tbuckley/cabot-search huggingface dataset:
An active inference strategy for prompting reliable responses from large language models in medical practice
Authors: Roma Shusterman, Allison C. Waters, Shannon O’Neill, Marshall Bangs, Phan Luu, Don M. Tucker
Journal: npj Digital Medicine (2025)

Continuing advances in Large Language Models (LLMs) are transforming medical knowledge access across education, training, and treatment. Early literature cautions their non-determinism, potential for harmful responses, and lack of quality control. To address these issues, we propose a domain-specific, validated dataset for LLM training and an actor–critic prompting protocol grounded in active inference. A Therapist agent generates initial responses to patient queries, while a Supervisor agent refines them. In a blind validation study, experienced cognitive behavior therapy for insomnia (CBT-I) therapists evaluated 100 patient queries. For each query, they were given either the LLM's response or one of two therapist-crafted responses—one appropriate and one deliberately inappropriate—and asked to rate the quality and accuracy of each reply. The LLM often received higher ratings than the appropriate responses, indicating effective alignment with expert standards. This structured approach lays the foundation for safely integrating advanced LLM technology into medical applications.
Correction: Anti-IL-5 Pathway Agents in Eosinophilic-Associated Disorders Across the Lifespan
Authors: Carlo Lombardi, Pasquale Comberiati, Erminia Ridolo, Marcello Cottini, Mona Rita Yacoub, Silvia Casagrande, Matteo Riccò, Marco Bottazzoli, Alvise Berti
Journal: Drugs (2025)
Efficacy and Safety of Biologics for Chronic Rhinosinusitis With Nasal Polyps: A Meta‐Analysis of Real‐World Evidence
Authors: Shiru Cai, Shenglong Xu, Yan Zhao, Luo Zhang
Journal: Allergy (2025)

ABSTRACT Dupilumab, omalizumab, mepolizumab, and benralizumab have demonstrated good efficacy and safety in the treatment of severe uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNP) in phase 3 randomised controlled trials (RCTs). With recent regulatory approvals, there has been a surge in real‐world studies (RWSs). This systematic review and meta‐analysis aimed to summarise the efficacy and safety of these four biologics in real‐world settings. Primary outcomes were nasal polyp score and sino‐nasal outcome test‐22 score. Secondary outcomes included smell identification test score, loss of smell score, nasal congestion score, overall nasal symptom score, treatment response, and adverse events (AEs) prompting discontinuation. Efficacy outcomes at 4, 6, 12, and over 12 months were summarised, and meta‐analyses of mean changes from baseline were conducted. Sixty‐four RWSs involving 3921 patients were included. Significant improvements in clinical outcomes were observed at most follow‐up time points, with dupilumab showing particularly notable effects. The efficacy observed in these RWSs was superior to that demonstrated in phase 3 RCTs. All biologics exhibited low discontinuation rates due to AEs. Overall, biologic treatments for CRSwNP in real‐world settings demonstrate strong efficacy and good safety. However, the limitations in current RWSs highlight the need for long‐term, high‐quality multicentre prospective studies and comprehensive healthcare database analyses.
Precision repair of zone-specific meniscal injuries using a tunable extracellular matrix-based hydrogel system
Authors: Se-Hwan Lee, Zizhao Li, Ellen Y Zhang, Dong Hwa Kim, Ziqi Huang, Yuna Heo, Sang Jin Lee, Hyun-Wook Kang, Jason A Burdick, Robert L Mauck, Su Chin Heo
Journal: Bioactive Materials (2025)
Minimally invasive modalities for keratinocyte carcinomas Part I: Diagnostics
Authors: Patrick McMullan, Sarah Balboul, Nathan Gasek, Lauren Skudalski, Albert E Zhou, Neelesh Patrick Jain, Nicholas Gulati, Silvana Ciardo, Francesca Farnetani, Brett Sloan, Jonathan Ungar, Jane M Grant-Kels, Jonas A Adalsteinsson
Journal: Journal of the American Academy of Dermatology (2025)
STING mediates increased self-renewal and lineage skewing in DNMT3A-mutated hematopoietic stem/progenitor cells
Authors: Jingru Huang, Jiaying Xie, Yin Wang, Mengyao Sheng, Yue Sun, Pingyue Chen, Shaoqin Rong, Dongrui Yin, Yuanxian Wang, Ping Zhu, Stefan K. Bohlander, Guo-Liang Xu, Hai Gao, Dan Zhou, Yuheng Shi
Journal: Leukemia (2025)

Somatic mutations in DNA methyltransferase 3 A (DNMT3A) are frequently observed in patients with hematological malignancies. Hematopoietic stem/progenitor cells (HSPCs) with mutated DNMT3A demonstrate increased self-renewal activity and skewed lineage differentiation. However, the molecular mechanisms underlying these changes remain largely unexplored. In this study, we show that Dnmt3a loss leads to the upregulation of endogenous retroviruses (ERVs) in HSPCs, subsequently activating the cGAS-STING pathway and triggering inflammatory responses in these cells. Both genetic and pharmacological inhibition of STING effectively corrects the increased self-renewal activity and differentiation skewing induced by Dnmt3a deficiency in mice. Notably, targeting STING showed inhibited acute myeloid leukemia (AML) development in a Dnmt3a-KO; Flt3-ITD AML model, comparable to AC220, an FDA-approved FLT3-ITD inhibitor. A patient-derived xenograft (PDX) model further demonstrated that targeting STING effectively alleviates the leukemic burden of DNMT3A-mutant AML. Collectively, our findings highlight a critical role for STING in hematopoietic disorders induced by DNMT3A mutations and propose STING as a potential therapeutic target for preventing the progression of DNMT3A mutation-associated leukemia.
Branched penetratin and penetramax display enhanced intestinal insulin delivery potency compared to their linear counterparts
Authors: Ragna Guldsmed Diedrichsen, Narendra Kumar Mishra, Freja Fredholt, Joanne Heade, Kasper Kildegaard Sørensen, Knud Jørgen Jensen, Hanne Mørck Nielsen
Journal: Journal of Controlled Release (2025)
Long-acting bioengineered platelets with internal doxorubicin loaded and external quercetin liposomes anchored for post-surgical tumor therapy
Authors: Qi Lu, Zeyu Han, Xia Wang, Lili Du, Xiaoyuan Fan, Jian Zhao, Ruihong Zhu, Helin Wang, Jiaxuan Song, Wenwen Shen, Haotian Zhang, Zhonggui He, Kaiyuan Wang, Jin Sun
Journal: Journal of Controlled Release (2025)
Combining oxygen delivery and generation for targeted atherosclerosis therapy
Authors: Yujie Wang, Qianru Zhou, Le Lu, Jianhua Xu, Gang Yang, Xuan Sun, Xue Bao, Lina Kang, Pin Lv, Renyuan Liu, Biao Xu, Qi Yang, Dan Mu, Bing Zhang
Journal: Journal of Controlled Release (2025)

Hypoxia plays an important role in the progression of atherosclerosis. However, ameliorating hypoxia at atherosclerotic lesions remains a great challenge. To achieve targeted oxygen delivery to atherosclerotic plaques, Lipid 5-doped, platelet membrane-encapsulated magnetic mesoporous organosilicon nanoparticles loaded with perfluoro-15-crown ether (PFCE) (FMMON@PL) were prepared. PFCE worked as an oxygen carrier, while iron oxide nanoparticles (IONPs) acted as nanozymes with catalase-like activity to facilitate oxygen generation. To enhance plaque targeting, platelet membranes were coated onto mesoporous organosilicon nanoparticles containing PFCE and IONPs. Lipid 5 containing a tertiary amine was doped into the platelet membranes for lysosomal escape. Our results demonstrated that FMMON@PL specifically targeted macrophages in atherosclerotic plaques. FMMON@PL significantly reduced HIF-1α expression, ameliorated oxidative stress, inhibited foam cell formation, and reduced M1 macrophage polarization. In conclusion, FMMON@PL successfully achieved oxygen delivery within plaques and inhibited plaque progression, demonstrating the feasibility of hypoxia alleviation for the treatment of atherosclerosis.
Conditional sequential delivery of ginkgetin and rapamycin orchestrates inflammation and autophagy to alleviate intervertebral disc degeneration
Authors: Jiaoxiang Chen, Xin Gan, Shenkai Su, Sizhe Jiao, Zailing Gong, Ziqiang Liu, Xiaopei Wu, Jun Jiang, Jiaming Zhang, Junlai Wan
Journal: Journal of Controlled Release (2025)
Multimodal machine learning to predict surgical site infection with healthcare workload impact assessment
Authors: Kenneth A. McLean, Alessandro Sgrò, Leo R. Brown, Louis F. Buijs, Katie E. Mountain, Catherine A. Shaw, Thomas M. Drake, Riinu Pius, Stephen R. Knight, Cameron J. Fairfield, Richard J. E. Skipworth, Sotirios A. Tsaftaris, Stephen J. Wigmore, Mark A. Potter, Matt-Mouley Bouamrane, Ewen M. Harrison, K. Baweja, W. A. Cambridge, V. Chauhan, K. Czyzykowska, M. Edirisooriya, A. Forsyth, B. Fox, J. Fretwell, C. Gent, A. Gherman, L. Green, J. Grewar, S. Heelan, D. Henshall, C. Iiuoma, S. Jayasangaran, C. Johnston, E. Kennedy, D. Kremel, J. Kung, J. Kwong, C. Leavy, J. Liu, S. Mackay, A. MacNamara, S. Mowitt, E. Musenga, N. Ng, Z. H. Ng, S. O’Neill, M. Ramage, J. Reed, A. Riad, C. Scott, V. Sehgal, A. Sgrò, L. Steven, B. Stutchfield, S. Tominey, W. Wilson, M. Wojtowicz, J. Yang
Journal: npj Digital Medicine (2025)

Abstract Remote monitoring is essential for healthcare digital transformation, however, this poses greater burdens on healthcare providers to review and respond as the data collected expands. This study developed a multimodal neural network to automate assessments of patient-generated data from remote postoperative wound monitoring. Two interventional studies including adult gastrointestinal surgery patients collected wound images and patient-reported outcome measures (PROMs) for 30-days postoperatively. Neural networks for PROMs and images were combined to predict surgical site infection (SSI) diagnosis within 48 h. The multimodal neural network model to predict confirmed SSI within 48 h remained comparable to clinician triage (0.762 [0.690–0.835] vs 0.777 [0.721–0.832]), with an excellent performance on external validation. Simulated usage indicated an 80% reduction in staff time (51.5 to 9.1 h) without compromising diagnostic accuracy. This multimodal approach can effectively support remote monitoring, alleviating provider burden while ensuring high-quality postoperative care.
Targeted delivery of CCL3 reprograms macrophage antigen presentation and enhances the efficacy of immune checkpoint blockade therapy in hepatocellular carcinoma
Authors: Muqi Liu, Linzhe Li, Lu Cao, Wei Li, Xingshi Gu, Min Yang, Di Wu, Yanan Li, Yao Deng, Juan Zhang, Cejun Yang, Qi Liang, Huaping Liu, Pengfei Rong, Xiaoqian Ma, Wei Wang
Journal: Journal for ImmunoTherapy of Cancer (2025)

Background Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related deaths worldwide, especially in advanced stages where limited treatment options result in poor prognosis. The immunosuppressive tumor immune microenvironment (TIME), characterized by low immune cell infiltration and exhaustion, limits immunotherapy efficacy. To address this, our study investigates the role of C-C motif chemokine ligand 3 (CCL3) in modulating the HCC TIME. Methods We analyzed CCL3 expression in human HCC samples from The Cancer Genome Atlas database, focusing on its correlation with inflammatory gene signatures and immune cell infiltration. High-dimensional single-cell RNA sequencing (scRNA-seq), flow cytometry, and multiplex immunofluorescence were used to investigate CCL3’s effects on macrophage function and T cell activation. The biological impact of CCL3 on macrophages was assessed using co-culture systems, confocal imaging, metabolite detection, and inhibition assays. Preclinical HCC models and ex vivo tumor fragment assays further explored how CCL3 modulates immune responses and enhances immune checkpoint blockade efficacy. Results Our study shows that CCL3 is suppressed in the tumor microenvironment and positively correlates with immune infiltration and inflammatory responses. Targeted liver delivery of rAAV-Ccl3 reprograms the immune microenvironment in HCC, promoting immune cell recruitment and tertiary lymphoid structure formation, thus suppressing tumor growth via immune engagement. Through scRNA-seq, flow cytometry, and multiplex immunofluorescence, we found that CCL3 enhances macrophage antigen uptake and activates cytotoxic T cells. In vivo and in vitro experiments confirmed that CCL3 facilitates T cell infiltration and upregulates MHC II expression on macrophages, enhancing antigen presentation. The CCL3-CCR5 pathway also boosts macrophage metabolism, increasing lysosomal activity and antigen uptake, thereby strengthening adaptive immune responses and increasing sensitivity to immune checkpoint blockade therapies in preclinical models. Conclusions This study highlights the pivotal role of CCL3 in reshaping the TIME and enhancing antitumor immunity in HCC. By promoting immune cell recruitment and enhancing antigen presentation, CCL3 demonstrates significant potential to improve the efficacy of immunotherapy, particularly in combination with immune checkpoint inhibitors. Targeting CCL3 may help to overcome the immunosuppressive TIME in HCC and improve patient outcomes.
Phosphatidylserine as a tumor target for CAR-T cell therapy
Authors: Celia Martín-Otal, Inés Sánchez-Moreno, Alvaro Gómez-Morón, Carla Castro, Noelia Casares, Flor Navarro, Marta Gorraiz, Pedro Justicia-Lirio, Felix Pareja, María Collantes, Iván Peñuelas, Mercedes Iñarrairaegui, Bruno Sangro, Isabel Vivas, Marta Larrayoz, Juan Roberto Rodriguez, Felipe Prosper, Sandra Hervas-Stubbs, Noa Martin-Cofreces, Juan Jose Lasarte, Teresa Lozano
Journal: Journal for ImmunoTherapy of Cancer (2025)

Background Phosphatidylserine (PS) exposed on apoptotic cells promotes immune clearance of dead cells without inducing inflammation. Conversely, PS exposure on live tumor cells promotes an immunosuppressive tumor microenvironment that hinders antitumor immune responses. After confirming elevated PS levels in various tumor cell lines and cancer tissues, we aimed to investigate its potential as a target antigen for chimeric antigen receptor T cell (CAR-T) therapy. Methods We used two different approaches to target PS. First, we employed the adaptor proteins, EDAnnexin or BCMAnnexin comprising annexin V and EDA (extra domain A of fibronectin) or B-cell maturation antigen (BCMA) antigens, to redirect the lytic activity of EDA CAR-T or BCMA CAR-T cells toward PS-expressing tumor cells. In a second approach, we developed an annexin V-based CAR (Anxa CAR-T) to directly recognize PS-positive tumor cells. Results The adaptors proteins EDAnnexin and BCMAnnexin successfully redirected EDA CAR-T or BCMA CAR-T cell activity, leading to an efficient recognition of PS + tumor cells in vitro. However, the established immunological synapse differs significantly from that observed when CAR-T cells recognize the tumor cells directly. In vivo administration of the adaptor proteins, combined with the corresponding CAR-T cells, displayed antitumor activity in mice bearing PS + tumors. Regarding the second approach, Anxa CAR-T cells effectively recognized and killed PS + tumor cells in vitro. Nonetheless, PS exposure on T-cell membranes during T-cell activation impeded efficient Anxa CAR-T cell manufacturing due to fratricide. By optimizing retroviral dose to reduce Anxa CAR expression on the cell membrane, or by using the multikinase inhibitor dasatinib, the fratricide effect was mitigated, enabling successful Anxa CAR Low -T cell production. Remarkably, Anxa CAR Low -T cells demonstrated antitumor activity in in vivo murine models of PS + hepatocarcinoma and teratocarcinoma. No signs of toxicity were observed after Anxa CAR-T cell administration. Conclusions PS holds promise as a target antigen for CAR-T cell therapy, underscoring the need to address fratricide as a key challenge in the development of PS-targeting CAR-T cells.
A Clinical Decision Support Intervention Results in a Clinically Significant Decrease in Mean Systolic Blood Pressure in a Pragmatic Clinical Trial in a Primary Care Setting
Authors: Lipika Samal, John L. Kilgallon, Stuart R. Lipsitz, Heather J. Baer, Michael P. Gannon, Ryan Dunk, Weng Ian Chay, Richard J. Fay, Pamela Garabedian, Edward Wu, Joseph V. Bonventre, Gearoid M. McMahon, Sushrut S. Waikar, Patricia Dykes
Journal: Journal of the American Society of Nephrology (2023)
ZENITH-CKD: A Phase 2B Study of Zibotentan in Combination with Dapagliflozin and Dapagliflozin Alone in Patients with CKD
Authors: Hiddo J. Heerspink, Arihiro Kiyosue, David C. Wheeler, Min Lin, Emma Wijkmark, Glenn F. Carlson, Anne-Kristina Mercier, Magnus Åstrand, Sebastian Ueckert, Peter J. Greasley, Philip D. Ambery
Journal: Journal of the American Society of Nephrology (2023)
Association of CKD-Associated Pruritus (CKDaP) with More Sleep Disorders, Increased Pain, and Worse Fatigue in US Hemodialysis Patients
Authors: Tejas Desai, Rachel A. Lasky, Kunal Malhotra, Hans-Juergen Arens, Juliana H. Oliveira, Michael S. Anger
Journal: Journal of the American Society of Nephrology (2023)
Long-Term Nedosiran Safety and Efficacy in Primary Hyperoxaluria Type 1 (PH1): Interim Analysis of PHYOX3
Authors: Jaap Groothoff, Anne-Laure A. Sellier-Leclerc, Lisa Deesker, Justine Bacchetta, Gesa Schalk, Burkhard Toenshoff, Graham W. Lipkin, Sandrine Lemoine, Horacio Plotkin, Thomas Bowman, Jing Zhou, Bernd Hoppe
Journal: Journal of the American Society of Nephrology (2023)
The FAGOTTO Trial: Randomized Controlled Trial for Impact on Renal Hemodynamics of the SGLT2 Inhibitor Canagliflozin in Diabetic Kidney Disease
Authors: Nobuhiro Nishibori, Sawako Kato, Yosuke Saka, Toshihiro Mizukoshi, Tomohiko Naruse, Hirotake Kasuga, Takashi Miyata, Masahiko Ando, Yachiyo Kuwatsuka, Hiroshi Arima, Shoichi Maruyama
Journal: Journal of the American Society of Nephrology (2023)
AYAME Study: Randomized, Double-Blind, Placebo-Controlled Phase 3 Study of Bardoxolone Methyl in Diabetic Kidney Disease (DKD) Patients
Authors: Tadao Akizawa, Kengo Yamawaki, Tomohiro Ichikawa, Kazuya Mukai, Masaomi Nangaku
Journal: Journal of the American Society of Nephrology (2023)
Real-World Effectiveness of SGLT2 Inhibitors on the Progression of Kidney Disease in Non-Diabetic CKD Patients with and Without Albuminuria
Authors: Afif Nakhleh, Sivan Gazit, Adi Gross, Adva Yarden, Naim Shehadeh, Muhammad Abdul-Ghani, Cheli Melzer Cohen
Journal: Journal of the American Society of Nephrology (2023)
Patient-Reported Health Status of Adults with Kidney Failure Receiving Hemodiafiltration vs. Hemodialysis: Results from the CONVINCE Randomized Controlled Clinical Trial
Authors: Matthias Rose, Felix Fischer, Gregor Liegl, Giovanni Strippoli, Carinna Hockham, Robin W. Vernooij, Claudia M. Barth, Bernard J. Canaud, Adrian Covic, Krister Cromm, Andrew Davenport, Kathrin I. Fischer, Jorgen B. Hegbrant, Hanna Jaha, Anna Schappert, Marietta Török, Michiel L. Bots, Peter J. Blankestijn
Journal: Journal of the American Society of Nephrology (2023)
Electronic Health Record-Based Population Health Management to Optimize Care in CKD: Kidney CHAMP Randomized Clinical Trial
Authors: Manisha Jhamb, Melanie R. Weltman, Susan M. Devaraj, Linda-Marie U. Lavenburg, Zhuoheng Han, Alaa A. Alghwiri, Gary Fischer, Bruce L. Rollman, Thomas D. Nolin, Jonathan Yabes
Journal: Journal of the American Society of Nephrology (2023)
A Phase 3 Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of Enarodustat for the Treatment of Renal Anemia in Chinese Non-Dialysis CKD Patients
Authors: Xueqing Yu, Zhiming Ye, Xinling Liang, Yanning Zhang, Weiping Hu, Xiaonong Chen, Tianjun Guan, Hua Zhou, Ping Fu, Yunhua Liao, Hui Xu, Aicheng Yang, Hongwen Zhao, Lili Yang, Yujie Sun, Yongzhen Xiao
Journal: Journal of the American Society of Nephrology (2023)
Pivotal Results of the Phase 3 PROTECT Trial of Sparsentan (SPAR) vs. Irbesartan (IRB) in Patients with Immunoglobulin A Nephropathy (IgAN)
Authors: Brad H. Rovin, Jonathan Barratt, Ulysses Diva, Radko Komers, Vlado Perkovic
Journal: Journal of the American Society of Nephrology (2023)
Clinical Impact of the Predigraft/iBox System as a Clinical Decision Support for Kidney Transplant Patients' Management: Mid-Term Results of a Prospective Randomized Controlled Trial (RCT)
Authors: Carmen Lefaucheur, Alexandre Loupy, Sunil Daga, Luis Guirado, Caroline Dudreuilh, Florian Grahammer, Annemarie Weissenbacher
Journal: Journal of the American Society of Nephrology (2023)
Effect of a Multi-Component Intervention to Improve Patient Access to Kidney Transplantation and Living Kidney Donation
Authors: Amit X. Garg, Seychelle Yohanna, Kyla L. Naylor, Susan Q. Mckenzie, Istvan Mucsi, Stephanie N. Dixon, Bin Luo, Jessica M. Sontrop, Peter G. Blake
Journal: Journal of the American Society of Nephrology (2023)
A Randomized, Controlled, Open-Label, Multicenter Study Evaluating the Efficacy and Safety of Lower Starting Dose Roxadustat for Anemia Treatment in Patients with CKD Not on Dialysis
Authors: Ping Li, Guangyan Cai, Xuefeng Sun, Yiqing Wu, Cuihua Huang, Shuting Pan, Xiangmei Chen
Journal: Journal of the American Society of Nephrology (2023)
Sibeprenlimab in Patients with IgA Nephropathy: A Phase 2 Trial
Authors: Jonathan Barratt, Mohit Mathur, Bobby Chacko, Tak Mao D. Chan, Laura Kooienga, Kook-Hwan Oh, Manisha Sahay, Yusuke Suzuki, Muh Geot Wong, Jill Yarbrough, Jing Xia, Brian J. Pereira
Journal: Journal of the American Society of Nephrology (2023)
ALdosterone Antagonist Chronic HEModialysis Interventional Survival Trial (ALCHEMIST): Primary Results
Authors: Patrick Rossignol, Faiez Zannad, Ziad Massy, Michel Azizi, Julien Coadic, Angélique Tenailleau, Dominique Mottier, Francis Guillemin, Fatima Chorfa, Delphine Maucort-Boulch, Luc Frimat
Journal: Journal of the American Society of Nephrology (2023)
Povetacicept, an Enhanced Dual BAFF/APRIL Antagonist, in Autoantibody-Associated Glomerulonephritis (GN)
Authors: James A. Tumlin, Harmeet Singh, Frank B. Cortazar, Arvind Madan, Jonathan Barratt, Brad H. Rovin, Hong Zhang, Rupert H. Davies, Amanda M. Enstrom, Allison G. Chunyk, Heather Thomas, Jiahua Li, Sreedhar A. Mandayam
Journal: Journal of the American Society of Nephrology (2023)
Aldosterone Synthase Inhibition with or Without Background Sodium Glucose Cotransporter 2 Inhibition in CKD: A Phase II Clinical Trial
Authors: Katherine R. Tuttle, Sibylle J. Hauske, Lisa Cronin, Zhichao Sun, Dick de Zeeuw, Hiddo J. Heerspink, Peter Rossing
Journal: Journal of the American Society of Nephrology (2023)