tbuckley/cabot-search huggingface dataset:
Cardiac Effects of Modern Breast Radiation Therapy in Patients Receiving Systemic Cancer Therapy
Authors: Eva Berlin, Kyunga Ko, Lin Ma, Ian Messing, Casey Hollawell, Amanda M Smith, Neil K Taunk, Vivek Narayan, Jenica N Upshaw, Amy S Clark, Payal D Shah, Hayley Knollman, Saveri Bhattacharya, Daniel Koropeckyj-Cox, Jessica Wang, Nikhil Yegya-Raman, Ivy S Han, Benedicte Lefebvre, Tang Li, Nicholas S Wilcox, Wonyoung Jung, Jinbo Chen, Gary M Freedman, Bonnie Ky
Journal: JACC CardioOncology (2025)

Radiation therapy (RT) improves breast cancer outcomes, but cardiac morbidity remains a concern. This study sought to evaluate changes in cardiac function after RT and the relationship between cardiac dose metrics and echocardiography-derived measures of function. In a longitudinal cohort study of women with breast cancer, radiation cardiac dose metrics and core lab quantitated echocardiographic measures of cardiac function were evaluated. Dose metrics included the whole heart, left ventricle, right ventricle, and left anterior descending artery (LAD). Echocardiographic measures included left ventricular ejection fraction (LVEF), longitudinal strain, circumferential strain, E/e' (ratio of early diastolic mitral inflow velocity to early diastolic mitral annular tissue velocity), Ea/Es (ventricular arterial coupling; ratio of effective arterial elastance to end systolic elastance), and right ventricular fractional area change. The mean change in echocardiographic measures over time and the association between cardiac dose metrics and echocardiographic measures were estimated by repeated-measures multivariable linear regression via generalized estimating equations. The cohort included 303 participants (median age 52 years, 33.3% African American) who received adjuvant RT (2010-2019) with a median mean heart dose of 1.19 Gy (Q1-Q3: 0.75-2.61 Gy), were followed over a median of 5.1 years (Q1-Q3: 3.2-7.1 years). Across all participants, there was a modest increase in LVEF (52.1% pre-RT to 54.3% at 5 years; P < 0.001) but a worsening in sensitive measures of function, such as circumferential strain (-23.7% pre-RT to -21.0% at 5 years; P = 0.003). Among left-sided/bilateral breast cancer participants, changes in cardiac function were observed across all parameters (P < 0.05). The maximum LAD dose was associated with a modest worsening in LVEF, longitudinal strain, circumferential strain, and E/e'. Over a median of 5.1 years, modest changes in cardiac function were observed with RT. Maximum LAD dose was associated with a worsening in systolic and diastolic function parameters.
Repair of Isoaspartyl Residues by PCMT1 and Kidney Fibrosis
Authors: Jia Xia, Yutong Hou, Jie Wang, Jiahui Zhang, Jiajia Wu, Xiang Yu, Hong Cai, Wen Yang, Yingjie Xu, Shan Mou
Journal: Journal of the American Society of Nephrology (2025)

Kidney fibrosis, the excessive accumulation and dysregulated remodeling of the extracellular matrix, is the principal pathophysiological process in chronic kidney disease (CKD). Protein L-isoaspartyl/D-aspartyl methyltransferase (PCMT1) is crucial in repairing post-translational modifications of L-isoaspartyl residues, which are important for extracellular matrix proteins because of their low turnover rate and susceptibility to accelerating factors. This study aimed to reveal a novel role of PCMT1 in kidney fibrosis. Kidney tissues from mice and humans were evaluated for PCMT1 expression and its association with fibrosis and kidney function. PCMT1's effects on the TGF-β1/Smad signaling were analyzed, and its functional role was assessed in tubule-specific Pcmt1 knockout murine models of kidney fibrosis. The ability of secreted PCMT1 to repair L-isoaspartyl residues on the ectodomain of transforming growth factor beta receptor 2 (TGFBR2) was investigated through immunoprecipitation, gene lentivirus overexpression or knockout, and post-translational modification mass spectrometry. PCMT1 expression was decreased in the tubules of human kidney biopsies from patients with CKD and murine fibrosis models. Renal tubule-specific PCMT1 deficiency in murine kidney fibrosis models worsened tubular injury, extracellular matrix protein deposition, myofibroblast activation, and TGF-β1/Smad signaling overactivation. Mechanistically, PCMT1 was unconventionally secreted and enzymatically inhibited TGF-β1-induced extracellular matrix protein deposition in vitro. PCMT1 interacted with TGFBR2, reversing N63 deamination on its ectodomain, which triggered TGFBR2 ubiquitination and degradation. PCMT1 supplementation in kidneys decreased TGFBR2 levels, attenuated TGF-β1/Smad overactivation, and impeded the profibrotic process. Our study highlights the importance of PCMT1 in maintaining extracellular matrix homeostasis and mitigating kidney fibrosis by regulating TGFBR2 deamination and its protein stability, suppressing the TGF-β1/Smad signaling.
ORCHESTRA Delphi Consensus: Diagnostic and Therapeutic Management of SARS-CoV-2 Infection in Rheumatological Patients
Authors: Maria Giulia Caponcello, Paula Olivares Navarro, Cecilia Bonazzetti, Caterina Campoli, Alessia Savoldi, Elisa Gentilotti, Antonella d'Arminio Monforte, Sergio Lo Caputo, Lucía Otero-Varela, Isabel Castrejón, Evelina Tacconelli, Jesús Rodríguez-Baño, Zaira R Palacios-Baena, Dolores Mendoza Mendoza, Virginia Moreira Navarrete, Alessandro Tomelleri, Lotta Ljung, Teresa Martins Rocha, Pedro Palma, Zaira R Palacios-Baena, Elena Salamanca-Rivera, María Paniagua-García, Angelo Fassio, Riccardo Bixio, Enrico Tombetti, Cristina Garufi, Fabrizio Conti
Journal: Clinical Microbiology and Infection (2025)
A Critical Appraisal of the Utility of Targeting Therapy-induced Senescence for Cancer Treatment
Authors: Tareq Saleh, Edward F. Greenberg, Anthony C. Faber, Hisashi Harada, David A. Gewirtz
Journal: Cancer Research (2025)

Cancer chemotherapy and radiotherapy are rarely successful in eliminating the entire tumor population, often leaving behind a subpopulation of senescent cells that can contribute to disease recurrence. These senescent tumor cells also secrete various chemokines and cytokines that may be tumor-promoting and immunosuppressive. Recognition of the deleterious impact of therapy-induced senescence has led to the preclinical development of senolytic compounds that eliminate senescent cells, representing a potential strategy to enhance the efficacy of conventional and targeted anticancer therapy. However, it remains uncertain whether this strategy can or will be translated to the clinic. This review provides a summary of the recent preclinical literature supporting the use of senolytics as an adjunct for cancer treatment, discusses the limitations associated with current preclinical models, and provides perspectives on the clinical development of senolytics in cancer treatment regimens. Overall, preclinical studies support the potential of senolytics to enhance efficacy and prolong the antitumor activity of current standard-of-care cancer therapies that promote senescence. However, further work is needed to develop optimal senolytic agents with the appropriate combination of properties for clinical testing, specifically activity in the context of therapy-induced senescence with acceptable tolerability.
Asian Conference on Tumor Ablation Guidelines for Hepatocellular Carcinoma
Authors: Shuichiro Shiina, Ryosuke Tateishi, Joon Il Choi, So Yeon Kim, Zhiqiang Meng, Lujun Shen, Sheng-Nan Lu, Jen-I Hwang, Maki Tobari, Hitoshi Maruyama, Terguunbileg Batsaikhan, Qing Deng, Lariza Marie Canseco, Yoshinari Asaoka, Shi-Ming Lin, Kai-Wen Huang, Hyunchul Rhim, Ping Liang, Uei Pua, Masatoshi Tanaka, Peihong Wu
Journal: Liver Cancer (2025)

Globally, the incidence and associated mortality of primary liver cancer have been steadily increasing. Currently, 80% of cases are found in Asia. Curative resection is applicable in only 20% of patients; therefore, various nonsurgical treatment modalities have been developed. Image-guided percutaneous liver tumor ablation is regarded as the best option for treating early-stage hepatocellular carcinoma (HCC). However, skills and knowledge in ablation can vary among operators. Furthermore, Asia has the highest number of ablation procedures for HCC and the largest number of doctors performing ablation worldwide. Thus, the Asian Conference on Tumor Ablation has developed guidelines for HCC. These guidelines will discuss indications, pre-ablative diagnosis and planning, techniques, peri-ablative management, evaluation of therapeutic effectiveness, complications, post-ablative follow-up, prevention of recurrence, and treatment of recurrence for HCC.
Depth and Duration of Response Are Associated With Survival in Patients With Unresectable Hepatocellular Carcinoma: Exploratory Analyses of IMbrave150
Authors: Masatoshi Kudo, Tatsuya Yamashita, Richard S Finn, Peter R Galle, Michel Ducreux, Ann-Lii Cheng, Kaoru Tsuchiya, Naoya Sakamoto, Shuhei Hige, Ryosuke Take, Kyoko Yamada, Yuki Nakagawa, Hayato Takahashi, Masafumi Ikeda
Journal: Liver Cancer (2025)

IMbrave150 established first-line atezolizumab plus bevacizumab as a global standard of care for unresectable hepatocellular carcinoma (HCC). We report exploratory analyses of associations between overall survival (OS) and depth of response (DpR) or duration of response (DoR). IMbrave150 was a phase III randomized study of atezolizumab plus bevacizumab versus sorafenib in patients with unresectable HCC. DpR was defined as maximum tumor shrinkage from baseline based on the sum of longest diameters per independent review facility (IRF)-assessed RECIST 1.1. DoR was defined as time from first complete/partial response by IRF-assessed RECIST 1.1 until progression or death. Associations between OS and DpR or DoR were evaluated by scatterplot in both arms; OS and PFS were evaluated by DpR in atezolizumab plus bevacizumab-treated patients. To minimize immortal time bias, the DpR analysis included patients who survived ≥6 months. Of 312 and 140 patients with baseline measurable disease in the atezolizumab plus bevacizumab and sorafenib arms, respectively, 264 and 99 surviving ≥6 months were included in the DpR analysis, and 97 and 18 in the DoR analysis. Tumor shrinkage occurred in 230/312 (74%) patients in the atezolizumab plus bevacizumab arm and 76/140 (54%) in the sorafenib arm; their mean (SD) DpR was -42.5% (32.4%) and -25.0% (21.9%), respectively. Atezolizumab plus bevacizumab-treated ≥6-month survivors with DpR <0% had improved OS versus those with DpR ≥0% (HR: 0.29; 95% CI: 0.19-0.44). Those with deeper responses (DpR -100% to -60%) had longer OS than those with DpR ≥20% (unstratified HR: 0.08; 95% CI: 0.03-0.21). In scatterplots, DpR and DoR were generally associated with OS in both arms; interpretation was limited by censored patients. DpR and DoR to atezolizumab plus bevacizumab and sorafenib were associated with OS in patients with unresectable HCC. More longer, deeper responses occurred with atezolizumab plus bevacizumab.
Expanded Hemodialysis with Theranova Dialyzer and Residual Kidney Function in Incident Hemodialysis Patients
Authors: Jeong-Hoon Lim, Yu Jin Seo, Yena Jeon, You Hyun Jeon, Hee-Yeon Jung, Ji-Young Choi, Sun-Hee Park, Chan-Duck Kim, Seok Hui Kang, Jung-Hwa Ryu, Duk-Hee Kang, Jang-Hee Cho, Yong-Lim Kim
Journal: Journal of the American Society of Nephrology (2025)

Expanded hemodialysis (HD) using a medium cut-off dialyzer improves the clearance of middle-molecular toxins compared to conventional HD. This study evaluated the effect of expanded HD on preserving residual kidney function in incident HD patients. Patients who initiated HD were randomized to receive dialysis with either a Theranova 400 (Baxter) or a high-flux dialyzer with a similar surface area over 12 months. The primary outcome was a change in glomerular filtration rate (GFR) over 12 months, as determined by the mean of urea and creatinine clearance. The secondary outcome was a change in 24-hour urine volume, middle molecules, and kidney injury markers. A total of 80 HD patients (mean age [SD]: 63 [12] years; male: 52 [65%]) underwent randomization. Over 12 months, the Theranova group demonstrated a significantly smaller decrease in GFR than the high-flux group (least-squares mean difference of change [95% confidence interval]: -1.4 [-2.4, -0.5] mL/min/1.73 m2). Theranova maintained greater 24-hour urine volume until 9 months, not at 12 months, compared to the high-flux dialyzer. The reduction ratio for κ/λ free light chains, TNF-α, and GDF-15 was higher in the Theranova group than in the high-flux group. The increase in the kidney injury marker, IGFBP7, was attenuated in the Theranova group. Hospitalization rate and mortality did not differ between the two groups. This trial suggests that expanded HD using the Theranova dialyzer may slow decline in residual kidney function compared with a high-flux dialyzer in incident HD patients.
Brain dopamine responses to ultra-processed milkshakes are highly variable and not significantly related to adiposity in humans
Authors: Valerie L Darcey, Juen Guo, Meible Chi, Stephanie T Chung, Amber B Courville, Isabelle Gallagher, Peter Herscovitch, Paule V Joseph, Rebecca Howard, Melissa La Noire, Lauren Milley, Alex Schick, Michael Stagliano, Sara Turner, Nicholas Urbanski, Shanna Yang, Nan Zhai, Megan S Zhou, Kevin D Hall
Journal: Cell Metabolism (2025)
Testing the carbohydrate-insulin model: Short-term metabolic responses to consumption of meals with varying glycemic index in healthy adults
Authors: Ying Liu, Huihui Mei, Li Xue, Chuanli Cheng, Yingtong Wu, Chao Zou, Ying Yu, Lin Gao, Huanan Zhang, Xinrui Gao, Qiang Li, Lu Wang, Jie Liu, Chaoqun Niu, Xueying Zhang, Sumei Hu, John R. Speakman
Journal: Cell Metabolism (2025)

The carbohydrate-insulin model predicts that meals with varying glycemic indices will elicit distinct metabolic and hunger responses, including greater intake at subsequent meals following high-glycemic-index meals. To test this, a randomized trial (NCT05804942) was conducted in healthy adults using intervention meals with low, medium, and high glycemic indices and a constant macronutrient composition. After intake of the intervention meals, glucose and insulin followed the predicted pattern, but subjective hunger did not. At the group level, low glycemic index meals led to lower energy intake changes. At the individual level, energy intake changes were unrelated to body fatness or levels of glucose, β-hydroxybutyrate, free fatty acids, L-lactate, leptin, adrenaline, glucagon-like peptide-1, glucagon, and insulin-glucagon ratio. A weak negative association was observed between energy intake changes and insulin or insulin-glucagon ratio at 300 min, opposite to the model's prediction. These data provide little support for the carbohydrate-insulin model.
CRTC2 Forms Co-condensates with YTHDF2 that Enhance Translational Efficiency of m6A-Modified mRNAs to Drive Hepatocarcinogenesis and Lenvatinib Resistance
Authors: Meixi Wang, Fangdi Zou, Shengxin Wang, Yichen Yang, Cong Xia, Lu Chen, Ben Liu, Lian Li, Mulin Jun Li, Haixin Li, Weijie Song, Ruifang Niu, Zhiyong Yuan, Jie Yang, Xiangchun Li, Kexin Chen, Zhiqiang Wu, Zeyun Mi
Journal: Cancer Research (2025)

As the third most common cause of cancer-related mortality, hepatocellular carcinoma (HCC) is a global health concern. Despite its prevalence, treatment options are limited, underscoring the need to identify potential therapeutic targets and strategies. Here, we identified amplification of CRTC2, situated in the 1q21.3 region, due to copy number alterations in HCC. In a cohort of patients with HCC, CRTC2 protein levels were frequently elevated and correlated with poor prognosis. Genetic deletion of CRTC2 significantly impeded the onset and progression of HCC in mouse models. CRTC2 formed cytoplasmic condensates that recruited the m6A reader YTHDF2. Furthermore, CRTC2 promoted the translocation of m6A-modified mRNAs from decay sites to polyribosomes by interacting with PABP1. The activities of CRTC2 counteracted YTHDF2-mediated mRNA degradation to enhance the translational efficiency of specific mRNAs, including those encoding LRP5 and c-Jun. Targeting CRTC2 in hepatocytes using AAV8.sgCRTC2 elicited substantial therapeutic benefits in HCC mouse model and significantly enhanced the sensitivity to lenvatinib. Together, this research elucidates the pivotal role and underlying molecular mechanisms of CRTC2 in hepatocarcinogenesis and lenvatinib-resistance, highlighting its potential clinical and therapeutic applications.
Adoption of Decentralized Trial Elements in Cancer Clinical Trials Supporting FDA Approvals During COVID-19
Authors: Timil H. Patel, Amy Corneli, Pamela Balcazar, Craig Lipset, Sara B. Calvert, Sabrena Mervin-Blake, Vinit Nalawade, Paul G. Kluetz
Journal: Clinical Cancer Research (2025)

The COVID-19 pandemic disrupted cancer clinical trials, prompting sponsors to adopt decentralized clinical trial (DCT) elements to ensure patient safety and trial continuity. Supported by FDA emergency guidance, the FDA Oncology Center of Excellence, in collaboration with the Clinical Trials Transformation Initiative (CTTI), conducted an assessment of DCT elements in cancer trials leading to FDA approval during the pandemic. Between December 6, 2022, and January 17, 2023, CTTI collected survey data from trial sponsors about DCT elements used in response to the pandemic, implementation challenges, and anticipated future use. Out of 52 eligible trials, 19 responses were received from 13 sponsors, predominantly large pharmaceutical companies. The majority of trials (89%) included both U.S. and international sites, and nearly all sponsors (95%) adopted at least one DCT element during the pandemic. Key DCT elements included remote site monitoring (89%), telemedicine (68%), remote laboratory assessments (63%), and remote distribution of investigational products (58%). Main challenges encountered included institutional policies (83%), technology adoption (61%), and regulatory restrictions (56%). Despite challenges, sponsors showed strong intent to continue DCT use, especially for remote monitoring, patient-reported outcomes collection, and telemedicine. This study demonstrates the viability of DCT elements for generating FDA-approvable data, suggesting potential for expanded trial access and reduced patient burden. Continued attention to site-level challenges is needed to sustain DCT adoption in cancer clinical trials.
On the causes of obesity and its treatment: The end of the beginning
Authors: Jeffrey M. Friedman
Journal: Cell Metabolism (2025)

Over the last 30 years, our understanding of the causes of obesity has been transformed, and new, highly effective medicines for reducing weight have been developed. This remarkable progress marks an end and a beginning. By establishing that obesity is a biologic disorder amenable to scientific inquiry and rational drug development, simplistic notions about its causes and treatment should be laid to rest. The future holds the promise that additional therapeutic approaches for inducing or maintaining weight loss will be developed, and that these treatments will be tailored to different subgroups to potentially address the pathogenic mechanisms.
Macrophage-Derived Itaconate Suppresses Dendritic Cell Function to Promote Acquired Resistance to Anti-PD-1 Immunotherapy
Authors: Xiao Yang, Yue Deng, Ying Ye, Jingshu Meng, Mengyao Su, Wenwen Wei, You Qin, Haibo Zhang, Yu Tian, Suke Deng, Zhiyun Liao, Zhiyuan Zhou, Jie Li, Yan Hu, Bin Zhang, Yajie Sun, Lu Wen, Zhanjie Zhang, Fang Huang, Chao Wan, Kunyu Yang
Journal: Cancer Research (2025)

Adaptive resistance to immunotherapy remains a significant challenge in cancer treatment. The reshaping of the tumor immune microenvironment in response to therapeutic pressures is a crucial factor contributing to this resistance. Here, by comprehensive metabolic profiling of tumor tissues, we identified elevated itaconate in response to anti-PD-1 therapy as an adaptive resistance mechanism that promoted immune escape and tumor progression. CD8+ T-cell-derived interferon (IFN)-γ induced a significant upregulation of cis-aconitate decarboxylase 1 (ACOD1) in macrophages via the JAK-STAT1 pathway, thereby rewiring the Krebs cycle toward itaconate production. In murine models, macrophage-specific deletion of Acod1 increased the anti-tumor efficacy of anti-PD-1 therapy and improved survival. Additionally, itaconate and its derivative, 4-octyl itaconate (4-OI), suppressed the tumor antigen presentation and cross-priming ability of dendritic cells (DCs), resulting in the impairment of antigen-specific T-cell anti-tumor responses. In summary, these findings identify an IFN-γ-dependent immunometabolic mechanism of anti-PD-1 resistance, providing a promising strategy for combination therapy.
MXene-loaded Multifunctional Nanoparticles with On-demand Controlled Antimicrobial and Antioxidant Capacity for Multi-modal Treating Bacterial Prostatitis
Authors: Kailai Liu, Yanyao Gao, Yuchen Zhang, Yunhe Zheng, Jiangchuan He, Yu Huang, Xi Chen, Ruixiao Li, Qiang Fu, Bin Song, He Wang, Lei Wang, Geng Zhang, Ke Wang
Journal: Biomaterials (2025)
Transfer learning radiomic model predicts intratumoral tertiary lymphoid structures in hepatocellular carcinoma: a multicenter study
Authors: Shichao Long, Mengsi Li, Juan Chen, Linhui Zhong, Ganmian Dai, Deng Pan, Wenguang Liu, Feng Yi, Yue Ruan, Bocheng Zou, Xiong Chen, Kai Fu, Wenzheng Li
Journal: Journal for ImmunoTherapy of Cancer (2025)

Intratumoral tertiary lymphoid structures (iTLS) in hepatocellular carcinoma (HCC) are associated with improved survival and may influence treatment decisions. However, their non-invasive detection remains challenging in HCC. We aim to develop a non-invasive model using baseline contrast-enhanced MRI to predict the iTLS status. A total of 660 patients with HCC who underwent surgery were retrospectively recruited from four centers between October 2015 and January 2023 and divided into training, internal test, and external validation sets. After features dimensionality and selection, corresponding features were used to construct transfer learning radiomic (TLR) models for diagnosing iTLS, and model interpretability was explored with pathway analysis in The Cancer Genome Atlas-Liver HCC. The performances of models were assessed using the area under the receiver operating characteristic curve (AUC). The log-rank test was used to evaluate the prognostic value of the TLR model. The combination therapy set of 101 patients with advanced HCC treated with first-line anti-programmed death 1 or ligand 1 plus antiangiogenic treatment between January 2021 and January 2024 was used to investigate the value of the TLR model for evaluating the treatment response. The presence of iTLS was identified in 46.0% (n=308) patients. The TLR model demonstrated excellent performance in predicting the presence of iTLS in training (AUC=0.91, 95% CI: 0.87, 0.94), internal test (AUC=0.85, 95% CI: 0.77, 0.93) and external validation set (AUC=0.85, 95% CI: 0.81, 0.90). The TLR model-predicted iTLS group has favorable overall survival (HR=0.66; 95% CI: 0.48, 0.90; p=0.007) and relapse-free survival (HR=0.64; 95% CI: 0.48, 0.85; p=0.001) in the external validation set. The model-predicted iTLS status was associated with inflammatory response and specific tumor-associated signaling activation (all p<0.001). The proportion of treatment responders was significantly higher in the model-predicted group with iTLS than in the group without iTLS (36% vs 13.73%, p=0.009). The TLR model has indicated accurate prediction of iTLS status, which may assist in the risk stratification for patients with HCC in clinical practice.