tbuckley/cabot-search huggingface dataset:
Closing the gap in the clinical adoption of computational pathology: a standardized, open-source framework to integrate deep-learning models into the laboratory information system
Authors: Miriam Angeloni, Davide Rizzi, Simon Schoen, Alessandro Caputo, Francesco Merolla, Arndt Hartmann, Fulvia Ferrazzi, Filippo Fraggetta
Journal: Genome Medicine (2025)

Abstract Background Digital pathology (DP) has revolutionized cancer diagnostics and enabled the development of deep-learning (DL) models aimed at supporting pathologists in their daily work and improving patient care. However, the clinical adoption of such models remains challenging. Here, we describe a proof-of-concept framework that, leveraging Health Level 7 (HL7) standard and open-source DP resources, allows a seamless integration of both publicly available and custom developed DL models in the clinical workflow. Methods Development and testing of the framework were carried out in a fully digitized Italian pathology department. A Python-based server-client architecture was implemented to interconnect through HL7 messaging the anatomic pathology laboratory information system (AP-LIS) with an external artificial intelligence-based decision support system (AI-DSS) containing 16 pre-trained DL models. Open-source toolboxes for DL model deployment were used to run DL model inference, and QuPath was used to provide an intuitive visualization of model predictions as colored heatmaps. Results A default deployment mode runs continuously in the background as each new slide is digitized, choosing the correct DL model(s) on the basis of the tissue type and staining. In addition, pathologists can initiate the analysis on-demand by selecting a specific DL model from the virtual slide tray. In both cases, the AP-LIS transmits an HL7 message to the AI-DSS, which processes the message, runs DL model inference, and creates the appropriate visualization style for the employed classification model. The AI-DSS transmits model inference results to the AP-LIS, where pathologists can visualize the output in QuPath and/or directly as slide description in the virtual slide tray. Conclusions Taken together, the developed integration framework through the use of the HL7 standard and freely available DP resources offers a standardized, portable, and open-source solution that lays the groundwork for the future widespread adoption of DL models in pathology diagnostics.
Attrition rates and treatment outcomes in multiple myeloma: real-world data over a 40-year period
Authors: Luis Gerardo Rodríguez-Lobato, Anna de Daniel, Arturo Pereira, Carlos Fernández de Larrea, Natalia Tovar, M Teresa Cibeira, David F Moreno, Jose Miguel Mateos, Noemí Llobet, Esther Carcelero, Daniel Munárriz, Joan Bladé, Laura Rosiñol
Journal: Blood Cancer Journal (2025)
Peripheral Blood Flow Cytometry-based Definition of Plasma Cell Leukemia
Authors: Arwa Bohra, Rafla Hassan, Saurabh Zanwar, Dragan Jevremovic, Horatiu Olteanu, Wilson I Gonsalves, Gregory Otteson, Pedro Horna, S Vincent Rajkumar, Shaji Kumar
Journal: Leukemia (2025)
An Osteochondral Tissue‐Mimicking Hydrogel‐Scaffold Di‐Block Patch for Rapid Repair of Focal Load‐Bearing Cartilage Lesions
Authors: Ge Zhou, Xiao Geng, Xinguang Wang, Xule Yang, Feng Li, Zijian Li, Liju Xu, Dong Qiu, Hua Tian
Journal: Advanced Healthcare Materials (2025)

Abstract Load‐bearing cartilage lesions are progressive, so focal lesions require rapid repair to support loading; otherwise, they may generate degeneration of a large area of cartilage till worse osteoarthritis occurs. Replacing the focally lesioned cartilage with synthetic grafts can instantly recover the damaged cartilage's load‐bearing capacity, but have issues with mismatched mechanical properties and weak cartilage integration. Inspired by natural osteochondral tissue, a hydrogel‐titanium scaffold (gel‐Ti) di‐block patch with a robust interlocking interface is developed. In this osteochondral tissue‐mimicking gel‐Ti patch, the hydrogel layer offers mechanical properties comparable to those of native cartilage, whereas the titanium scaffold layer with pores for bone ingrowth integrates the patch with subchondral bone and thus host cartilage. Consequently, the gel‐Ti patch achieves prompt and effective repair of load‐bearing cartilage defects in rabbit and canine models, in striking contrast to the dry and rigid ultra‐high‐molecular‐weight polyethylene (UHMWPE) patch that induces progressive cartilage destruction. Moreover, the gel‐Ti patch shows favorable chondroprotective effects, durable mechanical properties, and long‐term safety. This work reveals a new approach to address the urgent clinical need to rapidly restore focal cartilage damage to withstand loading, thereby preventing further worsening of cartilage and joints.
A Novel Aldehyde Scavenging Modification Boosted Pericardium Valve Materials against Calcification
Authors: Fei Kong, Jingjing Zhang, Yang Yang, Yunyang Zhang, Jian Ge, Jingwu Song, Changyu Shao, Haoran Li, Yunjiu Ren, Xianghui Kong, Chengyao Ni, Xiangdong Kong, Ruibo Zhao
Journal: Advanced Healthcare Materials (2025)

Abstract Calcific aortic valve disease is an inexorably degenerative pathology and a common cause of morbidity and mortality in heart disease. Clinically, it has no effective medical therapy but can be managed with artificial heart valve replacement, particularly using bioprosthetic heart valves (BHV), entailing high biocompatibility. Current BHV mainly derives from glutaraldehyde (GA) cross‐linked pericardium, however, residual aldehyde groups may inevitably remain during cross‐link, potentially binding with calcium and inducing in situ calcification after implantation, thus leading to valve re‐failure and posing a significant clinical challenge. Inspired by the high reducibility and clinical potential of sodium thiosulfate (STS), herein, STS as a novel modification post GA cross‐linking to eliminate residual aldehyde in pericardium is presented. Notably, in vitro and in vivo studies demonstrated high ability against calcification in STS‐modified porcine pericardium (SPP) with over 75% decrease of calcific density compared to GA alone cross‐linked pericardium (GPP). More importantly, SPP can reduce macrophages and T cell inflation, as well as their associated proinflammation cytokines, building an immune‐privileged microenvironment with a suppressed inflammation response. More generally, given the great potential of STS in treating vascular calcification clinically, these achievements further offer a new generation of BHV materials with boosted anti‐calcification.
Immunosuppressive Cytokine‐Tethered Hydrogel for Treating Rheumatoid Arthritis
Authors: Woojin Back, Moonkyoung Jeong, Huyen‐Thao Le, Ji‐Ho Park
Journal: Advanced Healthcare Materials (2025)

Abstract Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by persistent inflammation and progressive joint destruction. Current therapies primarily rely on general immune suppression, often leading to suboptimal outcomes and significant side effects. To address these challenges, an interleukin‐4 (IL‐4)‐tethered, hyaluronic acid‐based hydrogel is developed that withstands repeated mechanical stress in the joint space while fostering an immunomodulatory environment. The immunosuppressive hydrogel promotes anti‐inflammatory M2 macrophage polarization, creating an anti‐inflammatory microenvironment while preserving cartilage and mitigating joint damage. The mechanical properties of the hydrogel are carefully optimized for injectability and intra‐articular application. Its effectiveness is evaluated in a collagen‐induced arthritis (CIA) mouse model, demonstrating potential as a localized therapeutic approach. It is believed that this IL‐4‐tethered hydrogel platform will provide a foundation for the combinatorial treatment of RA and various inflammatory diseases.
Targeted Reprogramming of TREM2‐Positive Macrophages and MRI‐Guided Immune Monitoring in Colorectal Cancer Using CSF1R@Mn@MPDA‐Antitrem2 Nanoplatform
Authors: Jie Zhao, Ming Li, Qiong Wu, Guanzhong Qiao, Hao Jiang, Sheng Zhao, Linhan Zhang, Song Wang, Huijie Jiang
Journal: Advanced Healthcare Materials (2025)

Abstract Colorectal cancer (CRC) poses a significant therapeutic challenge due to its immunosuppressive tumor microenvironmentl (TME). In this environment, triggering receptors expressed on myeloid cells 2 (TREM2+) tumor‐associated macrophages (TAMs) drive immune evasion and therapy resistance. In this study, CSF1R‐IN‐3@Mn@MPDA‐antiTREM2 (CMMT) is presented, a manganese‐doped mesoporous polydopamine nanoplatform conjugated with anti‐TREM2 antibodies, which integrates TAM reprogramming and magnetic resonance imaging (MRI)‐guided immune monitoring. CMMT has three key characteristics: 1) pH‐responsive release of the Colony Stimulating Factor 1 Receptor (CSF1R) inhibitor CSF1R‐IN‐3 within acidic TME; 2) selective targeting of TREM2+ M2 macrophages, achieving 4.2‐fold higher uptake compared to M1 subsets ( P &lt; 0.001); and 3) dual modulation of TREM2 and CSF1R pathways, polarizing M2‐TAMs toward pro‐inflammatory M1 phenotypes. In orthotopic CRC models, CMMT synergizes with anti‐PD‐L1 therapy, reducing tumor volume by 72.5% compared to 42.1% for monotherapy ( P &lt; 0.001). It also extends median survival from 28 to 52 days. Importantly, CMMT acts as an MRI contrast agent, with T1 signal intensity correlating with intratumoral TREM2+ macrophage density (r‐ 0.71, P &lt; 0.05), enabling non‐invasive assessment of TME remodeling. This theranostic platform bridges immune modulation and real‐time monitoring, providing a promising strategy to overcome immunotherapy resistance in CRC.
Efficacy and safety of dotinurad versus febuxostat for the treatment of gout: a randomised, multicentre, double‐blind, phase 3 trial in China
Authors: Jia Sun, Yu Wang, Yongjing Cheng, Dongmei Guo, Jiankang Hu, Dongzhou Liu, Zhengnan Gao, Changgui Li, Yibing Lu, Xiaodan Kong, Yu Liu, Zhenyu Jiang, Bin Yi, Hongfeng Zhang, Baijie Xu, Shihao Yu, Rieko Kokan, Kohei Ishikawa, Mikiko Kawakatsu, Zhuoli Zhang
Journal: Arthritis & Rheumatology (2025)

Objectives Dotinurad is a selective urate reabsorption inhibitor that reduces serum urate levels. We compared the efficacy and safety of dotinurad with febuxostat in Chinese patients with gout. Methods This phase 3, multicentre, randomised, double‐blind, parallel‐group study randomly allocated (1:1) eligible patients with gout to receive oral dotinurad or febuxostat. The primary endpoint was the responder rate (proportion of patients achieving serum urate levels ≤6.0 mg/dL) at week 24 in the full analysis set (FAS) to demonstrate superiority of dotinurad 4 mg/day to febuxostat 40 mg/day. The secondary endpoints included the responder rate at week 12 to show the non‐inferiority of dotinurad 2 mg/day to febuxostat 40 mg/day. Treatment‐emergent adverse events (TEAEs) were also recorded. Results A total of 451 patients were randomised and 441 were included in the FAS. Baseline characteristics were well‐balanced between treatment groups. The responder rate at week 24 was significantly higher for dotinurad 4 mg/day vs febuxostat 40 mg/day (73.6% vs 38.1%; adjusted difference 35.9% [95% confidence interval (CI) 27.4%, 44.4%]; p&lt;0.0001), and that at week 12 in the dotinurad 2 mg/day was non‐inferior to the febuxostat 40 mg/day (55.5% vs 50.5%; adjusted difference 5.2% [95% CI −3.7%, 14.2%]). Incidences of TEAEs in the dotinurad and febuxostat groups were similar. Conclusions Dotinurad 4 mg/day was superior to febuxostat 40 mg/day in achieving serum urate levels ≤6.0 mg/dL at week 24 and was well tolerated in Chinese patients with gout.
Kirigami‐Inspired Breathable Smart Contact Lens for Wireless Monitoring of Corneal Hypoxia and Microenvironment
Authors: Jiaxue Zhu, Ling Yang, Qing Yang, Yin Huang, Yuhang Li, Yueqing He, Xuxu Yang, Zhiyan Yang, Yonghong Jiao, Wenbin Wei, Yihao Chen, Xue Feng
Journal: Advanced Healthcare Materials (2025)

Abstract Severe corneal dysfunctions caused by corneal hypoxia and microenvironmental imbalance threaten hundreds of millions of people's eye health, leading to neovascularization, keratitis, and even vision loss, particularly among contact lens wearers. However, there are no accessible digital tools for wearable and continuous monitoring of corneal oxygen and microenvironment status. Here, a kirigami‐inspired breathable smart contact lens for wireless monitoring of corneal hypoxia and microenvironment is presented. The ultrathin (55 µm) and flexible sensing device enables digitalized, in situ and precise monitoring of key eye health indicators: dissolved oxygen, humidity, and temperature ( R 2 &gt; 0.98). The flexible circuit, designed and processed using evolutionary kirigami structures and thermoforming, efficiently conforms to the soft curved surfaces with minimized contour dimensions and residual stress. Silicone/hydrogel hybrid layers encapsulate the electronics, achieving high oxygen permeability (380.26 Barrers), sufficient water content (&gt;80%), and excellent biocompatibility/heat safety. In vivo animal experiments in beagle eyes demonstrate the lens's capability for accurate, wireless corneal monitoring under controlled conditions.
A Self‐Powered Bioelectronic Suture via Hybrid Laser Treatment
Authors: Yuhong Xu, Tianyu Li, Hao Zhou, Yuyao Lu, Yuyang Yuan, Binhan Zhao, Yifan Wang, Huayong Yang, Xiujun Cai, Kewang Nan, Kaichen Xu
Journal: Advanced Healthcare Materials (2025)

Abstract Appropriate suture tension is crucial for effective wound healing, as improper tension may lead to wound dehiscence or ischemia. Advances in bioelectronic sutures enable monitoring and therapy, but reliance on external power or complex circuits limits their use in long‐term and minimally invasive applications. Herein, a self‐powered bioelectronic suture (B‐suture) is reported that enables real‐time tension monitoring during suturing. The B‐suture integrates a conductive composite within a capillary structure. Hybrid laser processing, combining continuous wave laser‐induced phase separation and femtosecond laser‐engraved microstructures, greatly enhances electro‐mechanical properties and triboelectric sensing performance. The triboelectric nanogenerator‐based principle enables tension detection in the 0–2 N range. In vitro and in vivo evaluations demonstrate biocompatibility and precise monitoring of suturing tightness. By providing real‐time quantitative feedback, the proposed B‐suture affords to improve wound closure quality, reduce postoperative complications, and advance bioelectronic applications in surgical practice.
Genetic evolution and relapse‐associated mutations in adult T‐cell acute lymphoblastic leukemia patients treated in PETHEMA trials
Authors: Celia González‐Gil, Thaysa Lopes, Mireia Morgades, Francisco Fuster‐Tormo, Pau Montesinos, Carlos Rodríguez Medina, Lourdes Hermosín, Teresa González‐Martínez, María‐Paz Queipo, José González‐Campos, Pilar Martínez‐Sánchez, Marina Díaz‐Beya, Rosa Coll, Clara Maluquer, Lurdes Zamora, Teresa Artola, Ferran Vall‐Llovera, Mar Tormo, Anna Torrent, Carolina Martínez‐Laperche, Cristina Gil‐Cortés, Pere Barba, Marta Cervera, Jordi Ribera, Manuel Fernández‐Delgado, Rosa Ayala, Antonia Cladera, María Carmen Mateos, María Jesús Vidal, Jesús Feliu, Ana Torres, Gemma Azaceta, María José Calasanz, Anna Bigas, Manel Esteller, Alberto Orfao, Josep Maria Ribera, Eulalia Genescà
Journal: HemaSphere (2025)

Abstract Relapse is the main cause of treatment failure in T‐cell acute lymphoblastic leukemia (T‐ALL). Despite this, data from adult T‐ALL patients treated with specific chemotherapeutic regimens that examine predictive markers and describe relapse mechanisms are scarce. In this study, we studied 74 paired diagnosis‐relapse samples from 37 patients homogeneously treated with three consecutive measurable residual disease‐oriented trials to identify genetic determinants involved in relapse in adult T‐ALL. Analysis of single‐nucleotide variants and copy number alterations consistently found N/KRAS mutations (20% relapsed cases) at diagnosis and at relapse (resistance profile). N/KRAS mut patients frequently relapse early during consolidation treatment. Relapse‐specific mutations in NT5C2, NR3C1 , SMARCA4 , and TP53 (40% relapse cases) were not detected at diagnosis by conventional molecular techniques (relapse profile). However, single‐cell‐based analysis revealed a very minor clone containing the NT5C2(p.R367Q) variant at diagnosis. Patients with the NT5C2(p.R367Q) variant mostly relapse later during maintenance treatment. Tracking the NT5C2 variant by digital PCR confirm the expansion of the NT5C2 clone at maintenance treatment. Overall, our exploratory analysis suggests a role for these genetic events, most of which have already been described in pediatric cases, driving resistance associated to specific chemotherapeutic agents, contributing to the relapse of a high proportion of adult T‐ALL patients (60%).
Skeletal muscle endothelial dysfunction through the activin A–PGC1α axis drives progression of cancer cachexia
Authors: Young-Mee Kim, Mark A Sanborn, Shaluah Vijeth, Priyanka Gajwani, Xinge Wang, Dahee Jung, Tibor Valyi-Nagy, Sreeparna Chakraborty, Georgina Mancinelli, Peter T Toth, Evan H Phillips, Paul Grippo, Ameen A Salahudeen, Jooman Park, Su Yeon Yeon, Vijayalakshmi Ananthanarayanan, Yuwei Jiang, Steve Seung-Young Lee, Klara Valyi-Nagy, Jalees Rehman
Journal: Nature Cancer (2025)
Pace of Aging analysis of healthspan and lifespan in older adults in the US and UK
Authors: Arun Balachandran, Heming Pei, Yifan Shi, John R Beard, Avshalom Caspi, Alan A Cohen, Benjamin W Domingue, Claire Eckstein Indik, Luigi Ferrucci, Alex Furuya, Meeraj Kothari, Terrie E Moffitt, Calen P Ryan, Vegard Skirbekk, Yuan S Zhang, Daniel W Belsky
Journal: Nature Aging (2025)
Base editing of trinucleotide repeats that cause Huntington’s disease and Friedreich’s ataxia reduces somatic repeat expansions in patient cells and in mice
Authors: Zaneta Matuszek, Mandana Arbab, Maheswaran Kesavan, Alvin Hsu, Jennie C L Roy, Jing Zhao, Tian Yu, Ben Weisburd, Gregory A Newby, Neil J Doherty, Muzhou Wu, Shota Shibata, Ana Cristian, Y Allen Tao, Liam G Fearnley, Melanie Bahlo, Heidi L Rehm, Jun Xie, Guangping Gao, Ricardo Mouro Pinto, David R Liu
Journal: Nature Genetics (2025)
Lentiviral gene therapy with reduced-intensity conditioning for sickle cell disease: a phase 1/2 trial
Authors: Michael Grimley, Stella M Davies, Archana Shrestha, Amy Shova, Monika Asnani, Michael Kent, Farzana Sayani, Charles T Quinn, Omar Niss, Carolyn Lutzko, Parinda A Mehta, Pooja Khandelwal, Courtney Little, Sharat Chandra, Sydney Felker, Mengna Chi, Theodosia A Kalfa, Jennifer Knight-Madden, Paritha I Arumugam, Kristie N Ramos, Scott Witting, Teresa Latham, Frederic D Bushman, Punam Malik
Journal: Nature Medicine (2025)
Cellular hierarchies of embryonal tumors with multilayered rosettes are shaped by oncogenic microRNAs and receptor–ligand interactions
Authors: Alexander Beck, Lisa Gabler-Pamer, Gustavo Alencastro Veiga Cruzeiro, Sander Lambo, Bernhard Englinger, McKenzie L Shaw, Olivia A Hack, Ilon Liu, Rebecca D Haase, Carlos A O de Biagi, Alicia Baumgartner, Andrezza Do Nascimento Silva, Marbod Klenner, Pia S Freidel, Jochen Herms, Louisa von Baumgarten, Joerg C Tonn, Niklas Thon, Katharina Bruckner, Sibylle Madlener, Lisa Mayr, Daniel Senfter, Andreas Peyrl, Irene Slavc, Daniela Lötsch, Christian Dorfer, Rene Geyregger, Nicole Amberg, Christine Haberler, Norman Mack, Benjamin Schwalm, Stefan M Pfister, Andrey Korshunov, Lissa C Baird, Edward Yang, Susan N Chi, Sanda Alexandrescu, Johannes Gojo, Marcel Kool, Volker Hovestadt, Mariella G Filbin
Journal: Nature Cancer (2025)
Comparative Cardiovascular Safety of <scp>NSAID</scp> versus Colchicine Use When Initiating Urate‐Lowering Therapy Among Patients with Gout: Target Trial Emulations
Authors: Chio Yokose, Natalie McCormick, Na Lu, Bohang Jiang, Kiara Tan, Saiajay Chigurupati, Sharan Rai, Greg Challener, J. Antonio Aviña‐Zubieta, Edoardo Cipolletta, Abhishek Abhishek, Angelo Gaffo, James L. Januzzi, Yuqing Zhang, Hyon K. Choi
Journal: Arthritis & Rheumatology (2025)

Objective Among patients with gout, NSAIDs are commonly used despite scarce safety data in this specific population. Therefore, we quantified the comparative cardiovascular safety of NSAIDs versus colchicine among patients with gout starting allopurinol. Methods We conducted a sequential, propensity score‐matched, new‐user comparative effectiveness study using the target trial emulation framework to compare the risk of MACE (composite of myocardial infarction [MI], stroke, or cardiovascular death) among patients with gout started on allopurinol who were prescribed NSAIDs or colchicine for gout flare prophylaxis. A sensivity analysis employed inverse probability of treatment weighting (IPTW). Secondarily, we examined the risk of MACE with colchicine or NSAIDs versus no prophylaxis. Results Among 18,120 propensity score‐matched adults with gout starting allopurinol with NSAIDs or colchicine (83.5% male, mean age 60.9 years), the incidence of MACE and cardiovascular death were higher among NSAID users compared to colchicine users, with rate differences of 38.8 (95% CI, 15.4 to 62.2) and 10.9 (0.7 to 21.1) per 1000 person‐years, respectively, and hazard ratios (HR) of 1.56 (1.11 to 2.17) and 2.50 (1.14 to 5.26), respectively. Results were similar when IPTW was applied. Compared to no prophylaxis, NSAID use was associated with a higher risk of MACE and MI with HRs 1.50 (1.17 to 1.91) and 1.93 (1.35 to 2.75), respectively. Conclusion In these target trial emulations of patients with gout starting allopurinol, NSAID prophylaxis was associated with a higher risk of MACE than colchicine or no prophylaxis, suggesting the avoidance of NSAID for gout flare prophylaxis.
Large-scale examination of early-age sex differences in neurotypical toddlers and those with autism spectrum disorder or other developmental conditions
Authors: Sanaz Nazari, Sara Ramos Cabo, Srinivasa Nalabolu, Cynthia Carter Barnes, Charlene Andreason, Javad Zahiri, Ahtziry Esquivel, Steven J Arias, Andrea Grzybowski, Michael V Lombardo, Linda Lopez, Eric Courchesne, Karen Pierce
Journal: Nature Human Behaviour (2025)
Development of human targeted extracellular vesicles loaded with shRNA minicircles to prevent parkinsonian pathology
Authors: Maria Izco, Carlos Sola, Martin Schleef, Marco Schmeer, María de Toro, Guglielmo Verona, Estefania Carlos, Alejandro Reinares-Sebastian, Sandra Colina, Maria Eugenia Marzo-Sola, Josune Garcia-Sanmartin, Joaquín Fernández-Irigoyen, Enrique Santamaría, Rodolfo Mugica-Vidal, Javier Blesa, Lydia Alvarez-Erviti
Journal: Translational Neurodegeneration (2025)
Tertiary amine N-oxide zwitterionic lipids facilitate muscle-selective mRNA vaccine delivery for enhancing cDC1-mediated antitumor efficacy
Authors: Haihong Yang, Zhan Gao, Yizi Zhou, Xueer Ge, Xiaorong Pan, Jiakun Li, Zhihui Zhang, Xuanli Jin, Guotao Liu, Zepeng He, Hong Liu, Zhijia Liu, Lixin Liu, Yongming Chen
Journal: Journal of Controlled Release (2025)