bluuebunny/crossref_metadata_2025_split huggingface dataset:
DNA methylome-wide association study of genetic risk for depression implicates antigen processing and immune responses
Authors: Shen Xueyi , Caramaschi Doretta , Adams Mark J , Walker Rosie M , Min Josine L , Kwong Alex , Hemani Gibran ,   Genetics of DNA Methylation Consortium, Barbu Miruna C , Whalley Heather C , Harris Sarah E , Deary Ian J , Morris Stewart W , Cox Simon R , Relton Caroline L , Marioni Riccardo E , Evans Kathryn L , McIntosh Andrew M 
Published: July 2021

AbstractBackgroundDepression is a disabling and highly prevalent condition where genetic and epigenetic differences, such as DNA methylation (DNAm), contribute to prediction of disease liability.MethodWe investigated the association between polygenic risk scores (PRS) for depression and DNAm by conducting a methylome-wide association study (MWAS) in Generation Scotland (N=8,898, mean age=49.8 years) with replication in the Lothian Birth Cohorts of 1921 and 1936 and adults in Avon Longitudinal Study of Parents and Children (ALSPAC) (Ncombined=2,049, mean age=79.1, 69.6 and 47.2 years, respectively). We also conducted a replication MWAS in the ALSPAC children (N=423, mean age=17.1 years).ResultWide-spread associations were found between PRS constructed using genetic risk variants for depression and DNAm in cytosine-guanine dinucleotide (CpG) probes that localised to genes involved in immune responses and neural development (NCpG=599, pBonferroni<0.05, p<6.5×10−8). The effect sizes for the significant associations were highly correlated between the discovery and replication samples in adults (r=0.83) and in adolescents (r=0.76). Additional analysis on the methylome-wide associations was conducted for each lead genetic risk variant. Over 40% of the independent genetic risk variants showed associations with CpG probe DNAm located in both the same (cis) and distal probes (trans) to the genetic loci (pBonferroni<0.045). Subsequent Mendelian randomisation analysis showed that DNAm and depression are mutually causal (pFDR<0.039), and there is a greater number of causal effects found from DNAm to depression (DNAm to depression: pFDR ranged from 0.045 to 2.06×10−120; depression to DNAm: pFDR ranged from 0.046 to 2.1×10−23).ConclusionPolygenic risk scores for depression, especially those constructed from genome-wide significant genetic risk variants, showed epigenome-wide methylation association differences in the methylome associated with immune responses and brain development. We also found evidence from Mendelian randomisation evidence that DNAm may be causal to depression, as well as a causal consequence of depression.
Urinary cell mRNA Profiling of Kidney Allograft Recipients: A Systematic Investigation of a Filtration Based Protocol for the Simplification of Urine Processing
Authors: Snopkowski Catherine , Salinas Thalia , Li Carol , Stryjniak Gabriel , Ding Ruchuang , Sharma Vijay , Suthanthiran Manikkam 
Published: July 2021

ABSTRACTBackgroundKidney transplantation is a life-restorative therapy, but immune rejection undermines allograft survival. Urinary cell mRNA profiles offer a noninvasive means of diagnosing kidney allograft rejection, but urine processing protocols have logistical constraints. We aimed to determine whether the centrifugation-based method for urinary cell mRNA profiling could be replaced with a simpler filtration-based method without undermining quality.MethodsWe isolated RNA from urine collected from kidney allograft recipients using the Cornell centrifugation-based protocol (CCBP) or the Zymo filter-based protocol (ZFBP) and compared RNA purity and yield using a spectrophotometer or a fluorometer and measured absolute copy number of transcripts using customized real-time quantitative PCR assays. We investigated the performance characteristics of RNA isolated using ZFBP and stored either at - 80°C or at ambient temperature for 2 to 4 days and also when shipped to our Gene Expression Monitoring (GEM) Core at ambient temperature. We examined the feasibility of initial processing of urine samples by kidney allograft recipients trained by the GEM Core staff and the diagnostic utility for acute rejection, of urine processed using the ZFBP.ResultsRNA purity (P=0.0007, Wilcoxon matched paired signed-ranks test) and yield (P<0.0001) were higher with ZFBP vs. CCBP, and absolute copy number of 18S rRNA was similar (P=0.79) following normalization of RNA yield by reverse transcribing a constant amount of RNA isolated using either protocol. RNA purity, yield, and absolute copy numbers of 18S rRNA, TGF-β1 mRNA and microRNA-26a were not different (P>0.05) in the filtrates containing RNA stored either at -80°C or at ambient temperature for 2 to 4 days or shipped overnight at ambient temperature. RNA purity, yield, and absolute copy numbers of 18S rRNA and TGF-β1 mRNA were also not different (P>0.05) between home processed and laboratory processed urine filtrates. Urinary cell levels of mRNA for granzyme B (P=0.01) and perforin (P=0.0002) in the filtrates were diagnostic of acute rejection in human kidney allografts.ConclusionsUrinary cell mRNA profiling was simplified using the ZFBP without undermining RNA quality or diagnostic utility. Home processing by the kidney allograft recipients, the stability of RNA containing filtrates at ambient temperature, and the elimination of the need for centrifuges and freezers represent some of the advantages of ZFBP over the CCBP for urinary cell mRNA profiling.
Phylogeography and transmission of M. tuberculosis in Moldova
Authors: Yang Chongguang , Sobkowiak Benjamin , Naidu Vijay , Codreanu Alexandru , Ciobanu Nelly , Gunasekera Kenneth S. , Chitwood Melanie H. , Alexandru Sofia , Bivol Stela , Russi Marcus , Havumaki Joshua , Cudahy Patrick , Fosburgh Heather , Allender Christopher J. ,   Heather Centner, Engelthaler David M. , Menzies Nicolas A. , Warren Joshua L. , Crudu Valeriu , Colijn Caroline , Cohen Ted 
Published: July 2021

AbstractBackgroundThe incidence of multidrug-resistant tuberculosis (MDR-TB) remains critically high in countries of the former Soviet Union, where >20% of new cases and >50% of previously-treated cases have resistance to rifampin and isoniazid. Transmission of resistant strains, as opposed to resistance selected through inadequate treatment of drug-susceptible TB, is the main driver of incident MDR-TB in these countries.MethodsWe conducted a prospective, genomic analysis of all culture-positive TB cases diagnosed in 2018 and 2019 in the Republic of Moldova. We used phylogenetic methods to identify putative transmission clusters; spatial and demographic data were analyzed to further describe local transmission of M. tuberculosis.ResultsOf 2236 participants, 779 (36%) had MDR-TB, of whom 386 (50%) had never been treated previously for TB. 92% of MDR M. tuberculosis strains belonged to putative transmission clusters. Phylogenetic reconstruction identified three large clades that were comprised nearly uniformly of MDR-TB; two of these clades were of Beijing lineage and one of Ural lineage, and each had additional distinct clade-specific second-line drug resistance mutations and geographic distributions. Spatial and temporal proximity between pairs of cases within a cluster was associated with greater genomic similarity.ConclusionsThe MDR-TB epidemic in Moldova is the result of local transmission of multiple M. tuberculosis strains, including distinct clades of highly drug-resistant M. tuberculosis with varying geographic distributions and drug resistance profiles. This study demonstrates the role of comprehensive genomic surveillance for understanding the transmission of M. tuberculosis and highlights the urgency of interventions to interrupt transmission of highly drug-resistant M. tuberculosis.
Monitoring SARS-CoV-2 in sewage: toward sentinels with analytical accuracy
Authors: Calderón-Franco David , Orschler Laura , Lackner Susanne , Agrawal Shelesh , Weissbrodt David G. 
Published: July 2021

AbstractThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemia has been one of the most difficult challenges humankind has recently faced. Wastewater-based epidemiology has emerged as a tool for surveillance and mitigation of potential viral outbreaks, circumventing biases introduced by clinical patient testing. Due to the situation urgency, protocols followed for isolating viral RNA from sewage were not adapted for such sample matrices. In parallel to their implementation for fast collection of data to sustain surveillance and mitigation decisions, molecular protocols need to be harmonized to deliver accurate, reproducible, and comparable analytical outputs. Here we studied analytical variabilities linked to viral RNA isolation methods from sewage. Three different influent wastewater volumes were used to assess the effect of filtered volumes (50, 100 or 500 mL) for capturing viral particles. Three different concentration strategies were tested by electronegative membranes, polyethersulfone membranes, and anion-exchange diethylaminoethyl cellulose columns. To compare the number of viral particles, different RNA isolation methods (column-based vs. magnetic beads) were compared. The effect of extra RNA purification steps and different RT-qPCR strategies (one step vs. two-step) were also evaluated. Results showed that the combination of 500 mL filtration volume through electronegative membranes and without multiple RNA purification steps (using column-based RNA purification) using two-step RT-qPCR avoided false negatives when basal viral load in sewage are present and yielded more consistent results during the surveillance done during the second-wave in Delft (The Hague area, The Netherlands). By paving the way for standardization of methods for the sampling, concentration and molecular detection of SARS-CoV-2 viruses from sewage, these findings can help water and health surveillance authorities to use and trust results coming from wastewater based epidemiology studies in order to anticipate SARS-CoV-2 outbreaks.Graphical Abstract
Incidence of outbreak-associated COVID-19 cases by industry in Ontario, Canada, April 1, 2020-March 31, 2021
Authors: Buchan Sarah A. , Smith Peter M. , Warren Christine , Murti Michelle , Mustard Cameron , Kim JinHee , Menon Sandya , Brown Kevin A. , van Ingen Trevor , Smith Brendan T. 
Published: July 2021

AbstractObjectivesThe objective of our study was to estimate the rate of workplace outbreak-associated cases of COVID-19 by industry in labour market participants aged 15-69 years who reported working the majority of hours outside the home in Ontario, Canada.MethodsWe conducted a population based cross-sectional study of COVID-19 workplace outbreaks and associated-cases reported in Ontario between April 1, 2020 and March 31, 2021. All outbreaks were manually classified into two digit North American Industry Classification System (NAICS) codes. We obtained denominator data from the Statistics Canada Labour Force Survey in order to estimate the incidence of outbreak-associated cases per 100,000,000 hours amongst individuals who reported the majority of hours were worked outside the home. We performed this analysis across industries and in three distinct time periods.ResultsOverall, 12% of cases were attributed to workplace outbreaks among working age adults across our study period. While incidence varied across the time periods, the five industries with the highest incidence rates across our study period were agriculture; healthcare and social assistance; food manufacturing; educational services; and, transportation and warehousing.ConclusionsCertain industries have consistently increased incidence of COVID-19 over the course of the pandemic. These results may assist in ongoing efforts to reduce transmission of COVID-19, by prioritizing resources, as well as industry-specific guidance, vaccination, and public health messaging.
Genome-wide contribution of common Short-Tandem Repeats to Parkinson’s Disease genetic risk
Authors: Bustos Bernabe I. , Billingsley Kimberley , Blauwendraat Cornelis , Gibbs J. Raphael , Gan-Or Ziv , Krainc Dimitri , Singleton Andrew B. , Lubbe Steven J. ,   For the International Parkinson’s Disease Genomics Consortium (IPDGC)
Published: July 2021

ABSTRACTParkinson’s disease (PD) is a complex neurodegenerative disorder with a strong genetic component, where most known disease-associated variants are single nucleotide polymorphisms (SNPs) and small insertions and deletions (Indels). DNA repetitive elements account for >50% of the human genome, however little is known of their contribution to PD etiology. While select short tandem repeats (STRs) within candidate genes have been studied in PD, their genome-wide contribution remains unknown. Here we present the first genome-wide association study (GWAS) of STRs in PD. Through a meta-analysis of 16 imputed GWAS cohorts from the International Parkinson’s Disease Genomic Consortium (IPDGC), totalling 39,087 individuals (16,642 PD cases and 22,445 controls of European ancestry) we identified 34 genome-wide significant STR loci (p < 5.34×10-6), with the strongest signal located inKANSL1(chr17:44205351:[T]11, p=3×10-39, OR=1.31 [CI 95%=1.26-1.36]). Conditional-joint analyses suggested that 4 significant STRs mapping nearbyNDUFAF2, TRIML2, MIRNA-129-1andNCOR1were independent from known PD risk SNPs. Including STRs in heritability estimates increased the variance explained by SNPs alone. Gene expression analysis of STRs (eSTR) in RNASeq data from 13 brain regions, identified significant associations of STRs influencing the expression of multiple genes, including PD known genes. Further functional annotation of candidate STRs revealed that significant eSTRs withinNUDFAF2andZSWIM7overlap with regulatory features and are associated with change in the expression levels of nearby genes. Here we show that STRs at known and novel candidate PD loci contribute to PD risk, and have functional effects in disease-relevant tissues and pathways, supporting previously reported disease-associated genes and giving further evidence for their functional prioritization. These data represent a valuable resource for researchers currently dissecting PD risk loci.
Risk factors for SARS-CoV-2 infection and hospitalisation in children and adolescents in Norway: A nationwide population-based study
Authors: Størdal Ketil , Ruiz Paz Lopez-Doriga , Greve-Isdahl Margrethe , Surén Pål , Knudsen Per Kristian , Løvdal Gulseth Hanne , Tapia German 
Published: July 2021

AbstractObjectiveTo determine risk factors for SARS-CoV-2 infection and hospitalisation among children and adolescents.DesignNationwide, population-based cohort study. Setting: Norway from 1 March 2020 to 31 April 2021. Participants: All Norwegian residents <18 years of age.Main outcome measuresPopulation-based health care and population registries were used to study risk factors for SARS-CoV-2 infection, including socioeconomic factors, country of origin, and pre-existing chronic comorbidities. All residents were followed until age 18, emigration, death, or end of follow-up. Hazard ratios (HR) estimated by Cox regression models were adjusted for testing frequency. Further, risk factors for admission to the hospital among the infected were investigated.ResultsOf 1 182 796 residents, 22608 (1.9%) tested positive by polymerase chain reaction or lateral flow tests, of whom 107 (0.5%) were admitted to a hospital. Low family income (aHR 1.40, 95% confidence interval 1.36 to 1.46), crowded housing (1.35, 1.30 to 1.39), household size, age, and area of living were independent risk factors for infection. A non-Nordic country of origin was the strongest risk factor (aHR 2.37, 95% CI 2.30 to 2.49), whereas chronic comorbidity was not associated with the risk of infection. Chronic comorbidity was associated with hospitalisation (aHR 4.15, 2.63 to 6.56), in addition to age, whereas socioeconomic status and country of origin did not predict hospitalisation among those infected.ConclusionsSocioeconomic factors, country of origin, and area of living were associated with the risk of SARS-CoV-2 infection. However, these factors did not predict hospitalisation among those infected. Chronic comorbidity was associated with the risk of admission but not with the overall risk of acquiring SARS-CoV-2.What is already known on this topicHospital admissions rates for covid-19 among children and adolescents are low compared to adults. Admission rates to hospitals and intensive care units for covid-19 have been higher in minority groups and in children and adolescents with chronic comorbidity.Whether underlying differences in susceptibility for severe disease or the incidence of infections are driving these associations have not been investigated.What this study addsLow family income, crowded housing and household size, and country of origin outside the Nordic countries were associated with increased risk of infection with SARS-CoV-2.None of these factors, but chronic comorbidities, were associated with the risk of hospital admission among those infected.
Survey of SARS-CoV-2 genetic diversity in two major Brazilian cities using a fast and affordable Sanger sequencing strategy
Authors: Dorlass Erick Gustavo , Lourenço Karine Lima , Miserani Magalhães Rubens Daniel , Sato Hugo , Fiorini Alex , Peixoto Renata , Coelho Helena Perez , Telezynski Bruna Larotonda , Scagion Guilherme Pereira , Ometto Tatiana , Thomazelli Luciano Matsumiya , Leal Oliveira Danielle Bruna , Fernandes Ana Paula , Durigon Edison Luiz , Guimarães Fonseca Flavio , Ribeiro Teixeira Santuza Maria 
Published: July 2021

AbstractGenetic variants of SARS-CoV-2 have been emerging and circulating in many places across the world. Rapid detection of these variants is essential since their dissemination can impact transmission rates, diagnostic procedures, disease severity, response to vaccines or patient management. Sanger sequencing has been used as the preferred approach for variant detection among circulating human immunodeficiency and measles virus genotypes. Using primers to amplify a fragment of the SARS-CoV-2 genome encoding part of the Spike protein, we showed that Sanger sequencing allowed us to rapidly detect the introduction and spread of three distinct SARS-CoV-2 variants in two major Brazilian cities. In both cities, after the predominance of variants closely related to the virus first identified in China, the emergence of the P.2 variant was quickly followed by the identification of the P1 variant, which became dominant in less than one month after it was first detected.
HAPPILEE: The Harvard Automated Processing Pipeline In Low Electrode Electroencephalography, a standardized software for low density EEG and ERP data
Authors: Lopez K.L. , Monachino A.D. , Morales S. , Leach S.C. , Bowers M.E. , Gabard-Durnam L.J. 
Published: July 2021

AbstractLow-density Electroencephalography (EEG) recordings (e.g. fewer than 32 electrodes) are widely-used in research and clinical practice and enable scalable brain function measurement across a variety of settings and populations. Though a number of automated pipelines have recently been proposed to standardize and optimize EEG preprocessing for high-density systems with state-of-the-art methods, few solutions have emerged that are compatible with low-density systems. However, low-density data often include long recording times and/or large sample sizes that would benefit from similar standardization and automation with contemporary methods. To address this need, we propose the HAPPE In Low Electrode Electroencephalography (HAPPILEE) pipeline as a standardized, automated pipeline optimized for EEG recordings with low density channel layouts of any size. HAPPILEE processes task-free (e.g. resting-state) and task-related EEG, and event-related potential (ERP) data, from raw files through a series of processing steps including filtering, line noise reduction, bad channel detection, artifact rejection from continuous data, segmentation, and bad segment rejection that have all been optimized for low density data. HAPPILEE also includes post-processing reports of data and pipeline quality metrics to facilitate the evaluation and reporting of data quality and processing-related changes to the data in a standardized manner. We describe multiple approaches with both recorded and simulated EEG data to optimize and validate pipeline performance. The HAPPILEE pipeline is freely available as part of HAPPE 2.0 software under the terms of the GNU General Public License at:https://github.com/PINE-Lab/HAPPE.
Atypical development of subcortico-cortical effective connectivity in autism
Authors: Lorenzini Luigi , van Wingen Guido , Cerliani Leonardo 
Published: July 2021

AbstractHypersensitivity, stereotyped behaviors and attentional problems in autism spectrum disorder (ASD) are compatible with inefficient filtering of undesired or irrelevant sensory information at early stages of neural processing. This could stem from delays in the neurotypical development of the functional segregation between cortical and subcortical brain processes, as suggested by previous findings of overconnectivity between primary sensory regions and deep brain nuclei in ASD.To test this hypothesis, we used dynamic causal modelling to quantify the effect of age on the development of (1) cortical functional segregation from subcortical activity and (2) directional influence of subcortical activity on cortical processing in 166 participants with ASD and 193 typically developing controls (TD) from the Autism Brain Imaging Data Exchange (ABIDE).We found that in TD participants age was significantly associated with increased functional segregation of cortical sensory processing from subcortical activity, paralleled by a decreased influence of subcortical activity on cortical processing. Instead these effects were highly reduced and mostly absent in ASD participants, suggesting a delayed or arrested development of the segregation between subcortical and cortical sensory processing in ASD.This atypical configuration of subcortico-cortical connectivity in ASD can result in an excessive amount of unprocessed sensory information relayed to the cortex, which is likely to impact cognitive functioning in everyday situations where it is beneficial to limit the influence of basic sensory information on cognitive processing, such as activities requiring focused attention or social interactions.
Neuronal activity drives pathway-specific depolarization of astrocyte distal processes
Authors: Armbruster Moritz , Naskar Saptarnab , Garcia Jacqueline , Sommer Mary , Kim Elliot , Adam Yoav , Haydon Philip G , Boyden Edward S , Cohen Adam E , Dulla Chris G 
Published: July 2021

AbstractAstrocytes are glial cells that interact with neuronal synapses via their distal processes, where they remove glutamate and potassium (K+) from the extracellular space following neuronal activity. Astrocyte clearance of both glutamate and K+is voltage-dependent, but astrocyte membrane potential (Vm) has been thought to be largely invariant. As a result, these voltage-dependencies have not been considered relevant to astrocyte function. Using genetically encoded voltage indicators enabling the measurement of Vmat distal astrocyte processes (DAPs), we report large, rapid, focal, and pathway-specific depolarizations in DAPs during neuronal activity. These activity-dependent astrocyte depolarizations are driven by action potential-mediated presynaptic K+efflux and electrogenic glutamate transporters. We find that DAP depolarization inhibits astrocyte glutamate clearance during neuronal activity, enhancing neuronal activation by glutamate. This represents a novel class of sub-cellular astrocyte membrane dynamics and a new form of astrocyte-neuron interaction.One Sentence SummaryGenetically encoded voltage imaging of astrocytes shows that presynaptic neuronal activity drives focal astrocyte depolarization, contributing to activity-dependent inhibition of glutamate uptake.