bluuebunny/crossref_metadata_2025_split huggingface dataset:
FedPyDESeq2: a federated framework for bulk RNA-seq differential expression analysis
Authors: Muzellec Boris , Marteau-Ferey Ulysse , Marchand Tanguy 
Published: December 2024

AbstractDespite opportunities for deeper clinical insights, large-scale transcriptome studies are often limited by data silos and risks of privacy leakage. While meta-analysis can be employed to aggregate local results, this is at the price of lower statistical power, especially in heterogeneous settings. A recent paradigm in distributed computing, federated learning (FL) is a means of fitting models from siloed data, while ensuring that private data does not leave its storage facilities. Here, we introduce FedPyDESeq2, a software for differential expression analysis (DEA) on siloed bulk RNA-seq. Building on FL tools,FedPyDESeq2implements theDESeq2pipeline for DEA on siloed datasets in a privacy-enhancing manner. We benchmarkFedPyDESeq2on datasets from The Cancer Genome Atlas corresponding to 8 different indications, split by geographical origin.FedPyDESeq2achieves near-identical results on siloed data compared withDESeq2on pooled data, and significantly outperforms meta-analysis baselines on siloed data.
COMPETENCES OF LOWER COMMUNITY HEALTH CENTRE LEADERS IN ANNUAL HEALTH WORK PLANS AND ITS INFLUENCE ON DISTRICT PERFORMANCE IMPROVEMENT IN BUSOGA SUB-REGION: A RETROSPECTIVE STUDY
Authors: Muluya Kharim Mwebaza , Muwanguzi Gangu David , Babatunde Aremu , Rashid Naziru , Wananda Irene , Kayemba Jonah Fred , Ogara Collin , Waibi Musa , Mugisha John Francis , Waiswa Peter 
Published: December 2024

AbstractBackgroundLower-level community health centres play a crucial role in the delivery of primary healthcare services, and the competences of their leaders can significantly influence district health performance.ObjectiveThe study assessed the influence of competences of lower community health centre leaders in annual health work planning on the district performance improvement. Staffs are recruited based on staffing standards and expected to participate in district health planning cycles, and use implementation manuals in developing annual health work plans to improve district health performance.MethodsA retrospective (case control) study design was employed to understand health centre performance data across various districts in the Busoga sub-region. There was a comparison of performance between the worst performing (case) and best performing (control) districts in the region according to the Annual Health Sector Performance reports from 2017/18 financial year to 2021/2022. Data was collected between 17thJuly, 2024 and 23rdAugust, 2024. Statistical analysis of data from 12 health centres in the case and 12 in the control was conducted using STATAversion 16to determine competences of lower community health centre leaders that influence district performance.ResultsThe study found that the district performance in annual health work planning was not good in both the case and control groups (26.4% and 47.2% respectively). Only three competences variables were statistically significantly associated with improved district health performance. Health centres that (1) met staffing levels in accordance with public facility standards (χ2, 7.756;p-value, 0.005*), (2) staff attended district planning cycle meetings (χ216.713;p-value, 0.001*), and (3) health centres utilized four or more implementation manuals for the development of their annual health work plans (χ243.333;p-value, 0.001*) demonstrated statistically significant improvements in performance. These competences enabled more effective service delivery, better alignment with district health priorities, and the implementation of comprehensive, evidence-based interventions.ConclusionThe competences of lower community health centre leaders is held together with health centres meeting staffing standards, their participation in district planning cycles, and the utilization of implementation manuals and are critical for improving district health performance in the Busoga sub-region. Strengthening these competences through targeted supportive meetings and capacity-building initiatives is recommended to enhance the overall effectiveness of health service delivery at the district level.
The two crystal structures of unloaded and cargo-loaded Vacuolar Sorting Receptor 1 lumenal domain (VSR1-Nt) reveal two cargo binding sites and a mechanism of transport
Authors: Borges Rafael J. , Eldahshoury Mahmoud K. , Parr Rebecca J. , Paul Marilyn , Fyfe Paul , Nettleship Joanne E. , An Jing , Shah Nita , Loureiro Levada Ana J. , Fontes Marcos R. M. , Owens Raymond J. , Denecke Jurgen , Quigley Andrew , Goldman Adrian , Postis Vincent , Usón Isabel , de Marcos Lousa Carine 
Published: December 2024

AbstractVacuolar sorting receptors (VSRs) are type I membrane proteins crucial for seed germination and plant development. While VSR trafficking has been extensively studied, the mechanism of cargo binding and release by the N-terminal lumenal region is less understood. We have elucidated the crystal structures of unloaded and cargo-loaded forms of the lumenal region of VSR1 containing the protease-associated domain, the Central domain and epidermal growth factor-like repeats. Calcium coordination induces remodeling of the linkers between domains, triggering large conformational changes that expose two binding sites, one across the PA and Central domain and a second site in the Central domain. Our findings provide a mechanistic model for cargo binding in a calcium rich environment, where VSR is locked in a conformation exposing the cargo binding sites, while cargo release is favoured by lower calcium concentrations and trimer formation. These results advance our current knowledge on VSRs and will inform future studies on vacuolar trafficking and cargo binding/release.
Genomic Epidemiology of 2023-2024 Oropouche Outbreak in Iquitos, Peru reveals independent origin from a concurrent outbreak in Brazil
Authors: Olortegui Maribel Paredes , Schiaffino Francesca , Peñataro_Yori Pablo , Colston Josh M. , Shapiama_Lopez Valentino , Pinedo_Vasquez Tackeshy , Garcia_Bardales Paul F. , Flynn Thomas G. , Ramal-Asayag Cesar , Hughes Holley R , Davis Emily , Russell Brandy J. , Brault Aaron C. , Palomino Yuri Alfonso Alegre , Munayco Cesar , Liu Jie , Houpt Eric , Cooper Kerry K. , Parker Craig T. , Kosek Margaret N. 
Published: December 2024

AbstractOropouche virus is an arbovirus endemic to the Americas. Periodic outbreaks have occurred since its description in 1955. In late 2023, an outbreak occurred in Peru, centered in and around Iquitos in the Eastern Peruvian Amazon. An existing acute febrile illness (AFI) surveillance program was able to document its emergence and characterize arthralgia and dysuria and the absence of diarrhea as distinctive clinical features of Oropouche virus-associated febrile illness relative to other causes of AFI. Sequencing of isolates from the outbreak demonstrated that strains from this region were distinct from those causing disease in Brazil, despite the large-scale movement of people along the Amazon corridor, but highly similar to strains from Colombia and Ecuador. Our findings suggest that the current outbreak in South America is fundamentally multifocal in origin and not the result of geographic spread from Brazil, which experienced an outbreak between 2022 and 2024.
Epidemiological Patterns, Treatment Response, and Metabolic Correlations of Idiopathic Intracranial Hypertension: A US-Based Study From 1990 to 2024
Authors: Azzam Ahmed Y. , Nassar Mahmoud , Morsy Mahmoud M. , Mohamed Adham A. , Wu Jin , Essibayi Muhammed Amir , Altschul David J. 
Published: December 2024

AbstractIntroductionIdiopathic Intracranial Hypertension (IIH) presents an increasing health burden with changing demographic patterns. We studied nationwide trends in IIH epidemiology, treatment patterns, and associated outcomes using a large-scale database analysis within the United States (US).Methods:We performed a retrospective analysis using the TriNetX US Collaborative Network database (1990-2024). We investigated demographic characteristics, time-based trends, geographic distribution, treatment pathways patterns, comorbidity profiles and associated risks with IIH. We used multivariate regression, Cox proportional hazards modeling, and standardized morbidity ratios to assess various outcomes and associations.Results:Among 51,526 patients, we found a significant increase in adult IIH incidence from 16.0 to 127.0 per 100,000 (adjusted RR: 6.94, 95% CI: 6.71-7.17). Female predominance increased over time (female-to-male ratio: 3.29, 95% CI: 3.18-3.40). Southern regions showed the highest prevalence (43.0%, n=21,417). Initial medical management success rates varied between acetazolamide (42.3%) and topiramate (28.7%). Advanced interventional procedures showed 82.5% success rates in refractory cases. Cox modeling revealed significant associations between IIH and metabolic syndrome (HR: 2.14, 95% CI: 1.89-2.39) and cardiovascular complications (HR: 1.76, 95% CI: 1.58-1.94), independent of BMI.Conclusions:Our findings highlight IIH as a systemic disorder with significant metabolic implications beyond its neurological manifestations. The marked regional disparities and rising incidence rates, especially among adults, suggest the need for targeted healthcare strategies.Early intervention success strongly predicts favorable outcomes, supporting prompt diagnosis and treatment initiation. These results advocate for an integrated approach combining traditional IIH management with broad metabolic screening care.
Circling back:Vespulaspp. re-invasion after knockout from volcanic ash fall in Patagonia
Authors: Pereira Ana Julia , Corley Juan Carlos , Giménez Gustavo , Masciocchi Maité 
Published: December 2024

AbstractEffective management of invasive species requires understanding re-invasion dynamics, to prevent control failures, refine methodologies, and enhance protocols. Re-invasion is the process by which eradicated or naturally disappeared exotic species establish themselves again, in previously occupied areas. Re-invasion often bypasses initial invasion phases such as transport and introduction. During re-establishment, changes in the invader, the invaded environment, and species interactions can influence the success of invasion.We investigated re-invasion patterns ofVespula germanicaandVespula vulgariswasps in NW Patagonia (Argentina) following a significant natural disturbance: the 2011 Puyehue-Cordón Caulle volcanic eruption, which caused unprecedented arthropod defaunation. By establishing 23 sampling sites in heavily affected regions, we conducted sampling events over three years (2012-2014).Our findings show that re-invasion of bothVespulaspp. occurs fast, with minimal interspecific competition among them observed. The proximity to urban centers, acting as refuges, further facilitated their establishment.This unique case study highlights the adaptability of these invasive wasps in the face of extreme environmental disruptions. By describing the importance of considering reinvasion routes and refuges, this research may help develop more effective management strategies to controlVespulapopulations.
The effectiveness of Cenobamate in patients previously treated with Vagus Nerve Stimulation for drug resistant epilepsy
Authors: Hogeveen Lara , Legros Benjamin , Meurs Alfred , De Herdt Veerle , Sprengers Mathieu , Hödl Stephanie , Mertens Ann , Gadeyne Stefanie , Raedt Robrecht , Dewaele Frank , Vandersteene Jelle , Boon Paul , Vonck Kristl 
Published: December 2024

AbstractBackgroundVagus Nerve Stimulation (VNS) is an efficacious neuromodulatory treatment for patients with drug resistant epilepsy (DRE). In many VNS treated patients, seizures are not fully controlled. These patients often represent a highly refractory group in whom novel anti-seizure medication (ASM) may be tried. This study evaluates the effectiveness of Cenobamate (CNB) in patients previously treated with VNS.MethodsThe medication history of all patients treated with VNS at Ghent University Hospital and HUB-Hôpital Erasme Brussels between 1995 and 2024 was reviewed. In patients who received an add-on treatment with CNB after at least 12 months of VNS therapy, mean monthly seizure frequency before VNS, after VNS, and after CNB was assessed.Results54/620 patients treated with VNS between March 1995 and November 2023 were treated with CNB after a median VNS treatment time of 9 years. With VNS, 13/52 (25%) had a seizure frequency reduction of ≥50%. Side-effects were mild and stimulation-related. After add-on of CNB (median daily dosage of 200mg) for a median follow-up of 10 months, 24/54 (44.4%) became responders. Of these patients, 6 (11.1% from total cohort) reported seizure freedom for a median duration of 26 weeks. Almost half (46.2%) of the VNS non-responders became CNB responder. The median number of concomitant ASM was 3. In 20/54 (37%), the number of ASM was reduced. 7/54 (13%) stopped CNB because of side-effects. Fatigue was the most prevalent side effect in 23/54 patients (42.6%).ConclusionIn DRE patients treated with VNS therapy who could benefit from further improvement in seizure control, add-on treatment with CNB is useful. This most recently marketed ASM leads to a significant improvement in seizure frequency in more than 40% of the patients.
Genome-wide association study identifies novel risk variants for celiac disease in the 5p15.33 locus: insights from a population-based screening of adults, the HUNT study
Authors: Alam Mohammad Sayeef , Thomas Laurent F. , Brumpton Ben , Hveem Kristian , Lundin Knut E. A. , Withoff Sebo , Jonkers Iris H. , Sollid Ludvig M. , Hjort Rebecka , Ness-Jensen Eivind 
Published: December 2024

AbstractPrevious studies have uncovered genetic loci associated with celiac disease (CeD) within both the human leukocyte antigen (HLA) and non-HLA regions. However, half of the heritability remains unexplained. This study aimed to identify novel loci associated with CeD in a general adult population screened for the disease, mitigating the likely selection bias observed in previous case-control studies. The study utilized data from the fourth Trøndelag Health Study (HUNT4) in Norway, where 52,358 adults were screened for CeD using serology, identifying 465 previously undiagnosed biopsy-confirmed cases. Additionally, 377 previously diagnosed cases were identified through hospital journal searches and registry data. Genotyping of 373,185 single nucleotide polymorphisms was performed on all participant using four Illumina HumanCoreExome arrays. Imputation, using the Haplotype Reference Consortium panel, resulted in approximately 24.9 million variants, post quality control. A genome-wide association study was performed using SAIGE, and functional mapping and pathway enrichment analysis was conducted using FUMA. All except one of the 42 known autosomal loci were present in the data, of which seven reached the suggestive significance threshold (P ≤ 5 × 10−6). Thirteen independent novel associations were observed (P ≤ 5× 10−8), with the 5p15.33 locus showing the highest potential for a true association with CeD, warranting further studies to validate the findings. Notably, theIRX1gene, located close to the 5p15.33 locus has also been associated with rheumatoid arthritis, suggesting a new shared autoimmune locus.
A Machine Learning Framework for Cancer Prognostics: Integrating Temporal and Immune Gene Dynamics via ARIMA-CNN
Authors: Lin Rui-Bin , Zhou Linlin , Lin Yu-Chun , Yu Yu , Yang Hung-Chih , Yu Chen-Wei 
Published: December 2024

AbstractHepatocellular carcinoma (HCC) poses a significant global health challenge due to its high incidence and mortality rates. Our study investigates the prognostic significance of chemokine (C-C motif) ligand 5 (CCL5) and various immune gene signatures in HCC using an innovative combination of Autoregressive Integrated Moving Average (ARIMA) and Convolutional Neural Network (CNN) models. Time series data were utilized to apply an ARIMA model that captures the temporal dynamics of CCL5 expression. This model’s residual was integrated with immune signature expression data, including lymphocytes and macrophages, to extract features using a CNN model. Our study demonstrates that CNN-extracted features yield a statistically more robust association with patient survival compared to the traditional median split method, which primarily focuses on single-gene analysis. Specifically, CNN-extracted features from CD8 T cells and effector T cells resulted in a hazard ratio (HR) of 0.7324 (p= 0.0008) with log-rankp-value (0.0131), underscoring their pivotal role in the anti-tumor immune response. This methodology highlights the superior prognostic value obtained through integrated multi-gene analyses, providing deeper insights into tumor-immune interactions than conventional single-gene approaches. Moreover, clustering immune genes based on non-parametric correlations unveiled distinct survival patterns. A cluster comprising B cells, Th2 cells, T cells, and NK cells exhibited a moderate protective effect (HR: 0.8714,p= 0.1093) alongside a significant log-rankp-value (0.0233). However, the cluster, including granulocytes, Tregs, macrophages, and myeloid-derived suppressor cells, showed no significant survival association, highlighting the intricate immune regulation within the tumor microenvironment. These findings emphasize the necessity of incorporating temporal dynamics and synergistic immune gene interactions for more accurate prognostic evaluations. Our integrated ARIMA-CNN framework represents a significant advancement, leveraging both linear and nonlinear modeling to uncover the dynamic influence of multiple immune genes. This framework holds excellent potential for identifying robust biomarkers and personalizing immunotherapy strategies, ultimately paving the way for innovative cancer management solutions.
Genetic Architecture of Postpartum Psychosis: From Common to Rare Genetic Variation
Authors: Jung Seulgi , Caballero Madison , Kępińska Adrianna , Smout Shelby , Munk-Olsen Trine , Robakis Thalia K. , Bergink Veerle , Mahjani Behrang 
Published: December 2024

AbstractPostpartum psychosis is a severe psychiatric condition marked by the abrupt onset of psychosis, mania, or psychotic depression following childbirth. Despite evidence for a strong genetic basis, the roles of common and rare genetic variation remain poorly understood. Leveraging data from Swedish national registers and genomic data from the All of Us Research Program, we estimated family-based heritability at 55% and WGS-based heritability at 37%, with an overrepresentation on the X chromosome. Rare coding variant analysis identifiedDNMT1andHMGCRas potential risk genes (q < 0.1). Analysis of 240,009 samples from All of Us demonstrated significant associations between these genes and multiple psychiatric disorders, supporting their biological relevance. Additionally, 17% of bipolar disorder, 21% of schizophrenia, and 16–25% of multiple autoimmune disorder risk genes overlapped with postpartum psychosis. These findings reveal unique genetic contributions and shared pathways, providing a foundation for understanding pathophysiology and advancing therapeutic strategies.
Diverging repeatomes in holoparasitic Hydnoraceae uncover a playground of genome evolution
Authors: Kim Woorin , Schmidt Nicola , Jost Matthias , Mkala Elijah Mbandi , Winkler Sylke , Hu Guang-Wan , Heitkam Tony , Wanke Stefan 
Published: December 2024

SummaryThe nuclear genomes of parasitic plants have undergone unique evolutionary trajectories to adapt to the heterotrophic lifestyle. These adaptations often involve large genomic alterations, potentially driven by repetitive DNAs. Despite the recognized role of repetitive DNAs for shaping plant genomes, their contribution to parasitic plant genome evolution remains largely unexplored. This study presents the first analysis of repetitive DNAs in eleven genomes of Hydnoraceae, a holoparasitic plant family.The repetitive DNAs were identified and annotatedde novo. Patterns of abundance and presence-absence were aligned with the phylogenetic relationships, geographical distribution, and host shifts, suggesting repetitive DNAs’ key role in shaping Hydnoraceae genomes.The two Hydnoraceae genera,HydnoraandProsopanche, exhibit distinct profiles. EightHydnoragenomes are largely populated by long terminal repeat retrotransposons, while threeProsopanchegenomes vary greatly in repetitive DNA composition, includingP. bonacinaewith massive amplifications of a single DNA transposon andP. panguanensiswith over 15% 5S rDNA, compared to <0.1% in some Hydnoraceae. Both extremely low and very high abundance of 5S rDNA challenges our current understanding on chromosomal stabilization and rDNA transcription.These genome dynamics, while inviting for further investigations, suggest rapidly evolving repeat profiles, potentially accelerated by the adaptation to the parasitic lifestyle.
A bacterial site 2 protease contributes to RNA phage resistance by targeting phage lysis protein
Authors: Bae Hee-Won , Kim So-Youn , Choi Shin-Yae , Ki Hyeong-Jun , Ahn Se-Jeong , Cho You-Hee 
Published: December 2024

ABSTRACTLytic phages culminate their lifecycle by causing lysis of the infected host cell. Despite extensive research on the molecular mechanisms of phage lysis, our understanding of anti-phage resistance mechanisms during the lysis stage remains less understood. Here, we demonstrated that MucP, a site 2 protease ofPseudomonas aeruginosa(PA), mitigates the activity of the RNA phage PP7 lysis protein (LP), which contains a transmembrane (TM) helix, suggesting that MucP act as a resistance mechanism against PP7-induced lysis. We identified an LP variant (LP*) having enhanced helical propensity due to P26L and S40L mutations, which was unaffected by MucP and exhibited killing activity against PA strains that are resistant to the wild type LP, with an inverse correlation between MucP activity and LP susceptibility. A PP7 mutant with LP* exhibited MucP-escaper phenotype such as discernable plaque formation on MucP-expressing cells. These results suggest that MucP targets the RNA phage LP at the TM helix in certain strains, providing a resistance function compromising phage lysis by utilizing an existing bacterial enzyme in PA.SIGNIFICANCEHost cell lysis is the last step of the phage lifecycle, occurring only when the progeny virions reach a certain number. The factors influencing coordinated lysis have not been well-studied, particularly in the context of the evolutionary arms race between phages and their hosts. Our study identifies MucP, a membrane protease inPseudomonas aeruginosa(PA), as a resistance mechanism against the RNA phage PP7 by destabilizing its lysis protein (LP), which has lower helical tendency at the transmembrane (TM) domain. An LP variant with higher helical tendency exhibits strong killing activity against PA strains normally resistant to LP-mediated killing, revealing an inverse correlation between MucP activity and LP susceptibility in various PA clinical stains. Given that MucP is a conserved protease critical for mucoid conversion in PA, we propose that MucP offers a phage resistance mechanism or an intrinsic or nonprofessional defense mechanism against the RNA phages, which varies among the phenotypically diverse PA isolates.SYNOPSISPseudomonas aeruginosaMucP, a site 2 protease, destabilizes the PP7 lysis protein (LP).Helical propensity of the LP transmembrane domain affects MucP-susceptibility.Clinical strains with higher MucP activity exhibit greater LP and RNA phage resistance.PP7* with MucP-resistant LP* shows broadened spectrum with no less reduced infectivity.Abstract Figure