tbuckley/cabot-search huggingface dataset:
Thalidomide can effectively prevent relapse in IgG4-related disease outweighing its side effects: a multicentre, randomised, double-blinded, placebo-controlled study
Authors: Yu Chen, Cong Ye, Pingting Yang, Wen Zhang, Lie Dai, Wei Wei, Rui Wu, Shuang Ding, Lefeng Chen, Xiuhua Wu, Jun Zhao, Chengqian Liao, Wei Sun, Hisanori Umehara, Shaozhe Cai, Lingli Dong
Journal: Annals of the Rheumatic Diseases (2025)

To investigate the effects of thalidomide in preventing disease relapse with 'zero' glucocorticoids (GCs) usage in IgG4-related disease (IgG4-RD). This was a multicentre, randomised, double-blinded, placebo-controlled study, in which eligible patients in disease active status were randomised into 2 groups (group 1: GCs+Thalidomide; group 2: GCs+Placebo) at a 1:1 ratio. The primary outcome of this trial was the disease relapse rate at month 12, whereas the secondary outcomes were the disease remission rate at month 12 and the incidence of adverse events (AEs). A total of 60 patients were randomised, and 57 patients (GCs+Thalidomide: 29; GCs+Placebo: 28) finished the study per protocol. The relapse rates of the GCs+Thalidomide and GCs+Placebo groups at month 12 were 13.8% and 67.8%, respectively. A 100% response rate was observed in both treatment group, while the remission rates of the GCs+Thalidomide and GCs+Placebo groups were 75.8% and 32.1%, respectively. In total. 49 AEs were recorded in 35 participants, in which 4 were graded as moderate, and 45 were graded as mild. The risk-benefit analysis based on the evaluation of rates of disease relapse and moderate AEs within the 12-month follow-up showed a NNT (number needed to treat) of 2 and a NNH (number needed to harm) of 8 for thalidomide treatment. Thalidomide can effectively prevent relapse in IgG4-RD outweighing its side effects, which indicating that thalidomide can be a potential safe therapeutic option for disease relapse prevention in parallel with steroid sparing in IgG4-RD.
An FDA-approved drug structurally and phenotypically corrects the K210del mutation in genetic cardiomyopathy models
Authors: Ping Wang, Mahmoud Salama Ahmed, Ngoc Uyen Nhi Nguyen, Ivan Menendez-Montes, Ching-Cheng Hsu, Ayman B Farag, Suwannee Thet, Nicholas T Lam, Janaka P Wansapura, Eric Crossley, Ning Ma, Shane Rui Zhao, Tiejun Zhang, Sachio Morimoto, Rohit Singh, Waleed Elhelaly, Tara C Tassin, Alisson C Cardoso, Noelle S Williams, Hayley L Pointer, David A Elliott, James W McNamara, Kevin I Watt, Enzo R Porrello, Sakthivel Sadayappan, Hesham A Sadek
Journal: Journal of Clinical Investigation (2025)

Dilated cardiomyopathy (DCM) due to genetic disorders results in decreased myocardial contractility, leading to high morbidity and mortality rates. There are several therapeutic challenges in treating DCM, including poor understanding of the underlying mechanism of impaired myocardial contractility and the difficulty of developing targeted therapies to reverse mutation-specific pathologies. In this report, we focused on K210del, a DCM-causing mutation, due to 3-nucleotide deletion of sarcomeric troponin T (TnnT), resulting in loss of Lysine210. We resolved the crystal structure of the troponin complex carrying the K210del mutation. K210del induced an allosteric shift in the troponin complex resulting in distortion of activation Ca2+-binding domain of troponin C (TnnC) at S69, resulting in calcium discoordination. Next, we adopted a structure-based drug repurposing approach to identify bisphosphonate risedronate as a potential structural corrector for the mutant troponin complex. Cocrystallization of risedronate with the mutant troponin complex restored the normal configuration of S69 and calcium coordination. Risedronate normalized force generation in K210del patient-induced pluripotent stem cell-derived (iPSC-derived) cardiomyocytes and improved calcium sensitivity in skinned papillary muscles isolated from K210del mice. Systemic administration of risedronate to K210del mice normalized left ventricular ejection fraction. Collectively, these results identify the structural basis for decreased calcium sensitivity in K210del and highlight structural and phenotypic correction as a potential therapeutic strategy in genetic cardiomyopathies.
The N-type calcium channel rises from the ashes
Authors: Maria A. Gandini, Gerald W. Zamponi
Journal: Journal of Clinical Investigation (2025)

Chronic pain is a debilitating condition that affects up to 1.5 billion people globally. Advancing pain management depends on a thorough understanding of the types of pain experienced by patients and the underlying mechanisms driving it. N-type calcium channels play a crucial role as therapeutic targets for managing chronic pain. In this issue of the JCI, Tang et al. introduce C2230, an N-type calcium channel blocker that inhibited CaV2.2 channels during high frequency stimulation with little effect on other ion channels in the pain pathway across multiple models. C2230 offers a promising analgesic for use in therapeutic intervention.
Liver transplantation for cholestatic liver diseases: Timing &amp; disease recurrence
Authors: Guilherme Grossi Lopes Cançado, Maya Deeb, Aliya Fatemah Gulamhusein
Journal: Hepatology (2025)

Though rare, primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) account for 8-14% of liver transplants (LT) in North America and Europe and the journey of these patients across the peri-transplant period is unique. Equitable access to LT is an important challenge, as the MELD score and its derivatives inadequately reflect the morbidity and mortality related to these diseases failing to capture disease-specific complications, such as recurrent cholangitis, malignancy risk, severe portal hypertension, and sarcopenia. The waitlist experience is high-risk, prolonged and a distinct form of “MELD purgatory”. Once barriers to access are overcome, post-transplant outcomes are generally excellent, however disease recurrence affects 15-35% at 5 to 10 years post-LT with increasing rates over time. Diagnosing recurrence is challenged by a broad differential for post-transplant biliary injury, and the risk factors for its development remain controversial. While post-LT use of ursodeoxycholic acid in PBC is clearly beneficial, no effective medical therapy currently exists for recurrent PSC. A heightened focus on control of inflammatory bowel disease activity is critical as a potentially important modifiable risk factor for rPSC, including with escalation of medical therapy as needed and timely colectomy when indicated. This review outlines the journey for patients with PBC and PSC, from transplant listing to post-transplant management, emphasizing the need for unique and tailored approaches to optimize outcomes and long-term survival.
Letter to the editor: Alcohol a confounding factor in assessment of resmetirom therapy
Authors: Aleksander Krag, Nikolaj Torp, Mads Israelsen
Journal: Hepatology (2025)

1Centre for Liver Research, Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark 2Institute of Clinical Research, University of Southern Denmark, Odense, Denmark Correspondence Odense Universitetshospital, Department of medical, gastroenterology and hepatology; Syddansk Universitet, Department of Clinical Research. Email: [email protected]
Letter to the Editor: Resmetirom therapy for metabolic dysfunction-associated steatotic liver disease: October 2024 updates to AASLD practice guidance
Authors: Jay H. Hoofnagleand, Averell H. Sherker
Journal: Hepatology (2025)

Liver Disease Research Branch, Division of Digestive Diseases and Nutrition, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD Correspondence Room 6003, 6707 Democracy Blvd, Bethesda, MD 20892. Email: [email protected]
Standardized Definitions of Changes in Kidney Function in Trials of Heart Failure
Authors: Anuradha Lala, Steven Coca, Jason Feinman, Carine E Hamo, Mona Fiuzat, William T Abraham, Christopher O'Connor, JoAnn Lindenfeld, James Januzzi, Isabella Cavagna, John R Teerlink, Mark J Sarnak, Chirag R Parikh, Wendy McCallum, Marvin A Konstam, Maria Rosa Costanzo
Journal: Journal of the American College of Cardiology (2025)
Genes Associated With Hypertrophic Cardiomyopathy
Authors: Sophie Hespe, Amber Waddell, Babken Asatryan, Emma Owens, Courtney Thaxton, Mhy-Lanie Adduru, Kailyn Anderson, Emily E Brown, Lily Hoffman-Andrews, Elizabeth Jordan, Katherine Josephs, Megan Mayers, Stacey Peters, Fergus Stafford, Richard D Bagnall, Lucas Bronicki, Bert Callewaert, C Anwar A Chahal, Cynthia A James, Olga Jarinova, Andrew P Landstrom, Elizabeth M McNally, Brittney Murray, Laura Muiño-Mosquera, Victoria Parikh, Chloe Reuter, Roddy Walsh, Bess Wayburn, James S Ware, Jodie Ingles
Journal: Journal of the American College of Cardiology (2025)
The tumor suppressor role and epigenetic regulation of 15-hydroxyprostaglandin dehydrogenase (15-PGDH) in cancer and tumor microenvironment (TME)
Authors: SubbaRao V Tulimilli, Medha Karnik, Anjali Devi S Bettadapura, Olga A Sukocheva, Edmund Tse, Gowthamarajan Kuppusamy, Suma M Natraj, SubbaRao V Madhunapantula
Journal: Pharmacology & Therapeutics (2025)
BBPs-Functionalized Tetrahedral Framework Nucleic Acid Hydrogel Scaffold Captures Endogenous BMP-2 to Promote Bone Regeneration
Authors: Wumeng Yin, Xingyu Chen, Long Bai, Yong Li, Wen Chen, Yueying Jiang, Yutian He, Yichen Yang, Yunfeng Lin, Taoran Tian, Xiaoxiao Cai
Journal: Biomaterials (2025)
Gambling Harms in the Era of Legal Gambling Expansion—A Growing Health Problem
Authors: Daria Ukhova, Rachel Volberg
Journal: JAMA Internal Medicine (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 Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Internal Medicine journal
Suicide and Suicidal Ideation Among Survivors of Childhood Cancer
Authors: Jia Yang Tan, Genevieve Ge, Chen Ee Low, Sounak Rana, Tessa Ying Zhen Tan, Nicholas Bao Jun Fang, Joie Yi Yun Teo, Yu Ting Yap, Chun En Yau, Ainsley Ryan Yan Bin Lee, Cyrus Su Hui Ho
Journal: JAMA Network Open (2025)

Importance Reliable estimates of the prevalence and risk of suicide and suicidal ideation (SI) among childhood cancer survivors (CCSs) are crucial in informing efforts to address this issue. Objective To systematically evaluate the prevalence and risk of suicide and SI among CCSs. Data Sources A literature search was conducted of PubMed, Embase, Cochrane Library, and PsycINFO from January 1, 2000, to November 17, 2024. Study Selection All noncontrolled and controlled studies that evaluated the prevalence and risk of suicide and SI and drew comparisons between CCSs and their counterparts. Studies including participants older than 25 years, no reported outcomes, case studies, case reviews, and review articles were excluded. Data Extraction and Synthesis The Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guideline was followed with prospective PROSPERO registration. Prevalence was pooled for single-arm studies. Relative risk ratio (RR) was pooled for double-arm studies. Metaprop was used to meta-analyze the prevalence of suicide and SI under a generalized linear mixed model. For dichotomous outcomes, meta-analyses were performed to compute the RR of the psychological outcome compared with controls. Main Outcomes and Measures Prevalence of suicide and SI, the RR of suicide and SI among CCSs compared with controls, and risk factors associated with suicidality outcomes. Results From 531 records, 16 studies were included. Studies on suicide included 148 869 participants and studies on SI included 20 140 participants. The prevalence of suicide among CCSs was 0.30% (0.13%-0.69%) and of SI was 9% (95% CI, 7%-11%). There was a significantly increased risk of SI among CCSs compared with controls (RR, 1.67 [95% Cl, 1.39-2.01]), but not of suicide (RR, 1.50 [95% CI, 0.63-3.62]). Subgroup analyses suggested that prevalence of SI is much higher during the active cancer period than years after (proportion, 0.14 [95% CI, 0.10-0.19] vs 0.08 [95% CI, 0.06-0.09]). The systematic review identified preexisting mental illness, poor physical health, older age, male sex, and being single as risk factors associated with suicidality outcomes. Conclusions and Relevance In this meta-analysis of suicide and SI among CCSs, the risk of suicide was no different among CCSs compared with controls, but CCSs had a higher risk of SI. Future studies are needed to explore suicidality outcomes among CCSs to guide targeted support policies.
Diagnosis and Management of Monoclonal Gammopathy of Undetermined Significance
Authors: Yuxin Liu, Anna L. Parks
Journal: JAMA Internal Medicine (2025)

Importance Nearly 5% of adults have the precursor malignant condition monoclonal gammopathy of unknown significance (MGUS). Management centers on differentiating MGUS from more serious conditions to determine additional diagnostic testing, monitoring, and potential therapy. Observations MGUS is defined by the absence of end-organ damage or symptoms, a small amount of monoclonal immunoglobulin (M protein), and low volume of plasma cells. MGUS must be distinguished from overt malignant diseases like multiple myeloma (MM), immunoglobulin light-chain (AL) amyloidosis, and monoclonal gammopathy of clinical significance (MGCS), all of which cause organ damage or symptoms. Although testing for M proteins is often prompted by clinical findings (eg, osteoporosis or autoimmune disease), recent evidence from screened populations suggests that previous MGUS disease associations were likely overestimated and that testing for M proteins should be reserved for when malignant disease or MGCS is suspected. Risk of progression to malignant disease ranges from 0.5% to 1%, meaning most patients have indolent disease. Guideline-concordant management of MGUS is determined by predicted risk of progression to malignant disease, which depends on subtype of immunoglobulin, M protein concentration, and free light chain ratio. Patients with low-risk MGUS can safely defer bone marrow biopsy and advanced imaging, and should undergo periodic laboratory monitoring. Intermediate- and high-risk MGUS should trigger bone marrow biopsy and bone imaging to detect overt MM and shorter monitoring intervals. Advanced molecular testing may improve on current risk stratification to target monitoring and treatment to those with highest risk of malignant progression and avoid overtreatment of those with low-risk disease. Management will also be informed by results of several clinical trials to clarify the risks and benefits of screening, optimal monitoring strategy, predictors of progression, and potential preventive or curative therapies. Conclusions and Relevance Evidence-based management of MGUS currently rests on separating clinically indolent from high-risk precursor disease. Research using novel detection methods, incorporating molecular testing into risk stratification, and evaluating screening, monitoring, and therapeutic or lifestyle interventions has the potential to improve outcomes.
Receipt of Federal Income Support by Eligible Low-Birth-Weight Infants
Authors: Muqi Guo, Michelle Woodford Martin, Nolan M. Kavanagh, Jarvis T. Chen, Jeffrey Hemmeter, Ichiro Kawachi, Margaret Parker, Margaret McConnell
Journal: JAMA Pediatrics (2025)

Importance While many infants with low birth weight (LBW) are eligible for Supplemental Security Income (SSI), more evidence is needed about whether they receive benefits and whether income supports reach infants from the most socioeconomically disadvantaged households. Objective To assess receipt of SSI among LBW-eligible infants (infants eligible due to LBW) and targeting of SSI to LBW and income-eligible infants across county-level measures of socioeconomic disadvantage. Design, Setting, and Participants This cross-sectional study used administrative data from the SSI program, vital records, and the American Community Survey. It included a population-based sample of 185 920 LBW infants born between January 1, 2012, and December 31, 2018, from 482 US counties, with 2003 revised birth certificates, Social Security Administration–defined LBW, and survival of more than 31 days, and born in a county-year with at least 20 LBW infants surviving their first month of life. Analyses were conducted from January 1, 2022, to December 31, 2023. Exposures Three measures of county-level socioeconomic disadvantage: poverty rates, median household income, and completion of postsecondary degrees. Main Outcomes and Measures Receipt of SSI among (1) infants who qualified due to LBW and (2) LBW- and likely income-eligible infants. In addition, whether receipt varied by county-level measures of socioeconomic disadvantage was evaluated using Poisson regression models. Results A total of 185 920 LBW-eligible infants were included in the study. During the study period, the proportion of LBW-eligible infants who received SSI was 0.38 (95% CI, 0.36-0.40). SSI receipt was higher in more disadvantaged counties measured by county poverty rates or median household income. After adjusting income eligibility, the proportion receiving SSI reached 0.65 (95% CI, 0.49-0.86). However, SSI receipt among LBW- and likely income-eligible infants decreased as the level of county socioeconomic disadvantage increased. Conclusions and Relevance In this cross-sectional study, most LBW infants who were eligible for SSI did not receive benefits. Likely income-eligible infants living in socioeconomically disadvantaged counties were covered by SSI at lower levels than those in more advantaged counties. More intensive outreach or reduced application burden may be necessary to ensure equitable access to social safety net programs in socioeconomically disadvantaged communities.
Determinants of Response to Sequential Pembrolizumab with Trastuzumab Plus Platinum/5FU in HER2-positive Gastric Cancer: A Phase II Chemoimmunotherapy Trial
Authors: Sung Hee Lim, Minae An, Hyuk Lee, You Jeong Heo, Byung-Hoon Min, Arnav Mehta, Samuel Wright, Kyoung-Mee Kim, Seung Tae Kim, Samuel J. Klempner, Jeeyun Lee
Journal: Clinical Cancer Research (2025)

Abstract Purpose: Adding pembrolizumab to first-line fluoropyrimidine (5-FU)/platinum chemotherapy plus trastuzumab improves outcomes in advanced HER2+ gastroesophageal adenocarcinomas, but the benefit is largely confined to dual HER2+ and PD-L1+ patients. To assess the contributions of components, we conducted a phase II trial evaluating 5-FU/platinum/trastuzumab and added pembrolizumab in cycle 2 in patients with metastatic HER2+ disease. Patients and Methods: Treatment-naïve patients with advanced HER2+ gastroesophageal cancer underwent a baseline biopsy and received a single dose of 5-FU/platinum with trastuzumab followed by repeat biopsy. Pembrolizumab was added, and a third biopsy was performed after six cycles. The primary endpoint was the objective response rate. Secondary endpoints included progression-free and overall survival. Exploratory biomarker analysis and dynamic changes in HER2 and PD-L1 were prespecified. Results: Sixteen patients were enrolled. The objective response rate was 69%, and the median progression-free survival was 11.9 months. Serial whole-exome, single-cell RNA, T-cell receptor sequencing, and spatial transcriptomics from pretreatment and on-treatment samples revealed early trastuzumab-induced NK cell infiltration in HER2+ tumor beds and an increase in Fc receptor gamma III expression in macrophages, suggesting that trastuzumab directs Fc receptor–mediated antibody-dependent cytotoxicity. This favorable remodeling was enhanced by the addition of pembrolizumab, primarily in PD-L1+ samples. We observed TGF-β signaling in HER2-negative tumor regions, which was associated with nonresponder status. Conclusions: These data highlight the biology of intratumoral heterogeneity and the impact of tumor and immune cell features on clinical outcomes and may partly explain the lesser magnitude of pembrolizumab benefit in HER2+ and PD-L1–negative subgroups.
Growing Health Concern Regarding Gambling Addiction in the Age of Sportsbooks
Authors: Atharva Yeola, Matthew R. Allen, Nimit Desai, Adam Poliak, Kevin H. Yang, Davey M. Smith, John W. Ayers
Journal: JAMA Internal Medicine (2025)

Importance The US Supreme Court decision Murphy v National Collegiate Athletic Association allowed states beyond Nevada to legalize sports betting, including online wagers. How sports betting has evolved and its association with gambling harms has not been studied. Objective To describe how US sports betting evolved after Murphy v National Collegiate Athletic Association and offer insights into the potential health effects of sportsbooks, which are platforms for wagering on sporting events. Exposure Enactment of (1) Murphy v National Collegiate Athletic Association nationally and (2) the opening of retail or online sportsbooks in states. Design, Setting, and Participants In this longitudinal study, aggregate US internet search trends for gambling addiction and wagers on sports were described before and after the emergence of legalized sportsbooks. Main Outcomes and Measures Internet searches per 10 million queries that mentioned gambling and addiction , addic t, anonymous , or hotline (such as gambling addiction hotline ) made to Google from January 1, 2016, through June 30, 2024. Results The number of states with operational sportsbooks increased from 1 during 2017 to 38 during 2024. Total sports wagers increased from $4.9 billion during 2017 to $121.1 billion during 2023, with 94% of wagers during 2023 being placed online. There were 23% (95% CI, 15%-30%) more searches nationally for gambling addiction help-seeking after Murphy v National Collegiate Athletic Association . Massachusetts (47%; 95% CI, 21%-79%), New Jersey (34%; 95% CI, 21%-45%), New York (37%; 95% CI, 26%-50%), and Pennsylvania (50%; 95% CI, 35%-66%) each had more searches than expected after the opening of any sportsbooks in their state. Additional analyses suggest the opening of online, vs retail, sportsbooks corresponded with a larger increase in searches. Conclusions and Relevance The results of this time series study suggest that access to sportsbooks, sports wagers, and potential help-seeking for gambling addiction increased substantially and highlight the need to address the health implications of sportsbooks, including recognition and treatment of gambling problems and their broader societal implications.
Bridging Quality Gaps in Rectal Cancer Care—Lessons From Knowledge Translation Intervention
Authors: Nicole M. Saur, Rahila Essani, Isacco Montroni
Journal: JAMA Network Open (2025)

Erin D. Kennedy, MD, PhD; Amandeep Pooni, MD, MSc; Selina Schmocker, MSc; Carl Brown, MD, MSc; Anthony MacLean, MD; Nancy N. Baxter, MD, PhD; Lara Williams, MD; Marko Simunovic, MD, MPH; Sender Liberman, MDCM; Sébastien Drolet, MD; Katerina Neumann, MD, PhD; Kartik Jhaveri, MD; Richard Kirsch, MBChB, PhD