ToxReason: A Benchmark for Mechanistic Chemical Toxicity Reasoning via Adverse Outcome Pathway

Recent advances in large language models (LLMs) have enabled molecular reasoning for property prediction. However, toxicity arises from complex biological mechanisms beyond chemical structure, necessitating mechanistic reasoning for reliable prediction. Despite its importance, current benchmarks fail to systematically evaluate this capability. LLMs can generate fluent but biologically unfaithful explanations, making it difficult to assess whether predicted toxicities are grounded invalid mechanisms. To bridge this gap, we introduce ToxReason, a benchmark grounded in the Adverse Outcome Pathway (AOP) that evaluates organ-level toxicity reasoning across multiple organs. ToxReason integrates experimental drug-target interaction evidence with toxicity labels, requiring models to infer both toxic outcomes and their underlying mechanisms from Molecular Initiating Event (MIE) to Adverse Outcome (AO). Using ToxReason, we evaluate toxicity prediction performance and reasoning quality across diverse LLMs. We find that strong predictive performance does not necessarily imply reliable reasoning. Furthermore, we show that reasoning-aware training improves mechanistic reasoning and, consequently, toxicity prediction performance. Together, these results underscore the necessity of integrating reasoning into both evaluation and training for trustworthy toxicity modeling.

When Choices Become Priors: Contrastive Decoding for Scientific Figure Multiple-Choice QA

Scientific figure multiple-choice question answering (MCQA) requires models to reason over diverse visual evidence, ranging from charts and multipanel figures to microscopy and biomedical images. However, this setting suffers from a distinctive bias: answer choices themselves can act as priors, steering multimodal models toward scientifically plausible options even when the figure supports a different answer. We investigate this failure mode through a simple question: what if decoding explicitly discounts what the model would prefer from text alone, so as to favor figure-grounded evidence? To this end, we propose SCICON, a training-free decoding method that scores each candidate by subtracting a text-only option score from its image-conditioned counterpart. Unlike prior contrastive decoding approaches that mitigate hallucinations by contrasting original inputs with distorted images or perturbed instructions, SCICON directly targets the choice-induced prior encoded in candidate text. Across three scientific figure QA benchmarks and three model backbones, SCICON consistently improves accuracy over standard decoding baselines. These results show that decoding against choice-induced priors is an effective and simple way to improve figure-grounded reasoning in scientific MCQA.

CLAG: Adaptive Memory Organization via Agent-Driven Clustering for Small Language Model Agents

Large language model agents heavily rely on external memory to support knowledge reuse and complex reasoning tasks. Yet most memory systems store experiences in a single global retrieval pool which can gradually dilute or corrupt stored knowledge. This problem is especially pronounced for small language models (SLMs), which are highly vulnerable to irrelevant context. We introduce CLAG, a CLustering-based AGentic memory framework where an SLM agent actively organizes memory by clustering. CLAG employs an SLM-driven router to assign incoming memories to semantically coherent clusters and autonomously generates cluster-specific profiles, including topic summaries and descriptive tags, to establish each cluster as a self-contained functional unit. By performing localized evolution within these structured neighborhoods, CLAG effectively reduces cross-topic interference and enhances internal memory density. During retrieval, the framework utilizes a two-stage process that first filters relevant clusters via their profiles, thereby excluding distractors and reducing the search space. Experiments on multiple QA datasets with three SLM backbones show that CLAG consistently improves answer quality and robustness over prior memory systems for agents, remaining lightweight and efficient.

ATTNSOM: Learning Cross-Isoform Attention for Cytochrome P450 Site-of-Metabolism

Identifying metabolic sites where cytochrome P450 enzymes metabolize small-molecule drugs is essential for drug discovery. Although existing computational approaches have been proposed for site-of-metabolism prediction, they typically ignore cytochrome P450 isoform identity or model isoforms independently, thereby failing to fully capture inherent cross-isoform metabolic patterns. In addition, prior evaluations often rely on top-k metrics, where false positive atoms may be included among the top predictions, underscoring the need for complementary metrics that more directly assess binary atom-level discrimination under severe class imbalance. We propose ATTNSOM, an atom-level site-of-metabolism prediction framework that integrates intrinsic molecular reactivity with cross-isoform relationships. The model combines a shared graph encoder, molecule-conditioned atom representations, and a cross-attention mechanism to capture correlated metabolic patterns across cytochrome P450 isoforms. The model is evaluated on two benchmark datasets annotated with site-of-metabolism labels at atom resolution. Across these benchmarks, the model achieves consistently strong top-k performance across multiple cytochrome P450 isoforms. Relative to ablated variants, the model yields higher Matthews correlation coefficient, indicating improved discrimination of true metabolic sites. These results support the importance of explicitly modeling cross-isoform relationships for site-of-metabolism prediction. The code and datasets are available at https://github.com/dmis-lab/ATTNSOM.

Benchmarking Direct Preference Optimization for Medical Large Vision-Language Models

Large Vision-Language Models (LVLMs) hold significant promise for medical applications, yet their deployment is often constrained by insufficient alignment and reliability. While Direct Preference Optimization (DPO) has emerged as a potent framework for refining model responses, its efficacy in high-stakes medical contexts remains underexplored, lacking the rigorous empirical groundwork necessary to guide future methodological advances. To bridge this gap, we present the first comprehensive examination of diverse DPO variants within the medical domain, evaluating nine distinct formulations across two medical LVLMs: LLaVA-Med and HuatuoGPT-Vision. Our results reveal several critical limitations: current DPO approaches often yield inconsistent gains over supervised fine-tuning, with their efficacy varying significantly across different tasks and backbones. Furthermore, they frequently fail to resolve fundamental visual misinterpretation errors. Building on these insights, we present a targeted preference construction strategy as a proof-of-concept that explicitly addresses visual misinterpretation errors frequently observed in existing DPO models. This design yields a 3.6% improvement over the strongest existing DPO baseline on visual question-answering tasks. To support future research, we release our complete framework, including all training data, model checkpoints, and our codebase at https://github.com/dmis-lab/med-vlm-dpo.

SCRIPTMIND: Crime Script Inference and Cognitive Evaluation for LLM-based Social Engineering Scam Detection System

Social engineering scams increasingly employ personalized, multi-turn deception, exposing the limits of traditional detection methods. While Large Language Models (LLMs) show promise in identifying deception, their cognitive assistance potential remains underexplored. We propose ScriptMind, an integrated framework for LLM-based scam detection that bridges automated reasoning and human cognition. It comprises three components: the Crime Script Inference Task (CSIT) for scam reasoning, the Crime Script-Aware Inference Dataset (CSID) for fine-tuning small LLMs, and the Cognitive Simulation-based Evaluation of Social Engineering Defense (CSED) for assessing real-time cognitive impact. Using 571 Korean phone scam cases, we built 22,712 structured scammer-sequence training instances. Experimental results show that the 11B small LLM fine-tuned with ScriptMind outperformed GPT-4o by 13%, achieving superior performance over commercial models in detection accuracy, false-positive reduction, scammer utterance prediction, and rationale quality. Moreover, in phone scam simulation experiments, it significantly enhanced and sustained users' suspicion levels, improving their cognitive awareness of scams. ScriptMind represents a step toward human-centered, cognitively adaptive LLMs for scam defense.

HiRef: Leveraging Hierarchical Ontology and Network Refinement for Robust Medication Recommendation

Medication recommendation is a crucial task for assisting physicians in making timely decisions from longitudinal patient medical records. However, real-world EHR data present significant challenges due to the presence of rarely observed medical entities and incomplete records that may not fully capture the clinical ground truth. While data-driven models trained on longitudinal Electronic Health Records often achieve strong empirical performance, they struggle to generalize under missing or novel conditions, largely due to their reliance on observed co-occurrence patterns. To address these issues, we propose Hierarchical Ontology and Network Refinement for Robust Medication Recommendation (HiRef), a unified framework that combines two complementary structures: (i) the hierarchical semantics encoded in curated medical ontologies, and (ii) refined co-occurrence patterns derived from real-world EHRs. We embed ontology entities in hyperbolic space, which naturally captures tree-like relationships and enables knowledge transfer through shared ancestors, thereby improving generalizability to unseen codes. To further improve robustness, we introduce a prior-guided sparse regularization scheme that refines the EHR co-occurrence graph by suppressing spurious edges while preserving clinically meaningful associations. Our model achieves strong performance on EHR benchmarks (MIMIC-III and MIMIC-IV) and maintains high accuracy under simulated unseen-code settings. Extensive experiments with comprehensive ablation studies demonstrate HiRef's resilience to unseen medical codes, supported by in-depth analyses of the learned sparsified graph structure and medical code embeddings.

Outlier-Safe Pre-Training for Robust 4-Bit Quantization of Large Language Models

Extreme activation outliers in Large Language Models (LLMs) critically degrade quantization performance, hindering efficient on-device deployment. While channel-wise operations and adaptive gradient scaling are recognized causes, practical mitigation remains challenging. We introduce Outlier-Safe Pre-Training (OSP), a practical guideline that proactively prevents outlier formation rather than relying on post-hoc mitigation. OSP combines three key innovations: (1) the Muon optimizer, eliminating privileged bases while maintaining training efficiency; (2) Single-Scale RMSNorm, preventing channel-wise amplification; and (3) a learnable embedding projection, redistributing activation magnitudes originating from embedding matrices. We validate OSP by training a 1.4B-parameter model on 1 trillion tokens, which is the first production-scale LLM trained without such outliers. Under aggressive 4-bit quantization, our OSP model achieves a 35.7 average score across 10 benchmarks (compared to 26.5 for an Adam-trained model), with only a 2% training overhead. Remarkably, OSP models exhibit near-zero excess kurtosis (0.04) compared to extreme values (1818.56) in standard models, fundamentally altering LLM quantization behavior. Our work demonstrates that outliers are not inherent to LLMs but are consequences of training strategies, paving the way for more efficient LLM deployment. The source code and pretrained checkpoints are available at https://github.com/dmis-lab/Outlier-Safe-Pre-Training.

Med-PRM: Medical Reasoning Models with Stepwise, Guideline-verified Process Rewards

Large language models have shown promise in clinical decision making, but current approaches struggle to localize and correct errors at specific steps of the reasoning process. This limitation is critical in medicine, where identifying and addressing reasoning errors is essential for accurate diagnosis and effective patient care. We introduce Med-PRM, a process reward modeling framework that leverages retrieval-augmented generation to verify each reasoning step against established medical knowledge bases. By verifying intermediate reasoning steps with evidence retrieved from clinical guidelines and literature, our model can precisely assess the reasoning quality in a fine-grained manner. Evaluations on five medical QA benchmarks and two open-ended diagnostic tasks demonstrate that Med-PRM achieves state-of-the-art performance, with improving the performance of base models by up to 13.50% using Med-PRM. Moreover, we demonstrate the generality of Med-PRM by integrating it in a plug-and-play fashion with strong policy models such as Meerkat, achieving over 80\% accuracy on MedQA for the first time using small-scale models of 8 billion parameters. Our code and data are available at: https://med-prm.github.io/

Does Time Have Its Place? Temporal Heads: Where Language Models Recall Time-specific Information

While the ability of language models to elicit facts has been widely investigated, how they handle temporally changing facts remains underexplored. We discover Temporal Heads, specific attention heads primarily responsible for processing temporal knowledge through circuit analysis. We confirm that these heads are present across multiple models, though their specific locations may vary, and their responses differ depending on the type of knowledge and its corresponding years. Disabling these heads degrades the model's ability to recall time-specific knowledge while maintaining its general capabilities without compromising time-invariant and question-answering performances. Moreover, the heads are activated not only numeric conditions ("In 2004") but also textual aliases ("In the year ..."), indicating that they encode a temporal dimension beyond simple numerical representation. Furthermore, we expand the potential of our findings by demonstrating how temporal knowledge can be edited by adjusting the values of these heads.