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Spatial evolution of a cachexia-promoting microenvironment in pancreatic cancer

Cell. 2026 Sep 29:S0092-8674(26)01081-0. doi: 10.1016/j.cell.2026.09.012. Online ahead of print.

ABSTRACT

Cachexia is a major cause of morbidity in pancreatic cancer, but the cellular circuitry linking tumor progression to systemic wasting remains incompletely understood. Integrating single-cell RNA sequencing, Xenium spatial transcriptomics, multiplex immunohistochemistry, bulk transcriptomics, and functional studies across human non-cachexia, pre-cachexia, and cachexia samples, together with mouse models, we define a cachexia-associated microenvironmental niche composed of SEMA4A+ tumor cells, AQP9+ macrophages, and LOXL2+ cancer-associated fibroblasts. Mechanistically, SEMA4A-associated signaling promotes bone morphogenetic protein-2 (BMP2)-dependent acquisition of an AQP9-associated macrophage phenotype, and macrophage-derived CXCL8 activates LOXL2+ fibroblasts. LOXL2+ fibroblasts reciprocally enhance tumor cell FOSL1/SEMA4A signaling through exosomal N-glycosylated LOXL2. Spatial analyses demonstrate progressive enrichment of this niche with cachexia severity and association with postoperative development of cachexia in previously non-cachectic patients. These findings provide a framework linking local tumor ecosystem dynamics to cachexia progression.

PMID:42810340 | DOI:10.1016/j.cell.2026.09.012

GlobalDentBench: A Multinational Benchmark for Evaluating LLM Clinical Reasoning in Dentistry with Expert Calibration

arXiv:2605.24636v2 Announce Type: new Abstract: While large language models (LLMs) hold transformative potential for medicine, their reasoning robustness and safety in real-world clinical scenarios remain critically underexplored, particularly in dentistry. Here we introduce GlobalDentBench, the first multinational dental benchmark, featuring a taxonomy that encompasses 14 dental specialties across 88 countries and regions spanning six continents. The benchmark comprises 8,978 expert-validated questions across three formats (multiple-choice, short-answer, and case-based questions) and assesses three progressive reasoning levels: knowledge recall (L1), routine reasoning (L2), and individualized reasoning (L3). To ensure data quality, the automated construction framework was calibrated by six senior dentists, achieving expert agreement rates of 99.98% for multiple-choice and short-answer questions and 96.78% for the more complex case-based questions. Evaluation of 12 frontier LLMs on GlobalDentBench revealed a sharp, stepwise performance degradation with increasing reasoning complexity. Specifically, accuracy plummeted from 81.34% on multiple-choice to 64.53% on short-answer and 22.34% on case-based questions, while declining markedly from 74.01% at L1 to 55.64% at L2 and 35.71% at L3. More critically, risk analysis of real-world dental cases demonstrated an alarming overall unsafe rate of 31.01% in LLM-generated clinical recommendations, with 4.51% posing risks of irreversible patient harm and risks particularly pronounced in specialties such as orthodontics. These findings expose fundamental limitations in the medical reasoning and safety of current LLMs. Consequently, GlobalDentBench provides a scalable foundation for trustworthy clinical AI evaluation, underscoring the urgent need for rigorous validation before the safe deployment of these models in healthcare.

CoMaTrack: Competitive Multi-Agent Game-Theoretic Tracking with Vision-Language-Action Models

arXiv:2603.22846v2 Announce Type: replace Abstract: Embodied Visual Tracking (EVT), a core dynamic task in embodied intelligence, requires an agent to precisely follow a language-specified target. Yet most existing methods rely on single-agent imitation learning, suffering from costly expert data and limited generalization due to static training environments. Inspired by competition-driven capability evolution, we propose CoMaTrack, a competitive game-theoretic multi-agent reinforcement learning framework that trains agents in a dynamic adversarial setting with competitive subtasks, yielding stronger adaptive planning and interference-resilient strategies. We further introduce CoMaTrack-Bench, the first open-source Habitat-based benchmark protocol and episode set for language-conditioned competitive EVT featuring dynamic dueling, featuring game scenarios between a tracker and adaptive opponents across diverse environments and instructions, enabling standardized robustness evaluation under active adversarial interactions. Experiments show that CoMaTrack achieves state-of-the-art results on both standard benchmarks and CoMaTrack-Bench. Notably, a 3B VLM trained with our framework surpasses previous single-agent imitation learning methods based on 7B models on the challenging EVT-Bench, achieving 92.1% in STT, 74.2% in DT, and 57.5% in AT. The benchmark code will be available at https://github.com/wlqcode/CoMaTrack-Bench.

Semantic Voting: A Self-Evaluation-Free Approach for Efficient LLM Self-Improvement on Unverifiable Open-ended Tasks

arXiv:2509.23067v2 Announce Type: replace-cross Abstract: The rising cost of acquiring supervised data has driven significant interest in self-improvement for large language models (LLMs). Straightforward unsupervised signals like majority voting have proven effective in generating pseudo-labels for verifiable tasks, while their applicability to unverifiable tasks (e.g., translation) is limited by the open-ended character of responses. As a result, self-evaluation mechanisms (e.g., self-judging and entropy minimization) are predominantly used to derive pseudo-labels. However, self-evaluation relying on LLMs typically incurs high computational overhead and introduces overconfidence issues due to intrinsic biases. To address these challenges, we propose a novel self-evaluation-free approach for unverifiable tasks, designed for lightweight yet effective self-improvement. Inspired by majority voting commonly employed in verifiable tasks, we propose semantic voting as a novel mechanism that relaxes the principle of hard matching (i.e., exact matching) toward soft matching (i.e., semantic similarity). Soft matching is achieved by leveraging a lightweight sentence embedding model to quantify semantic similarity, thereby mitigating excessive computational burden and intrinsic bias-associated limitations of self-evaluation. Comprehensive experiments demonstrate that our method achieves substantial gains in computational efficiency and overall better performance than self-evaluation methods across diverse model architectures and tasks.

CoMaTrack: Competitive Multi-Agent Game-Theoretic Tracking with Vision-Language-Action Models

arXiv:2603.22846v1 Announce Type: new Abstract: Embodied Visual Tracking (EVT), a core dynamic task in embodied intelligence, requires an agent to precisely follow a language-specified target. Yet most existing methods rely on single-agent imitation learning, suffering from costly expert data and limited generalization due to static training environments. Inspired by competition-driven capability evolution, we propose CoMaTrack, a competitive game-theoretic multi-agent reinforcement learning framework that trains agents in a dynamic adversarial setting with competitive subtasks, yielding stronger adaptive planning and interference-resilient strategies. We further introduce CoMaTrack-Bench, the first benchmark for competitive EVT, featuring game scenarios between a tracker and adaptive opponents across diverse environments and instructions, enabling standardized robustness evaluation under active adversarial interactions. Experiments show that CoMaTrack achieves state-of-the-art results on both standard benchmarks and CoMaTrack-Bench. Notably, a 3B VLM trained with our framework surpasses previous single-agent imitation learning methods based on 7B models on the challenging EVT-Bench, achieving 92.1% in STT, 74.2% in DT, and 57.5% in AT. The benchmark code will be available at https://github.com/wlqcode/CoMaTrack-Bench

A New Lower Bound for the Random Offerer Mechanism in Bilateral Trade using AI-Guided Evolutionary Search

arXiv:2603.08679v1 Announce Type: cross Abstract: The celebrated Myerson--Satterthwaite theorem shows that in bilateral trade, no mechanism can be simultaneously fully efficient, Bayesian incentive compatible (BIC), and budget balanced (BB). This naturally raises the question of how closely the gains from trade (GFT) achievable by a BIC and BB mechanism can approximate the first-best (fully efficient) benchmark. The optimal BIC and BB mechanism is typically complex and highly distribution-dependent, making it difficult to characterize directly. Consequently, much of the literature analyzes simpler mechanisms such as the Random-Offerer (RO) mechanism and establishes constant-factor guarantees relative to the first-best GFT. An important open question concerns the worst-case performance of the RO mechanism relative to first-best (FB) efficiency. While it was originally hypothesized that the approximation ratio $\frac{\text{GFT}_{\text{FB}}}{\text{GFT}_{\text{RO}}}$ is bounded by $2$, recent work provided counterexamples to this conjecture: Cai et al. proved that the ratio can be strictly larger than $2$, and Babaioff et al. exhibited an explicit example with ratio approximately $2.02$. In this work, we employ AlphaEvolve, an AI-guided evolutionary search framework, to explore the space of value distributions. We identify a new worst-case instance that yields an improved lower bound of $\frac{\text{GFT}_{\text{FB}}}{\text{GFT}_{\text{RO}}} \ge \textbf{2.0749}$. This establishes a new lower bound on the worst-case performance of the Random-Offerer mechanism, demonstrating a wider efficiency gap than previously known.
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