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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.

DarkForest: Less Talk, Higher Accuracy for Multi-Agent LLMs

arXiv:2605.25188v1 Announce Type: new Abstract: Multi-agent LLM systems improve reasoning by combining outputs from multiple agents, but interaction-heavy methods can introduce error propagation and high communication overhead. When agents exchange raw responses or reasoning traces, incorrect intermediate reasoning may be adopted and amplified, leading to confident but wrong consensus; multi-round communication also increases token consumption, latency, and inference cost. In this paper, we propose a controlled-communication coordination framework named DarkForest. DarkForest first keeps agents independent, so each agent produces an answer without seeing the others' outputs. It then parses the raw responses into structured candidate records, groups semantically equivalent candidates into clusters, and estimates a calibrated belief distribution over these clusters using agent reliability, confidence, parse quality, support-pattern reliability, and independence corrections. A coordinator receives only policy-permitted evidence from this belief state with controlled communication. Experiments on six reasoning benchmarks show that DarkForest achieves leading overall quality, improves the strongest baseline by up to 30.7\% on benchmark metrics, and reduces token consumption by up to $6.5\times$ compared with communication-heavy baselines.

FrontierOR: Benchmarking LLMs' Capacity for Efficient Algorithm Design in Large-Scale Optimization

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.

Towards end-to-end LLM-based censoring-aware survival analysis

arXiv:2605.25399v1 Announce Type: new Abstract: Objective: Survival analysis is central to medical prediction, yet large language models (LLMs) are rarely used as end-to-end survival models because censoring prevents straightforward supervised fine-tuning. Here we present LLMSurvival, a framework that enables censoring-aware survival analysis with unmodified LLMs operating directly on tabular clinical data. Materials and Methods: LLMSurvival reformulates time-to-event prediction as pairwise ranking among comparable subjects, and derives test-time risk by aggregating comparisons against anchor individuals from the training cohort. Results: Across two clinical tasks (ICU mortality prediction in MIMIC-IV and fragility fracture prediction in a NewYork-Presbyterian/Weill Cornell Medicine cohort), LLMSurvival improves overall concordance over Cox proportional hazards modeling by 3.1% for ICU mortality and 0.5% for fracture risk, 2.1% on average for ICU mortality and 2.8% for fracture risk over three established deep learning survival models. Discussion: The results show that survival modeling with censoring can be made compatible with LLM fine-tuning through comparison-based reformulation. The framework demonstrates high portability and superior performance over expert curated scores like SAPS-II and FRAX scores across diverse clinical context. Furthermore, the framework supports local deployment, as compact, publicly available base models provide sufficient performance. Conclusion: The LLMSurvival framework serves as a proof of concept for an integrated, censoring-conscious approach to survival analysis via LLMs.

AgentHijack: Benchmarking Computer Use Agent Robustness to Common Environment Corruptions

arXiv:2605.25707v1 Announce Type: new Abstract: Autonomous computer use agents that powered by multimodal large language models (MLLMs) are emerging as capable assistants for completing complex digital workflows. However, real-world execution environments are far from ideal: pop-ups, resolution changes, and competing applications frequently interfere with agent perception and control. We introduce AgentHijack, a benchmark designed to evaluate the robustness of computer-use agents under common corruptions, where the uncertainties in dynamic environment disrupt the execution flow without direct adversarial intent. Specifically, AgentHijack introduces 9 configurable common corruptions to replicate realistic imperfect scenarios. We evaluate a variety of desktop tasks that utilize MLLM-based agents and discover that even minor instances of corruption can result in substantial performance degradation, which emphasizes the fragility of agents and underscores the necessity of robustness evaluation. Afterward, we propose AgentHijack-Agent, a framework that integrates an action generator with enhanced grounding capabilities and an onlooker responsible for behavior summarization and environment checking. Extensive experiments validate its effectiveness. Our code, environment, baseline models and data are publicly available at: https://AgentHijack.github.io.

Agent Learning via Early Experience

arXiv:2510.08558v3 Announce Type: replace Abstract: A long-term goal of language agents is to learn and improve through their own experience, ultimately outperforming humans in complex, real-world tasks. However, training agents from experience data with reinforcement learning remains difficult in many environments, which either lack verifiable rewards (e.g., websites) or require inefficient long-horizon rollouts (e.g., multi-turn tool use). As a result, most current agents rely on supervised fine-tuning on expert data, which is challenging to scale and generalizes poorly. This limitation stems from the nature of expert demonstrations: they capture only a narrow range of scenarios, and expose the agent to limited environment diversity. We address this limitation with a middle-ground paradigm we call early experience: interaction data generated by the agent's own actions, where the resulting future states serve as supervision without reward signals. Within this paradigm, we study two strategies of using such data: (1) implicit world modeling, which uses collected states to ground the policy in environment dynamics; and (2) self-reflection, where the agent learns from its suboptimal actions to improve reasoning and decision-making. Evaluation across eight diverse environments and multiple model families shows that our approaches consistently improve effectiveness and out-of-domain generalization, highlighting the value of early experience. Moreover, in environments with verifiable rewards, our results provide promising signals that early experience offers a strong foundation for subsequent reinforcement learning, making it a practical bridge between imitation learning and fully experience-driven agents.

Agent World Model: Infinity Synthetic Environments for Agentic Reinforcement Learning

arXiv:2602.10090v3 Announce Type: replace Abstract: Recent advances in large language model (LLM) have empowered autonomous agents to perform multi-turn interactions with tools and environments. However, scaling such agent training is limited by the lack of diverse and reliable environments. In this paper, we propose Agent World Model (AWM), a fully synthetic environment generation pipeline. Using this pipeline, we scale to 1,000 environments covering everyday scenarios, in which agents can interact with rich toolsets and obtain high-quality observations. Notably, these environments are code-driven and backed by databases, providing more reliable and consistent state transitions than environments simulated by LLMs. Moreover, they enable more efficient agent interaction compared with collecting trajectories from realistic environments. To demonstrate the effectiveness of this resource, we perform large-scale reinforcement learning for multi-turn tool-use agents. Thanks to the fully executable environments and accessible database states, we can also design reliable reward functions. Experiments on three benchmarks show that training exclusively in synthetic environments, rather than benchmark-specific ones, yields strong out-of-distribution generalization. The code is available at https://github.com/Snowflake-Labs/agent-world-model.

Reliable AI Needs to Externalize Implicit Knowledge: A Human-AI Collaboration Perspective

arXiv:2605.02010v2 Announce Type: replace Abstract: This position paper argues that reliable AI requires infrastructure for human validation of implicit knowledge. AI learns from both explicit knowledge (papers, documentation, structured databases) and implicit knowledge (reasoning patterns, debugging processes, intermediate steps). Implicit knowledge remains unexternalized because documentation cost exceeds perceived value -- yet AI learns from it indiscriminately, acquiring both beneficial patterns and harmful biases. Current reliability methods can only verify explicit knowledge against sources, creating a fundamental gap: the most valuable AI capabilities (reasoning, judgment, intuition) are precisely those we cannot verify. We propose Knowledge Objects (KOs) -- structured artifacts that externalize implicit knowledge into forms humans can inspect, verify, and endorse. KOs transform verification economics: what was previously too costly to verify becomes feasible, enabling accumulated human validation to improve reliability over time.

Bridging Evolutionary Algorithms and Reinforcement Learning: A Comprehensive Survey on Hybrid Algorithms

arXiv:2401.11963v5 Announce Type: replace-cross Abstract: Evolutionary Reinforcement Learning (ERL), which integrates Evolutionary Algorithms (EAs) and Reinforcement Learning (RL) for optimization, has demonstrated remarkable performance advancements. By fusing both approaches, ERL has emerged as a promising research direction. This survey offers a comprehensive overview of the diverse research branches in ERL. Specifically, we systematically summarize recent advancements in related algorithms and identify three primary research directions: EA-assisted Optimization of RL, RL-assisted Optimization of EA, and synergistic optimization of EA and RL. Following that, we conduct an in-depth analysis of each research direction, organizing multiple research branches. We elucidate the problems that each branch aims to tackle and how the integration of EAs and RL addresses these challenges. In conclusion, we discuss potential challenges and prospective future research directions across various research directions. To facilitate researchers in delving into ERL, we organize the algorithms and codes involved on https://github.com/yeshenpy/Awesome-Evolutionary-Reinforcement-Learning.

Reward-free Alignment for Conflicting Objectives

arXiv:2602.02495v3 Announce Type: replace-cross Abstract: Direct alignment methods are increasingly used to align large language models (LLMs) with human preferences. However, many real-world alignment problems involve multiple conflicting objectives, where naive aggregation of preferences can lead to unstable training and poor trade-offs. In particular, weighted loss methods may fail to identify update directions that simultaneously improve all objectives, and existing multi-objective approaches often rely on explicit reward models, introducing additional complexity and distorting user-specified preferences. The contributions of this paper are two-fold. First, we propose a Reward-free Alignment framework for Conflicted Objectives (RACO) that directly leverages pairwise preference data and resolves gradient conflicts via a novel clipped variant of conflict-averse gradient descent. We provide convergence guarantees to Pareto-critical points that respect user-specified objective weights, and further show that clipping can strictly improve convergence rate in the two-objective setting. Second, we improve our method using some heuristics and conduct experiments to demonstrate the compatibility of the proposed framework for LLM alignment. Both qualitative and quantitative evaluations on multi-objective summarization and safety alignment tasks across multiple LLM families (Qwen 3, Llama 3, Gemma 3) show that our method consistently achieves better Pareto trade-offs compared to existing multi-objective alignment baselines.

SPA-Cache: Singular Proxies for Adaptive Caching in Diffusion Language Models

arXiv:2602.02544v2 Announce Type: replace-cross Abstract: While Diffusion Language Models (DLMs) offer a flexible, arbitrary-order alternative to the autoregressive paradigm, their non-causal nature precludes standard KV caching, forcing costly hidden state recomputation at every decoding step. Existing DLM caching approaches reduce this cost by selective hidden state updates; however, they are still limited by (i) costly token-wise update identification heuristics and (ii) rigid, uniform budget allocation that fails to account for heterogeneous hidden state dynamics. To address these challenges, we present SPA-Cache that jointly optimizes update identification and budget allocation in DLM cache. First, we derive a low-dimensional singular proxy that enables the identification of update-critical tokens in a low-dimensional subspace, substantially reducing the overhead of update identification. Second, we introduce an adaptive strategy that allocates fewer updates to stable layers without degrading generation quality. Together, these contributions significantly improve the efficiency of DLMs, yielding up to an $8\times$ throughput improvement over vanilla decoding and a $2$--$4\times$ speedup over existing caching baselines.

Safety in Embodied AI: A Survey of Risks, Attacks, and Defenses

arXiv:2605.02900v2 Announce Type: replace-cross Abstract: Embodied Artificial Intelligence (Embodied AI) integrates perception, cognition, planning, and interaction into agents that operate in open-world, safety-critical environments. As these systems gain autonomy and enter domains such as transportation, healthcare, and industrial or assistive robotics, ensuring their safety becomes both technically challenging and socially indispensable. Unlike digital AI systems, embodied agents must act under uncertain sensing, incomplete knowledge, and dynamic human-robot interactions, where failures can directly lead to physical harm. This survey provides a comprehensive and structured review of safety research in embodied AI, examining attacks and defenses across the full embodied pipeline, from perception and cognition to planning, action and interaction, and agentic system. We introduce a multi-level taxonomy that unifies fragmented lines of work and connects embodied-specific safety findings with broader advances in vision, language, and multimodal foundation models. Our review synthesizes insights from over 500 papers spanning adversarial, backdoor, jailbreak, and hardware-level attacks; attack detection, safe training and robust inference; and risk-aware human-agent interaction. This analysis reveals several overlooked challenges, including the fragility of multimodal perception fusion, the instability of planning under jailbreak attacks, and the trustworthiness of human-agent interaction in open-ended scenarios. By organizing the field into a coherent framework and identifying critical research gaps, this survey provides a roadmap for building embodied agents that are not only capable and autonomous but also safe, robust, and reliable in real-world deployment.

Machine learning-based identification of key genes underlying sex differences in hepatocellular carcinoma and targeted drug screening

Biomed Rep. 2026 Apr 24;24(6):74. doi: 10.3892/br.2026.2147. eCollection 2026 Jun.

ABSTRACT

Hepatocellular carcinoma (HCC) shows a marked predominance in men, yet the molecular basis for this sex disparity remains unclear. The present study leveraged multi-omics data and machine learning algorithms to identify key genes associated with sex-specific differences in HCC and to screen for putative candidate compounds, aiming to provide new insights for sex-specific therapy. The mRNA expression data of male and female patients with HCC and paracancerous tissues were obtained from the GEO and TCGA databases. To mitigate overfitting, data were partitioned into independent training and testing sets. Candidate genes were screened by differential expression analysis and weighted gene co-expression network analysis. A total of four complementary algorithms, random forest, support vector machines, generalized linear models and extreme gradient boosting were used to identify key genes with high predictive capability. CYP17A1 and IRX3 were identified as the top differentially expressed core genes associated with HCC in men. Pan-cancer analysis showed that CYP17A1 was lowly expressed in the majority of tumors, but significantly highly expressed in HCC, rectal adenocarcinoma and gastric cancer (P<0.001). Functional cell-based assays showed that knockout of CYP17A1 inhibited the proliferation, migration and invasion ability of HCC cells (P<0.001). Immunohistochemistry showed that CYP17A1 protein expression was significantly increased in HCC tissues from male patients when compared with that in paracancerous tissues (P<0.001), whereas there was no significant difference in female patient tissues (P>0.05). Notably, while IRX3 was identified computationally, its functional role remains to be experimentally validated. Molecular docking predicted a potential interaction between the natural compound Saikosaponin A and the CYP17A1 protein, and cellular assays revealed that it dose-dependently inhibits HCC cell malignant phenotypes. The present study suggests that CYP17A1 is associated with sex differences in HCC, potentially via the androgen signaling axis. Furthermore, IRX3 emerges as a novel hypothesis-generating candidate gene. Finally, the findings of the present study highlight Saikosaponin A as a putative therapeutic candidate for male patients with HCC, warranting further target-dependency investigations.

PMID:42125766 | PMC:PMC13158723 | DOI:10.3892/br.2026.2147

Phages communicate across species to shape microbial ecosystems

Gallego-del-Sol et al. show that arbitrium-coding phages can sense non-cognate peptide signals from other phages to regulate lysis-lysogeny decisions. This crosstalk affects lysis-lysogeny outcomes of phage infections, mixed lysogenic communities, and polylysogens. Our results demonstrate that crosstalk is an important mechanism that drives phage interactions in microbial communities.

FCGR2B (+) Macrophages as a Critical Node Linking Ferroptosis and Immunosuppression: A Multiomics Framework for Prognosis and Therapy in High-Grade Serous Ovarian Cancer

Hum Mutat. 2026 Apr 6;2026:8027584. doi: 10.1155/humu/8027584. eCollection 2026.

ABSTRACT

BACKGROUND: High-grade serous ovarian cancer (HGSOC) is characterized by a complex tumor microenvironment and poor prognosis, yet the roles of specific tumor-associated macrophages (TAMs) subpopulations in driving disease progression remain elusive.

METHODS: This study evaluated the prognostic relevance of FCGR2B in HGSOC. Single-cell RNA sequencing identified FCGR2B + TAMs as a distinct macrophage subpopulation with unique transcriptional features. Integrative analyses combining single-cell and bulk differentially expressed genes, macrophage-associated modules, and ferroptosis-related gene sets identified 26 candidate prognostic genes, from which a four-gene signature (CRYAB, PLAUR, EREG, and C5AR1) was derived to construct the prognostic risk model. The model was validated in an independent cohort. Immune infiltration, single-cell trajectory, copy number variation, and drug-gene associations were analyzed to explore the molecular and therapeutic implications of risk stratification.

RESULTS: HGSOC patients classified as high risk exhibited poorer survival outcomes, increased infiltration of M2-like macrophages, elevated expression of immune checkpoints, and enrichment of immune- and ferroptosis-related pathways. Trajectory and copy number variation analyses revealed stage-specific gene expression patterns and amplification-associated regulation. Drug-gene association analyses further suggested that high-risk patients may be more responsive to targeted therapies and proteasome inhibitors, whereas low-risk patients may benefit from conventional chemotherapy.

CONCLUSION: FCGR2B + TAMs are closely linked to HGSOC progression, and the proposed prognostic model based on FCGR2B + TAMs provides predictive value and potential therapeutic insights for patient stratification.

PMID:41953398 | PMC:PMC13054137 | DOI:10.1155/humu/8027584

Enhancing behavioral nudges with large language model-based iterative personalization: A field experiment on electricity and hot-water conservation

arXiv:2604.03881v1 Announce Type: cross Abstract: Nudging is widely used to promote behavioral change, but its effectiveness is often limited when recipients must repeatedly translate feedback into workable next steps under changing circumstances. Large language models (LLMs) may help reduce part of this cognitive work by generating personalized guidance and updating it iteratively across intervention rounds. We developed an LLM agent for iterative personalization and tested it in a three-arm randomized experiment among 233 university residents in China, using daily electricity and shower hot-water conservation as objectively measured cases differing in friction. LLM-personalized nudges (T2) produced the largest conservation effects, while image-enhanced conventional nudges (T1) and text-based conventional nudges (C) showed similar outcomes (omnibus p = 0.009). Relative to C, T2 reduced electricity consumption by 0.56 kWh per room-day (p = 0.014), corresponding to an 18.3 percentage-point higher adjusted saving rate. This advantage emerged within the first two intervention rounds, alongside iterative updating of personalized guidance, and persisted thereafter. Hot-water outcomes followed the same direction but were smaller, less precisely estimated, and attenuated over time, consistent with stronger friction in this domain. LLM-personalized nudges emphasized prospective and context-specific guidance and were associated with higher participant engagement. This study provides field evidence that LLM-based iterative personalization can enhance behavioral nudging, with behavioral friction as a potential boundary condition. Larger trials and extension to more behaviors are warranted.

Uncertainty as a Planning Signal: Multi-Turn Decision Making for Goal-Oriented Conversation

arXiv:2604.03924v1 Announce Type: cross Abstract: Goal-oriented conversational systems require making sequential decisions under uncertainty about the user's intent, where the algorithm must balance information acquisition and target commitment over multiple turns. Existing approaches address this challenge from different perspectives: structured methods enable multi-step planning but rely on predefined schemas, while LLM-based approaches support flexible interactions but lack long-horizon decision making, resulting in poor coordination between information acquisition and target commitment. To address this limitation, we formulate goal-oriented conversation as an uncertainty-aware sequential decision problem, where uncertainty serves as a guiding signal for multi-turn decision making. We propose a Conversation Uncertainty-aware Planning framework (CUP) that integrates language models with structured planning: a language model proposes feasible actions, and a planner evaluates their long-term impact on uncertainty reduction. Experiments on multiple conversational benchmarks show that CUP consistently improves success rates while requiring fewer interaction turns. Further analysis demonstrates that uncertainty-aware planning contributes to more efficient information acquisition and earlier confident commitment.

How AI Aggregation Affects Knowledge

arXiv:2604.04906v1 Announce Type: cross Abstract: Artificial intelligence (AI) changes social learning when aggregated outputs become training data for future predictions. To study this, we extend the DeGroot model by introducing an AI aggregator that trains on population beliefs and feeds synthesized signals back to agents. We define the learning gap as the deviation of long-run beliefs from the efficient benchmark, allowing us to capture how AI aggregation affects learning. Our main result identifies a threshold in the speed of updating: when the aggregator updates too quickly, there is no positive-measure set of training weights that robustly improves learning across a broad class of environments, whereas such weights exist when updating is sufficiently slow. We then compare global and local architectures. Local aggregators trained on proximate or topic-specific data robustly improve learning in all environments. Consequently, replacing specialized local aggregators with a single global aggregator worsens learning in at least one dimension of the state.

Autonomous Agents for Scientific Discovery: Orchestrating Scientists, Language, Code, and Physics

arXiv:2510.09901v2 Announce Type: replace Abstract: Computing has long served as a cornerstone of scientific discovery. Recently, a paradigm shift has emerged with the rise of large language models (LLMs), introducing autonomous systems, referred to as agents, that accelerate discovery across varying levels of autonomy. These language agents provide a flexible and versatile framework that orchestrates interactions with human scientists, natural language, computer language and code, and physics. This paper presents our view and vision of LLM-based scientific agents and their growing role in transforming the scientific discovery lifecycle, from hypothesis discovery, experimental design and execution, to result analysis and refinement. We critically examine current methodologies, emphasizing key innovations, practical achievements, and outstanding limitations. Additionally, we identify open research challenges and outline promising directions for building more robust, generalizable, and adaptive scientific agents. Our analysis highlights the transformative potential of autonomous agents to accelerate scientific discovery across diverse domains.
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