tbuckley/cabot-search huggingface dataset:
An engineered immunogen activates diverse HIV broadly neutralizing antibody precursors and promotes acquisition of improbable mutations
Authors: Olivia M. Swanson, Qianyi E. Zhang, Elizabeth Van Itallie, Ming Tian, Alecia R. Brown, Caitlin Harris, Anyway Brenda Kapingidza, Brianna Rhodes, Lena M. Smith, Sravani Venkatayogi, Kenneth Cronin, McKenzie Frazier, Rob Parks, Maggie Bar, Chuancang Jiang, Joshua S. Martin Beem, Hwei-Ling Cheng, Jillian Davis, Kelly McGovern, Amanda Newman, Robert J. Edwards, Derek Cain, S. Munir Alam, Kevin Wiehe, Kevin O. Saunders, Priyamvada Acharya, Fred Alt, Barton F. Haynes, Mihai L. Azoitei
Journal: Science Translational Medicine (2025)

Elicitation of HIV broadly neutralizing antibodies (bnAbs) by vaccination first requires the activation of diverse precursors, followed by successive boosts that guide these responses to enhanced breadth through the acquisition of somatic mutations. Because HIV bnAbs contain mutations in their B cell receptors (BCRs) that are rarely generated during conventional B cell maturation, HIV vaccine immunogens must robustly engage and expand B cells with BCRs that contain these improbable mutations. Here, we engineered an immunogen that activates diverse precursors of an HIV V3-glycan bnAb and promotes their acquisition of a functionally critical improbable mutation. This immunogen was validated biochemically, structurally, and in three different humanized immunoglobulin mouse models that were designed to test HIV immunogens. These results provide a blueprint for rationally designing priming immunogens that explicitly target the elicitation of antibodies with functional yet improbable mutations.
Detecting Hemorrhagic Myocardial Infarction With 3.0-T CMR
Authors: Yinyin Chen, Hang Jin, Xingming Guan, Hsin-Jung Yang, Xinheng Zhang, Zhenhui Chen, Shing Fai Chan, Dhirendra Singh, Nithya Jambunathan, Khalid Youssef, Keyur P Vora, Gabriel Gruionu, Sanjana K Dharmakumar, Glen Schmeisser, Richard Tang, Mengsu Zeng, Rohan Dharmakumar
Journal: JACC. Cardiovascular imaging (2025)
Growth Differentiation Factor–15 Is Associated With Congestion-Related Anorexia and Weight Loss in Advanced Heart Failure
Authors: Luca Monzo, Petr Jarolim, Barry A. Borlaug, Jan Benes, Ivana Jurcova, Dominik Jenca, Katerina Kroupova, Peter Wohlfahrt, Martin Kotrc, Vojtech Melenovsky
Journal: JACC Heart Failure (2025)

Growth differentiation factor (GDF)-15 is a pleiotropic cytokine that is associated with appetite-suppressing effects and weight loss in patients with malignancy. This study aims to investigate the relationships between GDF-15 levels, anorexia, cachexia, and clinical outcomes in patients with advanced heart failure with reduced ejection fraction (HFrEF). In this observational, retrospective analysis, a total of 344 patients with advanced HFrEF (age 58 ± 10 years, 85% male, 67% NYHA functional class III), underwent clinical and echocardiographic examination, body composition evaluation by skinfolds and dual-energy x-ray absorptiometry, circulating metabolite assessment, Minnesota Living with Heart Failure Questionnaire, and right heart catheterization. The median GDF-15 level was 1,503 ng/L (Q1-Q3: 955-2,332 ng/L) (reference range: <1,200 ng/L). Higher GDF-15 levels were associated with more prevalent anorexia and cachexia. Patients with higher GDF-15 had increased circulating free fatty acids and beta-hydroxybutyrate, lower albumin, cholesterol, and insulin/glucagon ratio, consistent with a catabolic state. Patients with higher GDF-15 had worse congestion and more severe right ventricular dysfunction. In multivariable Cox analysis, elevated GDF-15 was independently associated with risk of the combined endpoint of death, urgent transplantation, or left ventricular assist device implantation, even after adjusting for coexisting anorexia and cachexia (T3 vs T1 HR: 2.31 [95% CI: 1.47-3.66]; P < 0.001). In patients with advanced HFrEF, elevated circulating GDF-15 levels are associated with a higher prevalence of anorexia and cachexia, right ventricular dysfunction, and congestion, as well as an independently increased risk of adverse events. Further studies are warranted to determine whether therapies altering GDF-15 signaling pathways can affect metabolic status and clinical outcomes in advanced HFrEF.
Explainable endoscopic artificial intelligence method for real-time in situ significant rectal lesion characterisation – a prospective cohort study
Authors: Niall P Hardy, Pol MacAonghusa, Jeffrey Dalli, Jonathan P Epperlein, Paul Huxel, Mohammad F Khan, Alice Moynihan, Sergiy Zhuk, Johanna J Joosten, David Nijssen, Alberto Arezzo, Juriaan Tuynman, Peter M Neary, Roel Hompes, Ronan A Cahill
Journal: International Journal of Surgery (2025)
A nomogram for predicting lymph node metastases in nonmetastatic muscle-invasive bladder cancer: a SEER-based investigation
Authors: Jie Wu, Bing-Qing Shang, Jian-Zhong Shou, Zong-Ping Wang
Journal: International Journal of Surgery (2025)

Wu, Jie MD; Shang, Bing-Qing MD; Shou, Jian-Zhong MD; Wang, Zong-Ping MD Author Information
Large-scale network mechanisms underlying postoperative cognitive improvement after spine surgery
Authors: Daria Antonenko, Sophie Leroy, Jonas Müller, Frederik Behr, Anna E. Fromm, Falk von Dincklage, Robert Fleischmann
Journal: International Journal of Surgery (2025)

Background: The outcome of major surgery is determined not only by the success of the procedure itself but also by its neurocognitive effects. We previously reported improved cognition following spine surgery (Müller et al. 2023 Spine ), but the mechanisms underlying these changes remain unknown. Materials and Methods: We analyzed resting-state (rs) functional magnetic resonance images of 79 patients (mean/SD age: 71/7 years) acquired at baseline in this previously published trial. For 26 patients, data was additionally available at 3-months follow-up visits. To delineate large-scale connectivity, we calculated functional connectivity (FC) within and between three core neural networks, the central executive network (CEN), the salience network (SAL), and the default mode network (DMN). Results: FC between CEN and SAL predicted cognitive improvement (beta = 0.36, 95%-CI 0.28 to 0.45, P = 0.033). Average FC between all nodes of the CEN showed changes towards an increase after surgery (beta = 0.057, 95%-CI − 0.01 to 0.123, P = 0.086). Further seed-based FC analyses revealed that this increase was most pronounced in the functional coupling between left dorsolateral prefrontal and right posterior parietal cortex (beta = 0.10, T(24) = 2.73, P unc = 0.012, P FDR = 0.035). The increase of CEN-FC correlated with individual enhancements of executive scores (beta = 0.34, 95%-CI 0.32 to 0.36, P = 0.034). Conclusion: Integration of activity between the CEN and SAL networks predicted postoperative cognitive improvements, suggesting that less segregated large-scale functional networks may facilitate beneficial cognitive changes following surgery. Postoperative increases in functional coupling may serve as a biomarker for individual improvements in executive functions. These results indicate that surgery should not be routinely deferred in elderly patients due to concerns about postoperative neurocognitive complications. Moreover, our findings highlight potential targets for non-invasive brain stimulation interventions aimed at preventing neurocognitive complications.
Treatment of Pleural Mesothelioma: ASCO Guideline Update
Authors: Hedy L. Kindler, Nofisat Ismaila, Lyudmila Bazhenova, Quincy Chu, Jane E. Churpek, Ibiayi Dagogo-Jack, Darren S. Bryan, Michael W. Drazer, Patrick Forde, Aliya N. Husain, Jennifer L. Sauter, Valerie Rusch, Penelope A. Bradbury, B.C. John Cho, Marc de Perrot, Azam Ghafoor, David L. Graham, Ola Khorshid, Alexandra Lebensohn, Julie White, Raffit Hassan
Journal: Journal of Clinical Oncology (2025)

ASCO Guidelines provide recommendations with comprehensive review and analyses of the relevant literature for each recommendation, following the guideline development process as outlined in the ASCO Guidelines Methodology Manual . ASCO Guidelines follow the ASCO Conflict of Interest Policy for Clinical Practice Guidelines . Clinical Practice Guidelines and other guidance (“Guidance”) provided by ASCO is not a comprehensive or definitive guide to treatment options. It is intended for voluntary use by clinicians and should be used in conjunction with independent professional judgment. Guidance may not be applicable to all patients, interventions, diseases or stages of diseases. Guidance is based on review and analysis of relevant literature and is not intended as a statement of the standard of care. ASCO does not endorse third-party drugs, devices, services, or therapies and assumes no responsibility for any harm arising from or related to the use of this information. See complete disclaimer in Appendix 1 and 2 (online only) for more . PURPOSE To provide evidence-based recommendations to practicing physicians and others on the management of pleural mesothelioma (PM). METHODS ASCO convened an Expert Panel of medical oncology, thoracic surgery, radiation oncology, pathology, cancer genetics, and advocacy experts to conduct an updated literature search, which included systematic reviews, meta-analyses, randomized controlled trials, and prospective and retrospective comparative observational studies published from 2016 through 2024. Outcomes of interest included survival, disease-free or recurrence-free survival, and quality of life. Expert Panel members used available evidence and informal consensus to develop evidence-based guideline recommendations. RESULTS The literature search identified 110 additional relevant studies to inform the evidence base for this guideline. RECOMMENDATIONS Evidence-based recommendations were developed for surgical cytoreduction, immunotherapy, chemotherapy, pathology, and germline testing in patients with PM. Additional information is available at www.asco.org/thoracic-cancer-guidelines .
Neoadjuvant Nivolumab Plus Ipilimumab Versus Chemotherapy in Resectable Lung Cancer
Authors: Mark M. Awad, Patrick M. Forde, Nicolas Girard, Jonathan Spicer, Changli Wang, Shun Lu, Tetsuya Mitsudomi, Enriqueta Felip, Stephen R. Broderick, Scott J. Swanson, Julie Brahmer, Keith Kerr, Gene B. Saylors, Ke-Neng Chen, Vishwanath Gharpure, Jaclyn Neely, David Balli, Nan Hu, Mariano Provencio Pulla
Journal: Journal of Clinical Oncology (2025)

PURPOSE Neoadjuvant immune checkpoint blockade with nivolumab plus ipilimumab improves overall survival (OS) in non–small cell lung cancer (NSCLC); however, randomized data for resectable lung cancer are limited. We report results from the exploratory concurrently randomized nivolumab plus ipilimumab and chemotherapy arms of the international phase III CheckMate 816 trial. METHODS Adults with stage IB-IIIA (American Joint Committee on Cancer seventh edition) resectable NSCLC received three cycles of nivolumab once every 2 weeks plus one cycle of ipilimumab or three cycles of chemotherapy (on day 1 or days 1 and 8 of each 3-week cycle) followed by surgery. Analyses included event-free survival (EFS), OS, pathologic response, surgical outcomes, biomarker analyses, and safety. RESULTS A total of 221 patients were concurrently randomly assigned to nivolumab plus ipilimumab (n = 113) or chemotherapy (n = 108). At a median follow-up of 49.2 months, the median EFS was 54.8 months (95% CI, 24.4 to not reached [NR]) with nivolumab plus ipilimumab versus 20.9 months (95% CI, 14.2 to NR) with chemotherapy (HR, 0.77 [95% CI, 0.51 to 1.15]); 3-year EFS rates were 56% versus 44%. Higher rates of EFS events were initially seen, with later benefit favoring nivolumab plus ipilimumab; 3-year OS rates were 73% versus 61% (HR, 0.73 [95% CI, 0.47 to 1.14]); pathologic complete response rates were 20.4% versus 4.6%, respectively. In the respective arms, 83 (74%) and 82 patients (76%) underwent definitive surgery. Grade 3-4 treatment-related adverse events occurred in 14% and 36% of patients, respectively. CONCLUSION Neoadjuvant nivolumab plus ipilimumab showed potential long-term clinical benefit versus chemotherapy, despite early crossing of EFS curves in the preoperative phase and a lower rate of high-grade toxicity.
Melanoma Among Adult Survivors of Childhood Cancer: A Report From the Childhood Cancer Survivor Study
Authors: Seth J. Rotz, Kayla Stratton, Wendy M. Leisenring, Susan A. Smith, Rebecca M. Howell, James E. Bates, Alberto S. Pappo, Joseph P. Neglia, Gregory T. Armstrong, Lucie M. Turcotte
Journal: Journal of Clinical Oncology (2025)

PURPOSE Melanoma as a subsequent malignant neoplasm has been described among childhood cancer survivors; however, the risk factors and long-term survival are not well understood. METHODS We assessed incidence, risk factors, and outcomes for melanoma among participants in the Childhood Cancer Survivor Study cohort. Cumulative incidence and standardized incidence ratios (SIRs) were calculated, and multivariable Cox models were used to determine hazard ratios (HRs) and associated 95% CI for melanoma risk factors. Radiation exposure to seven body regions and melanoma status for each of eight regions per survivor were integrated into the Cox model. RESULTS Among 25,716 participants, 177 melanomas developed in 160 survivors (110 invasive, 62 in situ cutaneous, five ocular). The 40-year melanoma cumulative incidence was 1.1% (95% CI, 0.9 to 1.4) for all participants and 1.5% (95% CI, 1.0 to 2.1) among those receiving a cumulative radiation dose of ≥40 Gy. Compared with the general population, the SIR for invasive skin or ocular melanoma was 2.0 (95% CI, 1.6 to 2.4). A cumulative radiation dose of ≥40 Gy to the corresponding body region(s) of the melanoma (HR, 2.0 [95% CI, 1.1 to 3.7]), a cumulative cyclophosphamide equivalent dose of ≥20,000 mg/m 2 (HR, 1.9 [95% CI, 1.1 to 3.6]), and bleomycin exposure (HR, 2.2 [95% CI, 1.2 to 4.1]) were associated with increased cutaneous melanoma. Invasive melanoma at any site was associated with an increased risk of death (HR, 2.4 [95% CI, 1.7 to 3.3]). CONCLUSION Childhood cancer survivors have more than a two-fold increased risk of melanoma compared with the general population, and those with an invasive melanoma have more than a two-fold risk of death. High-dose radiation and alkylating agent exposure, and bleomycin are important risk factors for melanoma and should be considered in future patient guidance and screening.
Manufactured Chemicals and Children’s Health — The Need for New Law
Authors: David A Wirth, Maureen Cropper, Daniel A Axelrad, Caroline Bald, Aruni Bhatnagar, Linda S Birnbaum, Thomas A Burke, Thomas C Chiles, Ken Geiser, Carly Griffin, Pushpam Kumar, Daniele Mandrioli, Yongjoon Park, Hervé Raps, Apolline Roger, Ted R Smith, J Christopher States, Kurt Straif, Joel A Tickner, Wendy Wagner, Zhanyun Wang, Ella M Whitman, Tracey J Woodruff, Aroub Yousuf, Philip J Landrigan
Journal: New England Journal of Medicine (2025)

Multiple diseases in children have been linked to manufactured synthetic chemicals, which are subject to few legal or policy constraints. A revamping of law and restructuring of the chemical industry are required.
Talquetamab plus Teclistamab in Relapsed or Refractory Multiple Myeloma
Authors: Yael C. Cohen, Hila Magen, Moshe Gatt, Michael Sebag, Kihyun Kim, Chang-Ki Min, Enrique M. Ocio, Sung-Soo Yoon, Michael P. Chu, Paula Rodríguez-Otero, Irit Avivi, Natalia A. Quijano Cardé, Ashwini Kumar, Maria Krevvata, Michelle R. Peterson, Lilla Di Scala, Emma Scott, Brandi Hilder, Jill Vanak, Arnob Banerjee, Albert Oriol, Daniel Morillo, María-Victoria Mateos
Journal: New England Journal of Medicine (2025)

Talquetamab (anti-G protein-coupled receptor family C group 5 member D) and teclistamab (anti-B-cell maturation antigen) are bispecific antibodies that activate T cells by targeting CD3 and that have been approved for the treatment of triple-class-exposed relapsed or refractory multiple myeloma. We conducted a phase 1b-2 study of talquetamab plus teclistamab in patients with relapsed or refractory multiple myeloma. In phase 1, we investigated five dose levels in a dose-escalation study. Talquetamab at a dose of 0.8 mg per kilogram of body weight plus teclistamab at a dose of 3.0 mg per kilogram every other week was selected as the recommended phase 2 regimen. The primary objective was to evaluate adverse events and dose-limiting toxic effects. A total of 94 patients received treatment, with the recommended phase 2 regimen used in 44. The median follow-up was 20.3 months. Three patients had dose-limiting toxic effects (including grade 4 thrombocytopenia in 1 patient with the recommended phase 2 regimen). Across all dose levels, the most common adverse events were cytokine release syndrome, neutropenia, taste changes, and nonrash skin events. Grade 3 or 4 adverse events, most commonly hematologic events, occurred in 96% of the patients. Grade 3 or 4 infections occurred in 64% of the patients. With the recommended phase 2 regimen, a response occurred in 80% of the patients (including in 61% of those with extramedullary disease); across all dose levels, a response occurred in 78%. The likelihood of patients continuing in response at 18 months was 86% with the recommended phase 2 regimen (82% among those with extramedullary disease) and 77% across all dose levels. The incidence of grade 3 or 4 infections with talquetamab plus teclistamab was higher than has been observed with either therapy alone. A response was observed in a high percentage of patients across all dose levels, with durable responses with the recommended phase 2 regimen. (Funded by Janssen Research and Development; RedirecTT-1 ClinicalTrials.gov number, NCT04586426.).
The Role of Importation in Remediating U.S. Generic Drug Shortages
Authors: Thomas J Bollyky, Sarosh N Nagar, Chloe Searchinger, Aaron S Kesselheim
Journal: New England Journal of Medicine (2025)

U.S. shortages of critical drugs are a worsening problem, and the FDA has been too slow to authorize temporary importation of drugs from other well-regulated markets to meet pressing U.S. needs.
Human Infection with a Novel Tickborne Orthonairovirus Species in China
Authors: Ming-Zhu Zhang, Cai Bian, Run-Ze Ye, Xiao-Ming Cui, Yan-Li Chu, Nan-Nan Yao, Xiao-Wei Xu, Jin-Ling Ye, Lin Chen, Ji-Hu Yang, Xiao-Ling Su, Lin Huang, Xiao-Yu Shi, Lin Zhao, Yu-Guo Chen, Yuan-Chun Zheng, Xiao-Min Zheng, Jia-Fu Jiang, Wu-Chun Cao
Journal: New England Journal of Medicine (2025)
Clearance of Driver Mutations after Transplantation for Myelofibrosis
Authors: Nico Gagelmann, Marie Quarder, Anita Badbaran, Kristin Rathje, Dietlinde Janson, Catherina Lück, Johanna Richter, Franziska Marquard, Sofia Oechsler, Radwan Massoud, Evgeny Klyuchnikov, Ina Rudolph, Mathias Schäfersküpper, Christian Niederwieser, Silke Heidenreich, Carolina Berger, Boris Fehse, Christine Wolschke, Francis Ayuk, Nicolaus Kröger
Journal: New England Journal of Medicine (2025)

Allogeneic hematopoietic stem-cell transplantation is the only curative treatment for myelofibrosis. Driver mutations are the pathophysiological hallmark of the disease, but the role of mutation clearance after transplantation is unclear. We used highly sensitive polymerase-chain-reaction technology to analyze the dynamics of driver mutations in peripheral-blood samples from 324 patients with myelofibrosis (73% with JAK2 mutations, 23% with CALR mutations, and 4% with MPL mutations) who were undergoing transplantation after reduced-intensity conditioning. Mutations were detected before transplantation and at 30, 100, and 180 days after transplantation to measure clearance and its effect on relapse and cure. The two primary end points were relapse and disease-free survival. At day 30 after transplantation, mutation clearance was found in 42% of the patients who had JAK2 mutations, 73% of those who had CALR mutations, and 54% of those who had MPL mutations; the corresponding percentages at day 100 were 63%, 82%, and 100%. The cumulative incidence of relapse at 1 year was 6% (95% confidence interval [CI], 2 to 10) among patients with mutation clearance at day 30 after transplantation and 21% (95% CI, 15 to 27) among those without mutation clearance at day 30. Disease-free and overall survival at 6 years were 61% and 74%, respectively, among patients with mutation clearance at day 30 after transplantation and 41% and 60%, respectively, among those without mutation clearance at day 30. Mutation clearance at day 30 appeared to outperform traditional donor chimerism as a measure of response; it was independently associated with a reduced risk of relapse or progression (hazard ratio, 0.36; 95% CI, 0.21 to 0.61) and appeared to overcome differences in prognosis based on the type of driver mutation (JAK2 vs. MPL or CALR). In patients with myelofibrosis, clearance of driver mutations at day 30 after transplantation appeared to influence relapse and survival, irrespective of the underlying driver mutation.
A Comparison of Peripherally Inserted Central Catheter Materials
Authors: Amanda J. Ullman, Deanne August, Tricia M. Kleidon, Rachel M. Walker, Nicole Marsh, Andrew C. Bulmer, Ben Pearch, Naomi Runnegar, Joanne Leema, Paul Lee-Archer, Cathy Biles, Victoria Gibson, Ruth Royle, Katrina Southam, Joshua Byrnes, Vineet Chopra, Alan Coulthard, Peter Mollee, Claire M. Rickard, Patrick N. A. Harris, Robert S. Ware
Journal: New England Journal of Medicine (2025)

New catheter materials for peripherally inserted central catheters (PICCs) may reduce the risk of device failure due to infectious, thrombotic, and catheter occlusion events. However, data from randomized trials comparing these catheters are lacking. We conducted a randomized, controlled, superiority trial in three Australian tertiary hospitals. Adults and children who were referred for PICC placement were assigned in a 1:1:1 ratio to receive a hydrophobic or chlorhexidine PICC or a standard polyurethane PICC and were followed for 8 weeks. The primary outcome was device failure, which was a composite of infectious (bloodstream or local) or noninfectious (thrombosis, breakage, or occlusion) complications. A total of 1098 participants underwent randomization; 365 were assigned to the hydrophobic group, 365 to the chlorhexidine group, and 368 to the standard-polyurethane group. Device failure occurred in 21 of 358 participants (5.9%) in the hydrophobic group, in 36 of 363 (9.9%) in the chlorhexidine group, and in 22 of 359 (6.1%) in the standard-polyurethane group (risk difference, hydrophobic vs. standard polyurethane, -0.2 percentage points [95% confidence interval {CI}, -3.7 to 3.2; P = 0.89]; and chlorhexidine vs. standard polyurethane, 3.8 percentage points [95% CI, -0.1 to 7.8; P = 0.06]). In the hydrophobic group as compared with the standard-polyurethane group, the odds ratio for device failure was 0.96 (95% CI, 0.51 to 1.78), and in the chlorhexidine group as compared with the standard-polyurethane group, the odds ratio was 1.71 (95% CI, 0.98 to 2.99). Complications from any cause during the period of PICC placement occurred in 77 participants (21.5%) in the hydrophobic group, in 140 (38.6%) in the chlorhexidine group, and in 78 (21.7%) in the standard-polyurethane group (odds ratio, hydrophobic vs. standard polyurethane, 0.99 [95% CI, 0.69 to 1.42]; and chlorhexidine vs. standard polyurethane, 2.35 [95% CI, 1.68 to 3.29]). No adverse events were attributable to the interventions. Among adults and children who were referred for PICC placement, the risk of device failure due to noninfectious or infectious complications was not lower with hydrophobic or chlorhexidine PICCs than with standard polyurethane PICCs. (Funded by the National Health and Medical Research Council of Australia; PICNIC Australian New Zealand Clinical Trials Registry number, ACTRN12619000022167.).
FAIRS — A Framework for Evaluating the Inclusion of Sex in Clinical Algorithms
Authors: Katherine E Goodman, Jennifer Blumenthal-Barby, Rita F Redberg, Diane E Hoffmann
Journal: New England Journal of Medicine (2025)

If sex-based differences in risk result from biased care rather than biology, enshrining the associations in clinical algorithms may be inequitable and unlawful. How can appropriate boundaries be delineated?