bluuebunny/crossref_metadata_2025_split huggingface dataset:
PRC1 and CTCF-Mediated Transition from Poised to Active Chromatin Loops Drives Bivalent Gene Activation
Authors: Hanafiah Aflah , Geng Zhuangzhuang , Liu Tingting , Tai Yen Teng , Cai Wenjie , Wang Qiang , Christensen Neil , Liu Yan , Yue Feng , Gao Zhonghua 
Published: November 2024

AbstractPolycomb Repressive Complex 1 (PRC1) and CCCTC-binding factor (CTCF) are critical regulators of 3D chromatin architecture that influence cellular transcriptional programs. Spatial chromatin structures comprise conserved compartments, topologically associating domains (TADs), and dynamic, cell-type-specific chromatin loops. Although the role of CTCF in chromatin organization is well-known, the involvement of PRC1 is less understood. In this study, we identified an unexpected, essential role for the canonical Pcgf2-containing PRC1 complex (cPRC1.2), a known transcriptional repressor, in activating bivalent genes during differentiation. Our Hi-C analysis revealed that cPRC1.2 forms chromatin loops at bivalent promoters, rendering them silent yet poised for activation. Using mouse embryonic stem cells (ESCs) with CRISPR/Cas9-mediated gene editing, we found that the loss of Pcgf2, though not affecting the global level of H2AK119ub1, disrupts these cPRC1.2 loops in ESCs and impairs the transcriptional induction of crucial target genes necessary for neuronal differentiation. Furthermore, we identified CTCF enrichment at cPRC1.2 loop anchors and at Polycomb group (PcG) bodies, nuclear foci with concentrated PRC1 and its tethered chromatin domains, suggesting that PRC1 and CTCF cooperatively shape chromatin loop structures. Through virtual 4C and other genomic analyses, we discovered that establishing neuronal progenitor cell (NPC) identity involves a switch from cPRC1.2-mediated chromatin loops to CTCF-mediated active loops, enabling the expression of critical lineage-specific factors. This study uncovers a novel mechanism by which pre-formed PRC1 and CTCF loops at lineage-specific genes maintain a poised state for subsequent gene activation, advancing our understanding of the role of chromatin architecture in controlling cell fate transitions.
Redefining the spliceosomal introns of the sexually transmitted parasiteTrichomonas vaginalisand its close relatives in columbid birds
Authors: Callejas-Hernández Francisco , Shiratori Mari , Sullivan Steven A. , Blow Frances , Carlton Jane M. 
Published: November 2024

AbstractTrichomonas vaginalisinfects the urogenital tract of men and women and causes the sexually transmitted infection trichomoniasis. Since the publication of its draft genome in 2007, the genome has drawn attention for several reasons, including its unusually large size, massive expansion of gene families, and high repeat content. The fragmented nature of the draft assembly made it challenging to obtain accurate metrics of features, such as spliceosomal introns. The number of introns identified varied over the years, ranging from 41 when first characterized in 2005, to 32 in 2018 when the repertoire was revised. In both cases, the results suggested that more introns could be present in the genome. In this study, we exploited our newT. vaginalisG3 chromosome-scale assembly and annotation and high-coverage transcriptome datasets to provide a definitive analysis of the complete repertoire of spliceosomal introns in the species. We developed a custom pipeline that distinguishes true splicing events from chimeric alignments by utilizing the extended motifs required by the splicing machinery and experimentally verified the results using transcript evidence. We identified a total of 63 active introns and 34 putative “inactive” intron sequences inT. vaginalis, enabling an analysis of their length distribution, extended consensus motifs, intron phase distribution (including an unexpected expansion of UTR introns), and functional annotation. Notably, we found that the shortest intron inT. vaginalis, at only 23 nucleotides in size, is one of the shortest introns known to date. We tested our pipeline on a chromosome-scale assembly of the bird parasiteTrichomonas stableri, the closest known relative toT. vaginalis. Our results revealed some conservation of the main features (total intron count, sequence, length distribution, and motifs) of these two closely related species, although differences in their functional annotation and duplication suggest more specialized splicing machinery inT. vaginalis.
Uncertainty-aware genomic deep learning with knowledge distillation
Authors: Zhou Jessica , Rizzo Kaeli , Tang Ziqi , Koo Peter K 
Published: November 2024

ABSTRACTDeep neural networks (DNNs) have advanced predictive modeling for regulatory genomics, but challenges remain in ensuring the reliability of their predictions and understanding the key factors behind their decision making. Here we introduce DEGU (Distilling Ensembles for Genomic Uncertainty-aware models), a method that integrates ensemble learning and knowledge distillation to improve the robustness and explainability of DNN predictions. DEGU distills the predictions of an ensemble of DNNs into a single model, capturing both the average of the ensemble’s predictions and the variability across them, with the latter representing epistemic (or model-based) uncertainty. DEGU also includes an optional auxiliary task to estimate aleatoric, or data-based, uncertainty by modeling variability across experimental replicates. By applying DEGU across various functional genomic prediction tasks, we demonstrate that DEGU-trained models inherit the performance benefits of ensembles in a single model, with improved generalization to out-of-distribution sequences and more consistent explanations of cis-regulatory mechanisms through attribution analysis. Moreover, DEGU-trained models provide calibrated uncertainty estimates, with conformal prediction offering coverage guarantees under minimal assumptions. Overall, DEGU paves the way for robust and trustworthy applications of deep learning in genomics research.
Rate ofde novomutations in the three-spined stickleback
Authors: Zhang Chaowei , Reid Kerry , Schierup Mikkel Heide , Wang Hongbo , Candolin Ulrika , Merilä Juha 
Published: November 2024

AbstractBeing a fundamentally important genetic parameter and evolutionary force, estimates of germline mutation rates have many uses in evolutionary biology. However, accurate estimates ofde novomutation (DNM) rates are still relatively scarce even for extensively studied evolutionary biology models. We estimated DNM rates for the three-spined stickleback (Gasterosteus aculeatus), the ‘supermodel’ of ecology and evolutionary biology. Using a large number of family trios sequenced to depth of 45x coverage, we identified 115 unique mutations genome wide and estimated the DNM rate atµ= 5.05 × 10-9/bp/gen without any detectable sex bias. The localised DNM rate was found to be positively correlated with recombination rate supporting the notion that recombination is a mutagenic process. Comparison ofµand genomic characteristics to those of the related nine-spined stickleback (Pungitius pungitius) revealed a high degree of similarity suggesting that despite 17.5 million years of independent evolution, the mutational processes in the two species appear to have been conserved.
Validation of an innovative two-part algorithm for detecting self-propulsion in manual wheelchair users
Authors: Gagnon Rose , Best Krista L. , Routhier François 
Published: November 2024

AbstractIntroductionActimetry is increasingly used to measure physical activity (PA) for MWC users. However, conversion of raw data into interpretable PA outcomes remains imprecise, and the differentiation between propulsion and non-propulsion is challenging. Using a previously developed two-part algorithm, the objectives of this study were to 1) measure the accuracy of total distance collected, and 2) validate the algorithm’s accuracy in differentiating between self-propulsion and non-propulsion.MethodsExperimental study consisting of two data collection sessions. Actimetry data (Actigraph) were collected indoors (controlled conditions) during 100 repetitions (n=40 MWC propulsion, n=60 pushing the MWC) over three distances (10, 50 and 100 meters). Actimetry data (Actigraph) were also collected outdoors (uncontrolled condition) during self-propulsion over 1,000 meters (10 repetitions). Descriptive statistics (e.g., mean, standard deviation) with confidence intervals and accuracy measures (percentage of true value) were conducted for each trial.ResultsThe algorithm measured total distance covered indoors with an excellent accuracy (98.9% to 99.8%). It differentiated between self-propulsion and non-propulsion with an accuracy between 96.2% and 99.2% under controlled condition, and between 91.3% and 100.0% under uncontrolled condition.ConclusionsThe algorithm tested allowed precise measurement of total distance covered, as well as an excellent discrimination between self-propulsion and non-propulsion.
A Mass Casualty Event in a Gaza War Hospital
Authors: Alsalqawi Abdalkarim , Abu Tahoon Khader , Nijim Adnan , Halimy Mohammed , Villar Richard 
Published: November 2024

AbstractThis study examines the impact of a mass casualty event (MCE) on a Gaza hospital during a military operation in June 2024, highlighting unique challenges encountered in conflict-zone medical care. The research analyses 47 casualties received by the Shuhada al-Aqsa Hospital in Deir-al-Balah, Gaza, over a concentrated period. Data collected include demographics, injury types, and pre-hospital and emergency department treatment delays. Findings reveal a predominance of blast injuries (76.6%), with compound injuries being present in 78.7% of casualties, resulting in a high injury burden (mean 1.68 injuries per casualty). The mean age of all casualties was 30.57 years. Mortality reached 14.89%, with females disproportionately affected, comprising 71.43% of fatalities. Transportation delays averaged 18.7 minutes, often without pre-arrival notification, underscoring logistical challenges in the Gaza conflict setting. In-hospital delays for treatment averaged 17.4 minutes. Gender disparities in trauma outcomes suggest biological and sociocultural factors influencing survival rates. The study emphasises the need for conflict-sensitive, gender-informed medical interventions, improved trauma care resources, and pre-hospital coordination protocols. This work aims to inform international medical volunteers on the realities of conflict-zone healthcare and support system-level improvements in MCE responses in resource-limited settings.
Comprehensive analysis of key m6A RNA modification-related genes and immune infiltrates in hypertrophic cardiomyopathy
Authors: Hu Xia , Liang Bo 
Published: November 2024

AbstractHypertrophic cardiomyopathy (HCM) is the most common inherited heart disease. We performed a comprehensive analysis to construct the correlation of m6A and immune in HCM. Two HCM datasets (GSE141910 and GSE160997) and m6A-related regulators were obtained from GEO and published articles, respectively. Differentially expressed m6A-related regulators were obtained. Random forest model and nomogram were conducted to assess the risk of HCM, and finally, the m6A subtype was constructed. Functional enrichment analysis was conducted. Protein-protein interaction network of differentially expressed genes between m6A subtypes was performed. Furthermore, we constructed the Hubgene-chemical network, Hubgene-microRNA network, and Hubgene-transcription factor network of the top 10 hubgenes. Additionally, the immune subtype and hubgene subtype were constructed. PCR was performed to validate the m6A-related regulators. We obtained 20 m6A-related regulators in HCM. Among them, 8 m6A-related regulators differentially expressed (YTHDC1, HNRNPC, and FMR1 were up-regulated while YTHDC2, FTO, WTAP, IGF2BP2, and IGF2BP3 were down-regulated). FTO, FMR1, IGF2BP3, YTHDC1, and IGF2BP2 were the top 5 important m6A-related regulators and were used to conduct the nomogram. We obtained 329 differentially expressed genes in m6A subtype and these genes enriched HCM-related processes and pathways. Furthermore, we constructed the Hubgene-chemical network, Hubgene-microRNA network, and Hubgene-transcription factor network of the top 10 hubgenes (NFKBIA, NFKB1, PSMA3, PSMC4, PSMA2, PSMA4, PSMD7, PSMD10, PSMD8, and PSMA6). And then we constructed an immune subtype based on the immune cell infiltration levels and hubgene subtype based on the expression of the top 10 hubgenes. Finally, we verified the main results through experiments. In conclusion, we built a nomogram and identified 8 m6A-related regulators and 10 hubgenes, which were prominently associated with HCM. We found that m6A and the immune system may play a crucial role in the HCM. Accordingly, those genes and pathways might become therapeutic targets with clinical usefulness in the future.
Gompertz law based biological age (GOLD BioAge): a simple and practical measurement of biological aging to capture morbidity and mortality risks
Authors: Hao Meng , Zhang Hui , Wu Jingyi , Li Xiangnan , Huang Yaqi , Wang Meijia , Wang Shuming , Wang Jiaofeng , Chen Jie , Bao Zhi jun , Jin Li , Wang Xiaofeng , Hu Zixin , Jiang Shuai , Li Yi 
Published: November 2024

AbstractBiological age reflects actual aging and overall health, but current aging clocks are often complex and difficult to interpret, limiting their clinical application. In this study, we introduced a Gompertz law-based biological age (GOLD BioAge) model that simplified aging assessment. We estimated GOLD BioAge using clinical biomarkers and found significant associations of the difference from chronological age (BioAgeDiff) with risks of morbidity and mortality in NHANES. Moreover, we developed GOLD ProtAge and MetAge using proteomics and metabolomics data, which outperformed the clinical-only model in predicting mortality and chronic disease risks in UK Biobank. Benchmark analysis illustrated that our models exceeded common aging clocks in predicting mortality across diverse age groups in both NHANES and UK Biobank. The results demonstrated that the GOLD BioAge algorithm effectively applied to both clinical and omics data, showing excellent performance in predicting age-related outcomes. Additionally, we created a simplified version called the Light BioAge, which used three biomarkers for aging assessment. The Light model reliably captured mortality risks in three validation cohorts (CHARLS, RuLAS, CLHLS). It significantly predicted the onset of frailty, stratified frail individuals, and collectively identified individuals at high risk of mortality. In summary, the algorithm of GOLD BioAge could provide a valuable framework for aging assessment in public health and clinical practice.HighlightsThe algorithm of Gompertz law based biological age (GOLD BioAge) was proposed to construct biological aging clocks with convenient and interpretable calculations, which had better performance in predicting mortality risks.Our approach was applicable to proteomics and metabolomics, yielding ProtAge and MetAge with great clinical prospect to improve accuracy of aging assessment and prevent age-related diseases.The Light BioAge, a simplified version, was developed using age and three biomarkers, and it independently predicted mortality in three cohorts.The Light BioAgeDiff significantly predicted the onset of frailty, stratified frail individuals, and collectively identified individuals at high risk of mortality.
Dexmedetomidine as an Adjunctive Sedative in Patients Undergoing Endoscopic Submucosal Dissection: A Systematic Review and Meta-Analysis
Authors: Abosheaishaa Hazem , Abdallfatah Abdallfatah , Abdelghany Abdelmalek , Sethi Arshia , Ismail Abdellatif , Mohamed Doha , Aboeldahb Moataz , Abdelhalim Omar , Mohamed Islam , Azzam Ahmed Y. , Essibayi Muhammed Amir , Altschul David J. , Nassar Mahmoud , Bilal Mohammad 
Published: November 2024

AbstractIntroductionEndoscopic submucosal dissection (ESD) allows for curative en-bloc resection of dysplastic gastrointestinal (GI) tract lesions. However, it is associated with postoperative adverse events (AEs) such as pain, bleeding, and perforation. Dexmedetomidine, an α2-receptor agonist, has emerged as a promising adjunct sedative for ESD under moderate sedation, offering anxiolysis and analgesia. We conducted a systematic review and meta-analysis to evaluate its efficacy and safety for use in ESD.MethodsA comprehensive systematic search was conducted across multiple databases, including Embase, Medline, Scopus, and Web of Science. Studies that involved ESD utilizing dexmedetomidine as an adjunctive medication in combination with other sedatives, were included. Data extraction and risk of bias assessment were independently performed by two reviewers. Meta-analysis was carried out with RevMan using a random-effects model.ResultsEight studies were included in the final analysis. Dexmedetomidine showed no significant difference in en-bloc or complete resection rates compared to controls. Sedation and procedure times were similar between the two groups as well. Dexmedetomidine significantly reduced restlessness (OR 0.15, 95% CI:0.07 to 0.29) and increased bradycardia (OR 7.15, 95% CI 3.17 to 16.11) compared to controls. Upon subgroup analysis, Dexmedetomidine plus Propofol, and Dexmedetomidine plus Midazolam, revealed the same findings regarding restlessness and bradycardia compared to controls which confirmed the adjunctive effects of Dexmedetomidine.ConclusionsDexmedetomidine as an adjunctive sedative appears safe and effective in ESD, reducing restlessness without significant adverse events. The risk of bradycardia is increased, which may be reflective of reduced physiological stress. Future studies should explore optimal dosing and compare Dexmedetomidine with other sedatives in diverse populations.
Humanace2andtmprss2polymorphisms for predicting susceptibility to tuberculosis and COVID-19 co-infection in Cameroonian cohort
Authors: Kameni Mary Ngongang , Tchoupe Eric Berenger , Kamdem Severin Donald , Bhalla Nikhil , Jean Paul Assam Assam , Arnaud Tepa Njiguet , Neba Fuh Roger , Nanda Ranjan Kumar , Awuah Anthony Afum-Adjei , Amuasi John , Netongo Palmer Masumbe 
Published: November 2024

AbstractSARS-CoV-2 andMycobacterium tuberculosis(Mtb) share similarities in their modes of transmission, pathophysiological symptoms, and manifestations. An imbalance in the immune response characterized by significantly elevated levels of some inflammatory cytokines may increase the risk of developing both tuberculosis (TB) and COVID-19 as a comorbid condition. The role of SNPs inace2andtmprss2conferring higher susceptibility to TB-COVID-19 co-infection is relatively underexplored. In this study, a Cameroonian cohort consisting of COVID-19-infected (n = 31), TB-infected (n = 43), TB-COVID-19 co-infected (n = 21), and a control group (n = 24) was studied. The immune response and disease severity were estimated by quantitating inflammatory cytokine levels and self-reported and clinically diagnosed symptoms. We identified SNPs inace2andtmprss2genes previously associated with COVID-19 susceptibility and assessed their association with comorbid conditions. We identified genotypes (Allele AG: rs147311723, rs35803318; Allele AA: rs2074192; Allele CG: rs4240157; Allele AG: rs4646179) inace2gene and (Allele CA: rs61735791, Allele CT: rs12329760) intmprss2genes that are putatively associated with higher susceptibility to both TB and COVID-19. This study underscores the significant genetic and immunological factors contributing to susceptibility to TB and COVID-19 co-infections.
Direct Oral Anticoagulants vs. Heparin for Cancer-Related Stroke: Augmented Meta-Analysis
Authors: Essibayi Muhammed Amir , Azzam Ahmed Y. , Sener Ugur , Altschul David , Atik Merve , Keser Zafer 
Published: November 2024

ABSTRACTBackgroundIschemic stroke is common among patients with systemic malignancy, associated with increased risk of neurological deterioration and mortality compared to the general population. Optimal approach to secondary stroke prevention in cancer patients is unclear. In this meta-analysis, we evaluated available data on the use of direct oral anticoagulants (DOACs) and heparin products for stroke prevention in this population.MethodsUsing the Nested Knowledge AutoLit software, we performed PubMed search in September 2023 for articles reporting the use of antithrombotics for cancer-associated stroke. We conducted systematic review and meta-analysis. We also used a novel computational augmentation method to amplify the sample size to predict the effect before and after sample size augmentation and predict the results of further trials.ResultsAmong 253 potential studies screened, 7 were eligible for inclusion. 439 patients were treated with DOACs and 3968 with heparin products. Among patients treated with heparin, intracerebral hemorrhage (8.8 % vs 1.6, p=.02), overall hemorrhagic complications (17.9% vs 3.5%, p<.001), and mortality [28.1% vs 23.5%, p<.001] were respectively significantly higher than those reported among patients who received DOAC for cancer-associated ischemic stroke. No significant difference was observed in the rates of recurrent deep venous thrombosis, clinically significant hemorrhage, and clinical outcomes between the treatment groups. Similar results were shown with augmented meta-analysis.ConclusionsThis meta-analysis shows DOACs may have efficacy and safety profile similar to heparin products for recurrent stroke prevention in patients with cancer. Given the small number of studies and limited data, findings should be interpreted with caution.