bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exercise alleviates liver senescence but does not outmatch the effect of dietary restriction in diet-induced MASLD
Authors: Katsarou Angeliki , Papadopoulos Grigorios , Moustakas Ioannis I. , Papadopetraki Argyro , Moustogiannis Athanasios , Legaki Aigli-Ioanna , Giannousi Eirini , Veroutis Dimitris , Kotsinas Athanassios , Gorgoulis Vassilis G , Philippou Anastassios , Koutsilieris Michael , Chatzigeorgiou Antonios 
Published: December 2024

ABSTRACTBackgroundThe present study aims at deciphering the potential benefits of aerobic exercise and dietary restriction on liver senescence, which is an established hallmark of metabolic dysfunction-associated steatotic liver disease (MASLD), a condition with limited therapeutic options.MethodsC57BL6 mice were subjected to normal diet (ND, 10% of kilocalories from fat) or a high-fat diet (HFD, 60% of kilocalories deriving from fat and water supplemented with 5% High-fructose Corn Syrup, HFCS) for 12 weeks. Then, for additional 8 weeks, the ND group continued with the same diet, while the HFD group was divided into four subgroups: a) mice that continued with the same HFD-5% HFCS in water scheme (HFD), b) mice that continued with the same HFD-5% HFCS in water scheme and underwent supervised aerobic exercise 3-times/week (HFDEX), c) mice that were switched to ND (dietary restriction, DR) and d) mice that were switched to ND while undergoing supervised aerobic exercise 3-times/week (DREX). Phenotypic and histological characterization of obesity and MASLD were performed in all groups. Biomarkers of senescence were analyzed in terms of their mRNA expression levels to assess the impact of all interventions on MASLD-related senescence in the liver. GL13 and p21 immunohistochemical stainings were conducted to examine the protein levels of senescence-associated lipofuscin and p21WAF1/CIP1respectively, so as to finally investigate their relationship with the grade of steatosis observed in each individual animal.ResultsDR and DREX groups exhibited significantly reduced features of obesity and MASLD-related hepatic steatosis, to a greater extent than the respective amelioration driven by aerobic exercise-only in HFDEX animals. A statistically significant increase of the mRNA expression of cyclin-dependent kinase p21WAF1/CIP1was detected in HFD livers as compared to ND, which was also reversed upon DR-inclusive interventions. In contrast, the gene expression levels of cyclin-dependent kinase p16INK4aremained similar in all groups even after a combined intervention. Increased hepatic expression of the p27 and p53 components of the p53-p21CIP/WAF-driven axis of cellular senescence as well as their restoration to ND-like levels upon DR and DREX, suggest an active participation of the p21WAF1/CIP1mechanism of senescence in the emergence of MASLD, but also in its reversal through DR or/and EX interventions. Immunohistochemical stainingsforGL13 and p21 confirmed the aforementioned alterations of p21WAF1/CIP1at the tissular level.ConclusionLiver senescence is responsive both to exercise and dietary restriction, but its amelioration in the context of MASLD is more robust upon DR-inclusive interventions.
Tokenvizz: GraphRAG-Inspired Tokenization Tool for Genomic Data Discovery and Visualization
Authors: Oğuztüzün Çerağ , Gao Zhenxiang , Xu Rong 
Published: December 2024

ABSTRACTSummaryOne of the primary challenges in biomedical research is the interpretation of complex genomic relationships and the prediction of functional interactions across the genome. Tokenvizz is a novel tool for genomic analysis that enhances data discovery and visualization by combining GraphRAG-inspired tokenization with graph-based modeling. In Tokenvizz, genomic sequences are represented as graphs, where sequence k-mers (tokens) serve as nodes and attention scores as edge weights, enabling researchers to visually interpret complex, non-linear relationships within DNA sequences. Through a web-based visualization interface, researchers can interactively explore these genomic relationships and extract biologically meaningful insights about regulatory patterns and functional elements. Applied to promoter-enhancer interaction prediction tasks, Tokenvizz outperformed traditional sequential models while providing interpretable insights into genomic features, demonstrating the advantage of graph-based representations for biological discovery.Availability and ImplementationTokenvizz, along with its user guide, is freely accessible on GitHub at:https://github.com/ceragoguztuzun/tokenvizz.ACM Reference FormatÇerağ Oğuztüzün, Zhenxiang Gao, and Rong Xu. 2024. Tokenvizz: GraphRAG Inspired Tokenization Tool for Genomic Data Discovery and Visualization. InProceedings of (Bioinformatics). ACM, New York, NY, USA, 7 pages.https://doi.org/XXXXXXX.XXXXXXX
Integrating Whole Genome and Transcriptome Sequencing to Characterize the Genetic Architecture of Isoform Variation and its Implications for Health and Disease
Authors: Liu Chunyu , Joehanes Roby , Ma Jiantao , Xie Jiuyong , Yang Jian , Wang Mengyao , Huan Tianxiao , Hwang Shih-Jen , Wen Jia , Sun Quan , Cumhur Demirkale Y. , Heard-Costa Nancy L. , Orchard Peter , Carson April P. , Raffield Laura M. , Reiner Alexander , Li Yun , O’Connor George , Murabito Joanne M. , Munson Peter , Levy Daniel 
Published: December 2024

ABSTRACTWe created a comprehensive whole blood splice variation quantitative trait locus (sQTL) resource by analyzing isoform expression ratio (isoform-to-gene) in Framingham Heart Study (FHS) participants (discovery: n=2,622; validation: n=1,094) with whole genome (WGS) and transcriptome sequencing (RNA-seq) data. External replication was conducted using WGS and RNA-seq from the Jackson Heart Study (JHS, n=1,020). We identified over 3.5 millioncis-sQTL-isoform pairs (p<5e-8), comprising 1,176,624cis-sQTL variants and 10,883 isoform transcripts from 4,971 sGenes, with significant change in isoform-to-gene ratio due to allelic variation. We validated 61% of these pairs in the FHS validation sample (p<1e-4). External validation (p<1e-4) in JHS for the top 10,000 and 100,000 most significantcis-sQTL-isoform pairs was 88% and 69%, respectively, while overall pairs validated at 23%. For 20% ofcis-sQTLs in the FHS discovery sample, allelic variation did not significantly correlate with overall gene expression. sQTLs are enriched in splice donor and acceptor sites, as well as in GWAS SNPs, methylation QTLs, and protein QTLs. We detailed several sentinelcis-sQTLs influencing alternative splicing, with potential causal effects on cardiovascular disease risk. Notably, rs12898397 (T>C) affects splicing ofULK3, lowering levels of the full-length transcript ENST00000440863.7 and increasing levels of the truncated transcript ENST00000569437.5, encoding proteins of different lengths. Mendelian randomization analysis demonstrated that a lower ratio of the full-length isoform is causally associated with lower diastolic blood pressure and reduced lymphocyte percentages. This sQTL resource provides valuable insights into how transcriptomic variation may influence health outcomes.
Co-designed point-of-care ultrasound program development and implementation at a Veterans Affairs Emergency Department
Authors: Theophanous Rebecca G. , Staton Catherine A. , Ragsdale Luna C. , Tupetz Anna , Peethumnongsin Erica , Eucker Stephanie A. 
Published: December 2024

AbstractIntegrating point-of-care ultrasound (POCUS) into patient care requires a multi-faceted culture change using a multi-pronged approach. A standardized implementation method is lacking for POCUS program sustainability. We developed a standardized training curriculum and clinical POCUS documentation, archival, and image review process at a single Veterans Affairs Emergency Department (ED). We hypothesized that co-designed development and implementation of the multifaceted POCUS intervention would maximize ED provider uptake and sustainability.Using Participatory Action Research (PAR) and adapted Experience-Based Co-design (EBCD) methods, stakeholders collaboratively co-designed our POCUS intervention to optimize implementation. Using the PRODUCES framework, twelve stakeholder participants (co-creators including study researchers, ultrasound faculty, ED leadership, and ED providers (POCUS end-users)) met in four monthly co-design meetings from July to October 2021 to brainstorm, discuss, refine, and finalize the POCUS intervention and implementation plan.Throughout the co-design process, stakeholders reviewed findings from prior meetings, reflected on successes and failures, and held open discussions on refining and finalizing the proposed POCUS educational and clinical program. By involving stakeholders as co-creators throughout the co-design process, we maximized end-user POCUS enthusiasm, program uptake, and sustained use. This simple, streamlined, and generalizable user-centered co-design method serves as a framework for future POCUS implementation and dissemination plans.
Lifetime incidence and age of onset of mental disorders, and 12-month service utilization in primary and secondary care: a Finnish nationwide registry study
Authors: Suokas Kimmo , Niemi Ripsa , Gutvilig Mai , McGrath John J. , Komulainen Kaisla , Suvisaari Jaana , Elovainio Marko , Lumme Sonja , Pirkola Sami , Hakulinen Christian 
Published: December 2024

AbstractPrevious studies have estimated lifetime incidence, age-specific incidence, age of onset, and service utilization for mental disorders but none have used nationwide data from both primary and secondary care. This study used nationwide Finnish data (2000–2020), including both care settings for the first time. We followed 6.4 million individuals for 98.5 million person-years, calculating cumulative incidence while accounting for competing risks. By age 100, lifetime incidence of any diagnosed mental disorder was 76.7% (95% CI, 76.6–76.7) in women and 69.7% (69.6–69.8) in men. At age 75, stricter estimates for non-organic disorders (ICD-10: F10–F99) were 65.6% (65.5–65.7) for women and 60.0% (59.9–60.1). Anxiety disorders (F40–F48) had the highest cumulative incidence. Median age of onset of non–organic mental disorders was 24.1 (interquartile range 14.8–43.3) in women and 20.0 (7.3–42.2) in men. Service utilization within 12 months was 9.0% for women and 7.7% for men. Most, though not all, individuals experience at least one type of mental disorder, often during youth. Capturing the overall occurrence of mental disorders requires including both primary and secondary care data.
Predicting coronary artery disease severity through genomic profiling and machine learning modelling: The GEnetic SYNTAX Score (GESS) trial
Authors: Chatzopoulou Fani , Mittas Nikolaos , Chatzidimitriou Dimitrios , Giannopoulos-Dimitriou Alexandros , Saiti Aikaterini , Ganopoulou Maria , Karagiannidis Efstratios , Papazoglou Andreas S. , Stalikas Nikolaos , Papa Anna , Giannakoulas George , Sianos Georgios , Angelis Lefteris , Vizirianakis Ioannis S. 
Published: December 2024

AbstractCardiovascular diseases (CVDs) present multifactorial pathophysiology and produce immense health and economic burdens globally. The most common type, coronary artery disease (CAD), shows a complex etiology with multiple genetic variants to interplay with various clinical features and demographic traits affecting CAD risk and severity. The development and clinical validation of machine learning (ML) algorithms that integrate genetic biomarkers and clinical features can improve diagnostic accuracy for CAD avoiding, thereby, unnecessary invasive procedures. To this end, we present, here, the development of a data-driven ML approach able to predict the existence and severity of CAD based on the analysis of 228 single nucleotide polymorphisms (SNPs) and clinical and demographic data of 953 patients enrolled in the Genetic Syntax Score (GESS) trial (NCT03150680). Two competing ensemble models (one with clinical predictors and another with clinical plus genetic predictors) were built and evaluated to infer their prediction capabilities. The ensemble model with both clinical and genetic predictors exhibited superior diagnostic performance compared to the competing model with only clinical predictors. The proposed ML framework identified a total of eight contributing SNPs as predictors for the existence of obstructive CAD and seven significant SNPs for the severity of CAD. Such algorithms positively contributes to global efforts aiming to predict the risk and severity of CAD in early stages, thus lowering the cost as well as achieving prognostic, diagnostic, and therapeutic benefits in healthcare and improving patient outcomes in a non-invasive way. Overall, the design and execution of this trial reinforces clinical decision-making and facilitate the harmonization in digitized healthcare within the concept of precision medicine.Clinical Trial RegistrationNCT03150680;https://clinicaltrials.gov/study/NCT03150680?cond=NCT03150680&rank=1
Real-world safety of zonisamide: Mining and analysis of adverse events related to zonisamide based on FAERS database
Authors: Zhang Yongyi , Sun Zhongqian , Li Haoming , Kong Qingxia , Zhang Xuezheng , Li Chengde 
Published: December 2024

ABSTRACTPurposeTo investigate the real-world adverse event signals associated with zonisamide and provide a foundation for its safe clinical use.MethodsAdverse event reports involving zonisamide as the primary suspected drug were collected from the FDA Adverse Event Reporting System (FAERS) database, covering the period from the first quarter of 2004 to the fourth quarter of 2023. The data were analyzed utilizing the Reporting Odds Ratio (ROR) and Bayesian Confidence Propagation Neural Network (BCPNN) methods of the proportional imbalance technique.ResultsA total of 3205 adverse event reports involving zonisamide as the primary suspected drug were identified, resulting in 260 positive signals for preferred terms (PTs). These signals, derived from both the ROR and BCPNN methods, encompassed 27 systems and organs (SOCs), with a predominant focus on nervous system disorders and skin and subcutaneous tissue disorders. The most frequently reported PTs included seizures, drug reactions with eosinophilia and systemic symptoms, Stevens-Johnson syndrome, rash, and dizziness. Notably, the top PTs in terms of signal intensity included perinephritis, epilepsy with myoclonic-atonic, ocular mucocutaneous syndrome, ocular choroidal leakage, tonsillar exudate, and ovarian granulosa vesicular cell tumor. Interestingly, ten of the top 30 risk signals for adverse events, based on signal strength, were not detailed in the package inserts. Thses included perinephritis, myoclonic dystonic epilepsy, ovarian granulosa vesicular cell tumor, positive human herpesvirus 6 serology, and positive lymphocyte stimulation test.ConclusionCommon adverse reactions to zonisamide in real-world settings are generally in line with the established specification, with the most frequently observer signals related to neurological, skin, and subcutaneous tissue disorders. However, several newly suspected adverse reactions have been identified, including perinephritis, infectious pneumonitis, ovarian granulosa vesicular cell tumor, positive serology for human herpesvirus 6, and positive lymphocyte stimulation test. These findings indicate that these potential adverse reactions should be closely monitored in clinical practice.
Serious psychological distress among people with unstable housing in Ho Chi Minh City, Vietnam: Prevalence and associated factors
Authors: Murakami Hitoshi , Linh Nguyen Thuy , Fujita Masami , Thuy Lam Ngoc , Phuc Nguyen Hong , Mai Huong Kieu Thi , Anh Le Tuan , Ngoc Mai Pham Thi , Hai Oanh Khuat Thi 
Published: December 2024

AbstractPurposeThis study aimed to estimate the prevalence of serious psychological distress (SPD) among slum dwellers and homeless individuals in Ho Chi Minh City, Vietnam, and to identify factors associated with SPD.MethodA cross-sectional survey of 415 individuals with unstable housing, including 383 slum dwellers and 32 homeless individuals, was conducted from November 2023 to April 2024. Data were collected using a structured questionnaire that included the Kessler Psychological Distress Scale (K6).ResultsThe prevalence of SPD was 19.8% (18.5% among slum dwellers and 34.4% among the homeless). Multiple logistic regression revealed significant associations between SPD and female gender (p=0.000), labor exploitation (p=0.046), and debt (p=0.000). Notably, 68.7% of participants reported experiencing some form of labor exploitation, commonly involving contract rejections, forced overwork, wage theft, and physical or verbal abuse. Additionally, 43.7% were in debt, with 38.6% borrowing from moneylenders.ConclusionsThe prevalence of SPD among individuals with unstable housing in Ho Chi Minh City was significantly higher than that of the general population. Those with SPD frequently faced both labor and economic exploitation, without insufficient social protection. In terms of labor exploitation, policy interventions, particularly from an occupational health perspective, are necessary. To address economic exploitation through debt, given the prevalence of loan sharks, efforts to crack down on predatory lending and promote financial inclusion are essential.
Consultation informs strategies to improve functional evidence use in variant classification
Authors: Villani Rehan M. , Terrill Bronwyn , Tudini Emma , McKenzie Maddison E. , Cliffe Corrina C. , Hahn Christopher N. , Lundie Ben , Mattiske Tessa , Matotek Ebony , McEwen Abbye E. , Nickerson Sarah L. , Breen James , Fowler Douglas M. , Christodoulou John , Starita Lea , Rubin Alan F. , Spurdle Amanda B. 
Published: December 2024

AbstractTo determine if a variant identified by diagnostic genetic testing is causal for disease, applied genetics professionals evaluate all available evidence to assign a clinical classification. Experimental assay data can provide strong functional evidence for or against pathogenicity in variant classification, but appears to be underutilised. We surveyed genetic diagnostic professionals in Australasia to assess their application of functional evidence in clinical practice. Results indicated that survey respondents are not confident to apply functional evidence, mainly due to uncertainty around practice recommendations. Respondents also identified need for support resources, educational opportunities, and in particular requested expert recommendations and updated practice guidelines to improve translation of experimental data to curation evidence. As an initial step, we have collated a list of functional assays recommended by 19 ClinGen Variant Curation Expert Panels as a source of international expert opinion on functional evidence evaluation. Additional support resources for diagnostic practice are in development.
The striatum is an early, accurate indicator of amyloid burden using [11C]PiB in Down syndrome: comparison of two radiotracers
Authors: McLachlan Max , Bettcher Brecca , McVea Andrew , DiFillipo Alexandra , Zammit Matthew , LeMerise Lisette , Rouanet Jeremy , Price Julie , Tudorascu Dana , Laymon Charles , Keator David , Lao Patrick , Brickman Adam M. , Fryer Tim , Hartley Sigan , Ances Beau M. , Johnson Sterling , Betthauser Tobey , Stone Charles K. , Zaman Shahid , Handen Benjamin , Head Elizabeth , Mapstone Mark , Christian Bradley T. 
Published: December 2024

AbstractINTRODUCTIONAdults with Down syndrome demonstrate striatum-first amyloid accumulation with [11C]PiB PET imaging, which has not been replicated with [18F]florbetapir (FBP). Early striatal accumulation has not been temporally quantified with respect to global cortical measures.METHODSLongitudinal PiB (n=175 participants) and FBP (n=92 participants) data from the Alzheimer Biomarkers Consortium-Down Syndrome were used to measure cortical and striatal binding. Generalized temporal models for cortical and striatal amyloid accumulation were created using the sampled iterative local approximation (SILA) method.RESULTSPiB demonstrated greater striatal-to-cortical ratios than FBP. SILA analysis revealed striatal amyloid burden occurs 3.40 (2.39) years earlier than the cortex in PiB. There was no difference between the cortex and striatum in FBP.DISCUSSIONAmong adults with Down syndrome, the striatum consistently accumulates amyloid earlier than the cortex when measured with PiB. This suggests the striatum is more sensitive to the onset of PiB PET-detectable amyloid in Down syndrome.
Trends in Cardiac Arrest Among Heart Failure Patients Aged 25 and Older in the United States: Insights from the CDC WONDER Database
Authors: Muhammad Abdullah Naveed , Neppala Sivaram , Chigurupati Himaja Dutt , Ali Ahila , Rehan Muhammad Omer , Kapaganti Sowjanya , Iqbal Rabia , Naveed Hamza , Ahmed Mushood , Fonarow Gregg C. , Dani Sourbha 
Published: December 2024

AbstractBackgroundCardiac arrest (CA) is a significant cause of mortality in patients with heart failure (HF). Despite improvements in care, disparities in CA-related mortality among HF patients persist. This study seeks to explore demographic patterns and mortality rates.MethodsCDC WONDER (1999-2023) data was analyzed to assess CA-related mortality in HF patients aged≥25. Using the Joinpoint regression analysis, we calculated age-adjusted mortality rates (AAMR) per 100,000 patients and average annual percentage changes (AAPC) to analyze the mortality trends.ResultsCA is responsible for a staggering 1,139,963 deaths among HF patients. The AAMRs have decreased from 25.3 in 1999 to 20.6 in 2023 (AAPC: -0.88, p-value < 0.01), the decline was most significant from 1999 to 2011 (APC: -2.95, p < 0.01) before a concerning rise from 2018 to 2021 (APC: 5.10, p-value < 0.01). Disparities are evident, with men facing higher AAMRs than women (24.6 vs. 17.6) and Black individuals at the highest risk (AAMR: 28.8) followed by Hispanics (AAMR: 22.8). Regionally, Mississippi reports the highest AAMR at 52.5, contrasting with Maryland’s lowest rate of 4.3. Moreover, rural areas exhibited higher AAMRs than urban settings (20.9 vs. 20.1).ConclusionThe rising mortality rates from CA in HF patients—especially among men, Black individuals, and those in rural areas—require our immediate attention. By implementing targeted interventions and enhancing access to healthcare, we can reduce these disparities and improve patient outcomes.
Genetic diversity in the IIS6 domain of Voltage Gated Sodium Channel (VGSC) gene amongAedes aegyptipopulations from different geographical regions in India
Authors: Sumitha MK , Pandiyan G Navaneetha , Kalimuthu M , Paramasivan R , Gupta Bhavna 
Published: December 2024

AbstractThis study provides critical insights into the genetic diversity of the IIS6 domain of theVGSCgene inAedes aegyptipopulations across various regions in India, focusing on two mutations: S989P and V1016G. Samples were collected from seven different cities across the country, including Dibrugarh, Kolkata, Berhampur, Bhopal, Bengaluru, Ghaziabad, and Aurangabad. The IIS6 domain was amplified and sequenced, revealing that the V1016G mutation was found at a higher frequency compared to the S989P mutation. The S989P mutation was most prevalent in Berhampur, followed by Bengaluru, while V1016G mutation showed high frequencies in Dibrugarh, followed by Berhampur. Additionally, the study identified intron polymorphisms within theVGSCgene, with the type A intron being relatively rare. However, the type A intron was observed in samples harbouring both mutant and wild alleles for both mutations. The regional variation in the frequencies of these mutations indicates complex evolutionary dynamics potentially influenced by local environmental factors and insecticide application practices. Interestingly, the high frequency of these alleles also correlated with the genetic structure of the mosquito populations, suggesting that gene flow might be playing a role in spreading these mutations. Regular monitoring of these mutations could serve as important indicators in assessing the status of resistance to pyrethroids and guide nationwide mosquito control efforts. This research underscores the necessity for localized vector control strategies and continuous genetic surveillance to manage insecticide resistance effectively.