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From Verification Burden to Trusted Collaboration: Design Goals for LLM-Assisted Literature Reviews
Benchmarking AI Models in Software Engineering: A Review, Search Tool, and Unified Approach for Elevating Benchmark Quality
Understanding Prompt Management in GitHub Repositories: A Call for Best Practices
MetaVoxel: Joint Diffusion Modeling of Imaging and Clinical Metadata
High-Throughput Dissection of Inter-Organ Genetic Networks: A Multi-Omic Systems Biology Approach
SLAS Technol. 2025 Dec 11:100376. doi: 10.1016/j.slast.2025.100376. Online ahead of print.
ABSTRACT
The existing multi-omic analyses are frequently confined to individual tissues, and the regulatory picture of the systemic regulator of complex physiology and disease is hidden. To fill this gap, we have created a unified systems biology model of the high-throughput dissection of inter-organ genetic networks. Our model incorporates transcriptomic, epigenomic and proteomic analysis of five major organs (liver, kidney, heart, lung, brain) using the Multi-Omics Factor Analysis (MOFA+) tool, specifically, cross-tissue coordination. We characterized 27 evidence-heavy cross-tissue modules (FDR < 0.05) that are major hubs such as *HNF4Aenda NRF2cheng8loadmasterregulatingconstitutionembryonicstemcellularinfoncogenes recognize them. One notable observation was liver-kidney metabolic axis, significant cross-talks in hepatocyte organoids are confirmed with CRISPR knockdown, which suppresses the expression of transporters expressed by the kidney. Our work offers a scalable validated framework that goes beyond organ-centric perspectives, which can be used as a potent tool of systemic disease modelling and precision medicine.
PMID:41389879 | DOI:10.1016/j.slast.2025.100376
Stakeholder Criteria for Trust in Artificial Intelligence–Based Computer Perception Tools in Health Care: Qualitative Interview Study
Legal implications of AI standard of care integration on patients’ informed consent: lessons from surgery
npj Digital Medicine, Published online: 13 December 2025; doi:10.1038/s41746-025-02157-1
Legal implications of AI standard of care integration on patients’ informed consent: lessons from surgeryTrump’s AI executive order promises ‘one rulebook’ — startups may get legal limbo instead
Exploring Health Misinformation Detection with Multi-Agent Debate
Mind the Gap! Pathways Towards Unifying AI Safety and Ethics Research
Are ultrasensitive ctDNA assays ready for clinical use in early-stage NSCLC?
Macrophage-targeted immunocytokine leverages myeloid, T, and NK cell synergy for cancer immunotherapy
Pancreatic Cancer Organoids: Modeling Disease and Guiding Therapy
Cancers (Basel). 2025 Nov 30;17(23):3850. doi: 10.3390/cancers17233850.
ABSTRACT
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies. An unmet need exists for reliable biomarkers and in vitro models capable of predicting patient drug response to advance personalized medicine. Traditional models fail to represent the tumor's complexity and the role of the stromal environment in chemoresistance. Patient-derived organoids (PDOs) overcome these limitations, enabling multi-omics profiling and reliable drug testing for functional precision medicine. This review provides a comprehensive overview of PDAC PDO research, emphasizing the following major areas: (i) the genetic and phenotypic fidelity of PDOs, (ii) their predictive value for drug response and chemoresistance, (iii) the integration of the extracellular matrix and tumor microenvironment (TME) components, and (iv) emerging technologies. Studies confirm that PDOs faithfully represent the primary tumor's specific genetic features and retain intratumoral heterogeneity. PDO-based platforms have demonstrated a strong correlation between in vitro drug sensitivity and in vivo efficacy in xenograft models, validating their utility for identifying drug candidates, repurposing existing drugs, and determining effective combinations. Efforts are ongoing to integrate crucial TME components, like cancer-associated fibroblasts, using innovative co-culture platforms such as fused PDOs and InterOMaX, to better model desmoplasia and chemoresistance mechanisms. Furthermore, PDO technology is converging with microphysiological systems and artificial intelligence tools to facilitate high-throughput drug screening and dynamic, real-time monitoring of therapeutic effects. The integration of PDOs into biobanks and advanced screening platforms holds the potential to accelerate drug discovery and improve therapeutic outcomes for PDAC patients, if challenges related to protocol standardization and regulatory acceptance are addressed.
PMID:41375051 | PMC:PMC12690986 | DOI:10.3390/cancers17233850
Integrative network pharmacology, transcriptomics, and microbiomics elucidate the therapeutic mechanism of <em>Polygala tenuifolia</em> Willd water extract in chronic obstructive pulmonary disease
Front Microbiol. 2025 Nov 25;16:1703853. doi: 10.3389/fmicb.2025.1703853. eCollection 2025.
ABSTRACT
BACKGROUND: Polygala tenuifolia Willd (PT) is a plant with both medicinal and edible values. Traditionally, it has been used for sedation, enhancing cognition, resolving phlegm, and relieving cough. However, its protective effects and mechanisms against chronic obstructive pulmonary disease (COPD) remain unclear.
AIM OF THE STUDY: This study aims to observe the protective effects of the water extract of Polygala tenuifolia Willd (WEPT) on COPD, and to preliminarily elucidate its potential therapeutic mechanisms by integrating network pharmacology, molecular docking, multi-omics analysis, and molecular experiments.
METHODS AND MATERIALS: HPLC quantified WEPT constituents. COPD mice models established via chronic smoke exposure underwent WEPT treatment, and the therapeutic effect was evaluated by lung function test, histopathology and cytokine profiling. Integrated multi-omics analyses (network pharmacology, transcriptomics, microbiomics) identified bioactive compounds, therapeutic targets, pathway regulations, and microbiota dynamics. Molecular docking validated compound-target interactions, while immunohistochemical/fluorescence assays confirmed key protein expression in lung tissues.
RESULTS: WEPT administration effectively reduced inflammatory cytokine levels in COPD mice, improved lung function, and alleviated histopathological damage like alveolar structural injury and airway inflammation. Network pharmacology and transcriptomic analyses identified Norhyoscyamine and Onjixanthone I as key active components, targeting PIK3CA and AKT1 via PI3K-AKT pathway regulation. Microbiome analysis showed WEPT restored gut microbiota balance. Molecular docking confirmed strong binding of bioactive compounds to core targets, while immunostaining assays demonstrated WEPT suppressed p-PI3K and p-AKT protein expression.
CONCLUSION: WEPT may exert its intervention effects on COPD through a multi-target and multi-level comprehensive regulatory mechanism.
PMID:41377050 | PMC:PMC12685879 | DOI:10.3389/fmicb.2025.1703853
AI-driven virtual cell models in preclinical research: technical pathways, validation mechanisms, and clinical translation potential
npj Digital Medicine, Published online: 11 December 2025; doi:10.1038/s41746-025-02198-6
AI-driven virtual cell models in preclinical research: technical pathways, validation mechanisms, and clinical translation potentialPotential for Algorithmic Bias in Clinical Decision Instrument Development
npj Digital Medicine, Published online: 10 December 2025; doi:10.1038/s41746-025-02119-7
Potential for Algorithmic Bias in Clinical Decision Instrument Development