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M4-RAG: A Massive-Scale Multilingual Multi-Cultural Multimodal RAG
The AI Productivity Index (APEX)
Concept-Guided Backdoor Attack on Vision Language Models
Critical Appraisal Tools for Evaluating Artificial Intelligence in Clinical Studies: Scoping Review
Exploring a Digital Health Solution to Collect and Manage Health-Related Needs for Patients Who Undergo Complex Surgery: Mixed Methods Study
Molecular stratification of esophageal adenocarcinoma: implications for prognosis and treatment strategy
Oncogene, Published online: 08 December 2025; doi:10.1038/s41388-025-03650-3
Molecular stratification of esophageal adenocarcinoma: implications for prognosis and treatment strategyAI-driven transfer learning and classical molecular dynamics for strategic therapeutic repurposing and rational design of antiviral peptides targeting monkeypox virus DNA polymerase
Comput Biol Med. 2025 Dec 7;200:111372. doi: 10.1016/j.compbiomed.2025.111372. Online ahead of print.
ABSTRACT
The emergence of monkeypox virus (MPXV) as a global health threat has necessitated the rapid identification of novel antiviral therapeutics. Currently, no FDA-approved drugs are specifically designed against the disease. We used an in-house deep learning pharmacophore model for screening a library of 1974 FDA-approved drugs targeting the active site of MPXV DNA polymerase. Three drugs exhibited the strongest binding affinities, outperforming the control drug, Cidofovir diphosphate, and forming stable interactions with key active site residues. Among them, Paromomycin emerged as the most favourable drug, demonstrating stable, persistent, and adaptable interactions in molecular dynamics simulation. In parallel, we developed a novel automated peptide-generating AI pipeline that integrates active-site residues with knowledge-guided amino acid selection to generate and evaluate synthetic peptides. Cysteine-Phenylalanine-Cysteine (CFC), together with a panel of candidates, emerged through rational balancing of physicochemical properties and drug-likeness for accelerated therapeutic discovery. Synthetic peptides were evaluated to further understand the binding efficacies with DNA polymerase. CFC peptide demonstrated strong binding affinity (-8.08 kcal/mol) through stable interactions with key catalytic residues ASP549, ARG634 and LYS661, while MMGBSA analysis confirmed favourable binding energy (-33.02 kcal/mol). Consistent results in MD simulations indicate functional binding without destabilisation. Although ADMET predictions for CFC revealed limitations in permeability and oral bioavailability, its favourable binding profile and reduced predicted toxicity support its potential as a novel antiviral lead.
PMID:41360016 | DOI:10.1016/j.compbiomed.2025.111372
Mixed methods evaluation of a clinical decision support system to reduce variation in healthcare
npj Digital Medicine, Published online: 06 December 2025; doi:10.1038/s41746-025-02141-9
Mixed methods evaluation of a clinical decision support system to reduce variation in healthcareA typology of physician input approaches to using AI chatbots for clinical decision-making
npj Digital Medicine, Published online: 05 December 2025; doi:10.1038/s41746-025-02184-y
A typology of physician input approaches to using AI chatbots for clinical decision-makingA Definition of AGI
Scaling Multimodal Search and Recommendation with Small Language Models via Upside-Down Reinforcement Learning
Privacy is All You Need: Revolutionizing Wearable Health Data with Advanced PETs
Challenges and Limitations of Generative AI in Synthesizing Wearable Sensor Data
Harnessing cuproptosis for pancreatic cancer therapy: From molecular insights to clinical prospects
Biomed Pharmacother. 2025 Dec 2;193:118852. doi: 10.1016/j.biopha.2025.118852. Online ahead of print.
ABSTRACT
Pancreatic cancer (PC) remains a high-fatality malignancy with limited clinical progress, characterized by aggressive biology, marked resistance to standard therapies, and dismal outcomes. Even with state-of-the-art resection, radiotherapy, and multidrug chemotherapy, median survival benefits are modest, highlighting an urgent need for mechanism-based interventions. Cuproptosis, a newly delineated modality of regulated cell death initiated by intracellular copper accumulation and mitochondrial stress, presents a biologically coherent therapeutic avenue. Distinct from apoptosis, necroptosis, and ferroptosis, cuproptosis is driven by the direct binding of copper to lipoylated enzymes of the tricarboxylic acid (TCA) cycle, resulting in bioenergetic failure, misfolded protein aggregation, and collapse of cytotoxic proteostasis. Converging studies suggest that copper disequilibrium and metabolic reprogramming are recurrent features of PC, potentially contributing to malignant progression, immune evasion, and chemoresistance. These insights motivate two complementary strategies: first, therapeutic manipulation of copper flux, via chelators, ionophores, or transport modulators, to selectively trigger cuproptosis in tumor cells; and second, sensitization of mitochondrial metabolism, through targeting lipoic-acid pathway components, pyruvate utilization, or TCA load, to lower the threshold for cuproptotic killing. In parallel, multi-omic interrogation of cuproptosis-associated genes, proteins, and metabolites may yield prognostic and predictive biomarkers, enabling risk-adapted treatment selection and rational combinations with cytotoxic, targeted, or immunotherapeutic modalities. This review synthesizes recent advances on cuproptosis in PC and outlines its translational potential as both a therapeutic target and a biomarker framework.
PMID:41337879 | DOI:10.1016/j.biopha.2025.118852
Digital Biometrics in Predicting Risk for Obstructive Sleep Apnea and Hypertension: Decentralized, Prospective Cohort Study
Multi-omic profiling provides insights into the heterogeneity, microenvironmental features, and biomarker landscape of small-cell lung cancer
Mol Cancer. 2025 Dec 2. doi: 10.1186/s12943-025-02514-4. Online ahead of print.
ABSTRACT
BACKGROUND: Greater understanding of differential therapeutic sensitivity, specifically to immunotherapy, in small-cell lung cancer (SCLC) is required.
METHODS: We explored SCLC heterogeneity through integrated molecular characterization of tumor tissue samples from 159 treatment-naive patients, utilizing genetic, epigenetic, transcriptional, and proteomic profiling, immunohistochemistry staining for multiple biologically relevant markers including transcriptional subtype-defining proteins, and spatial immune profiling using multiplex immunofluorescence.
RESULTS: Multi-omics analysis confirmed high heterogeneity across/within neuroendocrine and non-neuroendocrine subtypes. Methylomics analysis identified four methylome clusters that may enhance subtype prediction, prognosis, and longitudinal monitoring of subtype evolution. Immunohistochemistry analysis showed high MHC-I expression in non-neuroendocrine subtypes, which have greatest potential benefit from adding immunotherapy to chemotherapy; high DLL3 expression associated with neuroendocrine subtypes and an immune-cold tumor microenvironment. Multiplex immunofluorescence demonstrated associations of MHC-I with spatial arrangement and phenotypic features of immune cells in the tumor microenvironment of high-MHC-I-expressing SCLC, providing mechanistic rationale for MHC-I as a potential biomarker of immunotherapy response.
CONCLUSIONS: This multimodal profiling analysis provides further insights into the biologic complexity of SCLC and highlights potential therapeutic vulnerabilities of distinct disease subtypes.
PMID:41331472 | DOI:10.1186/s12943-025-02514-4
Integrative Analysis of Multi-Omics Data for Biomarker Discovery
Annu Int Conf IEEE Eng Med Biol Soc. 2025 Jul;2025:1-7. doi: 10.1109/EMBC58623.2025.11254134.
ABSTRACT
The complexity of biological systems and the limitations of analyzing individual omics studies for biomarker discovery have raised the need for a holistic approach by multi-omics integration. By integrating data from multiple layers, researchers can gain insights into the entire system rather than just individual components. Also, integrative analysis can help identify molecular signatures that are more accurate in predicting disease onset, progression, and response to treatment, leading to better-targeted therapies and personalized medicine. In this paper, we explored statistical and deep learning methods for integrative analysis of metabolomics, lipidomics, peptidomics, proteomics, and glycoproteomics data acquired by LC-MS/MS analysis of serum samples from 20 hepatocellular carcinoma (HCC) cases and 20 patients with liver cirrhosis (CIRR). The goal is to identify a panel of multi-omics features that distinguish HCC cases from cirrhotic controls. A pathway analysis using these features identified biological pathways such as LXR/RXR Activation and Acute Response signaling as significantly enriched in our multi-omics datasets.
PMID:41336317 | PMC:PMC12694951 | DOI:10.1109/EMBC58623.2025.11254134