bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single-cell transcriptomic atlas of Alzheimer’s disease middle temporal gyrus reveals region, cell type and sex specificity of gene expression with novel genetic risk for MERTK in female
Authors: Zhang Le , He Chuan Hua , Coffey Sarah , Yin Dominic , Hsu I-Uen , Su Chang , Ye Yixuan , Zhang Chi , Spurrier Joshua , Nicholson LaShae , Rothlin Carla V. , Ghosh Sourav , Gopal Pallavi P. , Hafler David A. , Zhao Hongyu , Strittmatter Stephen M. 
Published: February 2023

AbstractAlzheimer’s disease, the most common age-related neurodegenerative disease, is closely associated with both amyloid-ß plaque and neuroinflammation. Two thirds of Alzheimer’s disease patients are females and they have a higher disease risk. Moreover, women with Alzheimer’s disease have more extensive brain histological changes than men along with more severe cognitive symptoms and neurodegeneration. To identify how sex difference induces structural brain changes, we performed unbiased massively parallel single nucleus RNA sequencing on Alzheimer’s disease and control brains focusing on the middle temporal gyrus, a brain region strongly affected by the disease but not previously studied with these methods. We identified a subpopulation of selectively vulnerable layer 2/3 excitatory neurons that that were RORB-negative and CDH9-expressing. This vulnerability differs from that reported for other brain regions, but there was no detectable difference between male and female patterns in middle temporal gyrus samples. Disease-associated, but sex-independent, reactive astrocyte signatures were also present. In clear contrast, the microglia signatures of diseased brains differed between males and females. Combining single cell transcriptomic data with results from genome-wide association studies (GWAS), we identifiedMERTKgenetic variation as a risk factor for Alzheimer’s disease selectively in females. Taken together, our single cell dataset revealed a unique cellular-level view of sex-specific transcriptional changes in Alzheimer’s disease, illuminating GWAS identification of sex-specific Alzheimer’s risk genes. These data serve as a rich resource for interrogation of the molecular and cellular basis of Alzheimer’s disease.
Estimating the Genetic Contribution to Astigmatism and Myopia in the Mexican population
Authors: Román-López Talía V. , García-Vilchis Brisa , Murillo-Lechuga Vanessa , Chiu-Han Enrique , Xanat López-Camaño , Aldana-Assad Oscar , Diaz-Torres Santiago , Caballero-Sánchez Ulises , Ivett E. Ortega-Mora I. , Ramirez-Gonzalez Diego , Zenteno Diego , Espinosa-Valdés Zaida , Tapia-Atilano Andrea , Pradel-Jiménez Sofía , Rentería Miguel E. , Medina-Rivera Alejandra , Ruiz-Contreras Alejandra E. , Alcauter Sarael 
Published: February 2023

AbstractAstigmatism and myopia are two common ocular refractive errors that can impact daily life, including student learning and productivity. Current understanding suggests that the etiology of these conditions is the result of a complex interplay between genetic and environmental factors. Studies in populations of European ancestry have demonstrated a higher concordance of refractive errors in monozygotic (MZ) twins compared to dizygotic (DZ) twins. However, there is a lack of studies on genetically informative samples of multi-ethnic ancestry. This study aimed to estimate the genetic contribution to astigmatism and myopia in the Mexican population. A sample of 1399 families, including 243 twin pairs and 1156 single twins, completed a medical questionnaire about their own and their co-twins diagnosis of astigmatism and myopia. Concordance rates for astigmatism and myopia were estimated in Mexican twins, and heritability and genetic correlations were determined using a bivariate ACE Cholesky decomposition method. The results showed a concordance rate of 0.74 for MZ twins and 0.50 for DZ twins for astigmatism, and a higher concordance rate in MZ twins, 0.74, compared to DZ twins, 0.54 for myopia. Heritability estimates were 0.66 for astigmatism and 0.62 for myopia, with a cross-trait genetic correlation of rA=0.82 and a phenotypic correlation of rP=0.80. These results are consistent with previous findings in other populations, providing evidence for a similar genetic architecture of these conditions in the multi-ethnic Mexican population.
Ethical dilemma arises from optimising interventions for epidemics in heterogeneous populations
Authors: Kollepara Pratyush K. , Chisholm Rebecca H. , Kiss István Z. , Miller Joel C. 
Published: February 2023

AbstractInterventions to mitigate the spread of infectious diseases, while succeeding in their goal, have economic and social costs associated with them. These limit the duration and intensity of the interventions. We study a class of interventions which reduce the reproduction number and find the optimal strength of the intervention which minimises the final epidemic size for an immunity inducing infection. The intervention works by eliminating the overshoot part of an epidemic, and avoids a second-wave of infections. We extend the framework by considering a heterogeneous population and find that the optimal intervention can pose an ethical dilemma for decision and policy makers. This ethical dilemma is shown to be analogous to the trolley problem. We apply this optimisation strategy to real world contact data and case fatality rates from three pandemics to underline the importance of this ethical dilemma in real world scenarios.
Phenome-wide analysis ofAPOL1risk variants reveals associations between one combination of haplotypes and multiple disease phenotypes in addition to chronic kidney disease
Authors: Adamson Walt E. , Noyes Harry , Johnson Paul , Cooper Anneli , Monckton Darren G. , Ogunsola John , Sullivan Michael , Mark Patrick , Parekh Rulan S. , MacLeod Annette 
Published: February 2023

AbstractBackgroundInfectious diseases are a major driving force of natural selection. One human gene associated with strong evolutionary selection isAPOL1. TwoAPOL1variants, G1 and G2, emerged in sub-Saharan Africa in the last 10,000 years, possibly due to protection from the fatal African sleeping sickness, analogous toPlasmodium-driven selection of the sickle-cell trait. As homozygosity for the HbS allele causes sickle cell anaemia, homozygosity for theAPOL1G1 and G2 variants has also been associated with chronic kidney disease (CKD) and other kidney-related conditions. What is not known is the extend of non-kidney-related disorders and if there are clusters of diseases associated with individual APOL1 genotypes.MethodsUsing principal component analysis, we identified a cohort of 10,179 UK Biobank participants with recent African ancestry. We conducted a phenome-wide association test between all combinations ofAPOL1G1 and G2 genotypes and conditions identified with International Classification of Disease phenotypes using Firth’s bias-reduced logistic regression and a false discovery rate to correct for multiple testing. We further examined associations with chronic kidney disease indicators: estimated glomerular filtration rate (eGFR) and urinary albumin:creatinine (uACR).ResultsThe phenome-wide screen revealed 74 (mostly deleterious) potential associations with hospitalisation for a range of conditions. G1/G2 compound heterozygotes were specifically associated with hospitalisation in 64 (86.5%) of these conditions, with an over-representation of infectious diseases (including COVID-19) and endocrine, nutritional, and metabolic diseases. The analysis also revealed complexities in the relationship betweenAPOL1and CKD that are not evident when the risk variants are grouped together: high uACR was associated specifically with G1 homozygosity; low eGFR with G2 homozygosity and G1/G2 compound heterozygosity; progression to end stage kidney disease was associated with G1/G2 compound heterozygosity.ConclusionsAmong 9,594 participants, stratifying individualAPOL1risk variant genotypes had a differential effect on associations with both kidney and non-kidney phenotypes. The compound heterozygous G1/G2 genotype was distinguished as uniquely deleterious in its association with a range of ICD-10 phenotypes. The epistatic nature of the G1/G2 interaction means that such associations may go undetected in a standard genome-wide association study. These observations have the potential to significantly impact the way that health risks are understood, particularly in populations whereAPOL1G1 and G2 are common such as in sub-Saharan Africa and its diaspora.
Impact of Pulmonary and Sleep Disorders on COVID-19 Infection Severity in a Large Clinical Biobank
Authors: Cade Brian E. , Hassan Syed Moin , Mullington Janet M. , Karlson Elizabeth W. , Redline Susan 
Published: February 2023

AbstractRationaleMultiple pulmonary, sleep, and other disorders are associated with the severity of Covid-19 infections but may or may not directly affect the etiology of acute Covid-19 infection. Identifying the relative importance of concurrent risk factors may prioritize respiratory disease outbreaks research.ObjectivesTo identify associations of common preexisting pulmonary and sleep disease on acute Covid-19 infection severity, investigate the relative contributions of each disease and selected risk factors, identify sex-specific effects, and examine whether additional electronic health record (EHR) information would affect these associations.Methods45 pulmonary and 6 sleep diseases were examined in 37,020 patients with Covid-19. We analyzed three outcomes: death; a composite measure of mechanical ventilation and/or ICU admission; and inpatient admission. The relative contribution of pre-infection covariates including other diseases, laboratory tests, clinical procedures, and clinical note terms was calculated using LASSO. Each pulmonary/sleep disease model was then further adjusted for covariates.Measurements and main results37 pulmonary/sleep diseases were associated with at least one outcome at Bonferroni significance, 6 of which had increased relative risk in LASSO analyses. Multiple prospectively collected non-pulmonary/sleep diseases, EHR terms and laboratory results attenuated the associations between preexisting disease and Covid-19 infection severity. Adjustment for counts of prior “blood urea nitrogen” phrases in clinical notes attenuated the odds ratio point estimates of 12 pulmonary disease associations with death in women by ≥1.ConclusionsPulmonary diseases are commonly associated with Covid-19 infection severity. Associations are partially attenuated by prospectively-collected EHR data, which may aid in risk stratification and physiological studies.
Longitudinal Humoral and Cell-Mediated Immune Responses in a Population-Based Cohort in Zurich, Switzerland between March and June 2022 - Evidence for Protection against Omicron SARS-CoV-2 Infection by Neutralizing Antibodies and Spike-specific T cell responses
Authors: Zens K.D. , Llanas-Cornejo D. , Menges D. , Fehr J.S. , Münz C. , Puhan M.A. , Frei A. 
Published: February 2023

ABSTRACTBackgroundThe correlate(s) of protection against SARS-CoV-2 remain incompletely defined. Additional information regarding the combinations of antibody and T cell-mediated immunity which can protect against (re)infection are needed.MethodsWe conducted a population-based, longitudinal cohort study including 1044 individuals of varying SARS-CoV-2 vaccination and infection statuses. We assessed Spike (S)- and Nucleocapsid (N)-IgG and wildtype, delta, and omicron neutralizing antibodies. In a subset of 328 individuals, we evaluated S, Membrane (M) and N-specific T cells. 3 months later, we reassessed antibody (n=964) and T cell (n=141) responses and evaluated factors associated with protection from (re)infection.ResultsAt study start, >98% of participants were S-IgG seropositive. N-IgG and M/N-T cell responses increased over time, indicating viral (re)exposure, despite existing S-IgG. Compared to N-IgG, M/N-T cells were a more sensitive measure of viral exposure. N-IgG titers in the top 33% of participants, omicron neutralizing antibodies in the top 25%, and S-specific T cell responses were all associated with reduced likelihood of (re)infection over time.ConclusionsPopulation-level SARS-CoV-2 immunity is S-IgG-dominated, but heterogenous. M/N T cell responses can distinguish previous infection from vaccination, and monitoring a combination of N-IgG, omicron neutralizing antibodies and S-T cell responses may help estimate protection against SARS-CoV-2 (re)infection.
The effectiveness of digital delivery versus group-based face-to-face delivery of the English National Health Service Diabetes Prevention Programme: a non-inferiority retrospective cohort comparison study
Authors: Marsden Antonia M. , Hann Mark , Barron Emma , McGough Ben , Murray Elizabeth , Valabhji Jonathan , Cotterill Sarah 
Published: February 2023

ABSTRACTIntroductionFace-to-face group-based diabetes prevention programmes have been shown to be effective in many settings. Digital delivery may suit some patients, but research comparing the effectiveness of digital with face-to-face delivery is scarce. The aim was to assess if digital delivery of the English National Health Service Diabetes Prevention Programme (NHS DPP) is non-inferior to group-based face-to-face delivery in terms of weight change, and evaluate factors associated with differential change. The study included those recruited to the NHS DPP in 2017-2018.Research design and methodsIndividual-level data from a face-to-face cohort was compared to two cohorts on a digital pilot who (i) were offered no choice of delivery mode, or (ii) chose digital over face-to-face. Changes in weight at 6 and 12 months were analysed using mixed effects linear regression, having matched participants from the digital pilot to similar participants from face-to-face.ResultsWeight change on the digital pilot was non-inferior to face-to-face at both time points: it was similar in the comparison of those with no choice (difference in weight change: −0.284kg [95% CI: −0.712, 0.144] at 6 months) and greater in digital when participants were offered a choice (−1.165kg [95% CI: −1.841, −0.489]). Interactions between delivery mode and sex, ethnicity, age and deprivation were observed.ConclusionsDigital delivery of the NHS DPP achieved weight loss at least as good as face-to-face. Patients who were offered a choice and opted for digital experienced better weight loss, compared to patients offered face-to-face only.
INTEGRATED NCDs TREATMENT AND CARE AMONG PEOPLE LIVING WITH HIV/AIDS ATTENDING CARE AND TREATMENT AT A HEALTH FACILITY
Authors: Musyani Atuganile , Mosi Grace , Kinyenje Erik , Damasceno Albertino , Mizinduko Mucho , Kishimba Rogath , Shimwela Meshack , Subi Leonard 
Published: February 2023

ABSTRACTIntroductionPersons living with HIV (PLHIV) in Tanzania now live longer due to the advancement of HIV care programs. For this reason, they are at an increased risk of developing Non-Communicable Diseases (NCDs). Despite many resources committed to HIV care programs, NCDs care is not effectively integrated into these programs. The study aimed at describing missed opportunities to diagnose and manage hypertension and diabetes and implementing and evaluating the effect of three months of preventive efforts among among PLHIV attending care and treatment centers (CTC)Materials and methodsWe evaluated 333 PLHIV attending CTC for blood pressure and blood sugar levels. Patients who were diagnosed with high blood pressure equal to or above 140/90 mm Hg, or on treatment for hypertension and a fasting blood sugar above 7.0 mmol/L (126 mg/dl) were subjected to a small intervention aimed at increasing health literacy on the adherence to and control of their pathologies. Re-evaluation of their blood pressure and blood sugar levels was done at the end of a 3 months intervention.ResultsOf the evaluated 333 PLHIV, 71 (21.32%) had hypertension and 9 (2.70%) had high blood sugar. Among 177 PLHIV who never had their BP measured before, 37/177 ((20.90%) were diagnosed with hypertension. The cohort group involved analysis of 76 patients with either uncontrolled hypertension or diabetes followed for three months. By the end of the 3rdmonth of intervention, 26/71 (36.6%) were able to control their blood pressure (BP < 140 SBP and < 90 DBP). The mean blood pressure decreased from 164/99.5 mmHg to 159 /96mmHg. Of the 9 PLHIV with high blood glucose levels, 5/9 (55.5%) had their blood sugar normalized at the end of the intervention. In a focused group discussion, most patients reported difficulties in controlling their BP due to the high cost of medication and consequently poor adherence to medication.ConclusionThe burden of undiagnosed NCDs among PLHIV attending care and treatment clinic is remarkably high. Interventions to address such diseases in CTC seem to work. HIV care and treatment programs should provide integrated care that includes NCDs care.
Active methods, and their educational strategies during residencies of health professions: a scope review
Authors: Garcia Vera Lúcia , Soeiro Everton , de Oliveira José Maurício , Schiesari Laura , Gomes Romeu , Riera Rachel 
Published: February 2023

AbstractThe objective of this study is to map and evaluate the scientific production, on the different strategies / active methods in the context of residences of health professions. The study will be developed at Hospital Sírio-Libanês, São Paulo, Brazil. The scope review will be developed based on the methodological framework of the Joanna Brigss Institute (Peters et al., 2017). The review report will follow recommendations of the Preferred Reporting Items for Systematic Reviews and Meta Analyses extension for scoping reviews (PRISMA ScR) (Tricco, 2018). The protocol for this review was planned and made available on the MEdRxiv preprint database prior to the start of conducting the review. The following research question will guide for searching in databases: What and how are the different active methods used in the context of residencies of health professions? A broad and sensitive search will be carried out in the literature through structured search strategies, with relevant descriptors and synonyms, for the following databases or data repositories in the areas of education and/or health listed below: Biblioteca Virtual de Saúde (BVS), British Education Index (BEI), Campbell Collaboration, Cochrane Library (via Wiley), Education Research Complete (via EBSCO), Educational Resources Information Center – ERIC, Excerpta Medica Database (EMBASE, via Elsevier), Medical Literature Analysis and Retrieval System Online (MEDLINE, via PubMed), Online Education Database.
A Compendium of manually annotated genetic variants for Alkaptonuria-AKUHub
Authors: Akila S , Arun Kumar T.C , Shofia S , Srividya S , Suriyamoorthy N , Vijhayalakshmi R , scaria Vinod , Mehta Ratnesh Bhai 
Published: February 2023

1.AbstractAlkaptonuria or ‘black urine disease’ is a rare autosomal recessive disorder caused by dysfunctional homogentisate 1,2-dioxygenase (HGD) gene (3q13.33) leading to accumulation of homogentisic acid in the body. This inborn error in metabolism of phenylalanine and tyrosine causes accumulation of homogentisic acid leading to ochronosis, pigmentation in the sclera, ear cartilage, mitral valve calcification and osteoarthropathy. Advances in sequencing technologies have helped us to map genetic variants associated with alkaptonuria in diverse populations and regions. Currently, no centralized resource of all the reported actionable variants with uniformity in annotation exists for the HGD gene. We have compiled HGD exonic variants from various data sources and systematically annotated their pathogenicity according to American College of Medical Genetics and the Association of Molecular Pathologists (ACMG/AMP) variant classification framework. A total of 1686 exonic variants were catalogued and manually curated, creating one of the most comprehensive Alkaptonuria variant databases (AKUHub) which is publicly available.
Multicenter analysis of atrioesophageal fistula rates before and after adoption of active esophageal cooling during atrial fibrillation ablation
Authors: Sanchez Javier , Woods Christopher , Zagrodzky Jason , Nazari Jose , Singleton Matthew , Schricker Amir , Ruppert Annie , Brumback Babette , Jenny Benjamin , Athill Charles , Joseph Christopher , Shah Dipak , Upadhyay Gaurav , Kulstad Erik , Cogan John , Leyton-Mange Jordan , Cooper Julie , Tamirisa Kamala , Omotoye Samuel , Timilsina Saroj , Perez-Verdia Alejandro , Kaplan Andrew , Patel Apoor , Ro Alex , Corsello Andrew , Kolli Arun , Greet Brian , Willms Danya , Burkland David , Castillo Demetrio , Zahwe Firas , Nayak Hemal , Daniels James , MacGregor John , Sackett Matthew , Kutayli Michael , Barakat Michel , Percell Robert , Akrivakis Spyridon , Hao Steven C. , Liu Taylor , Panico Ambrose , Ramireddy Archana , Lanes Daniel Benhayon , Sze Edward , Francisco Greg , Silva Jose , McHugh Julia , Sung Kai , Feldman Leon , Serafini Nicholas , Kawasaki Raymond , Hongo Richard , Kuk Richard , Hayward Robert , Park Shirley , Vu Andrew , Henry Christopher , Bailey Shane , Mickelsen Steven , Taneja Taresh , Fisher Westby , Metzl Mark 
Published: February 2023

ABSTRACTBackgroundActive esophageal cooling reduces the incidence of endoscopically identified severe esophageal lesions during radiofrequency (RF) catheter ablation of the left atrium for the treatment of atrial fibrillation. No atrioesophageal fistula (AEF) has been reported to date with active esophageal cooling, and only one pericardio-esophageal fistula has been reported; however, a formal analysis of the AEF rate with active esophageal cooling has not previously been performed.MethodsAtrial fibrillation ablation procedure volumes before and after adoption of active cooling using a dedicated esophageal cooling device (ensoETM, Attune Medical) were determined across 25 hospital systems with the highest total use of esophageal cooling during RF ablation. The number of AEFs occurring in equivalent time frames before and after adoption of cooling were then determined, and AEF rates were compared using generalized estimating equations robust to cluster correlation.ResultsThroughout the 25 hospital systems, which included a total of 30 separate hospitals, 14,224 patients received active esophageal cooling during RF ablation, with the earliest adoption beginning in March 2019 and the most recent beginning in March 2022. In the time frames prior to adoption of active cooling, a total of 10,962 patients received primarily luminal esophageal temperature (LET) monitoring during their RF ablations. In this pre-adoption cohort a total of 16 AEFs occurred, for an AEF rate of 0.146%, in line with other published estimates of <0.1% to 0.25%. No AEFs were found in the cohort treated after adoption of active esophageal cooling, yielding an AEF rate of 0% (P<0.0001).ConclusionAdoption of active esophageal cooling during RF ablation of the left atrium for the treatment of atrial fibrillation was associated with a significant reduction in AEF rate.