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Refined immune-based molecular subtypes of gastric cancer: Integrating mismatch repair status and tumor microenvironment for enhanced immunotherapy prediction

Chin J Cancer Res. 2026 Apr 30;38(2):234-251. doi: 10.21147/j.issn.1000-9604.2026.02.09.

ABSTRACT

OBJECTIVE: Gastric cancer (GC) is heterogeneous, and current mismatch repair (MMR)-based classifications incompletely predict response to immune checkpoint inhibitors (ICIs).

METHODS: RNA sequencing (RNA-seq) and immune infiltration profiles from 189 resected GC were used to derive four refined immune-MMR subtypes (R1-R4) by integrating MMR status, survival, and tumor microenvironment (TME) features. Multi-omics profiling and pathway analysis defined subtype biology. External transcriptomic cohorts and an ICI-treated cohort were classified with Nearest Template Prediction (NTP). Immune response-associated genes were identified from responder vs. non-responder comparisons within the ICI-sensitive subtype and validated by multiplex immunohistochemistry (mIHC).

RESULTS: R1 showed the best prognosis and highest immunotherapy response with objective response rate (ORR) 54.5%, while R4 had the worst prognosis. R2 represented an immune-unresponsive deficient mismatch repair (dMMR) subset, and R3 captured an immune-active proficient mismatch repair (pMMR) subgroup with moderate therapy sensitivity. Multi-omics integration revealed subtype-specific pathways (e.g., ECM remodeling in R1, metabolic reprogramming in R2). Reclassification of pMMR tumors based on transcriptional similarity to R1 identified a New R3 subset with enhanced immune features and higher ICI response. Eight immune response-associated genes (e.g., CXCL10, CXCL11, ELN, GAD1, IL32, MT1E, OR2I1P, SLC3A1) were identified and validated by mIHC for predictive relevance.

CONCLUSIONS: This immune-based molecular framework refines risk stratification beyond conventional MMR categories, identifies ICI-sensitive subsets among both dMMR and pMMR tumors, and proposes candidate biomarkers for patient selection.

PMID:42147371 | PMC:PMC13171420 | DOI:10.21147/j.issn.1000-9604.2026.02.09

Leptomeningeal metastatic cancer cells induce a permissive choroid plexus vasculature through extracellular-vesicle-derived 5-HIAA signaling

Nature Cancer, Published online: 03 April 2026; doi:10.1038/s43018-026-01145-y

Huang, Hou, Yang et al. demonstrate that leptomeningeal metastatic cells favor the formation of a premetastatic niche by remodeling the choroid plexus vasculature through the serotonin metabolite 5-hydroxyindoleacetic acid, which signals into endothelial cells through the aryl hydrocarbon receptor.

Heracles: Bridging Precise Tracking and Generative Synthesis for General Humanoid Control

arXiv:2603.27756v2 Announce Type: replace-cross Abstract: Achieving general-purpose humanoid control requires a delicate balance between the precise execution of commanded motions and the flexible, anthropomorphic adaptability needed to recover from unpredictable environmental perturbations. Current general controllers predominantly formulate motion control as a rigid reference-tracking problem. While effective in nominal conditions, these trackers often exhibit brittle, non-anthropomorphic failure modes under severe disturbances, lacking the generative adaptability inherent to human motor control. To overcome this limitation, we propose Heracles, a novel state-conditioned diffusion middleware that bridges precise motion tracking and generative synthesis. Rather than relying on rigid tracking paradigms or complex explicit mode-switching, Heracles operates as an intermediary layer between high-level reference motions and low-level physics trackers. By conditioning on the robot's real-time state, the diffusion model implicitly adapts its behavior: it approximates an identity map when the state closely aligns with the reference, preserving zero-shot tracking fidelity. Conversely, when encountering significant state deviations, it seamlessly transitions into a generative synthesizer to produce natural, anthropomorphic recovery trajectories. Our framework demonstrates that integrating generative priors into the control loop not only significantly enhances robustness against extreme perturbations but also elevates humanoid control from a rigid tracking paradigm to an open-ended, generative general-purpose architecture.

InnoEval: On Research Idea Evaluation as a Knowledge-Grounded, Multi-Perspective Reasoning Problem

arXiv:2602.14367v1 Announce Type: cross Abstract: The rapid evolution of Large Language Models has catalyzed a surge in scientific idea production, yet this leap has not been accompanied by a matching advance in idea evaluation. The fundamental nature of scientific evaluation needs knowledgeable grounding, collective deliberation, and multi-criteria decision-making. However, existing idea evaluation methods often suffer from narrow knowledge horizons, flattened evaluation dimensions, and the inherent bias in LLM-as-a-Judge. To address these, we regard idea evaluation as a knowledge-grounded, multi-perspective reasoning problem and introduce InnoEval, a deep innovation evaluation framework designed to emulate human-level idea assessment. We apply a heterogeneous deep knowledge search engine that retrieves and grounds dynamic evidence from diverse online sources. We further achieve review consensus with an innovation review board containing reviewers with distinct academic backgrounds, enabling a multi-dimensional decoupled evaluation across multiple metrics. We construct comprehensive datasets derived from authoritative peer-reviewed submissions to benchmark InnoEval. Experiments demonstrate that InnoEval can consistently outperform baselines in point-wise, pair-wise, and group-wise evaluation tasks, exhibiting judgment patterns and consensus highly aligned with human experts.

RV-Syn: Rational and Verifiable Mathematical Reasoning Data Synthesis based on Structured Function Library

arXiv:2504.20426v3 Announce Type: replace Abstract: The advancement of reasoning capabilities in Large Language Models (LLMs) requires substantial amounts of high-quality reasoning data, particularly in mathematics. Existing data synthesis methods, such as data augmentation from annotated training sets or direct question generation based on relevant knowledge points and documents, have expanded datasets but face challenges in mastering the inner logic of the problem during generation and ensuring the verifiability of the solutions. To address these issues, we propose RV-Syn, a novel Rational and Verifiable mathematical Synthesis approach. RV-Syn constructs a structured mathematical operation function library based on initial seed problems and generates computational graphs as solutions by combining Python-formatted functions from this library. These graphs are then back-translated into complex problems. Based on the constructed computation graph, we achieve solution-guided logic-aware problem generation. Furthermore, the executability of the computational graph ensures the verifiability of the solving process. Experimental results show that RV-Syn surpasses existing synthesis methods, including those involving human-generated problems, achieving greater efficient data scaling. This approach provides a scalable framework for generating high-quality reasoning datasets.
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