tbuckley/cabot-search huggingface dataset:
Nivolumab and stereotactic radiosurgery for patients with breast cancer brain metastases: long-term results and biomarker analysis from a non-randomized, open-label, phase Ib study
Authors: Kamran A Ahmed, Younchul Kim, Sungjune Kim, Min Hsuan Wang, Michelle DeJesus, John A Arrington, Aixa E Soyano, Avan J Armaghani, Ricardo L B Costa, Loretta S Loftus, Marilin Rosa, Jimmy J Caudell, Roberto Diaz, Arnold B Etame, Nam D Tran, Hatem Soliman, Brian J Czerniecki, Peter A Forsyth, Hsiang-Hsuan Michael Yu, Hyo S Han
Journal: Journal for ImmunoTherapy of Cancer (2025)

Background We hypothesized treatment with nivolumab and stereotactic radiosurgery (SRS) would be feasible, well tolerated, and may improve intracranial tumor control over SRS alone for breast cancer brain metastases (BCBM). Methods The study is a phase Ib trial of nivolumab and SRS for BCBM. Clinical trial information: NCT03807765 . Key eligibility criteria include BCBM of all subtypes, age ≥18, Eastern Cooperative Oncology Group Performace Status (ECOG-PS)≤2 with ≤10 brain metastases. Treatment was initiated with a dose of nivolumab (480 mg intravenously) that was repeated every 4 weeks. The initial dose of nivolumab was followed 1 week later by SRS. Blood was collected at baseline and every 4 weeks for flow cytometry and cell-free DNA (cfDNA) assessment. Results A total of 12 patients received SRS to 17 brain metastases. Breast cancer subtypes included triple negative (50%), hormone receptor (HR)+/HER2− (33%), and HR−/HER2+ (17%). Median follow-up from start of protocol therapy is 56 months. No cases of radionecrosis were noted. Two lesions were noted to undergo local failure, both pathologically confirmed, for a 12-month local control of 94%. Median distant intracranial control was 7.4 months with a 12-month control rate of 33%. Median systemic progression-free survival was 7.7 months with a 12-month rate of 42%. Median overall survival (OS) was 24.7 months with a 12-month OS of 75%. Most patients were noted to have an increase in cfDNA throughout study treatment, at week 5 compared with baseline (83%), week 25 compared with baseline (89%), and 100% at first follow-up. Intracranial control was associated with lower levels of CD4 regulatory T cells (Treg) (p=0.03) and higher levels of CD4 T effector memory (p=0.04). Conclusions Nivolumab and SRS is a safe and feasible treatment option in BCBM. Long-term follow-up revealed no cases of radiation necrosis. Trial registration number NCT03807765 .
Artificial intelligence in drug development for delirium and Alzheimer’s disease
Authors: Ruixue Ai, Xianglu Xiao, Shenglong Deng, Nan Yang, Xiaodan Xing, Leiv Otto Watne, Geir Selbæk, Yehani Wedatilake, Chenglong Xie, David C. Rubinsztein, Jennifer E. Palmer, Bjørn Erik Neerland, Hongming Chen, Zhangming Niu, Guang Yang, Evandro Fei Fang
Journal: Acta Pharmaceutica Sinica B (2025)
Myopia control efficacy of Asymmetric Multi-point Defocus Technique spectacle lenses: 1-year double-masked randomized controlled trial
Authors: Mengyi Wang, Runting Ma, Longhao Kuang, Xiaoqin Chen, Stephen J Vincent, Hongmei Tan, Zhipeng Lai, Shengsong Xu, Yin Hu, Mengya Han, Qiwen Chen, Zixin Wang, Lihua Li, Xiao Yang
Journal: Ophthalmology (2025)
Gemcitabine and miRNA34a mimic codelivery with magnetic nanoparticles enhanced anti-tumor effect against pancreatic cancer
Authors: Nuria Lafuente-Gómez, Mario Martínez-Mingo, Zamira Vanessa Díaz-Riascos, Belén García-Prats, Irene de la Iglesia, Mónica Dhanjani, David García-Soriano, Luis A Campos, Sandra Mancilla-Zamora, Gorka Salas, Ibane Abasolo, Álvaro Somoza
Journal: Journal of Controlled Release (2025)
Nanoparticle-mediated dual targeting of stromal and immune components to overcome fibrotic and immunosuppressive barriers in hepatocellular carcinoma
Authors: Xiangyi Yin, Xingyang Zhao, Yiming Shen, Weizhong Xie, Cheng He, Jianan Guo, Zirong Li, Feichao Xuan, Silue Zeng, Xiaojun Zeng, Chihua Fang
Journal: Journal of Controlled Release (2025)
Sexual Trauma, Suicide, and Overdose in a National Cohort of Older Veterans
Authors: Anita S. Hargrave, Beth E. Cohen, Carolyn J. Gibson, Salomeh Keyhani, Yixia Li, W. John Boscardin, Amy L. Byers
Journal: Annals of Internal Medicine (2025)

Little is known about the association between military sexual trauma (MST) and risk for suicide-related outcomes later in life. To determine the association between MST and risk for suicide, overdose, and related mortality among older men and women at specific age landmarks and to investigate whether posttraumatic stress disorder (PTSD) modifies risk. Longitudinal cohort study; baseline in 2012 to 2013, with follow-up through 31 December 2020. All U.S. Department of Veterans Affairs (VA) medical centers in the United States. 5 059 526 veterans aged 50 years or older. Positive MST screening result, nonfatal suicide attempt, death by suicide, or overdose death. MST was documented for 15.7% of older women and 1.3% of older men. The adjusted cumulative incidence of any suicide attempt was higher for those with MST (men, 18.67%; women, 8.66%) than for those without MST (men, 6.25%; women, 2.92%) at age 90 years. The adjusted risk differences among men and women were 12.41% (95% CI, 11.72% to 13.10%) and 5.74% (CI, 5.22% to 6.26%) for any late-life suicide attempt, 11.92% (CI, 11.27% to 12.57%) and 5.58% (CI, 5.08% to 6.08%) for nonfatal suicide attempt, 0.27% (CI, 0.00% to 0.54%) and 0.15% (CI, 0.00% to 0.30%) for fatal suicide attempt, and 1.05% (CI, 0.79% to 1.31%) and 0.48% (CI, 0.28% to 0.68%) for any drug overdose at age 90 years. MST remained a significant risk factor for any suicide attempt among people with and without PTSD. Selection bias, generalizability to non-VA veterans, possible unmeasured confounding, and missingness. Late-life suicide attempt and death by suicide or overdose are associated with prior MST. These findings advance our understanding of the lasting effect of sexual trauma on suicide risk and mortality and suggest that monitoring and treatment of MST-related conditions are vital over the long term. VA Office of Research and Development.
Sins of Omission: Model-Based Estimates of the Health Effects of Excluding Pregnant Participants From Randomized Controlled Trials
Authors: Alyssa Bilinski, Natalia Emanuel, Andrea Ciaranello
Journal: Annals of Internal Medicine (2025)

More than 90 million women in the United States have given birth. Randomized controlled trials (RCTs) of medications almost always exclude pregnant participants. To quantify the health effects of excluding pregnant participants from RCTs. Decision analytic framework applied to case studies of thalidomide, COVID-19 vaccines, and dolutegravir. Varied. Pregnant people and their children. The authors modeled the ex post facto health effects of RCTs, comparing projected health effects of medication uptake had an RCT been conducted versus historically observed outcomes. They also modeled the a priori health effects that could have been anticipated in trial planning. They converted health effect estimates to monetary value using standard benchmarks. Across case studies, health benefits from conducting RCTs during pregnancy were projected to far exceed expected adverse effects (AEs) from RCTs. For example, had thalidomide been tested in a completed RCT with 200 treated participants, about 33 children would have experienced severe AEs, whereas knowledge from the RCT would have prevented 8000 thalidomide-related birth defects, 99.6% of all thalidomide-related birth defects from 1956 to 1962. Likewise, if RCTs for COVID-19 vaccines had included pregnant participants and if posttrial pregnant uptake were conservatively assumed to mirror that of age- and state-matched nonpregnant women, a projected 20% of COVID-19-related maternal deaths and stillbirths (8% of all maternal deaths and 1% of all stillbirths) in the United States would have been prevented from March to November 2021. Across case studies, the a priori value of RCT data would have exceeded the approximately $100 million cost of phase 1 to 3 RCTs. Parameter uncertainty. Systematic inclusion in RCTs could benefit both pregnant people and their children by both speeding AE detection and increasing uptake of beneficial medications. None.
Empowering Physicians Through Collective Action: A Position Paper From the American College of Physicians
Authors: Ryan Crowley, David Hilden, Jenny R. Silberger, David Hilden, Jenny R. Silberger, Micah W. Beachy, Priscilla W. Carr, Jan K. Carney, Cynthia A. Jumper, Selvam Joseph Mascarenhas, Celeste Newby, Austin Oslock, Amelia Papadimitriou, Jamar Slocum, Priya Radhakrishnan, Michael J. Tan
Journal: Annals of Internal Medicine (2025)

Physicians are increasingly frustrated with the nation's health care system. The erosion of the patient-physician relationship, diminished clinical independence, the mounting burden of administrative tasks, and the growing influence of nonclinicians in the health care system have left many physicians disempowered, demoralized, and burned out. As a result, physicians, most of whom are employed by hospitals, health systems, and other organizations, are exploring collective action to enhance their ability to deliver high-quality care to patients, regain control of their profession, and improve their well-being. In this position paper, the American College of Physicians offers recommendations on how physicians can become effective advocates for their patients and their profession through advocacy, the organized medical staff, responsible collective bargaining, and other means.
High Frequency of Chronic Urticaria Following an Investigational HIV-1 BG505 MD39.3 Trimer mRNA Vaccine in a Phase 1, Randomized, Open-Label Clinical Trial (HVTN 302)
Authors: Sharon A. Riddler, Zoe Moodie, Jesse Clark, Catherine Yen, Mary Allen, Briana D. Furch, Huiyin Lu, Shannon Grant, Kajari Mondal, Maija Anderson, Janine Maenza, Maria P. Lemos, Amanda S. Woodward Davis, Stephen R. Walsh, Magdalena E. Sobieszczyk, Ian Frank, Paul Goepfert, Kathryn E. Stephenson, Lindsey R. Baden, Hong-Van Tieu, Michael C. Keefer, M. Juliana McElrath, James G. Kublin, Lawrence Corey
Journal: Annals of Internal Medicine (2025)

The mRNA platform is under investigation for many vaccines, including HIV-1 vaccines. To evaluate the safety and tolerability of 3 investigational HIV-1 trimer mRNA vaccines. Safety analysis of mRNA vaccination in a phase 1, randomized, open-label trial. (ClinicalTrials.gov: NCT05217641). Ten research sites in the United States. 108 volunteers aged 18 to 55 years without HIV-1. Investigational HIV-1 BG505 MD39.3 trimer mRNA vaccines (gp140 soluble trimer, gp151 membrane-bound trimer, and gp151 CD4KO membrane-bound trimer) at doses of 100 and 250 mcg at 0, 2, and 6 months. Solicited and unsolicited adverse reactions and events reported during the 12 months after the first vaccination. Participants (n = 108) were randomly assigned to 6 vaccine groups. Mild to moderate local and systemic solicited events were common. Eighty participants reported 190 unsolicited adverse events (AEs); 30 were considered to be related to a study product. Most (73%) related AEs were mild, and the rest were moderate. Among related AEs, urticaria was reported by 7 of 108 participants (7% [95% CI, 3% to 13%]), 4 of whom had unresolved, intermittent urticaria at 12 months. In post hoc analyses, demographic characteristics, history of allergy or medication use, and COVID-19 were not associated with urticaria. In a comparison of participants with versus without urticaria, 100% (7 of 7; CI, 65% to 100%) versus 37% (37 of 101; CI, 28% to 46%) reported previous Moderna COVID-19 vaccination, 29% (2 of 7; CI, 8% to 64%) versus 76% (77 of 101; CI, 67% to 84%) reported previous Pfizer-BioNTech COVID-19 vaccination, and 0% (0 of 7; CI, 0% to 35%) versus 5% (5 of 101; CI, 2% to 11%) reported no previous mRNA COVID-19 vaccination. Lack of a placebo group, open-label study, and post hoc evaluation of urticarial risk. Urticarial reactions associated with experimental HIV-1 mRNA vaccines were observed in this trial. Studies to investigate the mechanism and approaches to mitigate these reactions are underway to further advance HIV-1 vaccine research. National Institutes of Health, National Institute of Allergy and Infectious Diseases.
Impact of the COVID-19 Pandemic on Antibiotic Resistant Infection Burden in U.S. Hospitals
Authors: Christina Yek, Alex G. Mancera, Guoqing Diao, Morgan Walker, Maniraj Neupane, Emad A. Chishti, Roxana Amirahmadi, Mary E. Richert, Chanu Rhee, Michael Klompas, Bruce Swihart, Sarah R. Warner, Sameer S. Kadri, Christina Yek, Alex G. Mancera, Guoqing Diao, Morgan Walker, Maniraj Neupane, Emad A. Chishti, Roxana Amirahmadi, Mary E. Richert, Chanu Rhee, Michael Klompas, Bruce Swihart, Sarah R. Warner, Sameer S. Kadri
Journal: Annals of Internal Medicine (2025)

In 2022, the U.S. Centers for Disease Control and Prevention reported increases in antimicrobial resistance (AMR) across U.S. hospitals during the COVID-19 pandemic. The key drivers and lasting effects of this phenomenon remain unexplored. To determine the incidence of AMR infections in U.S. hospitals during and beyond the pandemic and identify factors contributing to AMR. Retrospective cohort study. 243 U.S. hospitals. Adult hospitalizations, excluding inpatient transfers. Prepandemic (January 2018 to December 2019), peak pandemic (March 2020 to February 2022), and waning pandemic (March to December 2022). Incidence of methicillin-resistant Staphylococcus aureus; vancomycin-resistant Enterococci; extended-spectrum cephalosporin-resistant Enterobacterales; and carbapenem-resistant Enterobacterales, Acinetobacter baumannii, and Pseudomonas aeruginosa infections was evaluated among 120 continuously reporting hospitals. Infections detected more than 3 days after admission were classified as hospital-onset. Antibiotic exposure was estimated using a duration- and spectrum-weighted index. A competing risks analysis was done in 243 hospitals to identify risk factors for resistance. During the peak of the COVID-19 pandemic, AMR infections increased from 182 to 193 per 10 000 hospitalizations (6.5% [95% CI, 5.1% to 8.0%]). Hospital-onset AMR infections increased from 28.9 to 38.0 per 10 000 hospitalizations (31.5% [CI, 27.3% to 35.8%]). Factors associated with hospital-onset AMR included illness severity (intensive care unit admission, mechanical ventilation, vasopressors, COVID-19 diagnosis), comorbidities (Elixhauser Comorbidity Index), and prior exposure to antibiotics, but not hospital factors. Prevalence of AMR returned to prepandemic levels as the pandemic waned (182 to 182 per 10 000 hospitalizations; 0.4% [CI, -1.4% to 2.2%]), however, hospital-onset AMR remained above baseline (28.9 to 32.3 per 10 000 hospitalizations; 11.6% [CI, 6.8% to 16.7%]). Residual confounding; unknown appropriateness of antibiotics. Sustained increases in hospital-onset AMR infections occurred in U.S. hospitals during the pandemic and were strongly associated with antibiotic exposure. National Institutes of Health Clinical Center; National Heart, Lung, and Blood Institute; and National Institute of Allergy and Infectious Diseases Intramural Research Programs.
PLT012, a Humanized CD36-Blocking Antibody, Is Effective for Unleashing Antitumor Immunity Against Liver Cancer and Liver Metastasis
Authors: Sheue-Fen Tzeng, Yi-Ru Yu, Jaeoh Park, Janusz von Renesse, Huey-Wen Hsiao, Chen-Hsuan Hsu, Josep Garnica, Jintian Chen, Lu-Ting Chiu, Jonas Santol, Tse-Yu Chen, Pei-Han Chung, Lana E. Kandalaft, Patrick Starlinger, Rodney Cheng-En Hsieh, Ming-Chin Yu, Pei-Wen Hsiao, Santiago J. Carmona, Hung-Kai Chen, Zhen Meng, Yun-Han Lin, Jingying Zhou, Chin-Hsien Tsai, Ping-Chih Ho
Journal: Cancer Discovery (2025)

Abstract Tumor cells develop various strategies to evade immune surveillance, one of which involves altering the metabolic state of the tumor microenvironment. In response to metabolic stress in the tumor microenvironment, several tumor-infiltrating immune subsets upregulate CD36 to take up lipids. This leads to impaired antitumor immunity, as intratumoral regulatory T cells exhibit increased survival and suppressive activity, whereas CD8+ T cells become more susceptible to ferroptosis and exhaustion. In this study, we develop a humanized anti-CD36 IgG4 antibody, PLT012, against the lipid-binding domain of CD36 with excellent safety and favorable pharmacokinetic features in mice and cynomolgus monkeys. PLT012 alone or in combination with PD-L1 blockade or standard-of-care immunotherapy results in robust antitumor immunity in both immunotherapy-sensitive and -resistant hepatocellular carcinomas (HCC). Notably, PLT012 also reprograms the immune landscape of human HCC ex vivo. Our findings provide proof-of-concept evidence that PLT012 reprograms antitumor immunity in HCC, positioning it as a first-in-class immunotherapy targeting CD36. Significance: Despite the success of cancer immunotherapies, like immune checkpoint inhibitors, many patients still fail to demonstrate significant responses because of metabolic constraints in tumors. PLT012 rejuvenates antitumor immunity by targeting metabolic pathways to reprogram the immune landscape of liver cancer and liver metastasis, with potential to influence future HCC immunotherapy.
Direct Inhibition of RAS Reveals the Features of Oncogenic Signaling Driven by RAS G12 and Q61 Mutations
Authors: Michelangelo Marasco, Dinesh Kumar, Santiago Garcia Borrego, Tessa Seale, Giulia Maddalena, Riccardo Mezzadra, Kylie Belanger, Soren Cole, Brayan Perez, Wei Luan, Radha Mukherjee, Ilinca Aricescu, Vladimir Markov, Yuxin Zhu, Sabrina Arena, Alberto Bardelli, Elisa de Stanchina, Scott W. Lowe, Richard A. Burkhart, Jacquelyn W. Zimmerman, Rona Yaeger, Scott E. Kopetz, Neal Rosen, Sandra Misale
Journal: Cancer Discovery (2025)

Abstract RAS genes are frequently mutated in cancer, often at codons 12 and 61. With the recent introduction of RAS inhibitors, we can now directly investigate the effects of specific RAS mutations in cancer cells. In this study, we demonstrate that in tumors with RASG12X mutations, mutant RAS can be activated by receptor tyrosine kinases (RTK), and PI3K activation is dependent on mutant RAS. Conversely, RASQ61X mutations activate the MAPK cascade independently of RTKs, and inhibition of RASQ61X impairs MAPK pathway activation but leaves the PI3K pathway unaffected. Our characterization of these distinct features of G12X and Q61X mutations suggests that co-inhibition of RAS and RTKs selectively inhibits the growth of RASG12X-mutant tumors, both in vitro and in vivo, regardless of the RAS isoform and tumor type. Additionally, our findings offer a mechanistic explanation for the increased frequency of RASQ61X mutations as a secondary resistance mechanism against EGFR inhibition in colorectal cancer. Significance: RAS inhibition in multiple tumor types reveals the difference between G12 mutants and Q61 mutants in their cooperation with upstream regulators and downstream effectors to promote oncogenic signaling. Our findings provide the rationale for combinatorial approaches and contribute to explaining the nonuniform distribution of RAS mutations, de novo and at resistance.
Intra-hepatic microbial heterogeneity in multifocal hepatocellular carcinoma and its association with host genomic and transcriptomic alterations
Authors: Yinghong Lu, Lixia Xu, Weikang Chen, Weixin Liu, Ying Zhang, Qianying Zhou, Na Wang, Yongxin Zhang, Haojie Bai, Shu Xu, Pingmei Huang, Kaili Fu, Wenxuan Xie, Xin Liu, Xueliang Wang, Chi Chun. Wong, Ming Kuang, Jun Yu
Journal: Cancer Discovery (2025)

Abstract The signature of intrahepatic microbiome in multifocal hepatocellular carcinoma (HCC) and its association with genomic alterations remain elusive. Here, we performed multi-omics profiling of 242 HCC tumor nodules and 58 adjacent non-tumor tissues from 58 multifocal HCC patients, revealing heterogeneous microbial communities in multifocal HCC. Presence of bacteria in HCC nodules was confirmed by gram-stain, LPS, LTA staining and TEM. Mutational profiling stratified patients into intrahepatic metastasis (IM)-HCC and multicentric occurrence (MO)-HCC. Bacterial communities differed between IM and MO nodules (P=0.01). A 9-bacteria biomarker panel could distinguish IM nodules from MO nodules with AUROC of 0.795. Epithelial-mesenchymal transition (EMT) pathway was up-regulated in IM nodules and correlated with IM-enriched bacteria. IM-enriched bacteria such as Enterococcus faecalis and Streptococcus anginosus promoted HCC cell migration and invasion, and tumor progression in orthotopic HCC mouse models by inducing immunosuppressive microenvironment and EMT. Collectively, intrahepatic microbiome contributes to heterogeneity and pathogenesis of multifocal HCC.
Target Attainment of Benzylpenicillin in Patients with Infective Endocarditis
Authors: Magnus Bock, Johan G C Van Hasselt, Kurt Fuursted, Nikolaj Ihlemann, Sabine Gill, Ulrik Christiansen, Niels Eske Bruun, Hanne Elming, Jonas A Povlsen, Lars Køber, Dan E Høfsten, Emil L Fosbøl, Mia M Pries-Heje, Jens Jørgen Christensen, Flemming S Rosenvinge, Christian Torp Pedersen, Jannik Helweg-Larsen, Niels Tønder, Kasper Iversen, Henning Bundgaard, Claus Moser
Journal: Clinical Microbiology and Infection (2025)
SARS-CoV-2 test sensitivity and duration of positivity in the UK during the 2023/2024 Winter: A Prospective Cohort Study Based on Self-Reported Data
Authors: Christopher E Overton, Martyn Fyles, Jonathon Mellor, Robert S Paton, Alexander M Phillips, Alex Glaser, Andre Charlett, Thomas Ward
Journal: Journal of Infection (2025)