bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expanding the genetic landscape of endometriosis: Integrative -omics analyses uncover key pathways from a multi-ancestry study of over 900,000 women
Authors: Guare Lindsay A , Das Jagyashila , Caruth Lannawill , Rajagopalan Ananya , Akerele Alexis T. , Brumpton Ben M , Chen Tzu-Ting , Kottyan Leah , Lin Yen-Feng , Moreno Elisa , Mulford Ashley J , Rovite Vita , Sanders Alan R , Dombrovska Marija Simona , Elhadad Noemie , Hill Andrew , Jarvik Gail , Jaworski James , Luo Yuan , Namba Shinichi , Okada Yukinori , Shi Yue , Shirai Yuya , Shortt Jonathan , Wei Wei-Qi , Weng Chunhua , Yamamoto Yuji , Chapman Sinead , Zhou Wei , Velez Edwards Digna R. , Setia-Verma Shefali 
Published: November 2024

AbstractWe report the findings of a genome-wide association study (GWAS) meta-analysis of endometriosis consisting of a large portion (31%) of non-European samples across 14 biobanks worldwide as part of the Global Biobank Meta-Analysis Initiative (GBMI). We identified 45 significant loci using a wide phenotype definition, seven of which are previously unreported and detected first genome-wide significant locus (POLR2M) among only African-ancestry. Our narrow phenotypes and surgically confirmed case definitions for endometriosis analyses replicated the known loci nearCDC42,SKAP1, andGREB1. Through this large ancestry stratified analyses, we document heritability estimates in range of 10-12% for all ancestral groups. Thirty-eight loci had at least one variant in the credible set after fine-mapping. An imputed transcriptome-wide association study (TWAS) identified 11 associated genes (two previously unreported), while the proteome-wide association study (PWAS) suggests significant association of R-spondin 3 (RSPO3) with wide endometriosis, which plays a crucial role in modulating the Wnt signaling pathway. Our diverse, comprehensive GWAS, coupled with integrative -omics analysis, identifies critical roles of immunopathogenesis, Wnt signaling, and balance between proliferation, differentiation, and migration of endometrial cells as hallmarks for endometriosis. These interconnected pathways and risk factors underscore a complex, multi-faceted etiology of endometriosis, suggesting multiple targets for precise and effective therapeutic interventions.
Advanced HIV Disease Burden in Selected Health Facilities in Mozambique, October–December 2023
Authors: Nguimfack Alexandre , Filipe Eudoxia , Filimao Dercio , Mizela José , Bila Erica , Matsinhe Mercia , Tomo de Deus Maria Inês , Gaspar Irenio , Ruano Maria , Armando Luis , Tiberi Orrin 
Published: November 2024

AbstractIntroductionAdvanced HIV Disease (AHD) is a remaining hurdle in the care and treatment cascade in Mozambique and has the potential to delay Mozambique’s progress towards the UNAIDS 95-95-95 goals for 2025. An improved understanding of the prevalence and demographics of AHD is critical to understanding this important condition.MethodsData from October to December 2023 were reviewed from the 79 health facilities implementing the AHD diagnosis and treatment package at the national level.ResultsOverall, 36% (7.811/21.452) of people living with HIV (PLHIV) newly initiated or reinitiated on treatment had a CD4 test, of which 1.986 were diagnosed with AHD. Most diagnosed cases were in the newly initiated PLHIV (1.814) versus reinitiated (179).ConclusionLow CD4 testing uptake means that AHD remains a serious challenge in Mozambique’s path towards the elimination of HIV as a public health threat.
Learning latent profiles via cognitive growth charting in psychosis: design and rationale for the PRECOGNITION project
Authors: Marquand Andre F. , Bučková Barbora Rehák , Cattaranusi Giulia , Flaaten Camilla , Busch Cecilie , Lemvigh Cecilie K. , Gupta Veenu , Fraza Charlotte , Westlye Lars T. , Andreassen Ole A. , Hlinka Jaroslav , Ebdrup Bjørn H. , Shiers David , Ueland Torill , Dazzan Paola 
Published: November 2024

AbstractCognitive impairments are a core feature of psychosis that are often evident before illness onset and have substantial impact on both clinical and real-world functional outcomes. Therefore, these are an excellent target for stratification and early detection in order to facilitate early intervention. While many studies have aimed to characterise the effects of cognition at the group level and others have aimed to detect individual differences by referencing subjects against existing norms, these studies have limited generalisability across clinical populations, demographic backgrounds and instruments and also do not fully account for the inter-individual heterogeneity inherent in psychosis. Here, we outline the rationale, design and analysis plan for the PRECOGNITION project which aims to address these challenges. This project is a collaboration between partners in five European countries, that aims to (i) translate normative modelling approaches that have been pioneered in brain imaging to psychosis data, to yield ‘cognitive growth charts’ for longitudinal tracking and prediction at the individual level (ii) develop machine learning models for harmonising and stratifying cohorts on the basis of these models; (iii) provide comprehensive reference models that provide broad sociodemographic coverage including different languages and distinct norms for individuals with psychosis and unaffected individuals and (iv) stratification models and predictions for functional outcome measures in psychosis cohorts. Crucially, this project will be guided throughout by experts with lived experience.
What does it cost to expand two-way texting for post-operative follow-up? A cost analysis in routine voluntary medical male circumcision settings in South Africa
Authors: Unsworth Molly , Fabens Isabella , Setswe Geoffrey , Moyo Khumbulani , Pienaar Jacqueline , Makhele Calsile , Phohole Motshana , Igaba Nelson , Hlongwane Sizwe , Sardini Maria , Dong Tracy , Sharma Monisha , Tweya Hannock , Ndebele Felex , Holec Marrianne , Feldacker Caryl 
Published: November 2024

AbstractUp to 98% of adult voluntary medical male circumcision (VMMC) clients heal without adverse events (AEs) in South Africa and in the sub-Saharan Africa (SSA) region, yet all clients in South Africa (SA) are still required to attend in-person reviews, creating added work for providers and barriers for clients. A randomized controlled trial (RCT) using our fee-free, open-source, two-way texting (2wT) approach showed that males could independently monitor their healing with support from VMMC nurse-led telehealth and that 2wT was more cost-effective than routine visits for quality post-operative monitoring. The objectives of this costing activity were to assess the additive cost of 2wT vs. SoC during a stepped wedge design (SWD) expansion trial; costing an augmentation of 2wT with dedicated personnel during peak VMMC periods; and estimate the cost savings of 2wT from the payer perspective if scaled in routine VMMC settings. Data was collected from routine financial reports and complemented by previous RCT time-motion estimates. We conducted activity-based costing of SWD and peak season periods; sensitivity analysis estimated 2wT costs at scale. We included data from 6,842 males, with 2,586 (38%) opting for 2wT. 2wT participants attended an average of zero visits; SoC males had an average of 2 visits. Under 2wT, quality care markers improved and AE ascertainment increased while loss to follow-up (LTFU) decreased. Given a VMMC population of 10,000 adults, scenario analysis suggests that: 1) 2wT becomes cost neutral with 45% 2wT enrollment; 2) 2wT saves $0.29/client with 60% 2wT enrollment; and 3) 2wT saves $0.46/client with 80% 2wT enrollment. When implemented at scale, 2wT appears to significantly reduce costs to the healthcare system while improving the quality of post-operative care and requiring no additional client costs. 2wT should be expanded for eligible males across VMMC and other post-operative contexts in South Africa.
Influence of Genetic Ancestry on Gene-Environment Interactions of Polygenic Risk and Sociocultural Factors: Results from the Hispanic Community Health Study/Study of Latinos
Authors: Sharma Jayati , McArdle Cristin E. , Graff Mariaelisa , Cordero Christina , Daviglus Martha , Gallo Linda C. , Isasi Carmen R. , Kelly Tanika N. , Perreira Krista M. , Talavera Gregory A. , Cai Jianwen , North Kari E. , Fernández-Rhodes Lindsay , Wojcik Genevieve L. 
Published: November 2024

ABSTRACTBackgroundMany present analyses of Hispanic/Latino populations in epidemiologic research aggregate all members of this ethnic group, despite immense diversity in genetic backgrounds, environment, and culture between and across Hispanic/Latino background groups. Using the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), we examined the role of self-identified background group and genetic ancestry proportions in gene-environment interactions influencing the relationship between body mass index (BMI) and a polygenic score for BMI (PGSBMI).MethodsWeighted univariate and multivariable generalized linear models were executed to compare the effects of environmental variables identifieda prioriby McArdle et al. 2021. Both Amerindigenous (AME) ancestry proportion and background group identity were statistically modeled as confounders both through stratified and joint analyses to understand their influence on the relationship between BMI and PGSBMI, while incorporating gene-environment interactions of PGS x diet and PGS x age-at-immigration.ResultsAfter complex survey weighting, 7,075 participants remained in the analytic sample, representing individuals of six background groups: Central American, Cuban, Dominican, Mexican, Puerto Rican, and South American. The distributions of key environmental and sociocultural variables were heterogeneous between Hispanic/Latino background groups. Associations of these variables with AME ancestry were similarly heterogeneous upon stratification, indicating confounding by background group. In a predictive model for BMI incorporating health, immigration, and environmental variables, PGSBMIperformance decreased with increasing AME ancestry proportion. In this model, most statistically significant GxE interactions lost significance after ancestry and background stratification, except for PGS x age-at-immigration interactions in some strata: Mexican background individuals born in the US compared to those >=21 years old at migration (β=1.33, p<0.01), Dominican background individuals 6-12 years old at migration compared to those >=21 years old at migration (β=4.38, p<0.001), and Cuban background individuals 0-5 years old at migration compared to those >=21 years old at migration (β=2.20, p=0.015), where US-born includes individuals born in the US 50 states/DC.ConclusionsControlling for self-identified background group identity and genetic ancestry did not eliminate statistically significant differences in interactions between AME ancestry and environmental variables in certain strata of AME ancestry among some Hispanic/Latino background groups in HCHS/SOL.
NIR-SC-UFES: A portable NIR spectral dataset to skin cancer in vivo
Authors: da Cunha Pedro Henrique P. , Zanoni Madson P. , Santos Francine D. , Nascimento Isadora Tavares , Rezende Isabella , Canuto Tania R. P. , de Paula Vieira Luciana , Rossoni Renan , Santos Maria C. S. , Romão Wanderson , Frasson Patricia H. L. , Krohling Renato A. , Filgueiras Paulo R. 
Published: November 2024

AbstractIn recent years, significant progress has been made in computer-aided diagnostics (CAD) for skin lesions, primarily using images and metadata. However, these methods have limitations, particularly in revealing the molecular structure of lesions. NIR spectroscopy offers additional data, capturing information not visible to the naked eye, which can improve automated CAD for skin lesions. Skin cancer remains a major cause of death, making early diagnosis crucial. A key challenge in applying machine and deep learning (MDL) techniques to spectroscopy is the lack of publicly available datasets. Previously, no public dataset of portable NIR spectral data for skin lesions existed. In collaboration with the Programa de Assistência Dermatológica (PAD) at UFES, we developed a new dataset, NIR-SC-UFES, for skin cancer diagnosis. This dataset includes portable NIR spectral data for six lesion skin, with 714 spectra captured between 900 and 1700 nm. The dataset is available atdata.mendeley.com/datasets/j9773cyr3k/1.Graphical abstractSpecifications Table
Telemedicine to Address Inequities in Access to Primary Health Care for Minority Groups: A protocol for a Systematic Review and Meta-Analysis
Authors: de Oliveira Laguna Silva Gabriela , Fernandes Gabriel Ricardo , Pereira Emmanuelle Moreira , da Rocha Jacqueline Castro , Aguilar Gabriela Tizianel , Linhares Tiago Sigal , Dode Andressa Dutra , Cabral Felipe Cezar , de Campos Moreira Taís , Chagas Maria Eulália Vinadé 
Published: November 2024

AbstractBackgroundThe present article outlines the protocol for a systematic review and meta-analysis aimed at consolidating the available evidence on how telemedicine can reduce inequities in access to Primary Health Care (PHC) among minority populations. The review seeks to identify barriers, facilitators, and factors that influence the effectiveness of this intervention across different settings.MethodsThis protocol for a systematic review and meta-analysis is reported in line with Prisma-P and the results will be reported using PRISMA-E flowchart. The eligibility criteria was defined using the PICOS approach. Population is minority groups that have used telemedicine, the intervention is synchronous and asynchronous telemedicine, the comparator will consist of minority groups that have received usual care, outcome is access to primary health care and we will include randomized controlled trials. We will search MEDLINE (via PubMed), Scopus, Latina American and Caribbean Health Sciences Literature (LILACS) databases. The risk of bias will be assessed using the ROBINS-I and the confidence in cumulative evidence will be assessed using the GRADE equity tool.DiscussionIt is expected to provide pragmatic results, such supporting decision-making regarding the creation and implementation of new public policies, the development of clinical guidelines, and the optimization of resources aimed at equitable access.Systematic review registrationPROSPERO CRD42024581305
Large language models for extracting histopathologic diagnoses from electronic health records
Authors: Johnson Brian , Bath Tyler , Huang Xinyi , Lamm Mark , Earles Ashley , Eddington Hyrum , Jih Lily J. , Gupta Samir , Shah Shailja C. , Curtius Kit 
Published: November 2024

AbstractBackground & AimsAccurate data resources are essential for impactful medical research. To date, most large-scale studies have relied on structured sources, such as International Classification of Diseases codes, to determine patient diagnoses and outcomes. However, these structured datasets are often incomplete or inaccurate. Recent advances in natural language processing, specifically the introduction of open-weight large language models (LLMs), enable more accurate data extraction from unstructured text in electronic health records (EHRs).MethodsWe created an approach using LLMs for identifying histopathologic diagnoses, including presence of dysplasia and cancer, in pathology reports from the Department of Veterans Affairs Healthcare System, including those patients with genotype data within the Million Veteran Program (MVP) biobank. Our approach requires no additional training and utilizes a simple ‘yes/no’ question prompt to obtain an answer. We validated the method on 3 diagnostic tasks by applying the same prompts to reports from patients with vs without diagnoses of inflammatory bowel disease (IBD) and calculating F-1 scores as a balanced accuracy measure.ResultsIn patients without IBD in MVP, we achieved F1-scores of 99.3% for identifying any dysplasia, 98.2% for identifying high-grade dysplasia and/or colorectal adenocarcinoma (HGD/CRC), and 96.2% for identifying CRC using LLM Gemma-2. In IBD patients in MVP, we achieved F1-scores of 97.1% for identifying dysplasia, 96.4% for identifying HGD/CRC, and 97.1% for identifying CRC.ConclusionLLMs provide excellent accuracy in extracting diagnoses from EHRs and can be applied to a variety of tasks with no additional human-led development required. Our validated methods generalized to unstructured pathology notes, even withstanding challenges of resource-limited computing environments.
Cooperative [2Fe-2S] cluster-binding regulates the functional transitions of theAspergillus fumigatusiron regulator HapX for adaptation to iron starvation, sufficiency and excess
Authors: Oberegger Simon , Misslinger Matthias , Haas Hubertus 
Published: November 2024

ABSTRACTAccurate sensing of cellular iron levels is vital, as this metal is essential but toxic in excess. The iron-sensing transcription factor HapX is crucial for virulence ofAspergillus fumigatus,the predominant human mold pathogen. Its absence impairs growth under iron limitation and excess, but not under moderate iron availability, suggesting that HapX switches between three states to adapt to varying iron availability.This study suggests that the HapX state transitions are regulated by the different propensities of four phylogenetically conserved cysteine-rich regions (CRRs) to coordinate [2Fe-2S] clusters resulting in cumulative occupancies that depend on iron availability. In the iron starvation state, CRR-B and -C lack [2Fe-2S] clusters, the iron sufficiency/”neutral” state features clusters in CRR-B and/or -C and the iron excess state has clusters in all CRR-A, B, and -C, while CRR-D plays a minor role. Combinatorial mutation of CRR-B and -C blocked growth by locking HapX in the iron starvation state, leading to uncontrolled iron uptake, iron accumulation, repression of iron-consuming pathways and impaired iron detoxification. Loss of the C-terminal 27 amino acid region of HapX, which is crucial for the iron starvation state and was found to contain a degron, rescued the severe growth defect. Noteworthy, the - Fe state of HapX induced several gene clusters encoding secondary metabolites.
Gut microbiota-derived GlcNAc-MurNAc is a TLR4 agonist that protects the host gut
Authors: Li Chenyu , Adamson Christopher , Ng Wee Ren Allan , Liang Yaquan , Hong Zebin , Loh Jia Tong , Ng Siu Kin , Kwan Mun Chung Jeric , Feng Shiliu , Ng Wei Long Evan , Kumar Nair Sajith , Ruedl Christiane , Wong Sunny Hei , Lam Kong-Peng , Qiao Yuan 
Published: November 2024

SummaryGut microbiota-derived peptidoglycan fragments (PGNs) are key signaling molecules that regulate multiple aspects of the host’s health. Yet the exact structures of natural PGNs in hosts have not been fully elucidated. Herein, we developed an LC-HRMS/MS analytical platform for global quantification and profiling of natural PGN subtypes in host gut and sera, unexpectedly revealing the abundance of PGN-derived saccharide moieties that do not resemble canonical ligands of mammalian NOD1/2 receptors. Focusing on the disaccharide GlcNAc-MurNAc (GM), a natural gut PGN that does not activate NOD1/2 yet still exhibits robust immunostimulatory effects in host immune cells, we unambiguously established GM as a TLR4 agonist, adding to the growing knowledge of NOD-independent mechanisms of PGN sensing in hosts. Importantly, the administration of GM effectively mitigates colonic inflammation in the DSS-induced colitis model in mice via TLR4-dependent mechanisms, highlighting thein vivosignificance of natural gut microbiota-derived PGNs in maintaining host intestinal homeostasis.
A new class of binding protein-dependent solute transporter exemplified by the TAXI-GltS system fromBordetella pertussis
Authors: Jaques Lily M. , Davies Joseph F.S. , Leone Vanessa , Kelly David J. , Mulligan Christopher 
Published: November 2024

AbstractTripartite ATP-dependent periplasmic (TRAP) transporters are widespread in prokaryotes, but absent in eukaryotes, and facilitate the uptake of a wide variety of substrates. TRAP transporters are composed of a substrate binding protein (SBP) and two unequally sized membrane components that exist as either separate proteins or are fused into a single polypeptide. Almost all TRAP SBPs exist as monomeric globular proteins that bind substrate and present it to the membrane component. Here, we describe the discovery and characterisation of a novel TRAP SBP from the TAXI subfamily with a previously unidentified architecture. BP0403 from the human pathogenBordetella pertussisis a predicted lipoprotein composed of 3 distinct domains; an α/β globular domain with a unique fold, a long helical domain and a C-terminal TAXI SBP domain. Expression and purification of the full-length protein reveals that it forms a stable dimer. Structural modelling of the dimer interface and molecular weight analysis using size exclusion chromatography of the individual domains reveals that the interdomain helical region is solely responsible for dimerization. Differential scanning fluorimetry (DSF) and intrinsic tyrosine fluorescence reveal that BP0403 binds L-glutamate with nanomolar affinity. Unexpectedly, analysis of the genome context of BP0403 reveals the complete absence of characteristic genes for TRAP membrane components but co-localisation and translational coupling withgltS, encoding a Na+/glutamate symporter. In other bacteria, we identified fused BP0403-GltS homologues, strongly suggesting that this constitutes a completely novel SBP-dependent secondary active transporter. Structural comparisons suggest GltS operates by an elevator-type mechanism, like TRAP transporters; the association of an SBP with this class of secondary transporter is an emerging theme.
Simultaneous mapping of RNA secondary, tertiary, and quaternary structure in living cells by multi-site DMS probing
Authors: Saleem Irfana , Miller Thomas , Kearns Lucas , Mitchell David , Bose Ritwika , Weidmann Chase A. , Mustoe Anthony M. 
Published: November 2024

ABSTRACTIdentifying tertiary structures and protein binding sites on RNA molecules remains a key challenge in RNA biology. We report a new chemical probing strategy termed multi-site DMS-MaP (msDMS-MaP) that exploits base tautomerization during mutational profiling reverse-transcription to measure typically invisible DMS-induced modifications at the N7 position of G. These N7-G modifications are now resolved concurrently with conventional N1 and N3 modifications with only minor modifications to established protocols, providing a multi-dimensional, single-molecule readout of RNA structure. We show that N7-G reactivity specifically reports on RNA tertiary and quaternary structure, enabling identification of diverse, functionally significant motifs such as cooperatively folding tertiary domains and protein binding sites in living cells. We apply msDMS-MaP to obtain a map of the quaternary structural ensemble of the 7SK non-coding snRNP, revealing unique protein binding sites across three 7SK structural isoforms. msDMS-MaP represents a broadly applicable strategy for enhanced RNA functional motif discovery and characterization.