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MSC-Bench: A Rigorous Benchmark for Multi-Server Tool Orchestration
KnowMol: Advancing Molecular Large Language Models with Multi-Level Chemical Knowledge
Insights into the Unknown: Federated Data Diversity Analysis on Molecular Data
Integrating Transparent Models, LLMs, and Practitioner-in-the-Loop: A Case of Nonprofit Program Evaluation
RoboGPT-R1: Enhancing Robot Planning with Reinforcement Learning
The Right to Be Remembered: Preserving Maximally Truthful Digital Memory in the Age of AI
ScholaWrite: A Dataset of End-to-End Scholarly Writing Process
TinySQL: A Progressive Text-to-SQL Dataset for Mechanistic Interpretability Research
LongCodeBench: Evaluating Coding LLMs at 1M Context Windows
With Limited Data for Multimodal Alignment, Let the STRUCTURE Guide You
ACT: Agentic Classification Tree
Landscape of T-cell exhaustion heterogeneity and HBV integration in virus-related HCC revealed by whole-exome, transcriptome, and single-cell sequencing
JHEP Rep. 2025 Jul 10;7(11):101518. doi: 10.1016/j.jhepr.2025.101518. eCollection 2025 Nov.
ABSTRACT
BACKGROUND & AIMS: To enhance our understanding of the tumor immune microenvironment (TIME) in hepatocellular carcinoma (HCC), we investigated the heterogeneity of T-cell exhaustion and its association with HBV integrations and direct oncogenic potential in HCC.
METHODS: We conducted a multi-omics analysis, including single-cell RNA sequencing, whole-exome sequencing, whole-transcriptome sequencing, and next-generation sequencing (NGS)-based HBV integration analysis, in eight patients with virus-related HCC. For validation, bulk RNA sequencing and NGS-based HBV integration analysis were performed in an independent cohort (n = 106).
RESULTS: Based on the expression scores of exhaustion markers in effector CD8+ T cells, patients were classified into high (n = 2) and low (n = 6) exhaustion groups (p <0.001). The high-exhaustion group exhibited higher clonal expansion (Gini index: 0.83 vs. 0.48, p = 0.006) and sharing of CD8+ T effector memory and cycling T cells with elevated exhaustion markers. This group also showed increased clonal expansion of CD4+ regulatory T cells and follicular helper T cells (p <0.001) with higher PDCD1 expression. In addition, the high-exhaustion group had higher TP53 mutation rates and signature scores for proliferation subtypes compared with the low-exhaustion group, who predominantly harbored TERT mutations. Moreover, the high-exhaustion group demonstrated more pronounced HBV integrations with elevated intrahepatic covalently closed circular DNA (cccDNA) and pregenomic (pg)RNA levels. Similarly, in the validation cohort, the high-exhaustion group (n = 28) demonstrated stronger proliferation subtype signatures (p <0.001), along with higher HBV integrations, S-fusion transcripts, and an increased intrahepatic viral reservoir (cccDNA/pgRNA) (p <0.05) compared with the low-exhaustion group (n = 78).
CONCLUSIONS: Our study revealed the heterogeneity in T-cell exhaustion in the TIME of HCC, along with differences in HBV integrations and molecular subtypes. These findings provide insight into the intricate relationship between high exhaustion, proliferation subtype, increased HBV integrations, and enhanced HBV-induced oncogenic potential in virus-related HCC.
IMPACT AND IMPLICATIONS: This study provides a comprehensive immune landscape of T-cell exhaustion using multi-omics analysis, offering critical insights into T cell heterogeneity in virus-related HCC. It establishes a strong association between higher HBV integration, enhanced oncogenic potential, T-cell exhaustion, and proliferation subtypes in HCC. Our results also establish a basis for personalized therapies tailored to the immune-exhaustion status within the TIME of each patient with HCC.
PMID:41113120 | PMC:PMC12529496 | DOI:10.1016/j.jhepr.2025.101518
Single-cell multi-omics analysis reveals cancer regulatory elements of transcriptional programs and clinical implications
Cell Death Dis. 2025 Oct 21;16(1):746. doi: 10.1038/s41419-025-08060-7.
ABSTRACT
The regulatory mechanisms governing transcriptional programs in the cancer genome remain elusive, particularly those concerning cell-type specificity. We carefully curated single-cell assay for transposase-accessible chromatin sequencing (scATAC-seq) and single-cell RNA sequencing (scRNA-seq) data from eight distinct carcinoma tissues, including breast, skin, colon, endometrium, lung, ovary, liver, and kidney. Using single-cell multi-omics analysis, we identified extensive open chromatin regions and constructed peak-gene link networks, which can reveal distinct cancer gene regulation and genetic risks. We further explored conserved epigenetic regulation across cell types within cancer and elucidated their functional implications. Moreover, we identified cell-type-associated transcription factors (TFs) that regulate key cellular functions, such as the TEAD family of TFs, which widely control cancer-related signaling pathways in tumor cells. In colon cancer, we further identified tumor-specific TFs that are more highly activated in tumor cells than in normal epithelial cells, including CEBPG, LEF1, SOX4, TCF7, and TEAD4, which are pivotal in driving malignant transcriptional programs and represent potential therapeutic targets, as corroborated by single-cell sequencing data from multiple sources and in vitro experiments. Our findings provide a comprehensive understanding of the regulatory dynamics underlying carcinomas and offer valuable insights into potential therapeutic interventions.
PMID:41120274 | PMC:PMC12541060 | DOI:10.1038/s41419-025-08060-7
Exploring Patient Perspectives, Engagement, and Output Quality in Doctor-Supervised Use of Artificial Intelligence During Informed Consent Consultation With ChatGPT and Retrieval Augmented Generation (RAG): Quantitative Exploratory Study
Global Adoption, Promotion, Impact, and Deployment of AI in Patient Care, Health Care Delivery, Management, and Health Care Systems Leadership: Cross-Sectional Survey
Assessing Large Language Models in Building a Structured Dataset From AskDocs Subreddit Data: Methodological Study
STAT+: European oncology experts roll out guidance for use of large language models in clinical care
BERLIN — The leading professional organization for European oncologists has rolled out its first set of guidance on how its members should use large language models, a type of artificial intelligence, in cancer medicine.
“The oncology community cannot ignore the potential benefits which AI technology can provide to cancer patients,” the authors of the guidance wrote, while simultaneously acknowledging that there aren’t enough evaluations of the chatbots available to patients or tools available to doctors to address the risks associated with generative AI in medicine.
The guidance’s release — it was published last Saturday in the Annals of Oncology — coincided with the annual meeting for the European Society for Clinical Oncology in Berlin. The American Society of Clinical Oncology has issued its own set of principles for the responsible use of AI in cancer medicine, but has not released recommendations specific to large language models (LLMs).
Continue to STAT+ to read the full story…


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Discovering state-of-the-art reinforcement learning algorithms
Nature, Published online: 22 October 2025; doi:10.1038/s41586-025-09761-x
Discovering state-of-the-art reinforcement learning algorithmsPancreatic cancer relies on opposing signalling pathways to drive its cellular diversity
Nature, Published online: 22 October 2025; doi:10.1038/d41586-025-03133-1
Communication between epithelial and mesenchymal cells in pancreatic cancer leads to a poor prognosis. The molecular basis for this signalling has now been revealed.