tbuckley/cabot-search huggingface dataset:
Cerium Dioxide Nanoparticles‐Based Inspector Enhances Mitochondrial Quality Control to Maintain Chondrocyte Homeostasis in Osteoarthritis Therapy
Authors: Li Chen, Jianye Yang, Zhengwei Cai, Yanran Huang, Qinyang Zhang, Chengqiang Zhou, Juan Wang, Wei Huang, Wenguo Cui, Ning Hu
Journal: Advanced Healthcare Materials (2025)

Abstract Imbalanced mitochondrial quality control is strongly linked to the onset and development of osteoarthritis (OA). However, current research primarily focuses on local cartilage repair and phenotype maintenance, lacking a systematic approach to subcellular mitochondrial quality control. To address this, the present study proposes a mitochondrial quality control strategy based on nanozyme hydrogel microspheres (“mitochondrial inspector”), constructed through electrostatic self‐assembly, incorporation of dynamic diselenide bonds, and microfluidic technology. The mitochondrial oxidative stress microenvironment is improved by cerium dioxide nanoparticles and combined with metformin to activate autophagy to clear persistently dysfunctional mitochondria, thereby inhibiting OA progression. In vitro results showed that “mitochondrial inspector” not only significantly improved the oxidative stress microenvironment of chondrocytes, but also efficiently scavenged the damaged mitochondria, increased the mitochondrial membrane potential by over 20‐fold, and notably improved the mitochondrial function and chondrocyte homeostasis. In a rat OA model, minimally invasive intra‐articular injection of the “mitochondrial inspector” effectively regulated mitochondrial quality, alleviated cartilage matrix degradation, reduced osteophyte formation by ≈80%, and reduced the Mankin score for cartilage damage by over 70%. In summary, this study presents a novel nanozyme microsphere‐based mitochondrial quality control strategy for the treatment of OA, providing new insights for subcellular therapies for other aging‐related diseases.
All‐In‐One Magnetic Nanoparticles for Thermo‐Immunotherapy of Malignant Melanoma
Authors: Masahiro Kaneko, Rintaro Saito, Ami Nishikawa, Akira Ito
Journal: Advanced Healthcare Materials (2025)

Abstract Hyperthermia using magnetic nanoparticles is a promising cancer therapy that locally destroys tumors and induces antitumor immunity by releasing tumor antigens from dying cells. However, magnetic hyperthermia in malignant melanomas with poor immunogenicity and an immunosuppressive microenvironment remains challenging. Here, all‐in‐one magnetic nanoparticles (αPD‐L1/CpG@MCL) are developed for thermo‐immunotherapy that enables hyperthermia with magnetic nanoparticles and immunotherapy with anti‐PD‐L1 antibody and CpG to improve the immunosuppressive tumor microenvironment. Magnetic hyperthermia with magnetite cationic liposomes (MCL, without anti‐PD‐L1 antibody and CpG) inhibits tumor growth in B16F10 melanoma; however, complete tumor regression is not observed. In contrast, complete tumor regression is observed when mice are treated with thermo‐immunotherapy using αPD‐L1/CpG@MCL. Additionally, mice cured after magnetic hyperthermia with αPD‐L1/CpG@MCL rejected rechallenge with B16F10 cells, and cytotoxicity assay using splenocytes from cured mice shows the induction of antitumor immunity against B16F10 cells. Analysis of tumor‐infiltrating lymphocytes reveals that magnetic hyperthermia with αPD‐L1/CpG@MCL increased CD8 + T lymphocytes and M1‐like macrophages, and decreased M2‐like macrophages, indicating an improvement in the tumor microenvironment. This study provides a key design strategy for all‐in‐one magnetic nanoparticles that could cure malignant melanomas.
Integrated Efficacy and Safety Analysis of Abrocitinib in Adolescents With Moderate‐to‐Severe Atopic Dermatitis
Authors: Amy S. Paller, Lawrence F. Eichenfield, Alan D. Irvine, Carsten Flohr, Andreas Wollenberg, Sébastien Barbarot, Christine Bangert, Jonathan M. Spergel, Andrew Selfridge, Pinaki Biswas, Haiyun Fan, Justine Alderfer, Melissa Watkins, Herwig Koppensteiner
Journal: Allergy (2025)

ABSTRACT Background Abrocitinib has demonstrated long‐term efficacy (48 weeks) and safety (~4 years) in adults and adolescents with moderate‐to‐severe atopic dermatitis (AD). This analysis evaluated abrocitinib efficacy in adolescents through 112 weeks, and safety of up to 4.6 years of exposure. Methods Data were from adolescents in JADE MONO‐1 (NCT03349060), MONO‐2 (NCT03575871), TEEN (NCT03796676), REGIMEN (NCT03627767; safety analysis only), and the ongoing phase 3 extension trial, EXTEND (NCT03422822; data cutoff: September 5, 2022). Efficacy assessments included proportions of patients achieving an Investigator's Global Assessment score of 0 or 1 (IGA 0/1) and ≥ 75%/≥ 90% improvement in Eczema Area and Severity Index (EASI‐75/‐90). Treatment‐emergent adverse events (TEAEs) and AEs of special interest were reported as incidence rate/100 patient‐years. A substudy of JADE TEEN assessed immune response to vaccination. Results Efficacy was assessed in 170 and 187 patients in the abrocitinib 200‐mg and 100‐mg arms, respectively; median exposure was 971.0 and 899.0 days. At Week 112, comparable proportions of patients treated with abrocitinib (200, 100 mg) achieved EASI‐75 (85%, 83%), EASI‐90 (62%, 60%), and IGA 0/1 (57%, 57%). Safety was assessed in 289 and 201 patients in the abrocitinib 200‐ and 100‐mg arms, respectively; median exposure was 882.0 and 863.0 days. Incidence rates were numerically higher with abrocitinib 200 mg versus 100 mg, with overlapping confidence intervals for serious TEAEs (IR [95% CI]; 5.47 [3.69–7.80] vs. 3.45 [1.89–5.80]) and TEAEs leading to discontinuation (6.78 [4.80–9.31] vs. 5.39 [3.38–8.16]). Conclusions Efficacy and safety results support long‐term abrocitinib use in adolescent patients. Trail Registration ClinicalTrials.gov Identifiers NCT03349060, NCT03575871, NCT03796676, NCT03627767, NCT03422822.
Check(point)s and balances: ‘Know thy enemy’
Authors: Kymberly D Watt
Journal: Hepatology (2025)

Department of Medicine, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA MESH terms: immunotherapy, checkpoint inhibitor, cancer, malignancy, rejection, liver transplant Moeckli B et al. Correspondence Kymberly D. Watt, Division of Gastroenterology and Hepatology, Mayo Clinic 200 First Street SW, Rochester, MN 55905. Email: [email protected]
Multifunctional nanoparticles for immune regulation and oxidative stress alleviation in myocarditis
Authors: Zhou Ye, Manman Zhu, Shaojie Li, Fan Zhang, Yingqi Ran, Cong Liu, Xiangchang Xu, Shujiao Liu, Xiang Xie, Yingchen Wang, Lan Yao
Journal: Journal of Controlled Release (2025)
Endoscopic En Bloc Versus Piecemeal Resection of Large Colonic Adenomas: carbon footprint post-hoc analysis of a randomized trial.
Authors: Raphaëlle Grau, Pierre-Jean Cottinet, Minh-Quyen Le, Marion Schaefer, Timothée Wallenhorst, Thomas Rösch, Vincent Lépilliez, Stanislas Chaussade, Jérôme Rivory, Romain Legros, Jean-Baptiste Chevaux, Sarah Leblanc, Pierre Lafeuille, Florian Rostain, Enrique Rodriguez de santiago, Heiko Pohl, Robin Baddeley, Daniel Grinberg, Charles Buiron, João A. Cunha Neves, Maximilien Barret, Jérémie Albouys, Arthur Belle, Hugo Lepetit, Martin Dahan, Franck Jacquette, Louis-Jean Masgnaux, Loic Marais, Thierry Ponchon, Jérémie Jacques, Mathieu Pioche
Journal: Clinical Gastroenterology and Hepatology (2025)
A Real-World Study of Cumulative Steroid Burden Among Patients with Eosinophilic Esophagitis in the United States
Authors: Mirna Chehade, David A. Katzka, Sarah Naeger, Ryan B. Thomas, Sarette T. Tilton, Juby Jacob-Nara, Amr Radwan
Journal: Clinical Gastroenterology and Hepatology (2025)
Myeloablative Radioligand Therapy Targeting C-X-C Motif Chemokine Receptor 4 in Advanced Multiple Myeloma
Authors: Niklas Dreher, Anna-Lena Dörrler, Sabrina Kraus, Leo Rasche, Takahiro Higuchi, Samuel Samnick, Constantin Lapa, Hermann Einsele, Sebastian E. Serfling, Andreas K. Buck, Rudolf A. Werner
Journal: Clinical Nuclear Medicine (2025)

Markedly expressed on hematopoietic stem cells, C-X-C motif chemokine receptor 4 (CXCR4)-directed radioligand therapy (RLT) has been used in relapsed/refractory (r/r) MM to prepare for hematopoietic stem cell transplantation (HSCT). We aimed to determine the myeloablative efficacy of CXCR4 RLT in MM patients and assessed the safety profile of this treatment. Thirty-eight patients with r/r MM were treated with 40 cycles of CXCR4-targeting [90Y]Y-PentixaTher or [177Lu]Lu-PentixaTher. Myeloablative dynamics were closely monitored by examining hematologic parameters before the application of RLT (day 1), on day 2, and on the start day of conditioning chemotherapy (CON, median day 10). Laboratory parameters evaluating organ toxicity were collected and categorized following the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Cairo-Bishop classification was also applied to identify patients experiencing laboratory tumor lysis syndrome (TLS) caused by RLT. After CON, we determined the rate of patients receiving hematopoietic stem cell transplantation (HSCT) followed by successful neutrophile engraftment. Forty cycles of CXCR4-directed RLT were applied. Myeloablative effects resulted in an 81.8% decline in leukocytes and a 69.4% decrease in neutrophil levels till the day of CON (P<0.0001, respectively), followed by platelets (63.1%; P<0.0001) and hemoglobin (9%; P=0.002). We observed 58 AE Events (1/58 [1.7%], ≥ grade 3). CON could be applied successfully after 39/40 (97.5%) cycles. After CON, in 39/39 (100%) of the cycles, HSCT was conducted, and successful neutrophil engraftment was reached after 37/39 (94.9%) of these cycles. CXCR4-directed RLT exerted relevant myeloablative effects. When performing HSCT after applying additional CON, successful neutrophile engraftment was reached in the vast majority of the cases.
FDG PET/CT in a Case of Solid Papillary Carcinoma of the Breast
Authors: Jiani He, Aisheng Dong
Journal: Clinical Nuclear Medicine (2025)

Solid papillary carcinoma of the breast is a rare low-grade tumor of the breast with unique histology and frequent neuroendocrine differentiation. The tumor usually affects older women with a favorable prognosis. We describe FDG PET/CT findings in a patient with unilateral invasive solid papillary carcinoma of the breast with ipsilateral axillary lymph node metastasis. The primary breast tumor showed focal intense activity (SUVmax, 8.8), and the enlarged metastatic axillary lymph node showed higher FDG uptake (SUVmax, 17.8) than the primary tumor. This case indicates that FDG PET/CT may be useful for staging this rare tumor, which needs further investigation.
99mTc-FAPI-46 Uptake in Simultaneous Occurrence of Benign Thyroid Nodule and Mixed-Mucinous-Invasive Ductal Breast Carcinoma
Authors: Nasrin Raeisi, Amin Saber Tanha, Kamran Aryana, Mahsa Akbari Oryani, Somaye Barashki
Journal: Clinical Nuclear Medicine (2025)

We present a case of a 65-year-old woman diagnosed with mixed mucinous-invasive ductal carcinoma, a rare subtype of breast cancer. Utilizing 99mTc-FAPI-46 scintigraphy, we observed a high target-to-background ratio in the breast mass and metastatic axillary lymph nodes. Notably, a benign follicular nodule was also detected in the thyroid which showed absent 99mTc-FAPI uptake. Our findings suggest that 99mTc-FAPI-46 shares similar characteristics with 68Ga-FAPI and may outperform 18F-FDG PET/CT in mucinous breast cancer. This case highlights the potential of FAPI as a predictive biomarker for malignancy and its role in benign findings.
Capturing cell-type-specific activities of cis-regulatory elements from peak-based single-cell ATAC-seq
Authors: Mengjie Chen
Journal: Cell Genomics (2025)

Single-cell ATAC sequencing (scATAC-seq), a state-of-the-art genomic technique designed to map chromatin accessibility at the single-cell level, presents unique analytical challenges due to limited sampling and data sparsity. In this study, we use case studies to highlight the limitations of conventional peak-based methods for processing scATAC-seq data. These methods can fail to capture precise cell-type-specific regulatory signals, producing results that are difficult to interpret and lack portability, thereby compromising the reproducibility of research findings. To overcome these issues, we introduce CREscendo, a method that utilizes Tn5 cleavage frequencies and regulatory annotations to identify differential usage of candidate regulatory elements (CREs) across cell types. Our research advocates for moving away from traditional peak-based quantification in scATAC-seq toward a more robust framework that relies on a standardized reference of annotated CREs, enhancing both the accuracy and reproducibility of genomic studies.
Tackling Cancer through Global Team Science
Authors: Rebecca L. Eccles, Gabriela Carreno, Lorenzo de la Rica, Gemma M. Balmer, David Scott
Journal: Cancer Discovery (2025)

Here, we discuss the seven new challenges set by Cancer Grand Challenges that are currently open for creative applications. We invite the research community to assemble global, interdisciplinary teams to tackle these challenges and ultimately change the way we think about, study, prevent, and treat cancer.
Antisense-mediated regulation of exon usage in the elastic spring region of Titin modulates sarcomere function
Authors: Selvi Celik, Ludvig Hyrefelt, Tomasz Czuba, Yuan Li, Juliana Assis, Julia Martinez, Markus Johansson, Oscar André, Jane Synnergren, Joakim Sandstedt, Pontus Nordenfelt, Kristina Vukusic, J Gustav Smith, Olof Gidlöf
Journal: Cardiovascular Research (2025)

Alternative splicing of Titin (TTN) I-band exons produce protein isoforms with variable size and elasticity, but the mechanisms whereby TTN splice factors regulate exon usage and thereby determining cardiomyocyte passive stiffness and diastolic function, is not well understood. Non-coding RNA transcripts from the antisense strand of protein-coding genes have been shown to regulate alternative splicing of the sense gene. The TTN gene locus harbours >80 natural antisense transcripts (NATs) with unknown function in the human heart. The aim of this study was to determine if TTN antisense transcripts play a role in alternative splicing of TTN. RNA-sequencing and RNA in situ hybridization (ISH) of cardiac tissue from heart failure patients (HF), unused donor hearts and human iPS-derived cardiomyocytes (iPS-CMs) were used to determine the expression and localization of TTN NATs. Live cell imaging was used to analyze the effect of NATs on sarcomere properties. RNA ISH, immunofluorescence was performed in iPS-CMs to study the interaction between NATs, TTN mRNA and splice factor protein RBM20.We found that TTN-AS1-276 was the predominant TTN NAT in the human heart and that it was upregulated in HF. Knock down of TTN-AS1-276 in human iPS-CMs resulted in decreased interaction between the splicing factor RBM20 and TTN pre-mRNA, decreased TTN I-band exon skipping, and markedly lower expression of the less compliant TTN isoform N2B. The effect on TTN exon usage was independent of sense-antisense exon overlap and polymerase II elongation rate. Furthermore, knockdown resulted in longer sarcomeres with preserved alignment, improved fractional shortening and relaxation times. We demonstrate a role for TTN-AS1-276 in facilitating alternative splicing of TTN and regulating sarcomere properties. This transcript could constitute a target for improving cardiac passive stiffness and diastolic function in conditions such as heart failure with preserved ejection fraction.
18F-FDG PET/CT predicts the prognosis of patients with hepatocellular carcinoma undergoing liver transplantation
Authors: Wen-Jing Zheng, Yang Xu, Hui Tan, Shu-Guang Chen, Peng-Xiang Wang, Hai-Xiang Sun, Rui-Zhe Li, Hai-Ying Zeng, Yu-Chen Zhong, Jian-Wen Cheng, Jia Fan, Jian Zhou, Hongcheng Shi, Xin-Rong Yang
Journal: Liver Cancer (2025)

In addition to radical resection, liver transplantation (LTx) is an effective treatment for hepatocellular carcinoma (HCC). However, tumor recurrence limits the efficacy of LTx in some patients. This study investigated the role of 18F-fludeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) in predicting the prognosis of patients with HCC after LTx. A total of 278 consecutive patients with HCC who underwent pre-LTx PET/CT were divided into derivation (n = 178) and temporal validation (n = 100) cohorts and evaluated for PET/CT values, immunohistochemical (IHC) findings, and DNA sequencing of tumor tissues. Patients with post-LTx recurrence exhibited significantly higher tumor maximum standardized uptake values (SUVmax) in pre-LTx PET/CT scans. Receiver operating characteristic curve analyses identified the tumor SUVmax to liver SUVmax ratio (TSUVmax/LSUVmax) as the strongest predictor of post-LTx recurrence, with an optimal cutoff value of 1.43. Kaplan-Meier analyses demonstrated that a TSUVmax/LSUVmax >1.43 was associated with a shorter time to recurrence (TTR) and overall survival (OS) in both cohorts (p < 0.001 for both). Multivariate Cox regression analyses confirmed that TSUVmax/LSUVmax >1.43 was an independent risk factor for tumor recurrence in both cohorts. IHC revealed that TSUVmax/LSUVmax >1.43 correlated with higher Ki-67 and CK19 expression. DNA sequencing indicated that tumors with TSUVmax/LSUVmax >1.43 had more mutations and a higher TMB. Furthermore, TSUVmax/LSUVmax >1.43 was significantly associated with mutations in TP53, EPPK1, MDM4, SLAMF7, SDHC, B4GALT3, RXRG, and FCGR family genes, as well as TP53 and PI3K signaling-related alterations. The preoperative TSUVmax/LSUVmax is a potential predictor of tumor recurrence in patients with HCC following LTx. Its use improves candidate selection and post-LTx management.
Global Burden of the Key Components of Cardiovascular-Kidney-Metabolic Syndrome
Authors: Zhaomin Xie, Chaolun Yu, Qingmei Cui, Xirui Zhao, Juncheng Zhuang, Shiqun Chen, Haixia Guan, Jie Li
Journal: Journal of the American Society of Nephrology (2025)

Cardiovascular-Kidney-Metabolic (CKM) syndrome highlights the interconnected nature of metabolic diseases, chronic kidney disease, and cardiovascular diseases, representing a significant and growing public health burden. This study aimed to quantify the global burden of CKM syndrome by examining its key components, including high body mass index (BMI), diabetes, chronic kidney disease, atrial fibrillation and flutter, lower extremity peripheral arterial disease, ischemic heart disease, and stroke. Data were derived from the Global Burden of Disease (GBD) 2021 platform, which provided estimates for incidence, prevalence, mortality, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life years (DALYs). A decomposition analysis was performed to assess the contributions of population growth, aging, and epidemiological changes to the burden of CKM syndrome. A NORDPRED model was employed to project future trends in DALYs, YLLs, and YLDs through 2046. Globally, ischemic heart disease and stroke were the major contributors to the CKM syndrome-related burden in 2021. Regions with a middle Socio-Demographic Index (SDI), such as Southeast Asia and the Western Pacific, experienced the largest burden. However, age-standardized DALY rates were inversely related to SDI, with regions of lower SDI exhibiting higher rates. From 1990 to 2021, DALYs for the seven key components of CKM syndrome increased, primarily driven by population growth and aging. However, age-standardized DALY rates varied across components, with stroke (-38.7% [95% uncertainty interval (UI): -43.4% to -34.0%]), peripheral arterial disease (-30.1% [-33.5% to -27.2%]), and ischemic heart disease (-28.8% [-32.5% to -25.2%]) showing a declining trend, while diabetes (38.2% [29.7% to 47.0%]) and high BMI (25.5% [16.6% to 33.7%]) exhibited an increasing trend. Further projection analysis suggested a consistent trend in the changes in CKM syndrome-related burden from 2022 to 2046, with increases ranging from 55.9% for stroke to 105.7% for atrial fibrillation and flutter. The findings of this study highlight the substantial and growing CKM syndrome-related burden, emphasizing the urgent need for comprehensive and targeted interventions.
Medical foundation large language models for comprehensive text analysis and beyond
Authors: Qianqian Xie, Qingyu Chen, Aokun Chen, Cheng Peng, Yan Hu, Fongci Lin, Xueqing Peng, Jimin Huang, Jeffrey Zhang, Vipina Keloth, Xinyu Zhou, Lingfei Qian, Huan He, Dennis Shung, Lucila Ohno-Machado, Yonghui Wu, Hua Xu, Jiang Bian
Journal: npj Digital Medicine (2025)

Recent advancements in large language models (LLMs) show significant potential in medical applications but are hindered by limited specialized medical knowledge. We present Me-LLaMA, a family of open-source medical LLMs integrating extensive domain-specific knowledge with robust instruction-following capabilities. Me-LLaMA is developed through continual pretraining and instruction tuning of LLaMA2 models using diverse biomedical and clinical data sources (e.g., biomedical literature and clinical notes). We evaluated Me-LLaMA on six text analysis tasks using 12 benchmarks (e.g., PubMedQA and MIMIC-CXR) and assessed its clinical utility in complex case diagnosis through automatic and human evaluations. Me-LLaMA outperforms existing open medical LLMs in zero-shot and supervised settings and surpasses ChatGPT and GPT-4 after task-specific instruction tuning for most text analysis tasks. Its performance is also comparable to ChatGPT and GPT-4 for diagnosing complex clinical cases. Our findings highlight the importance of combining domain-specific continual pretraining with instruction tuning to enhance performance in medical LLMs.
Neoadjuvant Chemotherapy with Dual Immune Checkpoint Inhibitors for Advanced-Stage Ovarian Cancer: Final Analysis of TRU-D Phase II Nonrandomized Clinical Trial
Authors: Junsik Park, Je-Gun Joung, Myong Cheol Lim, Jungbok Lee, Byoung-Gie Kim, Jae-Weon Kim, So Jin Shin, Sunghoon Kim, Eunhyang Park, Chel Hun Choi, Hee Seung Kim, Sang Yoon Park, Jung-Yun Lee
Journal: Clinical Cancer Research (2025)

This open-label, investigator-initiated, phase II study was conducted to evaluate the safety, survival and neoadjuvant outcomes of NAC combined with dual immune checkpoint inhibitors in advanced-stage EOC. Between June 2019 and July 2021, 45 patients with unresectable stage III-IV EOC were enrolled. The patients received three cycles of NAC combined with durvalumab and tremelimumab. All patients underwent interval debulking surgery and received three cycles of durvalumab and adjuvant chemotherapy, followed by 12 cycles of durvalumab as maintenance therapy. The primary endpoint was the 12-month progression-free survival (PFS) rate; the secondary endpoints were the objective response rate (ORR) after NAC, a chemotherapy response score (CRS), pathologic complete response (pCR), overall survival (OS), and safety. The pre-planned exploratory analyses assessed the lymphocyte infiltration, PD-L1 expression, and genomic profiles of pre-treatment tumors. The 12-month PFS rate was 65.9% (95% CI, 52.8-NE), while the 24- and 30-month PFS rates were 38.6% (95% CI, 26.7-NE) and 36.4% (95% CI, 24.7-NE), respectively. After NAC, the ORR was 86.7%, while 14 patients (31.1%) had a CRS 3, and five (11.1%) achieved pCR. The 30-month OS rate was 87.7%. The most common grade ≥ 3 adverse events was neutropenia (26.7%). In an exploratory analysis, patients with pre-NAC tumors showing PD-L1 (CPS) ≥1, high Mutation Signature 3, and a high extracellular matrix signature demonstrated improved PFS outcomes. NAC combined with dual immune checkpoint inhibitors is feasible for advanced-stage EOC and shows promising activity with a durable clinical response.