tbuckley/cabot-search huggingface dataset:
Childhood Asthma and Allergy Are Related to Accelerated Epigenetic Aging
Authors: Miriam Leskien, Elisabeth Thiering, Zhebin Yu, Anke Huels, Yueli Yao, Simon Kebede Merid, Olena Gruzieva, Stephan Weidinger, Melanie Waldenberger, Annette Peters, Erik Melén, Marie Standl
Journal: Allergy (2025)

ABSTRACT Background Few studies showed associations of childhood allergic diseases with epigenetic aging using traditional clocks trained mainly on adults. Tracking DNA methylation variation early in life has suggested poor performance of these clocks in children. Therefore, we aim to elucidate the association between allergic diseases and epigenetic age using a pediatric clock. Methods We used data from the German LISA birth cohort study at six ( N = 234) and ten ( N = 227) years. DNA methylation was measured in blood using the Infinium Methylation EPIC BeadChip. We calculated epigenetic age using the pediatric clock developed by Wu et al. (Aging 2019) (median absolute error = 0.04 years, Spearman correlation with chronological age r = 0.75). Linear mixed models were used to examine longitudinal associations of epigenetic age acceleration with doctor‐diagnosed asthma, rhinitis, and eczema, or a combination thereof (“any allergy”) as well as aeroallergen sensitization. Replication was performed in BAMSE at the 8‐year follow‐up ( N = 625) using linear models. Additionally, epigenetic age in adults from KORA F4 was estimated using Horvath's clocks and associations with allergic diseases were tested applying linear models. Results Having any allergy was significantly associated with a mean epigenetic age acceleration of 0.34 years (95% CI = [0.06; 0.63]) using Wu's clock in LISA. Associations with consistent effect directions were found for allergic rhinitis, asthma, and eczema. No associations with aeroallergen sensitization were observed. In BAMSE, an inverse association of epigenetic age acceleration with eczema was found (−0.52 years, 95% CI = [−0.97; −0.07]). In KORA, hay fever was significantly associated with accelerated epigenetic age when using the Horvath pan‐tissue clock (1.05 years, 95% CI = [0.21; 1.89]). Conclusions We found an increase in epigenetic age in children with allergic diseases from LISA. Our results suggest that epigenetic age acceleration seems to be related to the persistent burden of allergic diseases, but not to non‐symptomatic aeroallergen sensitization.
Comprehensive αβ T‐Cell Receptor Repertoire Analysis Reveals a Unique CD8+ TCR Landscape in DOCK8‐Deficient Patients
Authors: Ceren Bozkurt, Gökhan Cildir, Umran Aba, Rahmi Kutay Erdogan, Nicholas I Warnock, Chung Hoow Kok, Asena Pinar Sefer, Sule Haskologlu, Sidem Didar Tekeoglu, Gülşah Merve Kılınç, Canberk Ipsir, Tugba Arikoglu, Aylin Kont Ozhan, Saliha Esenboga, Ahmet Özen, Elif Karakoç‐Aydiner, Sevgi Bilgiç Eltan, Çigdem Aydogmus, Candan Islamoglu, Kübra Baskın, Betul Karaatmaca, Ayse Metin, Deniz Çagdaş, Figen Dogu, Aydan Ikinciogullari, Safa Baris, Baran Erman
Journal: Allergy (2025)

Dedicator of cytokinesis protein 8 (DOCK8) is a guanine nucleotide exchange factor highly expressed in, and critical for, the function of various innate and adaptive immune cells. DOCK8 deficiency leads to combined immunodeficiency characterized by susceptibility to infections, autoimmunity, and a severe Th2-type immune response. While dysfunction in various T cell subsets has been implicated in these phenotypes, a comprehensive analysis of the T-cell receptor (TCR) repertoire in these patients has not yet been documented. This study investigates the αβ TCR repertoire in DOCK8-deficient patients to identify features related to disease pathogenesis and explore the potential role of TCR repertoire alterations in disease development. We compared immune repertoire profiles determined by high-throughput TCR sequencing of circulating CD4+ and CD8+ T cells from patients with DOCK8 deficiency (n = 10) to healthy controls (n = 7) and patients with ataxia-telangiectasia (AT) (n = 5). Different diversity analyses revealed a restricted TRA and TRB repertoire in both CD4+ and CD8+ T cells from DOCK8-deficient patients, with the restriction being more pronounced in CD8+ T cells. Skewed usage of individual variable (V) and joining (J) genes and potentially self-reactive CD8+ T cell clones, as determined by hydrophobicity and cysteine indices, were identified in DOCK8-deficient patients. Our study represents the most comprehensive immune repertoire analysis in DOCK8 deficiency. The identification of a significantly restricted αβ TCR repertoire, along with the detection of potentially autoreactive clones, highlights the crucial role of immune repertoire profiling in elucidating the pathogenesis of DOCK8 deficiency.
Proteomic profiling reveals a higher presence of glycolytic enzymes in human atherosclerotic lesions with unfavourable histological characteristics
Authors: Kaylin C A Palm, Xiaoke Yin, Ferheen Baig, Konstantinos Theofilatos, Sander W van der Laan, Gert J de Borst, Dominique P V de Kleijn, Johann Wojta, Stefan Stojkovic, Manuel Mayr, Hester M den Ruijter, Gerard Pasterkamp, Ernest Diez Benavente, Michal Mokry
Journal: Cardiovascular Research (2025)

Abstract Aims Molecular characterization of vulnerable atherosclerotic plaques often relies on transcriptomic data. However, RNA expression may not consistently align with protein expression. The proteomic landscape linked to plaque vulnerability is underexplored in human lesions. In this study, we analyzed a large mass spectrometry-based proteomics dataset from the plaque tissue of 320 patients to identify the molecular mechanisms associated with vulnerable plaques. Previous studies have shown significant differences in cell metabolism in murine atherosclerosis models, prompting an in-depth description of expression of key enzymes in glycolysis in human atherosclerotic plaques. Methods and results Atherosclerotic lesions from 320 patients undergoing carotid endarterectomy surgery were collected (200 discovery set and 120 for the validation set) and underwent proteomic analyses. Plaque samples were digested, enriched for extracellular matrix proteins, and processed for untargeted proteomics analysis. The resulting protein levels were linked to pathological plaque characteristics, bulk and single cell transcriptomics, and clinical data. Proteomic analysis of 200 human atherosclerotic carotid lesions detected 1499 proteins with most showing poor correlation with RNA levels. We identified 240 proteins associated with plaque vulnerability index (PVI) (FDR&amp;lt;0.05), including key glycolysis enzymes: HK3 (P=0.003, FDR=0.03), PKM (P=0.008, FDR=0.05), and LDHA (P=0.006, FDR=0.04). The observed associations were mainly driven by macrophage content and fat content, reflected the severity of pre-operative symptoms, exhibited significant sex differences, and correlated with plaque haemorrhage biomarker BLVRB. Validation in 120 patients confirmed HK3 and PKM's association with plaque progression and clinical symptoms (all P&amp;lt;0.001). Conclusion Enzymes involved in the glycolysis process are more abundant in plaques with vulnerable histological characteristics and are significantly associated with plaque hemorrhage biomarker BLVRB. This implies that plaque destabilization may be driven by higher glycolysis metabolism, which may contribute to plaque haemorrhage. This association was stronger in women, underlining the important role of energy metabolism in sex-specific mechanisms of atherosclerotic disease.
Structures of Safety in Hospital Disposition: Five Ethical Responsibilities
Authors: Georgina D. Campelia, Maralyssa Bann, James N. Kirkpatrick, Denise M. Dudzinski
Journal: The American Journal of Bioethics (2025)

Complex hospital disposition is categorized by the difficulty or impossibility, despite efforts, to secure a medically safe discharge option for a patient. Discharge planning should negotiate limited inpatient resources that must be distributed justly, while also considering failures of outpatient and social resources to meet the patient's needs. This essay argues that recognition of these structural insufficiencies, which are inequitably distributed, must be a starting point for addressing safe hospital disposition. This recognition grounds five ethical responsibilities for navigating complex disposition planning: justice, common good, respect for persons, harm reduction, and care. Each responsibility is applied to common complex disposition vignettes, with attention to practical guidelines for implementation in clinical spaces.
Correction to: Mavacamten in Patients With Hypertrophic Cardiomyopathy Referred for Septal Reduction: Week 128 Results from VALOR-HCM
Authors: Milind Y. Desai, Kathy Wolski, Anjali Owens, Jeffrey B. Geske, Sara Saberi, Andrew Wang, Mark Sherrid, Paul C. Cremer, Neal K. Lakdawala, Albree Tower-Rader, David Fermin, Srihari S. Naidu, Nicholas G. Smedira, Hartzell Schaff, Zhiqun Gong, Lana Mudarris, Kathy Lampl, Amy J. Sehnert, Steven E. Nissen
Journal: Circulation (2025)
The Association Between Tirzepatide Versus Insulin Glargine and NT-proBNP Levels in People With Type 2 Diabetes With or at Elevated Risk for Cardiovascular Disease: Post hoc Analyses of SURPASS 4
Authors: Naveed Sattar, Govinda J. Weerakkody, Darren K. McGuire, Mikhail N. Kosiborod, Matthew M.Y. Lee, Paul Welsh, Ewan R. Pearson, Russell J. Wiese, Kevin Duffin, Jonathan Wilson, Noemi Pavo, Martin Hülsmann, Imre Pavo
Journal: Circulation (2025)
Health Outcomes of Produce Prescription Programs Associated with Gus Schumacher Nutrition Incentive Program Funding
Authors: Carmen Byker Shanks, Michelle S. Park, Amy L. Yaroch, Eliza Short, Hilary K. Seligman
Journal: Annual Review of Nutrition (2025)

The US Department of Agriculture's Gus Schumacher Nutrition Incentive Program (GusNIP) funds produce prescription (PPR) programs that allow healthcare to support patients in accessing fruits and vegetables. This hybrid systematic narrative review identified 16 studies of PPR programs associated with GusNIP funding in some way that examined health outcomes, including clinical measures and healthcare utilization. Program designs were heterogeneous, sample sizes were generally small, and methodological rigor was often low, with most studies using a prepost design and none using a randomized control group. Fewer than half of the studies examining clinical values showed an association between PPR participation and improved health outcomes (for example, three of eight studies measuring weight or body mass index showed a statistically significant reduction, as well as two of the six studies measuring glycosylated hemoglobin). Only three studies examined healthcare utilization, two of which showed improvements in hospitalization and/or emergency department utilization. Overall, evidence for the health impact of PPRs is nascent but growing. PPRs with capacity should engage in rigorous study designs and examine a variety of downstream health and utilization outcomes.
ESICM—ESPNIC international expert consensus on quantitative lung ultrasound in intensive care
Authors: Silvia Mongodi, Andrea Cortegiani, Almudena Alonso-Ojembarrena, Daniele Guerino Biasucci, Lieuwe D J Bos, Belaid Bouhemad, Massimo Cantinotti, Ioana Ciuca, Francesco Corradi, Martin Girard, Rebeca Gregorio-Hernandez, Maria Rosaria Gualano, Francesco Mojoli, George Ntoumenopoulos, Luigi Pisani, Francesco Raimondi, Javier Rodriguez-Fanjul, Marilena Savoia, Marry R Smit, Pieter R Tuinman, Laurent Zieleskiewicz, Daniele De Luca
Journal: Intensive Care Medicine (2025)
A Machine Learning-Based Strategy Predicts Selective and Synergistic Drug Combinations for Relapsed Acute Myeloid Leukemia
Authors: Yingjia Chen, Liye He, Aleksandr Ianevski, Kristen Nader, Tanja Ruokoranta, Nora Linnavirta, Juho J. Miettinen, Markus Vähä-Koskela, Ida Vänttinen, Heikki Kuusanmaki, Mika Kontro, Kimmo Porkka, Krister Wennerberg, Caroline A. Heckman, Anil K. Giri, Tero Aittokallio
Journal: Cancer Research (2025)

Abstract Combination therapies are one potential approach to improve the outcomes of patients with refractory or relapsed disease. However, comprehensive testing in scarce primary patient material is hampered by the many drug combination possibilities. Furthermore, inter- and intra-patient heterogeneity necessitates personalized treatment optimization approaches that effectively exploit patient-specific vulnerabilities to selectively target both the disease- and resistance-driving cell populations. Here, we developed a systematic combinatorial design strategy that uses machine learning to prioritize the most promising drug combinations for patients with relapsed/refractory (R/R) acute myeloid leukemia (AML). The predictive approach leveraged single-cell transcriptomics and single-agent response profiles measured in primary patient samples to identify targeted combinations that co-inhibit treatment resistant cancer cells individually in each AML patient sample. Cell type compositions evolved dynamically between the diagnostic and R/R stages uniquely in each patient, hence requiring personalized drug combination strategies to target therapy-resistant cancer cells. Cell population-specific drug combination assays demonstrated how patient-specific and disease stage-tailored combination predictions led to treatments with synergy and strong potency in R/R AML cells, while the same combinations elicited non-synergistic effects in the diagnostic stage and minimal co-inhibitory effects on normal cells. In preliminary experiments on clinical trial samples, the approach predicted clinical outcomes to venetoclax-azacitidine combination therapy in patients with AML. Overall, the computational-experimental approach provides a rational means to identify personalized combinatorial regimens for individual AML patients with R/R disease that target treatment-resistant leukemic cells, thereby increasing their likelihood for clinical translation.
Lyme Disease
Authors: Robert P. Smith
Journal: Annals of Internal Medicine (2025)

Lyme disease, caused by Borrelia burgdorferi, is the most common vector-borne disease in the United States, and the range of its tick vector continues to expand. Most Lyme disease cases are diagnosed with the onset of the erythema migrans rashes, which can be single or multiple and vary from a homogeneous erythema to bull's-eye patterns. Serologic antibody testing is of low sensitivity at onset but becomes highly sensitive after a few weeks. Early dissemination may lead to neurologic and cardiac complications. Mono- or oligoarticular arthritis may develop in untreated patients. Antibiotic treatment is highly effective, but approximately 10% of treated patients experience persistent symptoms.
Medical, Societal, and Ethical Considerations for Directed Blood Donation in 2025
Authors: Jeremy W. Jacobs, Garrett S. Booth, Mithya Lewis-Newby, Nabiha H. Saifee, Eamonn Ferguson, Claudia S. Cohn, Meghan Delaney, Sarah Morley, Stephen Thomas, Rachel Thorpe, Sheharyar Raza, Meaghann S. Weaver, Jennifer S. Woo, Deva Sharma, Cynthia So-Osman, Nalan Yurtsever, Christopher A. Tormey, Allison Waters, Mindy Goldman, Matthew T.S. Yan, Ross M. Fasano, Laura D. Stephens, Elizabeth S. Allen, Christian Erikstrup, Laura Infanti, Timothy D. Schlafer, Matthew A. Warner, Jeffrey L. Winters, Aaron A.R. Tobian, Evan M. Bloch
Journal: Annals of Internal Medicine (2025)

In the United States and other high-income countries, blood donation primarily relies on anonymous, voluntary donors. However, directed blood donation-where people donate for a specific recipient-has resurged, particularly due to misinformation surrounding COVID-19 vaccination. Requests for "nonvaccinated" blood, driven by misconceptions about vaccine safety, have led to legislative attempts to mandate compliance. Historically, directed donation was used to mitigate the risk for transfusion-related infections before modern screening techniques rendered it largely unnecessary. Today, it presents important patient safety risks, including increased infectious disease transmission, immunologic complications, and logistic burdens. Directed donations also introduce inefficiencies, diverting resources from the community blood supply and exacerbating shortages. Moreover, directed donation for nonmedical indications lacks scientific justification. Blood safety is ensured through rigorous donor screening, pathogen testing, and processing measures. There is no evidence that blood from vaccinated donors poses risk. Requests for nonvaccinated blood, as well as other directed donation preferences based on personal beliefs, introduce biases that are not grounded in medical necessity. Accommodating such requests undermines public trust in blood safety protocols and legitimizes unfounded fears. Ethical concerns arise as non-medically justified requests reinforce discriminatory practices, such as selecting donors based on race or gender. Allowing such preferences risks politicizing blood donation, spreading misinformation, and straining health care systems. Although autonomy is a core ethical principle in medicine, it does not justify non-evidence-based interventions. Given the potential harm and societal impact, directed blood donations should be limited to rare, medically necessary cases. Ongoing legislative efforts to mandate these requests require unified opposition from the medical and scientific community to uphold ethical, evidence-based, blood allocation practices.
Surgery for the treatment of arterial hypertension in patients with unilateral adrenal incidentalomas and mild autonomous cortisol secretion (CHIRACIC): a multicentre, open-label, superiority randomised controlled trial
Authors: Antoine Tabarin, Stéphanie Espiard, Timo Deutschbein, Laurence Amar, Delphine Vezzossi, Guido Di Dalmazi, Yves Reznik, Jacques Young, Rachel Desailloud, Bernard Goichot, Delphine Drui, Guillaume Assié, Hervé Lefebvre, Knut Mai, Frédéric Castinetti, Sandrine Laboureau, Massimo Terzolo, Amandine Ferriere, Aurore Georget, Eric Frison, Marie-Christine Vantyghem, Martin Fassnacht, Philippe Gosse
Journal: The Lancet Diabetes & Endocrinology (2025)
Effectiveness of integrated vector management on the incidence of dengue in urban Malaysia: a cluster-randomised controlled trial
Authors: Mitra Saadatian-Elahi, Muriel Rabilloud, Tim W R Möhlmann, Carole Langlois-Jacques, Farah Diana Ariffin, Marit Farenhorst, Mad-Hélénie Elsensohn, Frédéric Schmitt, Jason H Richardson, Frédéric Baur, Maxime Leduc, Nurul Nadia Romli, Lay Kim Tan, Mohd-Rosli Norazman, Hanipah Shahar, Rose Nani Mudin, Neal Alexander, Nurulhusna Ab Hamid
Journal: The Lancet Infectious Diseases (2025)
Long-Term Changes in Serum Vitamin D Testing After Implementation of Criteria-Based Testing
Authors: William K. Silverstein, Jagadish Rangrej, Kamil Malikov, Sping Wang, Shengli Shi, Nathan M. Stall, Jonathan S. Zipursky, Michael P. Hillmer
Journal: JAMA Internal Medicine (2025)

This cohort study assessed the association of criteria-based testing and the number of publicly funded vitamin D tests performed in Ontario, Canada.
Wearable fNIRS platform for dense sampling and precision functional neuroimaging
Authors: Ali Rahimpour Jounghani, Anupam Kumar, Laura Moreno Carbonell, Ester Patrize Lopez Aguilar, Tulla Bee Picardi, Seth Crawford, Audrey K Bowden, S M Hadi Hosseini
Journal: npj Digital Medicine (2025)

Precision mental health aims to improve care by tailoring interventions based on individual neurobiological features. Functional near-infrared spectroscopy (fNIRS) is a cost-effective and portable alternative to traditional neuroimaging, making it a promising tool for this purpose. This study evaluates a self-administered, wearable fNIRS platform designed for precision mental health applications, focusing on its reliability and specificity in capturing individualized functional connectivity patterns. The platform incorporates a wireless, portable multichannel fNIRS device, augmented reality guidance for reproducible device placement, and a cloud-based system for remote data access. In this proof-of-concept study, eight adults completed ten dense-sampled sessions involving cognitive tasks and resting-state measurements. Results demonstrated high test-retest reliability and within-participant consistency in functional connectivity and activation patterns. These findings support the platform's feasibility for individualized functional mapping. Future research with larger and more diverse cohorts, including clinical populations, is necessary to explore its potential for disorder-specific applications.
Digital twins, synthetic patient data, and in-silico trials: can they empower paediatric clinical trials?
Authors: Mohan Pammi, Prakesh S Shah, Liu K Yang, Joseph Hagan, Nima Aghaeepour, Josef Neu
Journal: The Lancet Digital Health (2025)

Randomised controlled trials are the gold standard to assess the effectiveness and safety of clinical interventions; however, many paediatric trials are discontinued early due to challenges in patient enrolment. Hence, most paediatric clinical trials suffer from lack of adequate power. Additionally, trials are expensive and might expose patients to unproven therapies. Alternatives to overcome these issues using virtual patient data-namely, digital twins, synthetic patient data, and in-silico trials-are now possible due to rapid advances in digital health-care tools and interventions. However, such digital innovations have been rarely used in paediatric trials. In this Viewpoint, we propose using virtual patient data to empower paediatric trials. The use of virtual patient data has the advantages of decreased exposure of children to potentially ineffective or risky interventions, shorter trial durations leading to more rapid ascertainment of safety and effectiveness of interventions, and faster drug approvals. Use of virtual patient data could lead to more personalised treatment options with low costs and could result in faster clinical implementation of interventions in children. However, ethical and regulatory concerns, including replacing humans with digital data, data privacy, and security should be addressed and the safety and sustainability of digital data innovation ensured before virtual patient data are adopted widely.
The gut–brain axis in Alzheimer’s disease is shaped by commensal gut microbiota derived extracellular vesicles
Authors: Junhua Xie, Lien Van Hoecke, Elien Van Wonterghem, Griet Van Imschoot, Vanessa Andries, Lars Vereecke, Roosmarijn E. Vandenbroucke
Journal: Gut Microbes (2025)

Emerging clinical and experimental evidence highlight the involvement of gut microbiota in the onset and progression of neurodegenerative diseases such as Alzheimer's disease (AD) via neuroinflammatory processes along the gut-brain axis. Despite this, the precise mechanisms governing gut microbial involvement in AD remain elusive. In this study, we observed that AppNL-G-F AD mice raised under germ-free (GF) conditions, display a reduced amyloid-β (Aβ) pathology, accompanied by a shift in microglial cells toward a less inflammatory state and increased phagocytotic efficiency. In addition, we demonstrate that gut microbiota depletion can protect against synaptic deficits in AD mice. Notably, administering bacterial extracellular vesicles (bEVs), i.e. nano-sized particles packed with bacterial components, derived from fecal slurry from specific pathogen-free housed AppNL-G-F AD mice, reversed the effects of GF conditions on both microglial activation and Aβ plaque accumulation. These findings reveal for the first time that commensal gut microbiota-derived bEVs have a major impact on AD pathology progression.
Bridging the Dermatological Divide: The Ethical Deployment of AI in Low-Resource Settings
Authors: Sach Thakker, Thomas Stirrat, Amanda Paredes-Barbeito, Soham Apte, Nicholas Gulati, Jonas A Adalsteinsson, Shari R Lipner, Melissa Laughter, Prince Adotama
Journal: Journal of the American Academy of Dermatology (2025)
Diagnostic Unmet Needs in Brachioradial Pruritus
Authors: Giulia Coscarella, Yael Rosen, Nathanael Singer, Eli Eyal, Linor Haimson, Orna Goren, Esther Hagai, Elise Edwards, Manuel P Pereira, Sonja Stander, Gil Yosipovitch
Journal: Journal of the American Academy of Dermatology (2025)