A Survey on Medical Large Language Models: Technology, Application, Trustworthiness, and Future Directions

Large language models (LLMs), such as GPT series models, have received substantial attention due to their impressive capabilities for generating and understanding human-level language. More recently, LLMs have emerged as an innovative and powerful adjunct in the medical field, transforming traditional practices and heralding a new era of enhanced healthcare services. This survey provides a comprehensive overview of Medical Large Language Models (Med-LLMs), outlining their evolution from general to the medical-specific domain (i.e, Technology and Application), as well as their transformative impact on healthcare (e.g., Trustworthiness and Safety). Concretely, starting from the fundamental history and technology of LLMs, we first delve into the progressive adaptation and refinements of general LLM models in the medical domain, especially emphasizing the advanced algorithms that boost the LLMs' performance in handling complicated medical environments, including clinical reasoning, knowledge graph, retrieval-augmented generation, human alignment, and multi-modal learning. Secondly, we explore the extensive applications of Med-LLMs across domains such as clinical decision support, report generation, and medical education, illustrating their potential to streamline healthcare services and augment patient outcomes. Finally, recognizing the imperative and responsible innovation, we discuss the challenges of ensuring fairness, accountability, privacy, and robustness in Med-LLMs applications. Finally, we conduct a concise discussion for anticipating possible future trajectories of Med-LLMs, identifying avenues for the prudent expansion of Med-LLMs. By consolidating above-mentioned insights, this review seeks to provide a comprehensive investigation of the potential strengths and limitations of Med-LLMs for professionals and researchers, ensuring a responsible landscape in the healthcare setting.

Towards Automatic Evaluation for LLMs' Clinical Capabilities: Metric, Data, and Algorithm

Large language models (LLMs) are gaining increasing interests to improve clinical efficiency for medical diagnosis, owing to their unprecedented performance in modelling natural language. Ensuring the safe and reliable clinical applications, the evaluation of LLMs indeed becomes critical for better mitigating the potential risks, e.g., hallucinations. However, current evaluation methods heavily rely on labor-intensive human participation to achieve human-preferred judgements. To overcome this challenge, we propose an automatic evaluation paradigm tailored to assess the LLMs' capabilities in delivering clinical services, e.g., disease diagnosis and treatment. The evaluation paradigm contains three basic elements: metric, data, and algorithm. Specifically, inspired by professional clinical practice pathways, we formulate a LLM-specific clinical pathway (LCP) to define the clinical capabilities that a doctor agent should possess. Then, Standardized Patients (SPs) from the medical education are introduced as the guideline for collecting medical data for evaluation, which can well ensure the completeness of the evaluation procedure. Leveraging these steps, we develop a multi-agent framework to simulate the interactive environment between SPs and a doctor agent, which is equipped with a Retrieval-Augmented Evaluation (RAE) to determine whether the behaviors of a doctor agent are in accordance with LCP. The above paradigm can be extended to any similar clinical scenarios to automatically evaluate the LLMs' medical capabilities. Applying such paradigm, we construct an evaluation benchmark in the field of urology, including a LCP, a SPs dataset, and an automated RAE. Extensive experiments are conducted to demonstrate the effectiveness of the proposed approach, providing more insights for LLMs' safe and reliable deployments in clinical practice.

Unified Hallucination Detection for Multimodal Large Language Models

Despite significant strides in multimodal tasks, Multimodal Large Language Models (MLLMs) are plagued by the critical issue of hallucination. The reliable detection of such hallucinations in MLLMs has, therefore, become a vital aspect of model evaluation and the safeguarding of practical application deployment. Prior research in this domain has been constrained by a narrow focus on singular tasks, an inadequate range of hallucination categories addressed, and a lack of detailed granularity. In response to these challenges, our work expands the investigative horizons of hallucination detection. We present a novel meta-evaluation benchmark, MHaluBench, meticulously crafted to facilitate the evaluation of advancements in hallucination detection methods. Additionally, we unveil a novel unified multimodal hallucination detection framework, UNIHD, which leverages a suite of auxiliary tools to validate the occurrence of hallucinations robustly. We demonstrate the effectiveness of UNIHD through meticulous evaluation and comprehensive analysis. We also provide strategic insights on the application of specific tools for addressing various categories of hallucinations.

RJUA-QA: A Comprehensive QA Dataset for Urology

We introduce RJUA-QA, a novel medical dataset for question answering (QA) and reasoning with clinical evidence, contributing to bridge the gap between general large language models (LLMs) and medical-specific LLM applications. RJUA-QA is derived from realistic clinical scenarios and aims to facilitate LLMs in generating reliable diagnostic and advice. The dataset contains 2,132 curated Question-Context-Answer pairs, corresponding about 25,000 diagnostic records and clinical cases. The dataset covers 67 common urological disease categories, where the disease coverage exceeds 97.6\% of the population seeking medical services in urology. Each data instance in RJUA-QA comprises: (1) a question mirroring real patient to inquiry about clinical symptoms and medical conditions, (2) a context including comprehensive expert knowledge, serving as a reference for medical examination and diagnosis, (3) a doctor response offering the diagnostic conclusion and suggested examination guidance, (4) a diagnosed clinical disease as the recommended diagnostic outcome, and (5) clinical advice providing recommendations for medical examination. RJUA-QA is the first medical QA dataset for clinical reasoning over the patient inquiries, where expert-level knowledge and experience are required for yielding diagnostic conclusions and medical examination advice. A comprehensive evaluation is conducted to evaluate the performance of both medical-specific and general LLMs on the RJUA-QA dataset. Our data is are publicly available at \url{https://github.com/alipay/RJU_Ant_QA}.

From Beginner to Expert: Modeling Medical Knowledge into General LLMs

Recently, large language model (LLM) based artificial intelligence (AI) systems have demonstrated remarkable capabilities in natural language understanding and generation. However, these models face a significant challenge when it comes to sensitive applications, such as reasoning over medical knowledge and answering medical questions in a physician-like manner. Prior studies attempted to overcome this challenge by increasing the model size (>100B) to learn more general medical knowledge, while there is still room for improvement in LLMs with smaller-scale model sizes (<100B). In this work, we start from a pre-trained general LLM model (AntGLM-10B) and fine-tune it from a medical beginner towards a medical expert (called AntGLM-Med-10B), which leverages a 3-stage optimization procedure, \textit{i.e.}, general medical knowledge injection, medical domain instruction tuning, and specific medical task adaptation. Our contributions are threefold: (1) We specifically investigate how to adapt a pre-trained general LLM in medical domain, especially for a specific medical task. (2) We collect and construct large-scale medical datasets for each stage of the optimization process. These datasets encompass various data types and tasks, such as question-answering, medical reasoning, multi-choice questions, and medical conversations. (3) Specifically for multi-choice questions in the medical domain, we propose a novel Verification-of-Choice approach for prompting engineering, which significantly enhances the reasoning ability of LLMs. Remarkably, by combining the above approaches, our AntGLM-Med-10B model can outperform the most of LLMs on PubMedQA, including both general and medical LLMs, even when these LLMs have larger model size.

Simple but Effective Unsupervised Classification for Specified Domain Images: A Case Study on Fungi Images

High-quality labeled datasets are essential for deep learning. Traditional manual annotation methods are not only costly and inefficient but also pose challenges in specialized domains where expert knowledge is needed. Self-supervised methods, despite leveraging unlabeled data for feature extraction, still require hundreds or thousands of labeled instances to guide the model for effective specialized image classification. Current unsupervised learning methods offer automatic classification without prior annotation but often compromise on accuracy. As a result, efficiently procuring high-quality labeled datasets remains a pressing challenge for specialized domain images devoid of annotated data. Addressing this, an unsupervised classification method with three key ideas is introduced: 1) dual-step feature dimensionality reduction using a pre-trained model and manifold learning, 2) a voting mechanism from multiple clustering algorithms, and 3) post-hoc instead of prior manual annotation. This approach outperforms supervised methods in classification accuracy, as demonstrated with fungal image data, achieving 94.1% and 96.7% on public and private datasets respectively. The proposed unsupervised classification method reduces dependency on pre-annotated datasets, enabling a closed-loop for data classification. The simplicity and ease of use of this method will also bring convenience to researchers in various fields in building datasets, promoting AI applications for images in specialized domains.

Think-in-Memory: Recalling and Post-thinking Enable LLMs with Long-Term Memory

Memory-augmented Large Language Models (LLMs) have demonstrated remarkable performance in long-term human-machine interactions, which basically relies on iterative recalling and reasoning of history to generate high-quality responses. However, such repeated recall-reason steps easily produce biased thoughts, \textit{i.e.}, inconsistent reasoning results when recalling the same history for different questions. On the contrary, humans can keep thoughts in the memory and recall them without repeated reasoning. Motivated by this human capability, we propose a novel memory mechanism called TiM (Think-in-Memory) that enables LLMs to maintain an evolved memory for storing historical thoughts along the conversation stream. The TiM framework consists of two crucial stages: (1) before generating a response, a LLM agent recalls relevant thoughts from memory, and (2) after generating a response, the LLM agent post-thinks and incorporates both historical and new thoughts to update the memory. Thus, TiM can eliminate the issue of repeated reasoning by saving the post-thinking thoughts as the history. Besides, we formulate the basic principles to organize the thoughts in memory based on the well-established operations, (\textit{i.e.}, insert, forget, and merge operations), allowing for dynamic updates and evolution of the thoughts. Furthermore, we introduce Locality-Sensitive Hashing into TiM to achieve efficient retrieval for the long-term conversations. We conduct qualitative and quantitative experiments on real-world and simulated dialogues covering a wide range of topics, demonstrating that equipping existing LLMs with TiM significantly enhances their performance in generating responses for long-term interactions.

CeRF: Convolutional Neural Radiance Fields for New View Synthesis with Derivatives of Ray Modeling

In recent years, novel view synthesis has gained popularity in generating high-fidelity images. While demonstrating superior performance in the task of synthesizing novel views, the majority of these methods are still based on the conventional multi-layer perceptron for scene embedding. Furthermore, light field models suffer from geometric blurring during pixel rendering, while radiance field-based volume rendering methods have multiple solutions for a certain target of density distribution integration. To address these issues, we introduce the Convolutional Neural Radiance Fields to model the derivatives of radiance along rays. Based on 1D convolutional operations, our proposed method effectively extracts potential ray representations through a structured neural network architecture. Besides, with the proposed ray modeling, a proposed recurrent module is employed to solve geometric ambiguity in the fully neural rendering process. Extensive experiments demonstrate the promising results of our proposed model compared with existing state-of-the-art methods.

Who Would be Interested in Services? An Entity Graph Learning System for User Targeting

With the growing popularity of various mobile devices, user targeting has received a growing amount of attention, which aims at effectively and efficiently locating target users that are interested in specific services. Most pioneering works for user targeting tasks commonly perform similarity-based expansion with a few active users as seeds, suffering from the following major issues: the unavailability of seed users for newcoming services and the unfriendliness of black-box procedures towards marketers. In this paper, we design an Entity Graph Learning (EGL) system to provide explainable user targeting ability meanwhile applicable to addressing the cold-start issue. EGL System follows the hybrid online-offline architecture to satisfy the requirements of scalability and timeliness. Specifically, in the offline stage, the system focuses on the heavyweight entity graph construction and user entity preference learning, in which we propose a Three-stage Relation Mining Procedure (TRMP), breaking loose from the expensive seed users. At the online stage, the system offers the ability of user targeting in real-time based on the entity graph from the offline stage. Since the user targeting process is based on graph reasoning, the whole process is transparent and operation-friendly to marketers. Finally, extensive offline experiments and online A/B testing demonstrate the superior performance of the proposed EGL System.

Time Series Domain Adaptation via Sparse Associative Structure Alignment

Domain adaptation on time series data is an important but challenging task. Most of the existing works in this area are based on the learning of the domain-invariant representation of the data with the help of restrictions like MMD. However, such extraction of the domain-invariant representation is a non-trivial task for time series data, due to the complex dependence among the timestamps. In detail, in the fully dependent time series, a small change of the time lags or the offsets may lead to difficulty in the domain invariant extraction. Fortunately, the stability of the causality inspired us to explore the domain invariant structure of the data. To reduce the difficulty in the discovery of causal structure, we relax it to the sparse associative structure and propose a novel sparse associative structure alignment model for domain adaptation. First, we generate the segment set to exclude the obstacle of offsets. Second, the intra-variables and inter-variables sparse attention mechanisms are devised to extract associative structure time-series data with considering time lags. Finally, the associative structure alignment is used to guide the transfer of knowledge from the source domain to the target one. Experimental studies not only verify the good performance of our methods on three real-world datasets but also provide some insightful discoveries on the transferred knowledge.