bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prediction and Characterization of Genetically Regulated Expression of Target Tissues in Asthma
Authors: Slack Sarah D. , Esquinca Erika , Arehart Christopher H. , Boorgula Meher Preethi , Szczesny Brooke , Romero Alex , Campbell Monica , Chavan Sameer , Rafaels Nicholas , Watson Harold , Landis R. Clive , Hansel Nadia N. , Rotimi Charles N. , Olopade Christopher O. , Figueiredo Camila A. , Ober Carole , Liu Andrew H. , Kenny Eimear E. , Kammers Kai , Ruczinski Ingo , Taub Margaret A. , Daya Michelle , Gignoux Christopher R. , Kechris Katerina , Barnes Kathleen C. , Mathias Rasika A. , Johnson Randi K. 
Published: February 2025

BackgroundGenetic control of gene expression in asthma-related tissues is not well-characterized, particularly for African-ancestry populations, limiting advancement in our understanding of the increased prevalence and severity of asthma in those populations.ObjectiveTo create novel transcriptome prediction models for asthma tissues (nasal epithelium and CD4+ T cells) and apply them in transcriptome-wide association study (TWAS) to discover candidate asthma genes.MethodsWe developed and validated gene expression prediction databases for unstimulated CD4+ T cells (CD4+T) and nasal epithelium using an elastic net framework. Combining these with existing prediction databases (N=51), we performed TWAS of 9,284 individuals of African-ancestry to identify tissue-specific and cross-tissue candidate genes for asthma. For detailed Methods, please see the Supplemental Methods.ResultsNovel databases for CD4+T and nasal epithelial gene expression prediction contain 8,351 and 10,296 genes, respectively, including four asthma loci (SCGB1A1, MUC5AC, ZNF366, LTC4S) not predictable with existing public databases. Prediction performance was comparable to existing databases and was most accurate for populations sharing ancestry with the training set (e.g. African ancestry). From TWAS, we identified 17 candidate causal asthma genes (adjustedP<0.1), including genes with tissue-specific (IL33in nasal epithelium) and cross-tissue (CCNCandFBXW7) effects.ConclusionsExpression ofIL33, CCNC, andFBXW7may affect asthma risk in African ancestry populations by mediating inflammatory responses. The addition of CD4+T and nasal epithelium prediction databases to the public sphere will improve ancestry representation and power to detect novel gene-trait associations from TWAS.Key MessagesFrom the largest African-ancestry TWAS of asthma to date (N=9,284), we identified 17 candidate causal asthma genes, including: nasal epithelial expression ofIL33, and cross-tissue expression ofCCNCandFBXW7.We provide gene expression prediction databases for CD4+ T cell and nasal epithelial tissues built in African-ancestry populations, improving ancestry representation and power to detect novel gene-trait associations from TWAS.Capsule SummaryWe developed novel gene expression prediction databases (CD4+ T cells, nasal airway epithelium) representing diverse populations across the African diaspora and identified 17 candidate causal asthma genes from TWAS.
Impacts of patient advisory councils on recovery for sepsis survivors: a case study
Authors: Sheehan Mia , Novakowski Stefanie K , Sheikh Fatima , Korstad Susan , MacDonald Kristin , Sacks Jordan , Russell Kristine , Bergeron Marie-Maxime , Vidler Marianne ,   Sepsis Canada
Published: February 2025

AbstractBackgroundSepsis is a life-threatening condition with significant long-term impacts for survivors and their families. The known benefits of patient engagement have led to increased efforts globally to involve survivors in sepsis research. This study aimed to characterize the experiences of sepsis survivors and their families in patient advisory councils (PACs) for two Canadian sepsis research networks (Action on Sepsis and Sepsis Canada) and explore how PAC involvement supports long-term recovery.MethodsThis mixed-methods cross-sectional study consisted of a structured survey, ten interviews, and one focus group discussion. All current members of the Sepsis Canada and Action on Sepsis PACs (n=29) were invited to participate. The results of the survey were analyzed descriptively and used to inform the development of the semi-structured interview guide. Qualitative data were analyzed using a thematic approach.ResultsOverall, 15 PAC members participated. The majority of participants were women and over 40 years old. Survey scores showed that most participants felt meaningfully engaged, while the qualitative findings highlighted how PACs supported recovery and fostered community connections between survivors, families, and researchers. Major themes included sepsis experience, recovery journey, characteristics of PACs, characteristics of PAC participation, and impacts of PAC involvement.InterpretationOur findings demonstrate that PACs provide critical benefits that extend beyond feeling valued or appreciated for contributing to a specific project. These findings highlight the value of patient-oriented research in shaping evidence-based practices and policies and emphasize the need for trauma-informed approaches and improved post-sepsis care pathways to enhance recovery outcomes.
A tissue multiplexing approach to maximise spatial transcriptomics output from precious pathology specimens
Authors: Kao Yung-Ching , Lee Katie J. , Zhou Chenhao , Causer Andrew , Oey Harald , Khosrotehrani Kiarash , O’Brien Blake , Collins Angus , Nguyen Quan , Soyer H. Peter , Stark Mitchell S. 
Published: February 2025

AbstractSince diagnostic specimens retrieved from pathology cannot be altered (except for sectioning) for ethicolegal reasons, we describe a method that combines multiple patient specimens, cut from individual blocks, allowing the measurement of several tissues in one capture array. This results in a cost-effective means to increase sample size to permit statistically robust data outputs and to fast-track clinical implementation. Importantly, our tissue multiplexing method is compatible with the standard 10X Genomics supported protocols. We have used skin biopsies in this instance as this is our primary area of research, but this method can be extended to any tissue of interest.
TELEHEALTH and digital health platforms in promoting access to sexual reproductive health self care among youth: A case of Rocket health services in Uganda
Authors: Ssenfuka Vincent , Bwanika John Mark , Kamulegeya Louis Henry , Kiracho Elizabeth Ekirapa , Akulume Martha , Atuyambe Lynn 
Published: February 2025

AbstractBackgroundSexual Reproductive Health (SRH) self-care offers a pathway for low income countries to advance towards Universal Health Coverage by empowering individuals, families, and communities to prioritize their SRH needs independently of healthcare providers. Facilitating access to SRH products is crucial for embracing self-care and digital health technologies hold promise for enhancing accessibility. This study explored the role played by rocket health digital platforms in enhancing accessibility to SRH self-care products among youth in Uganda.Research methodsEmploying a cross-sectional design with a mixed-method approach, the study involved key informant interviews with youth who had purchased SRH self-care products from Rocket Health in 2022, as well as key staff at Rocket Health.Quantitative data were extracted from Rocket Health’s Electronic Medical Records covering the period from January 2022 to December 2022.ResultsMore males (57%) utilized digital platforms for SRH compared to females (43%). The highest utilization was via the E-commerce platform (49%) while the least was via the voice call platforms (4%). A notable portion of youth (30%) still relied on visiting the pharmacy. Contraception products were predominantly consumed through digital platforms (44%), whereas self-testing were less frequently utilized (14%). The study also identified key resources such as the digital infrastructure that maximize the potential of digital health platforms in enhancing SRH self-care.ConclusionsBy gaining insights into the digital infrastructure, preferences, barriers, and financial considerations associated with accessing SRH self-care services through digital platforms, targeted interventions can be developed to promote positive SRH outcomes among youth
3D-Mapping of QRS Loops: Visualizing the Ventricular Electrical Activities
Authors: Ghosal Tania , Kumar Subhankar , Ahmed Imran , Goswami Damodar Prasad , Bandyopadhyay Anupam , Sengupta Arnab 
Published: February 2025

AbstractThis paper presents innovative visualization tools for the analysis and interpretation of three-dimensional vectorcardiogram (VCG), focusing on the QRS complex of the cardiac cycle. Traditional electrocardiography (ECG) lacks the spatial detail necessary for comprehensive cardiac evaluations; however, VCG provides a three-dimensional representation of electrical activity in the heart, allowing for a nuanced understanding of cardiac dynamics. We propose five distinct methodologies for representing spatial QRS VCG loops: (1) unmodified spatial VCG loops that track the progression of ventricular depolarization, (2) fixed-scale VCG loops that facilitate direct comparisons across individuals and conditions, (3) orientation of QRS loop with respect to three orthogonal planes in the 3D space. (4) octant-specific plots that offer insights into spatial distributions, and (5) unit vector and unit sphere representations that emphasize directional movement while normalizing magnitude. Each method has unique strengths in elucidating ventricular electrodynamics in normal and in cardiac conditions such as anterior wall myocardial infarction and inferior wall myocardial infarction, highlighting differences in loop size, directionality of propagation, orientation, and morphology. Together, these methodologies provide a robust framework for advancing VCG research and enhancing clinical assessments of cardiac function. Preliminary findings highlight the potential of these innovative tools.
Pitfalls in understanding how multiple long-term conditions cluster: whole population and age-stratified associations in 7,490,874 people in England
Authors: Romero Moreno Guillermo , Restocchi Valerio , Lone Nazir , Fleuriot Jacques D. , Palmer Jake , De Ferrari Luna , Guthrie Bruce 
Published: February 2025

AbstractStudies of how multiple long-term conditions (MLTC) cluster together in individuals vary in the populations studied, and whether they age and/or sex stratify, which limits comparison between studies and reproducibility. This study uses a large, UK primary-care dataset to examine how pairwise strength of association between 74 conditions varies by age in both men and women aged 30-99 years, and to explore implications for MLT cluster analyses. Joint prevalence of conditions was lowest in younger age-groups and progressively increased with age, whereas Association Beyond Chance (ABC) was highest in younger age-groups and progressively decreased with age. Condition clustering based on ABC identified different clusters in all men and all women aged 30-99 years, and these clusters differed from those identified in each age-group. Researchers examining how MLTC cluster should consider whether age and sex stratification is appropriate given their study aims and/or would improve comparability and reproducibility, and explicitly justify their choices.
Mathematically modeling worried-well behavior during infectious disease outbreaks
Authors: Singh Bismark , Gromov Dmitry 
Published: February 2025

AbstractMitigation and control of novel infectious disease outbreaks requires a strategic response from public health officials. Such a response requires curtailment of both the underlying pathogen as well as public concern. There is an extensive amount of literature on the former, however empirical models catered to the latter are lacking. We seek to fill this gap by presenting a mathematical model that governs spread of “worried-well” behavior within an infectious disease outbreak. Such behavioral concerns, that are marked by an absence of the underlying pathogen infection, manifest themselves in varied degrees ranging from protesting behavior against public health measures to overly isolating behavior leading to mental anxiety. Our work shows different strategies are required for different degrees of worried-well behavior. We provide a framework to mathematically formulate such behavior and provide guidance on controlling surges of such population groups under varied proportions. Since compliance to public health measures is strongly influenced by effective public health messaging, estimates of such population groups are imperative to public health officials.
Harms of short-course systemic corticosteroids among children and adolescents: a systematic review and meta-analysis of randomized controlled trials
Authors: Lima João Pedro , Chowdhury Saifur R. , Tangamornsuksan Wimonchat , Zhai Chunjuan , Chu Xiiajing , Matos Silva Jessyca , Rahman Chowdhury Mahmudur , Kabir Humayun , Couban Rachel , Eltorki Mohamed , Guyatt Gordon H , Chu Derek 
Published: February 2025

AbstractIntroductionShort courses of systemic corticosteroids are used in the clinical management of a number of acute clinical conditions. In this systematic review and meta-analysis of randomized controlled trials we document the harms of the short-term use (≤ 14 days) of systemic corticosteroids in children and adolescents (1-18 years old) across different clinical conditions.MethodsWe searched MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) databases from inception to January 2024 for randomized controlled trials evaluating the harms of short-course systemic corticosteroids We performed pairwise meta-analyses using the Mantel-Haenszel methods with risk difference. We assessed the certainty of evidence using the GRADE approach and subgroup analysis credibility with the ICEMAN instrument. PROSPERO registration (CRD42023400934).ResultsWe identified 45 trials that included 6,470 children. Corticosteroids probably cause few if any serious adverse events (RD 1 fewer per 1000 [95% CI 9 fewer to 7 more]; moderate certainty), but probably do result in adverse events leading to discontinuation (RD 4 more per 1000 [95%CI 3 fewer to 11 more]; moderate certainty) compared to usual care. Corticosteroids probably increase the risk of hyperglycemia (RD 38 more per 1000 [95%CI 11 to 64 more]; moderate certainty), sleep problems (RD 15 more [95% CI 1 to 28 more]; moderate certainty), change in behavior (RD 8 more [95% CI 5 fewer to 21 more]; moderate certainty) and gastrointestinal bleeding (RD 13 more per 1000 [95% CI 3 to 23 more]; moderate certainty).ConclusionCorticosteroids likely increase the risk of hyperglycemia, sleep problems, change in behavior and gastrointestinal bleeding, but these adverse events are very seldom if ever serious.
Characterizing Stroke Clots Using Single-Cell Sequencing
Authors: Renedo Daniela , Barak Tanyeri , DeLong Jonathan , Acosta Julian N. , Sujijantarat Nanthiya , Koo Andrew , Antonios Joseph , Rivier Cyprien , Clocchiatti-Tuozzo Santiago , Huo Shufan , Giles James , Falcone Guido J , Sheth Kevin N , Hebert Ryan , Gunel Murat , Sansing Lauren H , Navaratnam Dhasakumar S , Matouk Charles 
Published: February 2025

AbstractBackgroundIschemic stroke result in significant morbidity and mortality. By examining gene expression of cells comprising stroke clots, we aim to gain valuable insights into the underlying mechanisms of this disease and identify potential biomarkers of stroke etiology.MethodsWe employed single-cell RNA sequencing to analyze 10 clot samples from patients diagnosed with large vessel occlusion stroke. We aimed to identify and compare the immune cell compositions and gene expression profiles between stroke clots (atrial fibrillation vs carotid atherosclerosis). We also used MAGMA and GWAS summary statistics from the GIGASTROKE consortium to assess associations association between genetic variants and cell type-specific gene expression within the stroke subtypes.ResultsOur analysis revealed distinct immune cell populations, including monocytes, macrophages, dendritic cells, neutrophils, and T-cells in both clot types. Notably, we observed significant differences in gene expression within the mononuclear phagocytic system cells between clots from atrial fibrillation and carotid atherosclerosis patients.We identified specific genes associated with atherosclerosis and stroke-related processes, such asCD74, HLA- DRB1*01, HTRA1, C1Q, CD81, andCR1clots from carotid atherosclerosis patients. In atrial fibrillation clots, CD8 T-cells and NK-cells show upregulated expression of genes such as GZMH, GZMB, S100A4, FCGBP2, HLA-A, TIMP1, CLIC1, and IFITM2, indicating their involvement in cytotoxic activities and potential tissue damage. The MAGMA approach highlighted significant genetic associations within leukocytes, particularly in atrial fibrillation and carotid clots, underscoring the potential roles of B-cells, T-cells, and macrophages in clot pathogenesis.ConclusionsThis study illuminates the immune and transcriptomic landscape within clots, offering potential biomarkers and lays the foundation for future research.
Germline sequence variation within the ribosomal DNA is associated with human complex traits
Authors: Rodriguez-Algarra Francisco , Cooper Maia , Mardakheh Faraz K , Evans David M , Rakyan Vardhman K 
Published: February 2025

AbstractThe ribosome is one of the core macromolecules in the cell. The ribosomal RNAs (rRNA), which are essential components of the ribosome, are coded by the multi-copy ribosomal DNA (rDNA). Despite its highly conserved function, the rDNA displays substantial variation within all species analysed to date. This variation comprises both inter-individual differences in total copy number (CN) as well as inter- and intragenomic sequence variation in the form of single nucleotide variants (SNV) and insertions/deletions (INDELs) across rDNA copies. Whether germline variation of rDNA sequence associates with phenotypic traits in humans is, to date, unknown. Here, using the UK Biobank whole genome sequencing data, we first derive a high confidence list of rDNA-associated SNVs and INDELs that we validate in multiple ways. Using this list, we show that specific rDNA variants associate with several human traits. In particular, traits associated with body size appear enriched in variants within the Expansion Segment 15L region in the 28S rRNA. The strength of these associations does not diminish when accounting for the total rDNA CN of each individual. Our work represents the first large-scale association analysis of human traits with germline sequence variation in the rDNA, a source of human complex trait-relevant genetic variation that has thus far been largely ignored.
Ribbit: Accurate identification and annotation of complex tandem repeat sequences in genomes
Authors: Avvaru Akshay Kumar , Sharma Anukrati , Sowpati Divya Tej 
Published: February 2025

AbstractDNA tandem repeats (TRs) are crucial for genomic functions like protein binding, chromatin modulation, splicing, and gene regulation. Abnormal length variations in TRs, especially expansions, are associated with over 60 neurodegenerative diseases. The function and stability of a TR locus is dependent on its sequencing composition and purity. Recent studies report the disease-causing propensity of non-canonical motif expansions in TR loci, and highlight the intricate polymorphism dynamics in complex loci encompassing adjacent, overlapping, and nested TRs. These reports emphasize the need for precise definition and motif decomposition of TR loci. To address this, we present Ribbit, a tool that accurately and efficiently identifies and annotates TR loci in a genome. Ribbit uses 2-bit representation of DNA sequences for rapid identification of TRs of 2–100 bp motif size and resolves complex TR structures. Ribbit efficiently handles imperfections such as indels and substitutions, providing insights into nested and compound TR relationships through detailed motif decomposition. Comparative analyses using simulated data show Ribbit outperforms existing tools like Dot2dot and TRF in terms of runtime and accuracy. Ribbit reports TR loci in the human genome with lower redundancy than TRF and provides resolved TR regions comparable to variation clusters reported in recent catalogues. Therefore, Ribbit can be leveraged to understand the evolution and biology of complex TR regions in large genomes.
Psilocybin alters visual contextual computations
Authors: Aqil Marco , de Hollander Gilles , Vreugdenhil Nina , Knapen Tomas , Dumoulin Serge O. 
Published: February 2025

Psilocybin alters perception and brain dynamics. Contextual computations are ubiquitous in the brain. Here, we investigate the effects of psilocybin using psychophysics, ultra-high field functional MRI, and computational modeling. We find that 1) psilocybin alters contextual perception in the Ebbinghaus illusion, 2) psilocybin alters contextual modulation in cortical responses to visual stimuli, and 3) we propose a computational model capable of capturing and linking these changes. Leveraging vision as a beachhead, our findings highlight the alteration of contextual computations as a potential general mechanism underlying psychedelic action.TeaserPsilocybin alters visual-contextual computations, a potential general computational mechanism for psychedelic effects in the human brain.
Export dynamics of protists across the southern subtropical frontal zone reveal taxon-specific patterns
Authors: Ong Denise Rui Ying , Gutiérrez-Rodríguez Andrés , Bilewitch Jaret , Nodder Scott , Stukel Michael R. , Décima Moira , Lopes dos Santos Adriana 
Published: February 2025

AbstractGravitational particle sinking is the main mechanism for carbon export in the biological carbon pump. However, the export dynamics of the particle-associated protist community are not fully understood. We used 18S rRNA gene metabarcoding to characterise the exported protist community within sinking particles and bathypelagic surficial sediments in oligotrophic subtropical and high-nutrient, low-chlorophyll subantarctic waters. Sinking particles were collected with formalin-fixed and preservative-free particle interceptor traps (fixed and live traps, respectively) to identify the community involved in particle export (fixed) and protist loss from remineralisation (live). We paired this with community analysis of the upper and lower water column (mixed layer and below mixed layer to mesopelagic, respectively) to compare the relative sources of exported protists. Amplicon sequences variants (ASVs) from upper water column samples accounted for 2 to 4-fold higher proportion of reads and ASV rich-ness compared to lower water column samples in fixed trap and sediment samples, suggesting low influence of the suspended protist community from the lower water column on export. We further traced the export patterns of upper water column protist taxa by analysing the change in taxa relative abundance across the mixed layer to mesopelagic depths. Export patterns differed between taxa, which is similarly suggested by taxa-specific loss of ASV richness between fixed and live traps, but remained the same across biogeochemically-contrasting water masses. This could imply that the drivers for protist loss during export are related to characteristics consistent across environmental conditions, such as specific microbial interactions or inherent cell properties.