Daily Papers

Spatial proteomics technologies have transformed our understanding of complex tissue architectures by enabling simultaneous analysis of multiple molecular markers and their spatial organization. The high dimensionality of these data, varying marker combinations across experiments and heterogeneous study designs pose unique challenges for computational analysis. Here, we present Virtual Tissues (VirTues), a foundation model framework for biological tissues that operates across the molecular, cellular and tissue scale. VirTues introduces innovations in transformer architecture design, including a novel tokenization scheme that captures both spatial and marker dimensions, and attention mechanisms that scale to high-dimensional multiplex data while maintaining interpretability. Trained on diverse cancer and non-cancer tissue datasets, VirTues demonstrates strong generalization capabilities without task-specific fine-tuning, enabling cross-study analysis and novel marker integration. As a generalist model, VirTues outperforms existing approaches across clinical diagnostics, biological discovery and patient case retrieval tasks, while providing insights into tissue function and disease mechanisms.

Hepato-pancreato-biliary (HPB) disorders represent a global public health challenge due to their high morbidity and mortality. Although large language models (LLMs) have shown promising performance in general medical question-answering tasks, the current evaluation benchmarks are mostly derived from standardized examinations or manually designed questions, lacking HPB coverage and clinical cases. To address these issues, we systematically eatablish an HPB disease evaluation benchmark comprising 3,535 closed-ended multiple-choice questions and 337 open-ended real diagnosis cases, which encompasses all the 33 main categories and 465 subcategories of HPB diseases defined in the International Statistical Classification of Diseases, 10th Revision (ICD-10). The multiple-choice questions are curated from public datasets and synthesized data, and the clinical cases are collected from prestigious medical journals, case-sharing platforms, and collaborating hospitals. By evalauting commercial and open-source general and medical LLMs on our established benchmark, namely ClinBench-HBP, we find that while commercial LLMs perform competently on medical exam questions, they exhibit substantial performance degradation on HPB diagnosis tasks, especially on complex, inpatient clinical cases. Those medical LLMs also show limited generalizability to HPB diseases. Our results reveal the critical limitations of current LLMs in the domain of HPB diseases, underscoring the imperative need for future medical LLMs to handle real, complex clinical diagnostics rather than simple medical exam questions. The benchmark will be released at https://clinbench-hpb.github.io.

This study assesses deep learning models for audio classification in a clinical setting with the constraint of small datasets reflecting real-world prospective data collection. We analyze CNNs, including DenseNet and ConvNeXt, alongside transformer models like ViT, SWIN, and AST, and compare them against pre-trained audio models such as YAMNet and VGGish. Our method highlights the benefits of pre-training on large datasets before fine-tuning on specific clinical data. We prospectively collected two first-of-their-kind patient audio datasets from stroke patients. We investigated various preprocessing techniques, finding that RGB and grayscale spectrogram transformations affect model performance differently based on the priors they learn from pre-training. Our findings indicate CNNs can match or exceed transformer models in small dataset contexts, with DenseNet-Contrastive and AST models showing notable performance. This study highlights the significance of incremental marginal gains through model selection, pre-training, and preprocessing in sound classification; this offers valuable insights for clinical diagnostics that rely on audio classification.

Medical image segmentation is a cornerstone of modern clinical diagnostics. While Vision Transformers that leverage shifted window-based self-attention have established new benchmarks in this field, they are often hampered by a critical limitation: their localized attention mechanism struggles to effectively fuse local details with global context. This deficiency is particularly detrimental to challenging tasks such as the segmentation of microtumors and miniature organs, where both fine-grained boundary definition and broad contextual understanding are paramount. To address this gap, we propose HBFormer, a novel Hybrid-Bridge Transformer architecture. The 'Hybrid' design of HBFormer synergizes a classic U-shaped encoder-decoder framework with a powerful Swin Transformer backbone for robust hierarchical feature extraction. The core innovation lies in its 'Bridge' mechanism, a sophisticated nexus for multi-scale feature integration. This bridge is architecturally embodied by our novel Multi-Scale Feature Fusion (MFF) decoder. Departing from conventional symmetric designs, the MFF decoder is engineered to fuse multi-scale features from the encoder with global contextual information. It achieves this through a synergistic combination of channel and spatial attention modules, which are constructed from a series of dilated and depth-wise convolutions. These components work in concert to create a powerful feature bridge that explicitly captures long-range dependencies and refines object boundaries with exceptional precision. Comprehensive experiments on challenging medical image segmentation datasets, including multi-organ, liver tumor, and bladder tumor benchmarks, demonstrate that HBFormer achieves state-of-the-art results, showcasing its outstanding capabilities in microtumor and miniature organ segmentation. Code and models are available at: https://github.com/lzeeorno/HBFormer.

Accurate detection of cardiac abnormalities from electrocardiogram recordings is regarded as essential for clinical diagnostics and decision support. Traditional deep learning models such as residual networks and transformer architectures have been applied successfully to this task, but their performance has been limited when long sequential signals are processed. Recently, state space models have been introduced as an efficient alternative. In this study, a hybrid framework named One Dimensional Convolutional Neural Network Electrocardiogram Mamba is introduced, in which convolutional feature extraction is combined with Mamba, a selective state space model designed for effective sequence modeling. The model is built upon Vision Mamba, a bidirectional variant through which the representation of temporal dependencies in electrocardiogram data is enhanced. Comprehensive experiments on the PhysioNet Computing in Cardiology Challenges of 2020 and 2021 were conducted, and superior performance compared with existing methods was achieved. Specifically, the proposed model achieved substantially higher AUPRC and AUROC scores than those reported by the best previously published algorithms on twelve lead electrocardiograms. These results demonstrate the potential of Mamba-based architectures to advance reliable ECG classification. This capability supports early diagnosis and personalized treatment, while enhancing accessibility in telemedicine and resource-constrained healthcare systems.

Accurate interpretation of Electrocardiogram (ECG) signals is pivotal for diagnosing cardiovascular diseases. Integrating ECG signals with their accompanying textual reports holds immense potential to enhance clinical diagnostics through the combination of physiological data and qualitative insights. However, this integration faces significant challenges due to inherent modality disparities and the scarcity of labeled data for robust cross-modal learning. To address these obstacles, we propose C-MELT, a novel framework that pre-trains ECG and text data using a contrastive masked auto-encoder architecture. C-MELT uniquely combines the strengths of generative with enhanced discriminative capabilities to achieve robust cross-modal representations. This is accomplished through masked modality modeling, specialized loss functions, and an improved negative sampling strategy tailored for cross-modal alignment. Extensive experiments on five public datasets across diverse downstream tasks demonstrate that C-MELT significantly outperforms existing methods, achieving 15% and 2% increases in linear probing and zero-shot performance over state-of-the-art models, respectively. These results highlight the effectiveness of C-MELT, underscoring its potential to advance automated clinical diagnostics through multi-modal representations.

Early detection of gastric cancer, a leading cause of cancer-related mortality worldwide, remains hampered by the limitations of current diagnostic technologies, leading to high rates of misdiagnosis and missed diagnoses. To address these challenges, we propose an integrated system that synergizes advanced hardware and software technologies to balance speed-accuracy. Our study introduces the One Class Twin Cross Learning (OCT-X) algorithm. Leveraging a novel fast double-threshold grid search strategy (FDT-GS) and a patch-based deep fully convolutional network, OCT-X maximizes diagnostic accuracy through real-time data processing and seamless lesion surveillance. The hardware component includes an all-in-one point-of-care testing (POCT) device with high-resolution imaging sensors, real-time data processing, and wireless connectivity, facilitated by the NI CompactDAQ and LabVIEW software. Our integrated system achieved an unprecedented diagnostic accuracy of 99.70%, significantly outperforming existing models by up to 4.47%, and demonstrated a 10% improvement in multirate adaptability. These findings underscore the potential of OCT-X as well as the integrated system in clinical diagnostics, offering a path toward more accurate, efficient, and less invasive early gastric cancer detection. Future research will explore broader applications, further advancing oncological diagnostics. Code is available at https://github.com/liu37972/Multirate-Location-on-OCT-X-Learning.git.

Despite their widespread applications, Large Language Models (LLMs) often struggle to express uncertainty, posing a challenge for reliable deployment in high stakes and safety critical domains like clinical diagnostics. Existing standard baseline methods such as model logits and elicited probabilities produce overconfident and poorly calibrated estimates. In this work, we propose Approximate Bayesian Computation (ABC), a likelihood-free Bayesian inference, based approach that treats LLMs as a stochastic simulator to infer posterior distributions over predictive probabilities. We evaluate our ABC approach on two clinically relevant benchmarks: a synthetic oral lesion diagnosis dataset and the publicly available GretelAI symptom-to-diagnosis dataset. Compared to standard baselines, our approach improves accuracy by up to 46.9\%, reduces Brier scores by 74.4\%, and enhances calibration as measured by Expected Calibration Error (ECE) and predictive entropy.

Advanced autoregressive models have reshaped multimodal AI. However, their transformative potential in medical imaging remains largely untapped due to the absence of a unified visual tokenizer -- one capable of capturing fine-grained visual structures for faithful image reconstruction and realistic image synthesis, as well as rich semantics for accurate diagnosis and image interpretation. To this end, we present MedITok, the first unified tokenizer tailored for medical images, encoding both low-level structural details and high-level clinical semantics within a unified latent space. To balance these competing objectives, we introduce a novel two-stage training framework: a visual representation alignment stage that cold-starts the tokenizer reconstruction learning with a visual semantic constraint, followed by a textual semantic representation alignment stage that infuses detailed clinical semantics into the latent space. Trained on the meticulously collected large-scale dataset with over 30 million medical images and 2 million image-caption pairs, MedITok achieves state-of-the-art performance on more than 30 datasets across 9 imaging modalities and 4 different tasks. By providing a unified token space for autoregressive modeling, MedITok supports a wide range of tasks in clinical diagnostics and generative healthcare applications. Model and code will be made publicly available at: https://github.com/Masaaki-75/meditok.

The increasing prevalence of thyroid cancer globally has led to the development of various computer-aided detection methods. Accurate segmentation of thyroid nodules is a critical first step in the development of AI-assisted clinical decision support systems. This study focuses on instance segmentation of thyroid nodules using YOLOv5 algorithms on ultrasound images. We evaluated multiple YOLOv5 variants (Nano, Small, Medium, Large, and XLarge) across two dataset versions, with and without doppler images. The YOLOv5-Large algorithm achieved the highest performance with a dice score of 91\% and mAP of 0.87 on the dataset including doppler images. Notably, our results demonstrate that doppler images, typically excluded by physicians, can significantly improve segmentation performance. The YOLOv5-Small model achieved 79\% dice score when doppler images were excluded, while including them improved performance across all model variants. These findings suggest that instance segmentation with YOLOv5 provides an effective real-time approach for thyroid nodule detection, with potential clinical applications in automated diagnostic systems.

Current Vision-Language Models (VLMs) struggle to ground anatomical regions in 3D medical images and reason about them in a step-by-step manner, a key requirement of real-world diagnostic assessment. This ability is essential for aligning model outputs with the diagnostic workflows clinicians use in practice, enabling trustworthy clinician-AI collaboration. Existing 3D datasets provide localization labels, but none support this "grounded reasoning" ability. To address this gap, we introduce 3DReasonKnee, the first 3D grounded reasoning dataset for medical images, which provides 494k high-quality quintuples derived from 7,970 3D knee MRI volumes. Each quintuple includes: (1) the 3D MRI volume, (2) a diagnostic question targeting a specific anatomical region (3) a 3D bounding box localizing the relevant anatomical structures, (4) clinician-generated diagnostic reasoning steps that explicitly detail the 3D reasoning process, and (5) structured severity assessments for the relevant anatomical region. The creation and validation of 3DReasonKnee, involving over 450 hours of expert clinician time for manually segmenting MRIs and generating reasoning chains, ensures its superior quality and clinical relevance. We establish ReasonKnee-Bench to evaluate localization and diagnostic accuracy, providing insight into VLM ability to perform grounding and severity assessment across anatomical regions and diagnostic inquiries. We benchmark five state-of-the-art VLMs, providing baseline performance for ReasonKnee-Bench. By providing this unique resource of expert-annotated 3D reasoning pathways, 3DReasonKnee serves as a repository of orthopedic surgeons' diagnostic expertise and offers a vital testbed for advancing multimodal medical AI systems towards 3D, clinically aligned, localized decision-making capabilities. The dataset can be found in: https://huggingface.co/datasets/rajpurkarlab/3DReasonKnee

The proliferation of digital microscopy images, driven by advances in automated whole slide scanning, presents significant opportunities for biomedical research and clinical diagnostics. However, accurately annotating densely packed information in these images remains a major challenge. To address this, we introduce DiffKillR, a novel framework that reframes cell annotation as the combination of archetype matching and image registration tasks. DiffKillR employs two complementary neural networks: one that learns a diffeomorphism-invariant feature space for robust cell matching and another that computes the precise warping field between cells for annotation mapping. Using a small set of annotated archetypes, DiffKillR efficiently propagates annotations across large microscopy images, reducing the need for extensive manual labeling. More importantly, it is suitable for any type of pixel-level annotation. We will discuss the theoretical properties of DiffKillR and validate it on three microscopy tasks, demonstrating its advantages over existing supervised, semi-supervised, and unsupervised methods. The code is available at https://github.com/KrishnaswamyLab/DiffKillR.

Selective Classification, wherein models can reject low-confidence predictions, promises reliable translation of machine-learning based classification systems to real-world scenarios such as clinical diagnostics. While current evaluation of these systems typically assumes fixed working points based on pre-defined rejection thresholds, methodological progress requires benchmarking the general performance of systems akin to the AUROC in standard classification. In this work, we define 5 requirements for multi-threshold metrics in selective classification regarding task alignment, interpretability, and flexibility, and show how current approaches fail to meet them. We propose the Area under the Generalized Risk Coverage curve (AUGRC), which meets all requirements and can be directly interpreted as the average risk of undetected failures. We empirically demonstrate the relevance of AUGRC on a comprehensive benchmark spanning 6 data sets and 13 confidence scoring functions. We find that the proposed metric substantially changes metric rankings on 5 out of the 6 data sets.

Urine sediment examination (USE) is one of the main tests used in the evaluation of diseases such as kidney, urinary, metabolic, and diabetes and to determine the density and number of various cells in the urine. USE's manual microscopy is a labor-intensive and time-consuming, imprecise, subjective process. Recently, automatic analysis of urine sediment has become inevitable in the medical field. In this study, we propose a dataset that can be used by artificial intelligence techniques to automatically identify particles in urine sediment images. The data set consists of 8509 particle images obtained by examining the particles in the urine sediment obtained from 409 patients from the Biochemistry Clinics of Elazig Fethi Sekin Central Hospital. Particle images are collected in 8 classes in total and these are Erythrocyte, Leukocyte, Epithelial, Bacteria, Yeast, Cylinders, Crystals, and others (sperm, etc.).

Medical image segmentation poses challenges due to domain gaps, data modality variations, and dependency on domain knowledge or experts, especially for low- and middle-income countries (LMICs). Whereas for humans, given a few exemplars (with corresponding labels), we are able to segment different medical images even without exten-sive domain-specific clinical training. In addition, current SAM-based medical segmentation models use fine-grained visual prompts, such as the bounding rectangle generated from manually annotated target segmentation mask, as the bounding box (bbox) prompt during the testing phase. However, in actual clinical scenarios, no such precise prior knowledge is available. Our experimental results also reveal that previous models nearly fail to predict when given coarser bbox prompts. Considering these issues, in this paper, we introduce a domain-aware selective adaptation approach to adapt the general knowledge learned from a large model trained with natural images to the corresponding medical domains/modalities, with access to only a few (e.g. less than 5) exemplars. Our method mitigates the aforementioned limitations, providing an efficient and LMICs-friendly solution. Extensive experimental analysis showcases the effectiveness of our approach, offering potential advancements in healthcare diagnostics and clinical applications in LMICs.

Foundation models have demonstrated remarkable potential in medical domain. However, their application to complex cardiovascular diagnostics remains underexplored. In this paper, we present Cardiac-CLIP, a multi-modal foundation model designed for 3D cardiac CT images. Cardiac-CLIP is developed through a two-stage pre-training strategy. The first stage employs a 3D masked autoencoder (MAE) to perform self-supervised representation learning from large-scale unlabeled volumetric data, enabling the visual encoder to capture rich anatomical and contextual features. In the second stage, contrastive learning is introduced to align visual and textual representations, facilitating cross-modal understanding. To support the pre-training, we collect 16641 real clinical CT scans, supplemented by 114k publicly available data. Meanwhile, we standardize free-text radiology reports into unified templates and construct the pathology vectors according to diagnostic attributes, based on which the soft-label matrix is generated to supervise the contrastive learning process. On the other hand, to comprehensively evaluate the effectiveness of Cardiac-CLIP, we collect 6,722 real-clinical data from 12 independent institutions, along with the open-source data to construct the evaluation dataset. Specifically, Cardiac-CLIP is comprehensively evaluated across multiple tasks, including cardiovascular abnormality classification, information retrieval and clinical analysis. Experimental results demonstrate that Cardiac-CLIP achieves state-of-the-art performance across various downstream tasks in both internal and external data. Particularly, Cardiac-CLIP exhibits great effectiveness in supporting complex clinical tasks such as the prospective prediction of acute coronary syndrome, which is notoriously difficult in real-world scenarios.

Large Language Models (LLMs) have shown the potential to significantly contribute to patient care, diagnostics, and administrative processes. Emerging biomedical LLMs address healthcare-specific challenges, including privacy demands and computational constraints. However, evaluation of these models has primarily been limited to non-clinical tasks, which do not reflect the complexity of practical clinical applications. Additionally, there has been no thorough comparison between biomedical and general-domain LLMs for clinical tasks. To fill this gap, we present the Clinical Language Understanding Evaluation (CLUE), a benchmark tailored to evaluate LLMs on real-world clinical tasks. CLUE includes two novel datasets derived from MIMIC IV discharge letters and four existing tasks designed to test the practical applicability of LLMs in healthcare settings. Our evaluation covers several biomedical and general domain LLMs, providing insights into their clinical performance and applicability. CLUE represents a step towards a standardized approach to evaluating and developing LLMs in healthcare to align future model development with the real-world needs of clinical application. We publish our evaluation and data generation scripts: https://github.com/dadaamin/CLUE

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.

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.

LLMs for clinical decision support often fail under small but clinically meaningful input shifts such as masking a symptom or negating a finding, despite high performance on static benchmarks. These reasoning failures frequently go undetected by standard NLP metrics, which are insensitive to latent representation shifts that drive diagnosis instability. We propose a geometry-aware evaluation framework, LAPD (Latent Agentic Perturbation Diagnostics), which systematically probes the latent robustness of clinical LLMs under structured adversarial edits. Within this framework, we introduce Latent Diagnosis Flip Rate (LDFR), a model-agnostic diagnostic signal that captures representational instability when embeddings cross decision boundaries in PCA-reduced latent space. Clinical notes are generated using a structured prompting pipeline grounded in diagnostic reasoning, then perturbed along four axes: masking, negation, synonym replacement, and numeric variation to simulate common ambiguities and omissions. We compute LDFR across both foundation and clinical LLMs, finding that latent fragility emerges even under minimal surface-level changes. Finally, we validate our findings on 90 real clinical notes from the DiReCT benchmark (MIMIC-IV), confirming the generalizability of LDFR beyond synthetic settings. Our results reveal a persistent gap between surface robustness and semantic stability, underscoring the importance of geometry-aware auditing in safety-critical clinical AI.

Artificial intelligence is poised to augment dermatological care by enabling scalable image-based diagnostics. Yet, the development of robust and equitable models remains hindered by datasets that fail to capture the clinical and demographic complexity of real-world practice. This complexity stems from region-specific disease distributions, wide variation in skin tones, and the underrepresentation of outpatient scenarios from non-Western populations. We introduce DermaCon-IN, a prospectively curated dermatology dataset comprising over 5,450 clinical images from approximately 3,000 patients across outpatient clinics in South India. Each image is annotated by board-certified dermatologists with over 240 distinct diagnoses, structured under a hierarchical, etiology-based taxonomy adapted from Rook's classification. The dataset captures a wide spectrum of dermatologic conditions and tonal variation commonly seen in Indian outpatient care. We benchmark a range of architectures including convolutional models (ResNet, DenseNet, EfficientNet), transformer-based models (ViT, MaxViT, Swin), and Concept Bottleneck Models to establish baseline performance and explore how anatomical and concept-level cues may be integrated. These results are intended to guide future efforts toward interpretable and clinically realistic models. DermaCon-IN provides a scalable and representative foundation for advancing dermatology AI in real-world settings.

Medical imaging is critical for diagnostics, but clinical adoption of advanced AI-driven imaging faces challenges due to patient variability, image artifacts, and limited model generalization. While deep learning has transformed image analysis, 3D medical imaging still suffers from data scarcity and inconsistencies due to acquisition protocols, scanner differences, and patient motion. Traditional augmentation uses a single pipeline for all transformations, disregarding the unique traits of each augmentation and struggling with large data volumes. To address these challenges, we propose a Multi-encoder Augmentation-Aware Learning (MEAL) framework that leverages four distinct augmentation variants processed through dedicated encoders. Three fusion strategies such as concatenation (CC), fusion layer (FL), and adaptive controller block (BD) are integrated to build multi-encoder models that combine augmentation-specific features before decoding. MEAL-BD uniquely preserves augmentation-aware representations, enabling robust, protocol-invariant feature learning. As demonstrated in a Computed Tomography (CT)-to-T1-weighted Magnetic Resonance Imaging (MRI) translation study, MEAL-BD consistently achieved the best performance on both unseen- and predefined-test data. On both geometric transformations (like rotations and flips) and non-augmented inputs, MEAL-BD outperformed other competing methods, achieving higher mean peak signal-to-noise ratio (PSNR) and structural similarity index measure (SSIM) scores. These results establish MEAL as a reliable framework for preserving structural fidelity and generalizing across clinically relevant variability. By reframing augmentation as a source of diverse, generalizable features, MEAL supports robust, protocol-invariant learning, advancing clinically reliable medical imaging solutions.

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.

Electrocardiography plays a central role in cardiovascular diagnostics, yet existing automated approaches often struggle to generalize across clinical tasks and offer limited support for open-ended reasoning. We present DiagECG, a novel framework that integrates time-series and language modeling by enabling large language models to process 12-lead ECG signals for clinical text generation tasks. Our approach discretizes continuous ECG embeddings into symbolic tokens using a lead-independent encoder and quantization module. These tokens are then used to extend the vocabulary of LLM, allowing the model to handle both ECG and natural language inputs in a unified manner. To bridge the modality gap, we pretrain the model on an autoregressive ECG forecasting task, enabling the LLM to model temporal dynamics using its native language modeling capabilities. Finally, we perform instruction tuning on both ECG question answering and diagnostic report generation. Without modifying the core model, DiagECG achieves strong performance across tasks while maintaining generalization to out-of-distribution settings. Extensive experiments demonstrate the effectiveness of each component and highlight the potential of integrating symbolic ECG representations into LLMs for medical reasoning.

Ultrasound fetal imaging is beneficial to support prenatal development because it is affordable and non-intrusive. Nevertheless, fetal plane classification (FPC) remains challenging and time-consuming for obstetricians since it depends on nuanced clinical aspects, which increases the difficulty in identifying relevant features of the fetal anatomy. Thus, to assist with its accurate feature extraction, a lightweight artificial intelligence architecture leveraging convolutional neural networks and attention mechanisms is proposed to classify the largest benchmark ultrasound dataset. The approach fine-tunes from lightweight EfficientNet feature extraction backbones pre-trained on the ImageNet1k. to classify key fetal planes such as the brain, femur, thorax, cervix, and abdomen. Our methodology incorporates the attention mechanism to refine features and 3-layer perceptrons for classification, achieving superior performance with the highest Top-1 accuracy of 96.25%, Top-2 accuracy of 99.80% and F1-Score of 0.9576. Importantly, the model has 40x fewer trainable parameters than existing benchmark ensemble or transformer pipelines, facilitating easy deployment on edge devices to help clinical practitioners with real-time FPC. The findings are also interpreted using GradCAM to carry out clinical correlation to aid doctors with diagnostics and improve treatment plans for expectant mothers.

Magnetic Resonance Imaging (MRI) is a critical tool in modern medical diagnostics, yet its prolonged acquisition time remains a critical limitation, especially in time-sensitive clinical scenarios. While undersampling strategies can accelerate image acquisition, they often result in image artifacts and degraded quality. Recent diffusion models have shown promise for reconstructing high-fidelity images from undersampled data by learning powerful image priors; however, most existing approaches either (i) rely on unsupervised score functions without paired supervision or (ii) apply data consistency only as a post-processing step. In this work, we introduce a conditional denoising diffusion framework with iterative data-consistency correction, which differs from prior methods by embedding the measurement model directly into every reverse diffusion step and training the model on paired undersampled-ground truth data. This hybrid design bridges generative flexibility with explicit enforcement of MRI physics. Experiments on the fastMRI dataset demonstrate that our framework consistently outperforms recent state-of-the-art deep learning and diffusion-based methods in SSIM, PSNR, and LPIPS, with LPIPS capturing perceptual improvements more faithfully. These results demonstrate that integrating conditional supervision with iterative consistency updates yields substantial improvements in both pixel-level fidelity and perceptual realism, establishing a principled and practical advance toward robust, accelerated MRI reconstruction.

This research tests the role of Large Language Models (LLMs) as formal second opinion tools in professional decision-making, particularly focusing on complex medical cases where even experienced physicians seek peer consultation. The work analyzed 183 challenging medical cases from Medscape over a 20-month period, testing multiple LLMs' performance against crowd-sourced physician responses. A key finding was the high overall score possible in the latest foundational models (>80% accuracy compared to consensus opinion), which exceeds most human metrics reported on the same clinical cases (450 pages of patient profiles, test results). The study rates the LLMs' performance disparity between straightforward cases (>81% accuracy) and complex scenarios (43% accuracy), particularly in these cases generating substantial debate among human physicians. The research demonstrates that LLMs may be valuable as generators of comprehensive differential diagnoses rather than as primary diagnostic tools, potentially helping to counter cognitive biases in clinical decision-making, reduce cognitive loads, and thus remove some sources of medical error. The inclusion of a second comparative legal dataset (Supreme Court cases, N=21) provides added empirical context to the AI use to foster second opinions, though these legal challenges proved considerably easier for LLMs to analyze. In addition to the original contributions of empirical evidence for LLM accuracy, the research aggregated a novel benchmark for others to score highly contested question and answer reliability between both LLMs and disagreeing human practitioners. These results suggest that the optimal deployment of LLMs in professional settings may differ substantially from current approaches that emphasize automation of routine tasks.

Background: AI-based classification models are essential for improving lung cancer diagnosis. However, the relative performance of lesion-level versus chest-region models in internal and external datasets remains unclear. Purpose: This study evaluates the performance of lesion-level and chest-region models for lung cancer classification, comparing their effectiveness across internal Duke Lung Nodule Dataset 2024 (DLND24) and external (LUNA16, NLST) datasets, with a focus on subgroup analyses by demographics, histology, and imaging characteristics. Materials and Methods: Two AI models were trained: one using lesion-centric patches (64,64,64) and the other using chest-region patches (512,512,8). Internal validation was conducted on DLND24, while external validation utilized LUNA16 and NLST datasets. The models performances were assessed using AUC-ROC, with subgroup analyses for demographic, clinical, and imaging factors. Statistical comparisons were performed using DeLongs test. Gradient-based visualizations and probability distribution were further used for analysis. Results: The lesion-level model consistently outperformed the chest-region model across datasets. In internal validation, the lesion-level model achieved an AUC of 0.71(CI: 0.61-0.81), compared to 0.68(0.57-0.77) for the chest-region model. External validation showed similar trends, with AUCs of 0.90(0.87-0.92) and 0.81(0.79-0.82) on LUNA16 and NLST, respectively. Subgroup analyses revealed significant advantages for lesion-level models in certain histological subtypes (adenocarcinoma) and imaging conditions (CT manufacturers). Conclusion: Lesion-level models demonstrate superior classification performance, especially for external datasets and challenging subgroups, suggesting their clinical utility for precision lung cancer diagnostics.

The electrocardiogram (ECG) remains a fundamental tool in cardiac diagnostics, yet its interpretation traditionally reliant on the expertise of cardiologists. The emergence of deep learning has heralded a revolutionary era in medical data analysis, particularly in the domain of ECG diagnostics. However, inter-patient variability prohibit the generalibility of ECG-AI model trained on a population dataset, hence degrade the performance of ECG-AI on specific patient or patient group. Many studies have address this challenge using different deep learning technologies. This comprehensive review systematically synthesizes research from a wide range of studies to provide an in-depth examination of cutting-edge deep-learning techniques in personalized ECG diagnosis. The review outlines a rigorous methodology for the selection of pertinent scholarly articles and offers a comprehensive overview of deep learning approaches applied to personalized ECG diagnostics. Moreover, the challenges these methods encounter are investigated, along with future research directions, culminating in insights into how the integration of deep learning can transform personalized ECG diagnosis and enhance cardiac care. By emphasizing both the strengths and limitations of current methodologies, this review underscores the immense potential of deep learning to refine and redefine ECG analysis in clinical practice, paving the way for more accurate, efficient, and personalized cardiac diagnostics.

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.

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.

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.

Bridging clinical diagnostic reasoning with AI remains a central challenge in medical imaging. We introduce MedCLM, an automated pipeline that converts detection datasets into large-scale medical visual question answering (VQA) data with Chain-of-Thought (CoT) reasoning by linking lesion boxes to organ segmentation and structured rationales. These contextual signals enable medical vision-language models to generate question-answer pairs with step-by-step reasoning. To utilize this data effectively, we propose an Integrated CoT-Curriculum Strategy composed of an Easy stage with explicit lesion boxes for visual grounding, a Medium stage that encourages implicit localization, and a Hard stage for weakly supervised reasoning. Experimental results demonstrate that MedCLM attains state-of-the-art performance on several medical VQA benchmarks, providing a scalable framework for developing clinically aligned medical vision-language models.

In disentangling the heterogeneity observed in psychopathology, personality of the patients is considered crucial. While it has been demonstrated that personality traits are reflected in the language used by a patient, we hypothesize that this enables automatic inference of the personality type directly from speech utterances, potentially more accurately than through a traditional questionnaire-based approach explicitly designed for personality classification. To validate this hypothesis, we adopt natural language processing (NLP) and standard machine learning tools for classification. We test this on a dataset of recorded clinical diagnostic interviews (CDI) on a sample of 79 patients diagnosed with major depressive disorder (MDD) -- a condition for which differentiated treatment based on personality styles has been advocated -- and classified into anaclitic and introjective personality styles. We start by analyzing the interviews to see which linguistic features are associated with each style, in order to gain a better understanding of the styles. Then, we develop automatic classifiers based on (a) standardized questionnaire responses; (b) basic text features, i.e., TF-IDF scores of words and word sequences; (c) more advanced text features, using LIWC (linguistic inquiry and word count) and context-aware features using BERT (bidirectional encoder representations from transformers); (d) audio features. We find that automated classification with language-derived features (i.e., based on LIWC) significantly outperforms questionnaire-based classification models. Furthermore, the best performance is achieved by combining LIWC with the questionnaire features. This suggests that more work should be put into developing linguistically based automated techniques for characterizing personality, however questionnaires still to some extent complement such methods.

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.

Recently, Computer-Aided Diagnosis (CAD) systems have emerged as indispensable tools in clinical diagnostic workflows, significantly alleviating the burden on radiologists. Nevertheless, despite their integration into clinical settings, CAD systems encounter limitations. Specifically, while CAD systems can achieve high performance in the detection of lung nodules, they face challenges in accurately predicting multiple cancer types. This limitation can be attributed to the scarcity of publicly available datasets annotated with expert-level cancer type information. This research aims to bridge this gap by providing publicly accessible datasets and reliable tools for medical diagnosis, facilitating a finer categorization of different types of lung diseases so as to offer precise treatment recommendations. To achieve this objective, we curated a diverse dataset of lung Computed Tomography (CT) images, comprising 330 annotated nodules (nodules are labeled as bounding boxes) from 95 distinct patients. The quality of the dataset was evaluated using a variety of classical classification and detection models, and these promising results demonstrate that the dataset has a feasible application and further facilitate intelligent auxiliary diagnosis.

Electrocardiography (ECG) signals are often degraded by noise, which complicates diagnosis in clinical and wearable settings. This study proposes a diffusion-based framework for ECG noise quantification via reconstruction-based anomaly detection, addressing annotation inconsistencies and the limited generalizability of conventional methods. We introduce a distributional evaluation using the Wasserstein-1 distance (W_1), comparing the reconstruction error distributions between clean and noisy ECGs to mitigate inconsistent annotations. Our final model achieved robust noise quantification using only three reverse diffusion steps. The model recorded a macro-average W_1 score of 1.308 across the benchmarks, outperforming the next-best method by over 48%. External validations demonstrated strong generalizability, supporting the exclusion of low-quality segments to enhance diagnostic accuracy and enable timely clinical responses to signal degradation. The proposed method enhances clinical decision-making, diagnostic accuracy, and real-time ECG monitoring capabilities, supporting future advancements in clinical and wearable ECG applications.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Large Language Models (LLMs) hold great promise to revolutionize current clinical systems for their superior capacities on medical text processing tasks and medical licensing exams. Meanwhile, traditional ML models such as SVM and XGBoost have still been mainly adopted in clinical prediction tasks. An emerging question is Can LLMs beat traditional ML models in clinical prediction? Thus, we build a new benchmark ClinicalBench to comprehensively study the clinical predictive modeling capacities of both general-purpose and medical LLMs, and compare them with traditional ML models. ClinicalBench embraces three common clinical prediction tasks, two databases, 14 general-purpose LLMs, 8 medical LLMs, and 11 traditional ML models. Through extensive empirical investigation, we discover that both general-purpose and medical LLMs, even with different model scales, diverse prompting or fine-tuning strategies, still cannot beat traditional ML models in clinical prediction yet, shedding light on their potential deficiency in clinical reasoning and decision-making. We call for caution when practitioners adopt LLMs in clinical applications. ClinicalBench can be utilized to bridge the gap between LLMs' development for healthcare and real-world clinical practice.

Clinical natural language processing requires methods that can address domain-specific challenges, such as complex medical terminology and clinical contexts. Recently, large language models (LLMs) have shown promise in this domain. Yet, their direct deployment can lead to privacy issues and are constrained by resources. To address this challenge, we delve into synthetic clinical text generation using LLMs for clinical NLP tasks. We propose an innovative, resource-efficient approach, ClinGen, which infuses knowledge into the process. Our model involves clinical knowledge extraction and context-informed LLM prompting. Both clinical topics and writing styles are drawn from external domain-specific knowledge graphs and LLMs to guide data generation. Our extensive empirical study across 7 clinical NLP tasks and 16 datasets reveals that ClinGen consistently enhances performance across various tasks, effectively aligning the distribution of real datasets and significantly enriching the diversity of generated training instances. We will publish our code and all the generated data in https://github.com/ritaranx/ClinGen.

Many clinical tasks require an understanding of specialized data, such as medical images and genomics, which is not typically found in general-purpose large multimodal models. Building upon Gemini's multimodal models, we develop several models within the new Med-Gemini family that inherit core capabilities of Gemini and are optimized for medical use via fine-tuning with 2D and 3D radiology, histopathology, ophthalmology, dermatology and genomic data. Med-Gemini-2D sets a new standard for AI-based chest X-ray (CXR) report generation based on expert evaluation, exceeding previous best results across two separate datasets by an absolute margin of 1% and 12%, where 57% and 96% of AI reports on normal cases, and 43% and 65% on abnormal cases, are evaluated as "equivalent or better" than the original radiologists' reports. We demonstrate the first ever large multimodal model-based report generation for 3D computed tomography (CT) volumes using Med-Gemini-3D, with 53% of AI reports considered clinically acceptable, although additional research is needed to meet expert radiologist reporting quality. Beyond report generation, Med-Gemini-2D surpasses the previous best performance in CXR visual question answering (VQA) and performs well in CXR classification and radiology VQA, exceeding SoTA or baselines on 17 of 20 tasks. In histopathology, ophthalmology, and dermatology image classification, Med-Gemini-2D surpasses baselines across 18 out of 20 tasks and approaches task-specific model performance. Beyond imaging, Med-Gemini-Polygenic outperforms the standard linear polygenic risk score-based approach for disease risk prediction and generalizes to genetically correlated diseases for which it has never been trained. Although further development and evaluation are necessary in the safety-critical medical domain, our results highlight the potential of Med-Gemini across a wide range of medical tasks.

Cardiac MRI allows for a comprehensive assessment of myocardial structure, function, and tissue characteristics. Here we describe a foundational vision system for cardiac MRI, capable of representing the breadth of human cardiovascular disease and health. Our deep learning model is trained via self-supervised contrastive learning, by which visual concepts in cine-sequence cardiac MRI scans are learned from the raw text of the accompanying radiology reports. We train and evaluate our model on data from four large academic clinical institutions in the United States. We additionally showcase the performance of our models on the UK BioBank, and two additional publicly available external datasets. We explore emergent zero-shot capabilities of our system, and demonstrate remarkable performance across a range of tasks; including the problem of left ventricular ejection fraction regression, and the diagnosis of 35 different conditions such as cardiac amyloidosis and hypertrophic cardiomyopathy. We show that our deep learning system is capable of not only understanding the staggering complexity of human cardiovascular disease, but can be directed towards clinical problems of interest yielding impressive, clinical grade diagnostic accuracy with a fraction of the training data typically required for such tasks.

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.

Transformers-based models, such as BERT, have dramatically improved the performance for various natural language processing tasks. The clinical knowledge enriched model, namely ClinicalBERT, also achieved state-of-the-art results when performed on clinical named entity recognition and natural language inference tasks. One of the core limitations of these transformers is the substantial memory consumption due to their full self-attention mechanism. To overcome this, long sequence transformer models, e.g. Longformer and BigBird, were proposed with the idea of sparse attention mechanism to reduce the memory usage from quadratic to the sequence length to a linear scale. These models extended the maximum input sequence length from 512 to 4096, which enhanced the ability of modeling long-term dependency and consequently achieved optimal results in a variety of tasks. Inspired by the success of these long sequence transformer models, we introduce two domain enriched language models, namely Clinical-Longformer and Clinical-BigBird, which are pre-trained from large-scale clinical corpora. We evaluate both pre-trained models using 10 baseline tasks including named entity recognition, question answering, and document classification tasks. The results demonstrate that Clinical-Longformer and Clinical-BigBird consistently and significantly outperform ClinicalBERT as well as other short-sequence transformers in all downstream tasks. We have made our source code available at [https://github.com/luoyuanlab/Clinical-Longformer] the pre-trained models available for public download at: [https://huggingface.co/yikuan8/Clinical-Longformer].

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.

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.

Clinical notes contain information about patients that goes beyond structured data like lab values and medications. However, clinical notes have been underused relative to structured data, because notes are high-dimensional and sparse. This work develops and evaluates representations of clinical notes using bidirectional transformers (ClinicalBERT). ClinicalBERT uncovers high-quality relationships between medical concepts as judged by humans. ClinicalBert outperforms baselines on 30-day hospital readmission prediction using both discharge summaries and the first few days of notes in the intensive care unit. Code and model parameters are available.

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.

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.

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.

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.

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.

Clinical Natural Language Processing (NLP) has become an emerging technology in healthcare that leverages a large amount of free-text data in electronic health records (EHRs) to improve patient care, support clinical decisions, and facilitate clinical and translational science research. Recently, deep learning has achieved state-of-the-art performance in many clinical NLP tasks. However, training deep learning models usually requires large annotated datasets, which are normally not publicly available and can be time-consuming to build in clinical domains. Working with smaller annotated datasets is typical in clinical NLP and therefore, ensuring that deep learning models perform well is crucial for the models to be used in real-world applications. A widely adopted approach is fine-tuning existing Pre-trained Language Models (PLMs), but these attempts fall short when the training dataset contains only a few annotated samples. Few-Shot Learning (FSL) has recently been investigated to tackle this problem. Siamese Neural Network (SNN) has been widely utilized as an FSL approach in computer vision, but has not been studied well in NLP. Furthermore, the literature on its applications in clinical domains is scarce. In this paper, we propose two SNN-based FSL approaches for clinical NLP, including Pre-Trained SNN (PT-SNN) and SNN with Second-Order Embeddings (SOE-SNN). We evaluated the proposed approaches on two clinical tasks, namely clinical text classification and clinical named entity recognition. We tested three few-shot settings including 4-shot, 8-shot, and 16-shot learning. Both clinical NLP tasks were benchmarked using three PLMs, including BERT,BioBERT, and BioClinicalBERT. The experimental results verified the effectiveness of the proposed SNN-based FSL approaches in both NLP tasks.

Automated interpretation of electrocardiograms (ECG) has garnered significant attention with the advancements in machine learning methodologies. Despite the growing interest, most current studies focus solely on classification or regression tasks, which overlook a crucial aspect of clinical cardio-disease diagnosis: the diagnostic report generated by experienced human clinicians. In this paper, we introduce a novel approach to ECG interpretation, leveraging recent breakthroughs in Large Language Models (LLMs) and Vision-Transformer (ViT) models. Rather than treating ECG diagnosis as a classification or regression task, we propose an alternative method of automatically identifying the most similar clinical cases based on the input ECG data. Also, since interpreting ECG as images is more affordable and accessible, we process ECG as encoded images and adopt a vision-language learning paradigm to jointly learn vision-language alignment between encoded ECG images and ECG diagnosis reports. Encoding ECG into images can result in an efficient ECG retrieval system, which will be highly practical and useful in clinical applications. More importantly, our findings could serve as a crucial resource for providing diagnostic services in underdeveloped regions.

The use of deep neural models for diagnosis prediction from clinical text has shown promising results. However, in clinical practice such models must not only be accurate, but provide doctors with interpretable and helpful results. We introduce ProtoPatient, a novel method based on prototypical networks and label-wise attention with both of these abilities. ProtoPatient makes predictions based on parts of the text that are similar to prototypical patients - providing justifications that doctors understand. We evaluate the model on two publicly available clinical datasets and show that it outperforms existing baselines. Quantitative and qualitative evaluations with medical doctors further demonstrate that the model provides valuable explanations for clinical decision support.

Radiology reporting generative AI holds significant potential to alleviate clinical workloads and streamline medical care. However, achieving high clinical accuracy is challenging, as radiological images often feature subtle lesions and intricate structures. Existing systems often fall short, largely due to their reliance on fixed size, patch-level image features and insufficient incorporation of pathological information. This can result in the neglect of such subtle patterns and inconsistent descriptions of crucial pathologies. To address these challenges, we propose an innovative approach that leverages pathology-aware regional prompts to explicitly integrate anatomical and pathological information of various scales, significantly enhancing the precision and clinical relevance of generated reports. We develop an anatomical region detector that extracts features from distinct anatomical areas, coupled with a novel multi-label lesion detector that identifies global pathologies. Our approach emulates the diagnostic process of radiologists, producing clinically accurate reports with comprehensive diagnostic capabilities. Experimental results show that our model outperforms previous state-of-the-art methods on most natural language generation and clinical efficacy metrics, with formal expert evaluations affirming its potential to enhance radiology practice.

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.

Background: Electronic Health Records hold detailed longitudinal information about each patient's health status and general clinical history, a large portion of which is stored within the unstructured text. Existing approaches focus mostly on structured data and a subset of single-domain outcomes. We explore how temporal modelling of patients from free text and structured data, using deep generative transformers can be used to forecast a wide range of future disorders, substances, procedures or findings. Methods: We present Foresight, a novel transformer-based pipeline that uses named entity recognition and linking tools to convert document text into structured, coded concepts, followed by providing probabilistic forecasts for future medical events such as disorders, substances, procedures and findings. We processed the entire free-text portion from three different hospital datasets totalling 811336 patients covering both physical and mental health. Findings: On tests in two UK hospitals (King's College Hospital, South London and Maudsley) and the US MIMIC-III dataset precision@10 0.68, 0.76 and 0.88 was achieved for forecasting the next disorder in a patient timeline, while precision@10 of 0.80, 0.81 and 0.91 was achieved for forecasting the next biomedical concept. Foresight was also validated on 34 synthetic patient timelines by five clinicians and achieved relevancy of 97% for the top forecasted candidate disorder. As a generative model, it can forecast follow-on biomedical concepts for as many steps as required. Interpretation: Foresight is a general-purpose model for biomedical concept modelling that can be used for real-world risk forecasting, virtual trials and clinical research to study the progression of disorders, simulate interventions and counterfactuals, and educational purposes.

Clinical machine learning research and AI driven clinical decision support models rely on clinically accurate labels. Manually extracting these labels with the help of clinical specialists is often time-consuming and expensive. This study tests the feasibility of automatic span- and document-level diagnosis extraction from unstructured Dutch echocardiogram reports. We included 115,692 unstructured echocardiogram reports from the UMCU a large university hospital in the Netherlands. A randomly selected subset was manually annotated for the occurrence and severity of eleven commonly described cardiac characteristics. We developed and tested several automatic labelling techniques at both span and document levels, using weighted and macro F1-score, precision, and recall for performance evaluation. We compared the performance of span labelling against document labelling methods, which included both direct document classifiers and indirect document classifiers that rely on span classification results. The SpanCategorizer and MedRoBERTa.nl models outperformed all other span and document classifiers, respectively. The weighted F1-score varied between characteristics, ranging from 0.60 to 0.93 in SpanCategorizer and 0.96 to 0.98 in MedRoBERTa.nl. Direct document classification was superior to indirect document classification using span classifiers. SetFit achieved competitive document classification performance using only 10\% of the training data. Utilizing a reduced label set yielded near-perfect document classification results. We recommend using our published SpanCategorizer and MedRoBERTa.nl models for span- and document-level diagnosis extraction from Dutch echocardiography reports. For settings with limited training data, SetFit may be a promising alternative for document classification.

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

Several studies have shown that speech and language features, automatically extracted from clinical interviews or spontaneous discourse, have diagnostic value for mental disorders such as schizophrenia and bipolar disorder. They typically make use of a large feature set to train a classifier for distinguishing between two groups of interest, i.e. a clinical and control group. However, a purely data-driven approach runs the risk of overfitting to a particular data set, especially when sample sizes are limited. Here, we first down-select the set of language features to a small subset that is related to a well-validated test of functional ability, the Social Skills Performance Assessment (SSPA). This helps establish the concurrent validity of the selected features. We use only these features to train a simple classifier to distinguish between groups of interest. Linear regression reveals that a subset of language features can effectively model the SSPA, with a correlation coefficient of 0.75. Furthermore, the same feature set can be used to build a strong binary classifier to distinguish between healthy controls and a clinical group (AUC = 0.96) and also between patients within the clinical group with schizophrenia and bipolar I disorder (AUC = 0.83).

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.

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.

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.

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.

Clinical evidence, derived from rigorous research and data analysis, provides healthcare professionals with reliable scientific foundations for informed decision-making. Integrating clinical evidence into real-time practice is challenging due to the enormous workload, complex professional processes, and time constraints. This highlights the need for tools that automate evidence synthesis to support more efficient and accurate decision making in clinical settings. This study introduces Quicker, an evidence-based clinical decision support system powered by large language models (LLMs), designed to automate evidence synthesis and generate clinical recommendations modeled after standard clinical guideline development processes. Quicker implements a fully automated chain that covers all phases, from questions to clinical recommendations, and further enables customized decision-making through integrated tools and interactive user interfaces. To evaluate Quicker's capabilities, we developed the Q2CRBench-3 benchmark dataset, based on clinical guideline development records for three different diseases. Experimental results highlighted Quicker's strong performance, with fine-grained question decomposition tailored to user preferences, retrieval sensitivities comparable to human experts, and literature screening performance approaching comprehensive inclusion of relevant studies. In addition, Quicker-assisted evidence assessment effectively supported human reviewers, while Quicker's recommendations were more comprehensive and logically coherent than those of clinicians. In system-level testing, collaboration between a single reviewer and Quicker reduced the time required for recommendation development to 20-40 minutes. In general, our findings affirm the potential of Quicker to help physicians make quicker and more reliable evidence-based clinical decisions.

Large Language Models (LLMs) and multi-agent systems have shown impressive capabilities in natural language tasks but face challenges in clinical trial applications, primarily due to limited access to external knowledge. Recognizing the potential of advanced clinical trial tools that aggregate and predict based on the latest medical data, we propose an integrated solution to enhance their accessibility and utility. We introduce Clinical Agent System (ClinicalAgent), a clinical multi-agent system designed for clinical trial tasks, leveraging GPT-4, multi-agent architectures, LEAST-TO-MOST, and ReAct reasoning technology. This integration not only boosts LLM performance in clinical contexts but also introduces novel functionalities. The proposed method achieves competitive predictive performance in clinical trial outcome prediction (0.7908 PR-AUC), obtaining a 0.3326 improvement over the standard prompt Method. Publicly available code can be found at https://anonymous.4open.science/r/ClinicalAgent-6671.

Recent advances in large language models have led to renewed interest in natural language processing in healthcare using the free text of clinical notes. One distinguishing characteristic of clinical notes is their long time span over multiple long documents. The unique structure of clinical notes creates a new design choice: when the context length for a language model predictor is limited, which part of clinical notes should we choose as the input? Existing studies either choose the inputs with domain knowledge or simply truncate them. We propose a framework to analyze the sections with high predictive power. Using MIMIC-III, we show that: 1) predictive power distribution is different between nursing notes and discharge notes and 2) combining different types of notes could improve performance when the context length is large. Our findings suggest that a carefully selected sampling function could enable more efficient information extraction from clinical notes.

Clinical notes contain rich data, which is unexploited in predictive modeling compared to structured data. In this work, we developed a new text representation Clinical XLNet for clinical notes which also leverages the temporal information of the sequence of the notes. We evaluated our models on prolonged mechanical ventilation prediction problem and our experiments demonstrated that Clinical XLNet outperforms the best baselines consistently.

This technical report introduces a Named Clinical Entity Recognition Benchmark for evaluating language models in healthcare, addressing the crucial natural language processing (NLP) task of extracting structured information from clinical narratives to support applications like automated coding, clinical trial cohort identification, and clinical decision support. The leaderboard provides a standardized platform for assessing diverse language models, including encoder and decoder architectures, on their ability to identify and classify clinical entities across multiple medical domains. A curated collection of openly available clinical datasets is utilized, encompassing entities such as diseases, symptoms, medications, procedures, and laboratory measurements. Importantly, these entities are standardized according to the Observational Medical Outcomes Partnership (OMOP) Common Data Model, ensuring consistency and interoperability across different healthcare systems and datasets, and a comprehensive evaluation of model performance. Performance of models is primarily assessed using the F1-score, and it is complemented by various assessment modes to provide comprehensive insights into model performance. The report also includes a brief analysis of models evaluated to date, highlighting observed trends and limitations. By establishing this benchmarking framework, the leaderboard aims to promote transparency, facilitate comparative analyses, and drive innovation in clinical entity recognition tasks, addressing the need for robust evaluation methods in healthcare NLP.

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.

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.

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.

Skin carcinoma is the most prevalent form of cancer globally, accounting for over $8 billion in annual healthcare expenditures. In clinical settings, physicians document patient visits using detailed SOAP (Subjective, Objective, Assessment, and Plan) notes. However, manually generating these notes is labor-intensive and contributes to clinician burnout. In this work, we propose a weakly supervised multimodal framework to generate clinically structured SOAP notes from limited inputs, including lesion images and sparse clinical text. Our approach reduces reliance on manual annotations, enabling scalable, clinically grounded documentation while alleviating clinician burden and reducing the need for large annotated data. Our method achieves performance comparable to GPT-4o, Claude, and DeepSeek Janus Pro across key clinical relevance metrics. To evaluate clinical quality, we introduce two novel metrics MedConceptEval and Clinical Coherence Score (CCS) which assess semantic alignment with expert medical concepts and input features, respectively.

Coronavirus disease (COVID-19) is a pandemic disease, which has already caused thousands of causalities and infected several millions of people worldwide. Any technological tool enabling rapid screening of the COVID-19 infection with high accuracy can be crucially helpful to healthcare professionals. The main clinical tool currently in use for the diagnosis of COVID-19 is the Reverse transcription polymerase chain reaction (RT-PCR), which is expensive, less-sensitive and requires specialized medical personnel. X-ray imaging is an easily accessible tool that can be an excellent alternative in the COVID-19 diagnosis. This research was taken to investigate the utility of artificial intelligence (AI) in the rapid and accurate detection of COVID-19 from chest X-ray images. The aim of this paper is to propose a robust technique for automatic detection of COVID-19 pneumonia from digital chest X-ray images applying pre-trained deep-learning algorithms while maximizing the detection accuracy. A public database was created by the authors combining several public databases and also by collecting images from recently published articles. The database contains a mixture of 423 COVID-19, 1485 viral pneumonia, and 1579 normal chest X-ray images. Transfer learning technique was used with the help of image augmentation to train and validate several pre-trained deep Convolutional Neural Networks (CNNs). The networks were trained to classify two different schemes: i) normal and COVID-19 pneumonia; ii) normal, viral and COVID-19 pneumonia with and without image augmentation. The classification accuracy, precision, sensitivity, and specificity for both the schemes were 99.7%, 99.7%, 99.7% and 99.55% and 97.9%, 97.95%, 97.9%, and 98.8%, respectively.

Specialized clinical AI assistants are rapidly entering medical practice, often framed as safer or more reliable than general-purpose large language models (LLMs). Yet, unlike frontier models, these clinical tools are rarely subjected to independent, quantitative evaluation, creating a critical evidence gap despite their growing influence on diagnosis, triage, and guideline interpretation. We assessed two widely deployed clinical AI systems (OpenEvidence and UpToDate Expert AI) against three state-of-the-art generalist LLMs (GPT-5, Gemini 3 Pro, and Claude Sonnet 4.5) using a 1,000-item mini-benchmark combining MedQA (medical knowledge) and HealthBench (clinician-alignment) tasks. Generalist models consistently outperformed clinical tools, with GPT-5 achieving the highest scores, while OpenEvidence and UpToDate demonstrated deficits in completeness, communication quality, context awareness, and systems-based safety reasoning. These findings reveal that tools marketed for clinical decision support may often lag behind frontier LLMs, underscoring the urgent need for transparent, independent evaluation before deployment in patient-facing workflows.

Medical benchmark datasets significantly contribute to developing Large Language Models (LLMs) for medical knowledge extraction, diagnosis, summarization, and other uses. Yet, current benchmarks are mainly derived from exam questions given to medical students or cases described in the medical literature, lacking the complexity of real-world patient cases that deviate from classic textbook abstractions. These include rare diseases, uncommon presentations of common diseases, and unexpected treatment responses. Here, we construct Clinically Uncommon Patient Cases and Diagnosis Dataset (CUPCase) based on 3,562 real-world case reports from BMC, including diagnoses in open-ended textual format and as multiple-choice options with distractors. Using this dataset, we evaluate the ability of state-of-the-art LLMs, including both general-purpose and Clinical LLMs, to identify and correctly diagnose a patient case, and test models' performance when only partial information about cases is available. Our findings show that general-purpose GPT-4o attains the best performance in both the multiple-choice task (average accuracy of 87.9%) and the open-ended task (BERTScore F1 of 0.764), outperforming several LLMs with a focus on the medical domain such as Meditron-70B and MedLM-Large. Moreover, GPT-4o was able to maintain 87% and 88% of its performance with only the first 20% of tokens of the case presentation in multiple-choice and free text, respectively, highlighting the potential of LLMs to aid in early diagnosis in real-world cases. CUPCase expands our ability to evaluate LLMs for clinical decision support in an open and reproducible manner.

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.

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

Accurate breast lesion risk estimation can significantly reduce unnecessary biopsies and help doctors decide optimal treatment plans. Most existing computer-aided systems rely solely on mammogram features to classify breast lesions. While this approach is convenient, it does not fully exploit useful information in clinical reports to achieve the optimal performance. Would clinical features significantly improve breast lesion classification compared to using mammograms alone? How to handle missing clinical information caused by variation in medical practice? What is the best way to combine mammograms and clinical features? There is a compelling need for a systematic study to address these fundamental questions. This paper investigates several multimodal deep networks based on feature concatenation, cross-attention, and co-attention to combine mammograms and categorical clinical variables. We show that the proposed architectures significantly increase the lesion classification performance (average area under ROC curves from 0.89 to 0.94). We also evaluate the model when clinical variables are missing.

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.

The COVID-19 pandemic swept across the world rapidly, infecting millions of people. An efficient tool that can accurately recognize important clinical concepts of COVID-19 from free text in electronic health records (EHRs) will be valuable to accelerate COVID-19 clinical research. To this end, this study aims at adapting the existing CLAMP natural language processing tool to quickly build COVID-19 SignSym, which can extract COVID-19 signs/symptoms and their 8 attributes (body location, severity, temporal expression, subject, condition, uncertainty, negation, and course) from clinical text. The extracted information is also mapped to standard concepts in the Observational Medical Outcomes Partnership common data model. A hybrid approach of combining deep learning-based models, curated lexicons, and pattern-based rules was applied to quickly build the COVID-19 SignSym from CLAMP, with optimized performance. Our extensive evaluation using 3 external sites with clinical notes of COVID-19 patients, as well as the online medical dialogues of COVID-19, shows COVID-19 Sign-Sym can achieve high performance across data sources. The workflow used for this study can be generalized to other use cases, where existing clinical natural language processing tools need to be customized for specific information needs within a short time. COVID-19 SignSym is freely accessible to the research community as a downloadable package (https://clamp.uth.edu/covid/nlp.php) and has been used by 16 healthcare organizations to support clinical research of COVID-19.

The automated generation of imaging reports proves invaluable in alleviating the workload of radiologists. A clinically applicable reports generation algorithm should demonstrate its effectiveness in producing reports that accurately describe radiology findings and attend to patient-specific indications. In this paper, we introduce a novel method, Structural Entities extraction and patient indications Incorporation (SEI) for chest X-ray report generation. Specifically, we employ a structural entities extraction (SEE) approach to eliminate presentation-style vocabulary in reports and improve the quality of factual entity sequences. This reduces the noise in the following cross-modal alignment module by aligning X-ray images with factual entity sequences in reports, thereby enhancing the precision of cross-modal alignment and further aiding the model in gradient-free retrieval of similar historical cases. Subsequently, we propose a cross-modal fusion network to integrate information from X-ray images, similar historical cases, and patient-specific indications. This process allows the text decoder to attend to discriminative features of X-ray images, assimilate historical diagnostic information from similar cases, and understand the examination intention of patients. This, in turn, assists in triggering the text decoder to produce high-quality reports. Experiments conducted on MIMIC-CXR validate the superiority of SEI over state-of-the-art approaches on both natural language generation and clinical efficacy metrics.

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.

Large language models have exhibited exceptional performance on various Natural Language Processing (NLP) tasks, leveraging techniques such as the pre-training, and instruction fine-tuning. Despite these advances, their effectiveness in medical applications is limited, due to challenges such as factual inaccuracies, reasoning abilities, and lack grounding in real-world experience. In this study, we present ClinicalGPT, a language model explicitly designed and optimized for clinical scenarios. By incorporating extensive and diverse real-world data, such as medical records, domain-specific knowledge, and multi-round dialogue consultations in the training process, ClinicalGPT is better prepared to handle multiple clinical task. Furthermore, we introduce a comprehensive evaluation framework that includes medical knowledge question-answering, medical exams, patient consultations, and diagnostic analysis of medical records. Our results demonstrate that ClinicalGPT significantly outperforms other models in these tasks, highlighting the effectiveness of our approach in adapting large language models to the critical domain of healthcare.

Multimodal large language models (MLLMs) have made significant strides, yet they face challenges in the medical domain due to limited specialized knowledge. While recent medical MLLMs demonstrate strong performance in lab settings, they often struggle in real-world applications, highlighting a substantial gap between research and practice. In this paper, we seek to address this gap at various stages of the end-to-end learning pipeline, including data collection, model fine-tuning, and evaluation. At the data collection stage, we introduce SemiHVision, a dataset that combines human annotations with automated augmentation techniques to improve both medical knowledge representation and diagnostic reasoning. For model fine-tuning, we trained PMC-Cambrian-8B-AN over 2400 H100 GPU hours, resulting in performance that surpasses public medical models like HuatuoGPT-Vision-34B (79.0% vs. 66.7%) and private general models like Claude3-Opus (55.7%) on traditional benchmarks such as SLAKE and VQA-RAD. In the evaluation phase, we observed that traditional benchmarks cannot accurately reflect realistic clinical task capabilities. To overcome this limitation and provide more targeted guidance for model evaluation, we introduce the JAMA Clinical Challenge, a novel benchmark specifically designed to evaluate diagnostic reasoning. On this benchmark, PMC-Cambrian-AN achieves state-of-the-art performance with a GPT-4 score of 1.29, significantly outperforming HuatuoGPT-Vision-34B (1.13) and Claude3-Opus (1.17), demonstrating its superior diagnostic reasoning abilities.

Objective: To transform heterogeneous clinical data from electronic health records into clinically meaningful constructed features using data driven method that rely, in part, on temporal relations among data. Materials and Methods: The clinically meaningful representations of medical concepts and patients are the key for health analytic applications. Most of existing approaches directly construct features mapped to raw data (e.g., ICD or CPT codes), or utilize some ontology mapping such as SNOMED codes. However, none of the existing approaches leverage EHR data directly for learning such concept representation. We propose a new way to represent heterogeneous medical concepts (e.g., diagnoses, medications and procedures) based on co-occurrence patterns in longitudinal electronic health records. The intuition behind the method is to map medical concepts that are co-occuring closely in time to similar concept vectors so that their distance will be small. We also derive a simple method to construct patient vectors from the related medical concept vectors. Results: For qualitative evaluation, we study similar medical concepts across diagnosis, medication and procedure. In quantitative evaluation, our proposed representation significantly improves the predictive modeling performance for onset of heart failure (HF), where classification methods (e.g. logistic regression, neural network, support vector machine and K-nearest neighbors) achieve up to 23% improvement in area under the ROC curve (AUC) using this proposed representation. Conclusion: We proposed an effective method for patient and medical concept representation learning. The resulting representation can map relevant concepts together and also improves predictive modeling performance.

Skin carcinoma is the most prevalent form of cancer globally, accounting for over $8 billion in annual healthcare expenditures. Early diagnosis, accurate and timely treatment are critical to improving patient survival rates. In clinical settings, physicians document patient visits using detailed SOAP (Subjective, Objective, Assessment, and Plan) notes. However, manually generating these notes is labor-intensive and contributes to clinician burnout. In this work, we propose skin-SOAP, a weakly supervised multimodal framework to generate clinically structured SOAP notes from limited inputs, including lesion images and sparse clinical text. Our approach reduces reliance on manual annotations, enabling scalable, clinically grounded documentation while alleviating clinician burden and reducing the need for large annotated data. Our method achieves performance comparable to GPT-4o, Claude, and DeepSeek Janus Pro across key clinical relevance metrics. To evaluate this clinical relevance, we introduce two novel metrics MedConceptEval and Clinical Coherence Score (CCS) which assess semantic alignment with expert medical concepts and input features, respectively.

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.

Pathological diagnosis remains the definitive standard for identifying tumors. The rise of multimodal large models has simplified the process of integrating image analysis with textual descriptions. Despite this advancement, the substantial costs associated with training and deploying these complex multimodal models, together with a scarcity of high-quality training datasets, create a significant divide between cutting-edge technology and its application in the clinical setting. We had meticulously compiled a dataset of approximately 45,000 cases, covering over 6 different tasks, including the classification of organ tissues, generating pathology report descriptions, and addressing pathology-related questions and answers. We have fine-tuned multimodal large models, specifically LLaVA, Qwen-VL, InternLM, with this dataset to enhance instruction-based performance. We conducted a qualitative assessment of the capabilities of the base model and the fine-tuned model in performing image captioning and classification tasks on the specific dataset. The evaluation results demonstrate that the fine-tuned model exhibits proficiency in addressing typical pathological questions. We hope that by making both our models and datasets publicly available, they can be valuable to the medical and research communities.

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.

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.

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.

Spine disorders affect 619 million people globally and are a leading cause of disability, yet AI-assisted diagnosis remains limited by the lack of level-aware, multimodal datasets. Clinical decision-making for spine disorders requires sophisticated reasoning across X-ray, CT, and MRI at specific vertebral levels. However, progress has been constrained by the absence of traceable, clinically-grounded instruction data and standardized, spine-specific benchmarks. To address this, we introduce SpineMed, an ecosystem co-designed with practicing spine surgeons. It features SpineMed-450k, the first large-scale dataset explicitly designed for vertebral-level reasoning across imaging modalities with over 450,000 instruction instances, and SpineBench, a clinically-grounded evaluation framework. SpineMed-450k is curated from diverse sources, including textbooks, guidelines, open datasets, and ~1,000 de-identified hospital cases, using a clinician-in-the-loop pipeline with a two-stage LLM generation method (draft and revision) to ensure high-quality, traceable data for question-answering, multi-turn consultations, and report generation. SpineBench evaluates models on clinically salient axes, including level identification, pathology assessment, and surgical planning. Our comprehensive evaluation of several recently advanced large vision-language models (LVLMs) on SpineBench reveals systematic weaknesses in fine-grained, level-specific reasoning. In contrast, our model fine-tuned on SpineMed-450k demonstrates consistent and significant improvements across all tasks. Clinician assessments confirm the diagnostic clarity and practical utility of our model's outputs.

With the proliferation of Large Language Models (LLMs) in diverse domains, there is a particular need for unified evaluation standards in clinical medical scenarios, where models need to be examined very thoroughly. We present CliMedBench, a comprehensive benchmark with 14 expert-guided core clinical scenarios specifically designed to assess the medical ability of LLMs across 7 pivot dimensions. It comprises 33,735 questions derived from real-world medical reports of top-tier tertiary hospitals and authentic examination exercises. The reliability of this benchmark has been confirmed in several ways. Subsequent experiments with existing LLMs have led to the following findings: (i) Chinese medical LLMs underperform on this benchmark, especially where medical reasoning and factual consistency are vital, underscoring the need for advances in clinical knowledge and diagnostic accuracy. (ii) Several general-domain LLMs demonstrate substantial potential in medical clinics, while the limited input capacity of many medical LLMs hinders their practical use. These findings reveal both the strengths and limitations of LLMs in clinical scenarios and offer critical insights for medical research.

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).

Accurate interpretation of lab results is crucial in clinical medicine, yet most patient portals use universal normal ranges, ignoring conditional factors like age and gender. This study introduces Lab-AI, an interactive system that offers personalized normal ranges using retrieval-augmented generation (RAG) from credible health sources. Lab-AI has two modules: factor retrieval and normal range retrieval. We tested these on 122 lab tests: 40 with conditional factors and 82 without. For tests with factors, normal ranges depend on patient-specific information. Our results show GPT-4-turbo with RAG achieved a 0.948 F1 score for factor retrieval and 0.995 accuracy for normal range retrieval. GPT-4-turbo with RAG outperformed the best non-RAG system by 33.5% in factor retrieval and showed 132% and 100% improvements in question-level and lab-level performance, respectively, for normal range retrieval. These findings highlight Lab-AI's potential to enhance patient understanding of lab results.

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.

Recent advancements in Large Language Models (LLMs) have drawn increasing attention since the learned embeddings pretrained on large-scale datasets have shown powerful ability in various downstream applications. However, whether the learned knowledge by LLMs can be transferred to clinical cardiology remains unknown. In this work, we aim to bridge this gap by transferring the knowledge of LLMs to clinical Electrocardiography (ECG). We propose an approach for cardiovascular disease diagnosis and automatic ECG diagnosis report generation. We also introduce an additional loss function by Optimal Transport (OT) to align the distribution between ECG and language embedding. The learned embeddings are evaluated on two downstream tasks: (1) automatic ECG diagnosis report generation, and (2) zero-shot cardiovascular disease detection. Our approach is able to generate high-quality cardiac diagnosis reports and also achieves competitive zero-shot classification performance even compared with supervised baselines, which proves the feasibility of transferring knowledge from LLMs to the cardiac domain.

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.

As opposed to evaluating computation and logic-based reasoning, current benchmarks for evaluating large language models (LLMs) in medicine are primarily focused on question-answering involving domain knowledge and descriptive reasoning. While such qualitative capabilities are vital to medical diagnosis, in real-world scenarios, doctors frequently use clinical calculators that follow quantitative equations and rule-based reasoning paradigms for evidence-based decision support. To this end, we propose MedCalc-Bench, a first-of-its-kind dataset focused on evaluating the medical calculation capability of LLMs. MedCalc-Bench contains an evaluation set of over 1000 manually reviewed instances from 55 different medical calculation tasks. Each instance in MedCalc-Bench consists of a patient note, a question requesting to compute a specific medical value, a ground truth answer, and a step-by-step explanation showing how the answer is obtained. While our evaluation results show the potential of LLMs in this area, none of them are effective enough for clinical settings. Common issues include extracting the incorrect entities, not using the correct equation or rules for a calculation task, or incorrectly performing the arithmetic for the computation. We hope our study highlights the quantitative knowledge and reasoning gaps in LLMs within medical settings, encouraging future improvements of LLMs for various clinical calculation tasks.

Learning to represent free text is a core task in many clinical machine learning (ML) applications, as clinical text contains observations and plans not otherwise available for inference. State-of-the-art methods use large language models developed with immense computational resources and training data; however, applying these models is challenging because of the highly varying syntax and vocabulary in clinical free text. Structured information such as International Classification of Disease (ICD) codes often succinctly abstracts the most important facts of a clinical encounter and yields good performance, but is often not as available as clinical text in real-world scenarios. We propose a multi-view learning framework that jointly learns from codes and text to combine the availability and forward-looking nature of text and better performance of ICD codes. The learned text embeddings can be used as inputs to predictive algorithms independent of the ICD codes during inference. Our approach uses a Graph Neural Network (GNN) to process ICD codes, and Bi-LSTM to process text. We apply Deep Canonical Correlation Analysis (DCCA) to enforce the two views to learn a similar representation of each patient. In experiments using planned surgical procedure text, our model outperforms BERT models fine-tuned to clinical data, and in experiments using diverse text in MIMIC-III, our model is competitive to a fine-tuned BERT at a tiny fraction of its computational effort.

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.

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.

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.

Like other fields of Traditional Medicines, Unani Medicines have been found as an effective medical practice for ages. It is still widely used in the subcontinent, particularly in Pakistan and India. However, Unani Medicines Practitioners are lacking modern IT applications in their everyday clinical practices. An Online Clinical Decision Support System may address this challenge to assist apprentice Unani Medicines practitioners in their diagnostic processes. The proposed system provides a web-based interface to enter the patient's symptoms, which are then automatically analyzed by our system to generate a list of probable diseases. The system allows practitioners to choose the most likely disease and inform patients about the associated treatment options remotely. The system consists of three modules: an Online Clinical Decision Support System, an Artificial Intelligence Inference Engine, and a comprehensive Unani Medicines Database. The system employs advanced AI techniques such as Decision Trees, Deep Learning, and Natural Language Processing. For system development, the project team used a technology stack that includes React, FastAPI, and MySQL. Data and functionality of the application is exposed using APIs for integration and extension with similar domain applications. The novelty of the project is that it addresses the challenge of diagnosing diseases accurately and efficiently in the context of Unani Medicines principles. By leveraging the power of technology, the proposed Clinical Decision Support System has the potential to ease access to healthcare services and information, reduce cost, boost practitioner and patient satisfaction, improve speed and accuracy of the diagnostic process, and provide effective treatments remotely. The application will be useful for Unani Medicines Practitioners, Patients, Government Drug Regulators, Software Developers, and Medical Researchers.

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.

Current vision-language models (VLMs) in medicine are primarily designed for categorical question answering (e.g., "Is this normal or abnormal?") or qualitative descriptive tasks. However, clinical decision-making often relies on quantitative assessments, such as measuring the size of a tumor or the angle of a joint, from which physicians draw their own diagnostic conclusions. This quantitative reasoning capability remains underexplored and poorly supported in existing VLMs. In this work, we introduce MedVision, a large-scale dataset and benchmark specifically designed to evaluate and improve VLMs on quantitative medical image analysis. MedVision spans 22 public datasets covering diverse anatomies and modalities, with 30.8 million image-annotation pairs. We focus on three representative quantitative tasks: (1) detection of anatomical structures and abnormalities, (2) tumor/lesion (T/L) size estimation, and (3) angle/distance (A/D) measurement. Our benchmarks show that current off-the-shelf VLMs perform poorly on these tasks. However, with supervised fine-tuning on MedVision, we significantly enhance their performance across detection, T/L estimation, and A/D measurement, demonstrating reduced error rates and improved precision. This work provides a foundation for developing VLMs with robust quantitative reasoning capabilities in medical imaging. Code and data are available at https://medvision-vlm.github.io.

Large-language models have recently demonstrated impressive zero-shot capabilities in a variety of natural language tasks such as summarization, dialogue generation, and question-answering. Despite many promising applications in clinical medicine, adoption of these models in real-world settings has been largely limited by their tendency to generate incorrect and sometimes even toxic statements. In this study, we develop Almanac, a large language model framework augmented with retrieval capabilities for medical guideline and treatment recommendations. Performance on a novel dataset of clinical scenarios (n = 130) evaluated by a panel of 5 board-certified and resident physicians demonstrates significant increases in factuality (mean of 18% at p-value < 0.05) across all specialties, with improvements in completeness and safety. Our results demonstrate the potential for large language models to be effective tools in the clinical decision-making process, while also emphasizing the importance of careful testing and deployment to mitigate their shortcomings.

There is an increasing interest in developing artificial intelligence (AI) systems to process and interpret electronic health records (EHRs). Natural language processing (NLP) powered by pretrained language models is the key technology for medical AI systems utilizing clinical narratives. However, there are few clinical language models, the largest of which trained in the clinical domain is comparatively small at 110 million parameters (compared with billions of parameters in the general domain). It is not clear how large clinical language models with billions of parameters can help medical AI systems utilize unstructured EHRs. In this study, we develop from scratch a large clinical language model - GatorTron - using >90 billion words of text (including >82 billion words of de-identified clinical text) and systematically evaluate it on 5 clinical NLP tasks including clinical concept extraction, medical relation extraction, semantic textual similarity, natural language inference (NLI), and medical question answering (MQA). We examine how (1) scaling up the number of parameters and (2) scaling up the size of the training data could benefit these NLP tasks. GatorTron models scale up the clinical language model from 110 million to 8.9 billion parameters and improve 5 clinical NLP tasks (e.g., 9.6% and 9.5% improvement in accuracy for NLI and MQA), which can be applied to medical AI systems to improve healthcare delivery. The GatorTron models are publicly available at: https://catalog.ngc.nvidia.com/orgs/nvidia/teams/clara/models/gatortron_og.