bluuebunny/crossref_metadata_2025_split huggingface dataset:
The prevalence of hepatitis C virus (HCV) infection in β-thalassemia patients in Pakistan: a systematic review and meta-analysis
Authors: Akhtar Sohail , Nasir Jamal Abdul , Shah Farrukh , Hinde Andrew 
Published: November 2019

ABSTRACTObjectiveHepatitis C virus (HCV) infection is the most commonly reported bloodborne infection in Pakistan. Frequent blood transfusions in β-thalassemia patients expose them to a high risk of HCV infection. The purpose of this paper is to summarize the current data on the prevalence of HCV infection among β-thalassemia patients in Pakistan by using a systematic review and meta–analysis.DesignSystematic review and meta-analysis.Participantsβ-thalassemia patients in Pakistan.Data sourcesFollowing PRISMA guidelines, a comprehensive literature search in PubMed/MEDLINE and EMBASE was performed to identify published articles reporting on the prevalence of HCV among β-thalassemia patients in Pakistan. Only English language articles were considered. Two independent authors selected studies. The methodological quality of the included studies was assessed using the Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies.ResultsThe search conceded a total of 138 studies, of which 27 studies were finally considered for meta-analysis. The pooled prevalence of HCV in β-thalassemia patients in Pakistan was 36.21% (95% CI: 28.98– 43.75%) based on 5,789 β-thalassemia patients, but there was considerable heterogeneity. Meta-analysis estimated the HCV prevalence among the β-thalassemia patients at 45.98 % (95% CI: 38.15–53.90%) in Punjab, 31.81% (95% CI: 20.27–44.59%) in Sindh, and 28.04% (95% CI: 13.58–45.26%) in Khyber Pakhtunkhwa. Meta–regression analysis showed that geographical location was a key source of heterogeneity.ConclusionsThe pooled prevalence of hepatitis C virus among β-thalassemia patients in Pakistan was 36.21%, but varies regionally within the country. The prevalence is higher than in neighboring countries. With the use of standard prevention procedures during blood transfusion, the risk of HCV transmission among β-thalassemia patients could be controlled hence prevalence of HCV in β-thalassemia patients could be reduced.Strengths and limitations of this study➢This is the first systematic review and meta-analysis to estimate the pooled prevalence of HCV infection among the β-thalassemia patients in Pakistan➢We used of an extensive search strategy and adherence to predetermined inclusion and exclusion criteria.➢Strong and reliable methodological and statistical methods were used.➢Our analyses possessed a considerable amount of quantifiable heterogeneity.➢Not all regions in Pakistan were represented and most of the included studies were hospital-based, making it difficult to generalize the findings of this review.
Genetic variation near CXCL12 is associated with susceptibility to HIV-related non-Hodgkin lymphoma
Authors: Thorball Christian W. , Oudot-Mellakh Tiphaine , Hammer Christian , Santoni Federico A. , Niay Jonathan , Costagliola Dominique , Goujard Cécile , Meyer Laurence , Wang Sophia S. , Hussain Shehnaz K. , Theodorou Ioannis , Cavassini Matthias , Rauch Andri , Battegay Manuel , Hoffmann Matthias , Schmid Patrick , Bernasconi Enos , Günthard Huldrych F. , McLaren Paul J. , Rabkin Charles S. , Besson Caroline , Fellay Jacques 
Published: November 2019

AbstractHuman immunodeficiency virus (HIV) infection is associated with a substantially increased risk of non-Hodgkin lymphoma (NHL). High plasma viral load, low CD4+ T cell counts and absence of antiretroviral treatment (ART) are known predictive factors for NHL. Even in the era of suppressive ART, HIV-infected individuals remain at increased risk of developing NHL compared to the general population. To search for human genetic determinants of HIV-associated NHL, we performed case-control genome-wide association studies (GWAS) in three cohorts of HIV+ patients of European ancestry and meta-analyzed the results. In total, 278 cases and 1924 matched controls were included. We observed a significant association with NHL susceptibility in the C-X-C motif chemokine ligand 12 (CXCL12) region on chromosome 10. A fine mapping analysis identified rs7919208 as the most likely causal variant (P = 4.77e-11). The G>A polymorphism creates a new transcription factor binding site for BATF and JUND. Analyses of topologically associating domains and promoter capture Hi-C data revealed significant interactions between the rs7919208 region and the promoter of CXCL12, also known as stromal-derived factor 1 (SDF-1). These results suggest a modulatory role of CXCL12 regulation in the increased susceptibility to NHL observed in the HIV-infected population.
Mitochondrial DNA copy number and incident heart failure: The Atherosclerosis Risk in Communities (ARIC) study
Authors: Hong Yun Soo , Longchamps Ryan J. , Zhao Di , Castellani Christina A. , Loehr Laura R. , Chang Patricia P. , Matsushita Kunihiro , Grove Megan L. , Boerwinkle Eric , Arking Dan E. , Guallar Eliseo 
Published: November 2019

ABSTRACTBackgroundThe association between mitochondrial DNA-copy number (mtDNA-CN) and incident heart failure (HF) in the general population is unclear.MethodsWe examined the association between mtDNA-CN and the risk of incident HF among 10,802 participants free of HF at baseline from the Atherosclerosis Risk in Communities (ARIC) study, a large bi-racial population-based cohort. mtDNA-CN was estimated using probe intensities on the Affymetrix Genome-Wide Human single nucleotide polymorphisms Array 6.0. Incident HF events were identified through hospital discharge codes from 1987 until 2005 and through adjudication by the ARIC HF Classification Committee since 2005.ResultsDuring a median follow-up of 23.1 years, there were 2,227 incident HF events (incidence rate 10.3 per 1000 person-years). In fully adjusted models, the hazard ratios (95% confidence intervals) for HF comparing the 2nd through 5th quintiles of mtDNA-CN to the 1st quintile were 0.91 (0.80–1.04), 0.82 (0.72–0.93), 0.81 (0.71–0.92), and 0.74 (0.65–0.85), respectively (P for trend < 0.001). In stratified analyses, the associations between mtDNA-CN and HF were similar across examined subgroups. The inverse association between mtDNA-CN and incident HF was stronger in HF with reduced ejection fraction (HFrEF) than in HF with preserved ejection fraction (HFpEF).ConclusionsIn this prospective cohort, mtDNA-CN was inversely associated with the risk of incident HF suggesting that reduced levels of mtDNA-CN, a biomarker of mitochondrial dysfunction, could reflect early susceptibility to HF.
Genome-wide association study of Buruli ulcer in rural Benin
Authors: Manry Jeremy , Vincent Quentin B. , Chrabieh Maya , Lorenzo Lazaro , Theodorou Ioannis , Ardant Marie-Françoise , Johnson Christian , Marion Estelle , Chauty Annick , Marsollier Laurent , Abel Laurent , Alcaïs Alexandre 
Published: November 2019

AbstractBuruli ulcer, caused by Mycobacterium ulcerans, is the third mycobacterial disease worldwide characterized by devastating necrotizing skin lesions. The role of host genetics in susceptibility to Buruli ulcer has long been suggested. We conduct the first genome-wide association study of Buruli ulcer on a combined sample of 1,524 well characterized patients and controls from rural Benin. Two-stage analyses identify two novel associated loci located within lincRNA genes: rs9814705 in ENSG00000240095.1 (P = 2.85×10−7; odds ratio = 1.80 [1.43-2.27]), and rs76647377 in LINC01622 (P = 9.85×10−8; hazard ratio = 0.41 [0.28-0.60]). Furthermore, we replicate the protective effect of allele G of a missense variant located in ATG16L1, and previously shown to decrease bacterial autophagy (rs2241880, P = 0.003; odds ratio = 0.31 [0.14-0.68]). Our results suggest lincRNAs and the autophagy pathway as critical factors in the development of Buruli ulcer.
A Query Taxonomy Describes Performance of Patient-Level Retrieval from Electronic Health Record Data
Authors: Chamberlin Steven R. , Bedrick Steven D. , Cohen Aaron M. , Wang Yanshan , Wen Andrew , Liu Sijia , Liu Hongfang , Hersh William R. 
Published: November 2019

AbstractPerformance of systems used for patient cohort identification with electronic health record (EHR) data is not well-characterized. The objective of this research was to evaluate factors that might affect information retrieval (IR) methods and to investigate the interplay between commonly used IR approaches and the characteristics of the cohort definition structure.We used an IR test collection containing 56 test patient cohort definitions, 100,000 patient records originating from an academic medical institution EHR data warehouse, and automated word-base query tasks, varying four parameters. Performance was measured using B-Pref. We then designed 59 taxonomy characteristics to classify the structure of the 56 topics. In addition, six topic complexity measures were derived from these characteristics for further evaluation using a beta regression simulation.We did not find a strong association between the 59 taxonomy characteristics and patient retrieval performance, but we did find strong performance associations with the six topic complexity measures created from these characteristics, and interactions between these measures and the automated query parameter settings.Some of the characteristics derived from a query taxonomy could lead to improved selection of approaches based on the structure of the topic of interest. Insights gained here will help guide future work to develop new methods for patient-level cohort discovery with EHR data.
Prevalence and associated occupational factors for low back pain among the bank employees in Dhaka City
Authors: Ali Mohammad , Ahsan Gias U. , Hossain Ahmed 
Published: November 2019

AbstractObjectiveLow Back Pain (LBP) is one of the common health problems among full-time office employees that causes employees absenteeism from work. The purpose of the study is to identify the association between occupational factors and LBP among full-time bank employees in Dhaka City.Materials and MethodsWe conducted a cross-sectional study with 593 full-time bank employees. The one-month complaints of LBP were administered by a musculoskeletal subscale of subjective health complaints by Eriksen et al. A logistic model was performed to identify variables associated with LBP, and a random forest technique was performed to identify the top 5 important variables.ResultsThe one-month prevalence for LBP was found 36.6% among the bank employees and the prevalence was high (46.6%) for the 41 to 59-year-old age-group. The multiple logistic regression analysis indicates that age (41-59 years) (OR:2.11, CI=1.21-3.74), obesity (OR:2.06, CI=1.01-4.21) and long working hours (>9 hours) (OR:1.42, CI=1.01-2.0) are positively associated with LBP. Age and length of employment have a positive correlation of 0.87. The random forest technique identifies the top 5 important variables are, age, length of employment, long office hours, presence of chronic illness, and physical activity.ConclusionLBP is highly prevalent in full-time bank employees. The occupational factors like length of employment (>10 years) and long working hours (>9 hours) play a significant role in developing LBP among the bank employees. Moreover, the factors like age, chronic illness, obesity and physical activity should be taken into account in the prevention of LBP in bank employees.
Disruption of the Blood-Brain Barrier in 22q11.2 Deletion Syndrome
Authors: Crockett Alexis M. , Ryan Sean K. , Vasquez Adriana Hernandez , Canning Caroline , Kanyuch Nickole , Kebir Hania , Ceja Guadalupe , Gesualdi James , Viaene Angela , Kapoor Richa , Benallegue Naïl , Anderson Stewart A. , Alvarez Jorge I. 
Published: November 2019

ABSTRACTNeuroimmune dysregulation is implicated in neuropsychiatric disorders including schizophrenia (SZ). As the blood brain barrier (BBB) is the immunological interface between the brain and the periphery, we investigated whether the BBB is intrinsically compromised in the most common genetic risk factor for SZ, the hemizygous deletion of chromosome 22q11.2 (22qDS). BBB-like endothelium (iBBB) differentiated from human 22qDS+SZ-induced pluripotent stem cells exhibited impaired barrier integrity, a phenotype substantiated in a mouse model of 22qDS. The proinflammatory intercellular adhesion molecule-1 (ICAM-1) was upregulated in 22qDS+SZ iBBB and 22qDS mice, indicating compromise of the BBB immune privilege. This immune imbalance resulted in increased migration/activation of leukocytes crossing the 22qDS+SZ iBBB. Finally, we found heightened astrocyte activation in murine and human 22qDS, suggesting that the BBB promotes astrocyte-mediated neuroinflammation. Overall, the barrier-promoting and immune privilege properties of the 22qDS BBB are compromised, and this might increase the risk for neuropsychiatric disease.
Circulating miR-181 is a prognostic biomarker for amyotrophic lateral sclerosis
Authors: Magen Iddo , Yacovzada Nancy Sarah , Yanowski Eran , Coenen-Stass Anna , Grosskreutz Julian , Lu Ching-Hua , Greensmith Linda , Malaspina Andrea , Fratta Pietro , Hornstein Eran 
Published: November 2019

AbstractAmyotrophic lateral sclerosis (ALS) is a relentless neurodegenerative syndrome of the human motor neuron system, for which no effective treatment exists. Variability in the rate of disease progression limits the efficacy of ALS clinical trials, suggesting that developing of better biomarkers for prognosis will facilitate therapeutic progress. Here, we applied unbiased next-generation sequencing to investigate the potential of plasma cell-free microRNAs as biomarkers of ALS prognosis, in 252 patients with detailed clinical-phenotyping. First, we identified miRNAs, whose plasma levels remain stable over the course of disease in a longitudinal cohort of 22 patients. Next, we demonstrated that high levels of miR-181, a miRNA enriched in neurons of the brain and spinal cord, predicts a >2 fold risk of death in discovery cohort (126 patients) and an independent replication cohort (additional 122 patients). miR-181 performance is comparable with the established neurofilament light chain (NfL) biomarker and when combined together, miR-181+NfL establish a novel RNA-protein biomarker pair with superior prediction capacity of ALS prognosis. Therefore, plasma miR-181 predicts ALS disease course, and a novel miRNA-protein biomarker approach, based on miR-181+NfL, boosts precision of patient stratification and may greatly enhance the power of clinical trials.One Sentence Summaryplasma miR-181 levels indicate high mortality risk in ALS patients.
Quantifying genetic heterogeneity between continental populations for human height and body mass index
Authors: Guo Jing , Bakshi Andrew , Wang Ying , Jiang Longda , Yengo Loic , Goddard Michael E , Visscher Peter M , Yang Jian 
Published: November 2019

AbstractGenome-wide association studies (GWAS) in samples of European ancestry have identified thousands of genetic variants associated with complex traits in humans. However, it remains largely unclear whether these associations can be used in non-European populations. Here, we seek to quantify the proportion of genetic variation for a complex trait shared between continental populations. We estimated the between-population correlation of genetic effects at all SNPs (rg) or genome-wide significant SNPs (rg(GWS)) for height and body mass index (BMI) in samples of European (EUR;n= 49,839) and African (AFR;n= 17,426) ancestry. Thebetween EUR and AFR was 0.75 (s. e. = 0.035) for height and 0.68 (s. e. = 0.062) for BMI, and the correspondingwas 0.82 (s. e. = 0.030) for height and 0.87 (s. e. = 0.064) for BMI, suggesting that a large proportion of GWAS findings discovered in Europeans are likely applicable to non-Europeans for height and BMI. There was no evidence thatdiffers in SNP groups with different levels of between-population difference in allele frequency or linkage disequilibrium, which, however, can be due to the lack of power.
Meaning maps and saliency models based on deep convolutional neural networks are insensitive to image meaning when predicting human fixations
Authors: Pedziwiatr Marek A. , Kümmerer Matthias , Wallis Thomas S.A. , Bethge Matthias , Teufel Christoph 
Published: November 2019

AbstractEye movements are vital for human vision, and it is therefore important to understand how observers decide where to look. Meaning maps (MMs), a technique to capture the distribution of semantic importance across an image, have recently been proposed to support the hypothesis that meaning rather than image features guide human gaze. MMs have the potential to be an important tool far beyond eye-movements research. Here, we examine central assumptions underlying MMs. First, we compared the performance of MMs in predicting fixations to saliency models, showing that DeepGaze II – a deep neural network trained to predict fixations based on high-level features rather than meaning – outperforms MMs. Second, we show that whereas human observers respond to changes in meaning induced by manipulating object-context relationships, MMs and DeepGaze II do not. Together, these findings challenge central assumptions underlying the use of MMs to measure the distribution of meaning in images.
Remodeling of Crossbridges Controls Peptidoglycan Cross-linking Levels in Bacterial Cell Walls
Authors: Pidgeon Sean E. , Apostolos Alexis J. , Pires Marcos M. 
Published: November 2019

ABSTRACTCell walls are barriers found in almost all known bacterial cells. These structures establish a controlled interface between the external environment and vital cellular components. A primary component of cell wall is a highly crosslinked matrix called peptidoglycan (PG). PG crosslinking, carried out by transglycosylases and transpeptidases, is necessary for proper cell wall assembly. Transpeptidases, targets of β-lactam antibiotics, stitch together two neighboring PG stem peptides (acyl-donor and acyl-acceptor strands). We recently described a novel class of cellular PG probes that were processed exclusively as acyl-donor strands. Herein, we have accessed the other half of the transpeptidase reaction by developing probes that are processed exclusively as acyl-acceptor strands. The critical nature of the crossbridge on the PG peptide was demonstrated in live bacterial cells and surprising promiscuity in crossbridge primary sequence was found in various bacterial species. Additionally, acyl-acceptor probes provided insight into how chemical remodeling of the PG crossbridge (e.g., amidation) can modulate crosslinking levels, thus establishing a physiological role of PG structural variations. Together, the acyl-donor and -acceptor probes will provide a versatile platform to interrogate PG crosslinking in physiologically relevant settings.SYNOPSIS TOC
Whole-transcriptome RNA editing analysis in single cortical neurons links locus 15q11 with psychiatric illness
Authors: Ansell Brendan Robert E. , Thomas Simon N. , Bonelli Roberto , Munro Jacob E. , Freytag Saskia , Bahlo Melanie 
Published: November 2019

ABSTRACTBACKGROUNDConversion of adenosine to inosine in RNA by ADAR enzymes occurs at thousands of sites in the human transcriptome, and is essential for healthy brain development. This ‘RNA editing’ process is dysregulated in many neuropsychiatric diseases, but is little understood at the level of individual neurons.METHODSWe quantified RNA editing sites in full-length capture nuclear transcriptomes of 3055 neurons from six cortical regions of a neurotypical post-mortem female donor. Putative editing sites were intersected with sites in bulk human tissue transcriptomes including healthy and neuropsychiatric brain tissue, and sites identified in single nuclei from unrelated brain donors. Differential editing between cell types and cortical regions, and individual sites and genes therein, was quantified using linear models. Associations between gene expression and editing were also tested.RESULTSWe identified 41,930 RNA editing sites with robust read coverage in at least ten neuronal nuclei. Most sites were located within Alu repeats in introns or 3’ UTRs, and approximately 80% were catalogued in published RNA editing databases. We identified 9285 putative novel RNA editing sites, 29% of which were also detectable neuronal transcriptomes from unrelated donors. Inhibitory neurons showed higher overall transcriptome editing than excitatory neurons. Among the strongest correlates of global editing rates were snoRNAs from the SNORD115 and SNORD116 cluster (15q11), known to modulate serotonin receptor processing and to colocalize with ADAR2. We identified 29 genes preferentially edited in excitatory neurons and 44 genes edited more heavily in inhibitory neurons including RBFOX1, its target genes and small nucleolar RNA-associated genes in the autism-associated Prader-Willi locus 15q11. These results provide cell-type and spatial context for 1730 and 910 sites that are also edited in the brains of schizophrenic and autistic patients respectively, and a reference for future studies of RNA editing in single brain cells from these cohorts.CONCLUSIONSRNA editing, including thousands of previously unreported sites, is robustly detectable in single neuronal nuclei, where gene editing differences are stronger between cell subtypes than between cortical regions. Insufficient editing of ASD-related genes in inhibitory neurons may manifest in the specific perturbation of these cells in autism.