tbuckley/cabot-search huggingface dataset:
Harm-Benefit Balance of Immune Checkpoint Inhibitors in Non–Small Cell Lung Cancer
Authors: James Heyward, Catherine R. Lesko, Joseph C. Murray, Hemalkumar B. Mehta, Jodi B. Segal
Journal: JAMA Oncology (2025)

Importance The benefits and harms of immune checkpoint inhibitor (ICI) therapy for lung cancer vary across groups, including those typically underrepresented in randomized clinical trials. Objective To quantify the harms and benefits of ICI-containing regimens in individuals with non–small cell lung cancer and assess heterogeneity across priority subgroups. Design, Setting, and Participants This retrospective cohort study conducted in 2024 used 2013 to 2019 Surveillance, Epidemiology, and End Results (SEER) Medicare data of individuals 66 years or older with non–small cell lung cancer who were exposed to any ICI. Exposures ICI + chemotherapy, single ICI (reference group). Main Outcomes Severe immune-related adverse events (irAE; harm) and mortality (when delayed mortality was the benefit). Severe irAEs were defined using validated diagnosis and medication codes. Mortality was ascertained from Medicare data. Hazard ratios (HRs) were estimated and 95% CIs were stratified by whether an ICI was used as the first or second or later systemic anticancer treatment (SACT) and in subgroups defined by preexisting autoimmune disease, sex, and age. The harm-benefit tradeoff was described as excess severe irAEs per year of life gained in which the gain in survival time was assessed using restricted mean survival time. Results Of 17 681 Medicare beneficiaries, 8797 (49.5%) were female, and the mean (SD) age was 74 (6.0) years. Compared with a single ICI (14 249 [80.6%]), individuals treated with ICI + chemotherapy (3432 [19.4%]) had an elevated risk of severe irAE in the first SACT setting (hazard ratio [HR], 1.18; 95% CI, 1.06-1.30) but not in the second or later SACT setting (HR, 1.04; 95% CI, 0.92-1.19); there was a decreased risk of mortality in the first SACT setting (HR, 0.66; 95% CI, 0.62-0.72) but not in the second or later SACT setting (HR, 0.94; 95% CI, 0.68-1.03). In the first SACT setting, ICI + chemotherapy delayed mortality more among patients with (vs without) autoimmune disease at baseline. For each 1 year of life gained, the risk of severe irAEs was 0.31 (95% CI, 0.09-0.53) and the tradeoff was also statistically significant in men and patients without autoimmune disease. Conclusions The results of this cohort study suggest that given both treatment-related harms and benefits, ICI + chemotherapy use in the first SACT setting requires informed decision-making; the potential benefits of ICI + chemotherapy vs single ICI in high-risk subgroups is encouraging.
Prophylactic Irradiation of the Contralateral Breast for <i>BRCA</i> Carriers With Early Breast Cancer
Authors: Ella Evron, Benjamin W. Corn, Hadassah Goldberg, Roxolyana Abdah-Bortnyak, Ora Rosengarten, Diana Matceyevsky, David B. Geffen, Raphael Catane, M. Raphael Pfeffer, Orit Kaidar-Person, Merav A. Ben David
Journal: JAMA Oncology (2025)

This nonrandomized phase 2 clinical trial examines contralateral breast cancer risk reduction in women who choose radiation therapy or surveillance rather than mastectomy.
Proximity to Golf Courses and Risk of Parkinson Disease
Authors: Brittany Krzyzanowski, Aidan F. Mullan, E. Ray Dorsey, Sai Shivani Chirag, Pierpaolo Turcano, Emanuele Camerucci, James H. Bower, Rodolfo Savica
Journal: JAMA Network Open (2025)

Importance The role of pesticide exposure from golf courses in Parkinson disease (PD) risk remains unclear. Objective To assess whether proximity to golf courses is associated with increased PD risk and to use information on groundwater vulnerability and municipal well locations to investigate drinking water contamination as a potential route of exposure. Design, Setting, and Participants This case-control study included patients with incident PD and matched controls from the Rochester Epidemiology Project from 1991 to 2015. Data were analyzed between June and August 2024. Exposures Distance to golf courses, living in water service areas with a golf course, living in water service areas in vulnerable groundwater regions, living in water service areas with shallow municipal wells, and living in water service areas with a municipal well on a golf course. Main Outcome and Measures Risk of incident PD. All models adjusted for age, sex, race and ethnicity, year of index, median household income, and urban or rural category. Results A total of 419 incident PD cases were identified (median [IQR] age, 73 [65-80] years; 257 male [61.3%]) with 5113 matched controls (median [IQR] age, 72 [65-79] years; 3043 male [59.5%]; 4504 White [88.1%]). After adjusting for patient demographics and neighborhood characteristics, living within 1 mile of a golf course was associated with 126% increased odds of developing PD compared with individuals living more than 6 miles away from a golf course (adjusted odds ratio [aOR], 2.26; 95% CI, 1.09-4.70). Individuals living within water service areas with a golf course had nearly double the odds of PD compared with individuals in water service areas without golf courses (aOR, 1.96; 95% CI, 1.20-3.23) and 49% greater odds compared with individuals with private wells (aOR, 1.49; 95% CI, 1.05-2.13). Additionally, individuals living in water service areas with a golf course in vulnerable groundwater regions had 82% greater odds of developing PD compared with those in nonvulnerable groundwater regions (aOR, 1.82; 95% CI, 1.09-3.03). Conclusions and Relevance In this population-based case-control study, the greatest risk of PD was found within 1 to 3 miles of a golf course and risk generally decreased with distance. Associations with the largest effect sizes were in water service areas with a golf course and in vulnerable ground water regions.
Prevalence of sexual violence against children and age at first exposure: a global analysis by location, age, and sex (1990–2023)
Authors: Jack Cagney, Cory Spencer, Luisa Flor, Molly Herbert, Mariam Khalil, Erin O'Connell, Erin Mullany, Flavia Bustreo, Joht Singh Chandan, Nicholas Metheny, Felicia Knaul, Emmanuela Gakidou
Journal: The Lancet (2025)

Measuring sexual violence against children (SVAC) is vital to prevention and advocacy efforts, yet existing prevalence studies present estimates for few countries. Here we estimate the prevalence of SVAC for 204 countries by age and sex, from 1990 to 2023, and also report the age at which young survivors of lifetime sexual violence first experienced sexual violence. We reviewed publicly available repositories for data on the prevalence of SVAC. To harmonise heterogeneity in the identified input data, we adjusted for alternative case definitions of SVAC and differential disclosure by survey mode. We then used a spatiotemporal Gaussian process regression to estimate a full time series of exposure to SVAC for each age-sex-country combination. We accounted for uncertainty in the underlying data and modelling processes. We also analysed the age at which adolescent and young adult survivors of lifetime sexual violence first experienced this type of violence by sex, data source, and world region. We estimate that the global age-standardised prevalence of SVAC was 18·9% (95% uncertainty interval [UI] 16·0-25·2) for females and 14·8% (9·5-23·5) for males in 2023. At the super-region level, these estimates ranged from 12·2% (9·0-17·2) in southeast Asia, east Asia, and Oceania to 26·8% (21·9-32·7) in south Asia for females and from 12·3% (5·2-24·6) in central Europe, eastern Europe, and central Asia to 18·6% (9·7-32·3) in sub-Saharan Africa for males. At the country level, age-standardised estimates ranged from 6·9% (4·8-9·6) in Montenegro to 42·6% (34·4-52·1) in Solomon Islands among females and from 4·2% (1·7-9·2) in Mongolia to 28·3% (13·2-49·8) in Côte d'Ivoire among males. Globally, these estimates remained relatively stable since 1990, with slight variations at the country and regional levels. We also find that the first experience of sexual violence among adolescents and young people occurred before the age of 18 years for 67·3% of female and 71·9% of male survivors. The prevalence of SVAC is extremely high for both females and males across the globe. Given data sparsity and ongoing measurement challenges, findings probably underestimate the true pervasiveness of SVAC. An overwhelmingly high proportion of survivors first experienced sexual violence during childhood, revealing a narrow yet sensitive window that should be targeted in future prevention efforts. It is a moral imperative to protect children from violence and mitigate its compounding impacts on health across the lifecourse. The Gates Foundation.
Ultrasound-responsive release of CD39 inhibitor overcomes adenosine-mediated immunosuppression in triple-negative breast cancer
Authors: Yijie Chen, Yue Song, Chao Zhang, Peile Jin, Yuhan Fu, Guowei Wang, Lina Tang, Jifan Chen, Xiaodan Xu, Pintong Huang
Journal: Journal of Controlled Release (2025)
In Vivo Spatiotemporal Acquisition of Metabolic Vibrational Signatures for Unraveling Gastric Ulcer Genesis
Authors: Yuqi Cheng, Lingjin Zhao, Yijing Wen, Zhen Ren, Jiayu Zeng, Rui Shi, Xinqi Cai, Qian Dong, Long Chen, Changwei Lin, Zhuo Chen
Journal: Biomaterials (2025)
A Machine Learning-Based Clustering Analysis to Explore Bisphenol A and Phthalate Exposure from Medical Devices in Infants with Congenital Heart Defects
Authors: Wei-Chun Chou, J. William Gaynor, Eric M. Graham, Brenna Klepczynski, Tia Walker, Eric S. Coker, Richard F. Ittenbach, Zhoumeng Lin
Journal: Environmental Health Perspectives (2025)

Plastic-containing medical devices are commonly used in critical care units and other patient care settings. Patients are often exposed to xenobiotic agents that are leached out from plastic-containing medical devices, including bisphenol A (BPA) and phthalates. Given the potential health implications, there is an urgent need for a comprehensive understanding of this exposure. This multi-institutional study aimed to determine the time-dependent concentrations and analyze the exposure patterns of bisphenol A (BPA) and phthalate metabolites in urine obtained from infants with congenital heart defects (CHD) undergoing cardiac surgery during the peri-operative period. We collected daily urine samples from infants with CHD undergoing cardiac surgery during the peri-operative period (from birth to 21 days) and measured BPA, DEHP metabolites (MEHP, MEHHP, MEOHP, MECPP), and non-DEHP phthalate metabolites (MBP, MBzP, MMP, MEP, MCPP) using ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Machine learning-based cluster analysis was utilized to analyze these time-dependent data. Utilizing a machine learning-based clustering approach, six distinct clustering groups were identified among infants exhibiting similar time-series toxicokinetic exposure patterns. These distinct clustering groups correlated with the utilization of extracorporeal membrane oxygenation (ECMO) and cardiopulmonary bypass (CPB), as well as the intensity of medical care. Notably, clustering groups associated with ECMO use demonstrated elevated levels of urinary BPA and DEHP metabolites compared to those without ECMO use, a trend not observed with non-DEHP metabolites. Moreover, peak concentrations in toxicokinetic profiles were associated with intensity of medical care. Our findings suggest that dynamic changes of urinary BPA and DEHP metabolites corresponded to the type and number of medical devices used in infants. Further studies are needed to investigate the potential toxicological risks of infants with CHD undergoing cardiac surgery exposed to these chemicals in medical devices. https://doi.org/10.1289/EHP15034.
Hepatic stellate cell heterogeneity: Functional aspects and therapeutic implications
Authors: Yana Geng, Robert F. Schwabe
Journal: Hepatology (2025)

Hepatic stellate cells (HSCs) represent a highly heterogeneous mesenchymal cell population with multifaceted roles in liver homeostasis and disease. Beyond their well-established roles in vitamin A storage and scar formation, there is increasing evidence for HSCs in the regulation of hepatic metabolism, regeneration, immunity and carcinogenesis. Here, we will review the heterogeneity of HSCs in the healthy, aging and diseased liver, focusing on cell-cell interactions and their contributions to fibrosis, liver zonation and function, regeneration, and cancer. We explore the spatiotemporal diversity of HSCs, highlighting their subpopulations and their specialized roles, as well as the complex bidirectional communications between HSCs, hepatocytes, endothelial cells, macrophages/monocytes, T cells, and tumor cells. By integrating insights from single-cell sequencing, spatial transcriptomics, preclinical data and clinical data, this review aims to provide an updated understanding of how HSC heterogeneity contributes to liver homeostasis and disease and can be targeted for therapeutic purposes.
Drugs targeting novel pathways in pulmonary arterial hypertension
Authors: Olivier Sitbon, Athénaïs Boucly, Jason Weatherald, Fabrice Antigny, Christophe Guignabert, Mitja Jevnikar, Xavier Jaïs, Laura C Price, Martin R Wilkins, Roham T Zamanian, Laurent Savale, David Montani, Marc Humbert
Journal: European Respiratory Journal (2025)

Over the past three decades, several drugs have been developed to target three major dysfunctional pathways in PAH, including the prostacyclin, endothelin, and nitric oxide pathways. Despite these advances, PAH remains incurable, necessitating further drug discovery efforts. New therapies focus on previously untargeted pathways, especially the bone morphogenetic protein (BMP)/transforming growth factor-beta (TGF-β) signalling pathway. Dysregulation of this pathway, involving the Smad2/3 and Smad1/5/8 signalling branches, plays a key role in pulmonary vascular remodelling. Sotatercept, a fusion protein acting as an activin receptor ligand trap to rebalance growth-promoting and growth-inhibiting signalling has shown promise in clinical trials by reducing pulmonary vascular resistance and improving exercise capacity. Other emerging treatments aim to restore balance within the BMP/TGF-β pathway. Therapies targeting receptor tyrosine kinases (RTKs), such as imatinib, inhibit the platelet-derived growth factor pathway. Though oral imatinib has shown efficacy, its side effects have limited widespread use. Additional strategies exploring lower doses of imatinib and novel delivery methods, such as inhalation, to reduce systemic side effects failed to demonstrate clinical benefit. Novel RTK inhibitors like seralutinib administered by inhalation have shown promising results in a phase 2 clinical trial. Other emerging approaches include anti-inflammatory therapies, hormonal modulation, and metabolism-targeting agents like ranolazine and SGLT2 inhibitors, which could expand the therapeutic landscape for PAH. Overall, the continued development of novel drugs targeting these pathways offers hope for better disease management and improved outcomes for patients with PAH.
Implementation of European National Driving Regulations for Obstructive Sleep Apnoea: challenges and recommendations
Authors: Walter T McNicholas, Ysbrand D van der Werf, Sarah Hartley, Pierre Philip
Journal: European Respiratory Journal (2025)

Background : Obstructive sleep apnoea (OSA) carries an increased risk of motor vehicle accidents (MVA), which resulted in the European Commission introducing a legal directive (2014/85/EU) restricting driving in patients with moderate/severe OSA and sleepiness, unless effectively treated. We assessed the implementation of the directive in European Union (EU) member and non-member states. Methods National Sleep Societies and/or selected other sleep specialists in EU member states and selected other European countries completed a questionnaire on the local introduction of the EU Directive, or similar, the OSA severity to restrict driving, criteria to resume driving, and the validity period for different driving licences. Results Data were obtained from 25 of 27 EU member states and all 8 non-member states included, representing a population of ∼770 million. All EU members had introduced the Directive into national regulations, largely unchanged, although some countries applied stricter criteria such as mild OSA and a minimum treatment period before resuming driving. Only 5 non-member states had driving regulations for OSA. Problems with implementation of regulations were reported in most countries, including inadequate resources to diagnose/treat OSA patients, excessive restrictions regarding disease severity and certification to resume driving, and under-reporting of symptoms by patients fearing the loss of their licence, especially professional drivers. Conclusions Driving regulations for OSA apply in most European countries but excessively strict criteria for OSA severity, sleepiness, and delayed permission to resume driving are questionable. Further research is needed on whether such regulations result in fewer accidents and on the objective identification of sleepiness.
Interim Evaluation of Respiratory Syncytial Virus Hospitalization Rates Among Infants and Young Children After Introduction of Respiratory Syncytial Virus Prevention Products — United States, October 2024–February 2025
Authors: Monica E. Patton, Heidi L. Moline, Michael Whitaker, Ayzsa Tannis, Huong Pham, Ariana P. Toepfer, Christopher A. Taylor, Leah Goldstein, Arthur Reingold, Pam Daily Kirley, Nisha B. Alden, Breanna Kawasaki, James Meek, Daewi Kim, Lucy S. Witt, Kyle P. Openo, Patricia A. Ryan, Erica Mumm, Ruth Lynfield, Yadira Salazar-Sanchez, Francesca Pacheco, Fiona Keating, Bridget J. Anderson, Brenda L. Tesini, Christina B. Felsen, Melissa Sutton, Ann Thomas, William Schaffner, H. Keipp Talbot, Khalil Harbi, Emma Doran, Geoffrey A. Weinberg, Mary A. Staat, Daniel C. Payne, Natasha B. Halasa, Laura Stewart, Julie A. Boom, Leila C. Sahni, Eileen J. Klein, Janet A. Englund, John V. Williams, Marian G. Michaels, Jennifer E. Schuster, Rangaraj Selvarangan, Peter G. Szilagyi, Fiona P. Havers, Fatimah S. Dawood
Journal: MMWR Morbidity and Mortality Weekly Report (2025)

Maternal respiratory syncytial virus (RSV) vaccine and nirsevimab, a long-acting monoclonal antibody for infants aged 0-7 months and children aged 8-19 months who are at increased risk for severe RSV disease, became widely available for prevention of severe RSV disease among infants and young children during the 2024-25 RSV season. To evaluate the association between availability of these products and infant and child RSV-associated hospitalization rates, the rates among children aged <5 years were compared for the 2024-25 and 2018-20 RSV seasons using data from the RSV-Associated Hospitalization Surveillance Network (RSV-NET) and New Vaccine Surveillance Network (NVSN). Among infants aged 0-7 months (eligible for protection with maternal vaccination or nirsevimab), 2024-25 RSV-associated hospitalization rates were lower compared with 2018-20 pooled rates (estimated relative rate reductions of 43% [RSV-NET: 95% CI = 40%-46%] and 28% [NVSN: 95% CI = 18%-36%]). The largest estimated rate reduction was observed among infants aged 0-2 months (RSV-NET: 52%, 95% CI = 49%-56%; NVSN: 45%, 95% CI = 32%-57%) and during peak hospitalization periods (December-February). These findings support Advisory Committee on Immunization Practices' recommendations for maternal vaccination or nirsevimab to protect against severe RSV disease in infants and highlight the importance of implementing the recommendations to protect infants as early in the RSV season as possible, before peak transmission, and for infants born during the RSV season, within the first week of life, ideally during the birth hospitalization.
RANO criteria for response assessment of brain metastases based on amino acid PET imaging
Authors: Nathalie L Albert, Norbert Galldiks, Benjamin M Ellingson, Martin J van den Bent, Susan M Chang, Francesco Cicone, Eng-Siew Koh, Ian Law, Emilie Le Rhun, Maximilian J Mair, Jan-Michael Werner, Anna S Berghoff, Julia Furtner, Giuseppe Minniti, Andrew M Scott, Susan C Short, Jana Ivanidze, Derek R Johnson, Bogdana Suchorska, Nelleke Tolboom, Joerg-Christian Tonn, Antoine Verger, Eva Galanis, Priscilla K Brastianos, Patrick Y Wen, Michael Weller, Nancy U Lin, Matthias Preusser
Journal: Nature Medicine (2025)
Trends in Cancer Incidence and Mortality Rates in Early-Onset and Older-Onset Age Groups in the United States, 2010–2019
Authors: Meredith S. Shiels, Anika T. Haque, Amy Berrington de González, M. Constanza Camargo, Megan A. Clarke, Brittny C. Davis Lynn, Eric A. Engels, Neal D. Freedman, Gretchen L. Gierach, Jonathan N. Hofmann, Rena R. Jones, Erikka Loftfield, Rashmi Sinha, Lindsay M. Morton, Stephen J. Chanock
Journal: Cancer Discovery (2025)

Abstract We estimated age-standardized cancer incidence (2010–2019) and mortality rates (2010–2022) in the United States to investigate whether cancer rates have increased at younger ages. Fourteen cancers had incidence rates that increased in at least one early-onset age group (i.e., 15–29-, 30–39-, and 40–49-year-olds)—9 of these also increased in at least one older-onset age group (i.e., 50–59, 60–69, and 70–79; i.e., female breast, colorectal, kidney, testicular, uterine and pancreatic cancers, and several lymphoid neoplasms). The largest absolute increases in 2019 compared with expected diagnoses based on 2010 rates were female breast (n = 4,834 additional cancers), colorectal (n = 2,099), kidney (n = 1,793), and uterine cancers (n = 1,209). Although there were not concomitant increases in mortality rates for most cancers, colorectal, uterine, and testicular cancer mortality rates increased in early-onset age groups. The drivers of increasing incidence rates are cancer-specific and could include a combination of established and perhaps new etiologic factors, and increased detection. Significance: In the United States, incidence rates of some cancers have increased in early-onset age groups. For many of these cancers, rates have also increased in older-age groups, suggesting that the impact of changes in risk factor prevalence and/or improvements in detection could affect risk across the age range.