tbuckley/cabot-search huggingface dataset:
A Microneedle Patch Delivers Mitochondria‐ and Lysosomes‐ Dual Targeting Prodrug‐Like Photosensitizers with Regulated Photoactivity for Precise Photodynamic Therapy
Authors: Zheng Liu, Zhimin Tang, Ying Yin, Miaojian Wan, Jiezhao Zhan, Li Ren
Journal: Advanced Healthcare Materials (2025)

Antitumor photodynamic therapy (PDT) faces huge challenges as selectivity and phototoxic damage, requiring delivery photosensitizers (PSs) to specifically accumulate in tumors even in organelle, and avoid the phototoxic damage during delivery. Herein, a microneedle patch (AIE-mito-TPP@MN) containing mitochondria- and lysosomes- dual targeting prodrug-like PSs (AIE-mito-TPP/AlPcSNa4) that is self-assembled by mitochondria-targeted aggregation-induced-emission molecule (AIE-mito-TPP) and lysosome-targeted aluminum phthalocyanine tetrasulfonate (AlPcSNa4), is developed to achieve cancer-cell-organelle-specific targeting delivery for precise PDT with high selectivity and low phototoxic damage. AIE-mito-TPP/AlPcSNa4 displays prodrug-like activity via the regulated photoactivity to reduce the phototoxic damage caused by the "always on" PSs. Meanwhile, AIE-mito-TPP/AlPcSNa4@MN can insert into the epidermis to achieve rapid AIE-mito-TPP/AlPcSNa4 delivery in tumor lesion, and enhance selective accumulation in tumor cells. The higher lysosomal acidity in tumor cells facilitates AIE-mito-TPP/AlPcSNa4 disassembly and promotes targeting. Under light irradiation, AIE-mito-TPP/AlPcSNa4@MN impairs mitochondrial and lysosomal function to induce deeper tumor cells apoptosis at a low dose (≈6 µg), presenting greater therapeutic efficacy than AIE-mito-TPP@MN, AlPcSNa4@MN, or intravenous injection. Moreover, AIE-mito-TPP/AlPcSNa4@MN presents good biocompatibility as lower accumulation and targeting in normal cells, as well as the regulated photoactivity of prodrug-like PSs. Therefore, the dual organelle-targeting microneedle possesses great potential for precise PDT with high selectivity.
Continuous Dopamine D<sub>2</sub> Receptor Blockade and Long-Term Outcome in First-Episode Schizophrenia
Authors: Jari Tiihonen, Antti Tanskanen, Marco Solmi, Jose M. Rubio, Christoph U. Correll, John M. Kane, Heidi Taipale
Journal: American Journal of Psychiatry (2025)

It is not known what proportion of patients experience relapse in first-episode schizophrenia despite continuous dopamine D2 receptor blockade and whether breakthrough psychosis is attributable to long-term use of D2-blocking antipsychotics. Using data from a Finnish nationwide cohort, the authors sought to test the hypothesis that the incidence of breakthrough psychosis is accelerated among previously relapse-free patients receiving continuous D2 antagonist treatment beyond 5 years. All persons age 45 years or younger with first-episode schizophrenia were identified from the nationwide registry of inpatient care for the years 1996-2014. The primary outcome was a severe relapse leading to hospitalization among those treated continuously with long-acting injectable (LAI) antipsychotics. The secondary outcome was the incidence rate ratio (IRR) of relapse during years 2-10, using year 1 as the reference. A total of 305 patients initiated ensured LAI use during the first 30 days of follow-up. Kaplan-Meier analysis showed that during the 10-year follow-up, their cumulative probability of relapse was 45% (95% CI=35-57). The annual relapse incidence per person-year decreased from 0.26 (95% CI=0.20-0.35) during the first year to 0.05 (95% CI=0.01-0.19) during the fifth year, corresponding to an IRR of 0.18 (95% CI=0.04-0.74). During years 6-10, only four relapses occurred during 128 person-years, corresponding to an IRR of 0.12 (95% CI=0.03-0.33) compared with year 1. About 40%-50% of patients with first-episode schizophrenia will relapse despite continuous D2 blockade, apparently due to non-dopaminergic elements of the pathophysiology of the illness, as the results show that long-term dopamine receptor blockade is not associated with an increased risk of breakthrough psychosis.
Multieffect Specific Nanovesicles for Homing Resistant Tumors and Overcoming Osimertinib‐Acquired Resistance in NSCLC
Authors: Yuanyao Dou, Yihui Liu, Rui Han, Jie Zheng, Liping Wang, Chen Hu, Daijuan Huang, Chao He, Yimin Zhang, Caiyu Lin, Conghua Lu, Di Wu, Huan Tang, Tingting He, Liling Tang, Yong He
Journal: Advanced Healthcare Materials (2025)

Abstract Acquired resistance to osimertinib (Osi) remains a major obstacle in the treatment of patients with EGFR‐mutant non‐small cell lung cancer (NSCLC). AXL elevation is a known key mechanism of Osi‐resistance, and therapeutic strategies remain scarce. Emerging evidence reveals that an increased intracellular glutathione (GSH) level induces Osi resistance. In this study, a new mechanism is identified by which GSH regulates AXL expression via glutathione peroxidase 4 (GPX4) in Osi‐resistant cells. A multifunctional covalent organic framework (COF) nanoplatform for GSH consumption, AXL inhibition, and co‐delivery of the AXL inhibitor (Brigatinib) and Osi is creatively constructed to confirm whether Osi sensitivity improves by simultaneously targeting GSH‐AXL resistance mechanisms. Furthermore, it is coated, for the first time, the COF carrier system with specific vesicles to precisely home it into resistant tumors, where CDH2 adhesion molecules play a crucial role. The engineered multifunctional antiresistance‐specific nanovesicles effectively inhibited the GSH‐AXL axis, induced apoptosis in Osi‐resistant cells both in vitro and in vivo, and delayed the progression of Osi‐resistant tumors. Overall, these findings provide a novel strategy to overcome the Osi‐acquired resistance caused by high AXL levels in NSCLC.
KASL clinical practice guidelines for the management of metabolic dysfunction-associated steatotic liver disease 2025
Authors: Won Sohn, Young-Sun Lee, Soon Sun Kim, Jung Hee Kim, Young-Joo Jin, Ki-Ae Kim, Pil Soo Sung, Jeong-Ju Yoo, Young Chang, Eun Joo Lee, Hye Won Lee, Miyoung Choi, Su Jong Yu, Young Kul Jung, Byoung Kuk Jang
Journal: Clinical and Molecular Hepatology (2025)
Treatment of Osteoporosis and Osteoarthritis in the Oldest Old
Authors: Nicholas Fuggle, Andrea Laslop, René Rizzoli, Nasser Al-Daghri, Majed Alokail, Ewa Balkowiec-Iskra, Charlotte Beaudart, Olivier Bruyère, Angie Botto-van Bemden, Nansa Burlet, Etienne Cavalier, Francesca Cerreta, Manju Chandran, Antonio Cherubini, Mario Miguel Coelho da Silva Rosa, Philip Conaghan, Bernard Cortet, Alfonso Cruz Jentoft, Elizabeth M Curtis, Patrizia D'Amelio, Bess Dawson-Hughes, Elaine M Dennison, Mickaël Hiligsmann, Jean-Marc Kaufman, Stefania Maggi, Radmila Matijevic, Eugene McCloskey, Daniel Messina, Daniel Pinto, Maria Concepcion Prieto Yerro, Régis Pierre Radermecker, Yves Rolland, Carla Torre, Nicola Veronese, John A Kanis, Cyrus Cooper, Jean-Yves Reginster, Nicholas C Harvey
Journal: Drugs (2025)
Preoperative SGLT2 Inhibitor Use and Postoperative Diabetic Ketoacidosis
Authors: Anjali A. Dixit, Brian T. Bateman, Mary T. Hawn, Michelle C. Odden, Eric C. Sun
Journal: JAMA Surgery (2025)

Importance Case reports of postoperative diabetic ketoacidosis in patients using sodium-glucose cotransporter 2 inhibitor (SGLT2i) medications underlie guidance by the US Food and Drug Administration to withhold SGLT2i medication for at least 3 days prior to surgery. Given the potential negative consequences associated with preoperative medication withholding, a large-scale evaluation of the risk of diabetic ketoacidosis in this population is needed. Objective To estimate the association between preoperative SGLT2i medication use and postoperative diabetic ketoacidosis in a population of patients who underwent a variety of emergency surgeries. Emergency surgery was chosen given the assumption that a patient would be unable to withhold their SGLT2i medication per the current guidance. Design, Setting, and Participants This retrospective cohort study was conducted among a nationwide sample of patients aged 18 years or older with type 2 diabetes who were enrolled in commercial or Medicare fee-for-service insurance plans and who underwent 1 of 13 emergency surgeries between January 1, 2016, and December 15, 2022. Emergency surgeries were defined as those occurring on the same day or the 1 to 2 days after an emergency department claim. Data were analyzed from November 2023 through December 2024. Exposure SGLT2i medication use. Main Outcomes and Measures Diabetic ketoacidosis, defined by diagnosis codes, in the 0 to 14 days after surgery. Results Among 34 671 patients with type 2 diabetes who underwent emergency surgery (mean [SD] age, 63.9 [14.0] years; 19 175 female [55.3%] and 15 496 male [44.7%]), the most common surgeries were laparoscopic cholecystectomy (9385 patients) and transurethral procedures (12 246 patients). There were 2607 patients (7.5%) who used SGLT2i medications and 32 064 patients (92.5%) who did not. Unadjusted incidence of diabetic ketoacidosis was 127 patients (4.9%) for those exposed to SGLT2i medications and 1115 patients (3.5%) for those unexposed. After accounting for covariates, including demographic characteristics, indicators of diabetic severity, comorbidities, and surgery type, the incidence of the outcome was 3.8% for those exposed to SGLT2i medications and 3.5% for those unexposed. The average treatment effect [ATE] was 0.2% (95% CI, −1.7% to 2.2%). Results were robust to alternate specifications (eg, intensive care unit–level care as the outcome: ATE, −1.0%; 95% CI, −2.9% to 1.1%). Conclusions and Relevance This study found that preoperative use of SGLT2i medications in patients undergoing emergency surgery was not associated with an increased risk for postoperative diabetic ketoacidosis compared with no use of SGLT2i medications. These findings may justify liberalizing current guidance on preoperative SGLT2i medication withholding periods.
Histopathologic Grading of Acute Cutaneous Graft-vs-Host Disease and Nonrelapse Mortality
Authors: Jennifer Chen, Caroline Raymundo, Abigail Martinez, Stephanie J. Lee, Phillip A. Stevenson, Michi M. Shinohara
Journal: JAMA Dermatology (2025)

This cohort study examines clinical grade, skin stage, and histologic grade at posttransplant skin biopsy of patients with acute graft-vs-host disease.
Clinician Experiences With Ambient Scribe Technology to Assist With Documentation Burden and Efficiency
Authors: Matthew J. Duggan, Julietta Gervase, Anna Schoenbaum, William Hanson, John T. Howell, Michael Sheinberg, Kevin B. Johnson
Journal: JAMA Network Open (2025)

Importance Timely evaluation of ambient scribing technology is warranted to assess whether this technology can lessen the burden of clinical documentation on clinicians. Objective To investigate the association of ambient scribing technology with efficiency, quality, and perceived burden of clinical documentation in the outpatient setting. Design, Setting, and Participants This prospective, single-group pre-post quality improvement study was conducted between April and June 2024 in the outpatient setting of an academic health system in Philadelphia, Pennsylvania. Participants included physicians, nurse practitioners, and physician assistants. Data were analyzed from July to August 2024. Exposure Access to an artificial intelligence–driven ambient scribing tool for outpatient notes. Main Outcomes and Measures The primary outcomes were time in notes per appointment, same-day appointment closure, after-hours work time, perceived burden of clinical documentation, and comments on clinicians’ experiences using ambient scribing. A mixed-effects model was used. Both objective metrics and survey feedback were obtained. Targeted perspective questions, designed to assess clinician-perceived patient engagement and perceived documentation burden, were assessed on a 7-point Likert scale. Standard System Usability Scale (SUS) and net promoter score (NPS) formulas were used to analyze usability and recommendability data. Results This study included 46 clinicians from 17 different medical specialties, with a mean (SD) of 11.1 (8.7) years in practice. From baseline to post intervention, use of the ambient scribing tool was associated with 20.4% less time in notes per appointment (from 10.3 to 8.2 minutes; P &amp;amp;lt; .001), 9.3% greater same-day appointment closure (from 66.2% to 72.4%; P &amp;amp;lt;.001), and 30.0% less after-hours work time per workday (from 50.6 to 35.4 minutes per workday; P = .02). Targeted perspective questions showed more favorable scores. Open-ended qualitative feedback from clinicians showed a range of positive, negative, and mixed feedback regarding their use of ambient scribing technology. SUS scores showed that the ambient scribing tool was easy to use. NPSs reflected the mixed qualitative feedback. Conclusions and Relevance In this quality improvement study, the use of ambient scribe technology was associated with greater efficiency of outpatient clinical documentation, lower mental burden of documentation for clinicians, and greater sense of engagement with patients during outpatient appointments. Additional studies exploring urgent care settings, examining patient experience, and comparing multiple tools will be important to better understand the effect of ambient scribing on ambulatory care.
Percentage of Opioid Tests Available in US Injury Death Investigations, 2021
Authors: Alexander Lundberg, Lori Post, Jay Unick, Danielle McCarthy, Sarah Welch, Kena Noland, Katie Lawler, Maryann Mason
Journal: JAMA (2025)

This study uses 2021 data on the percentage of unavailable opioid tests in the US to examine how opioid involvement informs injury death investigations.
Rehab
Authors: Roshni Beeharry
Journal: JAMA (2025)

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Roadmap for alleviating the manifestations of ageing in the cardiovascular system
Authors: Luca Liberale, Simon Tual-Chalot, Simon Sedej, Stefano Ministrini, Georgios Georgiopoulos, Myriam Grunewald, Magnus Bäck, Marie-Luce Bochaton-Piallat, Reinier A. Boon, Gustavo Campos Ramos, Menno P. J. de Winther, Konstantinos Drosatos, Paul C. Evans, Jane F. Ferguson, Sofia K. Forslund-Startceva, Claudia Goettsch, Mauro Giacca, Judith Haendeler, Marinos Kallikourdis, Daniel F. J. Ketelhuth, Rory R. Koenen, Patrick Lacolley, Esther Lutgens, Pasquale Maffia, Satomi Miwa, Claudia Monaco, Fabrizio Montecucco, Giuseppe Danilo Norata, Elena Osto, Gavin D. Richardson, Niels P. Riksen, Oliver Soehnlein, Ioakim Spyridopoulos, Sophie Van Linthout, Gemma Vilahur, Jolanda J. Wentzel, Vicente Andrés, Lina Badimon, Athanase Benetos, Christoph J. Binder, Ralf P. Brandes, Filippo Crea, David Furman, Vera Gorbunova, Tomasz J. Guzik, Joseph A. Hill, Thomas F. Lüscher, María Mittelbrunn, Alessio Nencioni, Mihai G. Netea, João F. Passos, Kimon S. Stamatelopoulos, Nektarios Tavernarakis, Zoltan Ungvari, Joseph C. Wu, James L. Kirkland, Giovanni G. Camici, Stefanie Dimmeler, Guido Kroemer, Mahmoud Abdellatif, Konstantinos Stellos
Journal: Nature Reviews Cardiology (2025)
RSAD2: A pathogenic interferon-stimulated gene at the maternal-fetal interface of patients with systemic lupus erythematosus
Authors: Xiaoyu Ding, Yonggang Zhou, Xiaofeng Qiu, Xiuxiu Xu, Xinyu Hu, Jingkun Qin, Yulan Chen, Min Zhang, Jieqi Ke, Zhenbang Liu, Ying Zhou, Chen Ding, Nan Shen, Zhigang Tian, Binqing Fu, Haiming Wei
Journal: Cell Reports Medicine (2025)

Pregnancy disorders in patients with autoimmune diseases or viral infections are often associated with an excessive response of type I interferons. We identify radical S-adenosyl methionine domain containing 2 (RSAD2) as a pathogenic interferon-stimulated gene (ISG) associated with pregnancy complications in systemic lupus erythematosus (SLE). The increased expression of RSAD2 mainly occurs in macrophages and structural cell populations at the maternal-fetal interface of pregnant patients with SLE. The elevation of RSAD2 leads to the accumulation of diacylglycerol lipids in the placenta, impairing the necessary vascular development for the fetus. Depletion of Rsad2 in pregnant mice models exposed to type I interferon inducers significantly reduces lipid accumulation, vascular injury, and embryo development disorders. An RSAD2 inhibitor, L-chicoric acid (LCA), alleviates lipid accumulation and vascular damage, improving pregnancy outcomes in SLE-induced and spontaneous mouse models. This study proposes the potential of targeting RSAD2 to improve pregnancy outcomes in individuals with heightened type I interferon response.
Integrative spatial analysis reveals tumor heterogeneity and immune colony niche related to clinical outcomes in small cell lung cancer
Authors: Haiquan Chen, Chaoqiang Deng, Jian Gao, Jun Wang, Fangqiu Fu, Yue Wang, Qiming Wang, Mou Zhang, Shiyue Zhang, Fanfan Fan, Kun Liu, Bo Yang, Qiming He, Qiang Zheng, Xuxia Shen, Jin Wang, Tao Hu, Changbin Zhu, Fei Yang, Yonghong He, Hong Hu, Jialei Wang, Yuan Li, Yang Zhang, Zhiwei Cao
Journal: Cancer Cell (2025)
adiposetissue.org: A knowledge portal integrating clinical and experimental data from human adipose tissue
Authors: Jiawei Zhong, Danae Zareifi, Sophie Weinbrenner, Mattias Hansen, Felix Klingelhuber, Pamela A Nono Nankam, Scott Frendo-Cumbo, Nayanika Bhalla, Lina Cordeddu, Thais de Castro Barbosa, Peter Arner, Ingrid Dahlman, Maheswary Muniandy, Sini Heinonen, Kirsi H Pietiläinen, Anne Hoffmann, Adhideb Ghosh, Dorit John, Anke Tönjes, Patrik L Ståhl, Yvonne Böttcher, Maria Keller, Peter Kovacs, Alastair G Kerr, Dominique Langin, Christian Wolfrum, Matthias Blüher, Natalie Krahmer, Lucas Massier, Niklas Mejhert, Mikael Rydén
Journal: Cell Metabolism (2025)
Methionine intervention induces PD-L1 expression to enhance the immune checkpoint therapy response in MTAP-deleted osteosarcoma
Authors: Haoran Mu, Qi Zhang, Dongqing Zuo, Jinzeng Wang, Yining Tao, Zhen Li, Xin He, Huanliang Meng, Hongsheng Wang, Jiakang Shen, Mengxiong Sun, Yafei Jiang, Weisong Zhao, Jing Han, Mengkai Yang, Zhuoying Wang, Yu Lv, Yuqin Yang, Jing Xu, Tao Zhang, Liu Yang, Jun Lin, Feng Tang, Renhong Tang, Haiyan Hu, Zhengdong Cai, Wei Sun, Yingqi Hua
Journal: Cell Reports Medicine (2025)

Osteosarcoma (OS), a malignant bone tumor with limited treatment options, exhibits low sensitivity to immune checkpoint therapy (ICT). Through genomics and transcriptomics analyses, we identify a subgroup of OS with methylthioadenosine phosphorylase (MTAP) deletion, which contributes to ICT resistance, leading to a "cold" tumor microenvironment. MTAP-deleted OS relies on methionine metabolism and is sensitive to methionine intervention, achieved through either dietary restriction or inhibition of methionine adenosyltransferase 2a (MAT2A), a key enzyme in methionine metabolism. We further demonstrate that methionine intervention triggers programmed death-ligand 1 (PD-L1) transcription factor IKAROS family zinc finger 1 (IKZF1) and enhances PD-L1 expression in MTAP-deleted OS cells. Methionine intervention also activates the immune-related signaling pathways in MTAP-deleted OS cells and attracts CD8+ T cells, thereby enhancing the efficacy of ICT. Combining methionine intervention with ICT provides a significant survival benefit in MTAP-deleted OS murine models, suggesting a rationale for combination regimens in OS ICT.
Continuous replenishment of the dysfunctional CD8 T cell axis is associated with response to chemoimmunotherapy in advanced breast cancer
Authors: Christina Metoikidou, Vadim Karnaukhov, Bram Boeckx, Eleonora Timperi, Pierre-Emmanuel Bonté, Ling Wang, Marion Espenel, Benoit Albaud, Delphine Loirat, Xiaoxiao Wang, Christos Sotiriou, Philippe Aftimos, Kevin Punie, Hans Wildiers, Viktorija Labroska, Ming-Wei Wang, Joshua J Waterfall, Martine Piccart-Gebhart, Thierry Mora, Aleksandra Walczak, Olivier Lantz, Laurence Buisseret, Diether Lambrechts, Sebastian Amigorena, Emanuela Romano
Journal: Cell Reports Medicine (2025)

Chemotherapy combined with immune checkpoint blockade has shown clinical activity in breast cancer. Response, however, occurs in only a low proportion of patients. How the immune landscape of the tumor determines the immune and clinical responses to chemoimmunotherapy is not well understood. Here, using a combination of single-cell RNA sequencing (scRNA-seq) and single-cell T cell receptor sequencing (scTCR-seq), we profile 40 biopsies from 27 patients with metastatic triple-negative breast cancer (TNBC), receiving chemotherapy and anti-PD-L1 alone or in combination with anti-CD73, in a phase 2 randomized clinical trial. Our results show an enrichment of late-dysfunctional, clonally expanded CD8+ T cells in responder (R) patients. On treatment, R display an influx of newly emerging clonotypes, as well as expansion of the CD8+ precursors. Collectively, our data suggest that baseline clonal expansion could be a potential predictor of response and that both clonal reinvigoration of pre-existing tumor-reactive T cells and clonal replacement on-treatment are important for a protective response to chemoimmunotherapy.
Autologous TIL Infusion Plus Anti-PD-1 Therapy to Cure Advanced Hepatocellular Carcinoma Following Palliative Hepatectomy
Authors: Tian Xia, Tong Yuan, Lijun Chen, Changli Wang, Erlei Zhang, Binyong Liang, Zunyi Zhang, Mingwei Wang, Xiaoping Chen, Zhiyong Huang
Journal: Liver Cancer (2025)

Introduction: Adoptive cell therapy (ACT) derived from autologous tumor-infiltrating lymphocytes (TIL) has demonstrated promising therapeutic efficacy in several cancers. However, its possible synergistic effects with anti-PD-1 therapy in advanced hepatocellular carcinoma (aHCC) remain unexplored. This study aims to investigate the efficacy of TIL infusion combined with anti-PD-1 therapy for aHCC. Case Presentation: Referring to the current protocol of our clinical trial (NCT03658785), two patients with HCC at BCLC stage C were enrolled to receive autologous TIL infusion combined with anti-PD-1 therapy. They underwent unplanned palliative tumor resection to alleviate pain caused by tumor rupture prior to receiving TIL infusion plus anti-PD-1 therapy. Long-term outcomes and treatment-related adverse events were evaluated. Throughout the entire treatment process, both patients experienced only mild symptoms. Notably, both patients achieved complete responses to the treatment and have remained tumor-free for two and four years, respectively. Conclusion: Autologous TIL infusion combined with anti-PD-1 therapy is a safe and feasible strategy for patients with aHCC. Palliative hepatectomy with maximal tumor burden reduction may significantly improve its efficacy and even results in cure for aHCC patients.