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Shu Quan

Publications and source records attributed to Shu Quan.

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Dense Clinical Contrasts Enhance Medical Knowledge Updating in Large Language Models

Medical knowledge changes continually, making large language models vulnerable to relying on outdated yet clinically plausible information. We study whether the format of supervision affects medical knowledge updating under a matched training-budget setting. We introduce SEER-Bench, a temporally anchored oncology-staging benchmark curated from the latest versioned SEER Research Data release, and render identical medical update events from NCCN oncology guidelines into four supervision formats: EMQ, MSQ, FITB, and SAQ. Across SEER-Bench and HealthBench Professional, EMQ gives the most stable external transfer and retention among same-budget SFT variants. With EMQ supervision, the updated 4B model produces competitive results on temporally anchored oncology staging, reaching 64.8% answer accuracy and 59.6% rationale accuracy on SEER-Bench. Diagnostic analyses suggest that EMQ exposes denser clinical contrast signals while preserving discriminative representations with smaller movement from the base model. These results show that medical knowledge updating depends not only on the update algorithm, but also on how knowledge is structured as supervision.

cs.AI

A Blind Spot in Alignment: Quantifying Biosecurity Risks in Large Language Models

Large Language Models (LLMs) are accelerating biological research, yet this same capability poses a critical biosecurity threat: models that assist in protein engineering can equally be prompted to generate predicted toxin-like sequences, potentially lowering the barrier to biological misuse. Current safety evaluations, however, operate in natural language and cannot determine whether a model-generated amino acid sequence is biological gibberish or a computational risk signal. To address this evaluation blind spot, we introduce SPIKE-Bench, coupling 631 curated toxin-design prompts across seven functional categories with the SPIKE funnel, a three-stage protocol that filters output through compliance, biological plausibility, and predicted toxicity, producing stage-level diagnostics and an aggregate function-aware metric: the Functional Harmfulness Rate (FHR). An audit of 32 LLMs reveals that most models freely comply with toxin-design requests; FHR is driven primarily by biological generation capability rather than safety alignment, reaching 50.7%; and Refusal Rate fails to predict functional risk. As a first step toward mitigation, we provide BioSafe-Guard, a domain-specialized classifier that substantially reduces predicted functional risk while preserving benign utility. We release SPIKE-Bench and BioSafe-Guard at https://github.com/PKU-Alignment/SPIKE-Bench to support more rigorous biosecurity evaluation of LLMs.

q-bio.QM

Skill-Augmented AI Agents for Medical Research Analysis: An Exploratory Multi-Model Human Evaluation in an NSCLC Transcriptomic Biomarker Task

Background. Large language models and AI agents are increasingly used to support biomedical research, but native model outputs may omit key analytical steps, misuse methods, or overstate conclusions. We evaluated whether autonomous access to a medical research skill package was associated with higher-quality AI-generated transcriptomic research-analysis outputs compared with native AI without skills. Methods. We conducted an exploratory multi-model human evaluation using a non-small cell lung cancer immunotherapy biomarker task. Six model backbones were tested. The evaluation included 21 anonymized outputs: 9 native-AI outputs and 12 skill-augmented outputs generated through an AI agent implementation represented by OpenClaw. Four non-expert biomedical reviewers and two blinded experts evaluated each output, with two ratings from each reviewer type. The primary outcome was expert-rated overall quality. Results. Skill-augmented outputs showed directionally higher expert overall quality than native-AI outputs (mean 5.50 vs 5.11; difference=0.39; bootstrap 95\% CI, -0.04 to 0.90; Welch p=0.156). Non-expert reviewer quality showed the same direction (mean 4.72 vs 4.47; difference=0.26; bootstrap 95\% CI, -0.25 to 0.80; Welch p=0.373). Expert agreement was limited (single-rating ICC=-0.15), and model-specific effects were descriptive and heterogeneous. Conclusions. Autonomous skill access showed a directional quality signal in this exploratory sample, but the signal was smaller than expert-rating noise and should not be interpreted as confirmatory evidence. The findings primarily motivate larger evaluations of skill-augmented AI agents with stronger reliability controls, platform replication, and biological-validity assessment.

cs.AI