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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

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VANGUARD: Vehicle-Anchored Ground Sample Distance Estimation for UAVs in GPS-Denied Environments

arXiv:2603.04277v1 Announce Type: cross Abstract: Autonomous aerial robots operating in GPS-denied or communication-degraded environments frequently lose access to camera metadata and telemetry, leaving onboard perception systems unable to recover the absolute metric scale of the scene. As LLM/VLM-based planners are increasingly adopted as high-level agents for embodied systems, their ability to reason about physical dimensions becomes safety-critical -- yet our experiments show that five state-of-the-art VLMs suffer from spatial scale hallucinations, with median area estimation errors exceeding 50%. We propose VANGUARD, a lightweight, deterministic Geometric Perception Skill designed as a callable tool that any LLM-based agent can invoke to recover Ground Sample Distance (GSD) from ubiquitous environmental anchors: small vehicles detected via oriented bounding boxes, whose modal pixel length is robustly estimated through kernel density estimation and converted to GSD using a pre-calibrated reference length. The tool returns both a GSD estimate and a composite confidence score, enabling the calling agent to autonomously decide whether to trust the measurement or fall back to alternative strategies. On the DOTA~v1.5 benchmark, VANGUARD achieves 6.87% median GSD error on 306~images. Integrated with SAM-based segmentation for downstream area measurement, the pipeline yields 19.7% median error on a 100-entry benchmark -- with 2.6x lower category dependence and 4x fewer catastrophic failures than the best VLM baseline -- demonstrating that equipping agents with deterministic geometric tools is essential for safe autonomous spatial reasoning.
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