tbuckley/cabot-search huggingface dataset:
Factors in Time to Full Approval or Withdrawal for Anticancer Medicines Granted Accelerated Approval by the FDA
Authors: Ariadna Tibau, Thomas J. Hwang, Alejandra Romano, Maria Borrell, Ignasi Gich, Consolacion Molto, Aaron S. Kesselheim
Journal: JAMA Network Open (2025)

The accelerated approval pathway was developed to expedite US Food and Drug Administration (FDA) drug approval for life-threatening conditions based on changes to unvalidated surrogate measures, with conversion to regular approval then based on a required confirmatory trial. However, confirmatory trials may not be completed in a timely fashion. To analyze factors associated with time to conversion to regular approval. This cohort study of cancer drugs FDA-approved from 1992 to 2022 extracted pivotal and confirmatory trial characteristics, outcomes, safety data, and confirmatory study status at approval from drug labels and published reports. Clinical benefit was assessed using the European Society of Medical Oncology-Magnitude of Clinical Benefit Scale (ESMO-MCBS) for pivotal and confirmatory studies. High benefit was defined as grade A or B (for trials of curative intent) and 4 or 5 (palliative intent) and low benefit as grade C and 2 or below. Data were analyzed between August 2023 and August 2024. Time to full approval or withdrawal. This cohort study analyzed 102 cancer drug indications granted accelerated approval by the FDA between 1992 and 2022 and converted to regular approval by August 31, 2024. The median (IQR) time to conversion was 3.1 (1.9-4.8) years. Of these, 83 (81%) received priority review, and 27 (26%) carried boxed warnings. On the ESMO-MCBS scale, 12 of 101 pivotal trials that were scorable showed high benefit (12%), 27 intermediate benefit (27%), and 62 low benefit (61%). Twenty-one confirmatory trials (21%) were initiated after accelerated approval. Factors at the time of accelerated approval that were associated with shorter times to full approval included priority review designation, absence of boxed warnings, initiation of confirmatory studies before approval, and pivotal trials showing intermediate or high benefit on the ESMO-MCBS framework. Among the 102 confirmatory trials, 34 (33%) demonstrated significant improvements in overall survival, and 14 of 35 trials (40%) reporting on quality of life showed significant benefits. The ESMO-MCBS scale was applicable to 98 trials, with 46 (47%) scoring high clinical benefit, 29 (30%) intermediate, and 23 (23%) low. Indications with benefits in overall survival (median [IQR], 2.15 [1.40-3.38] vs 3.70 [2.33-5.78] years), quality of life (median [IQR], 2.29 [1.85-3.53] vs 4.22 [2.52-5.72] years), and high clinical benefit in confirmatory trials (median [IQR], 2.34 [1.52-3.39] vs 3.91 [2.59-6.42] years) were associated with faster conversion to full approval. In this cohort study, drugs with low clinical benefit or safety concerns at accelerated approval were linked to delayed confirmatory studies, while high clinical benefit in confirmatory trials correlated with faster conversion. These associations can help guide patient decision-making around accelerated approval drugs.
Two distinct fetal‐type signatures characterize juvenile myelomonocytic leukemia
Authors: Marion Strullu, Chloé Arfeuille, Aurélie Caye‐Eude, Loïc Maillard, Elodie Lainey, Florian Piques, Bruno Cassinat, Fabien Guimiot, Jean‐Hugues Dalle, André Baruchel, Christine Chomienne, Dominique Bonnet, Michèle Souyri, Hélène Cavé
Journal: HemaSphere (2025)

Abstract Juvenile myelomonocytic leukemia (JMML) is an aggressive clonal myeloproliferative neoplasm that affects infants and young children. The narrow window of onset suggests that age‐related factors are involved in leukemogenesis. To investigate whether ontogeny‐related features are involved in JMML oncogenesis, we compared the gene expression profile of hematopoietic progenitor cells isolated from JMML patients with that of healthy individuals at different stages of ontogeny. This analysis identified two main groups of JMML patients. In the first group, JMML progenitors exhibited a gene expression profile similar to that of embryo‐fetal progenitors. Progenitors showed a strong monocytic identity as evidenced by the overexpression of monocytic/dendritic, inflammasome, and innate immune markers. This resembled the monocyte‐predominant myelopoiesis characteristic of normal fetal hematopoiesis. However, in the second group, despite evidence of developmental dysregulation as indicated by the aberrant signature of the master oncofetal regulator LIN28B, JMML clustered separately from healthy prenatal and postnatal fractions. These findings highlight the intricate relationship between JMML and development, which will help inform future therapeutic approaches for this rare but severe form of leukemia.
Late-Onset Diffuse Xanthomas in an Adult Man
Authors: Reid Weisberg, Sameera Husain, Jason E. Liebowitz
Journal: JAMA Dermatology (2025)

A man in his 60s presented to the hospital with fever, joint pain, and second-degree atrioventricular block. Physical examination revealed diffuse xanthomata, most prominent in the periorbital region. What is your diagnosis?
Artemisinin Partial Resistance in Ugandan Children—Reply
Authors: Ruth Namazzi, Chandy C. John, Colin Sutherland
Journal: JAMA (2025)

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Integrating Plasma Cell-Free DNA Fragment End Motif and Size with Genomic Features Enables Lung Cancer Detection
Authors: Tae-Rim Lee, Jin Mo Ahn, Junnam Lee, Dasom Kim, Juntae Park, Byeong-Ho Jeong, Dongryul Oh, Sang Man Kim, Gyou-Chul Jung, Beom Hee Choi, Min-Jung Kwon, Mengchi Wang, Michael Salmans, Andrew Carson, Bryan Leatham, Kristin Fathe, Byung In Lee, Byoungsok Jung, Chang-Seok Ki, Young Sik Park, Eun-Hae Cho
Journal: Cancer Research (2025)

Early detection of lung cancer is important for improving patient survival rates. Liquid biopsy using whole-genome sequencing of cell-free DNA (cfDNA) offers a promising avenue for lung cancer screening, providing a potential alternative or complementary approach to current screening modalities. Here, we aimed to develop and validate an approach by integrating fragment and genomic features of cfDNA to enhance lung cancer detection accuracy across diverse populations. Deep learning-based classifiers were trained using comprehensive cfDNA fragmentomic features from participants in multi-institutional studies, including a Korean discovery dataset (218 patients with lung cancer and 2,559 controls), a Korean validation dataset (111 patients with lung cancer and 1,136 controls), and an independent Caucasian validation cohort (50 patients with lung cancer and 50 controls). In the discovery dataset, classifiers using fragment end motif by size, a feature that captures both fragment end motif and size profiles, outperformed standalone fragment end motif and fragment size classifiers, achieving an area under the curve (AUC) of 0.917. The ensemble classifier integrating fragment end motif by size and genomic coverage achieved an improved performance, with an AUC of 0.937. This performance extended to the Korean validation dataset and demonstrated ethnic generalizability in the Caucasian validation cohort. Overall, the development of a deep learning-based classifier integrating cfDNA fragmentomic and genomic features in this study highlights the potential for accurate lung cancer detection across diverse populations. Significance: Evaluating fragment-based features and genomic coverage in cell-free DNA offers an accurate lung cancer screening method, promising improvements in early cancer detection and addressing challenges associated with current screening methods.
Therapeutic advances for Cutaneous T Cell Lymphoma
Authors: Martine Bagot
Journal: British Journal of Dermatology (2025)

Cutaneous T cell lymphomas (CTCL) are a group of rare and heterogenous diseases. There is currently no curative treatment for patients with advanced mycosis fungoides (MF) and Sézary syndrome (SS). EORTC consensus recommendations for the treatment of MF/SS have been updated and focused on recently available treatments. Peginterferon, a new form of interferon, has a favorable risk-benefit profile for CTCL patients treatment. Recently approved monoclonal antibodies have completely modified the treatment algorithm of advanced CTCL treatment. Brentuximab vedotin is very efficient for tumor and transformed MF. Mogamulizumab can induce long term remission in patients with SS. Lacutamab has recently completed an international trial, both in SS and MF. Numerous novel targets have been identified, and several new monoclonal antibodies have been shown able to enhance specific immune responses and to induce targeted antibody dependent cytotoxicity and cytophagocytosis. These new antibodies warrant further evaluation in controlled trials. Kinase inhibitors and Chimeric Antigen Receptor (CAR)-T Therapy are promising new treatments. Finally, recent studies have demonstrated that allogeneic hematopoietic stem-cell transplantation can increase survival and quality of life in patients with advanced CTCL.
Older Adults’ Views on Insurance Coverage for Weight Management Medications
Authors: Lauren Oshman, Matthias Kirch, Erica Solway, Dianne C. Singer, Preeti N. Malani, J. Scott Roberts, Jeffrey T. Kullgren, Dina Hafez Griauzde
Journal: JAMA Network Open (2025)

Medicare and many commercial insurers do not cover US Food and Drug Administration-approved weight management medications, such as incretin mimetics (semaglutide, tirzepatide, and liraglutide), bupropion-naltrexone, and phentermine-topiramate). To assess older adults' interest in weight management medications and associated characteristics and to understand their perceptions about insurance coverage of weight management medications. This survey study used cross-sectional data from a nationally representative sample of US adults ages 50 to 80 years from the July 2023 National Poll on Healthy Aging. Data were analyzed from August to November 2023. Outcomes of interest were estimates of interest in taking weight management medication and perceptions about coverage for US Food and Drug Administration-approved weight management medications by insurers, including Medicare. Among 2657 respondents, 60.3% (95% CI, 56.7%-63.8%) were ages 50 to 64 years, 52.2% (95% CI, 49.8%-54.5%) were female, and 10.6% (95% CI, 9.3%-12.0%) were non-Hispanic Black, 11.4% (95% CI, 10.4%-12.6%) were Hispanic, and 70.3% (95% CI, 68.2%-72.4%) were non-Hispanic White. Overall, 35.1% (95% CI, 31.9%-38.4%) of participants were interested in using weight management medications, including 59.1% (95% CI, 53.4%-64.5%) of individuals with body mass index (BMI) of 30 or greater. Interest was most robustly associated with having used these medications in the past (adjusted odds ratio, 7.57 [95% CI, 4.41-13.02]) and BMI of 30 or greater (adjusted odds ratio, 5.04 [95% CI, 3.48-7.30]). Most participants (of any BMI) agreed that health insurance should cover weight management medications (2176 of 2625 respondents [83.2%]). When asked whether Medicare should cover such medications, most still favored coverage (2097 of 2616 respondents [75.7%]), but fewer approved of paying more for a Medicare premium to ensure coverage (829 of 2604 respondents [30.2%]). In this survey study of older US adults, most participants agreed that Medicare should cover weight management medications and more than half of those with BMI of 30 or greater were interested in using them. These results should inform decisions to include weight management medications in the Medicare and commercial insurance programs, as well as utilization policies to control health care costs.
Biodegradable Piezoelectric Janus Membrane with Enhanced Antibacterial and Osteoinductive Properties for Periodontitis Therapy
Authors: Jingrong Cheng, Liping Wu, Hongying Fu, Le Hu, Weijia Wang, Boon Chin Heng, Xuehui Zhang, Ousheng Liu, Xuliang Deng, Yang Liu
Journal: Advanced Healthcare Materials (2025)

An ideal guided bone regeneration (GBR) membrane for periodontitis treatment should incorporate biocompatibility, biodegradability, mechanical strength, antibacterial properties, and osteoconductivity. However, no commercially available GBR membrane meets all these criteria simultaneously. In this study, a novel biodegradable piezoelectric double-layered membrane is developed, with a non-piezoelectric Poly-L-lactic acid (PLLA) side facing the gingiva and a piezoelectric PLLA-ZnO side facing the alveolar bone. This asymmetric GBR membrane, with distinct fiber orientations and charge distribution, combines and synergizes mechanical strength, degradability, barrier function, antibacterial activity and osteogenic potential to enhance bone regeneration efficacy. The GBR membrane can effectively prevent fibroblast migration, inhibits bacterial infection, and promotes bone regeneration both in vitro and in vivo. In vitro testing shows good antibacterial rate against Porphyromonas gingivalis (P. gingivalis) and Staphylococcus aureus (S. aureus) after 10 min of ultrasound stimulation. Expression levels of osteogenic genes Bone morphogenetic Protein 2 (BMP2), Runt-related transcription factor 2 (RUNX2), Osteopontin (OPN) and Osteocalcin (OCN) are over twice that of the control. In a mouse P. gingivalis-mediated periodontitis model, our composite membrane demonstrates effective antimicrobial effects and promote bone regeneration after 2- and 4-weeks implantation, facilitated by mechanisms such as physical isolation, zinc ion release, piezoelectric effects, enhanced expression of osteogenic genes through activation of osteogenesis-related signaling pathways, underscoring its strong potential for GBR applications.
Hydrogel‐Based Tumor Tissue Microarchitecture Reshapes Dendritic Cell Metabolic Profile and Functions
Authors: Brian Chesney Quartey, Jiranuwat Sapudom, Paul Sean Tipay, Yamanappa Hunashal, Shaikha Alshehhi, Marc Arnoux, Thyago Cardoso, Javier Quilez, Fabio Piano, Jeremy CM Teo
Journal: Advanced Healthcare Materials (2025)

The extracellular matrix (ECM) plays a pivotal role in immunomodulation, providing structural and biochemical cues that shape immune cell function. In pathological conditions like cancer and chronic inflammation, dysregulated remodeling often results in altered ECM composition and architecture, with fibrillar alignment being a hallmark linked to disease progression. Here, how ECM alignment influences dendritic cell (DC) behavior using 3D biomimetic collagen matrices with controlled fibril anisotropy is investigated. This results show that immature DCs in aligned matrices exhibited increased expression of CD86 and HLA-DR with elevated secretion of CXCL8 and CCL2 chemokines, which may enhance immune cell recruitment. However, transcriptomic and metabolomic analysis revealed significant downregulation of oxidative phosphorylation and an insufficient compensatory shift toward glycolysis, resulting in reduced ATP production. This metabolic constraint correlated with impaired/reduced DC migratory speed and distance. In contrast, mature DCs displayed minimal sensitivity to ECM alignment, maintaining uniform differentiation and functional profiles across matrix conditions. T-cell coculture experiments revealed that ECM alignment dampens T-cell activation and proliferation, likely through direct modulation of T-cell behavior. These findings highlight the stage-specific effects of ECM alignment on DC function, highlighting its role in DC immunomodulation, with implications for therapeutic development in cancer and other pathological contexts.
Proton density fat fraction for diagnosis of metabolic dysfunction associated steatotic liver disease
Authors: Nikolaos Panagiotopoulos, Tanya Wolfson, David T. Harris, Danielle Batakis, Rashmi Agni, Lael Ceriani, Yesenia Covarrubias, Gavin Hamilton, Michael S. Middleton, Vitor F. Martins, Anthony C. Gamst, Thekla H. Oechtering, Ryan Sappenfield, Santiago Horgan, Eduardo Grunvald, Luke M. Funk, Garth R. Jacobsen, Anne O. Lidor, James A. Goodman, Sami B. Khoury, Claude B. Sirlin, Scott B. Reeder
Journal: Hepatology (2025)

Prior work has shown that magnetic resonance imaging (MRI)-derived proton density fat fraction (PDFF) can diagnose metabolic dysfunction-associated steatotic liver disease (MASLD) noninvasively, but there is a paucity of data on the performance of PDFF to classify more advanced forms of the MASLD spectrum. The purpose of this study was to assess the diagnostic performance of PDFF for the diagnoses of MASLD, metabolic dysfunction-associated steatohepatitis (MASH), and fibrotic MASH in adults with obesity undergoing bariatric surgery, using contemporaneous intraoperative liver biopsy as reference. PDFF was evaluated alone and with other potential classifiers (imaging, serum and anthropometric), using Bayesian Information Criterion-based stepwise logistic regression models. Areas under the receiver operating characteristic (ROC) curves (AUC) were computed for all models and single classifiers. Cross-validated sensitivity and specificity were calculated at Youden-based PDFF classification thresholds. Data analysis from 140 patients demonstrated that PDFF was the most accurate single classifier, with high AUC for MASLD (0.95), MASH (0.85), and fibrotic MASH (0.82) (all p<0.001). Multivariable models including PDFF outperformed those without PDFF. The Youden-based threshold for PDFF was 4.4% for MASLD (sensitivity: 87%, specificity: 86%), 6.9% for MASH (sensitivity: 77%, specificity: 66%), and 13.5% for fibrotic MASH (sensitivity: 67%, specificity: 85%). PDFF was the most accurate single classifier for diagnosing MASLD, MASH, and fibrotic MASH. The most accurate multivariable classification models for MASLD, MASH, and fibrotic MASH included PDFF, demonstrating the central importance of PDFF for noninvasive assessment of the MASLD spectrum.
Announcing the Lancet Global Health Commission on artificial intelligence (AI) and HIV: leveraging AI for equitable and sustainable impact
Authors: Michael J A Reid, Benedette A Otieno, Alastair van Heerden, Izukanji Sikazwe, Solange L Baptiste, Rouella Mendonca, Geoffrey Tasi, Maaya Sundaram
Journal: The Lancet Global Health (2025)
Electrocardiogram-based deep learning to predict left ventricular systolic dysfunction in paediatric and adult congenital heart disease in the USA: a multicentre modelling study
Authors: Joshua Mayourian, Ivor B Asztalos, Amr El-Bokl, Platon Lukyanenko, Ryan L Kobayashi, William G La Cava, Sunil J Ghelani, Victoria L Vetter, John K Triedman
Journal: The Lancet Digital Health (2025)
The effect of pertussis vaccination in pregnancy on the immunogenicity of acellular or whole-cell pertussis vaccination in Gambian infants (GaPS): a single-centre, randomised, controlled, double-blind, phase 4 trial
Authors: Anja Saso, Ebrima Kanteh, David Jeffries, Michael Okoye, Nuredin Mohammed, Michelle Kumado, Sophie Roetynck, Haddijatou Jobe, Amadou Faal, Elishia Roberts, Pieter Gageldonk, Anne-Marie Buisman, Janeri Fröberg, Breeze Cavell, Elodie Lesne, Alex-Mikael Barkoff, Qiushui He, Kiarash Tanha, Sagida Bibi, Dominic Kelly, Dimitri Diavatopoulos, Beate Kampmann
Journal: The Lancet Infectious Diseases (2025)
Low-dose CT for lung cancer screening in a high-risk population (SUMMIT): a prospective, longitudinal cohort study
Authors: Amyn Bhamani, Andrew Creamer, Priyam Verghese, Ruth Prendecki, Carolyn Horst, Sophie Tisi, Helen Hall, Chuen Ryan Khaw, Monica Mullin, John McCabe, Kylie Gyertson, Vicky Bowyer, Dominique Arancon, Jeannie Eng, Fanta Bojang, Claire Levermore, Anne-Marie Hacker, Esther Arthur-Darkwa, Laura Farrelly, Anant Patel, Sara Lock, Alan Shaw, Rajesh Banka, Angshu Bhowmik, Ugo Ekeowa, Zaheer Mangera, Christopher Valerio, William M Ricketts, Ali Mohammed, Terry O'Shaughnessy, Neal Navani, Samantha L Quaife, Arjun Nair, Anand Devaraj, Jennifer L Dickson, Allan Hackshaw, Sam M Janes
Journal: The Lancet Oncology (2025)
A roadmap for fostering timely regulatory and ethics approvals of international clinical trials in support of global health research systems
Authors: Marco Cavaleri, Claudiosvam M Alves de Sousa, Adam Hacker, Elisabeth S Higgs, Murray M Lumpkin, Christiane S Maia, Roli Mathur, Adam M Fimbo, Andreas Reis, Kyoung Seung Shin, David W Vaughn, Wei Zhang, Vasee Moorthy
Journal: The Lancet Global Health (2025)
Effects of the DPP-1 inhibitor HSK31858 in adults with bronchiectasis in China (SAVE-BE): a phase 2, multicentre, double-blind, randomised, placebo-controlled trial
Authors: Nan-Shan Zhong, Rong Qiu, Jie Cao, Yan-Ming Huang, Hua Zhou, Xing-Xiang Xu, Jin-Fu Xu, Huan Ye, Zhi-Ren Yang, Ling-Yun Gao, Yao Shen, Zu-Ke Xiao, Shi-Guang Xie, Dian-Jie Lin, Li Zhao, Hao Xiong, Xian-Ming Zhang, Fang-Qiong Li, Wei-Jie Guan, James D Chalmers
Journal: The Lancet Respiratory Medicine (2025)
Snapshot artificial intelligence—determination of ejection fraction from a single frame still image: a multi-institutional, retrospective model development and validation study
Authors: Jeffrey G Malins, D M Anisuzzaman, John I Jackson, Eunjung Lee, Jwan A Naser, Behrouz Rostami, Jared G Bird, Dan Spiegelstein, Talia Amar, Jae K Oh, Patricia A Pellikka, Jeremy J Thaden, Francisco Lopez-Jimenez, Sorin V Pislaru, Paul A Friedman, Garvan C Kane, Zachi I Attia
Journal: The Lancet Digital Health (2025)
In vitro isolation of contemporary Treponema pallidum strains directly from clinical samples of syphilis patients
Authors: Juraj Bosák, Matěj Hrala, Filip Skokan, Miroslav Nečas, Radim Strnadel, Eliška Vrbová, Petra Pospíšilová, Hana Jedličková, David Šmajs
Journal: Clinical Microbiology and Infection (2025)
A thiouracil desulfurase protects Clostridioides difficile RNA from 4-thiouracil incorporation, providing a competitive advantage in the gut
Authors: Matthew J Munneke, Yifeng Yuan, Eva C Preisner, Catherine D Shelton, Darian T Carroll, Nicole S Kirchoff, Ken P Dickson, Jose O Cantu, Martin V Douglass, M Wade Calcutt, Katherine N Gibson-Corley, Maribeth R Nicholson, Mariana X Byndloss, Robert A Britton, Valérie de Crécy-Lagard, Eric P Skaar
Journal: Cell Host & Microbe (2025)