tbuckley/cabot-search huggingface dataset:
PRODE recovers essential and context-essential genes through neighborhood-informed scores
Authors: Thomas Cantore, Paola Gasperini, Riccardo Bevilacqua, Yari Ciani, Sanju Sinha, Eytan Ruppin, Francesca Demichelis
Journal: Genome biology (2025)

Gene context-essentiality assessment supports precision oncology opportunities. The variability of gene effects inference from loss-of-function screenings across models and technologies limits identifying robust hits. We propose a computational framework named PRODE that integrates gene effects with protein–protein interactions to generate neighborhood-informed essential (NIE) and neighborhood-informed context essential (NICE) scores. It outperforms the canonical gene effect approach in recovering missed essential genes in shRNA screens and prioritizing context-essential hits from CRISPR-KO screens, as supported by in vitro validations. Applied to Her2 + breast cancer tumor samples, PRODE identifies oxidative phosphorylation genes as vulnerabilities with prognostic value, highlighting new therapeutic opportunities.
Impact of baseline genetic profile and treatment on outcome and hematological toxicity in CEBPA-mutated AML
Authors: Francesco Mannelli, Matteo Piccini, Marco Frigeni, Giacomo Gianfaldoni, Sara Bencini, Silvia Salmoiraghi, Barbara Scappini, Benedetta Peruzzi, Roberto Caporale, Gaia Ciolli, Francesca Crupi, Laura Fasano, Elisa Quinti, Andrea Pasquini, Jessica Caroprese, Fiorenza Vanderwert, Giada Rotunno, Fabiana Pancani, Leonardo Signori, Danilo Tarantino, Chiara Maccari, Francesco Annunziato, Orietta Spinelli, Paola Guglielmelli, Alessandro Rambaldi, Alessandro M. Vannucchi
Journal: Blood Cancer Journal (2025)
Breast, Colorectal, and Pancreatic Cancer Mortality With Pathogenic Variants in <i>ATM</i> , <i>CHEK2</i> , or <i>PALB2</i>
Authors: Christine M. Veenstra, Paul Abrahamse, Ann S. Hamilton, Kevin C. Ward, Scarlett L. Gomez, Lihua Liu, Steven J. Katz, Timothy P. Hofer, Allison W. Kurian
Journal: Journal of Clinical Oncology (2025)

PURPOSE Oncologists encounter patients with pathogenic variants (PVs) in ATM , CHEK2 , or PALB2 , but little is known about their cancer mortality. METHODS Patients who were 20 years or older, diagnosed in 2013-2019 with breast, colorectal, or pancreatic cancer, and reported to SEER registries in California and Georgia were linked to germline genetic testing results from four clinical laboratories and followed through 2021. Multivariable models of cancer mortality were fit; for each cancer, the reference group was the average hazard across all genetically tested patients with that diagnosis. Each cancer was modeled separately, followed by a single model that interacted the cancer type with all covariates. In addition to fixed effects models, random effects models were used as a regularization approach to reduce overfitting. RESULTS A total of 70,272 tested patients with breast (48,473 estrogen receptor–/progesterone receptor–positive, human epidermal growth factor receptor 2 (HER2)–negative; 9,957 HER2-positive; 11,842 triple-negative) cancer, 5,822 with colorectal cancer, and 1,861 with pancreatic cancer were analyzed; the mean follow-up was 3.9 years. Patients with ATM , CHEK2 , or PALB2 PVs had no differences in breast, colorectal, or pancreatic cancer mortality. Patients with ATM PVs in triple-negative breast cancer appeared to have higher mortality in fixed effects models (hazard ratio [HR], 3.7 [95% CI, 1.8 to 7.8]), but not in random effects models (HR, 1.2 [95% CI, 0.8 to 1.6]) that reduce overfitting. Patients with BRCA1 / 2 PVs had lower triple-negative breast cancer mortality in both models (fixed HR, 0.6 [95% CI, 0.5 to 0.9], random HR, 0.7 [95% CI, 0.6 to 0.8]). Patients with Lynch syndrome gene PVs had lower colorectal cancer mortality in both models (fixed HR, 0.5 [95% CI, 0.4 to 0.8], random HR, 0.7 [95% CI, 0.5 to 0.9]). CONCLUSION Patients with ATM , CHEK2 , or PALB2 PVs had similar breast, colorectal, and pancreatic cancer mortality to the average genetically tested patient with their cancer type.
Piezoelectric nanofilms fabricated by coaxial electrospun polycaprolactone/Barium titanate promote Achilles tendon regeneration by reducing IL-17A/NF-κB-mediated inflammation
Authors: Wufei Dai, Qi Xu, Qinglin Li, Xiansong Wang, Wenjie Zhang, Guangdong Zhou, Xu Chen, Wei Liu, Wenbo Wang
Journal: Bioactive Materials (2025)
Older adults living with gastrointestinal cancers in 2021
Authors: Pojsakorn Danpanichkul, Yanfang Pang, Torlap Inkongngam, Kornnatthanai Namsathimaphorn, Krittameth Rakwong, Chuthathip Kaeosri, Benjamin Nah, Kwanjit Duangsonk, Nicole Shu Ying Tang, Neha Mittal, Donghee Kim, Mazen Noureddin, Michael B. Wallace, Amit G. Singal, Karn Wijarnpreecha, Ju Dong Yang
Journal: Cancer Communications (2025)
Engineering Iridium Nanoclusters for Boosting Ferroptotic Cell Death by Regulating GPX4 and p53 Functions
Authors: Xiaoyu Cui, Bin Chen, Ying Chen, Mi Zhou, Lijun Cao, Bing Hu, Jianrong Wu, Xinxin Ma, Tao Ying
Journal: Advanced Healthcare Materials (2025)

Abstract Emerging evidence indicates that modulating glutathione peroxidase 4 (GPX4) to induce ferroptosis is a promising strategy for tumor treatment. However, most of the GPX4 small molecule inhibitors face limitations due to their poor delivery efficacy and low specificity of ferroptosis activation. Herein, a ferroptosis‐inducing nanomedicine is developed that integrates nutlin‐3 with iridium oxide nanoclusters (NUT‐IrO x NCs) for enhanced ferroptosis‐driven multimodal therapeutic efficacy in colorectal cancer (CRC). This NUT‐IrO x NCs can induce glutathione (GSH) depletion via enhanced Ir (VI)‐Ir (III) transition, while nutlin‐3, a well‐established inhibitor of the p53‐MDM2 interaction, suppresses GSH production by modulation of the p53/SLC7A11/xCT signaling pathway. The reduction of intracellular GSH results in pronounced reductions of GPX4 enzymatic activity, consequently leading to lipid peroxidation accumulation and further enhancing ferroptosis‐induced CRC therapy. This dual‐pronged approach demonstrates robust anticancer therapeutic effects with favorable biocompatibility in both in vitro and in vivo CRC models. This study provides an effective strategy that highlights the benefits of inhibiting of GSH/GPX4 by activating multiple ferroptosis regulatory pathways, providing an alternative therapeutic avenue for CRC treatment.
Self‐Doped and Biodegradable Glycosaminoglycan‐PEDOT Conductive Hydrogels Facilitate Electrical Pacing of iPSC‐Derived Cardiomyocytes
Authors: Daniel Hachim, Olivia Hernández‐Cruz, James E. J. Foote, Richard Wang, Matthew W. Delahaye, Daniel J. Stuckey, Zhiping Feng, Jonathan P. Wojciechowski, Luke C. B. Salter, Junliang Lin, Sian E. Harding, Molly M. Stevens
Journal: Advanced Healthcare Materials (2025)

Abstract Conductive polymers hold promise in biomedical applications owing to their distinct conductivity characteristics and unique properties. However, incorporating these polymers into biomaterials poses challenges related to mechanical performance, electrical stability, and biodegradation. This study proposes an injectable hydrogel scaffold composed of a self‐doped conductive polymer, constituted of a sulfated glycosaminoglycan (GAG) with side chains of PEDOT (poly 3,4‐ethylenedioxythiophene). This brush copolymer is synthesized via oxidative polymerization from an EDOT monomer grafted onto the backbone of the sulfated GAG. The GAG backbone offers biodegradability, while sulfate groups act as acidic self‐doping agents. Conductive hydrogels form through oxime crosslinking, initially existing as a liquid mixture that undergoes gelation within the tissue, allowing for injectability. The conductive hydrogels show tunable stiffness and gelation kinetics influenced by both concentration and pH, and exhibit adhesive properties. They showcase dual ionic and electronic conductivity, where sulfate groups in the GAG backbone act as doping moieties, enhancing conductivity and electrical stability. These properties of conductive hydrogels are associated with the facilitation of electrical pacing of iPSC‐cardiomyocytes. Furthermore, hydrogels exhibit biodegradation and show evidence of biocompatibility, highlighting their potential for diverse biomedical applications.
<scp>EAACI</scp> Guidelines on Environmental Science for Allergy and Asthma—Recommendations on the Impact of Indoor Air Pollutants on the Risk of New‐Onset Asthma and on Asthma‐Related Outcomes
Authors: Ioana Agache, Isabella Annesi‐Maesano, Lorenzo Cecchi, Benedetta Biagioni, Fan Chung, Gennaro D'Amato, Athanasios Damialis, Stefano del Giacco, Javier Dominguez Ortega, Carmen Galán, Stefanie Gilles, Stephen Holgate, Mohamed Jeebhay, Stelios Kazadzis, Kari Nadeau, Nikos G. Papadopoulos, Santiago Quirce, Joaquin Sastre, Claudia Traidl‐Hoffmann, Jolanta Walusiak‐Skorupa, Magdalena Zemelka‐Wiacek, Marek Jutel, Cezmi A. Akdis
Journal: Allergy (2025)

ABSTRACT The EAACI Guidelines used the GRADE approach to evaluate the impact of major indoor air pollutants (dampness and mould, cleaning agents, volatile organic compounds and pesticides) on the risk of new‐onset asthma and on asthma‐related outcomes. The guideline also acknowledges the synergies among indoor air pollutants and other components of the indoor exposome (allergens, viruses, endotoxins). Very low to low certainty of evidence was found for the association between exposure to indoor pollutants and increased risk of new‐onset asthma and asthma worsening. Only for mould exposure there was moderate certainty of evidence for new‐onset asthma. Due to the quality of evidence, conditional recommendations were formulated on the risk of exposure to all indoor pollutants. Recommendations are provided for prevention, patient care and mitigation in a framework supporting rational decisions for healthcare professionals and patients to individualize and improve asthma management. For policymakers and regulators this evidence‐informed guideline supports setting legally binding standards and goals for indoor air quality at international, national and local levels. Asthma management counselled by the current EAACI guidelines can improve asthma‐related outcomes but community and governmental measures for improved indoor air quality are needed to achieve significant impact.
3D Bioprinting of Double‐Layer Conductive Skin for Wound Healing
Authors: Yuhan Wang, Chen Gao, Shengnan Cheng, Yuxuan Li, Ying Huang, Xiaoling Cao, Zhijun Zhang, Jie Huang
Journal: Advanced Healthcare Materials (2025)

Abstract Conductive hydrogels are highly attractive in 3D bioprinting of tissue engineered scaffolds for skin injury repair. However, their application is limited by mismatched electrical signal conduction mode and poor printability. Herein, the 3D bioprinting‐assisted fabrication of a double‐layer ionic conductive skin scaffold using a newly designed ionic conductive biomimetic bioink (GHCM) is reported, which is composed of gelatin methacrylate (GelMA), oxidized hyaluronic acid (OHA), carboxymethyl chitosan (CMCS), and 2‐methacryloyloxyethyl phosphorylcholine (MPC) for the treatment of full‐thickness skin defects. The combination of rigid (GelMA) and dynamic (OHA‐CMCS) polymer networks imparts GHCM bioink excellent reversible thixotropy, enabling good printability, and allowing the creation of skin‐like constructs with high shape fidelity and cell activity by convenient one‐step bioprinting. Moreover, the incorporation of zwitterionic MPC endows the bioink with electrical signaling pattern similar to that of natural skin tissue. By integrating human foreskin fibroblasts (HFF‐1), human umbilical vein endothelial cells (HUVECs), and human immortalized keratinocytes (HaCaTs), a double‐layer conductive skin scaffold comprising an epidermal layer and a vascularized dermal layer is created. In vivo experiments have demonstrated that the conductive skin scaffolds provide an appropriate conductive microenvironment for cellular signaling, growth, migration, and differentiation, ultimately accelerating the re‐epithelialization, collagen deposition, and vascularization of skin wounds, which may represent a general and versatile strategy for precise engineering of electroactive tissues for regenerative medicine applications.
Ultrathin Nanofibers Ameliorate Commercial Gauze for Rapid Hemorrhage Control Via Improved Clotting Kinetics and Rbc Modulation
Authors: Shivangi Parhi, Ashmita Mukherjee, Pratik Das, Samsamul Hoque, K R Vaishak, Saikat Biswas, Suvro Sankha Datta, Samit Kumar Nandi, Santanu Dhara, Piyali Basak, Sujoy K. Das, Paulomi Ghosh
Journal: Advanced Healthcare Materials (2025)

Abstract Timely control of bleeding is crucial to reduce mortality in traumatic injuries, highlighting the urgent need for biomaterials with anti‐hemorrhagic properties. Polycaprolactone (PCL) is commonly used for producing nanofibers in the range of 100–200 nm. However, creating ultrafine PCL nanofibers with diameters below 100 nm remains a challenge, limiting its potential as a hemostatic bandage. In this study, various ratios of low molecular weight PCL are blended with reduced keratin to modulate the solution shear‐thinning behavior. The optimized blend enables the production of ultrafine nanofibers with a mean diameter of ≈50 nm, providing a high surface area. The surfaces of these nanofibers demonstrate excellent platelet adhesion, aggregation, and activation. Additionally, they are cytocompatible with fibroblasts. The ultrathin nanofibers are electrospun on gauze to create a hemostatic product that shows favorable plasma and blood clotting kinetics. An in vivo study demonstrates reduced clotting times for nanofiber‐based products compared to plain gauze. Mechanistically, the RBCs on the nanofiber composites attain a polyhedral shape reducing the space between them and creating a compact seal to prevent fresh blood from oozing out. The intrinsic hemostatic properties of keratin, combined with reduced fiber diameter and the hydrophilic nature of gauge make this a promising hemostatic bandage.
Urinary sodium analysis: The key to effective diuretic titration? <i>European Journal of Heart Failure</i> expert consensus document
Authors: Evelyne Meekers, Jeroen Dauw, Jozine M. ter Maaten, Pieter Martens, Petra Nijst, Frederik H. Verbrugge, Marnicq Van Es, Jonas Erzeel, Kevin Damman, Joan Carles Trullàs, Matthias Dupont, Wilfried Mullens
Journal: European Journal of Heart Failure (2025)
An interpretable machine learning approach for detecting psoriatic arthritis in a UK primary care psoriasis cohort using electronic health records from the Clinical Practice Research Datalink
Authors: Alexander Rudge, Neil McHugh, William Tillett, Theresa Smith
Journal: Annals of the Rheumatic Diseases (2025)

Develop an interpretable machine learning model to detect patients with newly diagnosed psoriatic arthritis (PsA) in a cohort of psoriasis patients and identify important clinical indicators of PsA in primary care. We developed models using UK primary care electronic health records from the Clinical Practice Research Datalink (CPRD). The study population consisted of a cohort of (PsA free) patients with incident psoriasis who were followed prospectively. We used Bayesian networks (BNs) to identify patients who developed PsA using primary care variables measured prior to diagnosis and compared the results to a random forest (RF). Variables included patient demographics, musculoskeletal symptoms, blood tests, and prescriptions. The importance of each variable used in the models was evaluated using permutation variable importance. Model discrimination was measured using the area under the receiver operating characteristic curve (AUC) and the area under the precision-recall curve (PRAUC). We identified a cohort of 122,330 patients with an incident psoriasis diagnosis between 1998 and 2019 in the CPRD, of whom 2460 patients went on to develop PsA. Our best BN achieved an AUC of 0.823, and PRAUC of 0.221, compared to the AUC of 0.851 and PRAUC of 0.261 of the RF. Psoriasis duration, nonsteroidal anti-inflammatory drug prescriptions, nonspecific arthritis, nonspecific arthralgia, and C-reactive protein blood tests were all important variables in our models. We were able to identify psoriasis patients at higher risk, and important indicators, of PsA in UK primary care. Further work is required to evaluate our model's usefulness in assisting PsA screening.
Transdermal delivery of Ultradeformable cationic liposomes complexed with miR211–5p (UCL-211) stabilizes BRAFV600E+ melanocytic nevi
Authors: Tanya Chhibber, Michael T Scherzer, Anastasia Prokofyeva, Carly Becker, Rebecca Goldstein Zitnay, Eric Smith, Nitish Khurana, Mikhail Skliar, Dekker C Deacon, Matthew W VanBrocklin, Hamidreza Ghandehari, Robert L Judson-Torres, Paris Jafari
Journal: Journal of Controlled Release (2025)
Injectable multifunctional hydrogels for adipose tissue remodeling to treat obesity and alleviate metabolic syndrome
Authors: Jian-Hua Yan, Pei-Ling Hao, Si-Min Zeng, Chun-Xiao Liang, Yu Chen, Ke-Wei Chen, Wen-Qiang Qu, Xuan Zeng, Zhenlin Zhong, Xian-Zheng Zhang
Journal: Journal of Controlled Release (2025)
Integrative Metabolism in MASLD and MASH: Pathophysiology and Emerging Mechanisms
Authors: Gregory R Steinberg, Celina M Valvano, William De Nardo, Matthew J Watt
Journal: Journal of Hepatology (2025)

The liver acts as a central metabolic hub, integrating signals from the gastrointestinal tract and adipose tissue to regulate carbohydrate, lipid, and amino acid metabolism. Gut-derived metabolites, such as acetate and ethanol and non-esterified fatty acids from white adipose tissue (WAT), influence hepatic processes, which rely on mitochondrial function to maintain systemic energy balance. Metabolic dysregulation from obesity, insulin resistance, and type 2 diabetes disrupt these pathways, leading to metabolic dysfunction-associated steatotic liver disease (MASLD) and steatohepatitis (MASH). This review explores the metabolic fluxes within the gut-adipose tissue-liver axis, focusing on the pivotal role of de novo lipogenesis (DNL), dietary substrates like glucose and fructose, and changes in mitochondrial function during MASLD progression. It highlights the contributions of white adipose tissue insulin resistance and impaired mitochondrial dynamics to hepatic lipid accumulation. Further understanding how the interplay between substrate flux from the gastro-intestinal tract integrates with adipose tissue and intersects with structural and functional alterations to liver mitochondria will be important to identify novel therapeutic targets and advance the treatment of MASLD and MASH.
Copper silicate nanoparticle-mediated delivery of astragaloside-IV for osteoarthritis treatment by remodeling the articular cartilage microenvironment
Authors: Jianfeng Yang, Hongyi Jiang, Congcong Wu, Yuzhe Lin, Guancan Tan, Juannan Zhan, Lijiang Han, Yiting Zhu, Ping Shang, Liangle Liu, Haixiao Liu
Journal: Journal of Controlled Release (2025)
Extensive dissemination of ESBL-producing Clonal Complex 14 Escherichia coli is likely spread through sexual transmission among men who have sex with men at risk of sexually transmitted infections
Authors: Maxime Danjean, Laure Surgers, Guilhem Royer, Vanessa Demontant, Hadrien Kimseng, Amandine Caillault, Bryan Jimenez-Araya, Sarah Seng, Elisabeth Trawinski, Hayette Rougier, Jean-Winoc Decousser, Hervé Jacquier, Anders Boyd, Paul-Louis Woerther
Journal: Journal of Infection (2025)

We characterized the genetic proximity of Sequence Type (ST) 131, 1193 and 14 Extended-Spectrum Beta-Lactamase-producing E. coli (ESBL-Ec) to assess human determinants of carriage in community settings. In this cross-sectional study, we included individuals seeking care at a sexually transmitted infection (STI) or HIV outpatient clinic. ESBL-Ec were compared using phylogeny, core-genome Multi-Locus Sequence Typing and Single-Nucleotide Polymorphism (SNP) determination. Determinants were compared between STs and correlated to genetic distances. 103 individuals carried 112 strains of ST131 (n=63), ST14 (n=26) and ST1193 (n=23). Compared to ST131, ST14 isolates were more commonly found in individuals with any STI (p=0.031), men who have sex with men (p<0.001) and recent antibiotic use (p=0.021); whereas ST1193 isolates were more commonly found in individuals who engaged in insertive anal sex in <6 months (p=0.017). ST131 isolates showed high genomic diversity, while other STs evidenced a high level of proximity. SNPs data indicated the likely spread of a single ST14 (range=1;32) and some ST1193 clusters (range=2;111), which were linked to ST-specific sexual behaviors. In populations of those at risk of acquiring STI, ST14 and ST1193 ESBL-Ec are emerging. Specific sexual transmissions routes are likely to play a role in their spread.
Nanomedicines as disruptors or inhibitors of biofilms: Opportunities in addressing antimicrobial resistance
Authors: Jiaming Lan, Jingyu Zou, He Xin, Jin Sun, Tao Han, Mengchi Sun, Meng Niu
Journal: Journal of Controlled Release (2025)

The problem of antimicrobial resistance (AMR) has caused global concern due to its great threat to human health. Evidences are emerging for a critical role of biofilms, one of the natural protective mechanisms developed by bacteria during growth, in resisting commonly used clinical antibiotics. Advances in nanomedicines with tunable physicochemical properties and unique anti-biofilm mechanisms provide opportunities for solving AMR risks more effectively. In this review, we summarize the five "A" stages (adhesion, amplification, alienation, aging and allocation) of biofilm formation and mechanisms through which they protect the internal bacteria. Aimed at the characteristics of biofilms, we emphasize the design "THAT" principles (targeting, hacking, adhering and transport) of nanomedicines in their interactions with biofilms and internal bacteria. Furthermore, recent progresses in multimodal antibacterial nanomedicines, including biofilms disruption and bactericidal activity, and the types of currently available antibiofilm nanomedicines contained organic and inorganic nanomedicines are outlined and highlighted their potential applications in the development of preclinical research. Last but not least, we offer a perspective for the effectiveness of nanomedicines designed to address AMR and challenges associated with their clinical translation.
Bioinspired programmed antibiofilm strategies for accelerated wound healing via spatiotemporally controlled enzyme nanoreactors
Authors: Juntao Hu, Yibing Huang, Hao Hao, Pujing Tian, Yinuo Yin, Yuting He, Fengjie Hao, Wantong Jiang, Yanping Zhang, Youzhong Wan, Quan Luo
Journal: Journal of Controlled Release (2025)
Efficacy and safety of twice per year depemokimab in chronic rhinosinusitis with nasal polyps (ANCHOR-1 and ANCHOR-2): phase 3, randomised, double-blind, parallel trials
Authors: Philippe Gevaert, Martin Desrosiers, Marjolein Cornet, Joaquim Mullol, Eugenio De Corso, Nesil Keles Turel, Jorge Maspero, Shigeharu Fujieda, Luo Zhang, Ana R Sousa, Samantha J Woods, Angela M Davis, Stein Schalkwijk, Dawn Edwards, Prerna Ranganathan, Richard Follows, Carolynne Marshall, Joseph K Han
Journal: The Lancet (2025)
Impact of a smartphone application for appropriate antibiotic prescribing at three tertiary hospitals; an international, multicentre stepped-wedge cluster randomised trial
Authors: R I Helou, G Catho, L Faxén, M Hulscher, S Teerenstra, J Conly, B D Huttner, T Tängdén, A Verbon
Journal: Clinical Microbiology and Infection (2025)