By selectively targeting peripheral 5-HT2AR without inducing psychedelic effects, a non-brain-penetrant agonist boosts antitumor CD8+ T cell immunity and improves immunotherapy responses in preclinical models of colorectal cancer.

arXiv:2605.25246v2 Announce Type: new Abstract: Large language models (LLMs) are increasingly used for optimization modeling and solver-code generation, yet practical operations research and optimization problems often require a harder capability: designing scalable algorithms that exploit problem structure and outperform direct formulation-and-solve baselines. Existing benchmarks are limited to small or simplified examples far below real-world scale and complexity. We introduce FrontierOR, among the first benchmarks to systematically evaluate LLM-based efficient algorithm design for realistic large-scale optimization problems. FrontierOR includes 180 tasks derived from methodologically diverse papers published in top-tier operations research venues, each with standardized instances and a hidden, expert-verified evaluation suite. We evaluate seven LLMs spanning frontier, cost-effective, and open-source models both in one-shot and test-time evolution settings. The results reveal that frontier models still struggle to move from executable formulations to efficient optimization algorithms: the strongest one-shot model outperforms Gurobi in only 31% of cases in both solution quality and computational efficiency, and even strong coding agents with test-time evolution achieve only 50% on selected hard tasks. FrontierOR establishes a practical evaluation platform for LLM-based optimization algorithm design, which enables future LLMs and agents to be systematically tested on whether they can move beyond correct formulation toward a feasible, high-quality, and efficient algorithm.

arXiv:2603.29871v1 Announce Type: new Abstract: In user-agent interaction scenarios such as recommendation, brainstorming, and code suggestion, Large Language Models (LLMs) often generate sets of candidate recommendations where the objective is to maximize the collective utility of the entire set rather than individual candidates independently. However, existing reinforcement learning post-training paradigms, such as Group Relative Policy Optimization (GRPO), typically assign the same set-level scalar reward to every candidate in the set. This leads to noisy training signals where poor candidates free-ride on the high reward produced by a single strong peer, resulting in suboptimal exploration. To address this, we propose Shapley-Enhanced GRPO (ShapE-GRPO). By leveraging the permutation-invariant nature of set-level utility, we derive a Shapley-enhanced formulation from cooperative game theory to decompose set-level rewards into granular, candidate-specific signals. We show that our formulation preserves the fundamental axioms of the Shapley value while remaining computationally efficient with polynomial-time complexity. Empirically, ShapE-GRPO consistently outperforms standard GRPO across diverse datasets with accelerated convergence during training.

arXiv:2603.12279v1 Announce Type: new Abstract: Intracranial language brain-computer interfaces (BCIs) are a promising route for restoring communication in people with severe motor and speech impairments, but clinical translation remains limited by fragmented evidence and unresolved design trade-offs across neuroscience, hardware, algorithm, evaluation, and clinical deployment. This review synthesizes progress in neural mechanisms of overt, mimed, and imagined speech; decision-oriented hardware comparisons of microelectrode array (MEA), electrocorticography (ECoG), and stereotactic electroencephalography (SEEG) recording modalities; experiment design for cross-subject and multilingual generalization; and neural decoding advances spanning sequence models, transformers, articulatory intermediates, and language-prior-assisted frameworks. We highlight persistent bottlenecks, including weak cross-subject transfer, long-term non-stationarity and recalibration burden, heterogeneous and non-comparable evaluation practices, limited naturalistic expressivity (especially for tonal/logosyllabic languages), and low signal-to-noise ratio (SNR) of neural activity in covert speech decoding. Our contributions are threefold: (1) an end-to-end, decision-oriented synthesis linking neural representations to recording choices, experimental design, decoding model architectures, and translational constraints; (2) a structured framework organized around five coupled design questions, together with a unified evaluation framework and a cross-language/cross-task benchmark template integrating objective, perceptual, expressive, conversational, and longitudinal metrics; and (3) user-centered translational guidance covering agency-preserving shared control, verifiable performance priorities, and scenario-specific minimum viable system (MVP) profiles for reliability-first home communication versus fidelity-first conversational speech restoration.

arXiv:2603.02215v1 Announce Type: cross Abstract: Chemical reaction prediction is pivotal for accelerating drug discovery and synthesis planning. Despite advances in data-driven models, current approaches are hindered by an overemphasis on parameter and dataset scaling. Some methods coupled with evaluation techniques that bypass fundamental challenges in reaction representation and fail to capture deep chemical intuition like reaction common sense and {topological atom mapping logic}. We argue that the core challenge lies in instilling these knowledge into the models. To this end, we propose a unified framework that prioritizes chemical understanding over scale through three key innovations: (1) a {Latent Chemical Consistency} objective that models reactions as movements on a continuous chemical manifold, ensuring reversible and physically plausible transformations; (2) a {Hierarchical Cognitive Curriculum} that trains the model through progressive stages, from syntax mastery to semantic reasoning, building robust chemical intuition; (3) {Atom-Map Permutation Invariance (AMPI)}, which force the model to learn invariant relational topology and balance multi-task learning. (4)and structured plan-based reasoning to improve the performance of the LLMs. Our compact {0.5B-parameter model}, \textbf{RxnNano} significantly outperforms fine-tuned LLMs ten times larger (>7B) and all the domain baselines, achieving a 23.5\% Top-1 accuracy improvement on rigorous benchmarks without test-time augmentation. https://github.com/rlisml/RxnNano.

arXiv:2602.18449v1 Announce Type: cross Abstract: We propose a diffusion-based framework for prompt optimization that leverages Diffusion Language Models (DLMs) to iteratively refine system prompts through masked denoising. By conditioning on interaction traces, including user queries, model responses, and optional feedback, our method enables flexible, span-level prompt updates without requiring gradient access or modifying the downstream language model. Across diverse benchmarks (e.g., $\tau$-bench, SST-2, SST-5), DLM-optimized prompts consistently improve the performance of a frozen target LLM (e.g., GPT-4o-mini). We further show that moderate diffusion step counts provide the best balance between refinement quality and stability. These results highlight diffusion-based prompt optimization as a general, model-agnostic, and scalable approach for enhancing LLM performance through iterative prompt refinement.

arXiv:2510.02240v2 Announce Type: replace-cross Abstract: Fine-grained visual reasoning remains a core challenge for multimodal large language models (MLLMs). The recently introduced ReasonMap highlights this gap by showing that even advanced MLLMs struggle with spatial reasoning in structured and information-rich settings such as transit maps, a task of clear practical and scientific importance. However, standard reinforcement learning (RL) on such tasks is impeded by sparse rewards and unstable optimization. To address this, we first construct ReasonMap-Plus, an extended dataset that introduces dense reward signals through Visual Question Answering (VQA) tasks, enabling effective cold-start training of fine-grained visual understanding skills. Next, we propose RewardMap, a multi-stage RL framework designed to improve both visual understanding and reasoning capabilities of MLLMs. RewardMap incorporates two key designs. First, we introduce a difficulty-aware reward design that incorporates detail rewards, directly tackling the sparse rewards while providing richer supervision. Second, we propose a multi-stage RL scheme that bootstraps training from simple perception to complex reasoning tasks, offering a more effective cold-start strategy than conventional Supervised Fine-Tuning (SFT). Experiments on ReasonMap and ReasonMap-Plus demonstrate that each component of RewardMap contributes to consistent performance gains, while their combination yields the best results. Moreover, models trained with RewardMap achieve an average improvement of 3.47% across 6 benchmarks spanning spatial reasoning, fine-grained visual reasoning, and general tasks beyond transit maps, underscoring enhanced visual understanding and reasoning capabilities.