tbuckley/cabot-search huggingface dataset:
The African Animal Breeding Network as a pathway towards genetic improvement of livestock
Authors: Appolinaire Djikeng, Victor E. Olori, Isidore Houaga, Samuel E. Aggrey, Okeyo Mwai, Eveline M. Ibeagha-Awemu, Raphael Mrode, Mizeck G. G. Chagunda, Christian K. Tiambo, Romdhane Rekaya, Oyenkanmi Nash, Zabron Nziku, Oluyinka Opoola, Mapholi Ntanganedzeni, Chinyere Ekine-Dzivenu, Alexander Kahi, Tobias Okeno, John M. Hickey, Negussie Enyew, Edward J. O. Rege
Journal: Nature Genetics (2025)
Digital twin brain simulator for real-time consciousness monitoring and virtual intervention using primate electrocorticogram data
Authors: Yuta Takahashi, Hayato Idei, Misako Komatsu, Jun Tani, Hiroaki Tomita, Yuichi Yamashita
Journal: npj Digital Medicine (2025)

At the forefront of bridging computational brain modeling with personalized medicine, this study introduces a novel, real-time, electrocorticogram (ECoG) simulator, based on the digital twin brain concept. Utilizing advanced data assimilation techniques, specifically a Variational Bayesian Recurrent Neural Network model with hierarchical latent units, the simulator dynamically predicts ECoG signals reflecting real-time brain latent states. By assimilating broad ECoG signals from macaque monkeys across awake and anesthetized conditions, the model successfully updated its latent states in real-time, enhancing precision of ECoG signal simulations. Behind successful data assimilation, self-organization of latent states in the model was observed, reflecting brain states and individuality. This self-organization facilitated simulation of virtual drug administration and uncovered functional networks underlying changes in brain function during anesthesia. These results show that the proposed model can simulate brain signals in real-time with high accuracy and is also useful for revealing underlying information processing dynamics.
<i>Helicobacter pylori</i> infection induces DNA double-strand breaks through the ACVR1/IRF3/POLD1 signaling axis to drive gastric tumorigenesis
Authors: Xinbo Xu, Xiao Fei, Huan Wang, Xidong Wu, Yuan Zhan, Xin Li, Yan’an Zhou, Chunxi Shu, Cong He, Yi Hu, Jianping Liu, Nonghua Lv, Nianshuang Li, Yin Zhu
Journal: Gut Microbes (2025)

Helicobacter pylori (H. pylori) infection plays a pivotal role in gastric carcinogenesis through inflammation-related mechanisms. Activin A receptor type I (ACVR1), known for encoding the type I receptor for bone morphogenetic proteins (BMPs), has been identified as a cancer diver gene across various tumors. However, the specific role of AVCR1 in H. pylori-induced gastric tumorigenesis remains incompletely understood. We conducted a comprehensive analysis of the clinical relevance of ACVR1 by integrating data from public databases and our local collection of human gastric tissues. In vitro cell cultures, patient-derived gastric organoids, and transgenic INS-GAS mouse models were used for Western blot, qRT-PCR, immunofluorescence, immunohistochemistry, luciferase assays, ChIP, and comet assays. Furthermore, to investigate the therapeutic potential, we utilized the ACVR1 inhibitor DM3189 in our in vivo studies. H. pylori infection led to increased expression of ACVR1 in gastric epithelial cells, gastric organoid and gastric mucosa of INS-GAS mice. ACVR1 activation led to DNA double-strand break (DSB) accumulation by inhibiting POLD1, a crucial DNA repair enzyme. The activation of POLD1 was facilitated by the transcription factor IRF3, with identified binding sites. Additionally, treatment with the ACVR1 inhibitor DM3189 significantly ameliorated H. pylori-induced gastric pathology and reduced DNA damage in INS-GAS mice. Immunohistochemistry analysis showed elevated levels of ACVR1 in H. pylori-positive gastritis tissues, showing a negative correlation with POLD1 expression. This study uncovers a novel signaling axis of AVCR1/IRF3/POLD1 in the pathogenesis of H. pylori infection. The upregulation of ACVR1 and the suppression of POLD1 upon H. pylori infection establish a connection between the infection, genomic instability, and the development of gastric carcinogenesis.
<i>Bifidobacterium</i> inhibits the progression of colorectal tumorigenesis in mice through fatty acid isomerization and gut microbiota modulation
Authors: Yang Chen, Huiting Fang, Haiqin Chen, Xiaoming Liu, Jianxin Zhao, Catherine Stanton, R. Paul Ross, Wei Chen, Bo Yang
Journal: Gut Microbes (2025)

Colorectal cancer (CRC) represents the third most common cancer worldwide. Consequently, there is an urgent need to identify novel preventive and therapeutic strategies for CRC. This study aimed to screen for beneficial bacteria that have a preventive effect on CRC and to elucidate the potential mechanisms. Initially, we compared gut bacteria and bacterial metabolites of healthy volunteers and CRC patients, which demonstrated that intestinal conjugated linoleic acid (CLA), butyric acid, and Bifidobacterium in CRC patients were significantly lower than those in healthy volunteers, and these indicators were significantly negatively correlated with CRC. Next, spontaneous CRC mouse model were conducted to explore the effect of supplemental CLA-producing Bifidobacterium on CRC. Supplementation of mice with CLA-producing Bifidobacterium breve CCFM683 and B. pseudocatenulatum MY40C significantly prevented CRC. Moreover, molecular approaches demonstrated that CLA and the CLA-producing gene, bbi, were the key metabolites and genes for CCFM683 to prevent CRC. Inhibitor intervention results showed that PPAR-γ was the key receptor for preventing CRC. CCFM683 inhibited the NF-κB signaling pathway, up-regulated MUC2, Claudin-1, and ZO-1, and promoted tumor cell apoptosis via the CLA-PPAR-γ axis. Additionally, fecal microbiota transplantation (FMT) and metagenomic analysis showed that CCFM683 up-regulated Odoribacter splanchnicus through CLA production, which then prevented CRC by producing butyric acid, up-regulating TJ proteins, regulating cytokines, and regulating gut microbiota. These results will contribute to the clinical trials of Bifidobacterium and the theoretical research and development of CRC dietary products.
Management of Coronary Stent Underexpansion
Authors: Primero Ng, Akiko Maehara, Ajay J Kirtane, Margaret McEntegart, Farouc A Jaffer, Darshan Doshi, Kevin J Croce, Brian A Bergmark, Jarrod D Frizzell, Emmanouil S Brilakis, Kathleen E Kearney, William L Lombardi, Lorenzo Azzalini
Journal: Journal of the American College of Cardiology (2025)
Insights into the results of Resmetirom trials: Can a thyroid hormone receptor agonist be the holy grail of MASH therapy?
Authors: Konstantinos Arvanitakis, Theocharis Koufakis, Evangelos Cholongitas, Sven Francque, Georgios Germanidis
Journal: Pharmacology & Therapeutics (2025)

Despite the heavy individual patient and socioeconomic burden of metabolic dysfunction-associated steatohepatitis (MASH), until recently, no pharmacological therapy for MASH was approved, with available treatment options geared towards associated cardiometabolic risk factors. Accelerated approval of resmetirom, a thyroid hormone receptor-β agonist to be used in conjunction with diet and exercise, marks a significant step forward in the treatment of MASH, offering tempered optimism to healthcare providers and millions of patients around the world for more effective management. Evidence from phase 2 and 3 clinical trials suggests that resmetirom has the potential to alleviate hepatic fibrosis and inflammation and significantly reduce liver lipid content. Notwithstanding this landmark event, the clinical implementation of resmetirom comes with important challenges, for example, ensuring patient access to treatment and demonstrating effects on hard MASH-related outcomes, such as progression to cirrhosis and hepatocellular carcinoma. Additional considerations include the evaluation of co-administration with other hepatoprotective treatments and the assessment of the efficacy in specific MASH sub-phenotypes. Furthermore, the accumulation of real-world data and experience is expected to help answer the remaining questions about the (long-term) effectiveness and safety profile of the drug. The purpose of this article is to provide an updated and critical review of the mechanisms of action, efficacy, and safety of resmetirom based on the latest clinical trials, to define its place within the broader landscape of MASH management, and to highlight current knowledge gaps and opportunities for future research in the field.
The Burden of Diabetes Mortality by County, Race, and Ethnicity in the U.S., 2000–2019
Authors: Hasan Nassereldine, Zhuochen Li, Kelly Compton, Parkes Kendrick, Ethan Kahn, Yekaterina O. Kelly, Mathew M. Baumann, Chris A. Schmidt, Dillon O. Sylte, Kanyin Liane Ong, Wichada La Motte-Kerr, Farah Daoud, Susan A. McLaughlin, Simon I. Hay, Erik J. Rodriquez, Anna M. Nápoles, George A. Mensah, Eliseo J. Pérez-Stable, Ali H. Mokdad, Laura Dwyer-Lindgren
Journal: Diabetes Care (2025)

OBJECTIVE Diabetes is a leading cause of death in the U.S. Previous studies have found substantial racial, ethnic, and geographical disparities in diabetes mortality; however, research considering racial, ethnic, and geographical disparities simultaneously has been limited. To fill this gap, we estimated trends in diabetes mortality rates from 2000 to 2019 at the county level for five racial and ethnic populations. RESEARCH DESIGN AND METHODS We applied small-area estimation methods to death registration data from the U.S. National Vital Statistics System and population data from the U.S. National Center for Health Statistics and corrected for misclassification of race and ethnicity on death certificates. RESULTS Age-standardized diabetes mortality rates decreased in the U.S. from 28.1 deaths per 100,000 (95% uncertainty interval 27.9–28.2) in 2000 to 19.1 deaths per 100,000 (19.0–19.2) in 2019. In 2019, national-level rates were highest for the American Indian or Alaska Native (AIAN) population (35.6 [32.1–39.4]), followed by the Black (31.9 [31.5–32.3]), Latino (19.7 [19.3–20.2]), White (17.6 [17.5–17.8]), and Asian (12.6 [12.1–13.1]) populations. There was substantial heterogeneity in diabetes mortality rates across counties within each racial and ethnic population, with the AIAN population experiencing the greatest heterogeneity in 2019 (interquartile range 18.7–50.3 [median 31.9]). For each racial and ethnic population, mortality rates declined in most counties from 2000 to 2019. CONCLUSIONS Since 2000, progress has been made in reducing diabetes mortality rates. Nonetheless, diabetes mortality remains too high for many Americans. Interventions focusing on communities at highest risk are vital to resolving persistent health inequities.
SOCS1 protects acute myeloid leukemia against allogeneic T cell-mediated cytotoxicity
Authors: Enoch Tin, Sergio Rutella, Ismat Khatri, Yoosu Na, Yongran Yan, Neil MacLean, Jayakumar Vadakekolathu, Mark D. Minden, Aaron D. Schimmer, JongBok Lee, Li Zhang
Journal: Blood Cancer Discovery (2025)

Abstract Despite the curative potential of allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia (AML), its efficacy is limited by intrinsic resistance of cancer cells to donor-derived T-cell cytotoxicity. Using a genome-wide CRISPR screen, we identified the SOCS1-JAK1-STAT1 pathway as a mediator of AML susceptibility to T cells. SOCS1 knockdown in AML cells sensitized them to killing by allogeneic T cells, whereas SOCS1 overexpression in AML cells induced resistance to T-cell anti-leukemic activity. Mechanistically, SOCS1 protected AML cells from T-cell killing by antagonizing IFNγ-JAK1-induced ICAM-1 expression. Furthermore, primary AML cells with lower SOCS1 expression correlated with better overall survival in patients, especially those with a lower exhausted CD8+ T-cell score. Thus, this study reveals SOCS1 and its downstream mediators as a potential targetable pathway to enhance T cell-based immunotherapy for AML.
Enhanced Bioprinting of 3D Corneal Stroma Patches with Reliability, Assessing Product Consistency and Quality through Optimized Electron Beam Sterilization
Authors: Jungbin Yoon, Yeon‐ju Lee, Minji Kim, Ju Young Park, Jinah Jang
Journal: Advanced Healthcare Materials (2025)

This study focuses on the optimization of sterilization methods for bioprinted three-dimensional (3D) corneal stroma patches prepared using cornea-derived decellularized extracellular matrix (Co-dECM) hydrogels and human keratocytes, with the aim of enhancing clinical applications in corneal tissue engineering. An essential aspect of this study is to refine the sterilization processes, particularly focusing on electron beam (EB) sterilization, to maintain the structural and functional integrity of the Co-dECM hydrogels while ensuring sterility. The study reveals that EB sterilization outperformed traditional methods like ethylene oxide (EtO) gas and autoclaving, which tend to degrade the biochemical properties of hydrogels. By optimizing the EB-sterilization process, the essential mechanical and biochemical characteristics needed for successful 3D bioprinting are retained, reducing batch variability in bioprinted 3D corneal stroma patches. Consistency in production is vital for meeting regulatory standards and ensuring patient safety. Moreover, the study investigates the immunomodulatory properties of sterilized hydrogels, emphasizing their potential to minimize inflammatory responses, which is crucial for maintaining keratocyte phenotype. These findings significantly advance biomedical engineering by providing a sterilization method that preserves material integrity, minimizes immunogenicity, and supports the clinical translation of bioprinted corneal stroma patches, offering a promising alternative to donor transplants and synthetic substitutes.
Recent Applications of Mesoporous Silica Nanoparticles in Gene Therapy
Authors: Tamanna Binte Huq, Punnya Anil Kumar Jeeja, Sudip Kumar Dam, Sabya Sachi Das, Juan L. Vivero‐Escoto
Journal: Advanced Healthcare Materials (2025)

Abstract Gene therapy offers transformative potential for treating genetic disorders by directly addressing the molecular root causes of diseases. However, the primary challenges of gene therapy involve the efficient delivery of therapeutic genetic material to target cells, crossing biological barriers, managing toxicity and immune responses. Mesoporous silica nanoparticles (MSNs), due to their unique structural features have emerged as a promising platform to overcome these challenges. In recent years, MSNs have gained significant attention as potential nanocarriers for the efficient delivery of various nucleic acids. This review comprehensively examines the role of MSNs in gene therapy, focusing on their capabilities in the targeted delivery of siRNA, DNA, CRISPR‐Cas systems, and other genetic therapeutics. This work explores the modern advancements in MSNs synthesis and functionalization strategies and the impact of structural modifications on their stability, cellular uptake, and controlled release under physiological conditions. Additionally, the review highlights the use of MSNs to develop theranostic systems, where gene delivery is combined with diagnostic imaging for real‐time monitoring and personalized treatment strategies. Finally, this work discusses the future perspectives of MSNs in gene delivery, addressing regulatory challenges, enhancing clinical translation, and expanding their application for treating various genetic disorders and cancers.
Breathable, Moisturizing Biomimetic Wound Dressing with Broad‐Spectrum Antimicrobial Properties
Authors: Yunge Liu, Xiao Chen, Chengzhi Zhang, Saiya Li, Hui Zheng, Wanting Tang, Qiannan Wang, Jinbo Liu, Kefan Fang, Yingmin Zhao, Jing Zhang, Dianyu Wang
Journal: Advanced Healthcare Materials (2025)

Maintaining wound breathability and preventing infection are crucial for moist wound healing. However, existing hydrogel dressings suffer from poor breathability and clinically used antimicrobial agents such as antibiotics, metal nanoparticles, and natural antimicrobial substances face challenges including resistance, toxicity, and high extraction costs, respectively. Inspired by the antimicrobial properties of airway surface liquid (ASL), a biomimetic moisturizing and antibacterial hydrogel dressing (BMAHD) is designed. It combines polyvinyl alcohol (PVA) hydrogel with ordinary gauze to achieve high breathability, while also secreting a water-glycerol mixture to moisturize the wound. Interestingly, Na2CO3 secreted by dressing achieves broad-spectrum bactericidal effects, with up to 99% sterilization rates within 24 h. Furthermore, co-cultivation experiments with mouse embryonic fibroblasts (L929) and sheep red blood cells (SRBC) demonstrate excellent cellular compatibility of the dressing. To prove of concept, the animal model confirms that BMAHD significantly promotes wound healing. The BMAHD provides a valuable reference for the design of novel medical dressings.
Real‐World Efficacy and Safety of Abrocitinib in Chinese Atopic Dermatitis Patients: A Single‐Center Prospective Study
Authors: Zheng Li, Yu Wang, Yuemeng Wu, Huibin Yin, Shangshang Wang, Hao Wu, Haihong Qin, Ce Wang, Xu Yao, Wei Li, Chaoying Gu
Journal: Allergy (2025)

Phase 3 trials have demonstrated the efficacy and safety of abrocitinib for atopic dermatitis (AD), but real-world evidence remains limited. This study prospectively enrolled 117 moderate-to-severe AD patients at Huashan Hospital, Shanghai, China. Physician- and patient-reported outcomes were evaluated at multiple time points. Blood eosinophil counts, serum IgE, and 24 cytokines/chemokines were measured. Abrocitinib treatment led to rapid and potent improvements in disease severity. At week 12, 74.3% and 50.5% of AD patients achieved at least 75% and 90% improvement in the eczema area and severity index (EASI), respectively. Compared to dupilumab, abrocitinib showed greater improvement in Itch-NRS at week 2 and a higher proportion of EASI-75 at week 4. Adverse events occurred in 42.7% of AD patients, with gastrointestinal symptoms being the most common (17.1%). No tuberculosis (TB) reactivation was observed in patients who screened positive for TB and received isoniazid prophylaxis during the study period. Lower body mass index (BMI < 24; adjusted OR: 4.01, 95% CI: 1.36-11.73) and no prior dupilumab use (adjusted OR: 5.81, 95% CI: 1.8-18.7) were identified as predictors of a good response. By week 4, blood eosinophil counts and serum IgE significantly decreased. Reductions in Th2-, Th1-, and Treg-related cytokines/chemokines after 4 weeks of abrocitinib treatment, including IL-5, CCL17, CCL18, TNF-α, IL-6, IL-10, and CD25/IL-2Rα, were more pronounced in good responders. Abrocitinib demonstrated robust efficacy and a well-tolerated safety profile in Chinese patients with moderate-to-severe AD in routine clinical practice, accompanied by normalization of elevated blood biomarkers. ChiCRT Identifier: ChiCTR2200063195.
Accurate Diagnosis of Pancreatic Ductal Adenocarcinoma by Detection of miRNA‐196a Biomarker in Exosome Using Solution‐Gated Graphene Transistor with Antifouling Design
Authors: Peng Song, Junqi Dong, Tingting Yu, Zexun Pan, Ziwen Chen, Ruixue Wang, Ming Wang, Liang Zhao, Xianbao Wang, Jinhua Li
Journal: Advanced Healthcare Materials (2025)

The accurate diagnosis of pancreatic ductal adenocarcinoma (PDAC) suffers low specify, and low sensitivity of biomarker detection. In complex biological fluid environments, nonspecific adsorption is prevalent, posing challenges to the accurate detection of biomarkers at low concentrations. Herein, a highly sensitive and selective solution-gated graphene transistor (SGGT) is fabricated for the detection of miRNA-196a in exosomes to diagnose PDAC. The antifouling modification on the surface of the gate electrode is employed through using bovine serum albumin as a common sealing agent and poly adenine (polyA8) to enhance surface hydrophilicity. The effect of background noise on the detection is effectively reduced. The limit of detection reached 1.82 × 10-19 m without the need for labeling or amplification, and the detection time is within 25 min. The clinical experiments verify that receiver operating characteristic curve values of miRNA-196a detection in clinical diagnosis are higher than that of carbohydrate antigen 19-9 biomarker, and are as high as 0.98. The miRNA-196a detection can well distinguish PDAC from non-PDAC subjects. The SGGT sensor platform demonstrates significant potential for the accurate detection and diagnosis of PDAC within the milieu of complex biological samples.
3D Microtumors Representing Ovarian Cancer Minimal Residual Disease Respond to the Fatty Acid Oxidation Inhibitor Perhexiline
Authors: Xingyun Yang, Mara Artibani, Yongcheng Jin, Aneesh Aggarwal, Yujia Zhang, Sandra Muñoz‐Galvan, Ellina Mikhailova, Lena Rai, Nobina Mukherjee, Ravinash Krishna Kumar, Ashwag Albukhari, Shaohua Ma, Linna Zhou, Ahmed Ashour Ahmed, Hagan Bayley
Journal: Advanced Healthcare Materials (2025)

The poor survival of ovarian cancer patients is linked to their high likelihood of relapse. In spite of full apparent macroscopic clearance, tumor recurrences arise from cells that are resistant to primary chemotherapy in the form of minimal residual disease (MRD). MRD exhibits distinct molecular drivers from bulk cancer and therefore necessitates alternative therapeutic strategies. However, there is a lack of 3D models that faithfully recapitulate MRD ex vivo for therapy development. This study constructs microfluidics-based 3D microtumors to generate a clinically-relevant model for ovarian cancer MRD. The microtumors recapitulate the non-genetic heterogeneity of ovarian cancer, capturing the "Oxford Classic" five molecular signatures. Gene expression in the 3D microtumors aligns closely with MRD from ovarian cancer patients and features the upregulation of fatty acid metabolism genes. Finally, the MRD 3D microtumors respond to the approved fatty acid oxidation inhibitor, perhexiline, demonstrating their utility in drug discovery. This system might be used as a drug-testing platform for the discovery of novel MRD-specific therapies in ovarian cancer.
Multifunctional Hydrogel Electronics for Synergistic Therapy and Visual Monitoring in Wound Healing
Authors: Yun‐Liang Ji, Yizhou Zhang, Jingqi Lu, Fan Gao, Xinyi Lv, Xinyu Qu, Guoyin Zhu, Tian Tian, Huan Pang, Yu Tian, Xiaochen Dong
Journal: Advanced Healthcare Materials (2025)

To overcome the limitations of precise monitoring and inefficient wound exudate management in wound healing, an advanced multifunctional hydrogel electronics (MHE) platform based on MXene@MOF/Fe3O4@C photonic crystal hydrogel is developed. This platform combines optical/electrical sensing, synergistic therapy, and real-time visual monitoring into a single, efficient system, offering a comprehensive solution for wound healing. Under photothermal stimulation, the hydrogel releases metal ions that generate hydroxyl radicals, effectively eliminating antibiotic-resistant bacteria. Beyond its antibacterial efficacy, this system offers unprecedented real-time monitoring through temperature-responsive visualization, while structural color changes upon wound exudate absorption provide a clear indication for dressing replacement. By integrating these functionalities, MHE platform allows for precise control of the therapeutic process, significantly improving wound healing and treatment monitoring. The platform's optical/electrical sensing capabilities further broaden its potential applications across other biomedical fields. This breakthrough technology provides clinicians with a powerful tool to optimize therapeutic outcomes, marking a major advancement in wound care and biomedical applications.