tbuckley/cabot-search huggingface dataset:
Atezolizumab plus bevacizumab and chemotherapy in metastatic nonsquamous NSCLC: the randomized double-blind phase 3 IMpower151 trial
Authors: Caicun Zhou, Xiaorong Dong, Gongyan Chen, Zhehai Wang, Xianghua Wu, Yu Yao, Yiping Zhang, Ying Cheng, Hongming Pan, Xiaodong Zhang, Jiuwei Cui, Lifeng Wang, Xi Chen, Xiaoling Li, Ziping Wang, Qiming Wang, Jianxing He, Mengzhao Wang, Iris Yan, Li Qian, Miao Xu, Xiayu Huang, Chun Sun, Jun Cai, Qiong Wu, Marcus Ballinger, Monika Kaul, Minu K Srivastava
Journal: Nature Medicine (2025)

After the global approval of atezolizumab plus bevacizumab and chemotherapy as first-line metastatic nonsquamous non-small-cell lung cancer (nsqNSCLC) treatment, the IMpower151 ( NCT04194203 ) trial was conducted in China to address regional differences. Chemotherapy-naive patients with metastatic nsqNSCLC (N = 305) were randomized 1:1 to receive either atezolizumab, bevacizumab, carboplatin and paclitaxel or pemetrexed (ABCPem/Pac; n = 152) or placebo plus bevacizumab, carboplatin and pemetrexed or paclitaxel (BCPem/Pac; n = 153). The primary endpoint was investigator-assessed progression-free survival (INV-PFS); secondary endpoints included subgroup analyses of INV-PFS, independent review facility-assessed PFS, overall survival, and investigator-assessed objective response rate and duration of response per RECIST v.1.1. Most patients (97%) received pemetrexed, and 53% had EGFR+ tumors. Median INV-PFS for ABCPem/Pac versus BCPem/Pac was 9.5 versus 7.1 months (stratified hazard ratio: 0.84; 95% confidence interval: 0.65, 1.09; P = 0.184). INV-PFS across subgroups and independent review facility-assessed PFS were consistent with INV-PFS in the intention-to-treat population. Median overall survival was 20.7 versus 18.7 months in the ABCPem/Pac versus BCPem/Pac arms, respectively (stratified hazard ratio: 0.93; 95% confidence interval: 0.67, 1.28). Confirmed objective response rate with ABCPem/Pac versus BCPem/Pac was 48% versus 50%, respectively; median duration of response was 11.3 versus 8.3 months. Adverse events of special interest for atezolizumab were observed in 68% (grades 3 and 4: 11%) and 71% (grades 3 and 4: 7%) of patients receiving ABCPem/Pac and BCPem/Pac, respectively. The most common adverse events of special interest for atezolizumab in the ABCPem/Pac and BCPem/Pac arms were hepatitis (driven by laboratory abnormalities; mostly low grade), hypothyroidism and rash. Overall, IMpower151 did not meet its primary endpoint (INV-PFS) in metastatic nsqNSCLC. ABCPem/Pac was generally well tolerated, with no new safety signals. Trial registration number: ClinicalTrials.gov, NCT02366143.
Endocrine-disrupting chemicals as prostate carcinogens
Authors: Mariana Feijó, Tiago M A Carvalho, Lara R S Fonseca, Cátia V Vaz, Bruno J Pereira, José Eduardo B Cavaco, Cláudio J Maia, Ana P Duarte, Endre Kiss-Toth, Sara Correia, Sílvia Socorro
Journal: Nature Reviews Urology (2025)
Large-scale network analysis of the cerebrospinal fluid proteome identifies molecular signatures of frontotemporal lobar degeneration
Authors: Rowan Saloner, Adam M Staffaroni, Eric B Dammer, Erik C B Johnson, Emily W Paolillo, Amy Wise, Hilary W Heuer, Leah K Forsberg, Argentina Lario-Lago, Julia D Webb, Jacob W Vogel, Alexander F Santillo, Oskar Hansson, Joel H Kramer, Bruce L Miller, Jingyao Li, Joseph Loureiro, Rajeev Sivasankaran, Kathleen A Worringer, Nicholas T Seyfried, Jennifer S Yokoyama, Salvatore Spina, Lea T Grinberg, William W Seeley, Lawren VandeVrede, Peter A Ljubenkov, Ece Bayram, Andrea Bozoki, Danielle Brushaber, Ciaran M Considine, Gregory S Day, Bradford C Dickerson, Kimiko Domoto-Reilly, Kelley Faber, Douglas R Galasko, Tania Gendron, Daniel H Geschwind, Nupur Ghoshal, Neill Graff-Radford, Chadwick M Hales, Lawrence S Honig, Ging-Yuek R Hsiung, Edward D Huey, John Kornak, Walter Kremers, Maria I Lapid, Suzee E Lee, Irene Litvan, Corey T McMillan, Mario F Mendez, Toji Miyagawa, Alexander Pantelyat, Belen Pascual, Joseph Masdeu, Henry L Paulson, Leonard Petrucelli, Peter Pressman, Rosa Rademakers, Eliana Marisa Ramos, Katya Rascovsky, Erik D Roberson, Rodolfo Savica, Allison Snyder, Anna Campbell Sullivan, M Carmela Tartaglia, Marijne Vandebergh, Brad F Boeve, Howie J Rosen, Julio C Rojas, Adam L Boxer, Kaitlin B Casaletto
Journal: Nature Aging (2025)
Sensitizing solid tumors to CAR-mediated cytotoxicity by lipid nanoparticle delivery of synthetic antigens
Authors: Lena Gamboa, Ali H Zamat, Chloé A Thiveaud, Hee Jun Lee, Elif Kulaksizoglu, Zizhen Zha, Noah S Campbell, Ching Shen Chan, Sydney Fábrega, S Abbey Oliver, Fang-Yi Su, Hathaichanok Phuengkham, Daryll Vanover, Hannah E Peck, Anirudh Sivakumar, Shreyas N Dahotre, Adrian M Harris, Philip J Santangelo, Gabriel A Kwong
Journal: Nature Cancer (2025)
APOBEC3 mutagenesis drives therapy resistance in breast cancer
Authors: Avantika Gupta, Andrea Gazzo, Pier Selenica, Anton Safonov, Fresia Pareja, Edaise M da Silva, David N Brown, Hong Shao, Yingjie Zhu, Juber Patel, Juan Blanco-Heredia, Bojana Stefanovska, Michael A Carpenter, Yanjun Chen, Isabella Vegas, Xin Pei, Denise Frosina, Achim A Jungbluth, Marc Ladanyi, Giuseppe Curigliano, Britta Weigelt, Nadeem Riaz, Simon N Powell, Pedram Razavi, Reuben S Harris, Jorge S Reis-Filho, Antonio Marra, Sarat Chandarlapaty
Journal: Nature Genetics (2025)

Acquired genetic alterations drive resistance to endocrine and targeted therapies in metastatic breast cancer; however, the underlying processes engendering these alterations are largely uncharacterized. To identify the underlying mutational processes, we utilized a clinically annotated cohort of 3,880 patient samples with tumor-normal sequencing. Mutational signatures associated with apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3 (APOBEC3) enzymes were prevalent and enriched in post-treatment hormone receptor-positive cancers. These signatures correlated with shorter progression-free survival on antiestrogen plus CDK4/6 inhibitor therapy in hormone receptor-positive metastatic breast cancer. Whole-genome sequencing of breast cancer models and paired primary-metastatic samples demonstrated that active APOBEC3 mutagenesis promoted therapy resistance through characteristic alterations such as RB1 loss. Evidence of APOBEC3 activity in pretreatment samples illustrated its pervasive role in breast cancer evolution. These studies reveal APOBEC3 mutagenesis to be a frequent mediator of therapy resistance in breast cancer and highlight its potential as a biomarker and target for overcoming resistance.
siRNA conjugate with high albumin affinity and degradation resistance for delivery and treatment of arthritis in mice and guinea pigs
Authors: Juan M Colazo, Megan C Keech, Veeraj Shah, Ella N Hoogenboezem, Justin H Lo, Nora Francini, Nina T Cassidy, Fang Yu, Alexander G Sorets, Joshua T McCune, Carlisle R DeJulius, Hongsik Cho, Danielle L Michell, Tristan Maerz, Kacey C Vickers, Katherine N Gibson-Corley, Karen A Hasty, Leslie J Crofford, Rebecca S Cook, Craig L Duvall
Journal: Nature Biomedical Engineering (2025)

Osteoarthritis and rheumatoid arthritis are debilitating joint diseases marked by pain, inflammation and cartilage destruction. Current osteoarthritis treatments only relieve symptoms, while rheumatoid arthritis therapies can cause immune suppression and provide variable efficacy. Here we developed an optimized small interfering RNA targeting matrix metalloproteinase 13 for preferential delivery to arthritic joints. Chemical modifications in a stabilizing 'zipper' pattern improved RNA resistance to degradation, and two independent linkers with 18 ethylene glycol repeats connecting to tandem C18 lipids enhanced albumin binding and targeted delivery to inflamed joints following intravenous administration. In preclinical models of post-traumatic osteoarthritis and rheumatoid arthritis, a single intravenous injection of the albumin-binding small interfering RNA achieved long-term joint retention, sustained gene silencing and reduced matrix metalloproteinase 13 activity over 30 days, resulting in decreased cartilage erosion and improved clinical outcomes, including reduced joint swelling and pressure sensitivity. This approach demonstrated superior efficacy over corticosteroids and small-molecule MMP inhibitors, highlighting the therapeutic promise of albumin 'hitchhiking' for targeted, systemic delivery of gene-silencing therapeutics to treat osteoarthritis and rheumatoid arthritis.
MCSP+ metastasis founder cells activate immunosuppression early in human melanoma metastatic colonization
Authors: Severin Guetter, Courtney König, Huiqin Koerkel-Qu, Aleksandra Markiewicz, Sebastian Scheitler, Marie Katzer, Mark Berneburg, Philipp Renner, Beatrix Cucuruz, Leonhard Guttenberger, Veronika Naimer, Kathrin Weidele, Steffi Treitschke, Christian Werno, Hanna Jaser, Tonia Bargmann, Armin Braun, Florian Weber, Katja Evert, Alexander Rochwarger, Christian M Schürch, Katharina Limm, Peter J Oefner, Reinhard Rachel, Felix Baumann, Jens Warfsmann, Lisa Schmidleithner, Kathrin Guetter, Parvaneh Mohammadi, Anja Ulmer, Sebastian Haferkamp, Christoph A Klein, Melanie Werner-Klein
Journal: Nature Cancer (2025)

To investigate the early, poorly understood events driving metastatic progression, we searched for the earliest detectable disseminated cancer cells (DCCs), also often referred to as disseminated tumor cells (DTCs), in sentinel lymph node (SLN) biopsies of 492 patients with stage I-III melanoma. Using micromanipulator-assisted isolation of rare DCCs, single-cell mRNA and DNA sequencing, codetection by indexing immunofluorescence imaging and survival analysis, we identified melanoma-associated chondroitin sulfate proteoglycan (MCSP)+ melanoma cells as metastasis founder cells (MFCs). We found that DCCs entering SLNs predominantly exhibited a transitory phenotype that, upon interferon-γ exposure triggered by CD8 T cells, dedifferentiated into a neural-crest-like phenotype. This was accompanied by increased production of small extracellular vesicles (sEVs) carrying the immunomodulatory proteins CD155 and CD276 but rarely programmed cell death protein 1 ligand 1. The sEVs suppressed CD8 T cell proliferation and function, facilitating colony formation. Targeting MCSP+ MFCs or their immune escape mechanisms could be key to curing melanoma early by preventing manifestation of metastasis.
Platelet‐to‐Neutrophil Ratio: A Novel Prognostic Indicator for Anti‐PD‐1‐Based Therapy in Relapsed/Refractory Hodgkin Lymphoma and Solid Tumors
Authors: Yuting Pan, Xin Zhang, Chunmeng Wang, Nannan Lu, Yang Liu, Yixin Chang, Xueting Qin, Weidong Han, Jing Nie
Journal: MedComm (2025)

Program cell death-1 (PD-1) blockade treatment has been shown effective in cases with relapsed/refractory classical Hodgkin Lymphoma (R/R cHL), while prognostic biomarkers remain unclear. Seventy-seven cases with R/R cHL who received immunotherapy for the first time were included. Receiver operator characteristic analysis displayed platelet-to-neutrophil ratio (PNR) as the most probable indicator among distinct inflammatory-cell ratios. Patients with high pretreatment PNR (≥ 51.6) achieved significantly higher complete response (CR) rate as compared with patients with low PNR (< 51.6), and PNRhigh patients displayed significantly longer progression-free survival (PFS) versus PNRlow patients (p = 0.001). Cox analysis indicated PNR as an independent factor for prognosis (hazard ratio, 0.34, 95% CI, 0.18-0.65, p = 0.001). Among patients acquiring CR, higher PNR was associated with improved PFS and relapse-free survival. Moreover, PNR correlations with CR rate and PFS were validated in external cohort of cHL. Notably, PNR was also a strong prognostic biomarker for PFS and overall survival after anti-PD-1 combination therapy in patients with solid tumors, such as biliary tract carcinoma, gastric carcinoma, or colon cancer. In conclusion, this study for the first time reveals a correlation between pretreatment peripheral PNR and prognosis of anti-PD-1-based therapy in patients with relapsed/refractory cHL and advanced solid tumor.
Application of <sup>68</sup>Ga‐ and <sup>177</sup>Lu‐Labeled FAP Inhibitor in Evaluation and Treatment of Cardiac Fibrosis After Myocardial Infarction
Authors: Yiheng Zhao, Xiangyu Su, Boyang Xiang, Shuchen Zhang, Xiang Zhou
Journal: MedComm (2025)

68Ga and 177Lu-labeled fibroblast activation protein inhibitor (FAPI) have been introduced for the diagnosis and treatment of multiple malignant and non-malignant diseases. While several studies have examined the application of 68Ga-FAPI in myocardial infarction (MI), research on the use of 177Lu-FAPI for the treatment of MI is still scarce. In this study, we evaluated the effects of 68Ga-FAPI and 177Lu-FAPI in cardiac fibrosis after MI using permanent coronary artery ligation rat models. 68Ga-FAPI-04 effectively targeted fibroblasts within the MI area. Rats treated with 177Lu-FAPI-04 had a significant increase in left ventricular ejection fraction at 28 days post-MI, with no obvious kidney or liver toxicity. Magnetic resonance imaging and histological analysis revealed a reduced fibrotic area in the 177Lu-FAPI group. 177Lu-FAPI-04 exerted its therapeutic effect by suppressing activation and inducing apoptosis of fibroblasts. In summary, we demonstrated that 177Lu-FAPI-04 could effectively target FAP and eliminate activated fibroblasts after MI, thereby contributing to the development of new strategies for the treatment of MI.
Study of cardiac structures and heart valves: analysing curvatures based on 3D ultrasound waves
Authors: Mersedeh Karvandi, Saeed Ranjbar
Journal:  (2025)

The geometry of the heart has been studied as a four-dimensional manifold allowing us to translate the 3D echocardiography images into different colours for distinguishing between regions and leaflets of heart valves that is the main objective of this article.
Rethinking post-colonoscopy colorectal cancer risk: endoscopist performance versus presence of high-risk polyps
Authors: Nanette S van Roermund, Veerle M H Coupé, Manon C W Spaander, Monique E van Leerdam, Evelien Dekker, Joep E G IJspeert
Journal: Clinical Gastroenterology and Hepatology (2025)
Whole-body MRI Versus [18F]FDG PET/CT in Diagnosing and Monitoring Plasmacytomas
Authors: Nieves Gómez León, Isabel Vicuña-Andrés, Beatriz Aguado-Bueno, Francisco Garrido-Enjamio, Itxaso Galán-González, Valentina Castillo-Morales, Adrián Alegre Amor, Roberto C. Delgado Bolton
Journal: Clinical Nuclear Medicine (2025)

Background/Objectives: Current guidelines recommend [ 18 F]FDG PET/CT as the preferred imaging modality for suspected extramedullary bone plasmacytomas, while whole-body magnetic resonance imaging (WB-MRI) is indicated for solitary bone plasmacytomas. Despite these recommendations, the available evidence comparing the diagnostic efficacy of both techniques remains limited. The aim of this study was to compare the diagnostic efficacy of WB-MRI and [ 18 F]FDG PET/CT in the initial evaluation of plasmacytomas. Methods: We performed a multicenter, observational, and retrospective analysis of patients diagnosed with plasmacytoma who underwent WB-MRI and/or [ 18 F]FDG PET/CT as part of their diagnostic workup. Lesions identified were categorized by anatomic location, and concordance between WB-MRI and [ 18 F]FDG PET/CT findings was assessed. The McNemar test and Pearson χ 2 test were used to compare detection rates between WB-MRI and [ 18 F]FDG PET/CT. Results: The study included 73 patients (33 men) recruited between 2012 and 2023, age range 30–94 years (mean 63.4 ± 12.2 y). Of these, 56 patients underwent both diagnostic tests. Diagnoses revealed solitary plasmacytoma in 16 patients, concurrent multiple myeloma (MM) and plasmacytoma in 18 patients, and plasmacytoma in 22 patients with a prior MM history. Out of the 56 plasmacytomas, 40 were osseous and 16 were extramedullary. WB-MRI detected 98.2% of plasmacytomas compared with 83.9% for [ 18 F]FDG PET/CT, with a statistically significant difference of OR 9 (95% CI: 1.2–394.5), P =0.021. Concordance was very high for osseous plasmacytomas but moderate for extramedullary plasmacytomas. Conclusions: These findings suggest WB-MRI is an alternative to [ 18 F]FDG PET/CT for detecting plasmacytomas. A comprehensive clinical and radiologic assessment is essential for the optimal evaluation of patients with plasmacytoma.
Local delivery of siRNA using lipid-based nanocarriers with ROS-scavenging ability for accelerated chronic wound healing in diabetes
Authors: Yuanfeng Li, Kaiyi Du, Danfeng Peng, Xuanlong Zhang, Yinzi Piao, Mengna Peng, Wei He, Yumeng Wang, Haoyue Wu, Yong Liu, Jian Xiao, Linqi Shi, Dongdong Li
Journal: Biomaterials (2025)
SLAMF receptors: key regulators of tumor progression and emerging targets for cancer immunotherapy
Authors: Jia Li, Tao Fan, Di Wang, Chu Xiao, Ziqin Deng, Wenpeng Cai, Yu Ji, Chunxiang Li, Jie He
Journal: Molecular Cancer (2025)

The signaling lymphocytic activation molecule family (SLAMF) consists of nine distinct cell surface receptors predominantly expressed on immune cells, each characterized by unique structural features, expression patterns, downstream signaling pathways, and biological functions. These receptors play critical roles in modulating various immune cell activities within the tumor microenvironment, thereby shaping immune responses in cancer. Although accumulating evidence demonstrates their value as therapeutic targets for developing cancer immunotherapies, the full spectrum of SLAMF receptors in cancer remains incompletely understood. This review aims to provide a comprehensive overview of the molecular characteristics and immunomodulatory functions of each SLAMF receptor, underscoring their pivotal contributions to cancer progression. Furthermore, we also highlight their potential as promising targets for advancing cancer immunotherapeutic strategies. Finally, we discuss clinical trials evaluating the efficacy and safety of SLAMF receptor-based immunotherapies, emphasizing their translational relevance in the development of cancer treatments.
Seeing Through the Leak: A Global Perspective on Aortic Regurgitation Assessment
Authors: Christina Binder, Lena Marie Schmid, Johanna Schlein, Christian Hengstenberg, Thomas Binder
Journal:  (2025)

Abstract Background Despite established guidelines, the echocardiographic quantification of aortic regurgitation (AR) remains challenging in clinical practice. While artificial intelligence (AI) solutions are being developed to support diagnostic assessment using echocardiography, their successful implementation will depend on understanding both current diagnostic challenges and clinician attitudes toward AI adoption. This study aimed to evaluate current practices in AR assessment, identify key challenges, and assess educational needs in AR diagnostics, while also investigating how healthcare professionals perceive AI assistance compared to human expert assessment. Methods We conducted a global online survey among sonographers and physicians. Participants answered questions about their current AR quantification practices, perceived limitations, and willingness to seek assistance from experienced colleagues or AI tools. Additionally, they were asked to grade AR severity in three sample echocardiographic cases. Results Among 1,032 participants from 104 countries, 42% considered AR the most challenging valve lesion to assess. While guidelines recommend a multi-parameter approach, most practitioners relied primarily on visual color jet assessment (51.5%) and basic measurements, with advanced quantitative parameters being notably underutilized (21.7%). Main limitations included eccentric jets (61.3%) and poor image quality (49.8%). Case-based assessments revealed significant variability in AR grading across experience levels (p &amp;lt; 0.001). Participants showed high confidence in both experienced colleagues and validated AI models (median confidence score of 7/10 for both) but less trust in newly developed AI tools (median confidence score 5/10). Conclusion This study demonstrates a substantial gap between guideline recommendations and clinical practice in AR quantification, with significant grading variability across and within expertise levels. While practitioners remain skeptical of newly developed AI tools, their openness to validated AI models suggests a potential pathway for improving the consistency of AR assessment.
Cardiovascular imaging in 2024: review of current research and innovations
Authors: Andrea Barison, Ana Teresa Timoteo, Saloua El Messaoudi, Sonia Borodzicz-Jazdzyk, Sara Moscatelli, Giulia Elena Mandoli, Christina Luong, Eylem Levelt, Arti Anushka Ramkisoensing, Zahra Raisi-Estabragh, Alexios Antonopoulos, Sarah Moharem-Elgamal, Riccardo Liga, Gianluca Pontone, Danilo Neglia
Journal:  (2025)

Abstract Cardiovascular imaging saw significant advancements in 2024, impacting technology, pathophysiology, and clinical applications. This review provides a comprehensive summary of the most impactful research in cardiovascular imaging published in 2024, highlighting technological advancements, as well as research on ischaemic heart disease, valvular heart disease, cardiomyopathies, and heart failure. It emphasizes the crucial role of artificial intelligence, large-scale studies, and technical improvements across echocardiography, cardiovascular magnetic resonance (CMR), computed tomography (CT), and nuclear medicine. In the context of ischaemic heart disease, non-invasive imaging strategies improve patient management and reduce invasive coronary angiograms and unnecessary follow-up testing. CT plaque characterisation is a growing area of research, with potential for predicting disease severity, atherosclerosis progression, and clinical outcomes. In valvular heart disease, several imaging studies focused on transcatheter treatments for aortic stenosis, mitral regurgitation, and tricuspid regurgitation, but also on specific conditions such as mitral valve prolapse and mitral annular disjunction. Finally, for heart failure and cardiomyopathies, imaging plays a vital role in early diagnosis and risk assessment, with newer techniques surpassing traditional methods in providing morpho-function characterisation and in predicting long-term outcomes.