Daily Papers

Evaluating test cases automatically generated by Large Language Models (LLMs) is a critical yet challenging task. Existing benchmarks often evaluate the exclusion ratio on large, unstructured collections of wrong codes, suffering from high computational costs and score inflation. Furthermore, they inadvertently reward generators that detect common, trivial bugs, while failing to penalize their inability to identify rare yet critical faults. In this work, we connect two fundamental questions: (1) What is the minimal set of wrong codes sufficient to represent the entire error space? and (2) What is the minimal set of test cases needed to distinguish them? We introduce a novel framework that formalizes benchmark construction as finding an optimal diagnostic basis in a binary code-test matrix, where rows represent wrong codes and columns represent test case results. The rank of this matrix specifies the minimal number of independent error patterns (wrong codes) and provides a tight upper bound on the number of test cases required for complete fault coverage. Our objective is to identify a basis of size equal to the matrix rank that maximizes internal diversity. To tackle this NP-hard problem, we propose WrongSelect, an efficient approximation algorithm to select maximally diverse wrong codes. Applying this framework to millions of competitive programming submissions, we construct TC-Bench, a compact, diverse, and inflation-resistant benchmark. Extensive experiments show that even the most advanced test case generation methods achieve only ~60% exclusion rates on TC-Bench, exposing a significant gap in their diagnostic power and highlighting substantial room for future improvement. Our dataset is available at: https://huggingface.co/datasets/Luoberta/TC-Bench and our code is at: https://github.com/Luowaterbi/TC-Bench.

Pre-trained Transformers often exhibit over-confidence in source patterns and difficulty in forming new target-domain patterns during fine-tuning. We formalize the mechanism of output saturation leading to gradient suppression through standard cross-entropy and softmax analysis, showing that gradient suppression at inflection layers confines adaptation to high-level recombination of existing features while preventing low-level reconstruction. We introduce a set of layer-wise diagnostic metrics -- attention entropy (saturation proxy), activation gradient norm, parameter gradient norm, and Delta-CKA under a shared PCA basis -- to identify inflection layers characterized by both low attention entropy and steep gradient decay. Building on these findings, we propose a diagnose-first, inject-light fine-tuning strategy: selectively inserting LoRA adapters at inflection layers to restore suppressed backward signals with minimal parameter overhead. Experiments on BERT-base transfer from SST-2 to Rotten Tomatoes under under-trained and over-trained source regimes reveal that over-trained initialization benefits from inflection-layer LoRA injection, while under-trained initialization suffers performance degradation. When base features are strong, unblocking inflection layers facilitates high-level compositional adaptation; when base features are weak, full-pathway unblocking is required for low-level reconstruction, as supported by joint analysis of layer-wise activation gradients and Delta-CKA dynamics.

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.

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.

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

Chest X-ray plays a central role in thoracic diagnosis, and its interpretation inherently requires multi-step, evidence-grounded reasoning. However, large vision-language models (LVLMs) often generate plausible responses that are not faithfully grounded in diagnostic evidence and provide limited visual evidence for verification, while also requiring costly retraining to support new diagnostic tasks, limiting their reliability and adaptability in clinical settings. To address these limitations, we present CXReasonAgent, a diagnostic agent that integrates a large language model (LLM) with clinically grounded diagnostic tools to perform evidence-grounded diagnostic reasoning using image-derived diagnostic and visual evidence. To evaluate these capabilities, we introduce CXReasonDial, a multi-turn dialogue benchmark with 1,946 dialogues across 12 diagnostic tasks, and show that CXReasonAgent produces faithfully grounded responses, enabling more reliable and verifiable diagnostic reasoning than LVLMs. These findings highlight the importance of integrating clinically grounded diagnostic tools, particularly in safety-critical clinical settings.

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.

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.

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.

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.

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.

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).

To investigate whether the pleurae, airways and vessels surrounding a nodule on non-contrast computed tomography (CT) can discriminate benign and malignant pulmonary nodules. The LIDC-IDRI dataset, one of the largest publicly available CT database, was exploited for study. A total of 1556 nodules from 694 patients were involved in statistical analysis, where nodules with average scorings <3 and >3 were respectively denoted as benign and malignant. Besides, 339 nodules from 113 patients with diagnosis ground-truth were independently evaluated. Computer algorithms were developed to segment pulmonary structures and quantify the distances to pleural surface, airways and vessels, as well as the counting number and normalized volume of airways and vessels near a nodule. Odds ratio (OR) and Chi-square (\chi^2) testing were performed to demonstrate the correlation between features of surrounding structures and nodule malignancy. A non-parametric receiver operating characteristic (ROC) analysis was conducted in logistic regression to evaluate discrimination ability of each structure. For benign and malignant groups, the average distances from nodules to pleural surface, airways and vessels are respectively (6.56, 5.19), (37.08, 26.43) and (1.42, 1.07) mm. The correlation between nodules and the counting number of airways and vessels that contact or project towards nodules are respectively (OR=22.96, \chi^2=105.04) and (OR=7.06, \chi^2=290.11). The correlation between nodules and the volume of airways and vessels are (OR=9.19, \chi^2=159.02) and (OR=2.29, \chi^2=55.89). The areas-under-curves (AUCs) for pleurae, airways and vessels are respectively 0.5202, 0.6943 and 0.6529. Our results show that malignant nodules are often surrounded by more pulmonary structures compared with benign ones, suggesting that features of these structures could be viewed as lung cancer biomarkers.

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

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.

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.

In clinical radiology reports, doctors capture important information about the patient's health status. They convey their observations from raw medical imaging data about the inner structures of a patient. As such, formulating reports requires medical experts to possess wide-ranging knowledge about anatomical regions with their normal, healthy appearance as well as the ability to recognize abnormalities. This explicit grasp on both the patient's anatomy and their appearance is missing in current medical image-processing systems as annotations are especially difficult to gather. This renders the models to be narrow experts e.g. for identifying specific diseases. In this work, we recover this missing link by adding human anatomy into the mix and enable the association of content in medical reports to their occurrence in associated imagery (medical phrase grounding). To exploit anatomical structures in this scenario, we present a sophisticated automatic pipeline to gather and integrate human bodily structures from computed tomography datasets, which we incorporate in our PAXRay: A Projected dataset for the segmentation of Anatomical structures in X-Ray data. Our evaluation shows that methods that take advantage of anatomical information benefit heavily in visually grounding radiologists' findings, as our anatomical segmentations allow for up to absolute 50% better grounding results on the OpenI dataset as compared to commonly used region proposals. The PAXRay dataset is available at https://constantinseibold.github.io/paxray/.

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.

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.

Healthcare data now span EHRs, medical imaging, genomics, and wearable sensors, but most diagnostic models still process these modalities in isolation. This limits their ability to capture early, cross-modal disease signatures. This paper introduces a multimodal foundation model built on a transformer architecture that integrates heterogeneous clinical data through modality-specific encoders and cross-modal attention. Each modality is mapped into a shared latent space and fused using multi-head attention with residual normalization. We implement the framework using a multimodal dataset that simulates early-stage disease patterns across EHR sequences, imaging patches, genomic profiles, and wearable signals, including missing-modality scenarios and label noise. The model is trained using supervised classification together with self-supervised reconstruction and contrastive alignment to improve robustness. Experimental evaluation demonstrates strong performance in early-detection settings, with stable classification metrics, reliable uncertainty estimates, and interpretable attention patterns. The approach moves toward a flexible, pretrain-and-fine-tune foundation model that supports precision diagnostics, handles incomplete inputs, and improves early disease detection across oncology, cardiology, and neurology applications.

We present a foundation model-derived method to identify highly informative tokens and events in electronic health records. Our approach considers incoming data in the entire context of a patient's hospitalization and so can flag anomalous events that rule-based approaches would consider within a normal range. We demonstrate that the events our model flags are significant for predicting downstream patient outcomes and that a fraction of events identified as carrying little information can safely be dropped. Additionally, we show how informativeness can help interpret the predictions of prognostic models trained on foundation model-derived representations.

Recent advancements in Large Language Models (LLMs) have demonstrated significant promise in clinical diagnosis. However, current models struggle to emulate the iterative, diagnostic hypothesis-driven reasoning of real clinical scenarios. Specifically, current LLMs suffer from three critical limitations: (1) generating hallucinated medical content due to weak grounding in verified knowledge, (2) asking redundant or inefficient questions rather than discriminative ones that hinder diagnostic progress, and (3) losing coherence over multi-turn dialogues, leading to contradictory or inconsistent conclusions. To address these challenges, we propose MedKGI, a diagnostic framework grounded in clinical practices. MedKGI integrates a medical knowledge graph (KG) to constrain reasoning to validated medical ontologies, selects questions based on information gain to maximize diagnostic efficiency, and adopts an OSCE-format structured state to maintain consistent evidence tracking across turns. Experiments on clinical benchmarks show that MedKGI outperforms strong LLM baselines in both diagnostic accuracy and inquiry efficiency, improving dialogue efficiency by 30% on average while maintaining state-of-the-art accuracy.

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 emergence of vision-language models (VLMs) has opened new possibilities for clinical reasoning and has shown promising performance in dermatological diagnosis. However, their trustworthiness and clinical utility are often limited by three major factors: (1) Data heterogeneity, where diverse datasets lack consistent diagnostic labels and clinical concept annotations; (2) Absence of grounded diagnostic rationales, leading to a scarcity of reliable reasoning supervision; and (3) Limited scalability and generalization, as models trained on small, densely annotated datasets struggle to transfer nuanced reasoning to large, sparsely-annotated ones. To address these limitations, we propose SkinR1, a novel dermatological VLM that combines deep, textbook-based reasoning with the broad generalization capabilities of reinforcement learning (RL). SkinR1 systematically resolves the key challenges through a unified, end-to-end framework. First, we design a textbook-based reasoning generator that synthesizes high-fidelity, hierarchy-aware, and differential-diagnosis (DDx)-informed trajectories, providing reliable expert-level supervision. Second, we leverage the constructed trajectories for supervised fine-tuning (SFT) empowering the model with grounded reasoning ability. Third, we develop a novel RL paradigm that, by incorporating the hierarchical structure of diseases, effectively transfers these grounded reasoning patterns to large-scale, sparse data. Extensive experiments on multiple dermatology datasets demonstrate that SkinR1 achieves superior diagnostic accuracy. The ablation study demonstrates the importance of the reasoning foundation instilled by SFT.

Medical report generation has achieved remarkable advancements yet has still been faced with several challenges. First, the inherent imbalance in the distribution of normal and abnormal cases may lead models to exhibit a biased focus on normal samples, resulting in unreliable diagnoses. Second, the frequent occurrence of common template sentences in the reports may overwhelm the critical abnormal information. Moreover, existing works focus on 2D chest X-rays, leaving CT report generation underexplored due to the high-dimensional nature of CT images and the limited availability of CT-report pairs. Recently, LLM has shown a great ability to generate reliable answers with appropriate prompts, which shed light on addressing the aforementioned challenges. In this paper, we propose Dia-LLaMA, a framework to adapt the LLaMA2-7B for CT report generation by incorporating diagnostic information as guidance prompts. Considering the high dimension of CT, we leverage a pre-trained ViT3D with perceiver to extract the visual information. To tailor the LLM for report generation and emphasize abnormality, we extract additional diagnostic information by referring to a disease prototype memory bank, which is updated during training to capture common disease representations. Furthermore, we introduce disease-aware attention to enable the model to adjust attention for different diseases. Experiments on the chest CT dataset demonstrated that our proposed method outperformed previous methods and achieved state-of-the-art on both clinical efficacy performance and natural language generation metrics. The code will be made publically available.

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.

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.

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.

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.

Breast cancer is one of the most threatening diseases in women's life; thus, the early and accurate diagnosis plays a key role in reducing the risk of death in a patient's life. Mammography stands as the reference technique for breast cancer screening; nevertheless, many countries still lack access to mammograms due to economic, social, and cultural issues. Latest advances in computational tools, infrared cameras and devices for bio-impedance quantification, have given a chance to emerge other reference techniques like thermography, infrared thermography, electrical impedance tomography and biomarkers found in blood tests, therefore being faster, reliable and cheaper than other methods. In the last two decades, the techniques mentioned above have been considered as parallel and extended approaches for breast cancer diagnosis, as well many authors concluded that false positives and false negatives rates are significantly reduced. Moreover, when a screening method works together with a computational technique, it generates a "computer-aided diagnosis" system. The present work aims to review the last breakthroughs about the three techniques mentioned earlier, suggested machine learning techniques to breast cancer diagnosis, thus, describing the benefits of some methods in relation with other ones, such as, logistic regression, decision trees, random forest, deep and convolutional neural networks. With this, we studied several hyperparameters optimization approaches with parzen tree optimizers to improve the performance of baseline models. An exploratory data analysis for each database and a benchmark of convolutional neural networks for the database of thermal images are presented. The benchmark process, reviews image classification techniques with convolutional neural networks, like, Resnet50, NasNetmobile, InceptionResnet and Xception.

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

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

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.

Clinical information extraction, which involves structuring clinical concepts from unstructured medical text, remains a challenging problem that could benefit from the inclusion of tabular background information available in electronic health records. Existing open-source datasets lack explicit links between structured features and clinical concepts in the text, motivating the need for a new research dataset. We introduce SimSUM, a benchmark dataset of 10,000 simulated patient records that link unstructured clinical notes with structured background variables. Each record simulates a patient encounter in the domain of respiratory diseases and includes tabular data (e.g., symptoms, diagnoses, underlying conditions) generated from a Bayesian network whose structure and parameters are defined by domain experts. A large language model (GPT-4o) is prompted to generate a clinical note describing the encounter, including symptoms and relevant context. These notes are annotated with span-level symptom mentions. We conduct an expert evaluation to assess note quality and run baseline predictive models on both the tabular and textual data. The SimSUM dataset is primarily designed to support research on clinical information extraction in the presence of tabular background variables, which can be linked through domain knowledge to concepts of interest to be extracted from the text -- namely, symptoms in the case of SimSUM. Secondary uses include research on the automation of clinical reasoning over both tabular data and text, causal effect estimation in the presence of tabular and/or textual confounders, and multi-modal synthetic data generation. SimSUM is not intended for training clinical decision support systems or production-grade models, but rather to facilitate reproducible research in a simplified and controlled setting.

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

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.

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.

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.

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.

Heart disease, also known as cardiovascular disease, is a prevalent and critical medical condition characterized by the impairment of the heart and blood vessels, leading to various complications such as coronary artery disease, heart failure, and myocardial infarction. The timely and accurate detection of heart disease is of paramount importance in clinical practice. Early identification of individuals at risk enables proactive interventions, preventive measures, and personalized treatment strategies to mitigate the progression of the disease and reduce adverse outcomes. In recent years, the field of heart disease detection has witnessed notable advancements due to the integration of sophisticated technologies and computational approaches. These include machine learning algorithms, data mining techniques, and predictive modeling frameworks that leverage vast amounts of clinical and physiological data to improve diagnostic accuracy and risk stratification. In this work, we propose to detect heart disease from ECG images using cutting-edge technologies, namely vision transformer models. These models are Google-Vit, Microsoft-Beit, and Swin-Tiny. To the best of our knowledge, this is the initial endeavor concentrating on the detection of heart diseases through image-based ECG data by employing cuttingedge technologies namely, transformer models. To demonstrate the contribution of the proposed framework, the performance of vision transformer models are compared with state-of-the-art studies. Experiment results show that the proposed framework exhibits remarkable classification results.

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.

For safety, medical AI systems undergo thorough evaluations before deployment, validating their predictions against a ground truth which is assumed to be fixed and certain. However, this ground truth is often curated in the form of differential diagnoses. While a single differential diagnosis reflects the uncertainty in one expert assessment, multiple experts introduce another layer of uncertainty through disagreement. Both forms of uncertainty are ignored in standard evaluation which aggregates these differential diagnoses to a single label. In this paper, we show that ignoring uncertainty leads to overly optimistic estimates of model performance, therefore underestimating risk associated with particular diagnostic decisions. To this end, we propose a statistical aggregation approach, where we infer a distribution on probabilities of underlying medical condition candidates themselves, based on observed annotations. This formulation naturally accounts for the potential disagreements between different experts, as well as uncertainty stemming from individual differential diagnoses, capturing the entire ground truth uncertainty. Our approach boils down to generating multiple samples of medical condition probabilities, then evaluating and averaging performance metrics based on these sampled probabilities. In skin condition classification, we find that a large portion of the dataset exhibits significant ground truth uncertainty and standard evaluation severely over-estimates performance without providing uncertainty estimates. In contrast, our framework provides uncertainty estimates on common metrics of interest such as top-k accuracy and average overlap, showing that performance can change multiple percentage points. We conclude that, while assuming a crisp ground truth can be acceptable for many AI applications, a more nuanced evaluation protocol should be utilized in medical diagnosis.

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.

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

The 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.

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.

Electrocardiography (ECG) serves as an indispensable diagnostic tool in clinical practice, yet existing multimodal large language models (MLLMs) remain unreliable for ECG interpretation, often producing plausible but clinically incorrect analyses. To address this, we propose ECG-R1, the first reasoning MLLM designed for reliable ECG interpretation via three innovations. First, we construct the interpretation corpus using Protocol-Guided Instruction Data Generation, grounding interpretation in measurable ECG features and monograph-defined quantitative thresholds and diagnostic logic. Second, we present a modality-decoupled architecture with Interleaved Modality Dropout to improve robustness and cross-modal consistency when either the ECG signal or ECG image is missing. Third, we present Reinforcement Learning with ECG Diagnostic Evidence Rewards to strengthen evidence-grounded ECG interpretation. Additionally, we systematically evaluate the ECG interpretation capabilities of proprietary, open-source, and medical MLLMs, and provide the first quantitative evidence that severe hallucinations are widespread, suggesting that the public should not directly trust these outputs without independent verification. Code and data are publicly available at https://github.com/PKUDigitalHealth/ECG-R1{here}, and an online platform can be accessed at http://ai.heartvoice.com.cn/ECG-R1/{here}.

Foundation models trained with self-supervised learning (SSL) on large-scale histological images have significantly accelerated the development of computational pathology. These models can serve as backbones for region-of-interest (ROI) image analysis or patch-level feature extractors in whole-slide images (WSIs) based on multiple instance learning (MIL). Existing pathology foundation models (PFMs) are typically pre-trained on Hematoxylin-Eosin (H&E) stained pathology images. However, images with special stains, such as immunohistochemistry, are also frequently used in clinical practice. PFMs pre-trained mainly on H\&E-stained images may be limited in clinical applications involving special stains. To address this issue, we propose StainNet, a specialized foundation model for special stains based on the vision transformer (ViT) architecture. StainNet adopts a self-distillation SSL approach and is trained on over 1.4 million patch images cropping from 20,231 publicly available special staining WSIs in the HISTAI database. To evaluate StainNet, we conduct experiments on an in-house slide-level liver malignancy classification task and two public ROI-level datasets to demonstrate its strong ability. We also perform few-ratio learning and retrieval evaluations, and compare StainNet with recently larger PFMs to further highlight its strengths. We have released the StainNet model weights at: https://huggingface.co/JWonderLand/StainNet.

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.

Lung cancer is the deadliest type of cancer worldwide and late detection is the major factor for the low survival rate of patients. Low dose computed tomography has been suggested as a potential screening tool but manual screening is costly, time-consuming and prone to variability. This has fueled the development of automatic methods for the detection, segmentation and characterisation of pulmonary nodules but its application to clinical routine is challenging. In this study, a new database for the development and testing of pulmonary nodule computer-aided strategies is presented which intends to complement current databases by giving additional focus to radiologist variability and local clinical reality. State-of-the-art nodule detection, segmentation and characterization methods are tested and compared to manual annotations as well as collaborative strategies combining multiple radiologists and radiologists and computer-aided systems. It is shown that state-of-the-art methodologies can determine a patient's follow-up recommendation as accurately as a radiologist, though the nodule detection method used shows decreased performance in this database.

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.

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.

Rationale: Computer aided detection (CAD) algorithms for Pulmonary Embolism (PE) algorithms have been shown to increase radiologists' sensitivity with a small increase in specificity. However, CAD for PE has not been adopted into clinical practice, likely because of the high number of false positives current CAD software produces. Objective: To generate a database of annotated computed tomography pulmonary angiographies, use it to compare the sensitivity and false positive rate of current algorithms and to develop new methods that improve such metrics. Methods: 91 Computed tomography pulmonary angiography scans were annotated by at least one radiologist by segmenting all pulmonary emboli visible on the study. 20 annotated CTPAs were open to the public in the form of a medical image analysis challenge. 20 more were kept for evaluation purposes. 51 were made available post-challenge. 8 submissions, 6 of them novel, were evaluated on the 20 evaluation CTPAs. Performance was measured as per embolus sensitivity vs. false positives per scan curve. Results: The best algorithms achieved a per-embolus sensitivity of 75% at 2 false positives per scan (fps) or of 70% at 1 fps, outperforming the state of the art. Deep learning approaches outperformed traditional machine learning ones, and their performance improved with the number of training cases. Significance: Through this work and challenge we have improved the state-of-the art of computer aided detection algorithms for pulmonary embolism. An open database and an evaluation benchmark for such algorithms have been generated, easing the development of further improvements. Implications on clinical practice will need further research.

Rare diseases collectively affect over 300 million individuals worldwide, yet timely and accurate diagnosis remains a pervasive challenge. This is largely due to their clinical heterogeneity, low individual prevalence, and the limited familiarity most clinicians have with rare conditions. Here, we introduce DeepRare, the first rare disease diagnosis agentic system powered by a large language model (LLM), capable of processing heterogeneous clinical inputs. The system generates ranked diagnostic hypotheses for rare diseases, each accompanied by a transparent chain of reasoning that links intermediate analytic steps to verifiable medical evidence. DeepRare comprises three key components: a central host with a long-term memory module; specialized agent servers responsible for domain-specific analytical tasks integrating over 40 specialized tools and web-scale, up-to-date medical knowledge sources, ensuring access to the most current clinical information. This modular and scalable design enables complex diagnostic reasoning while maintaining traceability and adaptability. We evaluate DeepRare on eight datasets. The system demonstrates exceptional diagnostic performance among 2,919 diseases, achieving 100% accuracy for 1013 diseases. In HPO-based evaluations, DeepRare significantly outperforms other 15 methods, like traditional bioinformatics diagnostic tools, LLMs, and other agentic systems, achieving an average Recall@1 score of 57.18% and surpassing the second-best method (Reasoning LLM) by a substantial margin of 23.79 percentage points. For multi-modal input scenarios, DeepRare achieves 70.60% at Recall@1 compared to Exomiser's 53.20% in 109 cases. Manual verification of reasoning chains by clinical experts achieves 95.40% agreements. Furthermore, the DeepRare system has been implemented as a user-friendly web application http://raredx.cn/doctor.

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.

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.

Metadata are general characteristics of the data in a well-curated and condensed format, and have been proven to be useful for decision making, knowledge discovery, and also heterogeneous data organization of biobank. Among all data types in the biobank, pathology is the key component of the biobank and also serves as the gold standard of diagnosis. To maximize the utility of biobank and allow the rapid progress of biomedical science, it is essential to organize the data with well-populated pathology metadata. However, manual annotation of such information is tedious and time-consuming. In the study, we develop a multimodal multitask learning framework to predict four major slide-level metadata of pathology images. The framework learns generalizable representations across tissue slides, pathology reports, and case-level structured data. We demonstrate improved performance across all four tasks with the proposed method compared to a single modal single task baseline on two test sets, one external test set from a distinct data source (TCGA) and one internal held-out test set (TTH). In the test sets, the performance improvements on the averaged area under receiver operating characteristic curve across the four tasks are 16.48% and 9.05% on TCGA and TTH, respectively. Such pathology metadata prediction system may be adopted to mitigate the effort of expert annotation and ultimately accelerate the data-driven research by better utilization of the pathology biobank.

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

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

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.

Foundation models, often pre-trained with large-scale data, have achieved paramount success in jump-starting various vision and language applications. Recent advances further enable adapting foundation models in downstream tasks efficiently using only a few training samples, e.g., in-context learning. Yet, the application of such learning paradigms in medical image analysis remains scarce due to the shortage of publicly accessible data and benchmarks. In this paper, we aim at approaches adapting the foundation models for medical image classification and present a novel dataset and benchmark for the evaluation, i.e., examining the overall performance of accommodating the large-scale foundation models downstream on a set of diverse real-world clinical tasks. We collect five sets of medical imaging data from multiple institutes targeting a variety of real-world clinical tasks (22,349 images in total), i.e., thoracic diseases screening in X-rays, pathological lesion tissue screening, lesion detection in endoscopy images, neonatal jaundice evaluation, and diabetic retinopathy grading. Results of multiple baseline methods are demonstrated using the proposed dataset from both accuracy and cost-effective perspectives.

Chest X-rays are widely used to diagnose thoracic diseases, but the lack of detailed information about these abnormalities makes it challenging to develop accurate automated diagnosis systems, which is crucial for early detection and effective treatment. To address this challenge, we employed deep learning techniques to identify patterns in chest X-rays that correspond to different diseases. We conducted experiments on the "ChestX-ray14" dataset using various pre-trained CNNs, transformers, hybrid(CNN+Transformer) models and classical models. The best individual model was the CoAtNet, which achieved an area under the receiver operating characteristic curve (AUROC) of 84.2%. By combining the predictions of all trained models using a weighted average ensemble where the weight of each model was determined using differential evolution, we further improved the AUROC to 85.4%, outperforming other state-of-the-art methods in this field. Our findings demonstrate the potential of deep learning techniques, particularly ensemble deep learning, for improving the accuracy of automatic diagnosis of thoracic diseases from chest X-rays. Code available at:https://github.com/syednabilashraf/SynthEnsemble

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

Idiopathic pulmonary fibrosis (IPF) is a progressive disease that irreversibly transforms lung tissue into rigid fibrotic structures, leading to debilitating symptoms such as shortness of breath and chronic fatigue. The heterogeneity and complexity of this disease, particularly regarding its severity and progression rate, have made predicting its future course a complex and challenging task. Besides, traditional diagnostic methods based on clinical evaluations and imaging have limitations in capturing the disease's complexity. Using the Kaggle Pulmonary Fibrosis Progression dataset, which includes computed tomography images, and clinical information, the model predicts changes in forced vital capacity (FVC), a key progression indicator. Our method uses a proposed context-aware sequential-parallel hybrid transformer model and clinical information enrichment for its prediction. The proposed method achieved a Laplace Log-Likelihood score of -6.508, outperforming prior methods and demonstrating superior predictive capabilities. These results highlight the potential of advanced deep learning techniques to provide more accurate and timely predictions, offering a transformative approach to the diagnosis and management of IPF, with implications for improved patient outcomes and therapeutic advancements.

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.

Respiratory diseases remain major global health challenges, and traditional auscultation is often limited by subjectivity, environmental noise, and inter-clinician variability. This study presents an explainable multimodal deep learning framework for automatic lung-disease detection using respiratory audio signals. The proposed system integrates two complementary representations: a spectral-temporal encoder based on a CNN-BiLSTM Attention architecture, and a handcrafted acoustic-feature encoder capturing physiologically meaningful descriptors such as MFCCs, spectral centroid, spectral bandwidth, and zero-crossing rate. These branches are combined through late-stage fusion to leverage both data-driven learning and domain-informed acoustic cues. The model is trained and evaluated on the Asthma Detection Dataset Version 2 using rigorous preprocessing, including resampling, normalization, noise filtering, data augmentation, and patient-level stratified partitioning. The study achieved strong generalization with 91.21% accuracy, 0.899 macro F1-score, and 0.9866 macro ROC-AUC, outperforming all ablated variants. An ablation study confirms the importance of temporal modeling, attention mechanisms, and multimodal fusion. The framework incorporates Grad-CAM, Integrated Gradients, and SHAP, generating interpretable spectral, temporal, and feature-level explanations aligned with known acoustic biomarkers to build clinical transparency. The findings demonstrate the framework's potential for telemedicine, point-of-care diagnostics, and real-world respiratory screening.

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.

WHO has declared that more than 2.2 billion people worldwide are suffering from visual disorders, such as media haze, glaucoma, and drusen. At least 1 billion of these cases could have been either prevented or successfully treated, yet they remain unaddressed due to poverty, a lack of specialists, inaccurate ocular fundus diagnoses by ophthalmologists, or the presence of a rare disease. To address this, the research has developed the Hybrid Trio-Network Model Algorithm for accurately diagnosing 12 distinct common and rare eye diseases. This algorithm utilized the RFMiD dataset of 3,200 fundus images and the Binary Relevance Method to detect diseases separately, ensuring expandability and avoiding incorrect correlations. Each detector, incorporating finely tuned hyperparameters to optimize performance, consisted of three feature components: A classical transfer learning CNN model, a two-stage CNN model, and a Siamese Network. The diagnosis was made using features extracted through this Trio-Model with Ensembled Machine Learning algorithms. The proposed model achieved an average accuracy of 97% and an AUC score of 0.96. Compared to past benchmark studies, an increase of over 10% in the F1-score was observed for most diseases. Furthermore, using the Siamese Network, the model successfully made predictions in diseases like optic disc pallor, which past studies failed to predict due to low confidence. This diagnostic tool presents a stable, adaptive, cost-effective, efficient, accessible, and fast solution for globalizing early detection of both common and rare diseases.

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.

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.

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.

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

As the global burden of Alzheimer's disease (AD) continues to grow, early and accurate detection has become increasingly critical, especially in regions with limited access to advanced diagnostic tools. We propose BRAINS (Biomedical Retrieval-Augmented Intelligence for Neurodegeneration Screening) to address this challenge. This novel system harnesses the powerful reasoning capabilities of Large Language Models (LLMs) for Alzheimer's detection and monitoring. BRAINS features a dual-module architecture: a cognitive diagnostic module and a case-retrieval module. The Diagnostic Module utilizes LLMs fine-tuned on cognitive and neuroimaging datasets -- including MMSE, CDR scores, and brain volume metrics -- to perform structured assessments of Alzheimer's risk. Meanwhile, the Case Retrieval Module encodes patient profiles into latent representations and retrieves similar cases from a curated knowledge base. These auxiliary cases are fused with the input profile via a Case Fusion Layer to enhance contextual understanding. The combined representation is then processed with clinical prompts for inference. Evaluations on real-world datasets demonstrate BRAINS effectiveness in classifying disease severity and identifying early signs of cognitive decline. This system not only shows strong potential as an assistive tool for scalable, explainable, and early-stage Alzheimer's disease detection, but also offers hope for future applications in the field.

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.

Seeking health-related advice on the internet has become a common practice in the digital era. Determining the trustworthiness of medical claims found online and finding appropriate evidence for this information is increasingly challenging. Fact-checking has emerged as an approach to assess the veracity of factual claims using evidence from credible knowledge sources. To help advance the automation of this task, in this paper, we introduce a novel dataset of 750 health-related claims, labeled for veracity by medical experts and backed with evidence from appropriate clinical studies. We provide an analysis of the dataset, highlighting its characteristics and challenges. The dataset can be used for Machine Learning tasks related to automated fact-checking such as evidence retrieval, veracity prediction, and explanation generation. For this purpose, we provide baseline models based on different approaches, examine their performance, and discuss the findings.

Electrocardiograms (ECGs), a medical monitoring technology recording cardiac activity, are widely used for diagnosing cardiac arrhythmia. The diagnosis is based on the analysis of the deformation of the signal shapes due to irregular heart rates associated with heart diseases. Due to the infeasibility of manual examination of large volumes of ECG data, this paper aims to propose an automated AI based system for ECG-based arrhythmia classification. To this front, a deep learning based solution has been proposed for ECG-based arrhythmia classification. Twelve lead electrocardiograms (ECG) of length 10 sec from 45, 152 individuals from Shaoxing People's Hospital (SPH) dataset from PhysioNet with four different types of arrhythmias were used. The sampling frequency utilized was 500 Hz. Median filtering was used to preprocess the ECG signals. For every 1 sec of ECG signal, the time-frequency (TF) scalogram was estimated and stacked row wise to obtain a single image from 12 channels, resulting in 10 stacked TF scalograms for each ECG signal. These stacked TF scalograms are fed to the pretrained convolutional neural network (CNN), 1D CNN, and 1D CNN-LSTM (Long short-term memory) models, for arrhythmia classification. The fine-tuned CNN models obtained the best test accuracy of about 98% followed by 95% test accuracy by basic CNN-LSTM in arrhythmia classification.

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

Databases of electronic health records (EHRs) are increasingly used to inform clinical decisions. Machine learning methods can find patterns in EHRs that are predictive of future adverse outcomes. However, statistical models may be built upon patterns of health-seeking behavior that vary across patient subpopulations, leading to poor predictive performance when training on one patient population and predicting on another. This note proposes two tests to better measure and understand model generalization. We use these tests to compare models derived from two data sources: (i) historical medical records, and (ii) electrocardiogram (EKG) waveforms. In a predictive task, we show that EKG-based models can be more stable than EHR-based models across different patient populations.

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

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.

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.

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.

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.

Background: Cancer remains one of the leading causes of morbidity and mortality worldwide. Comprehensive datasets that combine histopathological images with genetic and survival data across various tumour sites are essential for advancing computational pathology and personalised medicine. Results: We present SurGen, a dataset comprising 1,020 H&E-stained whole slide images (WSIs) from 843 colorectal cancer cases. The dataset includes detailed annotations for key genetic mutations (KRAS, NRAS, BRAF) and mismatch repair status, as well as survival data for 426 cases. To demonstrate SurGen's practical utility, we conducted a proof-of-concept machine learning experiment predicting mismatch repair status from the WSIs, achieving a test AUROC of 0.8316. These preliminary results underscore the dataset's potential to facilitate research in biomarker discovery, prognostic modelling, and advanced machine learning applications in colorectal cancer. Conclusions: SurGen offers a valuable resource for the scientific community, enabling studies that require high-quality WSIs linked with comprehensive clinical and genetic information on colorectal cancer. Our initial findings affirm the dataset's capacity to advance diagnostic precision and foster the development of personalised treatment strategies in colorectal oncology. Data available online at https://doi.org/10.6019/S-BIAD1285.

We present a labeled large-scale, high resolution chest x-ray dataset for the automated exploration of medical images along with their associated reports. This dataset includes more than 160,000 images obtained from 67,000 patients that were interpreted and reported by radiologists at Hospital San Juan Hospital (Spain) from 2009 to 2017, covering six different position views and additional information on image acquisition and patient demography. The reports were labeled with 174 different radiographic findings, 19 differential diagnoses and 104 anatomic locations organized as a hierarchical taxonomy and mapped onto standard Unified Medical Language System (UMLS) terminology. Of these reports, 27% were manually annotated by trained physicians and the remaining set was labeled using a supervised method based on a recurrent neural network with attention mechanisms. The labels generated were then validated in an independent test set achieving a 0.93 Micro-F1 score. To the best of our knowledge, this is one of the largest public chest x-ray database suitable for training supervised models concerning radiographs, and the first to contain radiographic reports in Spanish. The PadChest dataset can be downloaded from http://bimcv.cipf.es/bimcv-projects/padchest/.

Recent advances in medical multi-modal models focus on specialized image analysis like dermatology, pathology, or radiology. However, they do not fully capture the complexity of real-world clinical diagnostics, which involve heterogeneous inputs and require ongoing contextual understanding during patient-physician interactions. To bridge this gap, we introduce PulseMind, a new family of multi-modal diagnostic models that integrates a systematically curated dataset, a comprehensive evaluation benchmark, and a tailored training framework. Specifically, we first construct a diagnostic dataset, MediScope, which comprises 98,000 real-world multi-turn consultations and 601,500 medical images, spanning over 10 major clinical departments and more than 200 sub-specialties. Then, to better reflect the requirements of real-world clinical diagnosis, we develop the PulseMind Benchmark, a multi-turn diagnostic consultation benchmark with a four-dimensional evaluation protocol comprising proactiveness, accuracy, usefulness, and language quality. Finally, we design a training framework tailored for multi-modal clinical diagnostics, centered around a core component named Comparison-based Reinforcement Policy Optimization (CRPO). Compared to absolute score rewards, CRPO uses relative preference signals from multi-dimensional com-parisons to provide stable and human-aligned training guidance. Extensive experiments demonstrate that PulseMind achieves competitive performance on both the diagnostic consultation benchmark and public medical benchmarks.

POST-traumatic stress disorder (PTSD) is a chronic and debilitating mental condition that is developed in response to catastrophic life events, such as military combat, sexual assault, and natural disasters. PTSD is characterized by flashbacks of past traumatic events, intrusive thoughts, nightmares, hypervigilance, and sleep disturbance, all of which affect a person's life and lead to considerable social, occupational, and interpersonal dysfunction. The diagnosis of PTSD is done by medical professionals using self-assessment questionnaire of PTSD symptoms as defined in the Diagnostic and Statistical Manual of Mental Disorders (DSM). In this paper, and for the first time, we collected, annotated, and prepared for public distribution a new video database for automatic PTSD diagnosis, called PTSD in the wild dataset. The database exhibits "natural" and big variability in acquisition conditions with different pose, facial expression, lighting, focus, resolution, age, gender, race, occlusions and background. In addition to describing the details of the dataset collection, we provide a benchmark for evaluating computer vision and machine learning based approaches on PTSD in the wild dataset. In addition, we propose and we evaluate a deep learning based approach for PTSD detection in respect to the given benchmark. The proposed approach shows very promising results. Interested researcher can download a copy of PTSD-in-the wild dataset from: http://www.lissi.fr/PTSD-Dataset/

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

Automated structured radiology report generation (SRRG) from chest X-ray images offers significant potential to reduce workload of radiologists by generating reports in structured formats that ensure clarity, consistency, and adherence to clinical reporting standards. While radiologists effectively utilize available clinical contexts in their diagnostic reasoning, existing SRRG systems overlook these essential elements. This fundamental gap leads to critical problems including temporal hallucinations when referencing non-existent clinical contexts. To address these limitations, we propose contextualized SRRG (C-SRRG) that comprehensively incorporates rich clinical context for SRRG. We curate C-SRRG dataset by integrating comprehensive clinical context encompassing 1) multi-view X-ray images, 2) clinical indication, 3) imaging techniques, and 4) prior studies with corresponding comparisons based on patient histories. Through extensive benchmarking with state-of-the-art multimodal large language models, we demonstrate that incorporating clinical context with the proposed C-SRRG significantly improves report generation quality. We publicly release dataset, code, and checkpoints to facilitate future research for clinically-aligned automated RRG at https://github.com/vuno/contextualized-srrg.

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

The electrocardiogram (ECG) is a cost-effective, highly accessible and widely employed diagnostic tool. With the advent of Foundation Models (FMs), the field of AI-assisted ECG interpretation has begun to evolve, as they enable model reuse across different tasks by relying on embeddings. However, to responsibly employ FMs, it is crucial to rigorously assess to which extent the embeddings they produce are generalizable, particularly in error-sensitive domains such as healthcare. Although prior works have already addressed the problem of benchmarking ECG-expert FMs, they focus predominantly on the evaluation of downstream performance. To fill this gap, this study aims to find an in-depth, comprehensive benchmarking framework for FMs, with a specific focus on ECG-expert ones. To this aim, we introduce a benchmark methodology that complements performance-based evaluation with representation-level analysis, leveraging SHAP and UMAP techniques. Furthermore, we rely on the methodology for carrying out an extensive evaluation of several ECG-expert FMs pretrained via state-of-the-art techniques over different cross-continental datasets and data availability settings; this includes ones featuring data scarcity, a fairly common situation in real-world medical scenarios. Experimental results show that our benchmarking protocol provides a rich insight of ECG-expert FMs' embedded patterns, enabling a deeper understanding of their representational structure and generalizability.

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.

We introduce scientific claim verification, a new task to select abstracts from the research literature containing evidence that SUPPORTS or REFUTES a given scientific claim, and to identify rationales justifying each decision. To study this task, we construct SciFact, a dataset of 1.4K expert-written scientific claims paired with evidence-containing abstracts annotated with labels and rationales. We develop baseline models for SciFact, and demonstrate that simple domain adaptation techniques substantially improve performance compared to models trained on Wikipedia or political news. We show that our system is able to verify claims related to COVID-19 by identifying evidence from the CORD-19 corpus. Our experiments indicate that SciFact will provide a challenging testbed for the development of new systems designed to retrieve and reason over corpora containing specialized domain knowledge. Data and code for this new task are publicly available at https://github.com/allenai/scifact. A leaderboard and COVID-19 fact-checking demo are available at https://scifact.apps.allenai.org.

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.

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.

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.

While Multimodal Large Language Models (MLLMs) show promising performance in automated electrocardiogram interpretation, it remains unclear whether they genuinely perform actual step-by-step reasoning or just rely on superficial visual cues. To investigate this, we introduce ECG-Reasoning-Benchmark, a novel multi-turn evaluation framework comprising over 6,400 samples to systematically assess step-by-step reasoning across 17 core ECG diagnoses. Our comprehensive evaluation of state-of-the-art models reveals a critical failure in executing multi-step logical deduction. Although models possess the medical knowledge to retrieve clinical criteria for a diagnosis, they exhibit near-zero success rates (6% Completion) in maintaining a complete reasoning chain, primarily failing to ground the corresponding ECG findings to the actual visual evidence in the ECG signal. These results demonstrate that current MLLMs bypass actual visual interpretation, exposing a critical flaw in existing training paradigms and underscoring the necessity for robust, reasoning-centric medical AI. The code and data are available at https://github.com/Jwoo5/ecg-reasoning-benchmark.

Recent advances in reasoning-enhanced large language models (LLMs) and multimodal LLMs (MLLMs) have significantly improved performance in complex tasks, yet medical AI models often overlook the structured reasoning processes inherent in clinical practice. In this work, we present ChestX-Reasoner, a radiology diagnosis MLLM designed to leverage process supervision mined directly from clinical reports, reflecting the step-by-step reasoning followed by radiologists. We construct a large dataset by extracting and refining reasoning chains from routine radiology reports. Our two-stage training framework combines supervised fine-tuning and reinforcement learning guided by process rewards to better align model reasoning with clinical standards. We introduce RadRBench-CXR, a comprehensive benchmark featuring 59K visual question answering samples with 301K clinically validated reasoning steps, and propose RadRScore, a metric evaluating reasoning factuality, completeness, and effectiveness. ChestX-Reasoner outperforms existing medical and general-domain MLLMs in both diagnostic accuracy and reasoning ability, achieving 16%, 5.9%, and 18% improvements in reasoning ability compared to the best medical MLLM, the best general MLLM, and its base model, respectively, as well as 3.3%, 24%, and 27% improvements in outcome accuracy. All resources are open-sourced to facilitate further research in medical reasoning MLLMs.

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.

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.

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.

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

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

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

Bankart lesions, or anterior-inferior glenoid labral tears, are diagnostically challenging on standard MRIs due to their subtle imaging features-often necessitating invasive MRI arthrograms (MRAs). This study develops deep learning (DL) models to detect Bankart lesions on both standard MRIs and MRAs, aiming to improve diagnostic accuracy and reduce reliance on MRAs. We curated a dataset of 586 shoulder MRIs (335 standard, 251 MRAs) from 558 patients who underwent arthroscopy. Ground truth labels were derived from intraoperative findings, the gold standard for Bankart lesion diagnosis. Separate DL models for MRAs and standard MRIs were trained using the Swin Transformer architecture, pre-trained on a public knee MRI dataset. Predictions from sagittal, axial, and coronal views were ensembled to optimize performance. The models were evaluated on a 20% hold-out test set (117 MRIs: 46 MRAs, 71 standard MRIs). Bankart lesions were identified in 31.9% of MRAs and 8.6% of standard MRIs. The models achieved AUCs of 0.87 (86% accuracy, 83% sensitivity, 86% specificity) and 0.90 (85% accuracy, 82% sensitivity, 86% specificity) on standard MRIs and MRAs, respectively. These results match or surpass radiologist performance on our dataset and reported literature metrics. Notably, our model's performance on non-invasive standard MRIs matched or surpassed the radiologists interpreting MRAs. This study demonstrates the feasibility of using DL to address the diagnostic challenges posed by subtle pathologies like Bankart lesions. Our models demonstrate potential to improve diagnostic confidence, reduce reliance on invasive imaging, and enhance accessibility to care.

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

The 7-point checklist (7PCL) is a widely used diagnostic tool in dermoscopy for identifying malignant melanoma by assigning point values to seven specific attributes. However, the traditional 7PCL is limited to distinguishing between malignant melanoma and melanocytic Nevi, and falls short in scenarios where multiple skin diseases with appearances similar to melanoma coexist. To address this limitation, we propose a novel diagnostic framework that integrates a clinical knowledge-based topological graph (CKTG) with a gradient diagnostic strategy featuring a data-driven weighting system (GD-DDW). The CKTG captures both the internal and external relationships among the 7PCL attributes, while the GD-DDW emulates dermatologists' diagnostic processes, prioritizing visual observation before making predictions. Additionally, we introduce a multimodal feature extraction approach leveraging a dual-attention mechanism to enhance feature extraction through cross-modal interaction and unimodal collaboration. This method incorporates meta-information to uncover interactions between clinical data and image features, ensuring more accurate and robust predictions. Our approach, evaluated on the EDRA dataset, achieved an average AUC of 88.6%, demonstrating superior performance in melanoma detection and feature prediction. This integrated system provides data-driven benchmarks for clinicians, significantly enhancing the precision of melanoma diagnosis.

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.

A brain tumour is a mass or cluster of abnormal cells in the brain, which has the possibility of becoming life-threatening because of its ability to invade neighbouring tissues and also form metastases. An accurate diagnosis is essential for successful treatment planning and magnetic resonance imaging is the principal imaging modality for diagnostic of brain tumours and their extent. Deep Learning methods in computer vision applications have shown significant improvement in recent years, most of which can be credited to the fact that a sizeable amount of data is available to train models on, and the improvements in the model architectures yielding better approximations in a supervised setting. Classifying tumours using such deep learning methods has made significant progress with the availability of open datasets with reliable annotations. Typically those methods are either 3D models, which use 3D volumetric MRIs or even 2D models considering each slice separately. However, by treating the slice spatial dimension separately, spatiotemporal models can be employed as spatiospatial models for this task. These models have the capabilities of learning specific spatial and temporal relationship, while reducing computational costs. This paper uses two spatiotemporal models, ResNet (2+1)D and ResNet Mixed Convolution, to classify different types of brain tumours. It was observed that both these models performed superior to the pure 3D convolutional model, ResNet18. Furthermore, it was also observed that pre-training the models on a different, even unrelated dataset before training them for the task of tumour classification improves the performance. Finally, Pre-trained ResNet Mixed Convolution was observed to be the best model in these experiments, achieving a macro F1-score of 0.93 and a test accuracy of 96.98\%, while at the same time being the model with the least computational cost.

Most of the existing chest X-ray datasets include labels from a list of findings without specifying their locations on the radiographs. This limits the development of machine learning algorithms for the detection and localization of chest abnormalities. In this work, we describe a dataset of more than 100,000 chest X-ray scans that were retrospectively collected from two major hospitals in Vietnam. Out of this raw data, we release 18,000 images that were manually annotated by a total of 17 experienced radiologists with 22 local labels of rectangles surrounding abnormalities and 6 global labels of suspected diseases. The released dataset is divided into a training set of 15,000 and a test set of 3,000. Each scan in the training set was independently labeled by 3 radiologists, while each scan in the test set was labeled by the consensus of 5 radiologists. We designed and built a labeling platform for DICOM images to facilitate these annotation procedures. All images are made publicly available (https://www.physionet.org/content/vindr-cxr/1.0.0/) in DICOM format along with the labels of both the training set and the test set.

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.

In this paper, a 3D-RegNet-based neural network is proposed for diagnosing the physical condition of patients with coronavirus (Covid-19) infection. In the application of clinical medicine, lung CT images are utilized by practitioners to determine whether a patient is infected with coronavirus. However, there are some laybacks can be considered regarding to this diagnostic method, such as time consuming and low accuracy. As a relatively large organ of human body, important spatial features would be lost if the lungs were diagnosed utilizing two dimensional slice image. Therefore, in this paper, a deep learning model with 3D image was designed. The 3D image as input data was comprised of two-dimensional pulmonary image sequence and from which relevant coronavirus infection 3D features were extracted and classified. The results show that the test set of the 3D model, the result: f1 score of 0.8379 and AUC value of 0.8807 have been achieved.

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

Large Language Models (LLMs) are increasingly used for clinical decision support, where hallucinations and unsafe suggestions may pose direct risks to patient safety. These risks are particularly challenging as they often manifest as subtle clinical errors that evade detection by generic metrics, while expert-authored fine-grained rubrics remain costly to construct and difficult to scale. In this paper, we propose a retrieval-augmented multi-agent framework designed to automate the generation of instance-specific evaluation rubrics. Our approach grounds evaluation in authoritative medical evidence by decomposing retrieved content into atomic facts and synthesizing them with user interaction constraints to form verifiable, fine-grained evaluation criteria. Evaluated on HealthBench, our framework achieves a Clinical Intent Alignment (CIA) score of 60.12%, a statistically significant improvement over the GPT-4o baseline (55.16%). In discriminative tests, our rubrics yield a mean score delta (μ_Δ = 8.658) and an AUROC of 0.977, nearly doubling the quality separation achieved by GPT-4o baseline (4.972). Beyond evaluation, our rubrics effectively guide response refinement, improving quality by 9.2% (from 59.0% to 68.2%). This provides a scalable and transparent foundation for both evaluating and improving medical LLMs. The code is available at https://anonymous.4open.science/r/Automated-Rubric-Generation-AF3C/.

Medical foundation models, pre-trained with large-scale clinical data, demonstrate strong performance in diverse clinically relevant applications. RETFound, trained on nearly one million retinal images, exemplifies this approach in applications with retinal images. However, the emergence of increasingly powerful and multifold larger generalist foundation models such as DINOv2 and DINOv3 raises the question of whether domain-specific pre-training remains essential, and if so, what gap persists. To investigate this, we systematically evaluated the adaptability of DINOv2 and DINOv3 in retinal image applications, compared to two specialist RETFound models, RETFound-MAE and RETFound-DINOv2. We assessed performance on ocular disease detection and systemic disease prediction using two adaptation strategies: fine-tuning and linear probing. Data efficiency and adaptation efficiency were further analysed to characterise trade-offs between predictive performance and computational cost. Our results show that although scaling generalist models yields strong adaptability across diverse tasks, RETFound-DINOv2 consistently outperforms these generalist foundation models in ocular-disease detection and oculomics tasks, demonstrating stronger generalisability and data efficiency. These findings suggest that specialist retinal foundation models remain the most effective choice for clinical applications, while the narrowing gap with generalist foundation models suggests that continued data and model scaling can deliver domain-relevant gains and position them as strong foundations for future medical foundation models.

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

Computer-aided diagnosis establishes methods for robust assessment of medical image-based examination. Image processing introduced a promising strategy to facilitate disease classification and detection while diminishing unnecessary expenses. In this paper, we propose a novel metastatic cancer image classification model based on DenseNet Block, which can effectively identify metastatic cancer in small image patches taken from larger digital pathology scans. We evaluate the proposed approach to the slightly modified version of the PatchCamelyon (PCam) benchmark dataset. The dataset is the slightly modified version of the PatchCamelyon (PCam) benchmark dataset provided by Kaggle competition, which packs the clinically-relevant task of metastasis detection into a straight-forward binary image classification task. The experiments indicated that our model outperformed other classical methods like Resnet34, Vgg19. Moreover, we also conducted data augmentation experiment and study the relationship between Batches processed and loss value during the training and validation process.

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

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

Pathology diagnosis based on EEG signals and decoding brain activity holds immense importance in understanding neurological disorders. With the advancement of artificial intelligence methods and machine learning techniques, the potential for accurate data-driven diagnoses and effective treatments has grown significantly. However, applying machine learning algorithms to real-world datasets presents diverse challenges at multiple levels. The scarcity of labelled data, especially in low regime scenarios with limited availability of real patient cohorts due to high costs of recruitment, underscores the vital deployment of scaling and transfer learning techniques. In this study, we explore a real-world pathology classification task to highlight the effectiveness of data and model scaling and cross-dataset knowledge transfer. As such, we observe varying performance improvements through data scaling, indicating the need for careful evaluation and labelling. Additionally, we identify the challenges of possible negative transfer and emphasize the significance of some key components to overcome distribution shifts and potential spurious correlations and achieve positive transfer. We see improvement in the performance of the target model on the target (NMT) datasets by using the knowledge from the source dataset (TUAB) when a low amount of labelled data was available. Our findings indicate a small and generic model (e.g. ShallowNet) performs well on a single dataset, however, a larger model (e.g. TCN) performs better on transfer and learning from a larger and diverse dataset.