Daily Papers

The rapid advancement of large-scale vision-language models has showcased remarkable capabilities across various tasks. However, the lack of extensive and high-quality image-text data in medicine has greatly hindered the development of large-scale medical vision-language models. In this work, we present a diagnosis-guided bootstrapping strategy that exploits both image and label information to construct vision-language datasets. Based on the constructed dataset, we developed MedDr, a generalist foundation model for healthcare capable of handling diverse medical data modalities, including radiology, pathology, dermatology, retinography, and endoscopy. Moreover, during inference, we propose a simple but effective retrieval-augmented medical diagnosis strategy, which enhances the model's generalization ability. Extensive experiments on visual question answering, medical report generation, and medical image diagnosis demonstrate the superiority of our method.

Differential Diagnosis (DDx) is a fundamental yet complex aspect of clinical decision-making, in which physicians iteratively refine a ranked list of possible diseases based on symptoms, antecedents, and medical knowledge. While recent advances in large language models (LLMs) have shown promise in supporting DDx, existing approaches face key limitations, including single-dataset evaluations, isolated optimization of components, unrealistic assumptions about complete patient profiles, and single-attempt diagnosis. We introduce a Modular Explainable DDx Agent (MEDDxAgent) framework designed for interactive DDx, where diagnostic reasoning evolves through iterative learning, rather than assuming a complete patient profile is accessible. MEDDxAgent integrates three modular components: (1) an orchestrator (DDxDriver), (2) a history taking simulator, and (3) two specialized agents for knowledge retrieval and diagnosis strategy. To ensure robust evaluation, we introduce a comprehensive DDx benchmark covering respiratory, skin, and rare diseases. We analyze single-turn diagnostic approaches and demonstrate the importance of iterative refinement when patient profiles are not available at the outset. Our broad evaluation demonstrates that MEDDxAgent achieves over 10% accuracy improvements in interactive DDx across both large and small LLMs, while offering critical explainability into its diagnostic reasoning process.

Automated data labeling techniques are crucial for accelerating the development of deep learning models, particularly in complex medical imaging applications. However, ensuring accuracy and efficiency remains challenging. This paper presents iterative refinement strategies for automated data labeling in facial landmark diagnosis to enhance accuracy and efficiency for deep learning models in medical applications, including dermatology, plastic surgery, and ophthalmology. Leveraging feedback mechanisms and advanced algorithms, our approach iteratively refines initial labels, reducing reliance on manual intervention while improving label quality. Through empirical evaluation and case studies, we demonstrate the effectiveness of our proposed strategies in deep learning tasks across medical imaging domains. Our results highlight the importance of iterative refinement in automated data labeling to enhance the capabilities of deep learning systems in medical imaging applications.

Large annotated datasets are essential for training robust Computer-Aided Diagnosis (CAD) models for breast cancer detection or risk prediction. However, acquiring such datasets with fine-detailed annotation is both costly and time-consuming. Vision-Language Models (VLMs), such as CLIP, which are pre-trained on large image-text pairs, offer a promising solution by enhancing robustness and data efficiency in medical imaging tasks. This paper introduces a novel Multi-View Mammography and Language Model for breast cancer classification and risk prediction, trained on a dataset of paired mammogram images and synthetic radiology reports. Our MV-MLM leverages multi-view supervision to learn rich representations from extensive radiology data by employing cross-modal self-supervision across image-text pairs. This includes multiple views and the corresponding pseudo-radiology reports. We propose a novel joint visual-textual learning strategy to enhance generalization and accuracy performance over different data types and tasks to distinguish breast tissues or cancer characteristics(calcification, mass) and utilize these patterns to understand mammography images and predict cancer risk. We evaluated our method on both private and publicly available datasets, demonstrating that the proposed model achieves state-of-the-art performance in three classification tasks: (1) malignancy classification, (2) subtype classification, and (3) image-based cancer risk prediction. Furthermore, the model exhibits strong data efficiency, outperforming existing fully supervised or VLM baselines while trained on synthetic text reports and without the need for actual radiology reports.

Attention Deficit Hyperactivity Disorder (ADHD) is a common brain disorder in children that can persist into adulthood, affecting social, academic, and career life. Early diagnosis is crucial for managing these impacts on patients and the healthcare system but is often labor-intensive and time-consuming. This paper presents a novel method to improve ADHD diagnosis precision and timeliness by leveraging Deep Learning (DL) approaches and electroencephalogram (EEG) signals. We introduce ADHDeepNet, a DL model that utilizes comprehensive temporal-spatial characterization, attention modules, and explainability techniques optimized for EEG signals. ADHDeepNet integrates feature extraction and refinement processes to enhance ADHD diagnosis. The model was trained and validated on a dataset of 121 participants (61 ADHD, 60 Healthy Controls), employing nested cross-validation for robust performance. The proposed two-stage methodology uses a 10-fold cross-subject validation strategy. Initially, each iteration optimizes the model's hyper-parameters with inner 2-fold cross-validation. Then, Additive Gaussian Noise (AGN) with various standard deviations and magnification levels is applied for data augmentation. ADHDeepNet achieved 100% sensitivity and 99.17% accuracy in classifying ADHD/HC subjects. To clarify model explainability and identify key brain regions and frequency bands for ADHD diagnosis, we analyzed the learned weights and activation patterns of the model's primary layers. Additionally, t-distributed Stochastic Neighbor Embedding (t-SNE) visualized high-dimensional data, aiding in interpreting the model's decisions. This study highlights the potential of DL and EEG in enhancing ADHD diagnosis accuracy and efficiency.

LLM-based web agents have recently made significant progress, but much of it has occurred in closed-source systems, widening the gap with open-source alternatives. Progress has been held back by two key challenges: first, a narrow focus on single-step tasks that overlooks the complexity of multi-step web interactions; and second, the high compute costs required to post-train LLM-based web agents. To address this, we present the first statistically grounded study on compute allocation for LLM web-agent post-training. Our approach uses a two-stage pipeline, training a Llama 3.1 8B student to imitate a Llama 3.3 70B teacher via supervised fine-tuning (SFT), followed by on-policy reinforcement learning. We find this process highly sensitive to hyperparameter choices, making exhaustive sweeps impractical. To spare others from expensive trial-and-error, we sample 1,370 configurations and use bootstrapping to estimate effective hyperparameters. Our results show that combining SFT with on-policy RL consistently outperforms either approach alone on both WorkArena and MiniWob++. Further, this strategy requires only 55% of the compute to match the peak performance of pure SFT on MiniWob++, effectively pushing the compute-performance Pareto frontier, and is the only strategy that can close the gap with closed-source models.

While conversational generative AI has shown considerable potential in enhancing decision-making for agricultural professionals, its exploration has predominantly been anchored in text-based interactions. The evolution of multimodal conversational AI, leveraging vast amounts of image-text data from diverse sources, marks a significant stride forward. However, the application of such advanced vision-language models in the agricultural domain, particularly for crop disease diagnosis, remains underexplored. In this work, we present the crop disease domain multimodal (CDDM) dataset, a pioneering resource designed to advance the field of agricultural research through the application of multimodal learning techniques. The dataset comprises 137,000 images of various crop diseases, accompanied by 1 million question-answer pairs that span a broad spectrum of agricultural knowledge, from disease identification to management practices. By integrating visual and textual data, CDDM facilitates the development of sophisticated question-answering systems capable of providing precise, useful advice to farmers and agricultural professionals. We demonstrate the utility of the dataset by finetuning state-of-the-art multimodal models, showcasing significant improvements in crop disease diagnosis. Specifically, we employed a novel finetuning strategy that utilizes low-rank adaptation (LoRA) to finetune the visual encoder, adapter and language model simultaneously. Our contributions include not only the dataset but also a finetuning strategy and a benchmark to stimulate further research in agricultural technology, aiming to bridge the gap between advanced AI techniques and practical agricultural applications. The dataset is available at https: //github.com/UnicomAI/UnicomBenchmark/tree/main/CDDMBench.

Deep learning (DL) has proven highly effective for ultrasound-based computer-aided diagnosis (CAD) of breast cancers. In an automaticCAD system, lesion detection is critical for the following diagnosis. However, existing DL-based methods generally require voluminous manually-annotated region of interest (ROI) labels and class labels to train both the lesion detection and diagnosis models. In clinical practice, the ROI labels, i.e. ground truths, may not always be optimal for the classification task due to individual experience of sonologists, resulting in the issue of coarse annotation that limits the diagnosis performance of a CAD model. To address this issue, a novel Two-Stage Detection and Diagnosis Network (TSDDNet) is proposed based on weakly supervised learning to enhance diagnostic accuracy of the ultrasound-based CAD for breast cancers. In particular, all the ROI-level labels are considered as coarse labels in the first training stage, and then a candidate selection mechanism is designed to identify optimallesion areas for both the fully and partially annotated samples. It refines the current ROI-level labels in the fully annotated images and the detected ROIs in the partially annotated samples with a weakly supervised manner under the guidance of class labels. In the second training stage, a self-distillation strategy further is further proposed to integrate the detection network and classification network into a unified framework as the final CAD model for joint optimization, which then further improves the diagnosis performance. The proposed TSDDNet is evaluated on a B-mode ultrasound dataset, and the experimental results show that it achieves the best performance on both lesion detection and diagnosis tasks, suggesting promising application potential.

Chest X-ray imaging is crucial for diagnosing pulmonary and cardiac diseases, yet its interpretation demands extensive clinical experience and suffers from inter-observer variability. While deep learning models offer high diagnostic accuracy, their black-box nature hinders clinical adoption in high-stakes medical settings. To address this, we propose X-Ray-CoT (Chest X-Ray Chain-of-Thought), a novel framework leveraging Vision-Language Large Models (LVLMs) for intelligent chest X-ray diagnosis and interpretable report generation. X-Ray-CoT simulates human radiologists' "chain-of-thought" by first extracting multi-modal features and visual concepts, then employing an LLM-based component with a structured Chain-of-Thought prompting strategy to reason and produce detailed natural language diagnostic reports. Evaluated on the CORDA dataset, X-Ray-CoT achieves competitive quantitative performance, with a Balanced Accuracy of 80.52% and F1 score of 78.65% for disease diagnosis, slightly surpassing existing black-box models. Crucially, it uniquely generates high-quality, explainable reports, as validated by preliminary human evaluations. Our ablation studies confirm the integral role of each proposed component, highlighting the necessity of multi-modal fusion and CoT reasoning for robust and transparent medical AI. This work represents a significant step towards trustworthy and clinically actionable AI systems in medical imaging.

In recent years, Multimodal Large Language Models (MLLMs) have been extensively utilized for multimodal reasoning tasks, including Graphical User Interface (GUI) automation. Unlike general offline multimodal tasks, GUI automation is executed in online interactive environments, necessitating step-by-step decision-making based on real-time status of the environment. This task has a lower tolerance for decision-making errors at each step, as any mistakes may cumulatively disrupt the process and potentially lead to irreversible outcomes like deletions or payments. To address these issues, we introduce a pre-operative critic mechanism that provides effective feedback prior to the actual execution, by reasoning about the potential outcome and correctness of actions. Specifically, we propose a Suggestion-aware Gradient Relative Policy Optimization (S-GRPO) strategy to construct our pre-operative critic model GUI-Critic-R1, incorporating a novel suggestion reward to enhance the reliability of the model's feedback. Furthermore, we develop a reasoning-bootstrapping based data collection pipeline to create a GUI-Critic-Train and a GUI-Critic-Test, filling existing gaps in GUI critic data. Static experiments on the GUI-Critic-Test across both mobile and web domains reveal that our GUI-Critic-R1 offers significant advantages in critic accuracy compared to current MLLMs. Dynamic evaluation on GUI automation benchmark further highlights the effectiveness and superiority of our model, as evidenced by improved success rates and operational efficiency.

This paper presents our team's participation in the MEDIQA-ClinicalNLP2024 shared task B. We present a novel approach to diagnosing clinical dermatology cases by integrating large multimodal models, specifically leveraging the capabilities of GPT-4V under a retriever and a re-ranker framework. Our investigation reveals that GPT-4V, when used as a retrieval agent, can accurately retrieve the correct skin condition 85% of the time using dermatological images and brief patient histories. Additionally, we empirically show that Naive Chain-of-Thought (CoT) works well for retrieval while Medical Guidelines Grounded CoT is required for accurate dermatological diagnosis. Further, we introduce a Multi-Agent Conversation (MAC) framework and show its superior performance and potential over the best CoT strategy. The experiments suggest that using naive CoT for retrieval and multi-agent conversation for critique-based diagnosis, GPT-4V can lead to an early and accurate diagnosis of dermatological conditions. The implications of this work extend to improving diagnostic workflows, supporting dermatological education, and enhancing patient care by providing a scalable, accessible, and accurate diagnostic tool.

Dermatological diagnosis represents a complex multimodal challenge that requires integrating visual features with specialized clinical knowledge. While vision-language pretraining (VLP) has advanced medical AI, its effectiveness in dermatology is limited by text length constraints and the lack of structured texts. In this paper, we introduce MAKE, a Multi-Aspect Knowledge-Enhanced vision-language pretraining framework for zero-shot dermatological tasks. Recognizing that comprehensive dermatological descriptions require multiple knowledge aspects that exceed standard text constraints, our framework introduces: (1) a multi-aspect contrastive learning strategy that decomposes clinical narratives into knowledge-enhanced sub-texts through large language models, (2) a fine-grained alignment mechanism that connects subcaptions with diagnostically relevant image features, and (3) a diagnosis-guided weighting scheme that adaptively prioritizes different sub-captions based on clinical significance prior. Through pretraining on 403,563 dermatological image-text pairs collected from education resources, MAKE significantly outperforms state-of-the-art VLP models on eight datasets across zero-shot skin disease classification, concept annotation, and cross-modal retrieval tasks. Our code will be made publicly available at https: //github.com/SiyuanYan1/MAKE.

Clinical diagnosis is critical in medical practice, typically requiring a continuous and evolving process that includes primary diagnosis, differential diagnosis, and final diagnosis. However, most existing clinical diagnostic tasks are single-step processes, which does not align with the complex multi-step diagnostic procedures found in real-world clinical settings. In this paper, we propose a multi-step diagnostic task and annotate a clinical diagnostic dataset (MSDiagnosis). This dataset includes primary diagnosis, differential diagnosis, and final diagnosis questions. Additionally, we propose a novel and effective framework. This framework combines forward inference, backward inference, reflection, and refinement, enabling the LLM to self-evaluate and adjust its diagnostic results. To assess the effectiveness of our proposed method, we design and conduct extensive experiments. The experimental results demonstrate the effectiveness of the proposed method. We also provide a comprehensive experimental analysis and suggest future research directions for this task.

The emergence of groundbreaking large language models capable of performing complex reasoning tasks holds significant promise for addressing various scientific challenges, including those arising in complex clinical scenarios. To enable their safe and effective deployment in real-world healthcare settings, it is urgently necessary to benchmark the diagnostic capabilities of current models systematically. Given the limitations of existing medical benchmarks in evaluating advanced diagnostic reasoning, we present DiagnosisArena, a comprehensive and challenging benchmark designed to rigorously assess professional-level diagnostic competence. DiagnosisArena consists of 1,113 pairs of segmented patient cases and corresponding diagnoses, spanning 28 medical specialties, deriving from clinical case reports published in 10 top-tier medical journals. The benchmark is developed through a meticulous construction pipeline, involving multiple rounds of screening and review by both AI systems and human experts, with thorough checks conducted to prevent data leakage. Our study reveals that even the most advanced reasoning models, o3-mini, o1, and DeepSeek-R1, achieve only 45.82%, 31.09%, and 17.79% accuracy, respectively. This finding highlights a significant generalization bottleneck in current large language models when faced with clinical diagnostic reasoning challenges. Through DiagnosisArena, we aim to drive further advancements in AIs diagnostic reasoning capabilities, enabling more effective solutions for real-world clinical diagnostic challenges. We provide the benchmark and evaluation tools for further research and development https://github.com/SPIRAL-MED/DiagnosisArena.

In this paper, we present a framework for training large language models (LLMs) as diagnostic agents with reinforcement learning, enabling them to manage multi-turn diagnostic processes, adaptively select examinations, and commit to final diagnoses. Unlike instruction-tuned models trained on static case summaries, our method acquires diagnostic strategies through interactive exploration and outcome-based feedback. Our contributions are fourfold: (i) We present DiagGym, a diagnostics world model trained with electronic health records that emits examination outcomes conditioned on patient history and recommended examination, serving as a virtual clinical environment for realistic diagnosis training and evaluation; (ii) We train DiagAgent via end-to-end, multi-turn reinforcement learning to learn diagnostic policies that optimize both information yield and diagnostic accuracy; (iii) We introduce DiagBench, a diagnostic benchmark comprising 750 cases with physician-validated examination recommendations and 99 cases annotated with 973 physician-written rubrics on diagnosis process; (iv) we demonstrate superior performance across diverse diagnostic settings. DiagAgent significantly outperforms 10 state-of-the-art LLMs, including DeepSeek-v3 and GPT-4o, as well as two prompt-engineered agents. In single-turn settings, DiagAgent achieves 9.34% higher diagnostic accuracy and 44.03% improvement in examination recommendation hit ratio. In end-to-end settings, it delivers 15.12% increase in diagnostic accuracy and 23.09% boost in examination recommendation F1 score. In rubric-based evaluation, it surpasses the next-best model, Claude-sonnet-4, by 7.1% in weighted rubric score. These findings indicate that learning policies in interactive clinical environments confers dynamic and clinically meaningful diagnostic management abilities unattainable through passive training alone.

Clinical diagnosis is a highly specialized discipline requiring both domain expertise and strict adherence to rigorous guidelines. While current AI-driven medical research predominantly focuses on knowledge graphs or natural text pretraining paradigms to incorporate medical knowledge, these approaches primarily rely on implicitly encoded knowledge within model parameters, neglecting task-specific knowledge required by diverse downstream tasks. To address this limitation, we propose Retrieval-Augmented Diagnosis (RAD), a novel framework that explicitly injects external knowledge into multimodal models directly on downstream tasks. Specifically, RAD operates through three key mechanisms: retrieval and refinement of disease-centered knowledge from multiple medical sources, a guideline-enhanced contrastive loss that constrains the latent distance between multi-modal features and guideline knowledge, and the dual transformer decoder that employs guidelines as queries to steer cross-modal fusion, aligning the models with clinical diagnostic workflows from guideline acquisition to feature extraction and decision-making. Moreover, recognizing the lack of quantitative evaluation of interpretability for multimodal diagnostic models, we introduce a set of criteria to assess the interpretability from both image and text perspectives. Extensive evaluations across four datasets with different anatomies demonstrate RAD's generalizability, achieving state-of-the-art performance. Furthermore, RAD enables the model to concentrate more precisely on abnormal regions and critical indicators, ensuring evidence-based, trustworthy diagnosis. Our code is available at https://github.com/tdlhl/RAD.

Online medical consultation (OMC) restricts doctors to gathering patient information solely through inquiries, making the already complex sequential decision-making process of diagnosis even more challenging. Recently, the rapid advancement of large language models has demonstrated a significant potential to transform OMC. However, most studies have primarily focused on improving diagnostic accuracy under conditions of relatively sufficient information, while paying limited attention to the "inquiry" phase of the consultation process. This lack of focus has left the relationship between "inquiry" and "diagnosis" insufficiently explored. In this paper, we first extract real patient interaction strategies from authentic doctor-patient conversations and use these strategies to guide the training of a patient simulator that closely mirrors real-world behavior. By inputting medical records into our patient simulator to simulate patient responses, we conduct extensive experiments to explore the relationship between "inquiry" and "diagnosis" in the consultation process. Experimental results demonstrate that inquiry and diagnosis adhere to the Liebig's law: poor inquiry quality limits the effectiveness of diagnosis, regardless of diagnostic capability, and vice versa. Furthermore, the experiments reveal significant differences in the inquiry performance of various models. To investigate this phenomenon, we categorize the inquiry process into four types: (1) chief complaint inquiry; (2) specification of known symptoms; (3) inquiry about accompanying symptoms; and (4) gathering family or medical history. We analyze the distribution of inquiries across the four types for different models to explore the reasons behind their significant performance differences. We plan to open-source the weights and related code of our patient simulator at https://github.com/LIO-H-ZEN/PatientSimulator.

The field of medical diagnosis has undergone a significant transformation with the advent of large language models (LLMs), yet the challenges of interpretability within these models remain largely unaddressed. This study introduces Chain-of-Diagnosis (CoD) to enhance the interpretability of LLM-based medical diagnostics. CoD transforms the diagnostic process into a diagnostic chain that mirrors a physician's thought process, providing a transparent reasoning pathway. Additionally, CoD outputs the disease confidence distribution to ensure transparency in decision-making. This interpretability makes model diagnostics controllable and aids in identifying critical symptoms for inquiry through the entropy reduction of confidences. With CoD, we developed DiagnosisGPT, capable of diagnosing 9604 diseases. Experimental results demonstrate that DiagnosisGPT outperforms other LLMs on diagnostic benchmarks. Moreover, DiagnosisGPT provides interpretability while ensuring controllability in diagnostic rigor.

Daily progress notes are common types in the electronic health record (EHR) where healthcare providers document the patient's daily progress and treatment plans. The EHR is designed to document all the care provided to patients, but it also enables note bloat with extraneous information that distracts from the diagnoses and treatment plans. Applications of natural language processing (NLP) in the EHR is a growing field with the majority of methods in information extraction. Few tasks use NLP methods for downstream diagnostic decision support. We introduced the 2022 National NLP Clinical Challenge (N2C2) Track 3: Progress Note Understanding - Assessment and Plan Reasoning as one step towards a new suite of tasks. The Assessment and Plan Reasoning task focuses on the most critical components of progress notes, Assessment and Plan subsections where health problems and diagnoses are contained. The goal of the task was to develop and evaluate NLP systems that automatically predict causal relations between the overall status of the patient contained in the Assessment section and its relation to each component of the Plan section which contains the diagnoses and treatment plans. The goal of the task was to identify and prioritize diagnoses as the first steps in diagnostic decision support to find the most relevant information in long documents like daily progress notes. We present the results of 2022 n2c2 Track 3 and provide a description of the data, evaluation, participation and system performance.

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.

The differential diagnosis of neurodegenerative dementias is a challenging clinical task, mainly because of the overlap in symptom presentation and the similarity of patterns observed in structural neuroimaging. To improve diagnostic efficiency and accuracy, deep learning-based methods such as Convolutional Neural Networks and Vision Transformers have been proposed for the automatic classification of brain MRIs. However, despite their strong predictive performance, these models find limited clinical utility due to their opaque decision making. In this work, we propose a framework that integrates two core components to enhance diagnostic transparency. First, we introduce a modular pipeline for converting 3D T1-weighted brain MRIs into textual radiology reports. Second, we explore the potential of modern Large Language Models (LLMs) to assist clinicians in the differential diagnosis between Frontotemporal dementia subtypes, Alzheimer's disease, and normal aging based on the generated reports. To bridge the gap between predictive accuracy and explainability, we employ reinforcement learning to incentivize diagnostic reasoning in LLMs. Without requiring supervised reasoning traces or distillation from larger models, our approach enables the emergence of structured diagnostic rationales grounded in neuroimaging findings. Unlike post-hoc explainability methods that retrospectively justify model decisions, our framework generates diagnostic rationales as part of the inference process-producing causally grounded explanations that inform and guide the model's decision-making process. In doing so, our framework matches the diagnostic performance of existing deep learning methods while offering rationales that support its diagnostic conclusions.

Finding relevant literature underpins the practice of evidence-based medicine. From 2014 to 2016, TREC conducted a clinical decision support track, wherein participants were tasked with finding articles relevant to clinical questions posed by physicians. In total, 87 teams have participated over the past three years, generating 395 runs. During this period, each team has trialled a variety of methods. While there was significant overlap in the methods employed by different teams, the results were varied. Due to the diversity of the platforms used, the results arising from the different techniques are not directly comparable, reducing the ability to build on previous work. By using a stable platform, we have been able to compare different document and query processing techniques, allowing us to experiment with different search parameters. We have used our system to reproduce leading teams runs, and compare the results obtained. By benchmarking our indexing and search techniques, we can statistically test a variety of hypotheses, paving the way for further research.

Doctors and patients alike increasingly use Large Language Models (LLMs) to diagnose clinical cases. However, unlike domains such as math or coding, where correctness can be objectively defined by the final answer, medical diagnosis requires both the outcome and the reasoning process to be accurate. Currently, widely used medical benchmarks like MedQA and MMLU assess only accuracy in the final answer, overlooking the quality and faithfulness of the clinical reasoning process. To address this limitation, we introduce MedCaseReasoning, the first open-access dataset for evaluating LLMs on their ability to align with clinician-authored diagnostic reasoning. The dataset includes 14,489 diagnostic question-and-answer cases, each paired with detailed reasoning statements derived from open-access medical case reports. We evaluate state-of-the-art reasoning LLMs on MedCaseReasoning and find significant shortcomings in their diagnoses and reasoning: for instance, the top-performing open-source model, DeepSeek-R1, achieves only 48% 10-shot diagnostic accuracy and mentions only 64% of the clinician reasoning statements (recall). However, we demonstrate that fine-tuning LLMs on the reasoning traces derived from MedCaseReasoning significantly improves diagnostic accuracy and clinical reasoning recall by an average relative gain of 29% and 41%, respectively. The open-source dataset, code, and models are available at https://github.com/kevinwu23/Stanford-MedCaseReasoning.

Clinical diagnosis prediction models, when provided with a patient's medical history, aim to detect potential diseases early, facilitating timely intervention and improving prognostic outcomes. However, the inherent scarcity of patient data and large disease candidate space often pose challenges in developing satisfactory models for this intricate task. The exploration of leveraging Large Language Models (LLMs) for encapsulating clinical decision processes has been limited. We introduce MERA, a clinical diagnosis prediction model that bridges pertaining natural language knowledge with medical practice. We apply hierarchical contrastive learning on a disease candidate ranking list to alleviate the large decision space issue. With concept memorization through fine-tuning, we bridge the natural language clinical knowledge with medical codes. Experimental results on MIMIC-III and IV datasets show that MERA achieves the state-of-the-art diagnosis prediction performance and dramatically elevates the diagnosis prediction capabilities of generative LMs.

Explaining Artificial Intelligence (AI) decisions is a major challenge nowadays in AI, in particular when applied to sensitive scenarios like medicine and law. However, the need to explain the rationale behind decisions is a main issue also for human-based deliberation as it is important to justify why a certain decision has been taken. Resident medical doctors for instance are required not only to provide a (possibly correct) diagnosis, but also to explain how they reached a certain conclusion. Developing new tools to aid residents to train their explanation skills is therefore a central objective of AI in education. In this paper, we follow this direction, and we present, to the best of our knowledge, the first multilingual dataset for Medical Question Answering where correct and incorrect diagnoses for a clinical case are enriched with a natural language explanation written by doctors. These explanations have been manually annotated with argument components (i.e., premise, claim) and argument relations (i.e., attack, support), resulting in the Multilingual CasiMedicos-Arg dataset which consists of 558 clinical cases in four languages (English, Spanish, French, Italian) with explanations, where we annotated 5021 claims, 2313 premises, 2431 support relations, and 1106 attack relations. We conclude by showing how competitive baselines perform over this challenging dataset for the argument mining task.

Artificial intelligence has advanced in Medical Visual Question Answering (Med-VQA), but prevalent research tends to focus on the accuracy of the answers, often overlooking the reasoning paths and interpretability, which are crucial in clinical settings. Besides, current Med-VQA algorithms, typically reliant on singular models, lack the robustness needed for real-world medical diagnostics which usually require collaborative expert evaluation. To address these shortcomings, this paper presents MedCoT, a novel hierarchical expert verification reasoning chain method designed to enhance interpretability and accuracy in biomedical imaging inquiries. MedCoT is predicated on two principles: The necessity for explicit reasoning paths in Med-VQA and the requirement for multi-expert review to formulate accurate conclusions. The methodology involves an Initial Specialist proposing diagnostic rationales, followed by a Follow-up Specialist who validates these rationales, and finally, a consensus is reached through a vote among a sparse Mixture of Experts within the locally deployed Diagnostic Specialist, which then provides the definitive diagnosis. Experimental evaluations on four standard Med-VQA datasets demonstrate that MedCoT surpasses existing state-of-the-art approaches, providing significant improvements in performance and interpretability.

Building upon our previous investigations of O1 replication (Part 1: Journey Learning [Qin et al., 2024] and Part 2: Distillation [Huang et al., 2024]), this work explores the potential of inference-time scaling in large language models (LLMs) for medical reasoning tasks, ranging from diagnostic decision-making to treatment planning. Through extensive experiments on medical benchmarks of varying complexity (MedQA, Medbullets, and JAMA Clinical Challenges), our investigation reveals several key insights: (1) Increasing inference time does lead to improved performance. With a modest training set of 500 samples, our model yields substantial performance improvements of 6%-11%. (2) Task complexity directly correlates with the required length of reasoning chains, confirming the necessity of extended thought processes for challenging problems. (3) The differential diagnoses generated by our model adhere to the principles of the hypothetico-deductive method, producing a list of potential conditions that may explain a patient's symptoms and systematically narrowing these possibilities by evaluating the evidence. These findings demonstrate the promising synergy between inference-time scaling and journey learning in advancing LLMs' real-world clinical reasoning capabilities.

Accurate diagnosis with medical large language models is hindered by knowledge gaps and hallucinations. Retrieval and tool-augmented methods help, but their impact is limited by weak use of external knowledge and poor feedback-reasoning traceability. To address these challenges, We introduce Deep-DxSearch, an agentic RAG system trained end-to-end with reinforcement learning (RL) that enables steer tracebale retrieval-augmented reasoning for medical diagnosis. In Deep-DxSearch, we first construct a large-scale medical retrieval corpus comprising patient records and reliable medical knowledge sources to support retrieval-aware reasoning across diagnostic scenarios. More crutially, we frame the LLM as the core agent and the retrieval corpus as its environment, using tailored rewards on format, retrieval, reasoning structure, and diagnostic accuracy, thereby evolving the agentic RAG policy from large-scale data through RL. Experiments demonstrate that our end-to-end agentic RL training framework consistently outperforms prompt-engineering and training-free RAG approaches across multiple data centers. After training, Deep-DxSearch achieves substantial gains in diagnostic accuracy, surpassing strong diagnostic baselines such as GPT-4o, DeepSeek-R1, and other medical-specific frameworks for both common and rare disease diagnosis under in-distribution and out-of-distribution settings. Moreover, ablation studies on reward design and retrieval corpus components confirm their critical roles, underscoring the uniqueness and effectiveness of our approach compared with traditional implementations. Finally, case studies and interpretability analyses highlight improvements in Deep-DxSearch's diagnostic policy, providing deeper insight into its performance gains and supporting clinicians in delivering more reliable and precise preliminary diagnoses. See https://github.com/MAGIC-AI4Med/Deep-DxSearch.

Generalist Large Language Models (LLMs), such as GPT-4, have shown considerable promise in various domains, including medical diagnosis. Rare diseases, affecting approximately 300 million people worldwide, often have unsatisfactory clinical diagnosis rates primarily due to a lack of experienced physicians and the complexity of differentiating among many rare diseases. In this context, recent news such as "ChatGPT correctly diagnosed a 4-year-old's rare disease after 17 doctors failed" underscore LLMs' potential, yet underexplored, role in clinically diagnosing rare diseases. To bridge this research gap, we introduce RareBench, a pioneering benchmark designed to systematically evaluate the capabilities of LLMs on 4 critical dimensions within the realm of rare diseases. Meanwhile, we have compiled the largest open-source dataset on rare disease patients, establishing a benchmark for future studies in this domain. To facilitate differential diagnosis of rare diseases, we develop a dynamic few-shot prompt methodology, leveraging a comprehensive rare disease knowledge graph synthesized from multiple knowledge bases, significantly enhancing LLMs' diagnostic performance. Moreover, we present an exhaustive comparative study of GPT-4's diagnostic capabilities against those of specialist physicians. Our experimental findings underscore the promising potential of integrating LLMs into the clinical diagnostic process for rare diseases. This paves the way for exciting possibilities in future advancements in this field.

As the field of artificial intelligence progresses, assistive technologies are becoming more widely used across all industries. The healthcare industry is no different, with numerous studies being done to develop assistive tools for healthcare professionals. Automatic diagnostic systems are one such beneficial tool that can assist with a variety of tasks, including collecting patient information, analyzing test results, and diagnosing patients. However, the idea of developing systems that can provide a differential diagnosis has been largely overlooked in most of these research studies. In this study, we propose a transformer-based approach for providing differential diagnoses based on a patient's age, sex, medical history, and symptoms. We use the DDXPlus dataset, which provides differential diagnosis information for patients based on 49 disease types. Firstly, we propose a method to process the tabular patient data from the dataset and engineer them into patient reports to make them suitable for our research. In addition, we introduce two data modification modules to diversify the training data and consequently improve the robustness of the models. We approach the task as a multi-label classification problem and conduct extensive experiments using four transformer models. All the models displayed promising results by achieving over 97% F1 score on the held-out test set. Moreover, we design additional behavioral tests to get a broader understanding of the models. In particular, for one of our test cases, we prepared a custom test set of 100 samples with the assistance of a doctor. The results on the custom set showed that our proposed data modification modules improved the model's generalization capabilities. We hope our findings will provide future researchers with valuable insights and inspire them to develop reliable systems for automatic differential diagnosis.

The meaningful use of electronic health records (EHR) continues to progress in the digital era with clinical decision support systems augmented by artificial intelligence. A priority in improving provider experience is to overcome information overload and reduce the cognitive burden so fewer medical errors and cognitive biases are introduced during patient care. One major type of medical error is diagnostic error due to systematic or predictable errors in judgment that rely on heuristics. The potential for clinical natural language processing (cNLP) to model diagnostic reasoning in humans with forward reasoning from data to diagnosis and potentially reduce the cognitive burden and medical error has not been investigated. Existing tasks to advance the science in cNLP have largely focused on information extraction and named entity recognition through classification tasks. We introduce a novel suite of tasks coined as Diagnostic Reasoning Benchmarks, DR.BENCH, as a new benchmark for developing and evaluating cNLP models with clinical diagnostic reasoning ability. The suite includes six tasks from ten publicly available datasets addressing clinical text understanding, medical knowledge reasoning, and diagnosis generation. DR.BENCH is the first clinical suite of tasks designed to be a natural language generation framework to evaluate pre-trained language models. Experiments with state-of-the-art pre-trained generative language models using large general domain models and models that were continually trained on a medical corpus demonstrate opportunities for improvement when evaluated in DR. BENCH. We share DR. BENCH as a publicly available GitLab repository with a systematic approach to load and evaluate models for the cNLP community.

Artificial intelligence holds great promise for expanding access to expert medical knowledge and reasoning. However, most evaluations of language models rely on static vignettes and multiple-choice questions that fail to reflect the complexity and nuance of evidence-based medicine in real-world settings. In clinical practice, physicians iteratively formulate and revise diagnostic hypotheses, adapting each subsequent question and test to what they've just learned, and weigh the evolving evidence before committing to a final diagnosis. To emulate this iterative process, we introduce the Sequential Diagnosis Benchmark, which transforms 304 diagnostically challenging New England Journal of Medicine clinicopathological conference (NEJM-CPC) cases into stepwise diagnostic encounters. A physician or AI begins with a short case abstract and must iteratively request additional details from a gatekeeper model that reveals findings only when explicitly queried. Performance is assessed not just by diagnostic accuracy but also by the cost of physician visits and tests performed. We also present the MAI Diagnostic Orchestrator (MAI-DxO), a model-agnostic orchestrator that simulates a panel of physicians, proposes likely differential diagnoses and strategically selects high-value, cost-effective tests. When paired with OpenAI's o3 model, MAI-DxO achieves 80% diagnostic accuracy--four times higher than the 20% average of generalist physicians. MAI-DxO also reduces diagnostic costs by 20% compared to physicians, and 70% compared to off-the-shelf o3. When configured for maximum accuracy, MAI-DxO achieves 85.5% accuracy. These performance gains with MAI-DxO generalize across models from the OpenAI, Gemini, Claude, Grok, DeepSeek, and Llama families. We highlight how AI systems, when guided to think iteratively and act judiciously, can advance diagnostic precision and cost-effectiveness in clinical care.

In the light of the COVID-19 pandemic, deep learning methods have been widely investigated in detecting COVID-19 from chest X-rays. However, a more pragmatic approach to applying AI methods to a medical diagnosis is designing a framework that facilitates human-machine interaction and expert decision making. Studies have shown that categorization can play an essential rule in accelerating real-world decision making. Inspired by descriptive document clustering, we propose a domain-independent explanatory clustering framework to group contextually related instances and support radiologists' decision making. While most descriptive clustering approaches employ domain-specific characteristics to form meaningful clusters, we focus on model-level explanation as a more general-purpose element of every learning process to achieve cluster homogeneity. We employ DeepSHAP to generate homogeneous clusters in terms of disease severity and describe the clusters using favorable and unfavorable saliency maps, which visualize the class discriminating regions of an image. These human-interpretable maps complement radiologist knowledge to investigate the whole cluster at once. Besides, as part of this study, we evaluate a model based on VGG-19, which can identify COVID and pneumonia cases with a positive predictive value of 95% and 97%, respectively, comparable to the recent explainable approaches for COVID diagnosis.

Large language models (LLMs) offer a promising pre-screening tool, improving early disease detection and providing enhanced healthcare access for underprivileged communities. The early diagnosis of various diseases continues to be a significant challenge in healthcare, primarily due to the nonspecific nature of early symptoms, the shortage of expert medical practitioners, and the need for prolonged clinical evaluations, all of which can delay treatment and adversely affect patient outcomes. With impressive accuracy in prediction across a range of diseases, LLMs have the potential to revolutionize clinical pre-screening and decision-making for various medical conditions. In this work, we study the diagnostic capability of LLMs for Rheumatoid Arthritis (RA) with real world patients data. Patient data was collected alongside diagnoses from medical experts, and the performance of LLMs was evaluated in comparison to expert diagnoses for RA disease prediction. We notice an interesting pattern in disease diagnosis and find an unexpected misalignment between prediction and explanation. We conduct a series of multi-round analyses using different LLM agents. The best-performing model accurately predicts rheumatoid arthritis (RA) diseases approximately 95\% of the time. However, when medical experts evaluated the reasoning generated by the model, they found that nearly 68\% of the reasoning was incorrect. This study highlights a clear misalignment between LLMs high prediction accuracy and its flawed reasoning, raising important questions about relying on LLM explanations in clinical settings. LLMs provide incorrect reasoning to arrive at the correct answer for RA disease diagnosis.

Developing reliable AI systems to assist human clinicians in multi-modal medical diagnosis has long been a key objective for researchers. Recently, Multi-modal Large Language Models (MLLMs) have gained significant attention and achieved success across various domains. With strong reasoning capabilities and the ability to perform diverse tasks based on user instructions, they hold great potential for enhancing medical diagnosis. However, directly applying MLLMs to the medical domain still presents challenges. They lack detailed perception of visual inputs, limiting their ability to perform quantitative image analysis, which is crucial for medical diagnostics. Additionally, MLLMs often exhibit hallucinations and inconsistencies in reasoning, whereas clinical diagnoses must adhere strictly to established criteria. To address these challenges, we propose MedAgent-Pro, an evidence-based reasoning agentic system designed to achieve reliable, explainable, and precise medical diagnoses. This is accomplished through a hierarchical workflow: at the task level, knowledge-based reasoning generate reliable diagnostic plans for specific diseases following retrieved clinical criteria. While at the case level, multiple tool agents process multi-modal inputs, analyze different indicators according to the plan, and provide a final diagnosis based on both quantitative and qualitative evidence. Comprehensive experiments on both 2D and 3D medical diagnosis tasks demonstrate the superiority and effectiveness of MedAgent-Pro, while case studies further highlight its reliability and interpretability. The code is available at https://github.com/jinlab-imvr/MedAgent-Pro.

There has been a rapidly growing interest in Automatic Symptom Detection (ASD) and Automatic Diagnosis (AD) systems in the machine learning research literature, aiming to assist doctors in telemedicine services. These systems are designed to interact with patients, collect evidence about their symptoms and relevant antecedents, and possibly make predictions about the underlying diseases. Doctors would review the interactions, including the evidence and the predictions, collect if necessary additional information from patients, before deciding on next steps. Despite recent progress in this area, an important piece of doctors' interactions with patients is missing in the design of these systems, namely the differential diagnosis. Its absence is largely due to the lack of datasets that include such information for models to train on. In this work, we present a large-scale synthetic dataset of roughly 1.3 million patients that includes a differential diagnosis, along with the ground truth pathology, symptoms and antecedents for each patient. Unlike existing datasets which only contain binary symptoms and antecedents, this dataset also contains categorical and multi-choice symptoms and antecedents useful for efficient data collection. Moreover, some symptoms are organized in a hierarchy, making it possible to design systems able to interact with patients in a logical way. As a proof-of-concept, we extend two existing AD and ASD systems to incorporate the differential diagnosis, and provide empirical evidence that using differentials as training signals is essential for the efficiency of such systems or for helping doctors better understand the reasoning of those systems.

An accurate differential diagnosis (DDx) is a cornerstone of medical care, often reached through an iterative process of interpretation that combines clinical history, physical examination, investigations and procedures. Interactive interfaces powered by Large Language Models (LLMs) present new opportunities to both assist and automate aspects of this process. In this study, we introduce an LLM optimized for diagnostic reasoning, and evaluate its ability to generate a DDx alone or as an aid to clinicians. 20 clinicians evaluated 302 challenging, real-world medical cases sourced from the New England Journal of Medicine (NEJM) case reports. Each case report was read by two clinicians, who were randomized to one of two assistive conditions: either assistance from search engines and standard medical resources, or LLM assistance in addition to these tools. All clinicians provided a baseline, unassisted DDx prior to using the respective assistive tools. Our LLM for DDx exhibited standalone performance that exceeded that of unassisted clinicians (top-10 accuracy 59.1% vs 33.6%, [p = 0.04]). Comparing the two assisted study arms, the DDx quality score was higher for clinicians assisted by our LLM (top-10 accuracy 51.7%) compared to clinicians without its assistance (36.1%) (McNemar's Test: 45.7, p < 0.01) and clinicians with search (44.4%) (4.75, p = 0.03). Further, clinicians assisted by our LLM arrived at more comprehensive differential lists than those without its assistance. Our study suggests that our LLM for DDx has potential to improve clinicians' diagnostic reasoning and accuracy in challenging cases, meriting further real-world evaluation for its ability to empower physicians and widen patients' access to specialist-level expertise.

Background:Speech patterns have emerged as potential diagnostic markers for conditions with varying etiologies. Machine learning (ML) presents an opportunity to harness these patterns for accurate disease diagnosis. Objective: This review synthesized findings from studies exploring ML's capability in leveraging speech for the diagnosis of neurological, laryngeal and mental disorders. Methods: A systematic examination of 564 articles was conducted with 91 articles included in the study, which encompassed a wide spectrum of conditions, ranging from voice pathologies to mental and neurological disorders. Methods for speech classifications were assessed based on the relevant studies and scored between 0-10 based on the reported diagnostic accuracy of their ML models. Results: High diagnostic accuracies were consistently observed for laryngeal disorders, dysarthria, and changes related to speech in Parkinsons disease. These findings indicate the robust potential of speech as a diagnostic tool. Disorders like depression, schizophrenia, mild cognitive impairment and Alzheimers dementia also demonstrated high accuracies, albeit with some variability across studies. Meanwhile, disorders like OCD and autism highlighted the need for more extensive research to ascertain the relationship between speech patterns and the respective conditions. Conclusion: ML models utilizing speech patterns demonstrate promising potential in diagnosing a range of mental, laryngeal, and neurological disorders. However, the efficacy varies across conditions, and further research is needed. The integration of these models into clinical practice could potentially revolutionize the evaluation and diagnosis of a number of different medical conditions.

Speech patterns have been identified as potential diagnostic markers for neuropsychiatric conditions. However, most studies only compare a single clinical group to healthy controls, whereas clinical practice often requires differentiating between multiple potential diagnoses (multiclass settings). To address this, we assembled a dataset of repeated recordings from 420 participants (67 with major depressive disorder, 106 with schizophrenia and 46 with autism, as well as matched controls), and tested the performance of a range of conventional machine learning models and advanced Transformer models on both binary and multiclass classification, based on voice and text features. While binary models performed comparably to previous research (F1 scores between 0.54-0.75 for autism spectrum disorder, ASD; 0.67-0.92 for major depressive disorder, MDD; and 0.71-0.83 for schizophrenia); when differentiating between multiple diagnostic groups performance decreased markedly (F1 scores between 0.35-0.44 for ASD, 0.57-0.75 for MDD, 0.15-0.66 for schizophrenia, and 0.38-0.52 macro F1). Combining voice and text-based models yielded increased performance, suggesting that they capture complementary diagnostic information. Our results indicate that models trained on binary classification may learn to rely on markers of generic differences between clinical and non-clinical populations, or markers of clinical features that overlap across conditions, rather than identifying markers specific to individual conditions. We provide recommendations for future research in the field, suggesting increased focus on developing larger transdiagnostic datasets that include more fine-grained clinical features, and that can support the development of models that better capture the complexity of neuropsychiatric conditions and naturalistic diagnostic assessment.

Current medical retrieval benchmarks primarily emphasize lexical or shallow semantic similarity, overlooking the reasoning-intensive demands that are central to clinical decision-making. In practice, physicians often retrieve authoritative medical evidence to support diagnostic hypotheses. Such evidence typically aligns with an inferred diagnosis rather than the surface form of a patient's symptoms, leading to low lexical or semantic overlap between queries and relevant documents. To address this gap, we introduce R2MED, the first benchmark explicitly designed for reasoning-driven medical retrieval. It comprises 876 queries spanning three tasks: Q&A reference retrieval, clinical evidence retrieval, and clinical case retrieval. These tasks are drawn from five representative medical scenarios and twelve body systems, capturing the complexity and diversity of real-world medical information needs. We evaluate 15 widely-used retrieval systems on R2MED and find that even the best model achieves only 31.4 nDCG@10, demonstrating the benchmark's difficulty. Classical re-ranking and generation-augmented retrieval methods offer only modest improvements. Although large reasoning models improve performance via intermediate inference generation, the best results still peak at 41.4 nDCG@10. These findings underscore a substantial gap between current retrieval techniques and the reasoning demands of real clinical tasks. We release R2MED as a challenging benchmark to foster the development of next-generation medical retrieval systems with enhanced reasoning capabilities. Data and code are available at https://github.com/R2MED/R2MED

Large language models (LLMs) have demonstrated impressive capabilities in disease diagnosis. However, their effectiveness in identifying rarer diseases, which are inherently more challenging to diagnose, remains an open question. Rare disease performance is critical with the increasing use of LLMs in healthcare settings. This is especially true if a primary care physician needs to make a rarer prognosis from only a patient conversation so that they can take the appropriate next step. To that end, several clinical decision support systems are designed to support providers in rare disease identification. Yet their utility is limited due to their lack of knowledge of common disorders and difficulty of use. In this paper, we propose RareScale to combine the knowledge LLMs with expert systems. We use jointly use an expert system and LLM to simulate rare disease chats. This data is used to train a rare disease candidate predictor model. Candidates from this smaller model are then used as additional inputs to black-box LLM to make the final differential diagnosis. Thus, RareScale allows for a balance between rare and common diagnoses. We present results on over 575 rare diseases, beginning with Abdominal Actinomycosis and ending with Wilson's Disease. Our approach significantly improves the baseline performance of black-box LLMs by over 17% in Top-5 accuracy. We also find that our candidate generation performance is high (e.g. 88.8% on gpt-4o generated chats).

Recent advances in reasoning with large language models (LLMs)has shown remarkable reasoning capabilities in domains such as mathematics and coding, yet their application to clinical diagnosis remains underexplored. Here, we introduce ClinicalGPT-R1, a reasoning enhanced generalist large language model for disease diagnosis. Trained on a dataset of 20,000 real-world clinical records, ClinicalGPT-R1 leverages diverse training strategies to enhance diagnostic reasoning. To benchmark performance, we curated MedBench-Hard, a challenging dataset spanning seven major medical specialties and representative diseases. Experimental results demonstrate that ClinicalGPT-R1 outperforms GPT-4o in Chinese diagnostic tasks and achieves comparable performance to GPT-4 in English settings. This comparative study effectively validates the superior performance of ClinicalGPT-R1 in disease diagnosis tasks. Resources are available at https://github.com/medfound/medfound.

In recent years, the intersection of Natural Language Processing (NLP) and public health has opened innovative pathways for investigating various domains, including chronic pain in textual datasets. Despite the promise of NLP in chronic pain, the literature is dispersed across various disciplines, and there is a need to consolidate existing knowledge, identify knowledge gaps in the literature, and inform future research directions in this emerging field. This review aims to investigate the state of the research on NLP-based interventions designed for chronic pain research. A search strategy was formulated and executed across PubMed, Web of Science, IEEE Xplore, Scopus, and ACL Anthology to find studies published in English between 2014 and 2024. After screening 132 papers, 26 studies were included in the final review. Key findings from this review underscore the significant potential of NLP techniques to address pressing challenges in chronic pain research. The past 10 years in this field have showcased the utilization of advanced methods (transformers like RoBERTa and BERT) achieving high-performance metrics (e.g., F1>0.8) in classification tasks, while unsupervised approaches like Latent Dirichlet Allocation (LDA) and k-means clustering have proven effective for exploratory analyses. Results also reveal persistent challenges such as limited dataset diversity, inadequate sample sizes, and insufficient representation of underrepresented populations. Future research studies should explore multimodal data validation systems, context-aware mechanistic modeling, and the development of standardized evaluation metrics to enhance reproducibility and equity in chronic pain research.

In this work, we introduce MedAgentSim, an open-source simulated clinical environment with doctor, patient, and measurement agents designed to evaluate and enhance LLM performance in dynamic diagnostic settings. Unlike prior approaches, our framework requires doctor agents to actively engage with patients through multi-turn conversations, requesting relevant medical examinations (e.g., temperature, blood pressure, ECG) and imaging results (e.g., MRI, X-ray) from a measurement agent to mimic the real-world diagnostic process. Additionally, we incorporate self improvement mechanisms that allow models to iteratively refine their diagnostic strategies. We enhance LLM performance in our simulated setting by integrating multi-agent discussions, chain-of-thought reasoning, and experience-based knowledge retrieval, facilitating progressive learning as doctor agents interact with more patients. We also introduce an evaluation benchmark for assessing the LLM's ability to engage in dynamic, context-aware diagnostic interactions. While MedAgentSim is fully automated, it also supports a user-controlled mode, enabling human interaction with either the doctor or patient agent. Comprehensive evaluations in various simulated diagnostic scenarios demonstrate the effectiveness of our approach. Our code, simulation tool, and benchmark are available at https://medagentsim.netlify.app/.

Users typically engage with LLMs interactively, yet most existing benchmarks evaluate them in a static, single-turn format, posing reliability concerns in interactive scenarios. We identify a key obstacle towards reliability: LLMs are trained to answer any question, even with incomplete context or insufficient knowledge. In this paper, we propose to change the static paradigm to an interactive one, develop systems that proactively ask questions to gather more information and respond reliably, and introduce an benchmark - MediQ - to evaluate question-asking ability in LLMs. MediQ simulates clinical interactions consisting of a Patient System and an adaptive Expert System; with potentially incomplete initial information, the Expert refrains from making diagnostic decisions when unconfident, and instead elicits missing details via follow-up questions. We provide a pipeline to convert single-turn medical benchmarks into an interactive format. Our results show that directly prompting state-of-the-art LLMs to ask questions degrades performance, indicating that adapting LLMs to proactive information-seeking settings is nontrivial. We experiment with abstention strategies to better estimate model confidence and decide when to ask questions, improving diagnostic accuracy by 22.3%; however, performance still lags compared to an (unrealistic in practice) upper bound with complete information upfront. Further analyses show improved interactive performance with filtering irrelevant contexts and reformatting conversations. Overall, we introduce a novel problem towards LLM reliability, an interactive MediQ benchmark and a novel question-asking system, and highlight directions to extend LLMs' information-seeking abilities in critical domains.

Integrating Large Language Models (LLMs) in healthcare diagnosis demands systematic frameworks that can handle complex medical scenarios while maintaining specialized expertise. We present KG4Diagnosis, a novel hierarchical multi-agent framework that combines LLMs with automated knowledge graph construction, encompassing 362 common diseases across medical specialties. Our framework mirrors real-world medical systems through a two-tier architecture: a general practitioner (GP) agent for initial assessment and triage, coordinating with specialized agents for in-depth diagnosis in specific domains. The core innovation lies in our end-to-end knowledge graph generation methodology, incorporating: (1) semantic-driven entity and relation extraction optimized for medical terminology, (2) multi-dimensional decision relationship reconstruction from unstructured medical texts, and (3) human-guided reasoning for knowledge expansion. KG4Diagnosis serves as an extensible foundation for specialized medical diagnosis systems, with capabilities to incorporate new diseases and medical knowledge. The framework's modular design enables seamless integration of domain-specific enhancements, making it valuable for developing targeted medical diagnosis systems. We provide architectural guidelines and protocols to facilitate adoption across medical contexts.

With the rapid development of artificial intelligence, large language models (LLMs) have shown promising capabilities in mimicking human-level language comprehension and reasoning. This has sparked significant interest in applying LLMs to enhance various aspects of healthcare, ranging from medical education to clinical decision support. However, medicine involves multifaceted data modalities and nuanced reasoning skills, presenting challenges for integrating LLMs. This paper provides a comprehensive review on the applications and implications of LLMs in medicine. It begins by examining the fundamental applications of general-purpose and specialized LLMs, demonstrating their utilities in knowledge retrieval, research support, clinical workflow automation, and diagnostic assistance. Recognizing the inherent multimodality of medicine, the review then focuses on multimodal LLMs, investigating their ability to process diverse data types like medical imaging and EHRs to augment diagnostic accuracy. To address LLMs' limitations regarding personalization and complex clinical reasoning, the paper explores the emerging development of LLM-powered autonomous agents for healthcare. Furthermore, it summarizes the evaluation methodologies for assessing LLMs' reliability and safety in medical contexts. Overall, this review offers an extensive analysis on the transformative potential of LLMs in modern medicine. It also highlights the pivotal need for continuous optimizations and ethical oversight before these models can be effectively integrated into clinical practice. Visit https://github.com/mingze-yuan/Awesome-LLM-Healthcare for an accompanying GitHub repository containing latest papers.

Diabetic retinopathy (DR) is a growing health problem worldwide and is a leading cause of visual impairment and blindness, especially among working people aged 20-65. Its incidence is increasing along with the number of diabetes cases, and it is more common in developed countries than in developing countries. Recent research in the field of diabetic retinopathy diagnosis is using advanced technologies, such as analysis of images obtained by ophthalmoscopy. Automatic methods for analyzing eye images based on neural networks, deep learning and image analysis algorithms can improve the efficiency of diagnosis. This paper describes an automatic DR diagnosis method that includes processing and analysis of ophthalmoscopic images of the eye. It uses morphological algorithms to identify the optic disc and lesions characteristic of DR, such as microaneurysms, hemorrhages and exudates. Automated DR diagnosis has the potential to improve the efficiency of early detection of this disease and contribute to reducing the number of cases of diabetes-related visual impairment. The final step was to create an application with a graphical user interface that allowed retinal images taken at cooperating ophthalmology offices to be uploaded to the server. These images were then analyzed using a developed algorithm to make a diagnosis.

At the heart of medicine lies the physician-patient dialogue, where skillful history-taking paves the way for accurate diagnosis, effective management, and enduring trust. Artificial Intelligence (AI) systems capable of diagnostic dialogue could increase accessibility, consistency, and quality of care. However, approximating clinicians' expertise is an outstanding grand challenge. Here, we introduce AMIE (Articulate Medical Intelligence Explorer), a Large Language Model (LLM) based AI system optimized for diagnostic dialogue. AMIE uses a novel self-play based simulated environment with automated feedback mechanisms for scaling learning across diverse disease conditions, specialties, and contexts. We designed a framework for evaluating clinically-meaningful axes of performance including history-taking, diagnostic accuracy, management reasoning, communication skills, and empathy. We compared AMIE's performance to that of primary care physicians (PCPs) in a randomized, double-blind crossover study of text-based consultations with validated patient actors in the style of an Objective Structured Clinical Examination (OSCE). The study included 149 case scenarios from clinical providers in Canada, the UK, and India, 20 PCPs for comparison with AMIE, and evaluations by specialist physicians and patient actors. AMIE demonstrated greater diagnostic accuracy and superior performance on 28 of 32 axes according to specialist physicians and 24 of 26 axes according to patient actors. Our research has several limitations and should be interpreted with appropriate caution. Clinicians were limited to unfamiliar synchronous text-chat which permits large-scale LLM-patient interactions but is not representative of usual clinical practice. While further research is required before AMIE could be translated to real-world settings, the results represent a milestone towards conversational diagnostic AI.

Given the dominance of dense retrievers that do not generalize well beyond their training dataset distributions, domain-specific test sets are essential in evaluating retrieval. There are few test datasets for retrieval systems intended for use by healthcare providers in a point-of-care setting. To fill this gap we have collaborated with medical professionals to create CURE, an ad-hoc retrieval test dataset for passage ranking with 2000 queries spanning 10 medical domains with a monolingual (English) and two cross-lingual (French/Spanish -> English) conditions. In this paper, we describe how CURE was constructed and provide baseline results to showcase its effectiveness as an evaluation tool. CURE is published with a Creative Commons Attribution Non Commercial 4.0 license and can be accessed on Hugging Face.

Artificial intelligence has significantly advanced healthcare, particularly through large language models (LLMs) that excel in medical question answering benchmarks. However, their real-world clinical application remains limited due to the complexities of doctor-patient interactions. To address this, we introduce AI Hospital, a multi-agent framework simulating dynamic medical interactions between Doctor as player and NPCs including Patient, Examiner, Chief Physician. This setup allows for realistic assessments of LLMs in clinical scenarios. We develop the Multi-View Medical Evaluation (MVME) benchmark, utilizing high-quality Chinese medical records and NPCs to evaluate LLMs' performance in symptom collection, examination recommendations, and diagnoses. Additionally, a dispute resolution collaborative mechanism is proposed to enhance diagnostic accuracy through iterative discussions. Despite improvements, current LLMs exhibit significant performance gaps in multi-turn interactions compared to one-step approaches. Our findings highlight the need for further research to bridge these gaps and improve LLMs' clinical diagnostic capabilities. Our data, code, and experimental results are all open-sourced at https://github.com/LibertFan/AI_Hospital.

The integration of Artificial Intelligence (AI), especially Large Language Models (LLMs), into the clinical diagnosis process offers significant potential to improve the efficiency and accessibility of medical care. While LLMs have shown some promise in the medical domain, their application in clinical diagnosis remains underexplored, especially in real-world clinical practice, where highly sophisticated, patient-specific decisions need to be made. Current evaluations of LLMs in this field are often narrow in scope, focusing on specific diseases or specialties and employing simplified diagnostic tasks. To bridge this gap, we introduce CliBench, a novel benchmark developed from the MIMIC IV dataset, offering a comprehensive and realistic assessment of LLMs' capabilities in clinical diagnosis. This benchmark not only covers diagnoses from a diverse range of medical cases across various specialties but also incorporates tasks of clinical significance: treatment procedure identification, lab test ordering and medication prescriptions. Supported by structured output ontologies, CliBench enables a precise and multi-granular evaluation, offering an in-depth understanding of LLM's capability on diverse clinical tasks of desired granularity. We conduct a zero-shot evaluation of leading LLMs to assess their proficiency in clinical decision-making. Our preliminary results shed light on the potential and limitations of current LLMs in clinical settings, providing valuable insights for future advancements in LLM-powered healthcare.

Retrieval-augmented generation (RAG) is a well-suited technique for retrieving privacy-sensitive Electronic Health Records (EHR). It can serve as a key module of the healthcare copilot, helping reduce misdiagnosis for healthcare practitioners and patients. However, the diagnostic accuracy and specificity of existing heuristic-based RAG models used in the medical domain are inadequate, particularly for diseases with similar manifestations. This paper proposes MedRAG, a RAG model enhanced by knowledge graph (KG)-elicited reasoning for the medical domain that retrieves diagnosis and treatment recommendations based on manifestations. MedRAG systematically constructs a comprehensive four-tier hierarchical diagnostic KG encompassing critical diagnostic differences of various diseases. These differences are dynamically integrated with similar EHRs retrieved from an EHR database, and reasoned within a large language model. This process enables more accurate and specific decision support, while also proactively providing follow-up questions to enhance personalized medical decision-making. MedRAG is evaluated on both a public dataset DDXPlus and a private chronic pain diagnostic dataset (CPDD) collected from Tan Tock Seng Hospital, and its performance is compared against various existing RAG methods. Experimental results show that, leveraging the information integration and relational abilities of the KG, our MedRAG provides more specific diagnostic insights and outperforms state-of-the-art models in reducing misdiagnosis rates. Our code will be available at https://github.com/SNOWTEAM2023/MedRAG

Medical systematic reviews typically require assessing all the documents retrieved by a search. The reason is two-fold: the task aims for ``total recall''; and documents retrieved using Boolean search are an unordered set, and thus it is unclear how an assessor could examine only a subset. Screening prioritisation is the process of ranking the (unordered) set of retrieved documents, allowing assessors to begin the downstream processes of the systematic review creation earlier, leading to earlier completion of the review, or even avoiding screening documents ranked least relevant. Screening prioritisation requires highly effective ranking methods. Pre-trained language models are state-of-the-art on many IR tasks but have yet to be applied to systematic review screening prioritisation. In this paper, we apply several pre-trained language models to the systematic review document ranking task, both directly and fine-tuned. An empirical analysis compares how effective neural methods compare to traditional methods for this task. We also investigate different types of document representations for neural methods and their impact on ranking performance. Our results show that BERT-based rankers outperform the current state-of-the-art screening prioritisation methods. However, BERT rankers and existing methods can actually be complementary, and thus, further improvements may be achieved if used in conjunction.

Providing high quality explanations for AI predictions based on machine learning is a challenging and complex task. To work well it requires, among other factors: selecting a proper level of generality/specificity of the explanation; considering assumptions about the familiarity of the explanation beneficiary with the AI task under consideration; referring to specific elements that have contributed to the decision; making use of additional knowledge (e.g. expert evidence) which might not be part of the prediction process; and providing evidence supporting negative hypothesis. Finally, the system needs to formulate the explanation in a clearly interpretable, and possibly convincing, way. Given these considerations, ANTIDOTE fosters an integrated vision of explainable AI, where low-level characteristics of the deep learning process are combined with higher level schemes proper of the human argumentation capacity. ANTIDOTE will exploit cross-disciplinary competences in deep learning and argumentation to support a broader and innovative view of explainable AI, where the need for high-quality explanations for clinical cases deliberation is critical. As a first result of the project, we publish the Antidote CasiMedicos dataset to facilitate research on explainable AI in general, and argumentation in the medical domain in particular.

Identifying, tracking, and predicting wound heal-stage progression is a fundamental task towards proper diagnosis, effective treatment, facilitating healing, and reducing pain. Traditionally, a medical expert might observe a wound to determine the current healing state and recommend treatment. However, sourcing experts who can produce such a diagnosis solely from visual indicators can be difficult, time-consuming and expensive. In addition, lesions may take several weeks to undergo the healing process, demanding resources to monitor and diagnose continually. Automating this task can be challenging; datasets that follow wound progression from onset to maturation are small, rare, and often collected without computer vision in mind. To tackle these challenges, we introduce a self-supervised learning scheme composed of (a) learning embeddings of wound's temporal dynamics, (b) clustering for automatic stage discovery, and (c) fine-tuned classification. The proposed self-supervised and flexible learning framework is biologically inspired and trained on a small dataset with zero human labeling. The HealNet framework achieved high pre-text and downstream classification accuracy; when evaluated on held-out test data, HealNet achieved 97.7% pre-text accuracy and 90.62% heal-stage classification accuracy.

With the increasing availability of structured and unstructured data and the swift progress of analytical techniques, Artificial Intelligence (AI) is bringing a revolution to the healthcare industry. With the increasingly indispensable role of AI in healthcare, there are growing concerns over the lack of transparency and explainability in addition to potential bias encountered by predictions of the model. This is where Explainable Artificial Intelligence (XAI) comes into the picture. XAI increases the trust placed in an AI system by medical practitioners as well as AI researchers, and thus, eventually, leads to an increasingly widespread deployment of AI in healthcare. In this paper, we present different interpretability techniques. The aim is to enlighten practitioners on the understandability and interpretability of explainable AI systems using a variety of techniques available which can be very advantageous in the health-care domain. Medical diagnosis model is responsible for human life and we need to be confident enough to treat a patient as instructed by a black-box model. Our paper contains examples based on the heart disease dataset and elucidates on how the explainability techniques should be preferred to create trustworthiness while using AI systems in healthcare.

Accurate diagnosis of Parkinson disease, especially in its early stages, can be a challenging task. The application of machine learning techniques helps improve the diagnostic accuracy of Parkinson disease detection but only few studies have presented work towards the prediction of disease progression. In this research work, Long Short Term Memory LSTM was trained using the diagnostic features on Parkinson patients speech signals, to predict the disease progression while a Multilayer Perceptron MLP was trained on the same diagnostic features to detect the disease. Diagnostic features selected using two well-known feature selection methods named Relief-F and Sequential Forward Selection and applied on LSTM and MLP have shown to accurately predict the disease progression as stage 2 and 3 and its existence respectively.

Generalist foundation models such as GPT-4 have displayed surprising capabilities in a wide variety of domains and tasks. Yet, there is a prevalent assumption that they cannot match specialist capabilities of fine-tuned models. For example, most explorations to date on medical competency benchmarks have leveraged domain-specific training, as exemplified by efforts on BioGPT and Med-PaLM. We build on a prior study of GPT-4's capabilities on medical challenge benchmarks in the absence of special training. Rather than using simple prompting to highlight the model's out-of-the-box capabilities, we perform a systematic exploration of prompt engineering. We find that prompting innovation can unlock deeper specialist capabilities and show that GPT-4 easily tops prior leading results for medical benchmarks. The prompting methods we explore are general purpose, and make no specific use of domain expertise, removing the need for expert-curated content. Our experimental design carefully controls for overfitting during the prompt engineering process. We introduce Medprompt, based on a composition of several prompting strategies. With Medprompt, GPT-4 achieves state-of-the-art results on all nine of the benchmark datasets in the MultiMedQA suite. The method outperforms leading specialist models such as Med-PaLM 2 by a significant margin with an order of magnitude fewer calls to the model. Steering GPT-4 with Medprompt achieves a 27% reduction in error rate on the MedQA dataset over the best methods to date achieved with specialist models and surpasses a score of 90% for the first time. Beyond medical problems, we show the power of Medprompt to generalize to other domains and provide evidence for the broad applicability of the approach via studies of the strategy on exams in electrical engineering, machine learning, philosophy, accounting, law, nursing, and clinical psychology.

Clinical diagnosis of the eye is performed over multifarious data modalities including scalar clinical labels, vectorized biomarkers, two-dimensional fundus images, and three-dimensional Optical Coherence Tomography (OCT) scans. Clinical practitioners use all available data modalities for diagnosing and treating eye diseases like Diabetic Retinopathy (DR) or Diabetic Macular Edema (DME). Enabling usage of machine learning algorithms within the ophthalmic medical domain requires research into the relationships and interactions between all relevant data over a treatment period. Existing datasets are limited in that they neither provide data nor consider the explicit relationship modeling between the data modalities. In this paper, we introduce the Ophthalmic Labels for Investigating Visual Eye Semantics (OLIVES) dataset that addresses the above limitation. This is the first OCT and near-IR fundus dataset that includes clinical labels, biomarker labels, disease labels, and time-series patient treatment information from associated clinical trials. The dataset consists of 1268 near-IR fundus images each with at least 49 OCT scans, and 16 biomarkers, along with 4 clinical labels and a disease diagnosis of DR or DME. In total, there are 96 eyes' data averaged over a period of at least two years with each eye treated for an average of 66 weeks and 7 injections. We benchmark the utility of OLIVES dataset for ophthalmic data as well as provide benchmarks and concrete research directions for core and emerging machine learning paradigms within medical image analysis.

Incentivizing the reasoning ability of Multimodal Large Language Models (MLLMs) is essential for medical applications to transparently analyze medical scans and provide reliable diagnosis. However, existing medical MLLMs rely solely on internal knowledge during reasoning, leading to hallucinated reasoning and factual inaccuracies when encountering cases beyond their training scope. Although recent Agentic Retrieval-Augmented Generation (RAG) methods elicit the medical model's proactive retrieval ability during reasoning, they are confined to unimodal LLMs, neglecting the crucial visual information during reasoning and retrieval. Consequently, we propose the first Multimodal Medical Reasoning-with-Retrieval framework, Med-RwR, which actively retrieves external knowledge by querying observed symptoms or domain-specific medical concepts during reasoning. Specifically, we design a two-stage reinforcement learning strategy with tailored rewards that stimulate the model to leverage both visual diagnostic findings and textual clinical information for effective retrieval. Building on this foundation, we further propose a Confidence-Driven Image Re-retrieval (CDIR) method for test-time scaling when low prediction confidence is detected. Evaluation on various public medical benchmarks demonstrates Med-RwR's significant improvements over baseline models, proving the effectiveness of enhancing reasoning capabilities with external knowledge integration. Furthermore, Med-RwR demonstrates remarkable generalizability to unfamiliar domains, evidenced by 8.8% performance gain on our proposed EchoCardiography Benchmark (ECBench), despite the scarcity of echocardiography data in the training corpus. Our data, model, and codes will be made publicly available at https://github.com/xmed-lab/Med-RwR.

Medical images and radiology reports are crucial for diagnosing medical conditions, highlighting the importance of quantitative analysis for clinical decision-making. However, the diversity and cross-source heterogeneity of these data challenge the generalizability of current data-mining methods. Multimodal large language models (MLLMs) have recently transformed many domains, significantly affecting the medical field. Notably, Gemini-Vision-series (Gemini) and GPT-4-series (GPT-4) models have epitomized a paradigm shift in Artificial General Intelligence (AGI) for computer vision, showcasing their potential in the biomedical domain. In this study, we evaluated the performance of the Gemini, GPT-4, and 4 popular large models for an exhaustive evaluation across 14 medical imaging datasets, including 5 medical imaging categories (dermatology, radiology, dentistry, ophthalmology, and endoscopy), and 3 radiology report datasets. The investigated tasks encompass disease classification, lesion segmentation, anatomical localization, disease diagnosis, report generation, and lesion detection. Our experimental results demonstrated that Gemini-series models excelled in report generation and lesion detection but faces challenges in disease classification and anatomical localization. Conversely, GPT-series models exhibited proficiency in lesion segmentation and anatomical localization but encountered difficulties in disease diagnosis and lesion detection. Additionally, both the Gemini series and GPT series contain models that have demonstrated commendable generation efficiency. While both models hold promise in reducing physician workload, alleviating pressure on limited healthcare resources, and fostering collaboration between clinical practitioners and artificial intelligence technologies, substantial enhancements and comprehensive validations remain imperative before clinical deployment.

Diagnosing and managing a patient is a complex, sequential decision making process that requires physicians to obtain information -- such as which tests to perform -- and to act upon it. Recent advances in artificial intelligence (AI) and large language models (LLMs) promise to profoundly impact clinical care. However, current evaluation schemes overrely on static medical question-answering benchmarks, falling short on interactive decision-making that is required in real-life clinical work. Here, we present AgentClinic: a multimodal benchmark to evaluate LLMs in their ability to operate as agents in simulated clinical environments. In our benchmark, the doctor agent must uncover the patient's diagnosis through dialogue and active data collection. We present two open medical agent benchmarks: a multimodal image and dialogue environment, AgentClinic-NEJM, and a dialogue-only environment, AgentClinic-MedQA. We embed cognitive and implicit biases both in patient and doctor agents to emulate realistic interactions between biased agents. We find that introducing bias leads to large reductions in diagnostic accuracy of the doctor agents, as well as reduced compliance, confidence, and follow-up consultation willingness in patient agents. Evaluating a suite of state-of-the-art LLMs, we find that several models that excel in benchmarks like MedQA are performing poorly in AgentClinic-MedQA. We find that the LLM used in the patient agent is an important factor for performance in the AgentClinic benchmark. We show that both having limited interactions as well as too many interaction reduces diagnostic accuracy in doctor agents. The code and data for this work is publicly available at https://AgentClinic.github.io.

Large Multimodal Models (LMMs) have shown remarkable progress in the field of medical Visual Question Answering (Med-VQA), achieving high accuracy on existing benchmarks. However, their reliability under robust evaluation is questionable. This study reveals that state-of-the-art models, when subjected to simple probing evaluation, perform worse than random guessing on medical diagnosis questions. To address this critical evaluation problem, we introduce the Probing Evaluation for Medical Diagnosis (ProbMed) dataset to rigorously assess LMM performance in medical imaging through probing evaluation and procedural diagnosis. Particularly, probing evaluation features pairing original questions with negation questions with hallucinated attributes, while procedural diagnosis requires reasoning across various diagnostic dimensions for each image, including modality recognition, organ identification, clinical findings, abnormalities, and positional grounding. Our evaluation reveals that top-performing models like GPT-4V and Gemini Pro perform worse than random guessing on specialized diagnostic questions, indicating significant limitations in handling fine-grained medical inquiries. Besides, models like LLaVA-Med struggle even with more general questions, and results from CheXagent demonstrate the transferability of expertise across different modalities of the same organ, showing that specialized domain knowledge is still crucial for improving performance. This study underscores the urgent need for more robust evaluation to ensure the reliability of LMMs in critical fields like medical diagnosis, and current LMMs are still far from applicable to those fields.

A promising application of AI to healthcare is the retrieval of information from electronic health records (EHRs), e.g. to aid clinicians in finding relevant information for a consultation or to recruit suitable patients for a study. This requires search capabilities far beyond simple string matching, including the retrieval of concepts (diagnoses, symptoms, medications, etc.) related to the one in question. The suitability of AI methods for such applications is tested by predicting the relatedness of concepts with known relatedness scores. However, all existing biomedical concept relatedness datasets are notoriously small and consist of hand-picked concept pairs. We open-source a novel concept relatedness benchmark overcoming these issues: it is six times larger than existing datasets and concept pairs are chosen based on co-occurrence in EHRs, ensuring their relevance for the application of interest. We present an in-depth analysis of our new dataset and compare it to existing ones, highlighting that it is not only larger but also complements existing datasets in terms of the types of concepts included. Initial experiments with state-of-the-art embedding methods show that our dataset is a challenging new benchmark for testing concept relatedness models.

Automated diagnosis prediction from medical images is a valuable resource to support clinical decision-making. However, such systems usually need to be trained on large amounts of annotated data, which often is scarce in the medical domain. Zero-shot methods address this challenge by allowing a flexible adaption to new settings with different clinical findings without relying on labeled data. Further, to integrate automated diagnosis in the clinical workflow, methods should be transparent and explainable, increasing medical professionals' trust and facilitating correctness verification. In this work, we introduce Xplainer, a novel framework for explainable zero-shot diagnosis in the clinical setting. Xplainer adapts the classification-by-description approach of contrastive vision-language models to the multi-label medical diagnosis task. Specifically, instead of directly predicting a diagnosis, we prompt the model to classify the existence of descriptive observations, which a radiologist would look for on an X-Ray scan, and use the descriptor probabilities to estimate the likelihood of a diagnosis. Our model is explainable by design, as the final diagnosis prediction is directly based on the prediction of the underlying descriptors. We evaluate Xplainer on two chest X-ray datasets, CheXpert and ChestX-ray14, and demonstrate its effectiveness in improving the performance and explainability of zero-shot diagnosis. Our results suggest that Xplainer provides a more detailed understanding of the decision-making process and can be a valuable tool for clinical diagnosis.

Accurate diagnostic coding of medical notes is crucial for enhancing patient care, medical research, and error-free billing in healthcare organizations. Manual coding is a time-consuming task for providers, and diagnostic codes often exhibit low sensitivity and specificity, whereas the free text in medical notes can be a more precise description of a patients status. Thus, accurate automated diagnostic coding of medical notes has become critical for a learning healthcare system. Recent developments in long-document transformer architectures have enabled attention-based deep-learning models to adjudicate medical notes. In addition, contrastive loss functions have been used to jointly pre-train large language and image models with noisy labels. To further improve the automated adjudication of medical notes, we developed an approach based on i) models for ICD-10 diagnostic code sequences using a large real-world data set, ii) large language models for medical notes, and iii) contrastive pre-training to build an integrated model of both ICD-10 diagnostic codes and corresponding medical text. We demonstrate that a contrastive approach for pre-training improves performance over prior state-of-the-art models for the MIMIC-III-50, MIMIC-III-rare50, and MIMIC-III-full diagnostic coding tasks.

Automatic medical report generation (MRG), which possesses significant research value as it can aid radiologists in clinical diagnosis and report composition, has garnered increasing attention. Despite recent progress, generating accurate reports remains arduous due to the requirement for precise clinical comprehension and disease diagnosis inference. Furthermore, owing to the limited accessibility of medical data and the imbalanced distribution of diseases, the underrepresentation of rare diseases in training data makes large-scale medical visual language models (LVLMs) prone to hallucinations, such as omissions or fabrications, severely undermining diagnostic performance and further intensifying the challenges for MRG in practice. In this study, to effectively mitigate hallucinations in medical report generation, we propose a chain-of-medical-thought approach (CoMT), which intends to imitate the cognitive process of human doctors by decomposing diagnostic procedures. The radiological features with different importance are structured into fine-grained medical thought chains to enhance the inferential ability during diagnosis, thereby alleviating hallucination problems and enhancing the diagnostic accuracy of MRG. The code and dataset have been released at https://github.com/FRENKIE-CHIANG/CoMT.

Automatic medical report generation (MRG) is of great research value as it has the potential to relieve radiologists from the heavy burden of report writing. Despite recent advancements, accurate MRG remains challenging due to the need for precise clinical understanding and the identification of clinical findings. Moreover, the imbalanced distribution of diseases makes the challenge even more pronounced, as rare diseases are underrepresented in training data, making their diagnostic performance unreliable. To address these challenges, we propose diagnosis-driven prompts for medical report generation (PromptMRG), a novel framework that aims to improve the diagnostic accuracy of MRG with the guidance of diagnosis-aware prompts. Specifically, PromptMRG is based on encoder-decoder architecture with an extra disease classification branch. When generating reports, the diagnostic results from the classification branch are converted into token prompts to explicitly guide the generation process. To further improve the diagnostic accuracy, we design cross-modal feature enhancement, which retrieves similar reports from the database to assist the diagnosis of a query image by leveraging the knowledge from a pre-trained CLIP. Moreover, the disease imbalanced issue is addressed by applying an adaptive logit-adjusted loss to the classification branch based on the individual learning status of each disease, which overcomes the barrier of text decoder's inability to manipulate disease distributions. Experiments on two MRG benchmarks show the effectiveness of the proposed method, where it obtains state-of-the-art clinical efficacy performance on both datasets.

Future short or long-term space missions require a new generation of monitoring and diagnostic systems due to communication impasses as well as limitations in specialized crew and equipment. Machine learning supported diagnostic systems present a viable solution for medical and technical applications. We discuss challenges and applicability of such systems in light of upcoming missions and outline an example use case for a next-generation medical diagnostic system for future space operations. Additionally, we present approach recommendations and constraints for the successful generation and use of machine learning models aboard a spacecraft.

Medical phrase grounding is crucial for identifying relevant regions in medical images based on phrase queries, facilitating accurate image analysis and diagnosis. However, current methods rely on manual extraction of key phrases from medical reports, reducing efficiency and increasing the workload for clinicians. Additionally, the lack of model confidence estimation limits clinical trust and usability. In this paper, we introduce a novel task called Medical Report Grounding (MRG), which aims to directly identify diagnostic phrases and their corresponding grounding boxes from medical reports in an end-to-end manner. To address this challenge, we propose uMedGround, a robust and reliable framework that leverages a multimodal large language model to predict diagnostic phrases by embedding a unique token, <BOX>, into the vocabulary to enhance detection capabilities. A vision encoder-decoder processes the embedded token and input image to generate grounding boxes. Critically, uMedGround incorporates an uncertainty-aware prediction model, significantly improving the robustness and reliability of grounding predictions. Experimental results demonstrate that uMedGround outperforms state-of-the-art medical phrase grounding methods and fine-tuned large visual-language models, validating its effectiveness and reliability. This study represents a pioneering exploration of the MRG task, marking the first-ever endeavor in this domain. Additionally, we demonstrate the applicability of uMedGround in medical visual question answering and class-based localization tasks, where it highlights visual evidence aligned with key diagnostic phrases, supporting clinicians in interpreting various types of textual inputs, including free-text reports, visual question answering queries, and class labels.

The professionalism of a human doctor in outpatient service depends on two core abilities: the ability to make accurate medical decisions and the medical consultation skill to conduct strategic, empathetic patient inquiry. Existing Large Language Models (LLMs) have achieved remarkable accuracy on medical decision-making benchmarks. However, they often lack the ability to conduct the strategic and empathetic consultation, which is essential for real-world clinical scenarios. To address this gap, we propose Doctor-R1, an AI doctor agent trained to master both of the capabilities by ask high-yield questions and conduct strategic multi-turn inquiry to guide decision-making. Our framework introduces three key components: a multi-agent interactive environment, a two-tiered reward architecture that separately optimizes clinical decision-making and communicative inquiry skills, and an experience repository to ground policy learning in high-quality prior trajectories. We evaluate Doctor-R1 on OpenAI's HealthBench and MAQuE, assessed across multi-facet metrics, such as communication quality, user experience, and task accuracy. Remarkably, Doctor-R1 surpasses state-of-the-art open-source specialized LLMs by a substantial margin with higher parameter efficiency and outperforms powerful proprietary models. Furthermore, the human evaluations show a strong preference for Doctor-R1 to generate human-preferred clinical dialogue, demonstrating the effectiveness of the framework.

As machine learning models become increasingly prevalent in medical diagnostics, the need for interpretability and transparency becomes paramount. The XAI Renaissance signifies a significant shift in the field, aiming to redefine the interpretability of medical diagnostic models. This paper explores the innovative approaches and methodologies within the realm of Explainable AI (XAI) that are revolutionizing the interpretability of medical diagnostic models. By shedding light on the underlying decision-making process, XAI techniques empower healthcare professionals to understand, trust, and effectively utilize these models for accurate and reliable medical diagnoses. This review highlights the key advancements in XAI for medical diagnostics and their potential to transform the healthcare landscape, ultimately improving patient outcomes and fostering trust in AI-driven diagnostic systems.

International Classification of Disease (ICD) coding procedure which refers to tagging medical notes with diagnosis codes has been shown to be effective and crucial to the billing system in medical sector. Currently, ICD codes are assigned to a clinical note manually which is likely to cause many errors. Moreover, training skilled coders also requires time and human resources. Therefore, automating the ICD code determination process is an important task. With the advancement of artificial intelligence theory and computational hardware, machine learning approach has emerged as a suitable solution to automate this process. In this project, we apply a transformer-based architecture to capture the interdependence among the tokens of a document and then use a code-wise attention mechanism to learn code-specific representations of the entire document. Finally, they are fed to separate dense layers for corresponding code prediction. Furthermore, to handle the imbalance in the code frequency of clinical datasets, we employ a label distribution aware margin (LDAM) loss function. The experimental results on the MIMIC-III dataset show that our proposed model outperforms other baselines by a significant margin. In particular, our best setting achieves a micro-AUC score of 0.923 compared to 0.868 of bidirectional recurrent neural networks. We also show that by using the code-wise attention mechanism, the model can provide more insights about its prediction, and thus it can support clinicians to make reliable decisions. Our code is available online (https://github.com/biplob1ly/TransICD)

Multimodal large language models (MLLMs) have begun to demonstrate robust reasoning capabilities on general tasks, yet their application in the medical domain remains in its early stages. Constructing chain-of-thought (CoT) training data is essential for bolstering the reasoning abilities of medical MLLMs. However, existing approaches exhibit a deficiency in offering a comprehensive framework for searching and evaluating effective reasoning paths towards critical diagnosis. To address this challenge, we propose Mentor-Intern Collaborative Search (MICS), a novel reasoning-path searching scheme to generate rigorous and effective medical CoT data. MICS first leverages mentor models to initialize the reasoning, one step at a time, then prompts each intern model to continue the thinking along those initiated paths, and finally selects the optimal reasoning path according to the overall reasoning performance of multiple intern models. The reasoning performance is determined by an MICS-Score, which assesses the quality of generated reasoning paths. Eventually, we construct MMRP, a multi-task medical reasoning dataset with ranked difficulty, and Chiron-o1, a new medical MLLM devised via a curriculum learning strategy, with robust visual question-answering and generalizable reasoning capabilities. Extensive experiments demonstrate that Chiron-o1, trained on our CoT dataset constructed using MICS, achieves state-of-the-art performance across a list of medical visual question answering and reasoning benchmarks. Codes are available at GitHub - manglu097/Chiron-o1: Enhancing Step-by-Step and Verifiable Medical Reasoning in MLLMs

In recent years, there is strong emphasis on mining medical data using machine learning techniques. A common problem is to obtain a noiseless set of textual documents, with a relevant content for the research question, and developing a Question Answering (QA) model for a specific medical field. The purpose of this paper is to present a new methodology for building a medical dataset and obtain a QA model for analysis of symptoms and impact on daily life for a specific disease domain. The ``Mental Health'' forum was used, a forum dedicated to people suffering from schizophrenia and different mental disorders. Relevant posts of active users, who regularly participate, were extrapolated providing a new method of obtaining low-bias content and without privacy issues. Furthermore, it is shown how to pre-process the dataset to convert it into a QA dataset. The Bidirectional Encoder Representations from Transformers (BERT), DistilBERT, RoBERTa, and BioBERT models were fine-tuned and evaluated via F1-Score, Exact Match, Precision and Recall. Accurate empirical experiments demonstrated the effectiveness of the proposed method for obtaining an accurate dataset for QA model implementation. By fine-tuning the BioBERT QA model, we achieved an F1 score of 0.885, showing a considerable improvement and outperforming the state-of-the-art model for mental disorders domain.

The proliferation of Large Language Models (LLMs) in medicine has enabled impressive capabilities, yet a critical gap remains in their ability to perform systematic, transparent, and verifiable reasoning, a cornerstone of clinical practice. This has catalyzed a shift from single-step answer generation to the development of LLMs explicitly designed for medical reasoning. This paper provides the first systematic review of this emerging field. We propose a taxonomy of reasoning enhancement techniques, categorized into training-time strategies (e.g., supervised fine-tuning, reinforcement learning) and test-time mechanisms (e.g., prompt engineering, multi-agent systems). We analyze how these techniques are applied across different data modalities (text, image, code) and in key clinical applications such as diagnosis, education, and treatment planning. Furthermore, we survey the evolution of evaluation benchmarks from simple accuracy metrics to sophisticated assessments of reasoning quality and visual interpretability. Based on an analysis of 60 seminal studies from 2022-2025, we conclude by identifying critical challenges, including the faithfulness-plausibility gap and the need for native multimodal reasoning, and outlining future directions toward building efficient, robust, and sociotechnically responsible medical AI.

The need for improved diagnostic methods in ophthalmology is acute, especially in the underdeveloped regions with limited access to specialists and advanced equipment. Therefore, we introduce VisionUnite, a novel vision-language foundation model for ophthalmology enhanced with clinical knowledge. VisionUnite has been pretrained on an extensive dataset comprising 1.24 million image-text pairs, and further refined using our proposed MMFundus dataset, which includes 296,379 high-quality fundus image-text pairs and 889,137 simulated doctor-patient dialogue instances. Our experiments indicate that VisionUnite outperforms existing generative foundation models such as GPT-4V and Gemini Pro. It also demonstrates diagnostic capabilities comparable to junior ophthalmologists. VisionUnite performs well in various clinical scenarios including open-ended multi-disease diagnosis, clinical explanation, and patient interaction, making it a highly versatile tool for initial ophthalmic disease screening. VisionUnite can also serve as an educational aid for junior ophthalmologists, accelerating their acquisition of knowledge regarding both common and underrepresented ophthalmic conditions. VisionUnite represents a significant advancement in ophthalmology, with broad implications for diagnostics, medical education, and understanding of disease mechanisms. The source code is at https://github.com/HUANGLIZI/VisionUnite.

Keeping track of scientific challenges, advances and emerging directions is a fundamental part of research. However, researchers face a flood of papers that hinders discovery of important knowledge. In biomedicine, this directly impacts human lives. To address this problem, we present a novel task of extraction and search of scientific challenges and directions, to facilitate rapid knowledge discovery. We construct and release an expert-annotated corpus of texts sampled from full-length papers, labeled with novel semantic categories that generalize across many types of challenges and directions. We focus on a large corpus of interdisciplinary work relating to the COVID-19 pandemic, ranging from biomedicine to areas such as AI and economics. We apply a model trained on our data to identify challenges and directions across the corpus and build a dedicated search engine. In experiments with 19 researchers and clinicians using our system, we outperform a popular scientific search engine in assisting knowledge discovery. Finally, we show that models trained on our resource generalize to the wider biomedical domain and to AI papers, highlighting its broad utility. We make our data, model and search engine publicly available. https://challenges.apps.allenai.org/

Current medical language models, adapted from large language models (LLMs), typically predict ICD code-based diagnosis from electronic health records (EHRs) because these labels are readily available. However, ICD codes do not capture the nuanced, context-rich reasoning clinicians use for diagnosis. Clinicians synthesize diverse patient data and reference clinical practice guidelines (CPGs) to make evidence-based decisions. This misalignment limits the clinical utility of existing models. We introduce GARMLE-G, a Generation-Augmented Retrieval framework that grounds medical language model outputs in authoritative CPGs. Unlike conventional Retrieval-Augmented Generation based approaches, GARMLE-G enables hallucination-free outputs by directly retrieving authoritative guideline content without relying on model-generated text. It (1) integrates LLM predictions with EHR data to create semantically rich queries, (2) retrieves relevant CPG knowledge snippets via embedding similarity, and (3) fuses guideline content with model output to generate clinically aligned recommendations. A prototype system for hypertension diagnosis was developed and evaluated on multiple metrics, demonstrating superior retrieval precision, semantic relevance, and clinical guideline adherence compared to RAG-based baselines, while maintaining a lightweight architecture suitable for localized healthcare deployment. This work provides a scalable, low-cost, and hallucination-free method for grounding medical language models in evidence-based clinical practice, with strong potential for broader clinical deployment.

The emergence of advanced reasoning capabilities in Large Language Models (LLMs) marks a transformative development in healthcare applications. Beyond merely expanding functional capabilities, these reasoning mechanisms enhance decision transparency and explainability-critical requirements in medical contexts. This survey examines the transformation of medical LLMs from basic information retrieval tools to sophisticated clinical reasoning systems capable of supporting complex healthcare decisions. We provide a thorough analysis of the enabling technological foundations, with a particular focus on specialized prompting techniques like Chain-of-Thought and recent breakthroughs in Reinforcement Learning exemplified by DeepSeek-R1. Our investigation evaluates purpose-built medical frameworks while also examining emerging paradigms such as multi-agent collaborative systems and innovative prompting architectures. The survey critically assesses current evaluation methodologies for medical validation and addresses persistent challenges in field interpretation limitations, bias mitigation strategies, patient safety frameworks, and integration of multimodal clinical data. Through this survey, we seek to establish a roadmap for developing reliable LLMs that can serve as effective partners in clinical practice and medical research.

High-quality medical systematic reviews require comprehensive literature searches to ensure the recommendations and outcomes are sufficiently reliable. Indeed, searching for relevant medical literature is a key phase in constructing systematic reviews and often involves domain (medical researchers) and search (information specialists) experts in developing the search queries. Queries in this context are highly complex, based on Boolean logic, include free-text terms and index terms from standardised terminologies (e.g., MeSH), and are difficult and time-consuming to build. The use of MeSH terms, in particular, has been shown to improve the quality of the search results. However, identifying the correct MeSH terms to include in a query is difficult: information experts are often unfamiliar with the MeSH database and unsure about the appropriateness of MeSH terms for a query. Naturally, the full value of the MeSH terminology is often not fully exploited. This paper investigates methods to suggest MeSH terms based on an initial Boolean query that includes only free-text terms. These methods promise to automatically identify highly effective MeSH terms for inclusion in a systematic review query. Our study contributes an empirical evaluation of several MeSH term suggestion methods. We perform an extensive analysis of the retrieval, ranking, and refinement of MeSH term suggestions for each method and how these suggestions impact the effectiveness of Boolean queries.

Recent advancements in reasoning-enhanced large language models (LLMs), such as DeepSeek-R1 and OpenAI-o3, have demonstrated significant progress. However, their application in professional medical contexts remains underexplored, particularly in evaluating the quality of their reasoning processes alongside final outputs. Here, we introduce MedR-Bench, a benchmarking dataset of 1,453 structured patient cases, annotated with reasoning references derived from clinical case reports. Spanning 13 body systems and 10 specialties, it includes both common and rare diseases. To comprehensively evaluate LLM performance, we propose a framework encompassing three critical examination recommendation, diagnostic decision-making, and treatment planning, simulating the entire patient care journey. To assess reasoning quality, we present the Reasoning Evaluator, a novel automated system that objectively scores free-text reasoning responses based on efficiency, actuality, and completeness using dynamic cross-referencing and evidence checks. Using this benchmark, we evaluate five state-of-the-art reasoning LLMs, including DeepSeek-R1, OpenAI-o3-mini, and Gemini-2.0-Flash Thinking, etc. Our results show that current LLMs achieve over 85% accuracy in relatively simple diagnostic tasks when provided with sufficient examination results. However, performance declines in more complex tasks, such as examination recommendation and treatment planning. While reasoning outputs are generally reliable, with factuality scores exceeding 90%, critical reasoning steps are frequently missed. These findings underscore both the progress and limitations of clinical LLMs. Notably, open-source models like DeepSeek-R1 are narrowing the gap with proprietary systems, highlighting their potential to drive accessible and equitable advancements in healthcare.

Mental health is a significant and growing public health concern. As language usage can be leveraged to obtain crucial insights into mental health conditions, there is a need for large-scale, labeled, mental health-related datasets of users who have been diagnosed with one or more of such conditions. In this paper, we investigate the creation of high-precision patterns to identify self-reported diagnoses of nine different mental health conditions, and obtain high-quality labeled data without the need for manual labelling. We introduce the SMHD (Self-reported Mental Health Diagnoses) dataset and make it available. SMHD is a novel large dataset of social media posts from users with one or multiple mental health conditions along with matched control users. We examine distinctions in users' language, as measured by linguistic and psychological variables. We further explore text classification methods to identify individuals with mental conditions through their language.

The outbreak of COVID-19 has shocked the entire world with its fairly rapid spread and has challenged different sectors. One of the most effective ways to limit its spread is the early and accurate diagnosing infected patients. Medical imaging, such as X-ray and Computed Tomography (CT), combined with the potential of Artificial Intelligence (AI), plays an essential role in supporting medical personnel in the diagnosis process. Thus, in this article five different deep learning models (ResNet18, ResNet34, InceptionV3, InceptionResNetV2 and DenseNet161) and their ensemble, using majority voting have been used to classify COVID-19, pneumoni{\ae} and healthy subjects using chest X-ray images. Multilabel classification was performed to predict multiple pathologies for each patient, if present. Firstly, the interpretability of each of the networks was thoroughly studied using local interpretability methods - occlusion, saliency, input X gradient, guided backpropagation, integrated gradients, and DeepLIFT, and using a global technique - neuron activation profiles. The mean Micro-F1 score of the models for COVID-19 classifications ranges from 0.66 to 0.875, and is 0.89 for the ensemble of the network models. The qualitative results showed that the ResNets were the most interpretable models. This research demonstrates the importance of using interpretability methods to compare different models before making a decision regarding the best performing model.

Coronavirus disease 2019 (Covid-19) is highly contagious with limited treatment options. Early and accurate diagnosis of Covid-19 is crucial in reducing the spread of the disease and its accompanied mortality. Currently, detection by reverse transcriptase polymerase chain reaction (RT-PCR) is the gold standard of outpatient and inpatient detection of Covid-19. RT-PCR is a rapid method, however, its accuracy in detection is only ~70-75%. Another approved strategy is computed tomography (CT) imaging. CT imaging has a much higher sensitivity of ~80-98%, but similar accuracy of 70%. To enhance the accuracy of CT imaging detection, we developed an open-source set of algorithms called CovidCTNet that successfully differentiates Covid-19 from community-acquired pneumonia (CAP) and other lung diseases. CovidCTNet increases the accuracy of CT imaging detection to 90% compared to radiologists (70%). The model is designed to work with heterogeneous and small sample sizes independent of the CT imaging hardware. In order to facilitate the detection of Covid-19 globally and assist radiologists and physicians in the screening process, we are releasing all algorithms and parametric details in an open-source format. Open-source sharing of our CovidCTNet enables developers to rapidly improve and optimize services, while preserving user privacy and data ownership.

Integrating large language models (LLMs) like DeepSeek R1 into healthcare requires rigorous evaluation of their reasoning alignment with clinical expertise. This study assesses DeepSeek R1's medical reasoning against expert patterns using 100 MedQA clinical cases. The model achieved 93% diagnostic accuracy, demonstrating systematic clinical judgment through differential diagnosis, guideline-based treatment selection, and integration of patient-specific factors. However, error analysis of seven incorrect cases revealed persistent limitations: anchoring bias, challenges reconciling conflicting data, insufficient exploration of alternatives, overthinking, knowledge gaps, and premature prioritization of definitive treatment over intermediate care. Crucially, reasoning length correlated with accuracy - shorter responses (<5,000 characters) were more reliable, suggesting extended explanations may signal uncertainty or rationalization of errors. While DeepSeek R1 exhibits foundational clinical reasoning capabilities, recurring flaws highlight critical areas for refinement, including bias mitigation, knowledge updates, and structured reasoning frameworks. These findings underscore LLMs' potential to augment medical decision-making through artificial reasoning but emphasize the need for domain-specific validation, interpretability safeguards, and confidence metrics (e.g., response length thresholds) to ensure reliability in real-world applications.

Objective: Using natural language processing (NLP) to find sentences that state treatment plans in a clinical note, would automate plan extraction and would further enable their use in tools that help providers and care managers. However, as in the most NLP tasks on clinical text, creating gold standard to train and test NLP models is tedious and expensive. Fortuitously, sometimes but not always clinical notes contain sections with a heading that identifies the section as a plan. Leveraging contents of such labeled sections as a noisy training data, we assessed accuracy of NLP models trained with the data. Methods: We used common variations of plan headings and rule-based heuristics to find plan sections with headings in clinical notes, and we extracted sentences from them and formed a noisy training data of plan sentences. We trained Support Vector Machine (SVM) and Convolutional Neural Network (CNN) models with the data. We measured accuracy of the trained models on the noisy dataset using ten-fold cross validation and separately on a set-aside manually annotated dataset. Results: About 13% of 117,730 clinical notes contained treatment plans sections with recognizable headings in the 1001 longitudinal patient records that were obtained from Cleveland Clinic under an IRB approval. We were able to extract and create a noisy training data of 13,492 plan sentences from the clinical notes. CNN achieved best F measures, 0.91 and 0.97 in the cross-validation and set-aside evaluation experiments respectively. SVM slightly underperformed with F measures of 0.89 and 0.96 in the same experiments. Conclusion: Our study showed that the training supervised learning models using noisy plan sentences was effective in identifying them in all clinical notes. More broadly, sections with informal headings in clinical notes can be a good source for generating effective training data.

In response to the pressing need for advanced clinical problem-solving tools in healthcare, we introduce BooksMed, a novel framework based on a Large Language Model (LLM). BooksMed uniquely emulates human cognitive processes to deliver evidence-based and reliable responses, utilizing the GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) framework to effectively quantify evidence strength. For clinical decision-making to be appropriately assessed, an evaluation metric that is clinically aligned and validated is required. As a solution, we present ExpertMedQA, a multispecialty clinical benchmark comprised of open-ended, expert-level clinical questions, and validated by a diverse group of medical professionals. By demanding an in-depth understanding and critical appraisal of up-to-date clinical literature, ExpertMedQA rigorously evaluates LLM performance. BooksMed outperforms existing state-of-the-art models Med-PaLM 2, Almanac, and ChatGPT in a variety of medical scenarios. Therefore, a framework that mimics human cognitive stages could be a useful tool for providing reliable and evidence-based responses to clinical inquiries.

How do we most effectively treat a disease or condition? Ideally, we could consult a database of evidence gleaned from clinical trials to answer such questions. Unfortunately, no such database exists; clinical trial results are instead disseminated primarily via lengthy natural language articles. Perusing all such articles would be prohibitively time-consuming for healthcare practitioners; they instead tend to depend on manually compiled systematic reviews of medical literature to inform care. NLP may speed this process up, and eventually facilitate immediate consult of published evidence. The Evidence Inference dataset was recently released to facilitate research toward this end. This task entails inferring the comparative performance of two treatments, with respect to a given outcome, from a particular article (describing a clinical trial) and identifying supporting evidence. For instance: Does this article report that chemotherapy performed better than surgery for five-year survival rates of operable cancers? In this paper, we collect additional annotations to expand the Evidence Inference dataset by 25\%, provide stronger baseline models, systematically inspect the errors that these make, and probe dataset quality. We also release an abstract only (as opposed to full-texts) version of the task for rapid model prototyping. The updated corpus, documentation, and code for new baselines and evaluations are available at http://evidence-inference.ebm-nlp.com/.

Understanding the prevalence of misinformation in health topics online can inform public health policies and interventions. However, measuring such misinformation at scale remains a challenge, particularly for high-stakes but understudied topics like opioid-use disorder (OUD)--a leading cause of death in the U.S. We present the first large-scale study of OUD-related myths on YouTube, a widely-used platform for health information. With clinical experts, we validate 8 pervasive myths and release an expert-labeled video dataset. To scale labeling, we introduce MythTriage, an efficient triage pipeline that uses a lightweight model for routine cases and defers harder ones to a high-performing, but costlier, large language model (LLM). MythTriage achieves up to 0.86 macro F1-score while estimated to reduce annotation time and financial cost by over 76% compared to experts and full LLM labeling. We analyze 2.9K search results and 343K recommendations, uncovering how myths persist on YouTube and offering actionable insights for public health and platform moderation.

Depression poses significant challenges to patients and healthcare organizations, necessitating efficient assessment methods. Existing paradigms typically focus on a patient-doctor way that overlooks multi-role interactions, such as family involvement in the evaluation and caregiving process. Moreover, current automatic depression detection (ADD) methods usually model depression detection as a classification or regression task, lacking interpretability for the decision-making process. To address these issues, we developed InterMind, a doctor-patient-family interactive depression assessment system empowered by large language models (LLMs). Our system enables patients and families to contribute descriptions, generates assistive diagnostic reports for doctors, and provides actionable insights, improving diagnostic precision and efficiency. To enhance LLMs' performance in psychological counseling and diagnostic interpretability, we integrate retrieval-augmented generation (RAG) and chain-of-thoughts (CoT) techniques for data augmentation, which mitigates the hallucination issue of LLMs in specific scenarios after instruction fine-tuning. Quantitative experiments and professional assessments by clinicians validate the effectiveness of our system.

Chain-of-thought (COT) prompting can help large language models (LLMs) reason toward correct answers, but its efficacy in reasoning toward incorrect answers is unexplored. This process of elimination (PoE), when used with COT, can enhance self-consistency, interpretability, and tasks such as medical diagnoses of exclusion. Thus, we propose PoE with COT, where LLMs must reason toward incorrect options on multiple-choice questions. We evaluate the ability of GPT-3.5, LLaMA-2, and Falcon to perform PoE with COT on a total of four commonsense and scientific reasoning datasets. We find that the strategy of PoE always underperforms the strategy of choosing the correct answer. The agreement of these strategies is also lower than the self-consistency of each strategy. To study these issues further, we conduct error analyses and give suggestions for future work.

Medical question-answering (QA) is a critical task for evaluating how effectively large language models (LLMs) encode clinical knowledge and assessing their potential applications in medicine. Despite showing promise on multiple-choice tests, LLMs frequently struggle with open-ended medical questions, producing responses with dangerous hallucinations or lacking comprehensive coverage of critical aspects. Existing approaches attempt to address these challenges through domain-specific fine-tuning, but this proves resource-intensive and difficult to scale across models. To improve the comprehensiveness and factuality of medical responses, we propose a novel approach utilizing structured medical reasoning. Our method guides LLMs through an seven-step cognitive process inspired by clinical diagnosis, enabling more accurate and complete answers without additional training. Experiments on the MedLFQA benchmark demonstrate that our approach achieves the highest Factuality Score of 85.8, surpassing fine-tuned models. Notably, this improvement transfers to smaller models, highlighting the method's efficiency and scalability. Our code and datasets are available.

In recent years, medical information technology has made it possible for electronic health record (EHR) to store fairly complete clinical data. This has brought health care into the era of "big data". However, medical data are often sparse and strongly correlated, which means that medical problems cannot be solved effectively. With the rapid development of deep learning in recent years, it has provided opportunities for the use of big data in healthcare. In this paper, we propose a temporal-saptial correlation attention network (TSCAN) to handle some clinical characteristic prediction problems, such as predicting death, predicting length of stay, detecting physiologic decline, and classifying phenotypes. Based on the design of the attention mechanism model, our approach can effectively remove irrelevant items in clinical data and irrelevant nodes in time according to different tasks, so as to obtain more accurate prediction results. Our method can also find key clinical indicators of important outcomes that can be used to improve treatment options. Our experiments use information from the Medical Information Mart for Intensive Care (MIMIC-IV) database, which is open to the public. Finally, we have achieved significant performance benefits of 2.0\% (metric) compared to other SOTA prediction methods. We achieved a staggering 90.7\% on mortality rate, 45.1\% on length of stay. The source code can be find: https://github.com/yuyuheintju/TSCAN.

This article presents the Cogni-CISMeF project, which aims at improving medical information search in the CISMeF system (Catalog and Index of French-language health resources) by including a conversational agent to interact with the user in natural language. To study the cognitive processes involved during the information search, a bottom-up methodology was adopted. Experimentation has been set up to obtain human dialogs between a user (playing the role of patient) dealing with medical information search and a CISMeF expert refining the request. The analysis of these dialogs underlined the use of discursive evidence: vocabulary, reformulation, implicit or explicit expression of user intentions, conversational sequences, etc. A model of artificial agent is proposed. It leads the user in its information search by proposing to him examples, assistance and choices. This model was implemented and integrated in the CISMeF system. ---- Cet article d\'ecrit le projet Cogni-CISMeF qui propose un module de dialogue Homme-Machine \`a int\'egrer dans le syst\`eme d'indexation de connaissances m\'edicales CISMeF (Catalogue et Index des Sites M\'edicaux Francophones). Nous avons adopt\'e une d\'emarche de mod\'elisation cognitive en proc\'edant \`a un recueil de corpus de dialogues entre un utilisateur (jouant le r\^ole d'un patient) d\'esirant une information m\'edicale et un expert CISMeF af inant cette demande pour construire la requ\^ete. Nous avons analys\'e la structure des dialogues ainsi obtenus et avons \'etudi\'e un certain nombre d'indices discursifs : vocabulaire employ\'e, marques de reformulation, commentaires m\'eta et \'epilinguistiques, expression implicite ou explicite des intentions de l'utilisateur, encha\^inement conversationnel, etc. De cette analyse, nous avons construit un mod\`ele d'agent artificiel dot\'e de capacit\'es cognitives capables d'aider l'utilisateur dans sa t\^ache de recherche d'information. Ce mod\`ele a \'et\'e impl\'ement\'e et int\'egr\'e dans le syst\`eme CISMeF.

Lung cancer stands as the preeminent cause of cancer-related mortality globally. Prompt and precise diagnosis, coupled with effective treatment, is imperative to reduce the fatality rates associated with this formidable disease. This study introduces a cutting-edge deep learning framework for the classification of lung cancer from CT scan imagery. The research encompasses a suite of image pre-processing strategies, notably Canny edge detection, and wavelet transformations, which precede the extraction of salient features and subsequent classification via a Multi-Layer Perceptron (MLP). The optimization process is further refined using the Dragonfly Algorithm (DA). The methodology put forth has attained an impressive training and testing accuracy of 99.82\%, underscoring its efficacy and reliability in the accurate diagnosis of lung cancer.

Rare diseases, including Inborn Errors of Metabolism (IEM), pose significant diagnostic challenges. Case reports serve as key but computationally underutilized resources to inform diagnosis. Clinical dense information extraction refers to organizing medical information into structured predefined categories. Large Language Models (LLMs) may enable scalable information extraction from case reports but are rarely evaluated for this task. We introduce CaseReportBench, an expert-annotated dataset for dense information extraction of case reports, focusing on IEMs. Using this dataset, we assess various models and prompting strategies, introducing novel approaches such as category-specific prompting and subheading-filtered data integration. Zero-shot chain-of-thought prompting offers little advantage over standard zero-shot prompting. Category-specific prompting improves alignment with the benchmark. The open-source model Qwen2.5-7B outperforms GPT-4o for this task. Our clinician evaluations show that LLMs can extract clinically relevant details from case reports, supporting rare disease diagnosis and management. We also highlight areas for improvement, such as LLMs' limitations in recognizing negative findings important for differential diagnosis. This work advances LLM-driven clinical natural language processing and paves the way for scalable medical AI applications.

Global healthcare providers are exploring use of large language models (LLMs) to provide medical advice to the public. LLMs now achieve nearly perfect scores on medical licensing exams, but this does not necessarily translate to accurate performance in real-world settings. We tested if LLMs can assist members of the public in identifying underlying conditions and choosing a course of action (disposition) in ten medical scenarios in a controlled study with 1,298 participants. Participants were randomly assigned to receive assistance from an LLM (GPT-4o, Llama 3, Command R+) or a source of their choice (control). Tested alone, LLMs complete the scenarios accurately, correctly identifying conditions in 94.9% of cases and disposition in 56.3% on average. However, participants using the same LLMs identified relevant conditions in less than 34.5% of cases and disposition in less than 44.2%, both no better than the control group. We identify user interactions as a challenge to the deployment of LLMs for medical advice. Standard benchmarks for medical knowledge and simulated patient interactions do not predict the failures we find with human participants. Moving forward, we recommend systematic human user testing to evaluate interactive capabilities prior to public deployments in healthcare.

Diagnosing a whole-slide image is an interactive, multi-stage process involving changes in magnification and movement between fields. Although recent pathology foundation models are strong, practical agentic systems that decide what field to examine next, adjust magnification, and deliver explainable diagnoses are still lacking. The blocker is data: scalable, clinically aligned supervision of expert viewing behavior that is tacit and experience-based, not written in textbooks or online, and therefore absent from large language model training. We introduce the AI Session Recorder, which works with standard WSI viewers to unobtrusively record routine navigation and convert the viewer logs into standardized behavioral commands (inspect or peek at discrete magnifications) and bounding boxes. A lightweight human-in-the-loop review turns AI-drafted rationales into the Pathology-CoT dataset, a form of paired "where to look" and "why it matters" supervision produced at roughly six times lower labeling time. Using this behavioral data, we build Pathologist-o3, a two-stage agent that first proposes regions of interest and then performs behavior-guided reasoning. On gastrointestinal lymph-node metastasis detection, it achieved 84.5% precision, 100.0% recall, and 75.4% accuracy, exceeding the state-of-the-art OpenAI o3 model and generalizing across backbones. To our knowledge, this constitutes one of the first behavior-grounded agentic systems in pathology. Turning everyday viewer logs into scalable, expert-validated supervision, our framework makes agentic pathology practical and establishes a path to human-aligned, upgradeable clinical AI.

Background: Natural Language Processing (NLP) is widely used to extract clinical insights from Electronic Health Records (EHRs). However, the lack of annotated data, automated tools, and other challenges hinder the full utilisation of NLP for EHRs. Various Machine Learning (ML), Deep Learning (DL) and NLP techniques are studied and compared to understand the limitations and opportunities in this space comprehensively. Methodology: After screening 261 articles from 11 databases, we included 127 papers for full-text review covering seven categories of articles: 1) medical note classification, 2) clinical entity recognition, 3) text summarisation, 4) deep learning (DL) and transfer learning architecture, 5) information extraction, 6) Medical language translation and 7) other NLP applications. This study follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Result and Discussion: EHR was the most commonly used data type among the selected articles, and the datasets were primarily unstructured. Various ML and DL methods were used, with prediction or classification being the most common application of ML or DL. The most common use cases were: the International Classification of Diseases, Ninth Revision (ICD-9) classification, clinical note analysis, and named entity recognition (NER) for clinical descriptions and research on psychiatric disorders. Conclusion: We find that the adopted ML models were not adequately assessed. In addition, the data imbalance problem is quite important, yet we must find techniques to address this underlining problem. Future studies should address key limitations in studies, primarily identifying Lupus Nephritis, Suicide Attempts, perinatal self-harmed and ICD-9 classification.

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.

The rapid increase of computed tomography (CT) scans and their time-consuming manual analysis have created an urgent need for robust automated analysis techniques in clinical settings. These aim to assist radiologists and help them managing their growing workload. Existing methods typically generate entire reports directly from 3D CT images, without explicitly focusing on observed abnormalities. This unguided approach often results in repetitive content or incomplete reports, failing to prioritize anomaly-specific descriptions. We propose a new anomaly-guided report generation model, which first predicts abnormalities and then generates targeted descriptions for each. Evaluation on a public dataset demonstrates significant improvements in report quality and clinical relevance. We extend our work by conducting an ablation study to demonstrate its effectiveness.

Assessing scientific claims requires identifying, extracting, and reasoning with multimodal data expressed in information-rich figures in scientific literature. Despite the large body of work in scientific QA, figure captioning, and other multimodal reasoning tasks over chart-based data, there are no readily usable multimodal benchmarks that directly test claim verification abilities. To remedy this gap, we introduce a new benchmark MuSciClaims accompanied by diagnostics tasks. We automatically extract supported claims from scientific articles, which we manually perturb to produce contradicted claims. The perturbations are designed to test for a specific set of claim verification capabilities. We also introduce a suite of diagnostic tasks that help understand model failures. Our results show most vision-language models are poor (~0.3-0.5 F1), with even the best model only achieving 0.72 F1. They are also biased towards judging claims as supported, likely misunderstanding nuanced perturbations within the claims. Our diagnostics show models are bad at localizing correct evidence within figures, struggle with aggregating information across modalities, and often fail to understand basic components of the figure.

This paper explores the task of radiology report generation, which aims at generating free-text descriptions for a set of radiographs. One significant challenge of this task is how to correctly maintain the consistency between the images and the lengthy report. Previous research explored solving this issue through planning-based methods, which generate reports only based on high-level plans. However, these plans usually only contain the major observations from the radiographs (e.g., lung opacity), lacking much necessary information, such as the observation characteristics and preliminary clinical diagnoses. To address this problem, the system should also take the image information into account together with the textual plan and perform stronger reasoning during the generation process. In this paper, we propose an observation-guided radiology report generation framework (ORGAN). It first produces an observation plan and then feeds both the plan and radiographs for report generation, where an observation graph and a tree reasoning mechanism are adopted to precisely enrich the plan information by capturing the multi-formats of each observation. Experimental results demonstrate that our framework outperforms previous state-of-the-art methods regarding text quality and clinical efficacy

Rare diseases present unique challenges in healthcare, often suffering from delayed diagnosis and fragmented information landscapes. The scarcity of reliable knowledge in these conditions poses a distinct challenge for Large Language Models (LLMs) in supporting clinical management and delivering precise patient information underscoring the need for focused training on these 'zebra' cases. We present Zebra-Llama, a specialized context-aware language model with high precision Retrieval Augmented Generation (RAG) capability, focusing on Ehlers-Danlos Syndrome (EDS) as our case study. EDS, affecting 1 in 5,000 individuals, exemplifies the complexities of rare diseases with its diverse symptoms, multiple subtypes, and evolving diagnostic criteria. By implementing a novel context-aware fine-tuning methodology trained on questions derived from medical literature, patient experiences, and clinical resources, along with expertly curated responses, Zebra-Llama demonstrates unprecedented capabilities in handling EDS-related queries. On a test set of real-world questions collected from EDS patients and clinicians, medical experts evaluated the responses generated by both models, revealing Zebra-Llama's substantial improvements over base model (Llama 3.1-8B-Instruct) in thoroughness (77.5% vs. 70.1%), accuracy (83.0% vs. 78.8%), clarity (74.7% vs. 72.0%) and citation reliability (70.6% vs. 52.3%). Released as an open-source resource, Zebra-Llama not only provides more accessible and reliable EDS information but also establishes a framework for developing specialized AI solutions for other rare conditions. This work represents a crucial step towards democratizing expert-level knowledge in rare disease management, potentially transforming how healthcare providers and patients navigate the complex landscape of rare diseases.

Automatically summarizing patients' main problems from daily progress notes using natural language processing methods helps to battle against information and cognitive overload in hospital settings and potentially assists providers with computerized diagnostic decision support. Problem list summarization requires a model to understand, abstract, and generate clinical documentation. In this work, we propose a new NLP task that aims to generate a list of problems in a patient's daily care plan using input from the provider's progress notes during hospitalization. We investigate the performance of T5 and BART, two state-of-the-art seq2seq transformer architectures, in solving this problem. We provide a corpus built on top of progress notes from publicly available electronic health record progress notes in the Medical Information Mart for Intensive Care (MIMIC)-III. T5 and BART are trained on general domain text, and we experiment with a data augmentation method and a domain adaptation pre-training method to increase exposure to medical vocabulary and knowledge. Evaluation methods include ROUGE, BERTScore, cosine similarity on sentence embedding, and F-score on medical concepts. Results show that T5 with domain adaptive pre-training achieves significant performance gains compared to a rule-based system and general domain pre-trained language models, indicating a promising direction for tackling the problem summarization task.

Depression has proven to be a significant public health issue, profoundly affecting the psychological well-being of individuals. If it remains undiagnosed, depression can lead to severe health issues, which can manifest physically and even lead to suicide. Generally, Diagnosing depression or any other mental disorder involves conducting semi-structured interviews alongside supplementary questionnaires, including variants of the Patient Health Questionnaire (PHQ) by Clinicians and mental health professionals. This approach places significant reliance on the experience and judgment of trained physicians, making the diagnosis susceptible to personal biases. Given that the underlying mechanisms causing depression are still being actively researched, physicians often face challenges in diagnosing and treating the condition, particularly in its early stages of clinical presentation. Recently, significant strides have been made in Artificial neural computing to solve problems involving text, image, and speech in various domains. Our analysis has aimed to leverage these state-of-the-art (SOTA) models in our experiments to achieve optimal outcomes leveraging multiple modalities. The experiments were performed on the Extended Distress Analysis Interview Corpus Wizard of Oz dataset (E-DAIC) corpus presented in the Audio/Visual Emotion Challenge (AVEC) 2019 Challenge. The proposed solutions demonstrate better results achieved by Proprietary and Open-source Large Language Models (LLMs), which achieved a Root Mean Square Error (RMSE) score of 3.98 on Textual Modality, beating the AVEC 2019 challenge baseline results and current SOTA regression analysis architectures. Additionally, the proposed solution achieved an accuracy of 71.43% in the classification task. The paper also includes a novel audio-visual multi-modal network that predicts PHQ-8 scores with an RMSE of 6.51.

COVID-19 (coronavirus disease 2019) pandemic caused by SARS-CoV-2 has led to a treacherous and devastating catastrophe for humanity. At the time of writing, no specific antivirus drugs or vaccines are recommended to control infection transmission and spread. The current diagnosis of COVID-19 is done by Reverse-Transcription Polymer Chain Reaction (RT-PCR) testing. However, this method is expensive, time-consuming, and not easily available in straitened regions. An interpretable and COVID-19 diagnosis AI framework is devised and developed based on the cough sounds features and symptoms metadata to overcome these limitations. The proposed framework's performance was evaluated using a medical dataset containing Symptoms and Demographic data of 30000 audio segments, 328 cough sounds from 150 patients with four cough classes ( COVID-19, Asthma, Bronchitis, and Healthy). Experiments' results show that the model captures the better and robust feature embedding to distinguish between COVID-19 patient coughs and several types of non-COVID-19 coughs with higher specificity and accuracy of 95.04 pm 0.18% and 96.83pm 0.18% respectively, all the while maintaining interpretability.

The burgeoning integration of 3D medical imaging into healthcare has led to a substantial increase in the workload of medical professionals. To assist clinicians in their diagnostic processes and alleviate their workload, the development of a robust system for retrieving similar case studies presents a viable solution. While the concept holds great promise, the field of 3D medical text-image retrieval is currently limited by the absence of robust evaluation benchmarks and curated datasets. To remedy this, our study presents a groundbreaking dataset, BIMCV-R (This dataset will be released upon acceptance.), which includes an extensive collection of 8,069 3D CT volumes, encompassing over 2 million slices, paired with their respective radiological reports. Expanding upon the foundational work of our dataset, we craft a retrieval strategy, MedFinder. This approach employs a dual-stream network architecture, harnessing the potential of large language models to advance the field of medical image retrieval beyond existing text-image retrieval solutions. It marks our preliminary step towards developing a system capable of facilitating text-to-image, image-to-text, and keyword-based retrieval tasks.

The integration of Large Language Models (LLMs) into healthcare holds significant potential to enhance diagnostic accuracy and support medical treatment planning. These AI-driven systems can analyze vast datasets, assisting clinicians in identifying diseases, recommending treatments, and predicting patient outcomes. This study evaluates the performance of a range of contemporary LLMs, including both open-source and closed-source models, on the 2024 Portuguese National Exam for medical specialty access (PNA), a standardized medical knowledge assessment. Our results highlight considerable variation in accuracy and cost-effectiveness, with several models demonstrating performance exceeding human benchmarks for medical students on this specific task. We identify leading models based on a combined score of accuracy and cost, discuss the implications of reasoning methodologies like Chain-of-Thought, and underscore the potential for LLMs to function as valuable complementary tools aiding medical professionals in complex clinical decision-making.

Artificial Intelligence (AI) has demonstrated significant potential in healthcare, particularly in disease diagnosis and treatment planning. Recent progress in Medical Large Vision-Language Models (Med-LVLMs) has opened up new possibilities for interactive diagnostic tools. However, these models often suffer from factual hallucination, which can lead to incorrect diagnoses. Fine-tuning and retrieval-augmented generation (RAG) have emerged as methods to address these issues. However, the amount of high-quality data and distribution shifts between training data and deployment data limit the application of fine-tuning methods. Although RAG is lightweight and effective, existing RAG-based approaches are not sufficiently general to different medical domains and can potentially cause misalignment issues, both between modalities and between the model and the ground truth. In this paper, we propose a versatile multimodal RAG system, MMed-RAG, designed to enhance the factuality of Med-LVLMs. Our approach introduces a domain-aware retrieval mechanism, an adaptive retrieved contexts selection method, and a provable RAG-based preference fine-tuning strategy. These innovations make the RAG process sufficiently general and reliable, significantly improving alignment when introducing retrieved contexts. Experimental results across five medical datasets (involving radiology, ophthalmology, pathology) on medical VQA and report generation demonstrate that MMed-RAG can achieve an average improvement of 43.8% in the factual accuracy of Med-LVLMs. Our data and code are available in https://github.com/richard-peng-xia/MMed-RAG.

Medical Visual Question Answering (MedVQA), which offers language responses to image-based medical inquiries, represents a challenging task and significant advancement in healthcare. It assists medical experts to swiftly interpret medical images, thereby enabling faster and more accurate diagnoses. However, the model interpretability and transparency of existing MedVQA solutions are often limited, posing challenges in understanding their decision-making processes. To address this issue, we devise a semi-automated annotation process to streamline data preparation and build new benchmark MedVQA datasets R-RAD, R-SLAKE and R-Path. These datasets provide intermediate medical decision-making rationales generated by multimodal large language models and human annotations for question-answering pairs in existing MedVQA datasets, i.e., VQA-RAD, SLAKE and PathVQA. Moreover, we design a novel framework, MedThink, which finetunes lightweight pretrained generative models by incorporating medical decision-making rationales. MedThink includes three distinct strategies to generate decision outcomes and corresponding rationales, thereby clearly showcasing the medical decision-making process during reasoning. Our comprehensive experiments show that our method achieves an accuracy of 83.5% on R-RAD, 86.3% on R-SLAKE and 87.2% on R-Path. These results significantly exceed those of existing state-of-the-art models with comparable parameters. Datasets and code will be released.

Objective: Data unavailability has been one of the biggest barriers in clinical natural language processing. This paper is aimed at providing a large-scale and publicly available patient note dataset, named PMC-Patients, with relevant articles and similar patients annotations. The ultimate goal of PMC-Patients is to facilitate the development of retrieval-based clinical decision support systems. Materials and Methods: To collect PMC-Patients, we extract patient notes from case reports in PubMed Central by recognizing certain section patterns. Patient-article relevance and patient-patient similarity are annotated by citation relationships in PubMed. In addition, we perform three tasks with PMC-Patients to demonstrate its utility in providing clinical decision support for a given patient, including (1) classifying whether another patient is similar, (2) retrieving similar patients in PMC-Patients, and (3) retrieving relevant articles in PubMed. Results: We collect and release PMC-Patients under the CC BY-NC-SA license, which becomes the largest publicly available patient note dataset so far. PMC-Patients contains 167k patient notes that are annotated with 3.1M relevant articles and 293k similar patients. Qualitative and quantitative analyses reveal the high quality and richness of our dataset. Experiments show that classifying the similarity of patient pairs is relatively easy, but it is hard to retrieve similar patients or relevant articles for a given patient from a large set of candidates. Conclusion: We present PMC-Patients, a large-scale dataset of patient notes with high quality, easy access, diverse conditions, and rich annotations. The proposed dataset can also serve as a hard benchmark for evaluating retrieval-based clinical decision support systems.

Generalist vision language models (VLMs) have made significant strides in computer vision, but they fall short in specialized fields like healthcare, where expert knowledge is essential. In traditional computer vision tasks, creative or approximate answers may be acceptable, but in healthcare, precision is paramount.Current large multimodal models like Gemini and GPT-4o are insufficient for medical tasks due to their reliance on memorized internet knowledge rather than the nuanced expertise required in healthcare. VLMs are usually trained in three stages: vision pre-training, vision-language pre-training, and instruction fine-tuning (IFT). IFT has been typically applied using a mixture of generic and healthcare data. In contrast, we propose that for medical VLMs, a fourth stage of specialized IFT is necessary, which focuses on medical data and includes information from domain expert models. Domain expert models developed for medical use are crucial because they are specifically trained for certain clinical tasks, e.g. to detect tumors and classify abnormalities through segmentation and classification, which learn fine-grained features of medical data-features that are often too intricate for a VLM to capture effectively especially in radiology. This paper introduces a new framework, VILA-M3, for medical VLMs that utilizes domain knowledge via expert models. Through our experiments, we show an improved state-of-the-art (SOTA) performance with an average improvement of ~9% over the prior SOTA model Med-Gemini and ~6% over models trained on the specific tasks. Our approach emphasizes the importance of domain expertise in creating precise, reliable VLMs for medical applications.

Identifying disease phenotypes from electronic health records (EHRs) is critical for numerous secondary uses. Manually encoding physician knowledge into rules is particularly challenging for rare diseases due to inadequate EHR coding, necessitating review of clinical notes. Large language models (LLMs) offer promise in text understanding but may not efficiently handle real-world clinical documentation. We propose a zero-shot LLM-based method enriched by retrieval-augmented generation and MapReduce, which pre-identifies disease-related text snippets to be used in parallel as queries for the LLM to establish diagnosis. We show that this method as applied to pulmonary hypertension (PH), a rare disease characterized by elevated arterial pressures in the lungs, significantly outperforms physician logic rules (F_1 score of 0.62 vs. 0.75). This method has the potential to enhance rare disease cohort identification, expanding the scope of robust clinical research and care gap identification.

Color fundus photography and Optical Coherence Tomography (OCT) are the two most cost-effective tools for glaucoma screening. Both two modalities of images have prominent biomarkers to indicate glaucoma suspected. Clinically, it is often recommended to take both of the screenings for a more accurate and reliable diagnosis. However, although numerous algorithms are proposed based on fundus images or OCT volumes in computer-aided diagnosis, there are still few methods leveraging both of the modalities for the glaucoma assessment. Inspired by the success of Retinal Fundus Glaucoma Challenge (REFUGE) we held previously, we set up the Glaucoma grAding from Multi-Modality imAges (GAMMA) Challenge to encourage the development of fundus \& OCT-based glaucoma grading. The primary task of the challenge is to grade glaucoma from both the 2D fundus images and 3D OCT scanning volumes. As part of GAMMA, we have publicly released a glaucoma annotated dataset with both 2D fundus color photography and 3D OCT volumes, which is the first multi-modality dataset for glaucoma grading. In addition, an evaluation framework is also established to evaluate the performance of the submitted methods. During the challenge, 1272 results were submitted, and finally, top-10 teams were selected to the final stage. We analysis their results and summarize their methods in the paper. Since all these teams submitted their source code in the challenge, a detailed ablation study is also conducted to verify the effectiveness of the particular modules proposed. We find many of the proposed techniques are practical for the clinical diagnosis of glaucoma. As the first in-depth study of fundus \& OCT multi-modality glaucoma grading, we believe the GAMMA Challenge will be an essential starting point for future research.

Accurate and interpretable multi-disease diagnosis remains a critical challenge in medical research, particularly when leveraging heterogeneous multimodal medical data. Current approaches often rely on single-modal data, limiting their ability to comprehensively understand complex diseases. To address this, we propose MedTVT-R1, a novel Multimodal Large Language Model (MLLM) framework designed to integrate clinical multimodal data for reasoning and diagnosing multiple diseases. We construct MedTVT-QA, a curated instruction dataset that provides question-answer pairs for physiological-level interpretations and disease-level diagnoses with a Chain of Evidence approach. MedTVT-R1 incorporates a modality perception layer to capture inter-modal dependencies and adaptively weight modality contributions. Additionally, we employ Group Relative Policy Optimization (GRPO)-based Reinforcement Fine-Tuning with a Jaccard Reward function to enhance diagnostic reasoning. Experimental results demonstrate MedTVT-R1's superiority in multimodal feature utilization and multi-disease diagnosis, offering significant potential for clinical applications such as diagnostic report generation and comorbidity reasoning. The dataset and code are available at https://github.com/keke-nice/MedTVT-R1.

Alzheimer's disease (AD) is a degenerative brain disease impairing a person's ability to perform day to day activities. The clinical manifestations of Alzheimer's disease are characterized by heterogeneity in age, disease span, progression rate, impairment of memory and cognitive abilities. Due to these variabilities, personalized care and treatment planning, as well as patient counseling about their individual progression is limited. Recent developments in machine learning to detect hidden patterns in complex, multi-dimensional datasets provides significant opportunities to address this critical need. In this work, we use unsupervised and supervised machine learning approaches for subtype identification and prediction. We apply machine learning methods to the extensive clinical observations available at the Alzheimer's Disease Neuroimaging Initiative (ADNI) data set to identify patient subtypes and to predict disease progression. Our analysis depicts the progression space for the Alzheimer's disease into low, moderate and high disease progression zones. The proposed work will enable early detection and characterization of distinct disease subtypes based on clinical heterogeneity. We anticipate that our models will enable patient counseling, clinical trial design, and ultimately individualized clinical care.

Large language models (LLMs) have shown remarkable progress in encoding clinical knowledge and responding to complex medical queries with appropriate clinical reasoning. However, their applicability in subspecialist or complex medical settings remains underexplored. In this work, we probe the performance of AMIE, a research conversational diagnostic AI system, in the subspecialist domain of breast oncology care without specific fine-tuning to this challenging domain. To perform this evaluation, we curated a set of 50 synthetic breast cancer vignettes representing a range of treatment-naive and treatment-refractory cases and mirroring the key information available to a multidisciplinary tumor board for decision-making (openly released with this work). We developed a detailed clinical rubric for evaluating management plans, including axes such as the quality of case summarization, safety of the proposed care plan, and recommendations for chemotherapy, radiotherapy, surgery and hormonal therapy. To improve performance, we enhanced AMIE with the inference-time ability to perform web search retrieval to gather relevant and up-to-date clinical knowledge and refine its responses with a multi-stage self-critique pipeline. We compare response quality of AMIE with internal medicine trainees, oncology fellows, and general oncology attendings under both automated and specialist clinician evaluations. In our evaluations, AMIE outperformed trainees and fellows demonstrating the potential of the system in this challenging and important domain. We further demonstrate through qualitative examples, how systems such as AMIE might facilitate conversational interactions to assist clinicians in their decision making. However, AMIE's performance was overall inferior to attending oncologists suggesting that further research is needed prior to consideration of prospective uses.