bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multi-omic Characterization of HIV Effects at Single Cell Level across Human Brain Regions
Authors: Yang Junchen , Agrawal Kriti , Stanley Jay , Li Ruiqi , Jacobs Nicholas , Wang Haowei , Lu Chang , Qu Rihao , Clarke Declan , Chen Yuhang , Jiang Yunzhe , Bai Donglu , Zheng Suchen , Fox Howard , Ho Ya-chi , Huttner Anita , Gerstein Mark , Kluger Yuval , Zhang Le , Spudich Serena 
Published: February 2025

AbstractHIV infection exerts profound and long-lasting neurodegenerative effects on the central nervous system (CNS) that can persist despite antiretroviral therapy (ART). Here, we used single-nucleus multiome sequencing to map the transcriptomic and epigenetic landscapes of postmortem human brains from 13 healthy individuals and 20 individuals with HIV who have a history of treatment with ART. Our study spanned three distinct regions—the prefrontal cortex, insular cortex, and ventral striatum—enabling a comprehensive exploration of region-specific and cross-regional perturbations. We found widespread and persistent HIV-associated transcriptional and epigenetic alterations across multiple cell types. Detailed analyses of microglia revealed state changes marked by immune activation and metabolic dysregulation, while integrative multiomic profiling of astrocytes identified multiple subpopulations, including a reactive subpopulation unique to HIV-infected brains. These findings suggest that cells from people with HIV exhibit molecular shifts that may underlie ongoing neuroinflammation and CNS dysfunction. Furthermore, cell–cell communication analyses uncovered dysregulated and pro-inflammatory interactions among glial populations, underscoring the multifaceted and enduring impact of HIV on the brain milieu. Collectively, our comprehensive atlas of HIV-associated brain changes reveals distinct glial cell states with signatures of pro-inflammatory signaling and metabolic dysregulation, providing a framework for developing targeted therapies for HIV-associated neurological dysfunction.
Human differentiated adipocytes can serve as surrogate mature adipocytes for adipocyte-derived extracellular vesicle analysis
Authors: Butsch Bradley L. , Hade Mangesh Dattu , Palacio Paola Loreto , Nguyen Kim Truc , Shantaram Dharti , Noria Sabrena , Brethauer Stacy A. , Needleman Bradley J. , Hsueh Willa , Reátegui Eduardo , Magaña Setty M. 
Published: February 2025

AbstractObesity is a growing global health concern, contributing to diseases such as cancer, autoimmune disorders, and neurodegenerative conditions. Adipose tissue dysfunction, characterized by abnormal adipokine secretion and chronic inflammation, plays a key role in these conditions. Adipose-derived extracellular vesicles (ADEVs) have emerged as critical mediators in obesity-related diseases. However, the study of mature adipocyte-derived EVs (mAdipo-EVs) is limited due to the short lifespan of mature adipocytes in culture, low EV yields, and the low abundance of these EV subpopulations in the circulation. Additionally, most studies rely on rodent models, which have differences in adipose tissue biology compared to humans. To overcome these challenges, we developed a standardized approach for differentiating human preadipocytes (preAdipos) into mature differentiated adipocytes (difAdipos), which produce high-yield, human adipocyte EVs (Adipo-EVs). Using visceral adipose tissue from bariatric surgical patients, we isolated the stromal vascular fraction (SVF) and differentiated preAdipos into difAdipos. Brightfield microscopy revealed that difAdipos exhibited morphological characteristics comparable to mature adipocytes (mAdipos) directly isolated from visceral adipose tissue, confirming their structural similarity. Additionally, qPCR analysis demonstrated decreased preadipocyte markers and increased mature adipocyte markers, further validating successful differentiation. Functionally, difAdipos exhibited lipolytic activity comparable to mAdipos, supporting their functional resemblance to native adipocytes. We then isolated preAdipo-EVs and difAdipo-EVs using tangential flow filtration and characterized them using bulk and single EV analysis. DifAdipo-EVs displayed classical EV and adipocyte-specific markers, with significant differences in biomarker expression compared to preAdipo-EVs. These findings demonstrate that difAdipos serve as a reliable surrogate for mature adipocytes, offering a consistent and scalable source of adipocyte-derived EVs for studying obesity and its associated disorders.
Chronic alcohol consumption enhances the differentiation capacity of hematopoietic stem and progenitor cells into osteoclast precursors
Authors: Hemati Hami , Blanton Madison B. , koura Jude , Khadka Rupak , Grant Kathleen A. , Messaoudi Ilhem 
Published: February 2025

ABSTRACTChronic alcohol consumption (CAC) is associated with an enhanced risk of bone fracture, reduced bone density, and osteoporosis. We have previously shown using a rhesus macaque model of voluntary ethanol consumption that CAC induces functional, transcriptomic, and epigenomic changes in hematopoietic stem and progenitor cells (HSPCs) and their resultant monocytes/macrophages, skewing them towards a hyper-inflammatory response. Here, we extended those studies and investigated alterations in osteoclasts, which, in postnatal life, are differentiated from HSPCs and play a critical role in maintaining bone homeostasis. Analysis using spectral flow cytometry revealed a skewing of HSPCs towards granulocyte-monocyte progenitors (GMPs) with the CAC group that was in concordance with an increased number of colony-forming unit-granulocyte/macrophage (CFU-GM). Additionally, HSPCs from animals in the CAC group incubated with M-CSF and RANKL were more likely to differentiate into osteoclasts, as evidenced by increased Tartrate-Resistant Acid Phosphatase (TRAP) staining and bone resorption activity. Moreover, single-cell RNA sequencing of differentiated HSPCs identified three clusters of osteoclast precursors in the CAC group with enhanced gene expression in pathways associated with cellular response to stimuli, membrane trafficking, and vesicle-mediated transport. Collectively, these data show that CAC-derived hematopoietic progenitor cells exhibit a higher capacity to differentiate into osteoclast precursors. These findings provide critical insights for future research on the mechanisms by which CAC disrupts monopoiesis homeostasis and enhances osteoclast precursors, thereby contributing to reduced bone density.
The association between maternal parenting styles and eating disorders among Lebanese university students: The mediating role of the self-assessment dimension of self-esteem
Authors: Sawma Toni , El Khoury-Malhame Myriam , Hayek Tatiana , Mourad Jana , Bou Malhab Sandrella , Rizk Rana 
Published: February 2025

AbstractObjectiveEating disorders are influenced by an array of distinct factors such as genetics, personality traits, and history of childhood abuse. Recently maternal parenting styles have been investigated as one of the contributing aspects. These styles are intricately connected to children’s self-esteem. As such this study aims to examine the association between maternal parenting styles and eating disorders and better investigate the mediating role of the self-assessment, an essential understudied dimension of self-esteem.MethodA cross-sectional online study was conducted between November 2023 and May 2024. Around 300 Lebanese university students filled out surveys assessing demographic factors, maternal parenting style, eating disorders, and self-assessment.ResultsWe found that different maternal styles distinctly influence the development of eating disorders; with self-esteem mediating the relationship between different maternal parenting styles and eating disorders development. Self-assessment negatively mediated the association between maternal expectations and eating control and dieting, and it negatively mediated the association between maternal permissive and dieting and bulimia. Self-assessment positively mediated the association between maternal control and eating control, dieting, and bulimia.DiscussionThis study mostly provides healthcare professionals and clinical educators with valuable insights into the complex association between parenting and eating disorders and highlights the importance of developing skillsets to boost self-esteem for those at risk of developing eating disorders.
Gender Discrimination and Medical Student Development
Authors: Venkataraman Shruthi , Nguyen Mytien , Chaudhry Sarwat I. , Desai Mayur M. , Fancher Tonya L. , Hajduk Alexandra M. , Mason Hyacinth R. C. , Webber Alexis , Boatright Dowin 
Published: February 2025

AbstractBackgroundDespite prevalent gender discrimination in medical education, its influence on personal and professional development, foundational competencies in medical training per the Association of American Medical Colleges (AAMC), remains unclear. This retrospective cross-sectional study assesses how experiences of gender discrimination in medical school influence personal and professional identity formation (PPIF).MethodsDeidentified student-level data were procured from the AAMC data warehouse for 37,610 MD students who matriculated in 2014-2015 and took the Graduation Questionnaire (GQ) between 2016-2020. Gender discrimination frequency was categorized as ‘Never’, ‘Isolated’, and ‘Recurrent’ from GQ responses to questions about denial of opportunities, offensive remarks, and lower evaluations due to gender. Gender was binarized, due to dataset limitations. PPIF was assessed using two GQ metrics, personal and professional development, and dichotomized.ResultsFemale students experienced higher rates of isolated (12.6%) and recurrent (20.1%) gender discrimination than males (4.3% isolated, 6.2% recurrent). Females reported slightly lower personal (71.2%) but similar professional development (92.2%) rates compared to males (73.4% personal, 91.2% professional). Both genders experiencing gender discrimination had lower likelihoods of PPIF than their counterparts without these experiences. If recurrent discrimination occurred, the aRR (95%CI) of professional development was 0.89 (0.87-0.90) for females and 0.78 (0.74-0.81) for males, while for personal development, it was 0.69 (0.67-0.71) for females and 0.61 (0.58-0.66) for males. Compared to females, males showed sharper declines in professional development as discrimination frequency increased from never to isolated (exp(b)=0.93, 95% CI [0.92-0.94], p<0.001) and isolated to recurrent (exp(b)=0.95, 95% CI [0.93-0.97], p<0.001).ConclusionsGender discrimination negatively influences PPIF for both female and male medical students. Efforts to combat discrimination in medical training and promote holistic student development should be considered. Future work is needed to understand the influence of gender discrimination on the comprehensive development of gender-diverse medical students.
Uptake and rollout of the World Health Organization-endorsed technologies for Tuberculosis diagnosis in Africa: A systematic review of international evidence 2007-2021
Authors: Iragena Jean de Dieu , Uwimaana Esther , Semugenze Derrick , Komakech Kevin , Katamba Achilles , Martin Anandi , Joloba Moses , Ssengooba Willy 
Published: February 2025

BackgroundThe World Health Organization (WHO) has endorsed a range of diagnostic technologies for tuberculosis (TB) over the years, and at least one new endorsement is issued every year. However, little is documented about the uptake status in the WHO African Region (WHO/FR). We assessed the status of uptake of the WHO-endorsed TB diagnostics through a systematic review.MethodsWe conducted a systematic review of the peer-reviewed literature in French or English using PubMed, Google Scholar, and Embase for TB diagnostics endorsed by WHO between January 2007 and December 2017. We considered an extra period until December 2021 for the uptake and roll-out of the recently endorsed technologies and considered publications from the 47 countries in the WHO/AFR. We considered uptake as the use of the test in the country at any level and roll-out of the test as it is being used in the settings in which WHO endorsed for it. A summary number of articles was kept using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses diagrams (PRISMA) and the study protocol was registered with ISRCTN database. We used qualitative synthesis and quantitative data analysis by STATA version 14.0.ResultsWe recorded 3,399 articles searched in peer-reviewed databases, then we eliminated 1683 duplicates and finally kept 1,716 articles for screening and 92 articles qualified for analysis. For the uptake, out of 47 countries, the majority of articles were for Xpert MTB/RIF (XPERT) test 22 (47%), followed by Line Probe Assay (LPA), 10 (21%), and the Mycobacteria Growth Indicator Tube (MGIT) 9 (19%). For the rollout, 11 (24%) countries and 16 (36%) had publications on Lipoarabinomannan (LAM) and XPERT test use respectively. The median years (Interquartile Range: IQR) for uptake were 6 (3.2 - 7.9), 5 (2.5 - 6.5), and 2.5 (3.2 - 7.9) for MGIT, XPERT, and LPA respectively, and lower for other tests. For the rollout, the median years for MGIT, LPA, and XPERT were 7 (3 – 7), 6 (1.6 - 9.4), and 5 (4 - 7) respectively, and lower for other tests.ConclusionOur study shows that the uptake and rollout of TB diagnostic technologies upon the endorsement by WHO among WHO AFR countries is slow. Future studies are needed to document the key factors affecting rapid uptake and rollout. Strategies to document a rapid guide to inform rapid uptake and roll-out as well as best practices are highly recommended.
The genomic landscape of syndromic and non-syndromic hearing loss within the 100,000 Genomes Project cohort
Authors: Vestito Letizia , Smedley Damian , Cipriani Valentina , Moore Gudrun E , Stanier Philip , Bowl Michael R , Dawson Sally J , Clement Emma , Bitner-Glindzicz Maria 
Published: February 2025

AbstractObjectiveThis study aims to describe the genetic landscape of syndromic and non-syndromic hearing loss (HL) in the UK population using data from the 100,000 Genomes Project (100kGP).DesignCohort studySettingNHS EnglandParticipants2,271 families with syndromic and non-syndromic HL recruited to the 100kGP rare disease programme between 2013 and 2018. Participants with at least one Human Phenotype Ontology (HPO) term descendant of the term “Hearing impairment” (HP:0000365) were included; this equated to 5,488 individuals, comprising 2,762 affected individuals and 2,726 unaffected relatives.Main outcome measureDiagnostic rate and prevalence of different gene diagnoses by auditory phenotype identified by whole genome sequencing.ResultsThe overall diagnostic yield was conservatively estimated at 27.5% (625/2271), with diagnoses identified in 273 different genes. Common causative genes includedUSH2A, GJB2, COL1A1andMYO15A, accounting for approximately 20% of the diagnoses. This diagnostic rate excludes variants of uncertain significance (VUS), variants in genes where HL cannot be confidently attributed to the identified variant, or those still awaiting confirmation. The inclusion of these categories would increase the diagnostic yield to 39.6%. This work describes the 100kGP standard pipeline and supplementary analyses that include the use of Exomiser. Stratification of the cohort allowed quantification of the likelihood of genetic diagnosis with specific phenotypic combinations and identification of positive predictors for a genetic diagnosis by auditory phenotype. A statistically significant increase in diagnostic rate was reported for those with congenital (33.2%), bilateral (27%), and high-frequency (32.4%) hearing subtypes. Furthermore, in patients with HPO terms restricted to the auditory system alone, around 40% of diagnoses were attributed to genes that might have a broader syndromic phenotype (non-syndromic mimics). A high diagnostic yield (56%) was seen in patients with ear and eye abnormalities, largely driven by genes associated with Usher and Wolfram syndrome.ConclusionIn conclusion, this study offers valuable insights into the complex genomic and phenotypic architecture of both syndromic and non-syndromic HL, which has the potential to improve diagnostic pipelines and inform clinical care.
Validation of a Six-Item Multiple Sclerosis Impact Scale Short Form (MSIS-SF) for Efficient Assessment of Patient-Reported Physical Disturbance
Authors: Sumowski James F. , Levy Sarah 
Published: February 2025

ABSTRACTPatient-reported outcomes importantly reflect the lived experiences of persons with multiple sclerosis (MS); however, given the broad array of MS symptoms, comprehensive evaluation can be burdensome, especially with lengthy questionnaires. The MS Impact Scale queries twenty different physical difficulties (MSIS-20). In 1150 patients with MS, evaluation of internal consistency indicated redundancy in the MSIS-20 (Cronbach’s alpha: 0.96), but optimal internal consistency (0.90) of a six-item short form (MSIS-SF; first six MSIS items). The MSIS-20 and MSIS-SF showed comparably strong associations with objective physical disability. The MSIS-SF provides a psychometrically robust, less burdensome, and time-efficient option for assessing patient-reported physical disturbance.
Quantifying additive and multiplicative effects of socially stigmatized identities on self-reported overall health
Authors: LeStage Katrine , Vogel Robert , Vogel Julia Moore 
Published: February 2025

AbstractIndividuals with one or more socially stigmatized identities experience extensive health disparities. However, most studies consider the effects of only individual stigmatized identities. Further, the effects of individual identities and their intersections on overall health have not been quantified. We used participant-reported survey data collected in theAll of UsResearch Program and released to the controlled tier in April 2023 to statistically estimate the first and second order effects of 47 stigmatized identities on self-reported overall health. After using false discovery rate to adjust for testing multiple hypotheses, 29 individual stigmas had statistically significant effects on self-reported overall health and 116 pairs of stigmas did. All significant individual effects were negative or neutral except for skin cancer. Those with the largest negative effect on self-rated overall health are difficulty walking or climbing stairs, unemployed or unable to work, difficulty with errands, and low educational attainment. Pairs of intersecting stigmas had a mix of negative and positive incremental effects, indicating that some stigmatized identities are negative modifiers, such as depression, and other combinations are less negative that the sum of their individual negative effects, such as having difficulty with multiple types of activities of daily living. Taken together, there are numerous pairs of stigmatized identities that significantly affect self-reported overall health and therefore should be considered in research and clinical care.
Application of bidirectional Mendelian randomization to assess the relationship between the gut microbiome and esophageal cancer
Authors: Chataway James , Hamilton Georgina , Hatcher Charlie , Wade Kaitlin H. 
Published: February 2025

ABSTRACTBackgroundEsophageal cancer is the seventh most common cancer worldwide and typically carries a poor prognosis. Whilst smoking, alcohol and obesity are established risk factors, they do not fully account for disease variability and, increasingly, the gut microbiome has been implicated as a possible novel risk factor in observational studies. Mendelian randomization (MR), a technique that uses genetic variants as proxies for exposures to improve causal inference, is more robust to reverse causality and confounding, which typically bias observational studies.MethodsWe used summary statistics from large genome-wide association studies (GWASs) of both the gut microbiome and esophageal cancer phenotypes to conduct two-sample bidirectional MR analyses to investigate the causal relationship between 14 microbial traits and three esophageal cancer phenotypes: esophageal adenocarcinoma (EA), Barrett’s esophagus (BE) and both EA and BE as a combined phenotype (BE/EA). Where MR analyses provided evidence of causality between these phenotypes, several sensitivity analyses were conducted to interrogate its validity of MR assumptions.ResultsWhen assessing the causal role of the gut microbiome on esophageal cancer, there was little evidence that any microbial trait had a causal effect on any of the three esophageal cancer traits. In the reverse direction, MR analyses provided evidence that EA had a causal effect on two microbial traits. Specifically, an approximate doubling of the genetic liability to EA increased the odds of presence (vs. absence) of an unclassified group of bacteria within theFirmicutesphylum (odds ratio (OR): 1.66; 95% CI: 1.02, 2.70) and decreased the relative abundance of bacteria within theButyricicoccusgenus by 0.23 standard deviations (95% CI: 0.07, 0.40). However, importantly, sensitivity analyses showed that these observed effects were likely biased by horizontal pleiotropy and, thus, results should be interpreted with caution.ConclusionsAlthough initial analyses provided evidence of EA influencing two microbial traits, further sensitivity analyses indicated that these results were likely biased and unlikely to reflect causality. This highlights the importance of using robust MR methodology with appropriate sensitivity analyses, particularly in the setting of microbial traits, where host genetic effects are poorly understood and likely to be complex.
Virtual World Coupling with Photosynthesis Evaluation for Synthetic Data Production
Authors: Baker Dirk N. , Giraud Mona , Göbbert Jens Henrik , Scharr Hanno , Riedel Morris , Hvannberg Ebba Þóra , Schnepf Andrea 
Published: February 2025

AbstractIn this work, we couple the functional-structural plant model CPlantBox to the Unreal Engine by exploiting the implemented raytracing pipeline to evaluate light influx on the plant surface. There are many approaches for photosynthesis computation and light evaluation, though they typically are limited by versatility, compute speed, or operate on much coarser resolutions. This work specifically addresses the concern that data generation pipelines tend to be unresponsive and do not include model-based knowledge as part of the generation pipeline. Using established photosynthesis solvers, we model the interaction between the Unreal Engine and the FSPM to measure physical properties in the virtual world. This is successful if we are able to reproduce experimental results using an in silico model. As part of the pipeline, we generate a surface geometry and utilize material shaders that are designed to establish a baseline surface model for light interception and transmission, based on simple parameter sets that can be calibrated. Using a Selhausen field experiment as baseline, we reproduce the photosynthesis effectiveness of the plants in the 2016 winter wheat experiments. Our pipeline is deeply intertwined with data generation and has been proven to perform well at scale. In this work, we build on our previous work by showcasing both a simulation study of a light evaluation as well as quantifying how well our system performs on high-performance computing systems.