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A Definition of AGI
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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
A Framework for Causal Concept-based Model Explanations
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
Whole-genome landscapes of 1,364 breast cancers
Nature, Published online: 03 December 2025; doi:10.1038/s41586-025-09812-3
Whole-genome and transcriptome analysis of 1,364 cases of breast cancer from South Korea broadens our understanding of breast cancer biology and reveals genomic features that connect tumour biology with treatment responses and clinical outcomes.CACARA: Cross-Modal Alignment Leveraging a Text-Centric Approach for Cost-Effective Multimodal and Multilingual Learning
Slovak Conceptual Dictionary
Wikontic: Constructing Wikidata-Aligned, Ontology-Aware Knowledge Graphs with Large Language Models
Deep Learning-Based Computer Vision Models for Early Cancer Detection Using Multimodal Medical Imaging and Radiogenomic Integration Frameworks
Multi-Modal AI for Remote Patient Monitoring in Cancer Care
Will Humanity Be Rendered Obsolete by AI?
Life-Code: Central Dogma Modeling with Multi-Omics Sequence Unification
The AI Productivity Index (APEX)
Opinion: Racial bias in medicine can be as simple as dismissing Black patients as a ‘hard stick’
I was moments away from a routine screening colonoscopy when it happened again. The warm and professional pre-procedure nurse began preparing for intravenous insertion. She tied the tourniquet loosely around my arm, took a quick glance, and untied it within seconds. “I can’t find a vein. You must be dehydrated,” she said, moving immediately to the back of my hand.
I paused. I didn’t feel dehydrated. Yes, I had followed the bowel prep instructions, consuming only liquids the day before, but I had no signs of dehydration. I knew my body. I knew my veins.


© AIZAR RALDES/AFP via Getty Images
The role of digital twins in P4 medicine: A paradigm for modern healthcare
npj Digital Medicine, Published online: 01 December 2025; doi:10.1038/s41746-025-02115-x
The role of digital twins in P4 medicine: A paradigm for modern healthcareDNA-Based Liquid Biopsy for Evaluating Surgical and Postsurgical Outcomes in Gynecologic Malignancies: A Systematic Review
J Clin Lab Anal. 2025 Dec 1:e70139. doi: 10.1002/jcla.70139. Online ahead of print.
ABSTRACT
INTRODUCTION: DNA-based liquid biopsies, including circulating tumor DNA (ctDNA) and cell-free DNA (cfDNA), are emerging as minimally invasive biomarkers for monitoring surgical and postsurgical outcomes in gynecologic malignancies. These tools offer the potential to guide early intervention, refine risk stratification, and improve prognostic accuracy. This systematic review aimed to assess the clinical utility of DNA-based liquid biopsies in evaluating recurrence, surgical success, and preoperative diagnosis in gynecologic cancers.
METHODS: A systematic review was conducted in accordance with PRISMA guidelines, covering studies published from 2017 to 2025. Literature searches were performed in PubMed, Scopus, and Web of Science. A total of 32 eligible observational studies involving 3210 patients with ovarian, endometrial, uterine, and other gynecologic malignancies were included. Study quality was assessed using the Newcastle-Ottawa Scale (NOS).
RESULTS: The studies showed a broad geographic and methodological diversity, with a median NOS score of 7. CtDNA and cfDNA demonstrated promise in three key areas: (1) Recurrence prediction-postoperative ctDNA positivity was associated with higher relapse rates and reduced disease-free survival; (2) Monitoring surgical outcomes and treatment response-ctDNA dynamics more accurately reflected tumor burden than traditional markers like CA125; (3) Preoperative diagnostic support-cfDNA methylation profiling and cfDNA/CA125 models enhanced malignancy detection and risk stratification. Ovarian and endometrial cancers were most frequently studied.
CONCLUSIONS: DNA-based liquid biopsies show strong potential in perioperative care for gynecologic cancers. Their integration into clinical workflows could improve the detection of minimal residual disease and inform individualized surgical planning.
PMID:41327898 | DOI:10.1002/jcla.70139