Shuang Zhou

Shuang Zhou, Zidu Xu, Mian Zhang et al.

Automatic disease diagnosis has become increasingly valuable in clinical practice. The advent of large language models (LLMs) has catalyzed a paradigm shift in artificial intelligence, with growing evidence supporting the efficacy of LLMs in diagnostic tasks. Despite the increasing attention in this field, a holistic view is still lacking. Many critical aspects remain unclear, such as the diseases and clinical data to which LLMs have been applied, the LLM techniques employed, and the evaluation methods used. In this article, we perform a comprehensive review of LLM-based methods for disease diagnosis. Our review examines the existing literature across various dimensions, including disease types and associated clinical specialties, clinical data, LLM techniques, and evaluation methods. Additionally, we offer recommendations for applying and evaluating LLMs for diagnostic tasks. Furthermore, we assess the limitations of current research and discuss future directions. To our knowledge, this is the first comprehensive review for LLM-based disease diagnosis.

Shuang Zhou, Mingquan Lin, Sirui Ding et al.

Automatic differential diagnosis (DDx) is an essential medical task that generates a list of potential diseases as differentials based on patient symptom descriptions. In practice, interpreting these differential diagnoses yields significant value but remains under-explored. Given the powerful capabilities of large language models (LLMs), we investigated using LLMs for interpretable DDx. Specifically, we curated the first DDx dataset with expert-derived interpretation on 570 clinical notes. Besides, we proposed Dual-Inf, a novel framework that enabled LLMs to conduct bidirectional inference (i.e., from symptoms to diagnoses and vice versa) for DDx interpretation. Both human and automated evaluation validated its efficacy in predicting and elucidating differentials across four base LLMs. In addition, Dual-Inf could reduce interpretation errors and hold promise for rare disease explanations. To the best of our knowledge, it is the first work that customizes LLMs for DDx explanation and comprehensively evaluates their interpretation performance. Overall, our study bridges a critical gap in DDx interpretation and enhances clinical decision-making.

Zaifu Zhan, Shuang Zhou, Mingchen Li et al.

\textbf{Objective:} We aimed to develop an advanced multi-task large language model (LLM) framework to extract multiple types of information about dietary supplements (DS) from clinical records. \textbf{Methods:} We used four core DS information extraction tasks - namely, named entity recognition (NER: 2,949 clinical sentences), relation extraction (RE: 4,892 sentences), triple extraction (TE: 2,949 sentences), and usage classification (UC: 2,460 sentences) as our multitasks. We introduced a novel Retrieval-Augmented Multi-task Information Extraction (RAMIE) Framework, including: 1) employed instruction fine-tuning techniques with task-specific prompts, 2) trained LLMs for multiple tasks with improved storage efficiency and lower training costs, and 3) incorporated retrieval augmentation generation (RAG) techniques by retrieving similar examples from the training set. We compared RAMIE's performance to LLMs with instruction fine-tuning alone and conducted an ablation study to assess the contributions of multi-task learning and RAG to improved multitasking performance. \textbf{Results:} With the aid of the RAMIE framework, Llama2-13B achieved an F1 score of 87.39 (3.51\% improvement) on the NER task and demonstrated outstanding performance on the RE task with an F1 score of 93.74 (1.15\% improvement). For the TE task, Llama2-7B scored 79.45 (14.26\% improvement), and MedAlpaca-7B achieved the highest F1 score of 93.45 (0.94\% improvement) on the UC task. The ablation study revealed that while MTL increased efficiency with a slight trade-off in performance, RAG significantly boosted overall accuracy. \textbf{Conclusion:} This study presents a novel RAMIE framework that demonstrates substantial improvements in multi-task information extraction for DS-related data from clinical records. Our framework can potentially be applied to other domains.

Zaifu Zhan, Shuang Zhou, Huixue Zhou et al.

The advancement of Large Language Models (LLMs) has significantly impacted biomedical Natural Language Processing (NLP), enhancing tasks such as named entity recognition, relation extraction, event extraction, and text classification. In this context, the DeepSeek series of models have shown promising potential in general NLP tasks, yet their capabilities in the biomedical domain remain underexplored. This study evaluates multiple DeepSeek models (Distilled-DeepSeek-R1 series and Deepseek-LLMs) across four key biomedical NLP tasks using 12 datasets, benchmarking them against state-of-the-art alternatives (Llama3-8B, Qwen2.5-7B, Mistral-7B, Phi-4-14B, Gemma-2-9B). Our results reveal that while DeepSeek models perform competitively in named entity recognition and text classification, challenges persist in event and relation extraction due to precision-recall trade-offs. We provide task-specific model recommendations and highlight future research directions. This evaluation underscores the strengths and limitations of DeepSeek models in biomedical NLP, guiding their future deployment and optimization.

Shuang Zhou, Wenya Xie, Jiaxi Li et al.

As large language models (LLMs) become increasingly integrated into clinical decision-making, ensuring transparent and trustworthy reasoning is essential. However, existing evaluation strategies of LLMs' medical reasoning capability either suffer from unsatisfactory assessment or poor scalability, and a rigorous benchmark remains lacking. To address this, we introduce MedThink-Bench, a benchmark designed for rigorous, explainable, and scalable assessment of LLMs' medical reasoning. MedThink-Bench comprises 500 challenging questions across ten medical domains, each annotated with expert-crafted step-by-step rationales. Building on this, we propose LLM-w-Ref, a novel evaluation framework that leverages fine-grained rationales and LLM-as-a-Judge mechanisms to assess intermediate reasoning with expert-level fidelity while maintaining scalability. Experiments show that LLM-w-Ref exhibits a strong positive correlation with expert judgments. Benchmarking twelve state-of-the-art LLMs, we find that smaller models (e.g., MedGemma-27B) can surpass larger proprietary counterparts (e.g., OpenAI-o3). Overall, MedThink-Bench offers a foundational tool for evaluating LLMs' medical reasoning, advancing their safe and responsible deployment in clinical practice.

Zaifu Zhan, Shuang Zhou, Min Zeng et al.

Large language models have demonstrated remarkable capabilities in biomedical natural language processing, yet their rapid growth in size and computational requirements present a major barrier to adoption in healthcare settings where data privacy precludes cloud deployment and resources are limited. In this study, we systematically evaluated the impact of quantization on 12 state-of-the-art large language models, including both general-purpose and biomedical-specific models, across eight benchmark datasets covering four key tasks: named entity recognition, relation extraction, multi-label classification, and question answering. We show that quantization substantially reduces GPU memory requirements-by up to 75%-while preserving model performance across diverse tasks, enabling the deployment of 70B-parameter models on 40GB consumer-grade GPUs. In addition, domain-specific knowledge and responsiveness to advanced prompting methods are largely maintained. These findings provide significant practical and guiding value, highlighting quantization as a practical and effective strategy for enabling the secure, local deployment of large yet high-capacity language models in biomedical contexts, bridging the gap between technical advances in AI and real-world clinical translation.

Zhi Chang, Chukwudi Obite, Shuang Zhou et al.

Motivated by deep neural networks, the deep Gaussian process (DGP) generalizes the standard GP by stacking multiple layers of GPs. Despite the enhanced expressiveness, GP, as an $L_2$ regularization prior, tends to be over-smooth and sub-optimal for inhomogeneous subjects, such as images with edges. Recently, Q-exponential process (Q-EP) has been proposed as an $L_q$ relaxation to GP and demonstrated with more desirable regularization properties through a parameter $q>0$ with $q=2$ corresponding to GP. Sharing the similar tractability of posterior and predictive distributions with GP, Q-EP can also be stacked to improve its modeling flexibility. In this paper, we generalize Q-EP to deep Q-EP to enjoy both proper regularization and improved expressiveness. The generalization is realized by introducing shallow Q-EP as a latent variable model and then building a hierarchy of the shallow Q-EP layers. Sparse approximation by inducing points and scalable variational strategy are applied to facilitate the inference. We demonstrate the numerical advantages of the proposed deep Q-EP model by comparing with multiple state-of-the-art deep probabilistic models.

Sean Plummer, Shuang Zhou, Anirban Bhattacharya et al.

Transformation-based methods have been an attractive approach in non-parametric inference for problems such as unconditional and conditional density estimation due to their unique hierarchical structure that models the data as flexible transformation of a set of common latent variables. More recently, transformation-based models have been used in variational inference (VI) to construct flexible implicit families of variational distributions. However, their use in both non-parametric inference and variational inference lacks theoretical justification. We provide theoretical justification for the use of non-linear latent variable models (NL-LVMs) in non-parametric inference by showing that the support of the transformation induced prior in the space of densities is sufficiently large in the $L_1$ sense. We also show that, when a Gaussian process (GP) prior is placed on the transformation function, the posterior concentrates at the optimal rate up to a logarithmic factor. Adopting the flexibility demonstrated in the non-parametric setting, we use the NL-LVM to construct an implicit family of variational distributions, deemed GP-IVI. We delineate sufficient conditions under which GP-IVI achieves optimal risk bounds and approximates the true posterior in the sense of the Kullback-Leibler divergence. To the best of our knowledge, this is the first work on providing theoretical guarantees for implicit variational inference.