bluuebunny/crossref_metadata_2025_split huggingface dataset:
Using DNA to predict behaviour problems from preschool to adulthood
Authors: Gidziela Agnieszka , Rimfeld Kaili , Malanchini Margherita , Allegrini Andrea G. , McMillan Andrew , Selzam Saskia , Ronald Angelica , Viding Essi , von Stumm Sophie , Eley Thalia C. , Plomin Robert 
Published: February 2021

AbstractBackgroundOne goal of the DNA revolution is to predict problems in order to prevent them. We tested here if the prediction of behaviour problems from genome-wide polygenic scores (GPS) can be improved by creating composites across ages and across raters and by using a multi-GPS approach that includes GPS for adult psychiatric disorders as well as for childhood behaviour problems.MethodOur sample included 3,065 genotyped unrelated individuals from the Twins Early Development Study who were assessed longitudinally for hyperactivity, conduct, emotional problems and peer problems as rated by parents, teachers and children themselves. GPS created from 15 genome-wide association studies were used separately and jointly to test the prediction of behaviour problems composites (general behaviour problems, externalizing and internalizing) across ages (from age 2 to age 21) and across raters in penalized regression models. Based on the regression weights, we created multi-trait GPS reflecting the best prediction of behaviour problems. We compared GPS prediction to twin heritability using the same sample and measures.ResultsMulti-GPS prediction of behaviour problems increased from less than 2% of the variance for observed traits to up to 6% for cross-age and cross-rater composites. Twin study estimates of heritability mirrored patterns of multi-GPS prediction as they increased from less than 40% to up to 83%.ConclusionsThe ability of GPS to predict behaviour problems can be improved by using multiple GPS, cross-age composites and cross-rater composites, although the effect sizes remain modest, up to 6%. Our results can be used in any genotyped sample to create multi-trait GPS predictors of behaviour problems that will be more predictive than polygenic scores based on a single age, rater or GPS.Key pointsGenome-wide polygenic scores (GPS) can be used to predict behaviour problems in childhood, but the effect sizes are generally less than 3.5%.DNA-based prediction models of achieve greater accuracy if holistic approaches are employed, that is cross-trait, longitudinal and trans-situational approaches.The prediction of childhood behaviour problems can be improved by using multiple GPS to predict composites that aggregate behaviour problems across ages and across raters.Our results yield weights that can be applied to GPS in any study to create multi-trait GPS predictors of behaviour problems based on cross-age and cross-rater composites.As compared to individuals in the lowest multi-trait GPS decile, nearly three times as many individuals in the highest internalizing multi-trait GPS decile were diagnosed with anxiety disorder and 25% more individuals in the highest general behaviour problems and externalizing multi-trait GPS deciles have taken medication for mental health.
The Effect of NFL and NCAA Football Games on the Spread of COVID-19 in the United States: An Empirical Analysis
Authors: Toumi Asmae , Zhao Haoruo , Chhatwal Jagpreet , Linas Benjamin P. , Ayer Turgay 
Published: February 2021

ABSTRACTImportanceIn 2020 and early 2021, the National Football League (NFL) and National Collegiate Athletic Association (NCAA) had opted to host games in stadiums across the country. The in-person attendance of games has varied with time and from county to county. There is currently no evidence on whether limited in-person attendance of games has caused a substantial increase in coronavirus disease 2019 (COVID-19) cases.ObjectiveTo assess whether NFL and NCAA football games with limited in-person attendance have contributed to a substantial increase in COVID-19 cases in the counties they were held.DesignIn this time-series cross-sectional study, we matched every county hosting game(s) with in-person attendance (treated) in 2020 and 2021 with a county that has an identical game history for up to 14 days (control). We employed a standard matching method to further refine this matched set so that the treated and matched control counties have similar population size, non-pharmaceutical intervention(s) in place, and COVID-19 trends. We assessed the effect of hosting games with in-person attendance using a difference-in-difference estimator.SettingU.S. counties.ParticipantsU.S. counties hosting NFL and/or NCAA games.ExposureHosting NFL and/or NCAA games.Main outcomes and measuresEstimating the impact of NFL and NCAA games with in-person attendance on new, reported COVID-19 cases per 100,000 residents at the county-level up to 14 days post-game.ResultsThe matching algorithm returned 361 matching sets of counties. The effect of in-person attendance at NFL and NCAA games on community COVID-19 spread is not significant as it did not surpass 5 new daily cases of COVID-19 per 100,000 residents on average.Conclusions and relevanceThis time-series, cross-sectional matching study with a difference-in-differences design did not find an increase in COVID-19 cases per 100,000 residents in the counties where NFL and NCAA games were held with in-person attendance. Our study suggests that NFL and NCAA football games hosted with limited in-person attendance do not cause a significant increase in local COVID-19 cases.Key pointsQuestionDid NFL and NCAA football games with limited in-person attendance cause a substantia increase in coronavirus disease 2019 (COVID-19) cases in the U.S. counties where the games were held?FindingsThis time-series, cross-sectional study of U.S. counties with NFL and NCAA football games used matching and difference-in-differences design to estimate the effect of games with limited in-person attendance on county-level COVID-19 spread. Our study does not find an increase in county-level COVID-19 cases per 100,000 residents due to NFL and NCAA football games held with limited in-person attendance.MeaningThis study suggests that NFL and NCAA games held with limited in-person attendance do not cause an increase in COVID-19 cases in the counties they are held.
Genetic Connection to Drug-Induced Liver Injury (DILI) Through Statistical Learning Methods
Authors: Moore Roland , McEuen Kristin 
Published: February 2021

AbstractDrug-Induced Liver Injury (DILI) is one of the major causes of drug development failure or drug withdrawal from the market after development. Therefore, investigating factors associated with DILI is of paramount importance. Environmental factors that contribute to DILI have been investigated and are, by and large, known. However, recent genomic studies have indicated that genetic diversity can lead to inter-individual differences in drug response. Consequently, it has become necessary to also investigate how genetic factors contribute to the development of DILI in the presence of environmental factors. Thus, our aim is to find appropriate statistical methods to investigate gene-gene and/or gene-environment interactions that are associated with DILI. This is an initial study that only explores statistical learning methods to find gen-gene interactions (epistasis). We introduce Multifactor Dimensionality Reduction (MDR), Random Forest (plus logistic regression), and Multivariate Adaptive Regression Splines (MARS), as the few potential methodological approaches that we found. Next, we attempt to improve the MARS method by combining it with a variable selection method.
Altered immunity to microbiota, B cell activation and depleted γδ / resident memory T cells in colorectal cancer
Authors: Noble Alistair , Pring Edward T , Durant Lydia , Man Ripple , Dilke Stella M , Hoyles Lesley , James Steve A , Carding Simon R , Jenkins John T , Knight Stella C 
Published: February 2021

AbstractWe sought methods of rectifying microbiota:immune dysregulation as a route to prophylaxis and improved immunotherapy of colorectal cancer (CRC). CRC develops in gut epithelium, accompanied by low level inflammatory signaling, intestinal microbial dysbiosis and immune dysfunction. We examined populations of intraepithelial lymphocytes in non-affected colonic mucosa of CRC and healthy donors and circulating immune memory to commensal bacterial species and yeasts. Colonic tissue in CRC was significantly depleted of γδ T cells and resident memory T cells, populations with a regulatory CD39-expressing phenotype. T cell memory responses to a panel of commensals were distinct in CRC, while B cell memory responses to several bacteria/yeast were significantly increased, accompanied by increased proportions of effector memory B cells, transitional B cells and plasmablasts in blood. IgA responses to mucosal microbes were unchanged. Our data describe a novel immune signature with similarities to and differences from that of inflammatory bowel disease. They implicate B cell dysregulation as a potential contributor to parainflammation and identify pathways of weakened barrier function and tumor surveillance in CRC-susceptible individuals.
CREBRF missense variant rs373863828 has both direct and indirect effects on type 2 diabetes and fasting glucose in Polynesians living in Samoa and Aotearoa New Zealand
Authors: Russell Emily M. , Carlson Jenna C. , Krishnan Mohanraj , Hawley Nicola L. , Sun Guangyun , Cheng Hong , Naseri Take , Sefuiva Reupena Muagututi‘a , Viali Satupa‘itea , Tuitele John , Major Tanya J. , Miljkovic Iva , Merriman Tony R. , Deka Ranjan , Weeks Daniel E. , McGarvey Stephen T. , Minster Ryan L. 
Published: February 2021

AbstractObjectiveThe minor allele of rs373863828 in CREBRF is associated with higher BMI, lower fasting glucose, and lower odds of type 2 diabetes. We examined the associations between BMI and rs373863828 on type 2 diabetes and fasting glucose with a large sample of adult Polynesians from Samoa, American Samoa and Aotearoa New Zealand and estimated direct and indirect (via BMI) effects of rs373863828 on type 2 diabetes and fasting glucose.Research Design and MethodsWe regressed type 2 diabetes and fasting glucose on BMI and rs373863828 stratified by obesity, regressed type 2 diabetes and fasting glucose on BMI stratified by rs373863828 genotype, and assessed the effects of rs373863828 on type 2 diabetes and fasting glucose with path analysis.ResultsAssociation of BMI with fasting glucose was greater in those without obesity than in those with obesity. We did not observe evidence of differences by genotype. In the path analysis, the minor allele has direct negative and indirect positive effects on type 2 diabetes risk and fasting glucose, with the indirect effect mediated through a direct positive effect on BMI.ConclusionsThere may be a stronger effect of BMI on fasting glucose in Polynesians without obesity than in those with obesity. Carrying the rs373863828 minor allele does not decouple higher BMI from odds of type 2 diabetes. Given the current cost of genotyping compared to the accessibility of measuring BMI, including rs373863828 as a clinical predictor of type 2 diabetes may not be indicated.
Size and duration of COVID-19 clusters go along with a high SARS-CoV-2 viral load : a spatio-temporal investigation in Vaud state, Switzerland
Authors: Ladoy Anaïs , Opota Onya , Carron Pierre-Nicolas , Guessous Idris , Vuilleumier Séverine , Joost Stéphane , Greub Gilbert 
Published: February 2021

AbstractTo understand the geographical and temporal spread of SARS-CoV-2 during the first wave of infection documented in the canton of Vaud, Switzerland, we analysed clusters of positive cases using the precise place of residence of 33’651 individuals tested (RT-PCR) between January 10 and June 30, 2020. We identified both space-time (SaTScan) and transmission (MST-DBSCAN) clusters; we estimated their duration, their transmission behavior (emergence, growth, reduction, etc.) and relative risk. For each cluster, we computed the within number of individuals, their median age and viral load.Among 1’684 space-time clusters identified, 457 (27.1%) were significant (p ≤ 0.05), i.e. harboring a higher relative risk of infection, as compared to other regions. They lasted a median of 11 days (IQR 7-13) and included a median of 12 individuals per cluster (IQR 5-20). The majority of significant clusters (n=260; 56.9 %) had at least one person with an extremely high viral load (above 1 billion copies/ml). Those clusters were considerably larger (median of 17 infected individuals, p < 0.001) than clusters with subjects showing a viral load lower than 1 million copies/ml (median of 3 infected individuals). The highest viral loads were found in clusters with the lowest average age, while clusters with the highest average age had low to middle viral load. Interestingly, in 20 significant clusters the viral load of three first cases were all below 100’000 copies/ml suggesting that subjects with less than 100’000 copies/ml may still have been contagious. Noteworthy, the dynamics of transmission clusters made it possible to identify three diffusion zones, which mainly differentiated rural from urban areas, the latter being more prone to last and spread in a new nearby clusters.The use of geographic information is key for public health decision makers to mitigate the spread of the virus. This study suggests that early localization of clusters help implementing targeted protective measures limiting the spread of the SARS-CoV-2 virus.
Associations of Race/Ethnicity and Other Demographic and Socioeconomic Factors with Vaccine Initiation and Intention During the COVID-19 Pandemic in the United States
Authors: Kim Daniel 
Published: February 2021

AbstractBackgroundTo date, there has been limited data available to understand the associations between race/ethnicity and socioeconomic and related characteristics with novel coronavirus disease (COVID-19) vaccine initiation and planned vaccination in the United States.MethodsTo better characterize COVID-19 vaccinations nationally, we leveraged large cross-sectional surveys conducted between January and March 2021 with relatively complete race/ethnicity and socioeconomic data and nationally-representative of U.S. households to estimate trends in levels of COVID-19 vaccine initiation and vaccine intention. We further used survey data from January and March 2021 in adults aged 18-85 years to analyze the associations between race/ethnicity, education, pre-pandemic household income, and financial hardship during the pandemic and the adjusted odds of: 1) receipt of ≥1 dose of a COVID-19 vaccine; and 2) among those unvaccinated, the definite intention to receive a vaccine, controlling for other demographic and socioeconomic factors.ResultsWe observed persistent disparities in vaccine initiation for non-Hispanic Blacks, Hispanics, and non-Hispanic multiracial persons, and in vaccine intention for Blacks and multiracial persons, compared to non-Hispanic Whites and non-Hispanic Asians. In late March 2021, the prevalence estimates of Hispanics and Blacks receiving a vaccine were 12 percentage points and 8 percentage points lower than for Whites, respectively. Moreover, both education and income levels exhibited positive dose-response relationships with vaccine initiation (P for trend≤01 and <.001, respectively). Substantial financial hardship was linked to 35-44% lower odds of vaccination (P<.001). The most common reasons for vaccine hesitancy were concerns about side effects and safety, with evidence of higher levels of concerns about vaccine safety among Blacks vs. Whites.ConclusionsIn this large, nationally-representative study with relatively complete race/ethnicity and socioeconomic data, we find that being Black non-Hispanic and having the least education and income were each independently associated with a markedly lower likelihood of definitely planning to get vaccinated or having been vaccinated. In the ensuing months of the pandemic, addressing the persevering racial/ethnic and socioeconomic inequities in vaccination due to differential access and vaccine hesitancy is essential to mitigate the pandemic’s higher risks of infection and adverse health outcomes in Hispanic, Black, and socioeconomically-disadvantaged communities.
SEIR Filter: A Stochastic Model of Epidemics
Authors: Šmíd Martin , Berec Luděk , Kuběna Aleš Antonín , Levínský René , Trnka Jan , Tuček Vít , Zajíček Milan 
Published: February 2021

AbstractThere are many epidemiological models at hand to cope with the present pandemic; it is, however, difficult to calibrate these models when data are noisy, partial or observed only indirectly. It is also difficult to distinguish relevant data from noise, and to distinguish the impact of individual determinants of the epidemic.In mathematical statistics, the tools to handle all of these phenomena exist; however, they are seldom used for epidemiological models. The goal of this paper is to start filling this gap by proposing a general stochastic epidemiological model, which we call SEIR Filter.Technically our model is a heterogeneous partially observable vector autoregression model, in which we are able to express closed form formulas for the distribution of compartments and observations, so both maximum likelihood and least square estimators are analytically tractable. We give conditions for vanishing, explosion and stationary behaviour of the epidemic and we are able to express a closed form formula for reproduction number.Finally, we present several examples of the model’s application. We construct an estimate age-cohort model of the COVID-19 pandemic in the Czech Republic. To demonstrate the strengths of the model, we employ it to analyse and compare three vaccination scenarios.
Relationship Between Depression, Prefrontal Creatine and Gray Matter Volume
Authors: Faulkner Paul , Paioni Susanna Lucini , Kozhuharova Petya , Orlov Natasza , Lythgoe David J. , Daniju Yusuf , Morgenroth Elenor , Barker Holly , Allen Paul 
Published: February 2021

AbstractBackgroundDepression and low mood are leading contributors to disability worldwide. Research indicates that clinical depression may be associated with low creatine concentrations in the brain and low prefrontal gray matter volume. Because sub-clinical depression also contributes to difficulties in day-to-day life, understanding the neural mechanisms of depressive symptoms in all individuals, even at a sub-clinical level, may aid public health.MethodsEighty-four young adult participants completed the Depression, Anxiety and Stress Scale (DASS) to quantify severity of depression, anxiety and stress, and underwent 1H-Magnetic Resonance Spectroscopy of the medial prefrontal cortex and structural MRI to determine whole-brain gray matter volume.Results/OutcomesDASS depression scores were negatively associated with A) concentrations of creatine (but not other metabolites) in the prefrontal cortex, and B) with gray matter volume in the right superior medial frontal gyrus. Medial prefrontal creatine concentrations and right superior medial frontal gray matter volume were positively correlated. DASS anxiety and DASS stress scores were not related to prefrontal metabolite concentrations or whole-brain gray matter volume.Conclusions/InterpretationsThis study provides preliminary evidence from a representative group of individuals who exhibit a range of depression levels, that prefrontal creatine and gray matter volume are negatively associated with depression. While future research is needed to fully understand this relationship, these results provide support for previous findings which indicate that increasing creatine concentrations in the prefrontal cortex may improve mood and wellbeing.Declaration of Interest/FundingThis research was partly funded by a British Academy/Leverhulme Trust Research Grant, awarded to PA.
A Normative Database of A-Scan Data Using the Heidelberg Spectralis Spectral Domain Optical Coherence Tomography Machine
Authors: Meyer Joos , Karri Roshan , Danesh-Meyer Helen , Drummond Kate , Symons Andrew 
Published: February 2021

AbstractPurposeDevelop the first normative database of macular and circumpapillary scans with reference values at the level of the A-scan using the Heidelberg Spectralis Optical Coherence Tomography (OCT) machine.MethodsThis study is a retrospective cross sectional analysis of macular and circumpapillary OCT scans of healthy individuals. All participants had a full ophthalmic examination, including best corrected visual acuity, intraocular pressure, biomicroscopy, posterior segment examination and OCT scan. The volume and thickness of each of the nine Early Treatment Diabetic Retinopathy zones at the macula were analysed for the total retinal thickness, retinal nerve fibre layer (RNFL), ganglion cell layer (GCL) and inner plexiform layer (IPL). The thickness of the circumpapillary RNFL was analysed at the disc. De-identified A-scans were extracted from the OCT machine as separate tab-separated text file and made available according to the data sharing statement.ResultsTwo-hundred eyes from 144 participants were included of which 98 (49%) were female. The mean age (SD) was 48.52 (17.52). Participants were evenly distributed across four age groups and represented nine broad ethnic groups in proportions comparable to the local distribution. All the macular scans were 20° x 20° (5.9 mm x 5.9 mm), with a total scan density between 12,800 and 49,152 A-scans. The peripapillary scans were all 12° (3.5 mm), at a scan density of 768 A-scans. The mean retinal, GCL and IPL volumes were significantly greater in males than females. Age and total retinal volume (r = –0.2561), GCL volume (– 0.2911) and IPL volume (–0.3194) were negatively correlated. No significant correlation was found between the RNFL and age.ConclusionThis study provides a normative database of macular and circumpapillary scans with reference values at the level of the A-scan using the Heidelberg Spectralis Optical Coherence Tomography (OCT) machine.