Yuzhang Xie

Mingyang Wei, Dehai Min, Zewen Liu et al.

Reliable epidemiological reasoning requires synthesizing study evidence to infer disease burden, transmission dynamics, and intervention effects at the population level. Existing medical question answering benchmarks primarily emphasize clinical knowledge or patient-level reasoning, yet few systematically evaluate evidence-grounded epidemiological inference. We present EpiQAL, the first diagnostic benchmark for epidemiological question answering across diverse diseases, comprising three subsets built from open-access literature. The three subsets progressively test factual recall, multi-step inference, and conclusion reconstruction under incomplete information, and are constructed through a quality-controlled pipeline combining taxonomy guidance, multi-model verification, and difficulty screening. Experiments on fourteen models spanning open-source and proprietary systems reveal that current LLMs show limited performance on epidemiological reasoning, with multi-step inference posing the greatest challenge. Model rankings shift across subsets, and scale alone does not predict success. Chain-of-Thought prompting benefits multi-step inference but yields mixed results elsewhere. EpiQAL provides fine-grained diagnostic signals for evidence-grounding, inferential reasoning, and conclusion reconstruction.

Yuzhang Xie, Jiaying Lu, Joyce Ho et al.

Linking (aligning) biomedical concepts across diverse data sources enables various integrative analyses, but it is challenging due to the discrepancies in concept naming conventions. Various strategies have been developed to overcome this challenge, such as those based on string-matching rules, manually crafted thesauri, and machine learning models. However, these methods are constrained by limited prior biomedical knowledge and can hardly generalize beyond the limited amounts of rules, thesauri, or training samples. Recently, large language models (LLMs) have exhibited impressive results in diverse biomedical NLP tasks due to their unprecedentedly rich prior knowledge and strong zero-shot prediction abilities. However, LLMs suffer from issues including high costs, limited context length, and unreliable predictions. In this research, we propose PromptLink, a novel biomedical concept linking framework that leverages LLMs. It first employs a biomedical-specialized pre-trained language model to generate candidate concepts that can fit in the LLM context windows. Then it utilizes an LLM to link concepts through two-stage prompts, where the first-stage prompt aims to elicit the biomedical prior knowledge from the LLM for the concept linking task and the second-stage prompt enforces the LLM to reflect on its own predictions to further enhance their reliability. Empirical results on the concept linking task between two EHR datasets and an external biomedical KG demonstrate the effectiveness of PromptLink. Furthermore, PromptLink is a generic framework without reliance on additional prior knowledge, context, or training data, making it well-suited for concept linking across various types of data sources. The source code is available at https://github.com/constantjxyz/PromptLink.

Ziyang Zhang, Hejie Cui, Ran Xu et al.

The growing availability of well-organized Electronic Health Records (EHR) data has enabled the development of various machine learning models towards disease risk prediction. However, existing risk prediction methods overlook the heterogeneity of complex diseases, failing to model the potential disease subtypes regarding their corresponding patient visits and clinical concept subgroups. In this work, we introduce TACCO, a novel framework that jointly discovers clusters of clinical concepts and patient visits based on a hypergraph modeling of EHR data. Specifically, we develop a novel self-supervised co-clustering framework that can be guided by the risk prediction task of specific diseases. Furthermore, we enhance the hypergraph model of EHR data with textual embeddings and enforce the alignment between the clusters of clinical concepts and patient visits through a contrastive objective. Comprehensive experiments conducted on the public MIMIC-III dataset and Emory internal CRADLE dataset over the downstream clinical tasks of phenotype classification and cardiovascular risk prediction demonstrate an average 31.25% performance improvement compared to traditional ML baselines and a 5.26% improvement on top of the vanilla hypergraph model without our co-clustering mechanism. In-depth model analysis, clustering results analysis, and clinical case studies further validate the improved utilities and insightful interpretations delivered by TACCO. Code is available at https://github.com/PericlesHat/TACCO.

Yuzhang Xie, Yuhua Wu, Ruiyu Wang et al.

Atrial fibrillation (AF) is a major complication following embolic stroke of undetermined source (ESUS), elevating the risk of recurrent stroke and mortality. Early identification is clinically important, yet existing tools face limitations in accuracy, scalability, and cost. Machine learning (ML) offers promise but is hindered by small ESUS cohorts and high-dimensional medical features. To address these challenges, we introduce supervised and unsupervised hypergraph-based pre-training strategies to improve AF prediction in ESUS patients. We first pre-train hypergraph-based patient embedding models on a large stroke cohort (7,780 patients) to capture salient features and higher-order interactions. The resulting embeddings are transferred to a smaller ESUS cohort (510 patients), reducing feature dimensionality while preserving clinically meaningful information, enabling effective prediction with lightweight models. Experiments show that both pre-training approaches outperform traditional models trained on raw data, improving accuracy and robustness. This framework offers a scalable and efficient solution for AF risk prediction after stroke.

Guanchen Wu, Zhe Huang, Yuzhang Xie et al.

Reliable Alzheimer's disease (AD) diagnosis increasingly relies on multimodal assessments combining structural Magnetic Resonance Imaging (MRI) and Electronic Health Records (EHR). However, deploying these models is bottlenecked by modality missingness, as MRI scans are expensive and frequently unavailable in many patient cohorts. Furthermore, synthesizing de novo 3D anatomical scans from sparse, high-dimensional tabular records is technically challenging and poses severe clinical risks. To address this, we introduce MIRAGE, a novel framework that reframes the missing-MRI problem as an anatomy-guided cross-modal latent distillation task. First, MIRAGE leverages a Biomedical Knowledge Graph (KG) and Graph Attention Networks to map heterogeneous EHR variables into a unified embedding space that can be propagated from cohorts with real MRIs to cohorts without them. To bridge the semantic gap and enforce physical spatial awareness, we employ a frozen pre-trained 3D U-Net decoder strictly as an auxiliary regularization engine. Supported by a novel cohort-aggregated skip feature compensation strategy, this decoder acts as a rigorous structural penalty, forcing 1D latent representations to encode biologically plausible, macro-level pathological semantics. By exclusively utilizing this distilled "diagnostic-surrogate" representation during inference, MIRAGE completely bypasses computationally expensive 3D voxel reconstruction. Experiments demonstrate that our framework successfully bridges the missing-modality gap, improving the AD classification rate by 13% compared to unimodal baselines in cohorts without real MRIs.

Mingchen Shao, Yuzhang Xie, Carl Yang et al.

Accurate extraction of Alzheimer's Disease and Related Dementias (ADRD) phenotypes from electronic health records (EHR) is critical for early-stage detection and disease staging. However, this information is usually embedded in unstructured textual data rather than tabular data, making it difficult to be extracted accurately. We therefore propose LLM-MINE, a Large Language Model-based phenotype mining framework for automatic extraction of ADRD phenotypes from clinical notes. Using two expert-defined phenotype lists, we evaluate the extracted phenotypes by examining their statistical significance across cohorts and their utility for unsupervised disease staging. Chi-square analyses confirm statistically significant phenotype differences across cohorts, with memory impairment being the strongest discriminator. Few-shot prompting with the combined phenotype lists achieves the best clustering performance (ARI=0.290, NMI=0.232), substantially outperforming biomedical NER and dictionary-based baselines. Our results demonstrate that LLM-based phenotype extraction is a promising tool for discovering clinically meaningful ADRD signals from unstructured notes.

Yuzhang Xie, Xu Han, Ran Xu et al.

Knowledge graphs (KGs) are important products of the semantic web, which are widely used in various application domains. Healthcare is one of such domains where KGs are intensively used, due to the high requirement for knowledge accuracy and interconnected nature of healthcare data. However, KGs storing general factual information often lack the ability to account for important contexts of the knowledge such as the status of specific patients, which are crucial in precision healthcare. Meanwhile, electronic health records (EHRs) provide rich personal data, including various diagnoses and medications, which provide natural contexts for general KGs. In this paper, we propose HypKG, a framework that integrates patient information from EHRs into KGs to generate contextualized knowledge representations for accurate healthcare predictions. Using advanced entity-linking techniques, we connect relevant knowledge from general KGs with patient information from EHRs, and then utilize a hypergraph model to "contextualize" the knowledge with the patient information. Finally, we employ hypergraph transformers guided by downstream prediction tasks to jointly learn proper contextualized representations for both KGs and patients, fully leveraging existing knowledge in KGs and patient contexts in EHRs. In experiments using a large biomedical KG and two real-world EHR datasets, HypKG demonstrates significant improvements in healthcare prediction tasks across multiple evaluation metrics. Additionally, by integrating external contexts, HypKG can learn to adjust the representations of entities and relations in KG, potentially improving the quality and real-world utility of knowledge.

Balu Bhasuran, Qiao Jin, Yuzhang Xie et al.

Differential diagnosis is crucial for medicine as it helps healthcare providers systematically distinguish between conditions that share similar symptoms. This study assesses the impact of lab test results on differential diagnoses (DDx) made by large language models (LLMs). Clinical vignettes from 50 case reports from PubMed Central were created incorporating patient demographics, symptoms, and lab results. Five LLMs GPT-4, GPT-3.5, Llama-2-70b, Claude-2, and Mixtral-8x7B were tested to generate Top 10, Top 5, and Top 1 DDx with and without lab data. A comprehensive evaluation involving GPT-4, a knowledge graph, and clinicians was conducted. GPT-4 performed best, achieving 55% accuracy for Top 1 diagnoses and 60% for Top 10 with lab data, with lenient accuracy up to 80%. Lab results significantly improved accuracy, with GPT-4 and Mixtral excelling, though exact match rates were low. Lab tests, including liver function, metabolic/toxicology panels, and serology/immune tests, were generally interpreted correctly by LLMs for differential diagnosis.