Reading view
Data Visualization Support for Interdisciplinary Team Treatment Planning in Clinical Oncology: Scoping Review
WisPaper: Your AI Scholar Search Engine
A Field Guide to Deploying AI Agents in Clinical Practice
Algorithms Trained on Normal Chest X-rays Can Predict Health Insurance Types
XR-DT: Extended Reality-Enhanced Digital Twin for Agentic Mobile Robots
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