tbuckley/cabot-search huggingface dataset:
High-purity CTC RNA sequencing identifies prostate cancer lineage phenotypes prognostic for clinical outcomes
Authors: Marina N. Sharifi, Jamie M. Sperger, Amy K. Taylor, Katharine E. Tippins, Shannon R. Reese, Viridiana Carreno, Katherine R. Kaufmann, Alex H. Chang, Luke A. Nunamaker, Charlotte Linebarger, Leilani Mora-Rodriguez, Jennifer L. Schehr, Hannah M. Krause, Kyle T. Helzer, Matthew L. Bootsma, Grace C. Blitzer, John M. Floberg, Christos E. Kyriakopoulos, Hamid Emamekhoo, Elisabeth I. Heath, Meghan Wells, Scott T. Tagawa, Martin Sjöström, Atish D. Choudhury, Menggang Yu, Andrew J. Armstrong, Dana E. Rathkopf, Himisha Beltran, Peter S. Nelson, Felix Y. Feng, Scott M. Dehm, David Kosoff, Xiao X. Wei, Rana R. McKay, Shuang G. Zhao, Joshua M. Lang
Journal: Cancer Discovery (2025)

Abstract The development of treatment resistance remains universal for patients with metastatic prostate cancer, driven by AR alterations and lineage state transitions. Identifying the evolution of lineage transitions in treatment resistance has been limited by the challenges of collecting serial tissue biopsies on treatment, which can be overcome using blood-based liquid biopsies. Utilizing a novel circulating tumor cell (CTC) isolation approach, we collected 273 CTC samples from 117 patients with metastatic prostate cancer for RNA sequencing. 146 samples from 70 patients had tumor purity comparable to tissue biopsies. We identified four CTC transcriptional phenotypes, mirroring lineage states identified in tissue. Patients with a luminal-B-like CTC phenotype defined by persistent AR signaling and high proliferation, as well as those with a neuroendocrine CTC phenotype, had significantly shorter survival than patients with luminal-A-like and low proliferation phenotypes. In a prospective substudy, pre-treatment CTC luminal-B-like phenotype was associated with early progression on 177Lu-PSMA-617.
High-dose methotrexate, ibrutinib, and temozolomide in the treatment of newly diagnosed primary CNS lymphoma: a multicenter, prospective phase-II study
Authors: Yan Gao, Liqin Ping, Changguo Shan, He Huang, Zhiming Li, Hui Zhou, Mingyao Lai, Linbo Cai, Bing Bai, Cheng Huang, Haoqing Chen, Xiaoyu Hong, Xiaoxiao Wang, Huiqiang Huang
Journal: Blood Cancer Discovery (2025)

Genetic alterations of chronic active B-cell receptor signaling often occur in primary central nervous system lymphoma (PCNSL). We conducted a phase-II trial of high-dose methotrexate plus ibrutinib and temozolomide (MIT) in the treatment of newly diagnosed PCNSL. A total of 35 patients were enrolled, with 33 patients included in the analysis. The best overall response rate was 93.9% and complete response rate was 72.7% for induction therapy. The 2-year progression-free survival (PFS) and overall survival were 57.6% (95%CI: 49.0-66.2) and 84.8% (95%CI: 78.6-91.0). The incidence of grade ≧ 3 adverse events was 27.3% (10/33). Mutations in PIM1, MYD88, BTG2, and CD79B were most frequent among 475 genes tested by targeted sequencing of tumor and CSF samples at baseline. The consistency of ctDNA clearance from CSF/plasma and complete response on imaging were observed. Patients with clearance of ctDNA from CSF after two cycles achieved longer PFS (p = 0.044).
Circulating Tumor DNA as Measurable Residual Disease in Aggressive B-Cell Lymphoma
Authors: Mark Roschewski, Dan L. Longo, James O. Armitage
Journal: JAMA Oncology (2025)

Importance Achieving remission is the first step toward a cure in treating aggressive B-cell lymphomas. Radiographic imaging, such as fluorodeoxyglucose–positron emission tomography/computed tomography scans are the current standard to define remission at the end of therapy but lack specificity for lymphoma and cannot detect disease at the molecular level. Identifying measurable residual disease with ultrasensitive detection of circulating tumor DNA potentially offers the possibility of improving clinical outcomes. Observations Early studies of circulating tumor DNA in aggressive B-cell lymphomas showed a strong association with overall tumor burden, and baseline quantitative levels are associated with clinical outcomes after frontline chemotherapy. Next-generation sequencing methods that detect lymphoma-relevant genetic aberrations in circulating tumor DNA can also be used for noninvasive genotyping that strongly mirror tissue biopsies. Rapid changes in circulating tumor DNA dynamics after 1 or 2 cycles of frontline chemotherapy or within weeks of treatment with chimeric antigen receptor T-cell salvage therapy are also highly prognostic. Although serial monitoring of circulating tumor DNA can detect molecular relapse 3 to 6 months before clinical relapse, improved analytical thresholds are required to detect measurable residual disease at a singular point at the end of therapy. Modern advances in circulating tumor DNA methods now allow for the reliable detection of measurable residual disease, with an analytical detection threshold of 1 in 1 million cell-free DNA molecules. Conclusions and Relevance The results of this review suggest that modern ultrasensitive methods of detecting circulating tumor DNA may improve the current definition of remission in aggressive B-cell lymphomas. Incorporating circulating tumor DNA at the end of therapy assessment identifies patients who do not require surveillance monitoring and introduces paradigms of treating measurable residual disease within clinical trials. Practical barriers, including standardization of collection, availability, turnaround times, and cost, remain hurdles preventing widespread implementation into clinical practice.
Outcomes of Glaucoma Referrals in Adults Aged 18 to 40 Years
Authors: Tanner Frediani, Kristy Yoo, Austin Cho, Jennifer Louie, Kent Nguyen, Grace Richter, John Shan, Benjamin Y. Xu
Journal: JAMA Network Open (2025)

Importance While early detection of glaucoma is vital to prevent irreversible vision loss, there are sparse data on the effectiveness of glaucoma referrals and methods to establish evidence-based referral guidelines in large, diverse populations. Objective To assess the prevalence and risk factors for diagnosed glaucoma and loss to follow-up among adult patients aged 18 to 40 years after a new diagnosis of referable glaucoma (ie, with glaucoma or suspected glaucoma). Design, Setting, and Participants This retrospective cohort study included patients aged 18 to 40 years presenting to Kaiser Permanente Southern California, a large managed health care system, for first-time eye examinations between January 1, 2013, and December 31, 2018. Data analysis occurred between September 2022 and August 2024. Main Outcomes and Measures The primary outcome was glaucoma diagnosed within 2 years of the first eye examination. The secondary outcome was the loss to follow-up, defined as failure to receive a glaucoma evaluation with visual field or optical coherence tomography testing within 2 years. Results The cohort included 292 453 patients aged 18 to 40 years who underwent first-time eye evaluations (mean [SD] age, 29.8 [6.4] years). Among 12 050 identified patients with referable glaucoma (52.3% female), 6827 (56.7%) completed glaucoma evaluations, of whom 563 (8.2%) were diagnosed with glaucoma (344 [61.1%] with open angle, 28 [5.0%] with angle closure, 84 [14.9%] with secondary glaucoma, and 107 [19.0%] with unspecified glaucoma). On multivariable analysis, male sex (odds ratio [OR], 1.55 [95% CI, 1.07-2.27]), higher intraocular pressure (IOP) (OR, 1.19 [95% CI, 1.15-1.23] per 1 mm Hg), and greater cup-disc ratio (CDR) (OR, 1.53 [95% CI, 1.34-1.75] per 0.1 unit) were associated with greater odds of glaucoma. Dichotomized age, IOP, and CDR models stratified 51 of 1613 patients (3.2%) into the low-risk group and 202 of 1477 patients (13.7%) into the high-risk group. Being younger than 32 years and having an IOP less than 18 mm Hg and a CDR less than 0.7 yielded a negative predictive value of 98.2% for a glaucoma diagnosis. Conclusions and Relevance In this cohort study, the diagnostic yield of glaucoma referrals was low among adults aged 18 to 40 years with first-time eye examinations. A simple risk-stratification strategy could help identify individuals with low and high risks of developing glaucoma, and adoption of evidence-based risk stratification and referral guidelines by health care systems and clinicians could improve equity of glaucoma care and use of eye-care resources.
Can Poets Really Name All the Flowers?
Authors: Thomas Albert
Journal: JAMA (2025)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors JAMA+ AI Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2025 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Trends in Psychiatrist-Led Care for Medicare Part B Enrollees
Authors: John L. Havlik, Syed Wahid, Kelsey C. Priest, Lydia Ososanya, Marissa Igunbor, Keith Humphreys
Journal: JAMA Network Open (2025)

Importance The rising incidence of mental illness in the US underscores the need for timely access to psychiatric care, especially for vulnerable populations such as older adults and individuals with mental and physical disabilities who receive Medicare. Objective To assess changes in the number and proportion of active psychiatrists providing professional services to traditional Medicare Part B enrollees from 2014 to 2022. Design, Setting, and Participants This repeated cross-sectional study of Medicare Part B enrollees used publicly available data (for January 1, 2014, through December 31, 2022) from the Centers for Medicare &amp;amp;amp; Medicaid Services and the Kaiser Family Foundation. Data from all traditional Medicare Part B enrollees in all 50 states and the District of Columbia were analyzed. Main Outcomes and Measures Primary outcomes included changes in (1) the proportion of active psychiatrists billing traditional Medicare and (2) the number of psychiatrists providing care relative to the number of Medicare Part B enrollees nationally, regionally, and by state. Results The study population comprised 291 748 472 Medicare Part B enrollee-years (33 042 936 in 2014: 5 800 903 [17.6%] eligible due to disability alone and 27 242 030 [82.4%] eligible due to age). From 2014 to 2022, the number of Medicare Part B enrollees decreased by 3 497 942 enrollee-years (10.6%), while the number of psychiatrists submitting more than 10 claims to Medicare Part B decreased by 3772 (16.8%). The nationwide proportion of professionally active psychiatrists submitting claims to Medicare Part B for professional services during this period declined from 22 409 of 50 416 (44.4%) in 2014 to 18 637 of 56 492 (33.0%) in 2022 ( P &amp;amp;lt; .001 on univariable regression). From 2014 to 2022, state-level changes in Medicare Part B–serving psychiatrists per enrollee ranged from a 31.7% increase in Alabama (from 36.5 to 48.1 psychiatrists per 100 000 enrollees) to a 67.8% decrease in Wyoming (from 42.9 to 13.8 psychiatrists per 100 000 enrollees). Every state and district assessed saw a decrease in the percentage of active psychiatrists who billed Medicare Part B for professional services over the study period. Conclusions and Relevance In this study of Medicare Part B acceptance among active US psychiatrists, declining acceptance of Medicare Part B for professional services among psychiatrists was observed nationally and across all states. During a time of psychiatrist workforce growth, the number of psychiatrists accepting traditional Medicare decreased, indicating potential challenges in providing equitable access to psychiatric care.
Time to Act on a Growing Public Health Threat—Evidence of Elevated Mortality in Cannabis Use Disorder
Authors: Laura J. Bierut, Fang Fang
Journal: JAMA Network Open (2025)

The facts are clear: cannabis is addictive, its use is on the rise, and those affected by cannabis use disorder face a heightened risk of premature death. It is time to confront this public health crisis head-on.
Changes in Young Adult Handgun Carrying in the US
Authors: Max A. Halvorson, Margaret R. Kuklinski, Emma Gause, Julia P. Schleimer, Heather F. Terral, Elizabeth H. Weybright, Sabrina Oesterle, Ali Rowhani-Rahbar
Journal: JAMA Network Open (2025)

This cohort study evaluates changes in characteristics of young aduts who carried handguns from 2019 to 2021.
Public Understanding of Risk and Benefit of Mifepristone
Authors: Tamar Krishnamurti, Gianna White, Barry Dewitt, Elizabeth Mosley, Baruch Fischhoff
Journal: JAMA Network Open (2025)

This randomized clinical trial investigates whether a 1-page information sheet proposed by the US Food and Drug Administration (FDA) can provide patients with sufficient information to use mifepristone safely and effectively.
Recurrent respiratory papillomatosis in adults with lower respiratory tract involvement: a retrospective study of the OrphaLung and GETIF networks
Authors: Romy Ratsihorimanana, Thomas Maitre, Matthieu Dusselier, Minh Triet Ngo, Gilles Mangiapan, Clément Fournier, Arnaud Bourdin, Stephane Jouneau, Maroun Matar, Nicolas Favrolt, Thomas Egenod, Jean Michel Vergnon, Delphine Wermert, Jean François Boitiaux, Raphael Borie, Raffaele Caliandro, Olivia Freynet, Valérie Gounant, Julie Mankikian, Juliette Camuset, Alexandre Elabbadi, Antoine Parrot, Julien Calvani, Marc Fortin, Nicolas Guibert, Vincent Cottin, Jacques Cadranel
Journal: European Respiratory Journal (2025)

Recurrent respiratory papillomatosis (RRP) is a rare respiratory disease primarily caused by chronic human papillomavirus (HPV) infection of serotypes 6 and 11. It manifests in childhood (juvenile-onset recurrent respiratory papillomatosis (JoRRP)) and adulthood (adult-onset recurrent respiratory papillomatosis (AoRRP)), leading to progressive obstruction by papillomas in the upper airway and occasionally in the lower respiratory tract (LRT), including the lungs, with a potential for malignant transformation. This study aimed to delineate the characteristics of JoRRP and AoRRP with LRT involvement in adulthood. A multicentre French-speaking cohort study was conducted, coupled with a comprehensive literature review of clinical, histological, therapeutic and prognostic features associated with RRP with LRT involvement. Among the 122 cases of RRP with LRT involvement analysed, 55 (45%) had JoRRP and 67 (55%) had AoRRP. The mean age at diagnosis was 4 years for JoRRP and 54 years for AoRRP. Ear, nose and throat involvement was observed in all JoRRP cases and in 34 AoRRP cases (51%). Lung involvement occurred in 47 JoRRP cases (85%) and in 10 AoRRP cases (15%). Malignant transformation to squamous cell carcinoma in the trachea (n=6) or lung (n=36) was observed in 42 patients (34%). Factors associated with lung involvement included JoRRP, repeated debulking and malignant transformation; the only factor associated with malignant transformation was lung involvement. Overall mortality was 16%, with JoRRP, lung involvement and malignant transformation identified as risk factors for death. This study highlights the prevalence of lung involvement and malignant transformation in RRP with LRT involvement and advocates for targeted screening measures and preventive therapeutic strategies.
First Assessment of Photon-Counting CT for Virtual Bronchoscopic Navigation
Authors: Marcel Opitz, Faustina Funke, Kaid Darwiche, Sebastian Zensen, Marko Frings, Luca Salhöfer, Johannes Haubold, Michael Forsting, Fabian Doerr, Servet Bölükbas, Filiz Oezkan, Jane Winantea, Hanna Zellerhoff, Rüdiger Karpf-Wissel, Johannes Wienker, Dirk Westhölter, Matthias Welsner, Christian Taube, Erik Büscher
Journal: European Respiratory Journal (2025)
YAP/TAZ are Crucial Regulator of Macrophage-mediated Pulmonary Inflammation and Fibrosis after Bleomycin-induced Injury
Authors: Masum M Mia, Siti Aishah Binte Abdul Ghani, Dasan Mary Cibi, Hanumakumar Bogireddi, Uthayanan Nilanthi, Ashwatthaman Selvan, Wai Shiu, Fred Wong, Manvendra K Singh
Journal: European Respiratory Journal (2025)

Pulmonary fibrosis (PF) is the most prevalent and severe form of end-stage interstitial lung disease. Macrophages are crucial players in inflammation-induced PF, but the mechanisms driving macrophage polarization and their specific roles in PF pathogenesis remain poorly understood. Here, we demonstrate that both YAP and TAZ are activated in lung macrophages from patients with PF as well as in mice with bleomycin-induced PF. Myeloid-specific Yap/Taz deletion resulted in reduced recruitment of monocyte-derived alveolar macrophages (Mo-AMs), impaired inflammatory responses, decreased PF, and enhanced alveolar epithelial cell regeneration following bleomycin treatment. Conversely, the expression of a constitutively active YAP mutant (YAP 5SA ) exacerbated bleomycin-induced PF by increasing Mo-AM recruitment, elevating expression of proinflammatory and profibrotic markers, and impairing alveolar epithelial cell regeneration. We demonstrate that YAP/TAZ-CCL2 signaling plays a crucial role in bleomycin-induced PF, as blocking CCL2 with a neutralizing antibody effectively abrogated the YAP 5SA -induced recruitment of Mo-AMs, inflammatory and fibrotic responses. Additionally, we reveal that the YAP/TAZ-MBD2-TGFβ1-pSMAD2 signaling axis is crucial not only for profibrotic macrophage polarization but also for their crosstalk with lung fibroblasts, driving the fibroblast-to-myofibroblast transition. Collectively, these findings suggest that targeting aberrant YAP/TAZ activity to modulate inflammatory and fibrotic response could be a promising strategy for the prevention and treatment of PF.
SegmentAnyBone: A universal model that Segments Any Bone at any location on MRI
Authors: Hanxue Gu, Roy Colglazier, Haoyu Dong, Jikai Zhang, Yaqian Chen, Zafer Yildiz, Yuwen Chen, Lin Li, Jichen Yang, Jay Willhite, Alex M Meyer, Brian Guo, Yashvi Atul Shah, Emily Luo, Shipra Rajput, Sally Kuehn, Clark Bulleit, Kevin A Wu, Jisoo Lee, Brandon Ramirez, Darui Lu, Jay M Levin, Maciej A Mazurowski
Journal: Medical Image Analysis (2025)
Interleukin-37 attenuates aortic valve lesions by inhibiting m6A-mediated IRAK-M degradation
Authors: Gaopeng Xian, Rong Huang, Dongtu Hu, Minhui Xu, Yangchao Chen, Hao Ren, Dingli Xu, Qingchun Zeng
Journal: Cardiovascular Research (2025)

Abstract Aims Calcific aortic valve disease (CAVD) has become an increasingly important global medical problem without effective pharmacological intervention. Accumulating evidence indicates that aortic valve calcification is driven by inflammation. Interleukin-1 receptor-associated kinase M (IRAK-M) is a well-known negative regulator of inflammation, but its role in CAVD remains unclear. Methods and Results Here, we stimulated aortic valve interstitial cells (AVICs) with low-dose lipopolysaccharide (LPS) to mimic the inflammatory response in aortic valve calcification and observed the expression pattern of IRAK-M. Furthermore, we generated IRAK-M-/- mice to explore the effect of IRAK-M deficiency on the aortic valve in vivo. Additionally, overexpression and knockdown experiments were performed to verify the role of IRAK-M in AVICs. MeRIP‒qPCR was used to detect the N6-methyladenosine (m6A) level of IRAK-M, and recombinant interleukin (IL)-37-treated AVICs were used to determine the regulatory relationship between IL-37 and IRAK-M. We found that IRAK-M expression was upregulated in the early stages of inflammation as part of a negative feedback mechanism to modulate the immune response. However, persistent inflammation increased overall m6A levels, ultimately leading to reduced IRAK-M expression. In vivo, IRAK-M-/- mice exhibited a propensity for aortic valve thickening and calcification. Overexpression and knockdown experiments showed that IRAK-M inhibited inflammation and osteogenic responses in AVICs. In addition, IL-37 restored IRAK-M expression by inhibiting m6A-mediated IRAK-M degradation to suppress inflammation and aortic valve calcification. Conclusions Our findings confirm that inflammation and epigenetic modifications synergistically regulate IRAK-M expression. Moreover, IRAK-M represents a potential target for mitigating aortic valve calcification. Meanwhile, IL-37 exhibited inhibitory effects on CAVD development both in vivo and in vitro, giving us hope that CAVD can be treated with drugs rather than surgery.
A Roadmap for Disaster Risk Reduction and Management in Kidney Care
Authors: Shaifali Sandal, Saly El Wazze, Diya Nijjar, Isabelle Ethier, Alessia N. Paparella, Lindsay Hales, S. Neil Finkle, Vivekanand Jha, Caroline Stigant
Journal: Journal of the American Society of Nephrology (2025)

Background: Natural, technological and other disasters cause significant human suffering, and kidney patients are uniquely vulnerable. The safe provision of kidney replacement therapies necessitates the consistent provision of resources. Robust disaster risk reduction and management (DRRM) can mitigate risks associated with resource disruption. Individual kidney care programs may benefit from an organized approach to developing context-specific protocols. We aimed to synthesize contemporary literature in kidney care to create a roadmap in DRRM. Methods: We conducted a scoping review followed by a content analysis using the Framework Method. Literature that focused on lessons learned and proposed strategies or recommendations in DRRM was eligible. We contextualized this roadmap within the domains of disaster preparedness, response, and recovery. Results: Of 3,973 titles and abstracts screened, 52 articles were included. We developed the following roadmap: 1) the ‘ABC 4 s’ of disaster preparedness: Assess needs, risks, and vulnerabilities (regional risks, patients at risk); Build a task force network; Capacity building (tangible resources, intangible resources, monetary considerations, transportation); Communication (network and protocol, patients’ medical and dialysis information, contact information of all stakeholders, inclusive approach, reliable medium); Coaching (patients, caregivers, healthcare personnel, reinforce and repeat); Contingency planning (surge capacity, rationing care, resource distribution); and Strategic partnerships. 2) the ‘DIAL’ response: Damage and scope assessment; Initiate action plan (choose the plan, apply preparedness tenets, implications for receiving facilities); Appraise the action plan regularly (reassess, maintain ethical standards, address psychosocial needs); and Liaise, engage and update. 3) the ‘ARC’ to recovery: Assess damage; Return to the (new) norm; and Collect data to evaluate, improve, and share. Conclusions: We propose a roadmap to disaster preparedness, response and recovery that can guide individual kidney care programs globally to develop context-specific protocols aimed at building capacities and facilitating processes toward DRRM.
Low miR-224-5p in exosomes confers colorectal cancer 5-FU resistance by upregulating S100A4
Authors: Yan-Yan Yan, Zhuo-Fen Deng, Xing-Tao Wu, Yu Lu, Zhuang-Yan Zhu, Qing Wen, Wei Zhang, Hai-Yan Zhang, Xin-Zhu Chen, Yu-Song Wu, Xue-Bing He, Zi-Ang Ma, Jin-Shuo Li, Hong Bi, Jian-Ye Zhang
Journal: Drug Resistance Updates (2025)