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SAMark: A Self-Anchored Text Watermarking with Paragraph-Level Paraphrase Robustness
Dynamic Dual-Granularity Skill Bank for Agentic RL
AutoResearchClaw: Self-Reinforcing Autonomous Research with Human-AI Collaboration
Kolmogorov-Arnold Fourier Networks
Social Media Intervention Based on the Information-Motivation-Behavioral Skills Model Promotes HIV Testing and Reduces High-Risk Behaviors Among Men Who Have Sex With Men in Resource-Limited Settings in China: Randomized Controlled Trial
Combee: Scaling Prompt Learning for Self-Improving Language Model Agents
TreeGaussian: Tree-Guided Cascaded Contrastive Learning for Hierarchical Consistent 3D Gaussian Scene Segmentation and Understanding
Learning Additively Compositional Latent Actions for Embodied AI
Persistent Cross-Attempt State Optimization for Repository-Level Code Generation
Agentization of Digital Assets for the Agentic Web: Concepts, Techniques, and Benchmark
KLong: Training LLM Agent for Extremely Long-horizon Tasks
ToG-Bench: Task-Oriented Spatio-Temporal Grounding in Egocentric Videos
CogBias: Measuring and Mitigating Cognitive Bias in Large Language Models
Predicting Neuromodulation Outcome for Parkinson's Disease with Generative Virtual Brain Model
AGFT: Alignment-Guided Fine-Tuning for Zero-Shot Adversarial Robustness of Vision-Language Models
LaSM: Layer-wise Scaling Mechanism for Defending Pop-up Attack on GUI Agents
Robust transcriptomic hallmarks targeting intratumor heterogeneity in intrahepatic cholangiocarcinoma
Cell Rep Med. 2026 Mar 30:102708. doi: 10.1016/j.xcrm.2026.102708. Online ahead of print.
ABSTRACT
Intratumor heterogeneity (ITH) undermines transcriptome-based stratification in intrahepatic cholangiocarcinoma (iCCA). Here, we integrate multi-omics data from multi-region, single-region, and single-cell RNA sequencing cohorts to systematically characterize gene expression ITH. We uncover that immune and stromal heterogeneity are primary drivers of ITH, leading to misclassification of a median 27.8% of tumors by existing subtyping systems. To overcome this, we identify a low-intratumor-heterogeneity/high-intertumor-variability (LIHV) gene set and develop an ITH-insensitive classification system defining five subgroups: inflammatory (SI), metabolic (SII), atypical (SIII-1), immune-silent (SIII-2), and neurodegenerative (SIII-3). These subgroups exhibit distinct clinical outcomes, molecular features, immune landscapes, and therapeutic vulnerabilities. GPRC5A and VTCN1 serve as robust immunohistochemical biomarkers for SI and SIII tumors, while serum CEA and CA19-9 identify inflammatory iCCA. Therapeutically, HSP90 inhibition synergizes with anti-PD1 in inflammatory iCCA, whereas combined anti-PD1 and anti-TIM3 suppresses neurodegenerative iCCA. Collectively, our study provides a robust molecular framework and actionable therapeutic strategies for iCCA.
PMID:41916296 | DOI:10.1016/j.xcrm.2026.102708
Dynamic Targetable Extracellular Vesicle Surface Proteins Monitor Depth of Response to CAR T Therapy
Res Sq [Preprint]. 2026 Mar 18:rs.3.rs-8913641. doi: 10.21203/rs.3.rs-8913641/v1.
ABSTRACT
Extracellular vesicles (EVs) represent a promising liquid biopsy platform in multiple myeloma (MM). We developed an MM EV Surface Protein Assay to quantify and dynamically monitor four MM EV subpopulations defined by targetable MM surface proteins (BCMA, CD38, GPRC5D, and CD319) across 336 serial blood samples from 45 relapsed/refractory MM (RRMM) patients treated with anti-BCMA chimeric antigen receptor (CAR) T-cell therapy. All four MM EV subpopulations significantly decreased in 43 patients with initial response, while BCMA+, GPRC5D+, and CD319+ MM EVs increased in 19 patients with progression, and antigen escape was detected by BCMA+ MM EVs. MM EV subpopulations differentiated minimal residual disease (MRD) status and complemented MRD for detecting early relapse before clinical progression. Notably, CD319+ MM EVs were early predictors of progression-free and overall survival in MRD-negative patients. This assay enables noninvasive monitoring of deep response, progression, and antigen escape, and stratifies survival in MRD-negative patients with RRMM.
PMID:41890853 | PMC:PMC13015583 | DOI:10.21203/rs.3.rs-8913641/v1