tbuckley/cabot-search huggingface dataset:
Implementation report on pioneering federated data access for the German National Emergency Department Data Registry
Authors: Jonas Bienzeisler, Alexander Kombeiz, Saskia Ehrentreich, Ronny Otto, Wiebke Schirrmeister, Marco Pegoraro, Dominik Brammen, Behrus Puladi, Rainer Röhrig, Raphael W Majeed
Journal: npj Digital Medicine (2025)

Abstract Continuous access to electronic health records will fuel the digital transformation of medicine. For data-sharing initiatives, the challenge lies in ensuring data access aligns with the interests of data holders. Federated data access authorization, where data remains controlled locally, may offer a solution to balance these interests. This paper reports on a digital health implementation of the federated data access authorization system used in the German National Emergency Department Data Registry. Using data from 2017 to 2024, we analyzed the system’s effectiveness in managing data access in a nationwide research network of 58 emergency departments. Facilitating access to more than 7.9 million records, 75% of data access queries were authorized within 15 days. The system also supports periodic queries, enabling recurring real-time access. Query volumes grew from 15 to over 23,000 by 2024, with completion rates of 86%. The system may thus serve as a blueprint for data-sharing initiatives worldwide.
From mechanisms to future therapy: a synopsis of isolated REM sleep behavior disorder as early synuclein-related disease
Authors: Ambra Stefani, Elena Antelmi, Dario Arnaldi, Isabelle Arnulf, Emmanuel During, Birgit Högl, Michele M. T. Hu, Alex Iranzo, Russell Luke, John Peever, Ronald B. Postuma, Aleksandar Videnovic, Ziv Gan-Or
Journal: Molecular Neurodegeneration (2025)

Abstract Parkinson disease (PD), dementia with Lewy bodies (DLB) and multiple system atrophy are synucleinopathies, characterized by neuronal loss, gliosis and the abnormal deposition of α-synuclein in vulnerable areas of the nervous system. Neurodegeneration begins however several years before clinical onset of motor, cognitive or autonomic symptoms. The isolated form of REM sleep behavior disorder (RBD), a parasomnia with dream enactment behaviors and excessive muscle activity during REM sleep, is an early stage synucleinopathy. The neurophysiological hallmark of RBD is REM sleep without atonia (RWSA), i.e. the loss of physiological muscle atonia during REM sleep. RBD pathophysiology is not fully clarified yet, but clinical and basic science suggest that ɑ-syn pathology begins in the lower brainstem where REM atonia circuits are located, including the sublaterodorsal tegmental/subcoeruleus nucleus and the ventral medulla, then propagates rostrally to brain regions such as the substantia nigra, limbic system, cortex. Genetically, there is only a partial overlap between RBD, PD and DLB, and individuals with iRBD may represent a specific subpopulation. A genome-wide association study identified five loci, which all seem to revolve around the GBA1 pathway. iRBD patients often show subtle motor, cognitive, autonomic and/or sensory signs, neuroimaging alterations as well as biofluid and tissue markers of neurodegeneration (in particular pathologic α-synuclein aggregates), which can be useful for risk stratification. Patients with iRBD represent thus the ideal population for neuroprotective/neuromodulating trials. This review provides insights into these aspects, highlighting and substantiating the central role of iRBD in treatment development strategies for synucleinopathies.
Sex-Specific Blood Pressure Trajectories and Cardiovascular Disease in Type 1 Diabetes: 32-Year Follow-up of the Pittsburgh Epidemiology of Diabetes Complications Cohort
Authors: Rachel G. Miller, Trevor J. Orchard, Tina Costacou
Journal: Diabetes Care (2025)

OBJECTIVE We examined sex differences in longitudinal blood pressure (BP) and 32-year cardiovascular disease (CVD) incidence in the Pittsburgh Epidemiology of Diabetes Complications type 1 diabetes cohort. RESEARCH DESIGN AND METHODS BP was measured up to nine (median six) times between 1986–1988 baseline and 2016–2018; n = 300 women and 304 men without CVD at baseline were followed until December 2020 for incidence of total CVD, major adverse cardiovascular events (MACE) (CVD death, myocardial infarction [MI], or stroke), and hard coronary artery disease (hCAD) (CAD death, MI, or coronary revascularization/blockage ≥ 50%). We estimated associations between time to event and longitudinal systolic BP (SBP) and diastolic BP (DBP) by sex using joint models adjusted for time-varying longitudinal antihypertensive (AH) medication use, HbA1c, and overt nephropathy, baseline age, and other CVD risk factors. RESULTS Longitudinal SBP was 5.8 mmHg lower (P &amp;lt; 0.0001) and DBP 6.2 mmHg lower (P &amp;lt; 0.0001) in women versus men. Women had −0.3 mmHg/year faster DBP decline (P &amp;lt; 0.0001) despite similar AH rates by sex. Incidence of CVD was similar by sex. Each 5-mmHg increment in longitudinal SBP (hazard ratio [HR] = 1.23; 95% CI 1.04, 1.45) and DBP (HR = 1.56; 95% CI 1.20, 2.04) was associated with MACE in men only; DBP (HR = 1.28; 95% CI 1.05, 1.56) was associated with hCAD in women only. CONCLUSIONS BP was lower in women than men, and the strength of its association with the initial manifestation of CVD differed by sex. Further research into sex-specific BP mechanisms is needed to improve CVD risk reduction in people living with type 1 diabetes.
FarmGTEx TWAS-server: An Interactive Web Server for Customized TWAS Analysis
Authors: Zhenyang Zhang, Zitao Chen, Jinyan Teng, Shuli Liu, Qing Lin, Jun Wu, Yahui Gao, Zhonghao Bai, Bingjie Li, George Liu, Zhe Zhang, Yuchun Pan, Zhe Zhang, Lingzhao Fang, Qishan Wang
Journal: Genomics Proteomics & Bioinformatics (2025)

Abstract Transcriptome-wide association study (TWAS) is a powerful approach for investigating the molecular mechanisms linking genetic loci to complex phenotypes. However, the complexity of the TWAS analytical pipeline including the construction of gene expression reference panels, gene expression prediction, and association analysis using data from genome-wide association studies (GWAS) poses challenges for genetic studies in many species. In this study, we provide the Farm Animal Genotype-Tissue Expression (FarmGTEx) TWAS-server, an interactive and user-friendly multispecies platform designed to streamline the translation of genetic findings across tissues and species. The server incorporates gene expression data from 49 human tissues (838 individuals), 34 pig tissues (5457 individuals), and 23 cattle tissues (4889 individuals), providing prediction models for 38,180 human genes, 21,037 pig genes, and 17,942 cattle genes. It supports genotype-based gene expression prediction, GWAS summary statistics imputation, customizable TWAS analysis, functional annotations, and result visualization. Additionally, we provide 479,203, 1208, and 657 tissue–gene–trait associations for 1129 humans traits, 41cattle traits, and 11 pigs traits, respectively. Utilizing the TWAS-server, we validated the association of the ABCD4 gene with pig teat numbers. Furthermore, we identified that pig backfat thickness may share genetic similarities with human diastolic blood pressure, sarcoidosis (Lofgren syndrome), and body mass index (BMI). The FarmGTEx TWAS-server offers a comprehensive and accessible platform for researchers to perform TWAS analyses across tissues and species. It is freely available at https://twas.farmgtex.org, with regular updates planned as the FarmGTEx project expands to include more species.
PANE: fast and reliable ancestral reconstruction on ancient genotype data with non-negative least square and principal component analysis
Authors: Luciana de Gennaro, Ludovica Molinaro, Alessandro Raveane, Federica Santonastaso, Sandro Sublimi Saponetti, Michela Carlotta Massi, Luca Pagani, Mait Metspalu, Garrett Hellenthal, Toomas Kivisild, Mario Ventura, Francesco Montinaro
Journal: Genome biology (2025)

The history of human populations has been strongly shaped by admixture events, contributing to patterns of observed genetic diversity across populations. In this study, we introduce the Principal component Ancestry proportions using NNLS Estimation (PANE) method that leverages principal component analysis and non-negative least squares to assess the ancestral compositions of admixed individuals given a large set of populations. Our results show its ability to reliably estimate ancestry across several scenarios, even those with a significant proportion of missing genotypes, in a fraction of the time required when using other tools.
Comment on “Role of CD47 Gene Expression in Colorectal Cancer: A Comprehensive Molecular Profiling Study”
Authors: Zhang Chongjie, Li Jianjiong
Journal: Journal for ImmunoTherapy of Cancer (2025)

The study by Arai et al [1][1] provides significant insights into the role of CD47 gene expression in colorectal cancer (CRC) and its implications for immunotherapy. The authors present compelling evidence that CD47 expression is associated with the activation of several oncogenic pathways and an
Can longitudinal biomarkers guide treatment decisions? Time will tell
Authors: Mark Y. Jeng, Adam J. Schoenfeld
Journal: Clinical Cancer Research (2025)

Abstract Defining patterns of acquired resistance has important prognostic and therapeutic implications in patients with lung cancer. Longitudinal biomarker analysis has enhanced our understanding of tumor biology and treatment response. However, the role of temporally informed biomarkers in guiding clinical decisions, such as local therapy intervention, remains unproven.
Understanding the Impact of Diabetic Peripheral Neuropathy and Neuropathic Pain on Quality of Life and Mental Health in 6,960 People With Diabetes
Authors: Mette Krabsmark Borbjerg, Anne-Marie Wegeberg, Amar Nikontovic, Carsten Dahl Mørch, Lars Arendt-Nielsen, Niels Ejskjaer, Christina Brock, Peter Vestergaard, Johan Røikjer
Journal: Diabetes Care (2025)

OBJECTIVE Diabetic peripheral neuropathy (DPN) and neuropathic pain impacts quality of life (QoL) and mental health negatively. This cross-sectional survey study aimed to 1) elucidate the associations between painful and painless DPN and QoL, mental health, and socioeconomic factors, 2) assess the prevalence of sensory pain descriptors, and 3) evaluate the association between descriptors and the above factors. RESEARCH DESIGN AND METHODS Participants were grouped into people with (n = 1,601) and without (n = 5,359) DPN based on the Michigan Neuropathy Screening Instrument questionnaire. Participants with DPN were subsequently divided into people with (n = 1,085) and without (n = 516) concomitant neuropathic pain based on the modified Douleur Neuropathique en 4 Questions-interview. RESULTS The study showed diminished QoL (36-item Short Form Health Survey [SF-36]: 55.1 [interquartile range {IQR}36.7, 73.6], 82.2 [63.6, 90.9]) and poorer mental health (Hospital Anxiety and Depression Scale, subscale for anxiety: [HADS-A]: 5.00 [2, 9], 2.00 [1, 5]; HADS-subscale for depression [HADS-D]: 4.00 [1, 8], 1.00 [0, 3]) in participants with DPN compared with participants without DPN. The addition of pain diminished QoL (SF-36: 50.7 [34.8, 69.8]) and mental health (HADS-A: 6 [3, 10], HADS-D: 4 [1, 8]) further. The most prevalent pain descriptor in participants with painful DPN were burning pain (73%), while the most prevalent sensory descriptor was pins-and-needles (93%). An interesting finding is the high prevalence of itch (44%). Weak associations with mental health and QoL were present for cold pain, electric pain, and itch. CONCLUSIONS An increased focus on differences in QoL, mental health, and pain phenotypes is of importance to move the field forward toward more interdisciplinary, personalized treatment.
Basal T cell activation predicts yellow fever vaccine response independently of cytomegalovirus infection and sex-related immune variations
Authors: Antonio Santos-Peral, Magdalena Zaucha, Elena Nikolova, Ekin Yaman, Barbara Puzek, Elena Winheim, Sebastian Goresch, Magdalena K. Scheck, Lisa Lehmann, Frank Dahlstroem, Hadi Karimzadeh, Julia Thorn-Seshold, Shenzhi Jia, Fabian Luppa, Michael Pritsch, Julia Butt, Camila Metz-Zumaran, Giovanna Barba-Spaeth, Stefan Endres, Sarah Kim-Hellmuth, Tim Waterboer, Anne B. Krug, Simon Rothenfusser
Journal: Cell Reports Medicine (2025)

Highlights•Sex and CMV status affect baseline immune variation but not YF17D vaccine outcomes•High numbers of activated CD4+ T cells at baseline link to stronger vaccine responses•Elevated baseline CXCL10 levels are negatively associated with YF17D vaccine responses•Environmental factors contribute to the baseline immune status tied to vaccine responseSummaryThe live-attenuated yellow fever 17D (YF17D) vaccine is a model of acute viral infection that induces long-lasting protective immunity. Among immunocompetent adults, responses to YF17D vary significantly. To understand the sources of this variability, we investigate the influence of sex, age, human leukocyte antigen (HLA) type, and 20 prior infections on basal immune parameters and the cellular and antibody response to YF17D in 250 healthy young individuals. Multivariate regression found that sex and cytomegalovirus (CMV) infection significantly contribute to baseline immune variation but do not affect vaccine responses except for reduced YF17D-specific CD8+ frequencies in CMV-infected males. However, the abundance at baseline of non-specific cytokine-expressing T helper cells in circulation is associated with stronger vaccine responses, a state that smoking favors. Additionally, an elevated baseline level of interferon-stimulated CXCL10 is linked to poorer vaccination outcomes. Altogether, YF17D reactivity is conditioned by the baseline immune status independent of sex and CMV-related variations.Graphical abstract
Early-age efferocytosis directs macrophage arachidonic acid metabolism for tissue regeneration
Authors: Connor Lantz, Amanda Becker, Matthew DeBerge, Mallory Filipp, Kristofor Glinton, Aparnaa Ananthakrishnan, Jessica Urbanczyk, Madeline Cetlin, Afnan Alzamroon, Ahmed Abdel-Latif, Matthew Spite, Zhi-Dong Ge, Edward B. Thorp
Journal: Immunity (2025)
Interactions Between Ploidy and Resource Availability Shape Clonal Evolution in Glioblastoma
Authors: Zuzanna Nowicka, Frederika Rentzeperis, Vural Tagal, Jamie K. Teer, Didem Ilter, Richard J. Beck, Jackson P. Cole, Ana M. Forero Pinto, Joanne D. Tejero, Elisa Scanu, Thomas Veith, William Dominguez-Viqueira, Konstantin Maksin, Francisco M. Carrillo-Perez, Olivier Gevaert, Xiaonan Xu, Florian A. Karreth, Mahmoud A. Abdalah, Giada Fiandaca, Stefano Pasetto, Sandhya Prabhakaran, Andrew Schultz, Awino Maureiq E. Ojwang’, Jill S. Barnholtz-Sloan, Joaquim M. Farinhas, Ana P. Gomes, Parag Katira, Noemi Andor
Journal: Cancer Research (2025)

Abstract Glioblastoma (GBM) is the most aggressive form of primary brain tumor. The infiltrative nature of GBM makes complete surgical resection impossible. The selective forces that govern gliomagenesis are strong, shaping the composition of tumor cells during the initial progression to malignancy with late consequences for invasiveness and therapy response. Here, we developed a mathematical model that incorporates ploidy level and the nature of the brain tissue microenvironment to simulate the growth and invasion of GBM and used the model to make inferences about GBM initiation and response to standard-of-care treatment. The spatial distribution of resource access in the brain was approximated through integration of in silico modeling, multi-omics data, and image analysis of primary and recurrent GBM. The in silico results suggested that high ploidy cells transition faster from oxidative phosphorylation to glycolysis than low ploidy cells because they are more sensitive to hypoxia. Between surgeries, simulated tumors with different ploidy compositions progressed at different rates; however, whether higher ploidy predicted fast recurrence was a function of the brain microenvironment. Historical data supported the dependence on available resources in the brain, as shown by a significant correlation between the median oxygen levels in human tissues and the median ploidy of cancers that arise in the respective tissues. Taken together, these findings suggest that availability of metabolic substrates in the brain drives different cell fate decisions for cells with different ploidy, thereby modulating both gliomagenesis and GBM recurrence.
Glucose-Regulating Hydrogel for Immune Modulation and Angiogenesis through Metabolic Reprogramming and LARP7-SIRT1 Pathway in Infected Diabetic Wounds
Authors: Yuheng Liao, Zhenhe Zhang, Weixian Hu, Shengming Zhang, Yanzhi Zhao, Lizhi Ouyang, Chenyan Yu, Mengfei Liu, Bobin Mi, Guohui Liu
Journal: Biomaterials (2025)
Author Correction: A feeding-induced myokine modulates glucose homeostasis
Authors: Xiaoliu Shi, Xiao Hu, Xinlei Fang, Liangjie Jia, Fangchao Wei, Ying Peng, Menghao Liu, Aibo Gao, Ke Zhao, Fengyi Chen, Xiaoli Hu, Jie Hong, Guang Ning, Yongfeng Song, Jiqiu Wang, Yiguo Wang
Journal: Nature Metabolism (2025)
Dihydromyricetin mitigates abdominal aortic aneurysm via transcriptional and post-transcriptional regulation of heme oxygenase-1 in vascular smooth muscle cells
Authors: Weile Ye, Pinglian Yang, Mei Jin, Jiami Zou, Zhihua Zheng, Yuanyuan Li, Dongmei Zhang, Wencai Ye, Zunnan Huang, Jiaojiao Wang, Zhiping Liu
Journal: Acta Pharmaceutica Sinica B (2025)

Abdominal aortic aneurysm (AAA) is a deadly condition of the aorta, carrying a significant risk of death upon rupture. Currently, there is a dearth of efficacious pharmaceutical interventions to impede the advancement of AAA and avert it from rupturing. Here, we investigated dihydromyricetin (DHM), one of the predominant bioactive flavonoids in Ampelopsis grossedentata (A. grossedentata), as a potential agent for inhibiting AAA. DHM effectively blocked the formation of AAA in angiotensin II-infused apolipoprotein E-deficient (ApoE-/-) mice. A combination of network pharmacology and whole transcriptome sequencing analysis revealed that DHM's anti-AAA action is linked to heme oxygenase (HO)-1 (Hmox-1 for the rodent gene) and hypoxia-inducible factor (HIF)-1α in vascular smooth muscle cells (VSMCs). Remarkably, DHM caused a robust rise (∼10-fold) of HO-1 protein expression in VSMCs, thereby suppressing VSMC inflammation and oxidative stress and preserving the VSMC contractile phenotype. Intriguingly, the therapeutic effect of DHM on AAA was largely abrogated by VSMC-specific Hmox1 knockdown in mice. Mechanistically, on one hand, DHM increased the transcription of Hmox-1 by triggering the nuclear translocation and activation of HIF-1α, but not nuclear factor erythroid 2-related factor 2 (NRF2). On the other hand, molecular docking, combined with cellular thermal shift assay (CETSA), isothermal titration calorimetry (ITC), drug affinity responsive target stability (DARTS), co-immunoprecipitation (Co-IP), and site mutant experiments revealed that DHM bonded to HO-1 at Lys243 and prevented its degradation, thereby resulting in considerable HO-1 buildup. In summary, our findings suggest that naturally derived DHM has the capacity to markedly enhance HO-1 expression in VSMCs, which may hold promise as a therapeutic strategy for AAA.
Unveiling the Molecular Legacy of Transient Insulin Resistance: Implications for Hepatic Metabolic Adaptability
Authors: Alexandre Berthier, Céline Gheeraert, Manjula Vinod, Manuel Johanns, Loïc Guille, Joel T Haas, Julie Dubois-Chevalier, Jérôme Eeckhoute, Bart Staels, Philippe Lefebvre
Journal: Journal of Hepatology (2025)
Left atrial-to-coronary sinus shunting in HFmrEF/HFpEF The ALT-FLOW Trial (Early Feasibility Study) 2-year results
Authors: Francesco Fioretti, Benjamin Hibbert, Peter M Eckman, Trevor Simard, Marino Labinaz, Babak Nazer, Mark Wiley, Bhanu Gupta, Andrew J Sauer, Hirak Shah, Paul Sorajja, Andres M Pineda, Emil Missov, Lillian Aldaia, Konstantinos Koulogiannis, William A Gray, Firas Zahr, Javed Butler
Journal: JACC Heart Failure (2025)
Epidemiological and genomic evolution of the ongoing outbreak of clade Ib mpox virus in the eastern Democratic Republic of the Congo
Authors: Leandre Murhula Masirika, Jean Claude Udahemuka, Leonard Schuele, David F. Nieuwenhuijse, Pacifique Ndishimye, Marjan Boter, Justin Bengehya Mbiribindi, Cris Kacita, Trudie Lang, Christian Gortázar, Jean Pierre Musabyimana, Saria Otani, Frank M. Aarestrup, Freddy Belesi Siangoli, Bas B. Oude Munnink, Marion Koopmans
Journal: Nature Medicine (2025)

Abstract In September 2023, an ongoing mpox outbreak emerged in South Kivu (DRC) which spread to other regions and countries. We describe the epidemiological and genomic evolution of the outbreak between September 2023 and June 2024. Samples were collected from hospitalized patients, along with data on residence and possible exposures. Employee numbers and locations were recorded for bars with sex workers. Where possible, exposures were linked to genomic sequencing data for cluster analysis. In total, 670 cases were admitted to Kamituga hospital from 17 health areas. Of the cases, 52,4% were in females, and 47,6% in males. The majority (83,4%) were linked to professional sexual interactions. Seven deaths occurred and three healthcare workers acquired mpox. Eight of fourteen pregnant women had fetal loss. Phylogenetic analysis revealed three Clade Ib clusters. Longer branches of a sequence clustering with sequences from Kenya, Uganda, Sweden and Thailand indicate more undocumented spread. Mutations were mostly APOBEC3-type mutations indicative of sustained human-to-human transmission. No clear link between sequence cluster, bar or health area was observed. These data suggest rapid spread mostly through sexual contact within densely populated areas. Spread to neighboring countries highlights the need for extended cross-border collaboration, health education strategies focusing on sex workers, contact tracing, clinical care and surveillance.