tbuckley/cabot-search huggingface dataset:
SPRINT Treatment Among Adults With Chronic Kidney Disease From 2 Large Health Care Systems
Authors: Manjula Kurella Tamura, Mengjiao Huang, Jaejin An, Mengnan Zhou, Fang Niu, John J. Sim, Nicholas M. Pajewski, Sarah A. Gaussoin, June Li, Michelle C. Odden, Tara I. Chang, Vivek Charu, Maria E. Montez-Rath
Journal: JAMA Network Open (2025)

Importance It is unclear whether the effects of intensive vs standard blood pressure (BP) targets seen in clinical trials generalize to patients with chronic kidney disease (CKD) encountered in everyday practice due to differences in the distribution of cardiovascular risk factors and coexisting conditions. Objective To evaluate whether the beneficial and adverse effects of intensive vs standard BP control observed in the Systolic Blood Pressure Intervention Trial (SPRINT) are transportable to a target population of adults with CKD in clinical practice. Design, Setting, and Participants This comparative effectiveness study identified 2 populations with CKD who met the eligibility criteria for SPRINT between January 1 and December 31, 2019, in the Veterans Health Administration (VHA) and Kaiser Permanente of Southern California (KPSC). Baseline covariate, treatment, and outcome data from SPRINT were combined with covariate data from these populations to estimate the treatment effects in the target population, applying models that estimated outcomes using distributions in the trial. Analysis was performed between May 2023 and October 2024. Main Outcomes and Measures The main outcomes were major cardiovascular events, all-cause death, cognitive impairment, CKD progression, and adverse events at 4 years. Results A total of 85 938 patients (mean [SD] age, 75.7 [10.0] years; 81 628 [95.0%] male) from the VHA and 13 983 patients (mean [SD] age, 77.4 [9.6] years; 5371 [38.4%] male) from KPSC were included. Compared with 9361 SPRINT participants (mean [SD] age, 67.9 [9.4] years; 6029 [64.4%] male), these patients were older, had less prevalent cardiovascular disease, higher albuminuria, and used more statins. The associations of intensive vs standard BP control with major cardiovascular events, all-cause death, and adverse events were transportable from the trial to the VHA and KPSC populations; however, the trial’s effects on cognitive and CKD outcomes were not transportable in 1 or both clinical populations. Intensive vs standard BP treatment was associated with lower absolute risks for major cardiovascular events at 4 years by 5.1% (95% CI, −9.8% to 3.2%) in the VHA population and 3.0% (95% CI, −6.3% to 0.3%) in the KPSC population and higher risks for adverse events by 1.3% (95% CI, −5.5% to 7.7%) in the VHA population and 3.1% (95% CI, −1.5% to 8.3%) in the KPSC population. Conclusions and Relevance In this comparative effectiveness study, the reduction in fatal and nonfatal cardiovascular end points and the increase in adverse events observed in SPRINT were largely transportable to trial-eligible CKD populations from clinical practice, suggesting benefits of implementing intensive BP targets.
Severe Maternal Morbidity Among Pregnant People With Opioid Use Disorder Enrolled in Medicaid
Authors: Samantha G. Auty, Austin B. Frakt, Paul R. Shafer, Michael D. Stein, Sarah H. Gordon
Journal: JAMA Network Open (2025)

Importance Pregnant people with opioid use disorder (OUD) are at high risk for potentially avoidable maternal morbidity. The majority of pregnant people with OUD receive health insurance through state Medicaid programs, but there is little comprehensive data on the burden of severe maternal morbidity (SMM)—a composite measure of adverse maternal health outcomes—among this high-risk group. Objective To estimate rates of SMM among Medicaid-enrolled pregnant people with OUD from 2016 to 2018. Design, Setting, and Participants Using the Transformed Medicaid Statistical Information System Analytic Files, this cross-sectional study identified 96 309 pregnant people with OUD enrolled in Medicaid in 47 states with 108 975 deliveries between March 1, 2016, and November 16, 2018. Data were analyzed from August 1, 2023, to September 1, 2024. Main Outcome and Measures SMM was identified using International Statistical Classification of Diseases and Related Health Problems, Tenth Revision diagnosis and procedure codes for 20 relevant conditions and was measured per 10 000 live births nationally and by state. Rates of SMM were also stratified by the timing of Medicaid enrollment before delivery. Results From 2016 to 2018, 96 309 Medicaid enrollees had a diagnosis of OUD before a live birth (108 975 deliveries). The mean (SD) age of Medicaid-enrolled pregnant people with OUD was 28.8 (5.0) years. The mean (SD) rate of OUD among pregnant people enrolled in Medicaid was 324.8 (260.9) per 10 000 live births across states. Among this group, the mean (SD) unadjusted rate of SMM excluding blood transfusions among those with OUD was 292.1 (112.3) per 10 000 live births, with these rates varying substantially across states, from 101.0 per 10 000 live births in South Dakota to 682.2 per 10 000 live births in California. Adjustment for enrollee characteristics and comorbidities did not meaningfully alter the estimated rate of SMM (305.6 [95% CI, 245.2-408.2] per 10 000 live births). Rates of SMM generally increased with decreased durations of Medicaid enrollment. Conclusions and Relevance This cross-sectional study of pregnant people enrolled in Medicaid found that the rate of OUD among this group was more than twice as high as previous estimates. Pregnant people with OUD face a disproportionately high risk of SMM, particularly those who enroll in Medicaid later in pregnancy. Targeted interventions that facilitate early Medicaid enrollment and coverage continuity may be needed to reduce the burden of adverse outcomes in this group.
Exploring Surgeon Preference in the Treatment of Degenerative Lumbar Spondylolisthesis
Authors: Nathan J. Winans, Farhan Khan, Andrew K. Chan
Journal: JAMA Network Open (2025)

Andreas Seip, MD; Christian Hellum, MD, PhD; Morten Wang Fagerland, PhD; Tore Solberg, MD, PhD; Jens Ivar Brox, MD, PhD; Kjersti Storheim, PT, PhD; Erland Hermansen, MD, PhD; Clemens Weber, MD, PhD; Helena Brisby, MD, PhD; Hasan Banitalebi, MD, PhD; Håvard Furunes, MD, PhD; Kari Indrekvam, MD, PhD; Inger Ljøstad; Ivar Magne Austevoll, MD, PhD
Macronutrients in Human Milk Exposed to Antidepressant and Anti-Inflammatory Medications
Authors: Essi Whaites Heinonen, Kerri Bertrand, Christina Chambers
Journal: JAMA Network Open (2025)

Importance The association between maternal medications and the macronutrient composition of human milk has not been studied. Objective To compare macronutrient levels in milk samples from mothers treated with long-term medications with samples from untreated healthy and disease-matched control mothers (DMCs). Design, Setting, and Participants A cross-sectional study using samples collected between October 2014 and January 2024 from breastfeeding mothers in the US and Canada invited to participate to the Mommy’s Milk Human Milk Research Biorepository at the University of California, San Diego. Of 3974 samples from unique individuals in the biorepository, 310 were from mothers treated with 1 of 4 categories of medications, 151 from DMCs with the same underlying disorders, and 73 from healthy untreated mothers, frequency matched on infant age and sex. Of these, 150 were excluded because they had more than 1 medication exposure or were outliers. Data were analyzed from March to June 2024. Exposures Continuous treatment with selective serotonin reuptake inhibitors (SSRIs), monoclonal antibodies (MABs), systemic steroids, and other anti-inflammatory drugs (ADs) in the 14 days before milk sample collection. Main Outcomes and Measures Levels of protein, fat, carbohydrate, and total energy were measured with SpectraStar 2400 near infrared analyzer and compared across groups with analysis of covariance adjusted for infant and maternal age, parity, maternal body mass index, infant sex, exclusive breastfeeding, feeding frequency, collection time, maternal cannabis use, and occupation. Results A total of 384 samples were collected; 194 infants (50.5%) were female; the mean (SD) age of the maternal cohort was 33.5 (4.4) years, and infant age at collection was 6.6 (5.4) months. Mean (SD) protein levels were 15% to 21% lower in samples from exposed mothers (0.92 [0.56] g/100 mL for 63 SSRIs, 0.85 [0.51] g/100 mL for 63 MABs, 0.88 [0.37] g/100 mL for 33 steroids, and 0.85 [0.54] g/100 mL for 20 other ADs) compared with 64 samples from healthy mothers (1.08 [0.50] g/100 mL). Adjusted differences were significant for SSRIs and steroids ( F 1, 91 = 4.32; P = .04 and F 1,59 = 5.00, P = 0.03, respectively). Mean (SD) fat and energy were 10% to 22% lower in samples from mothers with other ADs (3.40 [1.21] g/100 mL for fat and 69.56 [15.35] kcal/100 mL for energy) than from healthy (3.85 [1.66] g/100 mL for fat and 77.16 [22.08] kcal/100 mL for energy) and DMC (4.38 [1.90] g/100 mL for fat and 80.60 [24.70] kcal/100 mL for energy) mothers. Adjusted differences were only significant for fat compared with DMC ( F 1,88 = 6.22; P = .01). Conclusions and Relevance In this cross-sectional study, some maternal medications were associated with lower levels of protein and fat in milk, which could impose health risks for breastfed infants. Other factors that could influence macronutrient levels need to be clarified before the clinical implications of these findings can be confirmed.
<i>KRAS</i> Mutation Status and Treatment Outcomes in Patients With Metastatic Pancreatic Adenocarcinoma
Authors: Carter Norton, Matthew Steven Shaw, Zachary Rubnitz, Jarrod Smith, Heloisa P. Soares, Christopher D. Nevala-Plagemann, Ignacio Garrido-Laguna, Vaia Florou
Journal: JAMA Network Open (2025)

Importance Despite the high prevalence of KRAS alterations in pancreatic ductal adenocarcinoma (PDAC), the clinical impact of common KRAS mutations with different cytotoxic regimens is unknown. This evidence is important to inform current treatment and provide a benchmark for emergent targeted KRAS therapies in metastatic PDAC. Objective To assess the clinical implications of common KRAS G12 mutations in PDAC and to compare outcomes of standard-of-care multiagent therapies across these common mutations. Design, Setting, and Participants This retrospective cohort study obtained deidentified clinical data for 5382 patients from a nationwide (US-based) clinicogenomic database. The deidentified data originated from approximately 280 US cancer clinics (approximately 800 sites of care). Patients diagnosed with metastatic PDAC from February 9, 2010, to September 20, 2022, and with sufficient follow-up and treatment data were included. Main Outcomes and Measures Median overall survival (OS) and time to next treatment (TTNT) were calculated for each KRAS mutation group. Hazard ratios (HRs) were generated using multivariate Cox proportional hazards models for KRAS mutations and mutation-treatment combinations. Results A total of 2433 patients with PDAC were included in the analysis (mean age at first treatment, 67.0 [range, 66.0-68.0] years; 1340 male [55.1%]). Among 2023 patients with KRAS mutations, those with G12R had the longest median TTNT (6.0 [95% CI, 5.2-6.6] months) and the longest median OS (13.2 [95% CI, 10.6-15.2] months). Patients with KRAS G12D and G12V mutations had a significantly higher risk of disease progression (HRs, 1.15; [95% CI, 1.04-1.29; P = .009] and 1.16 [95% CI, 1.04-1.30; P = .01], respectively) and death (HRs, 1.29 [95% CI, 1.15-1.45; P &amp;amp;lt; .001] and 1.23 [95% CI, 1.09-1.39; P &amp;amp;lt; .001], respectively) compared with KRAS wild type. The FOLFIRINOX regimen (fluorouracil, irinotecan, oxaliplatin, and leucovorin) had a significantly lower risk of treatment progression and death than gemcitabine with (HRs, 1.19 [95% CI, [1.09-1.29; P &amp;amp;lt; .001] and 1.18 [95% CI, 1.07-1.29; P &amp;amp;lt; .001], respectively) or without (HRs, 1.37 [95% CI, 1.11-1.69; P = .003] and 1.41 [95% CI 1.13-1.75; P = .002], respectively) nab-paclitaxel across all patients. Conclusions and Relevance In this cohort study of 2433 patients with PDAC, KRAS G12D and G12V mutations were associated with worse patient outcomes compared with KRAS wild type. KRAS G12R was associated with more favorable patient outcomes, and FOLFIRINOX was associated with better patient outcomes than gemcitabine-based therapies. These findings highlight the need for more effective systemic therapies for these groups of patients.
Health ministers in England face hard choices in 2025
Authors: Chris Ham
Journal: BMJ (2025)

professor of health policy and management Two narratives emerged from Wes Streeting's first appearance before the House of Commons Health and Social Care Committee on 18 December 2024. 1 The first focused on the pressures faced by the NHS, notwithstanding funding increases announced in October's budget.In discussion with members of the committee, Streeting showed that he has moved on from campaigning to governing in acknowledging the hard choices
Predatory journals: what can we do to protect their prey?
Authors: Christine Laine, Dianne Babski, Vivienne C. Bachelet, Till W Bärnighausen, Christopher Baethge, Kirsten Bibbins-Domingo, Frank Frizelle, Laragh Gollogy, Sabine Kleinert, Elizabeth Loder, João Monteiro, Eric J Rubin, Peush Sahni, Christina C Wee, Jin-Hong Yoo, Lilia Zakhama
Journal: Nature Medicine (2025)
Mental health practitioners’ perspectives on supporting transgender and gender diverse youth: a scoping review
Authors: Jessica Wilson, Milena Heinsch, Justin Canty
Journal: International Journal of Transgender Health (2025)

Background Gender diverse (GD) youth face unique stressors that result in disproportionate mental health challenges compared to their peers. Although mental healthcare is a crucial resource for addressing these challenges, GD youth often report negative experiences, leading to avoidance of services and worsening distress. Understanding mental health practitioners (MHPs) perspectives of supporting GD youth is important for improving their capacity to deliver appropriate, supportive care.
Effects of an initial anti-CD19 CAR T-cell therapy on subsequent anti-CD22 CAR T-cell manufacturing and clinical outcomes in patients with r/r LBCL
Authors: Yi-Jiun Su, Anne Marijn Kramer, Mark P. Hamilton, Neha Agarwal, Hrishikesh K. Srinagesh, John H. Baird, Bita Sahaf, Adam Kuo, Zachary J. Ehlinger, Moksha H. Desai, Skyler P. Rietberg, Ramya Tunuguntla, Shabnum Patel, Harshini Chinnasamy, Nikolaos Gkitsas-Long, Dorota D. Klysz, Annie Kathleen. Brown, Sushma Bharadwaj, Saurabh Dahiya, Melody Smith, Lori Muffly, Crystal L. Mackall, Zinaida Good, Steven A. Feldman, David B. Miklos, Matthew J. Frank
Journal: Cancer Discovery (2025)

Abstract Patients with large B-cell lymphoma (LBCL) progressing after anti-CD19 CAR T-cell (CAR19) therapy have poor outcomes. Subsequent CAR T-cell therapy shows promise, but the impact of residual CAR19 and early relapse remains unclear. We evaluated 37 CAR19-refractory LBCL patients who received anti-CD22 CAR T-cell (CAR22) in a phase 1b trial (NCT04088890). Residual CAR19 was unquantifiable in 17 of 33 evaluable patients post-CAR22 infusion. Single-cell RNA sequencing revealed minimal CAR19/CAR22 co-transduction. Peak CAR19 transgene levels did not affect CAR22 efficacy or toxicities. CAR22 products from patients undergoing leukapheresis &amp;gt; 6 months post-CAR19 had higher CD4+ naïve T and CD4+/CD8+ T- central memory (TCM) cells, with lower CD4+ T-effector memory cells. High and low percentages of CAR22 TCM and TEM, respectively, were correlated with CAR22 transduction efficiency and achieving complete response. Residual CAR19 and leukapheresis timing did not significantly affect outcomes, while CAR22 product composition was significantly correlated with treatment response.
Chronic viral mimicry induction following p53 loss promotes immune evasion
Authors: Charles A. Ishak, Sajid A. Marhon, Nairi Tchrakian, Anjelica Hodgson, Helen Loo Yau, Isabela M. Gonzaga, Melanie Peralta, Ilinca M. Lungu, Stephanie Gomez, Sheng-Ben Liang, Shu Yi Shen, Raymond Chen, Jocelyn Chen, Biji Chatterjee, Kevin N. Wanniarachchi, Junwoo Lee, Nicholas Zehrbach, Amir Hosseini, Parinaz Mehdipour, Siyu Sun, Alexander Solovyov, Ilias Ettayebi, Kyle E. Francis, Aobo He, Taiyi Wu, Shengrui Feng, Tiago da Silva Medina, Felipe Campos de Almeida, Jane Bayani, Jason Li, Spencer MacDonald, Yadong Wang, Sarah S. Garcia, Elisa Arthofer, Noor Diab, Aneil Srivastava, Paul Tran. Austin, Peter J.B. Sabatini, Benjamin D. Greenbaum, Catherine A. O'Brien, Trevor G. Shepherd, Ming Sound Tsao, Katherine B. Chiappinelli, Amit M. Oza, Blaise A. Clarke, Robert Rottapel, Stephanie Lheureux, Daniel D. De Carvalho
Journal: Cancer Discovery (2025)

Abstract Epigenetic therapies facilitate transcription of immunogenic repetitive elements that cull cancer cells through ‘viral mimicry’ responses. Paradoxically, cancer-initiating events also facilitate transcription of repetitive elements. Contributions of repetitive element transcription towards cancer initiation, and the mechanisms by which cancer cells evade lethal viral mimicry responses during tumor initiation remain poorly understood. In this report, we characterize premalignant lesions of the fallopian tube along with syngeneic epithelial ovarian cancer models to explore the earliest events of tumorigenesis following loss of the p53 tumor suppressor protein. We report that p53 loss permits transcription of immunogenic repetitive elements and chronic viral mimicry activation that increases cellular tolerance of cytosolic nucleic acids and diminishes cellular immunogenicity. This selection process can be partially attenuated pharmacologically. Altogether, these results reveal that viral mimicry conditioning following p53 loss promotes immune evasion and may represent a pharmacological target for early cancer interception.
EZH2 modulates mRNA splicing and exerts part of its oncogenic function through repression of splicing factors in CML
Authors: Reinhard Brunmeir, Li Ying, Junli Yan, Yan Ting Hee, Baohong Lin, Harvinder Kaur, Qiao Zheng Leong, Wei Wen Teo, Gerald Choong, Wei-Ying Jen, Liang Piu Koh, Lip Kun Tan, Esther Chan, Melissa Ooi, Henry Yang, Wee Joo Chng
Journal: Leukemia (2025)

The polycomb protein EZH2 is up-regulated in Chronic Myeloid Leukaemia (CML) and associated with transcriptional reprogramming. Here we tested whether EZH2 might also act as a modulator of the mRNA splicing landscape to elicit its oncogenic function in CML. We treated CML cell lines with EZH2 inhibitors and detected differential splicing of several hundreds of events, potentially caused by the transcriptional regulation of splicing factors. Amongst those genes, CELF2 was identified as a candidate to mediate part of the EZH2 inhibitor induced phenotype. Upon over-expression, we observed (1) reduced cell growth, viability, and colony formation of CML cell lines, (2) a change in the splicing landscape, partially overlapping with EZH2 mediated changes, (3) the down-regulation of MYC signalling. Importantly, these findings were successfully validated in a cohort of CML patient samples, confirming the role of CELF2 as EZH2-regulated tumour-suppressor, contributing to the severe splicing de-regulation present in CML. Based on this we propose that EZH2 exerts part of its oncogenic function in CML through the transcriptional repression of splicing factors. Finally, analysis of publicly available datasets suggests that splicing modulation by EZH2 might not be restricted to CML.
Breaking the Bone Marrow Barrier: Peripheral Blood as a Gateway to Measurable Residual Disease Detection in Acute Myelogenous Leukemia
Authors: John T. Butler, William M. Yashar, Ronan Swords
Journal: American Journal of Hematology (2025)

ABSTRACT Acute myeloid leukemia (AML) is a genetically heterogeneous disease with high rates of relapse after initial treatment. Identifying measurable residual disease (MRD) following initial therapy is essential to assess response, predict patient outcomes, and identify those in need of additional intervention. Currently, MRD analysis relies on invasive, serial bone marrow (BM) biopsies, which complicate sample availability and processing time and negatively impact patient experience. Additionally, finding a positive result can generate more questions than answers, causing anxiety for both the patient and the provider. Peripheral blood (PB) evaluation has shown promise in detecting MRD and is now recommended by the European Leukemia Net for AML for certain genetic abnormalities. PB‐based sampling allows for more frequent testing intervals and better temporal resolution of malignant expansion while sparing patients additional invasive procedures. In this review, we will discuss the current state of PB testing for MRD evaluation with a focus on next‐generation sequencing methodologies that are capable of MRD detection across AML subtypes.
Nationwide real-world implementation of AI for cancer detection in population-based mammography screening
Authors: Nora Eisemann, Stefan Bunk, Trasias Mukama, Hannah Baltus, Susanne A. Elsner, Timo Gomille, Gerold Hecht, Sylvia Heywang-Köbrunner, Regine Rathmann, Katja Siegmann-Luz, Thilo Töllner, Toni Werner Vomweg, Christian Leibig, Alexander Katalinic
Journal: Nature Medicine (2025)

Abstract Artificial intelligence (AI) in mammography screening has shown promise in retrospective evaluations, but few prospective studies exist. PRAIM is an observational, multicenter, real-world, noninferiority, implementation study comparing the performance of AI-supported double reading to standard double reading (without AI) among women (50–69 years old) undergoing organized mammography screening at 12 sites in Germany. Radiologists in this study voluntarily chose whether to use the AI system. From July 2021 to February 2023, a total of 463,094 women were screened (260,739 with AI support) by 119 radiologists. Radiologists in the AI-supported screening group achieved a breast cancer detection rate of 6.7 per 1,000, which was 17.6% (95% confidence interval: +5.7%, +30.8%) higher than and statistically superior to the rate (5.7 per 1,000) achieved in the control group. The recall rate in the AI group was 37.4 per 1,000, which was lower than and noninferior to that (38.3 per 1,000) in the control group (percentage difference: −2.5% (−6.5%, +1.7%)). The positive predictive value (PPV) of recall was 17.9% in the AI group compared to 14.9% in the control group. The PPV of biopsy was 64.5% in the AI group versus 59.2% in the control group. Compared to standard double reading, AI-supported double reading was associated with a higher breast cancer detection rate without negatively affecting the recall rate, strongly indicating that AI can improve mammography screening metrics.