for the BKV tendency to reactivate and that examining the level of subtype-specific antibodies and T-cell response in individual patients could help to predict the risk of BKV reactivation and HC. Evaluation of the risk of HC in relation to pretransplant anti-BKV1,2,4 IgG levels together with clinical factors known before transplantation revealed that patients with „medium” anti-BKV IgG and significant clinical risk (SR) have a very significantly increased HC risk in comparison with the reference group of “low” anti-BKV IgG level and low clinical risk (LR) (P=0.0009). Predictive value of pretransplant BKV specific IgG was confirmed on the level of virus genotypes. Analysis of pretransplant T cell immunity to BKV antigens VP1 and LTag has shown that magnitude of IFN-gamma T cell response inversely corelated with posttransplant DNAuria. We hypothesize that the control of BKV latency by BKV specific T cells before HSCT would be one of the factors that influence BKV reactivation after HSCT. Our study has shown that prediction using a combination of clinical and immunological pretransplant risk factors can help early identification of patients who are at risk of developing BKV disease after HSCT.
Heterozygous deleterious MUTYH variants as a driver for tumorigenesis
Authors: Barreiro Rodrigo Araujo Sequeira , Sabbaga Jorge , Rossi Benedito M. , Achatz Maria Isabel W , Camargo Anamaria A , Asprino Paula F , Galante Pedro A F 
Published: June 2021

AbstractMUTYH is a glycosylase involved in the base excision repair of the DNA. Biallelic mutations in the MUTYH gene cause the autosomal recessive condition known as MUTYH-associated adenomatous polyposis and increase colorectal cancer risk. However, the cancer risk associated with germline variants in individuals carrying only one MUTYH defective allele is controversial and based on studies involving few samples. Here, we described a comprehensive investigation of monoallelic deleterious MUTYH carriers among approximately 10,400 patients across 33 different tumor types and more than 117 thousand samples of normal individuals. Our results indicate MUTYH deficiency in heterozygosity can lead to tumorigenesis through a mechanism of Loss Of Heterozygosity (LOH) of the functional MUTYH allele. We confirmed that the frequency of damaging MUTYH monoallelic variant carriers is higher in individuals with cancer than in the general population, though its frequency is not homogeneous among tumor types. We also demonstrate that MUTYH related mutational signature is elevated only in those patients with loss of the functional allele. We also find that MUTYH characteristic base substitution (C>A) increases stop codon generation and we identify key genes affected during tumorigenesis. In conclusion, we propose that deleterious germline monoallelic MUTYH variant carriers are at a higher risk of developing tumors, especially those types with frequent LOH events, such as adrenal adenocarcinoma.
Creation of an Expert Curated Variant List for Clinical Genomic Test Development and Validation: A ClinGen and GeT-RM Collaborative Project
Authors: Wilcox Emma , Harrison Steven M. , Lockhart Edward , Voelkerding Karl , Lubin Ira M. ,   ClinGen Expert Panels, Rehm Heidi L. , Kalman Lisa , Funke Birgit 
Published: June 2021

AbstractModern genomic sequencing tests often interrogate large numbers of genes. Identification of appropriate reference materials for development, validation studies, and quality assurance of these tests poses a significant challenge for laboratories. It is difficult to develop and maintain expert knowledge to identify all variants that must be validated to assure analytic and clinical validity. Additionally, it is usually not possible to procure appropriate and characterized genomic DNA reference materials containing the number and scope of variants required. To address these challenges, the Centers for Disease Control and Prevention’s Genetic Testing Reference Material Program (GeT-RM) has partnered with the Clinical Genome Resource (ClinGen) to develop a publicly available list of expert curated, clinically important variants. ClinGen Variant Curation Expert Panels nominated 546 variants found in 84 disease associated genes, including common pathogenic and difficult to detect variants. Variant types nominated included 346 SNVs, 104 deletions, 37 CNVs, 25 duplications, 18 deletion-insertions, 5 inversions, 4 insertions, 2 complex rearrangements, 3 in difficult to sequence regions, and 2 fusions. This expert-curated variant list is a resource that provides a foundation for designing comprehensive validation studies and for creating in silico reference materials for clinical genomic test development and validation.
Polymorphism of NAT2, PXR, ABCB1, and GSTT1 genes among tuberculosis patients of North Eastern States of India
Authors: Meitei Heikrujam Nilkanta , Pandey Anupama , Faruquee Hossain Md. , Thokchom Maria , Athokpam Sonia , Guha Hritusree , Das Ranjit , Saha Sourav , Kupa Rukuwe-u , Kapfo Wetetsho , Keppen Joshua , Mohapatara Amit Kumar , Priyadarsini Haripriya , Koijam Arunkumar Singh , Dasgupta Arunabha , Goswami Bidhan , Thong Aseno , Meru Kezhasino , Konyak Wungyong , Gupta Dinesh , Das Anjan , Khamo Vinotsole , Huidrom Lokhendro Singh , Haobam Sunita , Nanda Ranjan Kumar , Haobam Reena 
Published: June 2021

AbstractBackgroundAnti-tuberculosis drug-induced liver injury (AT-DILI) in tuberculosis (TB) patients has been linked to polymorphisms in genes encoding drug metabolism enzymes and proteins.ObjectiveThis study aimed to monitor polymorphisms of NAT2, PXR, ABCB1, and GSTT1 genes in TB patients from three states (Manipur, Tripura, and Nagaland) in the North Eastern Region of India.MethodsGenomic DNA was isolated from the whole blood samples of TB patients (n=219; Manipur:139; Tripura: 60; Nagaland: 20). The TaqMan allelic discrimination assay and statistical tools were used to investigate single nucleotide polymorphisms (SNP) patterns in NAT2, PXR, ABCB1, and GSTT1 genes.ResultsIn the study population, ten distinct genotypes of the NAT2 gene and single variation in the PXR, ABCB1, and GSTT1 genes were identified. A strong linkage disequilibrium (LD) was observed between rs1801280 and rs1799931 of the NAT2 gene. Majority of the study populations were intermediate (~46.1%), rest were either slow acetylators (~35.6%) or fast acetylators. Interestingly, ~55% of the TB patients in Tripura were slow acetylators and majority in Manipur and Nagaland were of intermediate acetylator genotypes. For all of the markers investigated, the population had a greater prevalence of ancestral alleles and genotypes. According to a combinational study of the genotypes linked to AT-DILI, ~26.1% of the population possessed the risk genotypes.ConclusionThese TB patients from north eastern states of India were found as carriers of the ancestral alleles and genotypes. And the risk for AT-DILI during TB treatment is low. Expanding such studies with additional markers and larger sample sizes will be useful to generate precise population-specific pharmacogenomics details for efficient TB management.
Genetic and early environmental predictors of adulthood self-reports of trauma
Authors: Peel Alicia J. , Purves Kirstin L. , Baldwin Jessie R. , Breen Gerome , Coleman Jonathan R.I. , Pingault Jean-Baptiste , Skelton Megan , Kuile Abigail R. ter , Danese Andrea , Eley Thalia C. 
Published: June 2021

AbstractBackgroundEvidence suggests that retrospective self-reports of childhood trauma are associated with a greater risk of psychopathology in adulthood than are prospective measures. However, it remains unclear why retrospectively reported trauma confers a greater risk for poor outcomes. Investigating the heritable characteristics and environmental adversities associated with measures of self-reported trauma could increase understanding of this risk pathway to psychopathology.MethodsOur sample included 3,963 unrelated individuals from the Twins Early Development Study. We tested whether polygenic scores for 21 psychiatric, cognitive, anthropometric and personality traits were associated with childhood emotional and physical abuse retrospectively self-reported in adulthood. To assess the presence of gene-environment correlation, we investigated whether these associations remained after controlling for composite scores of environmental adversity between birth and age 16.ResultsRetrospectively self-reported childhood trauma was associated with polygenic scores for autism spectrum disorder (ASD), body mass index and risky behaviours. When composite scores of environmental adversity were included in one model, only associations with parent-reported environmental adversity in middle childhood, self-reported environmental adversity in early adolescence and the polygenic score for ASD remained significant.ConclusionsRetrospective self-reports of childhood trauma are associated with heritable characteristics of the reporter. Genetic predisposition to ASD may increase liability to experiencing or interpreting events as traumatic. Associations between genetic predisposition for risky behaviour and high BMI with self-reported childhood trauma may be environmentally-mediated. Studies of the association between retrospectively self-reported childhood trauma and later life outcomes should consider that genetically-influenced reporter characteristics may confound associations, both directly and through gene-environment correlation.
Second wave of COVID-19 in India could be predicted with genomic surveillance of SARS-CoV-2 variants coupled with epidemiological data: A tool for future
Authors: Kumar Ashutosh , Asghar Adil , Dwivedi Prakhar , Kumar Gopichand , Narayan Ravi K. , Jha Rakesh K. , Parashar Rakesh , Sahni Chetan , Pandey Sada N. 
Published: June 2021

AbstractIndia recently witnessed a devastating second wave of COVID-19, which peaked by the end of the first week of May 2021. We aimed to understand formation and spread of the second wave in the country. We analyzed time series distribution of the genomic sequence data for SARS-CoV-2 and correlated that with the epidemiological data for new cases and deaths, for the corresponding period of the second wave. Further we analyzed the phylodynamics of the circulating SARS-CoV-2 variants in the Indian population in the period of study. Our analysis shows that the first indications of arrival of the second wave were observable by the end of January 2021, and by the end of March, 2021 it was clearly indicated. B.1.617 lineage variants drove the wave, particularly B.1.617.2 (a.k.a. delta variant). Based on the observations of this study, we propose that genomic surveillance of the SARS-CoV-2 variants augmented with epidemiological data can be a promising tool for forecasting imminent COVID-19 waves.