MingKe You

Xi Chen, Hongru Zhou, Huahui Yi et al.

Missed and delayed diagnosis remains a major challenge in rare disease care. At the initial clinical encounters, physicians assess rare disease risk using only limited information under high uncertainty. When high-risk patients are not recognised at this stage, targeted diagnostic testing is often not initiated, resulting in missed diagnosis. Existing primary care triage processes are structurally insufficient to reliably identify patients with rare diseases at initial clinical presentation and universal screening is needed to reduce diagnostic delay. Here we present RareAlert, an early screening system which predict patient-level rare disease risk from routinely available primary-visit information. RareAlert integrates reasoning generated by ten LLMs, calibrates and weights these signals using machine learning, and distils the aligned reasoning into a single locally deployable model. To develop and evaluate RareAlert, we curated RareBench, a real-world dataset of 158,666 cases covering 33 Orphanet disease categories and more than 7,000 rare conditions, including both rare and non-rare presentations. The results showed that rare disease identification can be reconceptualised as a universal uncertainty resolution process applied to the general patient population. On an independent test set, RareAlert, a Qwen3-4B based model trained with calibrated reasoning signals, achieved an AUC of 0.917, outperforming the best machine learning ensemble and all evaluated LLMs, including GPT-5, DeepSeek-R1, Claude-3.7-Sonnet, o3-mini, Gemini-2.5-Pro, and Qwen3-235B. These findings demonstrate the diversity in LLM medical reasoning and the effectiveness of aligning such reasoning in highly uncertain clinical tasks. By incorporating calibrated reasoning into a single model, RareAlert enables accurate, privacy-preserving, and scalable rare disease risk screening suitable for large-scale local deployment.

Weizhi Liu, Xi Chen, Zekun Jiang et al.

Knee osteoarthritis (KOA) affects more than 600 million individuals globally and is associated with significant pain, functional impairment, and disability. While personalized multidisciplinary interventions have the potential to slow disease progression and enhance quality of life, they typically require substantial medical resources and expertise, making them difficult to implement in resource-limited settings. To address this challenge, we developed KOM, a multi-agent system designed to automate KOA evaluation, risk prediction, and treatment prescription. This system assists clinicians in performing essential tasks across the KOA care pathway and supports the generation of tailored management plans based on individual patient profiles, disease status, risk factors, and contraindications. In benchmark experiments, KOM demonstrated superior performance compared to several general-purpose large language models in imaging analysis and prescription generation. A randomized three-arm simulation study further revealed that collaboration between KOM and clinicians reduced total diagnostic and planning time by 38.5% and resulted in improved treatment quality compared to each approach used independently. These findings indicate that KOM could help facilitate automated KOA management and, when integrated into clinical workflows, has the potential to enhance care efficiency. The modular architecture of KOM may also offer valuable insights for developing AI-assisted management systems for other chronic conditions.

Xi Chen, Yang Xu, MingKe You et al.

This study evaluates whether large language models (LLMs) exhibit biases towards medical professionals. Fictitious candidate resumes were created to control for identity factors while maintaining consistent qualifications. Three LLMs (GPT-4, Claude-3-haiku, and Mistral-Large) were tested using a standardized prompt to evaluate resumes for specific residency programs. Explicit bias was tested by changing gender and race information, while implicit bias was tested by changing names while hiding race and gender. Physician data from the Association of American Medical Colleges was used to compare with real-world demographics. 900,000 resumes were evaluated. All LLMs exhibited significant gender and racial biases across medical specialties. Gender preferences varied, favoring male candidates in surgery and orthopedics, while preferring females in dermatology, family medicine, obstetrics and gynecology, pediatrics, and psychiatry. Claude-3 and Mistral-Large generally favored Asian candidates, while GPT-4 preferred Black and Hispanic candidates in several specialties. Tests revealed strong preferences towards Hispanic females and Asian males in various specialties. Compared to real-world data, LLMs consistently chose higher proportions of female and underrepresented racial candidates than their actual representation in the medical workforce. GPT-4, Claude-3, and Mistral-Large showed significant gender and racial biases when evaluating medical professionals for residency selection. These findings highlight the potential for LLMs to perpetuate biases and compromise healthcare workforce diversity if used without proper bias mitigation strategies.

Xi Chen, MingKe You, Li Wang et al.

The efficacy of large language models (LLMs) in domain-specific medicine, particularly for managing complex diseases such as osteoarthritis (OA), remains largely unexplored. This study focused on evaluating and enhancing the clinical capabilities of LLMs in specific domains, using osteoarthritis (OA) management as a case study. A domain specific benchmark framework was developed, which evaluate LLMs across a spectrum from domain-specific knowledge to clinical applications in real-world clinical scenarios. DocOA, a specialized LLM tailored for OA management that integrates retrieval-augmented generation (RAG) and instruction prompts, was developed. The study compared the performance of GPT-3.5, GPT-4, and a specialized assistant, DocOA, using objective and human evaluations. Results showed that general LLMs like GPT-3.5 and GPT-4 were less effective in the specialized domain of OA management, particularly in providing personalized treatment recommendations. However, DocOA showed significant improvements. This study introduces a novel benchmark framework which assesses the domain-specific abilities of LLMs in multiple aspects, highlights the limitations of generalized LLMs in clinical contexts, and demonstrates the potential of tailored approaches for developing domain-specific medical LLMs.