tbuckley/cabot-search huggingface dataset:
Synovium‐on‐a‐Chip Reveals Fibroblast–Macrophage Crosstalk Underpinning Joint Homeostasis and Evaluation of Gout Therapies
Authors: Min Seok Lee, Soohyun Kim, Jong‐Hwan Lee, Yoe‐Sik Bae, Sung Kyun Lee
Journal: Advanced Healthcare Materials (2025)

Abstract The synovium maintains joint homeostasis and regulates immune responses through fibroblast‐like synoviocytes (FLS) and macrophage‐like synoviocytes (MLS). However, investigation of the intricate FLS‐MLS interactions is limited by the lack of physiologically relevant in vitro models. Here, this work presents a synovium‐on‐a‐chip model that faithfully mimics the structural and functional properties of the human synovial lining, established with collagen/alginate hybrid hydrogel (CAHG). The functional phenotype of FLS observed in vivo is replicated on chip when cultured with CAHG. Moreover, co‐culture with M2c macrophages derived from CD14+ monocytes enables the reconstruction of key immune functions of the synovial lining, including expression of junction proteins (ZO‐1 and CLD5) and immunoregulatory markers (TREM2 and VSIG4). CD44 blockade, disrupting FLS‐MLS interactions, significantly suppresses inflammasome‐related pathways, underscoring the regulatory role of FLS in synovial immune responses. Our model is further validated by modeling gout, where treatment with monosodium urate crystals trigger NLRP3 inflammasome activation, macrophage polarization, and neutrophil extravasation. Pharmacological interventions with MCC950 and entrectinib effectively inhibit the inflammasome activation, demonstrating the platform's utility for preclinical drug evaluation. This synovium‐on‐a‐chip provides a reliable in vitro model for studying synovial inflammation and serves as a valuable tool for the therapeutic discovery of inflammatory joint diseases.
Lipoprotein‐Based Nanocatalyst Enables Targeted Treatment of APAP‐Induced Liver Injury via Enhanced Macropinocytosis
Authors: Yaoxing Chen, Gan Jiang, Yan Huang, Shuying Song, Haoshuang Fu, Bingying Du, Yuelin Xiao, Peiying Li, Kexin Shi, Yukun Huang, Qingxiang Song, Xiaoling Gao, Qing Xie
Journal: Advanced Healthcare Materials (2025)

Abstract Drug‐induced liver injury (DILI), predominantly caused by acetaminophen (APAP) overdose, is characterized by excessive reactive oxygen species (ROS) production and subsequent hepatocyte necrosis. Although N ‐acetylcysteine (NAC) remains the only approved treatment, its effectiveness is limited by a narrow therapeutic time window and reduced efficacy in advanced cases. To address these limitations, an innovative therapeutic approach is developed utilizing ceria's antioxidant properties. In this study, a reconstituted high‐density lipoprotein‐encapsulated ceria nanocatalyst (CeO 2 ‐rHDL) is engineered to overcome the aggregation tendency and targeting limitation of naked ceria nanoparticles. These findings revealed that CeO 2 ‐rHDL enters hepatocytes through macropinocytosis, a process synergistically enhanced by both APAP and NAC, facilitating efficient liver targeting. The nanocatalyst demonstrated remarkable therapeutic efficacy by restoring mitochondrial function through ROS reduction. When combined with NAC, CeO 2 ‐rHDL significantly improved survival outcomes in DILI mice. This lipoprotein‐based nanocatalyst system represents a promising therapeutic strategy for DILI treatment, offering enhanced targeting capabilities and improved therapeutic efficacy.
Carbon‐Based Flexible Electrode for Efficient Electrochemical Generation of Reactive Chlorine Species in Tumor Therapy
Authors: Cuinan Jiang, Zhaoyu Chen, Ruihao Yang, Ziga Luogu, Qian Ren, Hao Hu, Kaixin Wang, Senlin Li, Changlin Deng, Meng Li, Lu Zheng
Journal: Advanced Healthcare Materials (2025)

Abstract Reactive chlorine species (RCS) are alternatives to reactive oxygen species (ROS) in tumor therapeutics. Unlike ROS, whose generation is limited by hypoxic conditions or insufficient H 2 O 2 levels in the tumor, RCS can be generated through the electrochemical oxidation of abundant Cl − present in body fluids. However, traditional electrochemical therapy modalities have shown suboptimal outcomes. Herein, a flexible anodic electrode is fabricated by growing a carbon nanowire network (C‐NWN) onto carbon cloth (CC). Attributing to its excellent hydrophilicity, high specific surface area, and electrochemical surface area, CC@C‐NWN demonstrates a superior capability for RCS generation. Additionally, the carbon vacancies in CC@C‐NWN not only enhance Cl − adsorption but also reduce the reaction free energy of the chlorine evolution reaction (CER) more significantly compared to that of the oxygen evolution reaction, thereby promoting the CER process. RCS generated from the CC@C‐NWN electrochemical system induces severe oxidative stress, disrupting the redox homeostasis in tumor cells and promoting the synergistic anti‐tumor effect of apoptosis and ferroptosis. The pliability of CC@C‐NWN enables it to conform closely to the tumor, and it has demonstrated remarkable tumor‐suppressive efficacy under low‐voltage (3 V) condition in in vivo experiments. Therefore, the work holds significant promise for the development of novel tumor treatment strategies.
Advancing efficacy prediction for electronic health records based emulated trials in repurposing heart failure therapies
Authors: Nansu Zong, Shaika Chowdhury, Shibo Zhou, Sivaraman Rajaganapathy, Yue Yu, Liewei Wang, Qiying Dai, Pengyang Li, Xiaoke Liu, Suzette J Bielinski, Jun Chen, Yongbin Chen, James R Cerhan
Journal: npj Digital Medicine (2025)

The complexities inherent in EHR data create discrepancies between real-world evidence and RCTs, posing substantial challenges in determining whether a treatment is likely to have a beneficial impact compared to the standard of care in RCTs. The objective of this study is to enhance the prediction of efficacy direction for repurposed drugs tested in RCTs for heart failure (HF). To achieve this, we propose an efficacy direction prediction framework that integrates drug-target predictions with EHR-based Emulation Trials (ET) to derive surrogate endpoints for prediction using HF prognostic markers. Our validation of the proposed novel drug-target prediction model against the BETA benchmark demonstrates superior performance, surpassing existing baseline algorithms. Furthermore, an evaluation of our framework in identifying 17 repurposed drugs-derived from 266 phase 3 HF RCTs-using data from 59,000 patients at the Mayo Clinic highlights its remarkable predictive accuracy.
NIR-II-Activated iridium single-atom nanozymes for synergistic antibacterial therapy and tissue regeneration in MRSA-infected wounds and acute lung injury
Authors: Danyan Wang, Hui Jin, Yetao Shen, Dandan Wang, Jingjing He, Jinmiao Qu, Xiaojun He, Zhengli Jiang
Journal: Bioactive Materials (2025)
Evaluation of Combination Therapy With Secukinumab and Systemic Corticosteroids for Acute Generalized Exanthematous Pustulosis : A Retrospective Cohort Study
Authors: Xiao-Qing Lv, Shi-Fan Ruan, Jia-Wen Chen, Xin-Hong Su, Kun Qin, Xue-Ting Zeng, Li-Hong Chen, Niu Xiang, Ting Gong, Chao Ji
Journal: Journal of the American Academy of Dermatology (2025)
Validation of the definition of gastro-oesophageal junctional zone: an immunohistochemical study using resected mucosal specimens
Authors: Kazuhiro Ota, Ken-Ichi Mukaisho, Yuto Shimamura, Tetsuo Ushiku, Mitsuaki Ishida, Shun Sasaki, Taro Iwatsubo, Noriaki Sugawara, Akitoshi Hakoda, Hiroki Nishikawa, Kazuhide Higuchi, Mitsuhiro Fujishiro, Takuji Gotoda, Michio Kaminishi, Kentaro Sugano
Journal: Gut (2025)
Adoptively transferred macrophages for cancer immunotherapy
Authors: Kyung Soo Park, Alexander P Gottlieb, Morgan E Janes, Supriya Prakash, Neha Kapate, Vineeth Chandran Suja, Lily Li-Wen Wang, Jennifer L Guerriero, Samir Mitragotri
Journal: Journal for ImmunoTherapy of Cancer (2025)

Background Macrophages have been classically associated with their innate immune functions of responding to acute injury or pathogenic insult, but they have been largely overlooked as primary initiators of adaptive immune responses. Here, we demonstrate that adoptively transferred macrophages, with optimal activation prior to administration, act as a potent cellular cancer therapeutic platform against a murine melanoma model. Method The macrophage therapy was prepared from bone marrow-derived macrophages, pretreated ex vivo with an activation cocktail containing interferon-γ, tumor necrosis factor-α, polyinosinic:polycytidylic acid, and anti-CD40 antibody. The therapy was administered to tumor-bearing mice via the tail vein. Tumor growth and survival of the treated mice were monitored to evaluate therapeutic efficacy. Tumors and spleens were processed to examine immune responses and underlying mechanisms. Results This immunotherapy platform elicits systemic immune responses while infiltrating the tumor to exert direct antitumor effects in support of the systemic adaptive response. The macrophage-based immunotherapy produced a strong CD8+T cell response along with robust natural killer and CD4+T cell activation, inducing a “hot” tumor transition and achieving effective tumor suppression. Conclusions Owing to their inherent ability to home to and infiltrate inflamed tissues, macrophage-based cancer immunotherapies exhibited a unique in vivo trafficking behavior, efficiently reaching and persisting within tumors. Macrophages orchestrated a multiarmed immune attack led by CD8+T cells, with the potential for local, intratumoral activation of effector cells, demonstrating a novel cancer immunotherapy platform with meaningfully different characteristics than clinically evaluated alternatives.
Nanoparticles-incorporated hydrogel microneedle for biomedical applications: fabrication strategies, emerging trends and future prospects
Authors: Zejun Xu, Jiaying Chi, Fei Qin, Dongyan Liu, Yecai Lai, Yingxia Bao, Ruizhi Guo, Yiqiu liao, Zhoufan Xie, Jieqiong Jiang, Juyan Liu, Jianfeng Cai, Chao Lu, Jiansong Wang, Chuanbin Wu
Journal: Asian Journal of Pharmaceutical Sciences (2025)
IL-1β blockade prevents cardiotoxicity and improves the efficacy of immune checkpoint blockers and chemotherapy against pancreatic cancer in mice with obesity
Authors: Nilesh P Talele, Heena Kumra, Igor L Gomes-Santos, William W Ho, Patrik Andersson, Marie Siwicki, Peigen Huang, Dan G Duda, Mikael J Pittet, Dai Fukumura, Rakesh K Jain
Journal: Journal for ImmunoTherapy of Cancer (2025)

Background Immune checkpoint blockers (ICBs) have revolutionized cancer therapy, yet they remain largely ineffective in treating pancreatic ductal adenocarcinoma (PDAC). Moreover, ICBs can cause severe immune-related adverse events (irAEs), including fatal cardiac toxicity. Finally, obesity is a risk factor in PDAC that may differentially modulate ICB efficacy in a malignancy-dependent manner. Methods We investigated the mechanisms underlying irAEs induced by dual ICB therapy and sought to identify strategies to mitigate them while improving ICB efficacy in the obese setting. To this end, we used a clinically relevant mouse model that integrated key features of human PDAC: (1) high-fat diet-induced obesity, (2) an orthotopic PDAC, and (3) a therapeutic regimen combining chemotherapy (FOLFIRINOX) with ICBs (α-programmed cell death protein-1 + α-cytotoxic T-lymphocyte associated protein-4 antibodies). Results Obese mice developed cardiac irAEs and had elevated serum interleukin (IL)-1β levels after chemoimmunotherapy. IL-1β blockade not only prevented myocarditis and reduced cardiac fibrosis but also enhanced the antitumor efficacy of the combination of chemotherapy plus dual ICB therapy and significantly improved the overall survival of PDAC-bearing obese mice. Conclusions Our findings provide the rationale and compelling data to test a Food and Drug Administration-approved anti-IL-1β antibody in combination with chemotherapy and dual ICB therapy in patients with pancreatic cancer with obesity.
Avelumab-based neoadjuvant therapy in patients with muscle-invasive bladder cancer (AURA Oncodistinct-004): a phase 2 multicenter clinical trial
Authors: Jérémy Blanc, Aurélien Carnot, Philippe Barthélémy, Vinciane Casert, Brieuc Sautois, Jan Van den Brande, Vincent Vanhaudenarde, Lionel Staudacher, Emmanuel Seront, Veronique Debien, Lieveke Ameye, Nuria Kotecki, Françoise Rothé, Sandrine Rorive, Jean-Christophe Fantoni, Thibault Tricard, Thierry Roumeguère, Ahmad Awada, Nieves Martinez Chanza
Journal: Journal for ImmunoTherapy of Cancer (2025)

Background Immunotherapy is becoming a standard of care for non-metastatic muscle-invasive bladder cancer (MIBC). The optimal chemotherapy partner for chemo-immunotherapy combinations remains unknown. We evaluated the efficacy and safety of neoadjuvant avelumab-based regimens in patients with MIBC. Methods The multicenter phase 2 AURA trial ( NCT03674424 ) enrolled patients with non-metastatic MIBC undergoing radical cystectomy. Cisplatin-eligible patients were randomized to receive avelumab with either dose-dense methotrexate-vinblastine-doxorubicin-cisplatin (ddMVAC-A) or gemcitabine-cisplatin (GC-A). Cisplatin-ineligible patients received either avelumab alone (A) or combined with paclitaxel-gemcitabine (PG-A). The primary endpoint was pathological complete response (pCR). Secondary endpoints included safety, event-free survival, and overall survival (OS). Results Between July 2018 and September 2021, 137 eligible patients were enrolled in the trial. In the cisplatin-eligible cohort (n=79), pCR rates were 58% (95% CI: 42% to 72%) in the ddMVAC-A arm and 53% (95% CI: 37% to 68%) in the GC-A arm. The 36-month OS rates were 87% (95% CI: 76% to 98%) for ddMVAC-A and 67% (95% CI: 53% to 84%) for GC-A. In the cisplatin-ineligible cohort (n=58), pCR rates were 14% (95% CI: 6% to 31%) in the PG-A arm and 32% (95% CI: 18% to 51%) in the A arm. The 36-month OS rates were 48% (95% CI: 33% to 71%) for PG-A and 42% (95% CI: 27% to 65%) for A. Overall, 51 (38%) patients experienced grade 3–4 treatment-related adverse events. Conclusions Avelumab combined with cisplatin-based neoadjuvant chemotherapy showed promising efficacy in MIBC with a favorable safety profile, also with the ddMVAC regimen. Among cisplatin-ineligible patients, avelumab monotherapy showed encouraging activity, with no additional benefit observed from the PG-A regimen. These results support the use of the ddMVAC regimen as a potential chemotherapy partner for neoadjuvant chemo-immunotherapy combinations in future phase 3 trials, providing an alternative to the GC regimen currently under investigation. Trial registration number NCT03674424 .
Tislelizumab as adjuvant therapy following endoscopic surgery for resectable recurrent nasopharyngeal carcinoma: a randomized clinical trial
Authors: Wanpeng Li, Tian Wang, Haoyuan Xu, Quan Liu, Huankang Zhang, Yufei Yang, Xicai Sun, Huapeng Yu, Yurong Gu, Houyong Li, Hao Ding, Dehui Wang
Journal: Journal for ImmunoTherapy of Cancer (2025)

Background Endoscopic surgery has become the first-line treatment for surgically resectable recurrent nasopharyngeal carcinoma (rNPC), but it is associated with a high risk of postoperative tumor progression. Currently, there is a lack of effective and well-tolerated adjuvant treatment regimens. Thus, the primary objective was to investigate the efficacy and safety of tislelizumab as adjuvant therapy with endoscopic surgery for the treatment of patients with rNPC. Methods This was a single-center, open-label, randomized, controlled, phase 2 trial between November 23, 2021, and May 8, 2024. Eligible patients included those with complete tumor disappearance as indicated by postoperative imaging, histopathologically diagnosed with undifferentiated or differentiated non-keratinizing rNPC. Patients with rNPC were randomized to receive endoscopic surgery alone or adjuvant tislelizumab treatment 2–6 weeks after endoscopic surgery. Tislelizumab was administered as a 200 mg intravenous infusion every 3 weeks until disease progression, death, unacceptable toxicity, withdrawal of consent, investigator’s decision, or 1 year. The primary endpoint was progression-free survival (PFS) at 1 year, and secondary endpoints included 1-year progression-free interval (PFI), 1-year overall survival (OS), and safety. Results The trial is ongoing. 42 patients were enrolled at a median follow-up of 18 months (IQR 10–27), the 1-year PFS was significantly higher in the tislelizumab group (94%, 95% CI: 83% to 100%) than in the endoscopic surgery alone group (57%, 95% CI: 38% to 85%). The 1-year PFI was also higher in the tislelizumab group (100%, 95% CI: 100% to 100%) than in the endoscopic surgery alone group (60%, 95% CI: 40% to 89%). No significant difference in the 1-year OS was observed at the data cut-off. Grade ≥3 immune-related adverse events (irAEs) occurred in 9% of tislelizumab recipients, and all of these events were elevated blood creatine phosphokinase levels. Additionally, the most common irAEs in this group were hypothyroidism, affecting 27%, and pruritus, observed in 9%. Conclusions Tislelizumab as adjuvant therapy significantly enhanced PFS and PFI, with a favorable safety profile. Longer follow-up is necessary to determine whether this regimen can be considered as the standard of care for patients with resectable rNPC following endoscopic surgery. Trial registration number NCT05092217 .
Whole-genome sequencing, strain composition, and predicted antimicrobial resistance of Streptococcus pneumoniae causing invasive disease in England in 2017–20: a prospective national surveillance study
Authors: Joshua C D’Aeth, Marta Bertran, Fariyo Abdullahi, Seyi Eletu, Erjola Hani, Norman K Fry, Shamez N Ladhani, David J Litt
Journal: The Lancet Microbe (2025)
Sex and socioeconomic differences in 15-year prevalence trends for modifiable dementia risk factors in Australia: a cross-sectional, time series analysis
Authors: Heidi J Welberry, Louisa R Jorm, Kim M Kiely, Hamidul Huque, Ruth Peters, Kaarin J Anstey
Journal: The Lancet Healthy Longevity (2025)

Potentially modifiable risk factors could account for approximately 45% of dementia cases globally. For targeted prevention, understanding population-specific patterns of risk is essential. We aimed to track changes in dementia prevalence across Australia, and calculate population attributable fractions of dementia, for 12 risk factors (ie, low education, hypertension, obesity, high cholesterol, smoking, high alcohol intake, poor diet, physical inactivity, hearing loss, depression, diabetes, and social isolation). In this cross-sectional, time series analysis we calculated the prevalence of dementia using five national Australian health surveys from 2007-08 to 2022. Adjusted prevalence ratios and combined population attributable fractions were estimated. Population subgroups were defined by sex and socioeconomic disadvantage (lowest 40% household income vs highest 60%). Results were disaggregated by life-stage (mid-life aged 45-64 years and late life aged 65-84 years). In mid-life, the sample sizes ranged from 4100 in 2022 to 5589 in 2017-18 and in late-life from 2799 in 2011-12 to 3762 in 2017-18. Smoking, high alcohol intake, physical inactivity, hearing loss, and low education in mid-life decreased and obesity, depression, and poor diet increased; resulting in no change in population attributable fraction (47·2% [95% CI 46·5-48·0] in 2007-08 and 46·9% [45·9-47·7] in 2022). High alcohol intake, physical inactivity, and low education in late-life decreased; depression and poor diet increased; and there was no change in population attributable fraction (51·5% [50·9-52·5] in 2007-08 and 51·4% [50·7-52·4] in 2022). In mid-life, modifiable risk was higher among low-income groups and males and depression was the leading modifiable risk factor in 2022, disproportionately affecting low-income households and females. The modifiable population attributable fraction of dementia in Australia in the past 15 years remained stable, but the profile of risk has changed. Low-income groups (compared with high-income groups) have substantially higher modifiable risk and targeted multidomain interventions could help reduce disparities. National Health and Medical Research.
Once-Weekly Mazdutide in Chinese Adults with Obesity or Overweight
Authors: Linong Ji, Hongwei Jiang, Yan Bi, Hua Li, Junhang Tian, Dexue Liu, Yuzhu Zhao, Wei Qiu, Chongbing Huang, Lei Chen, Shao Zhong, Jie Han, Yawei Zhang, Qiufang Lian, Ping Yang, Lingchun Lv, Jieyu Gu, Zihan Liu, Huan Deng, Yanqi Wang, Li Li, Lijuan Pei, Lei Qian
Journal: New England Journal of Medicine (2025)

Evidence suggests that incretin-based dual agonist pharmacotherapy is helpful in persons with obesity. Mazdutide, a glucagon-like peptide-1 and glucagon receptor dual agonist, may have efficacy in persons with overweight or obesity. In a phase 3, double-blind, placebo-controlled trial in China, we randomly assigned, in a 1:1:1 ratio, adults 18 to 75 years of age who had a body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) of at least 28 or had a BMI of 24 to less than 28 plus at least one weight-related coexisting condition to receive 4 mg of mazdutide, 6 mg of mazdutide, or placebo for 48 weeks. The two primary end points were the percentage change in body weight from baseline and a weight reduction of at least 5% at week 32, as assessed in a treatment-policy estimand analysis (which assessed effects regardless of early discontinuation of mazdutide or placebo and the initiation of new antiobesity therapies). Among 610 participants, the mean body weight was 87.2 kg and the mean BMI was 31.1 at baseline. At week 32, the mean percentage change in body weight from baseline was -10.09% (95% confidence interval [CI], -11.15 to -9.04) in the 4-mg mazdutide group, -12.55% (95% CI, -13.64 to -11.45) in the 6-mg mazdutide group, and 0.45% (95% CI, -0.61 to 1.52) in the placebo group, and 73.9%, 82.0%, and 10.5% of the participants, respectively, had a weight reduction of at least 5% (P<0.001 for all comparisons with placebo). At week 48, the mean percentage change in body weight from baseline was -11.00% (95% CI, -12.27 to -9.73) in the 4-mg mazdutide group, -14.01% (95% CI, -15.36 to -12.66) in the 6-mg mazdutide group, and 0.30% (95% CI, -0.98 to 1.58) in the placebo group, and 35.7%, 49.5%, and 2.0% of the participants, respectively, had a weight reduction of at least 15% (P<0.001 for all comparisons with placebo). Beneficial effects on all prespecified cardiometabolic measures were seen with mazdutide. The most frequently reported adverse events were gastrointestinal and mostly mild to moderate in severity. The incidence of adverse events leading to discontinuation of the trial regimen was 1.5% with the 4-mg mazdutide dose, 0.5% with the 6-mg mazdutide dose, and 1.0% with placebo. In Chinese adults with overweight or obesity, once-weekly mazdutide at a dose of 4 mg or 6 mg for 32 weeks led to clinically relevant reductions in body weight. (Funded by Innovent Biologics; GLORY-1 ClinicalTrials.gov number, NCT05607680.).