tbuckley/cabot-search huggingface dataset:
Tackling the growing burden of nitrous oxide-induced public health harms
Authors: Safiya A Zaloum, Devan Mair, Alvar Paris, Laura J Smith, Marta Patyjewicz, Barbara L Onen, Alastair J Noyce
Journal: The Lancet Public Health (2025)

Nitrous oxide has been increasing in popularity as a recreational drug in the past decade, and with this an increase in health harms related to nitrous oxide use, particularly nitrous oxide-induced myeloneuropathy. In response, governments in many countries have adopted new laws that either target the end user, by criminalising possession, or target suppliers. The effect of these measures remains to be seen, but the potential to exacerbate harm by targeting the user and thus affecting health-care-seeking behaviour is a concern. Education around the preventable harm from recreational use of nitrous oxide and tightening regulations on suppliers are essential in mitigating the increase in nitrous oxide-related health harms.
Biomarkers of Inflammation Associated with Radon Exposure in the School Inner-City Asthma Study (SICAS)
Authors: Tina M Banzon, Youn Soo Jung, Kimberly F Greco, Longxiang Li, Kari Nadeau, Perdita Permaul, Petros Koutrakis, Jonathan M Gaffin, Wanda Phipatanakul
Journal: Journal of Allergy and Clinical Immunology (2025)
Vodobatinib for patients with Philadelphia chromosome-positive chronic myeloid leukaemia resistant or intolerant to multiple lines of previous therapy: an open-label, multicentre, phase 1/2 trial
Authors: Jorge E Cortes, Dong-Wook Kim, Tapan Saikia, Navin Khattry, Krishnakumar Rathnam, Yesid Alvarado, Guy Hannah, Srinivas K Tantravahi, Jane F Apperley, Aude Charbonnier, Valentin García-Gutiérrez, Alessandro Lucchesi, Delia Dima, Árpád Illés, Viola M Popov, Elisabetta Abruzzese, Arijit Nag, Shashikant Apte, Talha Badar, Siu-Long Yao, Unnati Saxena, Jayasree Sreenivasan, Sandeep Inamdar, Geetanjali Chimote, Franck E Nicolini
Journal: The Lancet Haematology (2025)
Efficacy and safety of GR1802 in uncontrolled CRSwNP: placebo-controlled phase 2 trial
Authors: Ming Zheng, Di Wu, Yingshi Piao, Jun Tang, Fang Quan, Bing Guan, Hongmeng Yu, Xiaowen Zhang, Gang He, Yucheng Yang, Lijia Wan, Xuezhong Li, Wen Liu, Zhendong Xu, Jing Ye, Wen Liu, Xicheng Song, Yuxiao Du, Yu Xu, Jianjun Chen, Wei Wang, Feng Lan, Chengshuo Wang, Luo Zhang
Journal: Journal of Allergy and Clinical Immunology (2025)

Anti-interleukin-4 receptor subunit alpha (IL-4Rα) treatments can effectively treat eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP). However, their impact on the overall population of uncontrolled CRSwNP remains unclear. To evaluate the safety and efficacy of GR1802, a novel anti-IL-4Rα monoclonal antibody, in uncontrolled CRSwNP patients. Seventy uncontrolled CRSwNP participants were randomized (1:1) to receive either GR1802 (300 mg with an initial doubled dose) or placebo every 2 weeks. Primary endpoints were the changes from baseline in nasal polyp score (NPS) and nasal congestion score (NCS) at week 16. Secondary endpoints mainly included change from baseline in total nasal symptom score (TNSS), 22-item Sino-Nasal Outcome Test (SNOT-22) score, and Lund-Mackay score. Efficacy (exploratory) was also analyzed in ECRSwNP and NECRSwNP subgroups. Safety was evaluated throughout the study. In uncontrolled CRSwNP participants, GR1802 significantly improved NPS and NCS when compared to placebo, with least squares (LS) mean differences of -2·1 (95% confidence interval [CI] [-2·6, -1·5]) and -0·8 (95% CI [-1·1, -0·4]) respectively. Participants treated with GR1802 had significantly decreased TNSS, SNOT-22 score, and Lund-Mackay score. The subgroup analysis demonstrated that GR1802 improved the symptoms and life quality both in ECRSwNP and NECRSwNP participants, as evidenced by changes in NPS, University of Pennsylvania Smell Identification Test (UPSIT) score, and Lund-Mackay score. Treatment-related adverse events occurred in 19·4 % of the GR1802 group and 17·6 % of the placebo group. GR1802 is well-tolerated and effective in treating the overall population with uncontrolled CRSwNP.
Real-life observation of wildfire-smoke impaired COVID-19 vaccine immunity
Authors: Gursharan Kaur Sanghar, Melissa Teuber, Resmi Ravindran, Emma Jean Keller, Sean Raffuse, Pedro Hernandez, Angela Linderholm, Gabrielle Echt, Lisa Franzi, Kaelyn Tuermer-Lee, Maya Juarez, Timothy Albertson, Imran Khan, Angela Haczku
Journal: Journal of Allergy and Clinical Immunology (2025)
Deficiency of adenosine deaminase 2 skews adaptive immune repertoires towards specific sets of T and B cell receptors
Authors: Christoph Schultheiß, Paul Schmidt-Barbo, Lisa Paschold, Carl Esperanzate, Alissa Behn, Rafael Mikolajczyk, Daniel L Kastner, Ivona Aksentijevich, Mascha Binder
Journal: Journal of Allergy and Clinical Immunology (2025)
Venetoclax plus Daunorubicin and Cytarabine for Newly Diagnosed Acute Myeloid Leukemia: Results of a Phase 1b Study
Authors: Ioannis Mantzaris, Mendel Goldfinger, Matan Uriel, Aditi Shastri, Nishi Shah, Kira Gritsman, Noah Kornblum, Lauren C Shapiro, Alejandro Sica, Anne Munoz, Nicole Chambers, Aradhika Dhawan, Jhannine Alyssa Verceles, Karen Fehn, Balda Tirone, Lamisha Shah, Shaunmonique Clark, Chenxin Zhang, Mimi Y Kim, Dennis L Cooper, Amit Verma, Marina Y. Konopleva, Eric J Feldman
Journal: Blood (2025)
GLP-1 Receptor Agonist Use Is Associated with Increased Rates of Acne Vulgaris Diagnosis In Non-Diabetic Obese Women but Not Men: A Retrospective Cohort Study
Authors: Seo Won Cho, Tarun Sontam, Aaron Chen, Emily E Limmer, Stanislav N Tolkachjov
Journal: Journal of the American Academy of Dermatology (2025)
Glomerular Filtration Rate Measurement Utilizing Transdermal Detection Methodology
Authors: Richard B. Dorshow, Martin P. Debreczeny, Stuart L. Goldstein
Journal: Journal of the American Society of Nephrology (2025)

The well-known accuracy limitations of estimated GFR (eGFR) currently employed in clinical practice present barriers to optimal care for patients with, or at-risk for, decreased kidney function. A point-of-care glomerular filtration rate (GFR) measurement methodology has the potential to address these limitations. We prospectively assessed transdermal detection of the novel fluorescent GFR tracer agent relmapirazin in participants having normal or impaired kidney function across all human skin colors on the Fitzpatrick Skin Scale (FSS). A multi-center study comprising 74 participants with eGFR from normal to Stage 4 CKD was performed. Forty-six participants were FSS types I-III, and twenty-eight were FSS type IV-VI. A module containing an LED and photodetector to activate and collect transdermal relmapirazin fluorescence was attached adhesively to the upper chest of each participant. Relmapirazin (1.5mg/kg) was administered by intravenous push, and fluorescence emission was acquired for 12 hours. A two-compartment pharmacokinetic model fit the fluorescent intensity vs time data, and the fluorescence clearance rate (FCR) was extracted from the second (terminal) compartment. Plasma relmapirazin concentrations were measured contemporaneously and the corresponding plasma GFR for each participant was determined. Linear regression analysis was used to compare the FCR to the indexed plasma GFR. Participant age range was 23 to 80 years old, with 59% females. The two-compartment pharmacokinetic behavior was observed in the fluorescence intensity vs time data and a FCR was successfully deduced for every participant completing the 12-hour study. The FCR vs. the indexed plasma GFR yielded an excellent correlation over the range of GFR measured and for all skin colors with a r2 = 0.90 (95% confidence interval 0.85 to 0.94). No severe adverse events were reported. Point-of-care transdermal detection of the fluorescent GFR tracer agent relmapirazin was feasible in patients with normal to impaired kidney function and for a range of skin color types.
Disparate and shared transcriptomic signatures associated with cortical atrophy in genetic behavioral variant frontotemporal degeneration
Authors: Ting Shen, Jacob W. Vogel, Vivianna M. Van Deerlin, EunRan Suh, Laynie Dratch, Jeffrey S. Phillips, Lauren Massimo, Edward B. Lee, David J. Irwin, Corey T. McMillan
Journal: Molecular Neurodegeneration (2025)

Cortical atrophy is a common manifestation in behavioral variant frontotemporal degeneration (bvFTD), exhibiting spatial heterogeneity across various genetic subgroups, which may be driven by distinct biological mechanisms. We employed an integrative imaging transcriptomics approach to identify both disparate and shared transcriptomic signatures associated with cortical thickness in bvFTD with C9orf72 repeat expansions or pathogenic variants in GRN or MAPT. Functional enrichment analyses were conducted on each gene list significantly associated with cortical thickness. Additionally, we mapped neurotransmitter receptor/transporter density maps to the cortical thickness maps, to uncover different correlation patterns for each genetic form. Furthermore, we examined whether the identified genes were enriched for pathology-related genes by using previously identified genes linked to TDP-43 positive neurons and genes associated with tau pathology. For each genetic form of bvFTD, we identified cortical thickness signatures and gene sets associated with them. The cortical thickness associated genes for GRN-bvFTD were significantly involved in neurotransmitter system and circadian entrainment. The different patterns of spatial correlations between synaptic density and cortical thinning, further confirmed the critical role of neurotransmission and synaptic signaling in shaping brain structure, especially in the GRN-bvFTD group. Furthermore, we observed significant overlap between genes linked to TDP-43 pathology and the gene sets associated with cortical thickness in C9orf72-bvFTD and GRN-bvFTD but not the MAPT-bvFTD group providing specificity for our associations. C9orf72-bvFTD and GRN-bvFTD also shared genes displaying consistent directionality, with those exhibiting either positive or negative correlations with cortical thickness in C9orf72-bvFTD showing the same direction (positive or negative) in GRN-bvFTD. MAPT-bvFTD displayed more pronounced differences in transcriptomic signatures compared to the other two genetic forms. The genes that exhibited significantly positive or negative correlations with cortical thickness in MAPT-bvFTD showed opposing directionality in C9orf72-bvFTD and GRN-bvFTD. Overall, this integrative transcriptomic approach identified several new shared and disparate genes associated with regional vulnerability with increased biological interpretation including overlap with synaptic density maps and pathologically-specific gene expression. These findings illuminated the intricate molecular underpinnings contributing to the heterogeneous nature of disease distribution in bvFTD with distinct genetic backgrounds.
Pharmacological activity of OST-01, a natural product from baccharis coridifolia, on breast cancer cells
Authors: HyunJun Kang, Dinh Hoa Hoang, Melissa Valerio, Khyatiben Pathak, William Graff, Alexis LeVee, Jun Wu, Mark A. LaBarge, David Frankhouser, Russell C. Rockne, Patrick Pirrotte, Bin Zhang, Joanne Mortimer, Le Xuan Truong Nguyen, Guido Marcucci
Journal: Journal of Hematology & Oncology (2025)

Natural products have long been a viable source of therapeutic agents, providing unique structures and mechanisms that may be beneficial for cancer treatment. Herein we first report on the anticancer activity OST-01, a natural product from Baccharis Coridifolia, on breast cancer cells, including triple-negative breast cancer (TNBC). OST-01 significantly inhibited cell proliferation and oncogenic activities of TNBC cells in vitro. OST-01 also markedly inhibited TNBC tumor growth in vivo, with > 50% reduction in tumor size compared to vehicle control treatment in different in vivo models, i.e., cell line-derived (CDX), patient-derived (PDX), and mammary fat pad xenografts. Mechanistically, OST-01 induces ferroptosis by downregulating LRP8-regulated selenoproteins, i.e., GPX4. A shift from a basal-mesenchymal to a luminal-epithelial state of breast cancer stem cells (BCSCs) as supported by the downregulation of stemness (e.g., CD44) and mesenchymal (e.g., FN1 and vimentin) markers, along with the upregulation of differentiation markers (e.g., CD24) and luminal-epithelial markers (e.g., CK19), was also observed.
Academic medicine: integrating community insights and equity
Authors: Shahzad K Jamil, Mark I Johnson
Journal: BMJ (2025)

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Anti-LAG-3 antibody LBL-007 plus anti-PD-1 antibody toripalimab in advanced nasopharyngeal carcinoma and other solid tumors: an open-label, multicenter, phase Ib/II trial
Authors: Gang Chen, Dong-Chen Sun, Yi Ba, Ya-Xiong Zhang, Ting Zhou, Yuan-Yuan Zhao, Hong-Yun Zhao, Wen-Feng Fang, Yan Huang, Zhen Wang, Chao Deng, De-Sheng Hu, Wei Wang, Jin-Guan Lin, Gui-Ling Li, Su-Xia Luo, Zhi-Chao Fu, Hai-Sheng Zhu, Hui-Li Wang, Sheng-Li Cai, Xiao-Qiang Kang, Li Zhang, Yun-Peng Yang
Journal: Journal of Hematology & Oncology (2025)
Continuous Monitoring for Atrial Fibrillation in Individuals at Increased Risk of Acute Exacerbations of COPD
Authors: David M. MacDonald, Trent Fischer, Selcuk Adabag, Shakeel Amanullah, Jose Diaz, Philip Diaz, Ken M Kunisaki, Pamela L Lutsey, Christine H. Wendt
Journal: American Journal of Respiratory and Critical Care Medicine (2025)
Fibroblast growth factor 23 and fibroblast growth factor receptor 4 promote cardiac metabolic remodeling in chronic kidney disease.
Authors: Michaela A A Fuchs, Emily J Burke, Nejla Latic, Susan Murray, Hanjun Li, Matthew A Sparks, Dennis Abraham, Hengtao Zhang, Paul Rosenberg, Umber Saleem, Arne Hansen, Sara E Miller, Davis Ferreira, Sonja Hänzelmann, Fabian Hausmann, Tobias Huber, Reinhold Erben, Kelsey Fisher-Wellman, Nenad Bursac, Myles Wolf, Alexander Grabner
Journal: Kidney International (2025)
Anlotinib versus placebo as adjuvant therapy for localized high-grade soft tissue sarcomas: a phase 2, double-blinded, randomized controlled trial
Authors: Chunmeng Wang, Xianglin Hu, Lingge Yang, Yu Xu, Biqiang Zheng, Jilong Yang, Zhichao Liao, Zhengwang Sun, Shengjian Zhang, Lin Yu, Yan Yan, Yong Chen, Tomohiro Fujiwara, Jianrong Zhang, Ilia N. Buhtoiarov, Yangbai Sun, Wangjun Yan
Journal: Clinical Cancer Research (2025)

Abstract Purpose: We aimed to investigate the efficacy and safety of anlotinib as adjuvant targeted therapy for completely resected localized high-grade soft-tissue sarcomas (STS). Patients and Methods: Patients with localized high-grade STS after complete resection were randomly assigned in a 1:1 ratio to receive either oral 12 mg anlotinib or placebo once daily on days 1 to 14 every 21 days as a cycle, with up to six cycles until disease relapse, unmanageable toxicity, or death. The efficacy and safety were analyzed. This trial was the first trial exploring adjuvant targeted therapy for STS (NCT03951571). Results: Between June 2019 and November 2023, 88 patients were randomly assigned to receive anlotinib (n = 44) or placebo (n = 44). With a median follow-up of 30.95 months, the 1- and 2-year disease-free survival rates were 88% and 77% in the anlotinib group compared with 64% and 58% in the placebo group, respectively. Compared with patients treated with surgery alone, patients receiving adjuvant anlotinib combined with surgery had a reduced risk of disease recurrence [HR, 0.47; 95% confidence interval (CI), 0.22–1.00; P = 0.0445]. Based on the tumor histology, the reduced risk of disease recurrence with anlotinib versus placebo was observed in patients with myxofibrosarcoma (HR, 0.54; 95% CI, 0.17–1.65; P = 0.2698) and undifferentiated pleomorphic sarcoma (HR, 0.58; 95% CI, 0.12–2.87; P = 0.4971). Four patients discontinued anlotinib: two for proteinuria/hematuria (2/44, 5%) and two for poor healing of surgical wound (2/44, 5%). Conclusions: Compared with surgery alone, adjuvant anlotinib following surgery reduces the incidence of disease relapse in localized high-grade STS, with acceptable toxicity.
Bioengineering of a human iPSC-derived vascularized endocrine pancreas for type 1 diabetes
Authors: Francesco Campo, Alessia Neroni, Cataldo Pignatelli, Silvia Pellegrini, Ilaria Marzinotto, Libera Valla, Fabio Manenti, Martina Policardi, Vito Lampasona, Lorenzo Piemonti, Antonio Citro
Journal: Cell Reports Medicine (2025)

Intrahepatic islet transplantation in patients with type 1 diabetes is limited by donor availability and lack of engraftment. Alternative β cell sources and transplantation sites are needed. We demonstrate the feasibility to repurpose a decellularized lung as an endocrine pancreas for β cell replacement. We bioengineer an induced pluripotent stem cell (iPSC)-based version, fabricating a human iPSC-based vascularized endocrine pancreas (iVEP) using iPSC-derived β cells (iPSC-derived islets [SC-islets]) and endothelial cells (iECs). SC-islets and iECs are aggregated into vascularized iβ spheroids (ViβeSs), and over 7 days of culture, spheroids integrate into the bioengineered vasculature, generating a functional, perfusable human endocrine organ. In vitro, the vascularized extracellular matrix (ECM) sustained SC-islet engraftment and survival with a significantly preserved β cell mass and a physiologic insulin release. In vivo, iVEP restores normoglycemia in diabetic NSG mice. We report a human iVEP providing a controlled in vitro insulin-secreting phenotype and in vivo function.
Author Correction: β-Glucan reprograms neutrophils to promote disease tolerance against influenza A virus
Authors: Nargis Khan, Kim A. Tran, Raphael Chevre, Veronica Locher, Mathis Richter, Sarah Sun, Mina Sadeghi, Erwan Pernet, Andrea Herrero-Cervera, Alexandre Grant, Ahmed Saif, Jeffrey Downey, Eva Kaufmann, Shabaana Abdul Khader, Philippe Joubert, Luis B. Barreiro, Bryan G. Yipp, Oliver Soehnlein, Maziar Divangahi
Journal: Nature Immunology (2025)
Air quality, respiratory health and performance in athletes: a summary of the IOC consensus subgroup narrative review on ‘Acute Respiratory Illness in Athletes’
Authors: Valerie Bougault, Christopher Carlsten, Paolo Emilio Adami, Nicola Sewry, Wolfgang Schobersberger, Torbjørn Soligard, Lars Engebretsen, Richard Budgett, Martin Schwellnus, Ken Fitch
Journal: British Journal of Sports Medicine (2025)

With the WHO stating that nearly 99% of the global population is exposed to air pollution levels that increase the risk of chronic diseases, the question of exercising in polluted environments is relevant to the health of athletes. Major sporting events held under conditions of poor air quality (AQ) have highlighted the lack of answers to concerns raised by organisers and athletes about the associated health risks. This evidence-based narrative review compiles current knowledge and identifies gaps regarding the relationship between AQ and sport. It is a summary of a more comprehensive report prepared for the International Olympic Committee (IOC) Medical and Scientific Commission. This article discusses the various sources of air pollutants encountered during exercise, summarises current AQ guidelines and provides insights into AQ conditions during the Paris 2024 Olympic and Paralympic Games (OPG) as well as in Los Angeles over the past four summers, in preparation for the 2028 OPG. It also summarises the effects of air pollution on the respiratory health and performance of athletes, while proposing mitigation strategies, with a particular emphasis on AQ education.
Combined inhibition of focal adhesion kinase and RAF/MEK elicits synergistic inhibition of melanoma growth and reduces metastases
Authors: Jared Almazan, Tursun Turapov, David A. Kircher, Karly A. Stanley, Katie Culver, A. Paulina Medellin, MiKaela N. Field, Gennie L. Parkman, Howard Colman, Silvia Coma, Jonathan A. Pachter, Sheri L. Holmen
Journal: Cell Reports Medicine (2025)

This study addresses the urgent need for effective therapies for patients with brain metastases from cutaneous melanoma, a major cause of treatment failure despite recent therapeutic advances. Utilizing mouse models that mimic human melanoma brain metastases, this study investigates the necessity of focal adhesion kinase (FAK) in the development of distant metastases and its potential as a therapeutic target. Pharmacological inhibition of FAK demonstrates significant efficacy in reducing the development of brain metastases in preclinical mouse models. Importantly, the study provides insight into the crosstalk between FAK and mitogen-activated protein kinase (MAPK) pathway signaling and highlights the synergistic effects of combined inhibition of FAK, rapidly accelerated fibrosarcoma (RAF), and mitogen-activated protein kinase kinase (MEK) in cutaneous melanoma. These findings provide the rationale for clinical evaluation of the efficacy of the FAK inhibitor defactinib and the RAF/MEK inhibitor avutometinib in patients with brain metastases from cutaneous melanoma.
Association of remnant cholesterol with unhealthy lifestyle and risk of coronary heart disease: a population-based cohort study
Authors: Mia Ø. Johansen, Signe Vedel-Krogh, Sune F. Nielsen, Shoaib Afzal, George Davey Smith, Børge G. Nordestgaard
Journal: The Lancet Regional Health - Europe (2025)

SummaryBackgroundUnhealthy lifestyle is a major risk factor for coronary heart disease, which may be explained by elevated remnant cholesterol. However, this question remains incompletely clarified. In this study, we aimed to investigate whether elevated remnant cholesterol explains part of the excess risk of myocardial infarction and coronary heart disease in individuals with unhealthy lifestyle.MethodsWe included 104,867 individuals (58,286 women and 46,581 men) from the Copenhagen General Population Study free from coronary heart disease at examination. During a median follow-up of 9.2 years, 2484 developed myocardial infarction and 3570 developed coronary heart disease. To understand explained risk from elevated remnant cholesterol due to unhealthy lifestyle on risk of myocardial infarction and coronary heart disease, we used mediation analyses.FindingsCurrent smoking, low physical activity, and low adherence to dietary guidelines were all associated with higher levels of remnant cholesterol. For current smoking, remnant cholesterol explained 15% (95% confidence interval: 9.7%–20%) of the excess risk of myocardial infarction and 16% (11%–21%) of the excess risk of coronary heart disease. Corresponding values for low physical activity were 20% (13%–27%) and 21% (15%–28%), and for low adherence to dietary guidelines 12% (6.6%–18%) and 14% (8.0%–19%), respectively. Results were similar in women and men separately and in analyses where each lifestyle factor were additionally adjusted for the other three lifestyle factors.InterpretationElevated remnant cholesterol explained part of excess myocardial infarction and coronary heart disease in individuals with an unhealthy lifestyle. Clinically, these novel findings underline the importance of both elevated remnant cholesterol and promotion of healthy lifestyle in primary prevention of myocardial infarction and coronary heart disease.FundingIndependent Research Fund Denmark; Johan Boserup and Lise Boserups Grant; Medical Research Council.