tbuckley/cabot-search huggingface dataset:
Modelling MRD changes in myeloma to understand treatment effects, predict outcomes, and investigate curative potential
Authors: Walter M. Gregory, Thomas J. Prior, J.Blake Bartlett, Pieter Sonneveld, Meletios A. Dimopoulos, Philippe Moreau, Saad Usmani, Thierry Facon
Journal: Clinical Cancer Research (2025)

Abstract Purpose: We designed mathematical models to describe and quantify the mechanisms and dynamics of minimal residual disease (MRD) in order to better understand these MRD dynamics, to inform future treatment design, including when to stop or change treatment, and to extrapolate from current PFS times to predict future PFS curves. Experimental Design: To model individual sequential MRD data from phase III clinical trials (MAIA, CASTOR, and POLLUX) using previously developed mathematical models which would be modified as necessary to accurately correspond with the actual MRD data. These models would then be used to extrapolate PFS curves ahead in time. Results: Patients with low MRD values either showed rapid disease regrowth or the MRD values remained low for a prolonged period. Treatment appeared to be most effective in terms of cell-kill within the first 6 to 12 months. Regrowth rates were correlated with estimated initial residual disease, particularly in MRD negative patients. Three-year model extrapolations of PFS were closely comparable to clinical trial data. Conclusions: This model could provide early prediction of PFS outcomes, which otherwise takes lengthy periods of time to observe with clinical trials. Patients showing rapid rebound from low MRD values may benefit from adding another treatment before reaching progressive disease. The MRD analyses and results presented, such as the results about efficacy occurring early in the first 6 to 12 months, may help guide the development and selection of optimal regimens. Longer follow-up periods and application to other trials and datasets are required to substantiate these findings.
Zerlasiran for the Treatment of Atherosclerotic Cardiovascular Disease—Reply
Authors: Steven E. Nissen
Journal: JAMA (2025)

Steven E. Nissen, MD; Qiuqing Wang, MS; Stephen J. Nicholls, MBBS, PhD; Ann Marie Navar, MD, PhD; Kausik K. Ray, MD, MPhil; Gregory G. Schwartz, MD, PhD; Michael Szarek, PhD; Erik S. G. Stroes, MD, PhD; Roland Troquay, MD; Jannick A. N. Dorresteijn, MD, PhD; Henry Fok, MBBS, PhD; David A. Rider, PhD; Steven Romano, MD; Kathy Wolski, MPH; Curtis Rambaran, MBBS, MD
ERS Clinical Research Collaboration programme: more than research networking – enriching respiratory science and impacting clinical practice in Europe and beyond
Authors: Joanna Pepke-Żaba, Joanna Chorostowska-Wynimko, Silke Ryan, Winfried Randerath, Silke Meiners, Sejal Saglani, Elise Heuvelin, Céline Genton, Monika Gappa, Pippa Powell, Eva Polverino, Nicolas Roche, Salman Siddiqui
Journal: European Respiratory Journal (2025)
Smoking Status of the US Cancer Population and a New Perspective From the National Cancer Database
Authors: Giorgio Caturegli, Xuan Zhu, Bryan Palis, Timothy W. Mullett, Benjamin J. Resio, Daniel J. Boffa
Journal: JAMA Oncology (2025)

This cross-sectional study analyzes the smoking status of patients newly diagnosed with cancer, which has implications for cancer care and outcomes.
“Lung transcriptome of e-cigarette users reveals changes related to chronic lung disease.” B. Kidane, S. Kahnamoui, S. Srinathan, R. Liu, L. Tan, M. Morris, A. Shawyer, A.J. Halayko and C.D. Pascoe.<i>Eur Respir J</i>2024; 63: 2301623.
Journal: European Respiratory Journal (2025)
A Proteogenomic View of Synchronous Endometrioid Endometrial and Ovarian Cancer
Authors: Fabian Coscia, Annelaura B. Nielsen, Melanie Weigert, Karen Watters, Melissa Javellana, Michael Anglesio, S. Diane Yamada, Ricardo R. Lastra, Matthias Mann, Ernst Lengyel
Journal: Clinical Cancer Research (2025)

Abstract Purpose: Increasing genomics-based evidence suggests that synchronous endometrial and ovarian cancer (SEOC) represents clonally related primary and metastatic tumors. A systematic analysis of the global protein landscape of SEOCs, heretofore lacking, could reveal functional and disease-specific consequences of known genetic alterations, the directionality of metastasis, and accurate histological markers to distinguish SEOCs from single-site tumors. Experimental Design: We performed a systematic proteogenomic analysis of 29 patients diagnosed with SEOC at three international gynecologic oncology treatment centers (Chicago, Vancouver, Tübingen). For direct comparison to single-site tumors, we included 9 patients with single-site endometrioid ovarian and 26 patients with single-site endometrial endometrioid cancer. For all 64 patients, we performed sequencing of a 275-gene cancer panel combined with compartment-resolved mass spectrometry (MS) based proteomics of consecutive tissue sections to compare global (6,000+ proteins), tumor, and stromal proteomes. Results: DNA-based panel sequencing confirmed that most SEOCs are clonally related. Global proteome profiling uncovered pronounced differences between SEOCs and single tumors and underscored the importance of the stromal proteome in defining and identifying SEOCs. We identified molecularly unique SEOC stromal proteomes, which were globally more related to single endometrial cancers. We finally derived a proteomic predictor distinguishing SEOCs from single-site ovarian and uterine tumors. Conclusions: The integrated proteogenomic data show that SEOCs are distinguishable from endometrial endometrioid or endometrioid ovarian cancers. Based on their proteogenomic similarity to endometrial endometrioid cancers, we conclude that most synchronous endometrial and ovarian cancers represent primary endometrial endometrioid cancers that have metastasized to the ovary.
Gap Years
Authors: Elias Lugo-Fagundo, Charles K. Crawford, Elliot K. Fishman
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
Identification of Early-Stage Breast Cancer with Minimal Risk of Recurrence by Breast Cancer Index
Authors: Marie-France Jilderda, Yi Zhang, Valerie Rebattu, Ranelle Salunga, Wilma Mesker, Jenna Wong, Linda de Munck, Tommy Fornander, Bo Nordenskjöld, Olle Stål, Amanda K.L. Anderson, Esther Bastiaannet, Kai Treuner, Gerrit-Jan Liefers
Journal: Clinical Cancer Research (2025)

Abstract Purpose: This study assessed the prognostic ability of Breast Cancer Index (BCI) to identify patients at minimal risk (&amp;lt;5%) of 10-year distant recurrence (DR) who are unlikely to benefit from adjuvant endocrine therapy. Experimental Design: This prospective translational study included postmenopausal patients with early-stage, HR+ N0 breast cancer from the Stockholm (STO-3) trial who underwent surgery alone (“untreated”) or surgery plus adjuvant tamoxifen (“treated”) and the Netherlands Cancer Registry (NCR; surgery alone). The primary endpoint was time to DR. An adjusted BCI model with an additional cut-point was developed that stratified patients into 4 prognostic risk groups. Results: Across cohorts, 16%-22% of patients were classified as minimal risk of 10-year DR. In the Stockholm untreated cohort (n = 283), risks in the minimal, low, intermediate, and high risk groups were 2.3%, 15.5% (hazard ratio, 4.71 [95% CI, 1.09-20.29] versus minimal risk), 19.8% (6.97 [1.61-30.18]), and 35.9% (13.21 [3.07-56.76]), respectively (P &amp;lt; .001). In the Stockholm treated cohort (n = 317), risks were 4.3%, 5.0% (1.16 [0.35-3.85]), 11.7% (2.45 [0.74-8.14]), and 21.1% (5.27 [1.72-16.16]; P &amp;lt; .001). In the NCR cohort (n = 1245), risks were 4.5%, 7.5% (sub-distribution hazard ratio, 1.67 [95% CI, 0.81-3.45]), 10.3% (2.40 [1.14-5.03]), and 13.1% (3.13 [1.50-6.55]; P = .005). BCI risk scores provided additional independent information over standard prognostic factors (likelihood ratio, c2 = 7.98; P = .004). Conclusions: The adjusted BCI model identified women with early-stage, HR+ N0 breast cancer at minimal risk of DR who may consider de-escalating adjuvant endocrine therapy.
Identifying Who Is at Risk of Interval Breast Cancers
Authors: Christoph I. Lee, Kathryn P. Lowry
Journal: JAMA Oncology (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 Oncology 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 Oncology journal
Notice of Retraction. Xu LL, et al. Efficacy and Safety of Esketamine for Supplemental Analgesia During Elective Cesarean Delivery: A Randomized Clinical Trial. <i>JAMA Netw Open.</i> 2023;6(4):e239321.
Authors: Xin-Zhong Chen, Dong-Xin Wang
Journal: JAMA Network Open (2025)

This Notice of Retraction is to retract an article by Xu LL, et al.
Liposomal irinotecan for previously treated patients with biliary tract cancer: A pooled analysis of NIFTY and NALIRICC trials
Authors: Changhoon Yoo, Anna Saborowski, Jaewon Hyung, Patrick Wenzel, Ilhwan Kim, Henning Wege, Kyu-Pyo Kim, Gunnar Folprecht, Baek-Yeol Ryoo, Phillip Schütt, Jaekyung Cheon, Thorsten Götze, Hyewon Ryu, Ji Sung Lee, Arndt Vogel
Journal: Journal of Hepatology (2025)

Liposomal irinotecan (nal-IRI) combined with fluorouracil (5-FU)/leucovorin (LV) as a second-line treatment for biliary tract cancer (BTC) following progression on gemcitabine-based therapy in the Korean NIFTY and German NALIRICC trials yielded conflicting outcomes. This necessitated a comprehensive pooled analysis to evaluate its efficacy and safety. Individual patient data were pooled from the intention-to-treat populations of the NIFTY and NALIRICC trials. The primary endpoint was progression-free survival (PFS). A total of 278 patients were included: 137 in the nal-IRI plus 5-FU/LV group and 141 in the 5-FU/LV group. The nal-IRI plus 5-FU/LV group showed significantly longer median PFS (3.6 months [95% confidence interval [CI], 2.7-4.4] vs 1.8 months (95% CI, 1.5-2.6), hazard ratio [HR) 0.65, p<0.001). Median overall survival was 8.1 months (95% CI, 6.0-8.9) and 6.1 months (95% CI, 5.3-7.5), respectively (HR 0.77, p=0.051). Overall response rates (ORR) was also higher in the nal-IRI plus 5-FU/LV group (17.5% vs 2.8%; p<0.001) than in the 5-FU/LV group. Post-study irinotecan-containing therapy was administered in 4 (2.9%) and 21 (15.3%) patients in the nal-IRI plus 5-FU/LV group and 5-FU/LV group, respectively. Adverse events varied by ethnicity, with gastrointestinal toxicities more common in Germans and neutropenia more prevalent in Koreans; treatment discontinuation without disease progression was 31.3% vs 8.0%, respectively. The addition of nal-IRI to 5-FU/LV significantly improved PFS and ORR, supporting its potential as subsequent-line therapy. Differences in safety profiles underscore the relevance of ethnicity for nal-IRI in patients with BTC. Current standard of care for second-line therapy in patients with advanced biliary tract cancer (BTC) is FOLFOX. This study provides robust evidence supporting the potential role of additional liposomal irinotecan (nal-IRI) to fluorouracil and leucovorin (5-FU/LV) as a subsequent therapy for patients with BTC who have progressed on gemcitabine-based regimens. The findings demonstrate significant improvements in progression-free survival and overall response rates, emphasizing its potential to address the limited treatment options in this patient population. Furthermore, the study underscores the necessity of considering ethnic differences in adverse event profiles to optimize treatment administration and patient outcomes. NCT03524508 and NCT03043547.
Incidence and Risk Factors of Interval and Screen-Detected Breast Cancer
Authors: Yuqi Zhang, Juan Rodriguez, Xinhe Mao, Felix Grassmann, Jose Tapia, Mikael Eriksson, Per Hall, Kamila Czene
Journal: JAMA Oncology (2025)

Importance Mammographic screening is the only proven method for early detection and mortality reduction of breast cancer (BC). However, many patients are missed at prior screening; thus, they receive their diagnosis between the interval of screening rounds, called interval cancer (IntCa). Some IntCas are fast growing between screening rounds. Objective To investigate the incidence and proportion of IntCa and screen-detected breast cancer (ScrCa) and identify factors associated with IntCa. Design, Setting, and Participants This population-based cohort study was conducted from January 1989 to March 2020, with follow-up until 2020 and a mean (SD) follow-up of 13 (8.3) years. The statistical analysis was performed from February 2023 to June 2024. It included cancer-free women (N = 527 144) residing in Stockholm, Sweden, who were invited to undergo mammography screening (aged 40-74 years) during 1989 to 2020. An additional cohort of women were included who were participating in the Karolinska Mammography Project for Risk Prediction of Breast Cancer study and had mammography data available. Exposures Family cancer history (defined from the Swedish Multi-Generation Register and Cancer Register), mammographic density, and various demographic, reproductive, and other factors (multiple Swedish registers). Main Outcomes and Measures Incidence of ScrCa and IntCa (defined from the Swedish Cancer Register in conjunction with individual screening histories). Results A total of 29 049 women (5.5%) received a diagnosis of BC, of whom 10 631 (2.0%) had ScrCa and 4369 (0.8%) IntCa. ScrCa and IntCa incidences increased during the period. The proportion of IntCa among screened patients with BC was around 30%, which decreased with older age. Factors associated with increased risk of IntCa included older age at first childbirth, higher education level, hormone replacement therapy, and higher mammographic density. Risk estimates of family cancer history on IntCa were family history of BC (hazard ratio [HR], 1.85; 95% CI, 1.72-1.99), family history of IntCa (HR, 2.92; 95% CI, 2.39-3.55), and hereditary breast and ovarian cancers (HR, 1.45; 95% CI, 1.36-1.54), with risk further elevated with the number of relatives who received a diagnosis when younger than the median age. Women with IntCa were more likely to have estrogen receptor (ER)–negative cancers than women with ScrCa (22% vs 11%), and having family history of ER-negative BC was associated with 3-fold risk for ER-negative IntCa. Conclusions and Relevance The results of this cohort study suggest that IntCa rates have not decreased with age-based screening, and implementing risk-based screening considering IntCa-specific risk factors is necessary for improving outcomes.
Identifying Pregnant Women With Disabilities and Maternal and Newborn Outcomes
Authors: Alka Dev, Willi Horner-Johnson, Andrew Schaefer, Cecilia Ganduglia-Cazaban, Thérèse A. Stukel, David C. Goodman, JoAnna K. Leyenaar
Journal: JAMA Network Open (2025)

Importance Pregnant women with disabilities are at higher risk of poor pregnancy and birth outcomes. Different methods for identifying disability may affect estimates of health disparities in this population. Objective To compare pregnancy and birth outcomes among pregnant women using different ways of identifying maternal disability. Design, Setting, and Participants Retrospective cohort study of linked vital records and maternal and newborn claims for Medicaid-insured live births from January 2010 to December 2014 in Texas. Data analysis was conducted from October 2023 to May 2024. Exposure Births grouped into 5 maternal cohorts: no identified disability, disability benefits enrollment only, disability diagnostic code only, both benefits enrollment and a diagnostic code, and either disability benefits or a diagnostic code. Main Outcomes and Measures Mode of delivery (cesarean) and severe maternal morbidity (SMM) were identified from maternal claims. Low birthweight (LBW), preterm birth (PTB), and small for gestational age (SGA) were identified from birth certificates. Modified Poisson regression with robust variance estimators was used to estimate adjusted risk ratios (aRRs) for the association of each of the 5 outcomes with disability group status. Results Among 921 218 births (mean [SD] maternal age at birth, 25.1 [5.7] years), 895 201 (97.2%) were to mothers with no disability, 6160 (0.7%) were to mothers enrolled in disability benefits only, 17 742 (1.9%) were to mothers with a disability diagnostic code only, 2115 (0.2%) were to mothers with both benefits enrollment and a disability code, and 26 017 (2.8%) were to mothers meeting either disability definition. Compared with those without disabilities, those with only disability diagnostic codes had the highest rates for cesarean delivery (306 589 births [34.3%] vs 7658 births [43.2%]), LBW (750 058 births [8.4%] vs 869 births [14.2%]), and PTB (92 807 births [10.4%] vs 977 births [15.9%]). Compared with those with no disability, the adjusted relative risks were highest in the diagnostic codes only group for cesarean delivery (aRR, 1.22; 95% CI, 1.20-1.24), LBW (aRR, 1.77, 95% CI, 1.71-1.84), and PTB (aRR, 1.68; 95% CI, 1.62-1.74). The risk for SMM (aRR, 4.82; 95% CI, 3.96-5.86) and SGA (aRR, 1.43; 95% CI, 1.24-1.66) were highest in those with both benefits enrollment and a disability code. Conclusions and relevance In this cohort study, disability was associated with adverse outcomes, regardless of definition. However, the burden of disparities was dependent on how disability was defined, suggesting that the assessment of disability-associated health risks should consider how disability is conceptualized.
Partial Effects in Environmental Mixtures—Evidence and Guidance on Methods and Implications
Authors: Maria E. Kamenetsky, Barrett M. Welch, Paige A. Bommarito, Jessie P. Buckley, Katie M. O'Brien, Alexandra J. White, Thomas F. McElrath, David E. Cantonwine, Kelly K. Ferguson, Alexander P. Keil
Journal: Environmental Health Perspectives (2025)

The effects of a mixture of exposures on health outcomes are of interest to public health, but pose methodological hurdles. These exposures may impact the outcome in opposing ways, which we call the positive and negative partial effects of a mixture. There has been growing interest in estimating these partial effects and their ability to inform public health interventions.
Gene Therapy for Hemophilia – From Basic Science to First Approvals of “One-and-Done” Therapies
Authors: Roland W Herzog, Radoslaw Kaczmarek, Katherine A High
Journal: Molecular Therapy (2025)

Realistic paths to gene therapy for the X-linked bleeding disorder hemophilia started to materialize in the mid 1990s, resulting in disease correction in small and large animal models. Out of a diversity of approaches, in vivo adeno-associated viral (AAV) gene transfer to hepatocytes emerged as the most promising strategy, eventually forming the basis for multiple advanced clinical trials and regulatory approval of two products for the treatment of hemophilia B (coagulation factor IX deficiency) and one for hemophilia A (factor VIII deficiency). Ideally, gene therapy is effective with a single administration, thus providing therapeutic factor levels over a period of years, without the need for frequent injections. Overcoming multiple obstacles, some not predicted by pre-clinical studies, sustained partial to complete correction of coagulation for several years to an entire decade has now been documented in patients, with observation ongoing. A hyperactive form of FIX improved efficacy in hemophilia B, and superior engineered variants of FVIII are emerging. Nonetheless, challenges remain, including pre-existing immunity to AAV capsids, toxicities, inter-patient variability in response to treatment, and difficulty in obtaining durable therapeutic expression of FVIII. In alternative approaches, in vivo gene editing and ex vivo gene therapies targeting hemopoietic cells are in development.
Decoding microglial immunometabolism: a new frontier in Alzheimer's disease research
Authors: Eun Sun Jung, Hayoung Choi, Inhee Mook-Jung
Journal: Molecular Neurodegeneration (2025)

Abstract Alzheimer’s disease (AD) involves a dynamic interaction between neuroinflammation and metabolic dysregulation, where microglia play a central role. These immune cells undergo metabolic reprogramming in response to AD-related pathology, with key genes such as TREM2, APOE, and HIF-1α orchestrating these processes. Microglial metabolism adapts to environmental stimuli, shifting between oxidative phosphorylation and glycolysis. Hexokinase-2 facilitates glycolytic flux, while AMPK acts as an energy sensor, coordinating lipid and glucose metabolism. TREM2 and APOE regulate microglial lipid homeostasis, influencing Aβ clearance and immune responses. LPL and ABCA7, both associated with AD risk, modulate lipid processing and cholesterol transport, linking lipid metabolism to neurodegeneration. PPARG further supports lipid metabolism by regulating microglial inflammatory responses. Amino acid metabolism also contributes to microglial function. Indoleamine 2,3-dioxygenase controls the kynurenine pathway, producing neurotoxic metabolites linked to AD pathology. Additionally, glucose-6-phosphate dehydrogenase regulates the pentose phosphate pathway, maintaining redox balance and immune activation. Dysregulated glucose and lipid metabolism, influenced by genetic variants such as APOE4, impair microglial responses and exacerbate AD progression. Recent findings highlight the interplay between metabolic regulators like REV-ERBα, which modulates lipid metabolism and inflammation, and Syk, which influences immune responses and Aβ clearance. These insights offer promising therapeutic targets, including strategies aimed at HIF-1α modulation, which could restore microglial function depending on disease stage. By integrating metabolic, immune, and genetic factors, this review underscores the importance of microglial immunometabolism in AD. Targeting key metabolic pathways could provide novel therapeutic strategies for mitigating neuroinflammation and restoring microglial function, ultimately paving the way for innovative treatments in neurodegenerative diseases.