tbuckley/cabot-search huggingface dataset:
Pharmacogenetics and adverse drug reports: Insights from a United Kingdom national pharmacovigilance database
Authors: Emma F. Magavern, Maia Megase, Jack Thompson, Gabriel Marengo, Julius Jacobsen, Damian Smedley, Mark J. Caulfield
Journal: PLoS Medicine (2025)

Background Adverse drug reactions (ADRs) harm patients and are costly for healthcare systems. Genetic variation contributes to variability in medication response and prospective knowledge of these variants can decrease risk of ADRs, as shown in the PREPARE trial. Reduction in ADRs would affect only those reactions to drugs contained in well-validated pharmacogene–drug pairs. The scope of ADRs represented by these drugs on a population scale is unclear. The objective of this study was to characterize the pharmacogene–drug-associated ADR reporting landscape from a national regulatory pharmacovigilance dataset to elucidate the scale of potential ADR mitigation by pharmacogenomics (PGx) implementation. Methods and findings All publicly available Yellow Card ADR reports to the United Kingdom Medicines and Healthcare Products Regulatory Agency, from 1963 to 2024, were compiled using programmatic data extraction. The ADRs were analysed with descriptive statistics, stratified by PGx status and by associated genes. Prescribing prevalence from the literature was compared with age range matched ADR reports for PGx-associated drugs. There were 1,345,712 ADR reports, attributed to 2,499 different substances. 115,789 adverse drug reports (9%) were associated with drugs for which ADR risk can be modified based on pharmacogenomic prescribing guidance. Seventy-five percent of these ( n = 87,339) were due to medicines which interact with only three pharmacokinetic pharmacogenes ( CYP2C19 , CYP2D6 , SLCO1B1 ). Forty-seven percent of all the PGx mitigatable ADRs identified were attributed to psychiatric medications ( n = 54,846), followed by 24% attributed to cardiovascular medications ( n = 28,279). Those experiencing PGx mitigatable ADRs, as compared with non-PGx mitigatable ADRs, were older and the ADRs more often consisted of severe non-fatal reactions. Many PGx-associated psychiatric drug ADRs were overrepresented as compared with prescribing prevalence, but fatal cardiac arrhythmias were uncommon consequences, comprising only 0.4% of these ADRs ( n = 172 of n = 48,315 total ADRs). Limitations of this data source include under reporting of ADRs and reporting bias. These findings are based on analysis of the Yellow Card dataset described and may not represent all ADRs from a generalised patient population. Conclusions Nine percent of all reported ADRs are associated with drugs where a genetic variant can cause heightened risk of an ADR and inform prescribing. A panel of only three pharmacogenes could potentially mitigate three in every four PGx modifiable ADRs. Based on our findings, Psychiatry may be the single highest impact specialty to pilot PGx to reduce ADRs and associated morbidity, mortality and costs.
CD301b+ monocyte-derived dendritic cells mediate resistance to radiotherapy
Authors: Sirimuvva Tadepalli, Derek R. Clements, Hayley M. Raquer-McKay, Anja Lüdtke, Sanjana Saravanan, David Seong, Lorraine Vitek, Christopher M. Richards, Jan E. Carette, Matthias Mack, Andres Gottfried-Blackmore, Edward E. Graves, Juliana Idoyaga
Journal: The Journal of Experimental Medicine (2025)

Monocytes infiltrating tumors acquire various states that distinctly impact cancer treatment. Here, we show that resistance of tumors to radiotherapy (RT) is controlled by the accumulation of monocyte-derived dendritic cells (moDCs). These moDCs are characterized by the expression of CD301b and have a superior capacity to generate regulatory T cells (Tregs). Accordingly, moDC depletion limits Treg generation and improves the therapeutic outcome of RT. Mechanistically, we demonstrate that granulocyte–macrophage colony-stimulating factor (GM-CSF) derived from radioresistant tumor cells following RT is necessary for the accumulation of moDCs. Our results unravel the immunosuppressive function of moDCs and identify GM-CSF as an immunotherapeutic target during RT.
Reducing clinical trial eligibility barriers for patients with MDS: an icMDS position statement
Authors: Uma Borate, Kelly Pugh, Allyson Waller, Rina Li Welkie, Ying Huang, Jan Philipp Bewersdorf, Maximilian Stahl, Amy E. DeZern, Uwe Platzbecker, Mikkael A. Sekeres, Andrew H. Wei, Rena J. Buckstein, Gail J. Roboz, Michael R. Savona, Sanam Loghavi, Robert P. Hasserjian, Pierre Fenaux, David A. Sallman, Christopher S. Hourigan, Matteo Giovanni Della Porta, Stephen Nimer, Richard F. Little, Valeria Santini, Fabio Efficace, Justin Taylor, Guillermo Garcia-Manero, Olatoyosi Odenike, Tae Kon Kim, Stephanie Halene, Rami S. Komrokji, Elizabeth A. Griffiths, Peter L. Greenberg, Mina L. Xu, Zhuoer Xie, Rafael Bejar, Guillermo F. Sanz, Mrinal M. Patnaik, Maria Figueroa, Hetty E. Carraway, Omar Abdel-Wahab, Daniel Starczynowski, Eric Padron, Jacqueline Boultwood, Steven Gore, Naval G. Daver, Jane E. Churpek, Ravindra Majeti, John M. Bennett, Alan F. List, Andrew M. Brunner, Amer M. Zeidan
Journal: Blood (2025)
Immunotherapy Strategies After Immune Checkpoint Inhibitor Exposure in Renal Cell Carcinoma
Authors: Giulia Claire Giudice, Kathryn E. Beckermann, Paulo Siqueira Do Amaral, Brian I. Rini
Journal: JAMA Oncology (2025)

Importance Immune checkpoint inhibitors have transformed the treatment landscape for metastatic renal cell carcinoma; however, the failure of first-line therapeutic strategies remains a considerable challenge. Currently, clinicians face various issues, such as managing cases in patients who progress during treatment or relapse after adjuvant immunotherapy. Observations This review evaluates different strategies for treating patients with advanced kidney cancer previously exposed to immunotherapy. Evidence from other malignant neoplasms suggests potential effectiveness for rechallenging with immune checkpoint inhibitors. The most important available data are presented, including retrospective, prospective, and randomized clinical trials, to explore the role of immunotherapy in patients with renal cell carcinoma who have experienced prior failure of immune checkpoint inhibitors. Conclusions and Relevance Although retrospective data suggest modest effectiveness of an immunotherapy rechallenge treatment, larger phase 3 trials failed to demonstrate substantial benefit in progression-free survival and overall survival. Currently, no randomized evidence supports the use of agents targeting conventional immune checkpoints in patients with renal cell carcinoma who have previously received immunotherapy.
State Minimum Wage and Food Insecurity Among US Households With Children
Authors: Megan R. Winkler, Rachel Clohan, Kelli A. Komro, Melvin D. Livingston, Sara Markowitz
Journal: JAMA Network Open (2025)

Importance Food insecurity among households with children and economic hardship is a persistent US challenge. Federal food assistance programs have been unable to fully address food insecurity, leading to interest in the role other labor and economic policies could play. One relevant state-level policy that has received limited attention is the state minimum wage. Objective To assess whether state minimum wage generosity was associated with change in food insecurity among households with children and explore differential policy impacts across sociodemographic groups. Design, Setting, and Participants This cross-sectional study of a national sample of US households from the Current Population Survey used a 2-way fixed effects modeling approach to test whether increases in state minimum wage from 2005 to 2022 were associated with improvements in food insecurity controlling for household- and state-level time-varying covariates. Working households with children who were most likely to be affected by policy changes (ie, limited educational attainment) were included. Analyses were conducted in July through September 2024. Exposure The 2022 inflation-adjusted effective minimum wage for each state in December which was derived from legal sources. Main Outcomes and Measures Past-month household food insecurity assessed in December 2022. Results The sample of 97 944 working households with children and limited educational attainment were mostly female headed (54 077 [55.2%]) with a mean (SD) 1.8 (1.1) children in the home; 22 130 households (22.6%) reported Hispanic identity, 10 545 non-Hispanic Black (10.8%), and 59 500 non-Hispanic White (60.8%). Inflation-adjusted state minimum wage ranged from $7.15 to $16.85 over the 18-year study period. We observed that a 10% increase in the state minimum wage was significantly associated with a 0.39 percentage point reduction (95% CI, −0.74 to −0.04 percentage points; P = .03) in food insecurity. There was limited evidence of differences in the association across race and ethnicity, participation in the US Supplemental Nutrition Assistance Program, or household composition. Conclusions and Relevance In this pooled cross-sectional study, findings suggest that state legislatures that elected to increase their state minimum wage may have also improved state food security rates among households with children at risk for economic hardship. Findings provide policymakers with actionable evidence to consider in setting minimum wages that could reduce the burden of food insecurity among US children and families.
Electronic Screen Use and Sleep Duration and Timing in Adults
Authors: Charlie Zhong, Matthew Masters, Sidney M. Donzella, W. Ryan Diver, Alpa V. Patel
Journal: JAMA Network Open (2025)

Importance Electronic screen use before bed may disrupt circadian rhythms, leading to poorer sleep. Objective To investigate the association between screen use before bed and sleep outcomes among adults. Design, Setting, and Participants This cross-sectional study included participants in the American Cancer Society Cancer Prevention Study–3, a prospective cohort of men and women from 35 US states and Puerto Rico, who responded to a 2018 survey. Analyses were conducted from February 3, 2023, to January 10, 2025. Exposures Self-reported electronic screen use in the hour prior to bed. Main Outcomes and Measures Self-reported sleep-wake times (used to calculate duration), sleep quality, and chronotype. Mean differences for sleep duration and bedtimes, and prevalence ratios for sleep quality were calculated by screen use using multivariable linear and Poisson regression, respectively. Whether these associations differed by chronotype was also examined. Results Of the 122 058 participants (97 658 women [80.0%]; median [IQR] age, 56 [47-62] years; range, 27-85 years), 70 638 (57.9%) reported a morning chronotype. Daily screen use before bed was reported by 50 289 participants (41.2%), whereas 21 275 (17.4%) reported no screen use. Compared with no screen use, daily screen use prior to bed was associated with a 33% higher prevalence of poor sleep quality (prevalence ratio, 1.33; 95% CI, 1.27-1.39) and 7.64 fewer minutes of sleep on workdays (95% CI, 6.65-8.63 minutes). The association was more pronounced among participants with evening chronotypes (8.36 minutes; 95% CI, 4.94-11.78 minutes) vs those with morning chronotypes (5.64 minutes; 95% CI, 3.98-7.29 minutes). Daily screen use was associated with 5.04 fewer minutes of sleep (95% CI, 4.03-6.05 minutes) on nonworkdays. Daily screen users with morning chronotype went to bed 9.33 minutes later (95% CI, 7.61-11.06 minutes), and those with evening chronotypes went to bed 15.62 minutes later (95% CI, 11.93-19.31 minutes) on workdays. Results were similar for nonworkdays. Conclusions and Relevance Daily screen use was associated with later bedtimes and approximately 50 minutes less sleep each week. Associations were greater among those with evening chronotypes, who are at risk for poor sleep due to social jetlag (ie, misalignment between circadian rhythms and social commitments). These findings confirm disruptions to sleep from electronic screens are not limited to children and adolescents. Further work is needed to understand the best mechanisms for intervention.
Biophysical and Biochemical Roles of Shear Stress on Endothelium: A Revisit and New Insights
Authors: Chak Kwong Cheng, Nanping Wang, Li Wang, Yu Huang
Journal: Circulation Research (2025)

Hemodynamic shear stress, the frictional force exerted by blood flow on the endothelium, mediates vascular homeostasis. This review examines the biophysical nature and biochemical effects of shear stress on endothelial cells, with a particular focus on its impact on cardiovascular pathophysiology. Atherosclerosis develops preferentially at arterial branches and curvatures, where disturbed flow patterns are most prevalent. The review also highlights the range of shear stress across diverse human arteries and its temporal variations, including aging-related alterations. This review presents a summary of the critical mechanosensors and flow-sensitive effectors that respond to shear stress, along with the downstream cellular events that they regulate. The review evaluates experimental models for studying shear stress in vitro and in vivo, as well as their potential limitations. The review discusses strategies targeting shear stress, including pharmacological approaches, physiological means, surgical interventions, and gene therapies. Furthermore, the review addresses emerging perspectives in hemodynamic research, including single-cell sequencing, spatial omics, metabolomics, and multiomics technologies. By integrating the biophysical and biochemical aspects of shear stress, this review offers insights into the complex interplay between hemodynamics and endothelial homeostasis at the preclinical and clinical levels.
Cardiac Fibrosis in the Multi-Omics Era: Implications for Heart Failure
Authors: Rachad Ghazal, Min Wang, Duan Liu, Daniel J. Tschumperlin, Naveen L. Pereira
Journal: Circulation Research (2025)

Cardiac fibrosis, a hallmark of heart failure and various cardiomyopathies, represents a complex pathological process that has long challenged therapeutic intervention. High-throughput omics technologies have begun revolutionizing our understanding of the molecular mechanisms driving cardiac fibrosis and are providing unprecedented insights into its heterogeneity and progression. This review provides a comprehensive analysis of how techniques—encompassing genomics, epigenomics, transcriptomics, proteomics, and metabolomics—are providing insight into our understanding of cardiac fibrosis. Genomic studies have identified novel genetic variants and regulatory networks associated with fibrosis susceptibility and progression, and single-cell transcriptomics has unveiled distinct cardiac fibroblast subpopulations with unique molecular signatures. Epigenomic profiling has revealed dynamic chromatin modifications controlling fibroblast activation states, and proteomic analyses have identified novel biomarkers and potential therapeutic targets. Metabolomic studies have uncovered important alterations in cardiac energetics and substrate utilization during fibrotic remodeling. The integration of these multi-omic data sets has led to the identification of previously unrecognized pathogenic mechanisms and potential therapeutic targets, including cell-type-specific interventions and metabolic modulators. We discuss how these advances are driving the development of precision medicine approaches for cardiac fibrosis while highlighting current challenges and future directions in translating multi-omic insights into effective therapeutic strategies. This review provides a systems-level perspective on cardiac fibrosis that may inform the development of more effective, personalized therapeutic approaches for heart failure and related cardiovascular diseases.
Correction to: LncRNA PSR Regulates Vascular Remodeling Through Encoding a Novel Protein Arteridin
Authors: Junyi Yu, Wei Wang, Jining Yang, Ye Zhang, Xue Gong, Hao Luo, Nian Cao, Zaicheng Xu, Miao Tian, Peili Yang, Qiao Mei, Zhi Chen, Zhuxin Li, Chuanwei Li, Xudong Duan, Qing Rex Lyu, Chen Gao, Bing Zhang, Yibin Wang, Gengze Wu, Chunyu Zeng
Journal: Circulation Research (2025)
From classical approaches to artificial intelligence, old and new tools for PDAC risk stratification and prediction
Authors: Riccardo Farinella, Alessio Felici, Giulia Peduzzi, Sabrina Gloria Giulia Testoni, Eithne Costello, Paolo Aretini, Ricardo Blazquez-Encinas, Elif Oz, Aldo Pastore, Matteo Tacelli, Burcak Otlu, Daniele Campa, Manuel Gentiluomo
Journal: Seminars in Cancer Biology (2025)
Epigenetic alteration of smooth muscle cells regulates endothelin-dependent blood pressure and hypertensive arterial remodeling
Authors: Kevin D Mangum, Qinmengge Li, Katherine Hartmann, Tyler M Bauer, Sonya J. Wolf, James Shadiow, Jadie Y. Moon, Emily Barrett, Amrita Joshi, Gabriela Saldana de Jimenez, Sabrina A. Rocco, Zara Ahmed, Rachael Bogle, Kylie Boyer, Andrea Obi, Frank M Davis, Lin Chang, Lam Tsoi, Johann Gudjonsson, Scott M. Damrauer, Katherine Gallagher
Journal: Journal of Clinical Investigation (2025)

Long-standing hypertension (HTN) affects multiple organs and leads to pathologic arterial remodeling, which is driven by smooth muscle cell (SMC) plasticity. To identify relevant genes regulating SMC function in HTN, we considered Genome Wide Association Studies (GWAS) of blood pressure, focusing on genes encoding epigenetic enzymes, which control SMC fate in cardiovascular disease. Using statistical fine mapping of the KDM6 (JMJD3) locus, we found that rs62059712 is the most likely casual variant, with each major T allele copy associated with a 0.47 mmHg increase in systolic blood pressure. We show that the T allele decreased JMJD3 transcription in SMCs via decreased SP1 binding to the JMJD3 promoter. Using our unique SMC-specific Jmjd3-deficient murine model (Jmjd3flox/floxMyh11CreERT), we show that loss of Jmjd3 in SMCs results in HTN due to decreased EDNRB expression and increased EDNRA expression. Importantly, the Endothelin Receptor A antagonist, BQ-123, reversed HTN after Jmjd3 deletion in vivo. Additionally, single cell RNA-sequencing (scRNA-seq) of human arteries revealed strong correlation between JMJD3 and EDNRB in SMCs. Further, JMJD3 is required for SMC-specific gene expression, and loss of JMJD3 in SMCs increased HTN-induced arterial remodeling. Our findings link a HTN-associated human DNA variant with regulation of SMC plasticity, revealing targets that may be used in personalized management of HTN.
Zerlasiran for the Treatment of Atherosclerotic Cardiovascular Disease
Authors: Yumei Wu, Jiahao Meng, Shuguang Gao
Journal: JAMA (2025)

To the Editor A recent article1 reported that zerlasiran was well tolerated, with a time-averaged percent change in lipoprotein(a) concentration of more than 80% from baseline to 36 weeks in patients with atherosclerotic cardiovascular disease. However, we have some concerns about this study.
Nicotine Concentration of E-Cigarettes Used by Youths
Authors: Junhan Cho, Richard A. Miech, Alyssa F. Harlow, Dae-Hee Han, Hongying D. Dai, Steve Sussman, Adam M. Leventhal
Journal: JAMA Network Open (2025)

This cross-sectional study investigates rates of nicotine concentrations vaped by US youths and associated substance use characteristics.
Prefrontal correlates of fear generalization during endocannabinoid depletion
Authors: Luis E. Rosas-Vidal, Saptarnab Naskar, Leah M. Mayo, Irene Perini, Rameen Masroor, Megan Altemus, Liorimar Ramos-Medina, S. Danyal Zaidi, Hilda Engelbrektsson, Puja Jagasia, Markus Heilig, Sachin Patel
Journal: Journal of Clinical Investigation (2025)

Maladaptive fear generalization is one of the hallmarks of trauma-related disorders. The endocannabinoid 2-arachidonoylglycerol (2-AG) is crucial for modulating anxiety, fear, and stress adaptation but its role in balancing fear discrimination versus generalization is not known. To address this, we used a combination of plasma endocannabinoid measurement and neuroimaging from a childhood maltreatment-exposed and non-exposed mixed population combined with human and rodent fear conditioning models. Here we show that 2-AG levels are inversely associated with fear generalization at the behavioral level in both mice and humans. In mice, 2-AG depletion increases the proportion of neurons, and the similarity between neuronal representations, of threat-predictive and neutral stimuli within prelimbic prefrontal cortex neuronal ensembles. In humans, increased dorsolateral prefrontal cortical-amygdala resting state connectivity is inversely correlated with fear generalization. These data provide convergent cross-species evidence that 2-AG is a key regulator of fear generalization and further support the notion that 2-AG deficiency could represent a trauma-related disorder susceptibility endophenotype.
Use of machine learning techniques to predict poor survival after hematopoietic cell transplantation for myelofibrosis
Authors: Juan Carlos Hernandez-Boluda, Adrian Mosquera Orgueira, Luuk Gras, Linda Koster, Joe Tuffnell, Nicolaus Kröger, Massimiliano Gambella, Thomas Schroeder, Marie Robin, Katja Sockel, Jakob R Passweg, Igor Wolfgang Blau, Ibrahim Yakoub-Agha, Ruben Van Dijck, Matthias Stelljes, Henrik Sengeloev, Jan Vydra, Uwe Platzbecker, Moniek Dewitte, Frédéric Baron, Kristina Carlson, Javier Alberto Rojas Martínez, Carlos Pérez Míguez, Davide Crucitti, Kavita Raj, Joanna Drozd-Sokolowska, Giorgia Battipaglia, Nicola Polverelli, Tomasz Czerw, Donal P McLornan
Journal: Blood (2025)
<i>Notes from the Field:</i> Fatal <i>Acanthamoeba</i> Encephalitis in a Patient Who Regularly Used Tap Water in an Electronic Nasal Irrigation Device and a Continuous Positive Airway Pressure Machine at Home — New Mexico, 2023
Authors: Julia C. Haston, Ibne K. Ali, Shantanu Roy, Alexis Roundtree, Jessica Hofstetter, Savannah Pierson, Emily Helmrich, Paul Torres, Kodi Lockey, Roosecelis B. Martines, Mia Mattioli
Journal: MMWR Morbidity and Mortality Weekly Report (2025)
Fatal Case of Splash Pad–Associated <i>Naegleria fowleri</i> Meningoencephalitis — Pulaski County, Arkansas, September 2023
Authors: Theresa M. Dulski, Forrest Montgomery, Jeanette M. Ramos, Eric R. Rosenbaum, Bobby L. Boyanton, Courtney M. Cox, Steven Dahl, Cole Kitchens, Terry Paul, Amy Kahler, Alexis Roundtree, Mia Mattioli, Michele C. Hlavsa, Ibne K. Ali, Shantanu Roy, Julia C. Haston, Naveen Patil
Journal: MMWR Morbidity and Mortality Weekly Report (2025)

A fatal case of primary amebic meningoencephalitis (PAM), an infection caused by Naegleria fowleri, was diagnosed in Arkansas in a young child in September 2023. A public health investigation was completed, with epidemiologic, laboratory, and environmental data suggesting that a splash pad (an interactive water play venue that sprays or jets water on users and has little or no standing water) with inadequately disinfected water was the most likely site of the patient's N. fowleri exposure. This case is the third occurrence of splash pad-associated PAM reported in the United States; all three cases involved inadequately disinfected water. PAM should be considered in patients with acute meningoencephalitis and a history of recent possible exposure to fresh water, including treated recreational water (e.g., in splash pads or pools), via the nasal passages. Proper design, construction, operation, and management of splash pads can help prevent illnesses, including N. fowleri infections. Increased awareness, collaboration, and communication among clinicians, hospitals, laboratories, CDC, health departments, the aquatics sector, and the public can help support N. fowleri infection identification, treatment, prevention, and control efforts.