Daily Papers

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.

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.

Skin conditions affect an estimated 1.9 billion people worldwide. A shortage of dermatologists causes long wait times and leads patients to seek dermatologic care from general practitioners. However, the diagnostic accuracy of general practitioners has been reported to be only 0.24-0.70 (compared to 0.77-0.96 for dermatologists), resulting in referral errors, delays in care, and errors in diagnosis and treatment. In this paper, we developed a deep learning system (DLS) to provide a differential diagnosis of skin conditions for clinical cases (skin photographs and associated medical histories). The DLS distinguishes between 26 skin conditions that represent roughly 80% of the volume of skin conditions seen in primary care. The DLS was developed and validated using de-identified cases from a teledermatology practice serving 17 clinical sites via a temporal split: the first 14,021 cases for development and the last 3,756 cases for validation. On the validation set, where a panel of three board-certified dermatologists defined the reference standard for every case, the DLS achieved 0.71 and 0.93 top-1 and top-3 accuracies respectively. For a random subset of the validation set (n=963 cases), 18 clinicians reviewed the cases for comparison. On this subset, the DLS achieved a 0.67 top-1 accuracy, non-inferior to board-certified dermatologists (0.63, p<0.001), and higher than primary care physicians (PCPs, 0.45) and nurse practitioners (NPs, 0.41). The top-3 accuracy showed a similar trend: 0.90 DLS, 0.75 dermatologists, 0.60 PCPs, and 0.55 NPs. These results highlight the potential of the DLS to augment general practitioners to accurately diagnose skin conditions by suggesting differential diagnoses that may not have been considered. Future work will be needed to prospectively assess the clinical impact of using this tool in actual clinical workflows.

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.

Neuroimaging is a ubiquitous tool for evaluating patients with neurological diseases. The global demand for magnetic resonance imaging (MRI) studies has risen steadily, placing significant strain on health systems, prolonging turnaround times, and intensifying physician burnout. These challenges disproportionately impact patients in low-resource and rural settings. Here, we utilized a large academic health system as a data engine to develop Prima, the first vision language model (VLM) serving as an AI foundation for neuroimaging that supports real-world, clinical MRI studies as input. Trained on over 220,000 MRI studies, Prima uses a hierarchical vision architecture that provides general and transferable MRI features. Prima was tested in a 1-year health system-wide study that included 30K MRI studies. Across 52 radiologic diagnoses from the major neurologic disorders, including neoplastic, inflammatory, infectious, and developmental lesions, Prima achieved a mean diagnostic area under the ROC curve of 92.0, outperforming other state-of-the-art general and medical AI models. Prima offers explainable differential diagnoses, worklist priority for radiologists, and clinical referral recommendations across diverse patient demographics and MRI systems. Prima demonstrates algorithmic fairness across sensitive groups and can help mitigate health system biases, such as prolonged turnaround times for low-resource populations. These findings highlight the transformative potential of health system-scale VLMs and Prima's role in advancing AI-driven healthcare.

Ontology rankers remain useful for rare-disease diagnosis because each candidate can be traced to matched patient phenotypes. Large language models (LLMs) can generate differential diagnoses from the same patient description, but their predictions lack an equally clear evidence trail. Rather than asking which system should replace the other, we ask whether an LLM can improve the ranker without giving up its evidence. Our behavior-based fusion model examines the two ranked lists, their agreement, and the ontology support behind each candidate, and learns how much to rely on each system for the individual case. Before comparison, we remove a documented test-set leakage pathway caused by benchmark cases and ontology annotations being derived from the same publications. Across eight open LLMs, fusion improves Phenomizer Recall@1 by 7.86 percentage points on Phenopacket Store and 20.18 points on RAMEDIS. When paired with DeepSeek-V4-Flash through an API, a fusion model trained only on the other LLMs improves Recall@1 from 0.1657 to 0.2176, a 5.19-point gain, without retraining. For 90.8% of correct fused diagnoses, the disease retains candidate-level ontology evidence that can be inspected. These results show that LLMs can strengthen an established diagnostic tool without discarding the structured evidence that makes it useful.

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.

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

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/.

Fracture detection and its clinical interpretability see notable improvements when deep vision models are integrated with agentic AI architectures. While deep learning models achieve high diagnostic performance, their black-box nature limits clinical adoption. We propose FRAC-MAS, an agentic AI system for automated, explainable, and safe bone fracture detection. The framework combines a stacked ensemble of four vision models with conformal prediction to produce statistically grounded differential diagnoses, while a multi-agent workflow performs independent verification, retrieves clinical guidelines, and generates patient-friendly reports. A pipeline-depth ablation study confirms that our multi-agent critic triages 86.6% of cases into a high-confidence auto-confirmed cohort while escalating uncertain cases, outperforming a single-agent baseline. Patient preference studies against Llama, MedGemma, and Gemini further demonstrate significantly more comprehensible clinical reports. These results suggest that integrating multi-agent critics with conformal guarantees enables safer radiology triage while preserving clinician oversight. More broadly, FRAC-MAS demonstrates how cooperative agentic architectures can serve as auditable, human-in-the-loop decision support systems for safety-critical healthcare. Our code is available at https://github.com/hardik1712/FRAC-MAS, and the website is available at https://frac-mas.vercel.app.

Diagnostic consultation is an online sequential decision-making process in which clinicians gather evidence through patient interaction until a diagnosis is sufficiently supported. Automating this process requires adaptive inquiry and interpretable decisions. Bayesian networks offer a natural foundation by updating diagnostic posteriors as evidence accumulates, but their use in open-ended consultation raises two challenges: linking diagnostic hypotheses to potential inquiries and translating evolving posteriors into consultation decisions. We introduce AutoDisym, an automated pipeline that integrates diagnostic knowledge with heterogeneous diagnosis-labeled clinical narratives to construct a Disorder--Symptom Bayesian Network (DSBN). Building on the DSBN, we propose ConsultMind, an uncertainty-aware framework that updates disorder posteriors after each response and uses posterior uncertainty to guide inquiry and diagnosis. We evaluate both methods across psychiatry, respiratory medicine, fever clinics, and three public datasets. The results show that AutoDisym can automatically construct high-quality DSBNs and that ConsultMind consistently improves diagnostic performance and explanation soundness. For example, AutoDisym achieves macro-averaged F1 scores of 81.37 for canonical symptoms and 72.19 for manifestations using GPT-5.6-Sol. ConsultMind improves Top-1 and Top-3 diagnostic accuracy by up to 22.15 and 37.89 percentage points, respectively. Physician evaluation further shows that ConsultMind improves the quality of ranking explanations, differential diagnoses, and diagnosis rationales across LLMs of different scales. This work offers a promising approach to automatic diagnostic consultation.

The application of Large Language Models (LLMs) to diagnostic decision-making has garnered growing interest. However, existing benchmarks largely focus on textual reasoning or isolated visual question-answering (VQA) tasks, lacking holistic integration of clinical narratives and medical imaging, and thus failing to assess the multimodal diagnostic synthesis capability central to expert clinical judgment. To bridge this gap, we introduce MedReaMM, a benchmark specifically designed to evaluate models' ability to synthesize heterogeneous clinical evidence consisting of detailed patient histories alongside multiple medical images into accurate differential diagnoses under a complete-information paradigm. Constructed from case reports sourced from top-tier medical journals and curated clinical case databases, MedReaMM comprises 625 expert-validated cases with an average of 2.79 medical images per case and a total of 1,042 standardized diagnoses annotated with ICD-11 codes. These cases predominantly represent rare, atypical, or multi-system presentations that demand expert-level evidence integration beyond routine pattern recognition. We evaluate 23 Large Multimodal Models (LMMs) and find that most achieve diagnostic accuracy scores below 50%, underscoring a substantial gap in multimodal diagnostic synthesis capability. Further analysis reveals that medical knowledge proficiency, medical image understanding, and evidence integration are all highly correlated with diagnostic performance.

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.

We present NV-Reason-CT, a generative vision--language model for chest and abdominal CT combining native 3D visual encoding with radiologist-guided reasoning. The model couples a native 3D vision transformer with a language model, passing all visual tokens and their explicit 3D coordinates into language decoding without further spatial token merging. This retains volumetric spatial information within the vision encoder and through the language model's positional encoding during joint processing with text. We train on a curated corpus of approximately 550,000 multimodal instruction examples from 70,111 unique CT image inputs, combining standardized reports, abnormality-focused and anatomy-specific questions, multi-turn interactions, and radiologist-authored reasoning from recorded and transcribed expert CT interpretations. Expert annotations provide direct supervision and guide additional report-grounded synthetic reasoning. End-to-end supervised fine-tuning (SFT) is followed by Group Relative Policy Optimization (GRPO), with verifiable rewards over chest and abdominal abnormality sets. The model supports abnormality classification, report generation, and interactive reasoning with reviewable observations, differential diagnoses, and uncertainty. Evaluation spans public CT benchmarks and a held-out NIH cohort. On CT-RATE, NV-Reason-CT achieves a macro-F1 of 0.614 and macro-AUROC of 0.871 without a task-specific classification head; generated reports achieve a report-derived macro-F1 of 0.592. In a preliminary study with expert radiologists, AI-assisted review received favorable confidence ratings and was associated with a 50% reduction in average reported interpretation and reporting time. We release the model and training code to support reproducible research on explainable AI for volumetric medical imaging.

Multimodal in-context learning (ICL) remains underexplored despite significant potential for domains such as medicine. Clinicians routinely encounter diverse, specialized tasks requiring adaptation from limited examples, such as drawing insights from a few relevant prior cases or considering a constrained set of differential diagnoses. While multimodal large language models (MLLMs) have shown advances in medical visual question answering (VQA), their ability to learn multimodal tasks from context is largely unknown. We introduce SMMILE, the first expert-driven multimodal ICL benchmark for medical tasks. Eleven medical experts curated problems, each including a multimodal query and multimodal in-context examples as task demonstrations. SMMILE encompasses 111 problems (517 question-image-answer triplets) covering 6 medical specialties and 13 imaging modalities. We further introduce SMMILE++, an augmented variant with 1038 permuted problems. A comprehensive evaluation of 15 MLLMs demonstrates that most models exhibit moderate to poor multimodal ICL ability in medical tasks. In open-ended evaluations, ICL contributes only 8% average improvement over zero-shot on SMMILE and 9.4% on SMMILE++. We observe a susceptibility for irrelevant in-context examples: even a single noisy or irrelevant example can degrade performance by up to 9.5%. Moreover, example ordering exhibits a recency bias, i.e., placing the most relevant example last can lead to substantial performance improvements by up to 71%. Our findings highlight critical limitations and biases in current MLLMs when learning multimodal medical tasks from context.

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

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.

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.

Controlling the COVID-19 pandemic largely hinges upon the existence of fast, safe, and highly-available diagnostic tools. Ultrasound, in contrast to CT or X-Ray, has many practical advantages and can serve as a globally-applicable first-line examination technique. We provide the largest publicly available lung ultrasound (US) dataset for COVID-19 consisting of 106 videos from three classes (COVID-19, bacterial pneumonia, and healthy controls); curated and approved by medical experts. On this dataset, we perform an in-depth study of the value of deep learning methods for differential diagnosis of COVID-19. We propose a frame-based convolutional neural network that correctly classifies COVID-19 US videos with a sensitivity of 0.98+-0.04 and a specificity of 0.91+-08 (frame-based sensitivity 0.93+-0.05, specificity 0.87+-0.07). We further employ class activation maps for the spatio-temporal localization of pulmonary biomarkers, which we subsequently validate for human-in-the-loop scenarios in a blindfolded study with medical experts. Aiming for scalability and robustness, we perform ablation studies comparing mobile-friendly, frame- and video-based architectures and show reliability of the best model by aleatoric and epistemic uncertainty estimates. We hope to pave the road for a community effort toward an accessible, efficient and interpretable screening method and we have started to work on a clinical validation of the proposed method. Data and code are publicly available.

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.

Pancreatic cancer is one of the leading causes of cancer-related death. Accurate detection, segmentation, and differential diagnosis of the full taxonomy of pancreatic lesions, i.e., normal, seven major types of lesions, and other lesions, is critical to aid the clinical decision-making of patient management and treatment. However, existing works focus on segmentation and classification for very specific lesion types (PDAC) or groups. Moreover, none of the previous work considers using lesion prevalence-related non-imaging patient information to assist the differential diagnosis. To this end, we develop a meta-information-aware dual-path transformer and exploit the feasibility of classification and segmentation of the full taxonomy of pancreatic lesions. Specifically, the proposed method consists of a CNN-based segmentation path (S-path) and a transformer-based classification path (C-path). The S-path focuses on initial feature extraction by semantic segmentation using a UNet-based network. The C-path utilizes both the extracted features and meta-information for patient-level classification based on stacks of dual-path transformer blocks that enhance the modeling of global contextual information. A large-scale multi-phase CT dataset of 3,096 patients with pathology-confirmed pancreatic lesion class labels, voxel-wise manual annotations of lesions from radiologists, and patient meta-information, was collected for training and evaluations. Our results show that our method can enable accurate classification and segmentation of the full taxonomy of pancreatic lesions, approaching the accuracy of the radiologist's report and significantly outperforming previous baselines. Results also show that adding the common meta-information, i.e., gender and age, can boost the model's performance, thus demonstrating the importance of meta-information for aiding pancreatic disease diagnosis.

Despite achieving high accuracy on medical benchmarks, LLMs exhibit the Einstellung Effect in clinical diagnosis--relying on statistical shortcuts rather than patient-specific evidence, causing misdiagnosis in atypical cases. Existing benchmarks fail to detect this critical failure mode. We introduce MedEinst, a counterfactual benchmark with 5,383 paired clinical cases across 49 diseases. Each pair contains a control case and a "trap" case with altered discriminative evidence that flips the diagnosis. We measure susceptibility via Bias Trap Rate--probability of misdiagnosing traps despite correctly diagnosing controls. Extensive Evaluation of 17 LLMs shows frontier models achieve high baseline accuracy but severe bias trap rates. Thus, we propose ECR-Agent, aligning LLM reasoning with Evidence-Based Medicine standard via two components: (1) Dynamic Causal Inference (DCI) performs structured reasoning through dual-pathway perception, dynamic causal graph reasoning across three levels (association, intervention, counterfactual), and evidence audit for final diagnosis; (2) Critic-Driven Graph and Memory Evolution (CGME) iteratively refines the system by storing validated reasoning paths in an exemplar base and consolidating disease-specific knowledge into evolving illness graphs. Source code is to be released.

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.

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.

Electrocardiogram (ECG) interpretation is essential for cardiovascular disease diagnosis, but current automated systems often struggle with transparency and generalization to unseen conditions. To address this, we introduce ZETA, a zero-shot multimodal framework designed for interpretable ECG diagnosis aligned with clinical workflows. ZETA uniquely compares ECG signals against structured positive and negative clinical observations, which are curated through an LLM-assisted, expert-validated process, thereby mimicking differential diagnosis. Our approach leverages a pre-trained multimodal model to align ECG and text embeddings without disease-specific fine-tuning. Empirical evaluations demonstrate ZETA's competitive zero-shot classification performance and, importantly, provide qualitative and quantitative evidence of enhanced interpretability, grounding predictions in specific, clinically relevant positive and negative diagnostic features. ZETA underscores the potential of aligning ECG analysis with structured clinical knowledge for building more transparent, generalizable, and trustworthy AI diagnostic systems. We will release the curated observation dataset and code to facilitate future research.

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.

Diagnosing a patient from video requires more than recognizing the sign: a vision-language model must turn what it sees into hypotheses, questions and tests. DynamicDx evaluates each step in 71 neurological consultations across 11 sign categories, linking authentic patient videos to confirmed diagnoses and fixed charts built from the same case reports, so that every model queries the same evidence. Across five such models, video improves accuracy by 9.9-22.5 percentage points over blind input, but neither recognition alone nor temporal order explains the gain: the cause is usually missing from the model's video-only differential diagnosis even when the sign is recognized, and shuffling the frames produces no reliable accuracy loss. Instead, a trajectory replay traces most of the gain to the investigation results the video prompts. Evidence acquisition is the bottleneck: supplying the decisive investigations raises accuracy to 73.2-93.0%. Two interventions act on it. A post-trained 4B video describer improves sign descriptions, especially from a short, densely sampled segment, and source-clean literature retrieval expands initial hypotheses; both bring the tests a model orders closer to those the treating clinicians documented and, through them, raise accuracy. For video-based diagnosis, seeing better helps when it leads to asking better.

Mental disorders are highly prevalent worldwide, but the shortage of psychiatrists and the inherent subjectivity of interview-based diagnosis create substantial barriers to timely and consistent mental-health assessment. Progress in AI-assisted psychiatric diagnosis is constrained by the absence of benchmarks that simultaneously provide realistic patient simulation, clinician-verified diagnostic labels, and support for dynamic multi-turn consultation. We present LingxiDiagBench, a large-scale multi-agent benchmark that evaluates LLMs on both static diagnostic inference and dynamic multi-turn psychiatric consultation in Chinese. At its core is LingxiDiag-16K, a dataset of 16,000 EMR-aligned synthetic consultation dialogues designed to reproduce real clinical demographic and diagnostic distributions across 12 ICD-10 psychiatric categories. Through extensive experiments across state-of-the-art LLMs, we establish key findings: (1) although LLMs achieve high accuracy on binary depression--anxiety classification (up to 92.3%), performance deteriorates substantially for depression--anxiety comorbidity recognition (43.0%) and 12-way differential diagnosis (28.5%); (2) dynamic consultation often underperforms static evaluation, indicating that ineffective information-gathering strategies significantly impair downstream diagnostic reasoning; (3) consultation quality assessed by LLM-as-a-Judge shows only moderate correlation with diagnostic accuracy, suggesting that well-structured questioning alone does not ensure correct diagnostic decisions. We release LingxiDiag-16K and the full evaluation framework to support reproducible research at https://github.com/Lingxi-mental-health/LingxiDiagBench.

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.

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 are transforming the support for clinical decision and their application in real scenarios. Yet, most benchmarks are conducted in English, and cross-lingual evaluation is needed to tackle the language gaps in global access. We introduce ClinicalBr, the first bilingual benchmark for clinical decision built from real Brazilian case reports. The corpus contains 2,892 cases drawn from 28 SciELO medical journals, spanning 18 specialties, and is structured as parallel Portuguese-English pairs. Each case supports four evaluation tasks: diagnosis retrieval, differential diagnosis, exam recommendation, and treatment planning. We evaluate four models: MedGemma-27B, Sabiá-4, DeepSeek-R1, and o3-mini, across both languages. The central finding is that the Portuguese-English performance gap is task-dependent, not general. In diagnosis retrieval, English yields a consistent advantage across all models, with +7.5-12.1 accuracy points. This advantage disappears in differential diagnosis, exam recommendation, and treatment planning, where confidence intervals cross zero for most models and Portuguese completeness scores are marginally higher. Brazilian-endemic conditions proved easier than the full corpus, not harder, indicating that tropical presentations are adequately represented in current pre-training. Exam recommendation was the hardest task across all models and both languages, with F1 scores below 0.10, well below the differential diagnosis ceiling of 0.20-0.27.

Alzheimer's Disease (AD) is the most common form of dementia and often difficult to diagnose due to the multifactorial etiology of dementia. Recent works on neuroimaging-based computer-aided diagnosis with deep neural networks (DNNs) showed that fusing structural magnetic resonance images (sMRI) and fluorodeoxyglucose positron emission tomography (FDG-PET) leads to improved accuracy in a study population of healthy controls and subjects with AD. However, this result conflicts with the established clinical knowledge that FDG-PET better captures AD-specific pathologies than sMRI. Therefore, we propose a framework for the systematic evaluation of multi-modal DNNs and critically re-evaluate single- and multi-modal DNNs based on FDG-PET and sMRI for binary healthy vs. AD, and three-way healthy/mild cognitive impairment/AD classification. Our experiments demonstrate that a single-modality network using FDG-PET performs better than MRI (accuracy 0.91 vs 0.87) and does not show improvement when combined. This conforms with the established clinical knowledge on AD biomarkers, but raises questions about the true benefit of multi-modal DNNs. We argue that future work on multi-modal fusion should systematically assess the contribution of individual modalities following our proposed evaluation framework. Finally, we encourage the community to go beyond healthy vs. AD classification and focus on differential diagnosis of dementia, where fusing multi-modal image information conforms with a clinical need.

Background: Health datasets from clinical sources do not reflect the breadth and diversity of disease in the real world, impacting research, medical education, and artificial intelligence (AI) tool development. Dermatology is a suitable area to develop and test a new and scalable method to create representative health datasets. Methods: We used Google Search advertisements to invite contributions to an open access dataset of images of dermatology conditions, demographic and symptom information. With informed contributor consent, we describe and release this dataset containing 10,408 images from 5,033 contributions from internet users in the United States over 8 months starting March 2023. The dataset includes dermatologist condition labels as well as estimated Fitzpatrick Skin Type (eFST) and Monk Skin Tone (eMST) labels for the images. Results: We received a median of 22 submissions/day (IQR 14-30). Female (66.72%) and younger (52% < age 40) contributors had a higher representation in the dataset compared to the US population, and 32.6% of contributors reported a non-White racial or ethnic identity. Over 97.5% of contributions were genuine images of skin conditions. Dermatologist confidence in assigning a differential diagnosis increased with the number of available variables, and showed a weaker correlation with image sharpness (Spearman's P values <0.001 and 0.01 respectively). Most contributions were short-duration (54% with onset < 7 days ago ) and 89% were allergic, infectious, or inflammatory conditions. eFST and eMST distributions reflected the geographical origin of the dataset. The dataset is available at github.com/google-research-datasets/scin . Conclusion: Search ads are effective at crowdsourcing images of health conditions. The SCIN dataset bridges important gaps in the availability of representative images of common skin conditions.

Experts in various fields routinely perform methodical writing tasks to plan, organize, and report their work. From a clinician writing a differential diagnosis for a patient, to a teacher writing a lesson plan for students, these tasks are pervasive, requiring to methodically generate structured long-form output for a given input. We develop a typology of methodical tasks structured in the form of a task objective, procedure, input, and output, and introduce DoLoMiTes, a novel benchmark with specifications for 519 such tasks elicited from hundreds of experts from across 25 fields. Our benchmark further contains specific instantiations of methodical tasks with concrete input and output examples (1,857 in total) which we obtain by collecting expert revisions of up to 10 model-generated examples of each task. We use these examples to evaluate contemporary language models highlighting that automating methodical tasks is a challenging long-form generation problem, as it requires performing complex inferences, while drawing upon the given context as well as domain knowledge.

Most existing LLM diagnoses are evaluated on static, single-turn settings where complete patient information is provided upfront, an oversimplification of real clinical practice. We study active diagnosis: the real-life clinical process of starting from initial observation, ordering tests, interpreting results, and updating a differential diagnosis across multiple turns. Through systematic analysis, we identify three recurring failure modes in current LLMs: ungrounded test ordering, unreliable diagnostic update, and degraded multi-turn coherence. Together, these failures reveal a core deficit: existing medical training data teaches models to reason from complete information but not to act under evolving, partial evidence. To address this gap, we introduce MedAction, a tree-structured distillation pipeline that synthesizes diverse and high-quality multi-turn diagnostic trajectories via LLM-environment interaction. We propose two knowledge-graph-grounded metrics to filter trajectory quality: Disease Trajectory Consistency (DTC), which tracks whether the model's hypothesis converges toward the correct diagnosis, and Reasoning-Action Consistency (RAC), which verifies that belief updates are driven by gathered evidence. Using this pipeline, we construct MedAction-32K, a dataset of 32,681 trajectories from 2,896 PMC cases. Fine-tuning an 8B model on MedAction-32K achieves state-of-the-art performance among open-source models on both MedR-Bench and our curated MedAction-300-Hard benchmark, pushing the edge for open-source medical LLMs.

MRI is an indispensable clinical tool, offering a rich variety of tissue contrasts to support broad diagnostic and research applications. Clinical exams routinely acquire multiple structural sequences that provide complementary information for differential diagnosis, while research protocols often incorporate advanced functional, diffusion, spectroscopic, and relaxometry sequences to capture multidimensional insights into tissue structure and composition. However, these capabilities come at the cost of prolonged scan times, which reduce patient throughput, increase susceptibility to motion artifacts, and may require trade-offs in image quality or diagnostic scope. Over the last two decades, advances in image reconstruction algorithms--alongside improvements in hardware and pulse sequence design--have made it possible to accelerate acquisitions while preserving diagnostic quality. Central to this progress is the ability to incorporate prior information to regularize the solutions to the reconstruction problem. In this tutorial, we overview the basics of MRI reconstruction and highlight state-of-the-art approaches, beginning with classical methods that rely on explicit hand-crafted priors, and then turning to deep learning methods that leverage a combination of learned and crafted priors to further push the performance envelope. We also explore the translational aspects and eventual clinical implications of these methods. We conclude by discussing future directions to address remaining challenges in MRI reconstruction. The tutorial is accompanied by a Python toolbox (https://github.com/tutorial-MRI-recon/tutorial) to demonstrate select methods discussed in the article.

Language models excel at diagnostic assessments on currated medical case-studies and vignettes, performing on par with, or better than, clinical professionals. However, existing studies focus on complex scenarios with rich context making it difficult to draw conclusions about how these systems perform for patients reporting symptoms in everyday life. We deployed SymptomAI, a set of conversational AI agents for end-to-end patient interviewing and differential diagnosis (DDx), via the Fitbit app in a study that randomized participants (N=13,917) to interact with five AI agents. This corpus captures diverse communication and a realistic distribution of illnesses from a real world population. A subset of 1,228 participants reported a clinician-provided diagnosis, and 517 of these were further evaluated by a panel of clinicians during over 250 hours of annotation. SymptomAI DDx were significantly more accurate (OR = 2.47, p < 0.001) than those from independent clinicians given the same dialogue in a blinded randomized comparison. Moreover, agentic strategies which conduct a dedicated symptom interview that elicit additional symptom information before providing a diagnosis, perform substantially better than baseline, user-guided conversations (p < 0.001). An auxiliary analysis on 1,509 conversations from a general US population panel validated that these results generalize beyond wearable device users. We used SymptomAI diagnoses as labels for all 13,917 participants to analyze over 500,000 days of wearable metrics across nearly 400 unique conditions. We identified strong associations between acute infections and physiological shifts (e.g., OR > 7 for influenza). While limited by self-reported ground truth, these results demonstrate the benefits of a dedicated and complete symptom interview compared to a user-guided symptom discussion, which is the default of most consumer LLMs.

The goal of automated summarization techniques (Paice, 1990; Kupiec et al, 1995) is to condense text by focusing on the most critical information. Generative large language models (LLMs) have shown to be robust summarizers, yet traditional metrics struggle to capture resulting performance (Goyal et al, 2022) in more powerful LLMs. In safety-critical domains such as medicine, more rigorous evaluation is required, especially given the potential for LLMs to omit important information in the resulting summary. We propose MED-OMIT, a new omission benchmark for medical summarization. Given a doctor-patient conversation and a generated summary, MED-OMIT categorizes the chat into a set of facts and identifies which are omitted from the summary. We further propose to determine fact importance by simulating the impact of each fact on a downstream clinical task: differential diagnosis (DDx) generation. MED-OMIT leverages LLM prompt-based approaches which categorize the importance of facts and cluster them as supporting or negating evidence to the diagnosis. We evaluate MED-OMIT on a publicly-released dataset of patient-doctor conversations and find that MED-OMIT captures omissions better than alternative metrics.

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

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.

Recent advancements in large language models (LLMs) have shown promise in medical applications such as disease diagnosis and treatment planning. However, most existing medical LLMs struggle with the advanced reasoning required for complex clinical scenarios, such as differential diagnosis or personalized treatment suggestions. We proposed FineMedLM-o1, which leverages high-quality synthetic medical data and long-form reasoning data for Supervised Fine-Tuning (SFT) and Direct Preference Optimization (DPO), enabling advanced dialogue and deep reasoning capabilities. Additionally, we introduced Test-Time Training (TTT) in the medical domain for the first time, facilitating domain adaptation and ensuring reliable, accurate reasoning. Experimental results demonstrate that FineMedLM-o1 achieves a 23% average performance improvement over prior models on key medical benchmarks. Furthermore, the introduction of TTT provides an additional 14% performance boost, highlighting its effectiveness in enhancing medical reasoning capabilities. To support this process, we also proposed a novel method for synthesizing medical dialogue. Compared to other open-source datasets, our dataset stands out as superior in both quality and complexity. The project and data will be released on GitHub.

Diagnosing and treating skin diseases require advanced visual skills across domains and the ability to synthesize information from multiple imaging modalities. While current deep learning models excel at specific tasks like skin cancer diagnosis from dermoscopic images, they struggle to meet the complex, multimodal requirements of clinical practice. Here, we introduce PanDerm, a multimodal dermatology foundation model pretrained through self-supervised learning on over 2 million real-world skin disease images from 11 clinical institutions across 4 imaging modalities. We evaluated PanDerm on 28 diverse benchmarks, including skin cancer screening, risk stratification, differential diagnosis of common and rare skin conditions, lesion segmentation, longitudinal monitoring, and metastasis prediction and prognosis. PanDerm achieved state-of-the-art performance across all evaluated tasks, often outperforming existing models when using only 10% of labeled data. We conducted three reader studies to assess PanDerm's potential clinical utility. PanDerm outperformed clinicians by 10.2% in early-stage melanoma detection through longitudinal analysis, improved clinicians' skin cancer diagnostic accuracy by 11% on dermoscopy images, and enhanced non-dermatologist healthcare providers' differential diagnosis by 16.5% across 128 skin conditions on clinical photographs. These results demonstrate PanDerm's potential to improve patient care across diverse clinical scenarios and serve as a model for developing multimodal foundation models in other medical specialties, potentially accelerating the integration of AI support in healthcare. The code can be found at https://github.com/SiyuanYan1/PanDerm.

We present ReXVQA, the largest and most comprehensive benchmark for visual question answering (VQA) in chest radiology, comprising approximately 696,000 questions paired with 160,000 chest X-rays studies across training, validation, and test sets. Unlike prior efforts that rely heavily on template based queries, ReXVQA introduces a diverse and clinically authentic task suite reflecting five core radiological reasoning skills: presence assessment, location analysis, negation detection, differential diagnosis, and geometric reasoning. We evaluate eight state-of-the-art multimodal large language models, including MedGemma-4B-it, Qwen2.5-VL, Janus-Pro-7B, and Eagle2-9B. The best-performing model (MedGemma) achieves 83.24% overall accuracy. To bridge the gap between AI performance and clinical expertise, we conducted a comprehensive human reader study involving 3 radiology residents on 200 randomly sampled cases. Our evaluation demonstrates that MedGemma achieved superior performance (83.84% accuracy) compared to human readers (best radiology resident: 77.27%), representing a significant milestone where AI performance exceeds expert human evaluation on chest X-ray interpretation. The reader study reveals distinct performance patterns between AI models and human experts, with strong inter-reader agreement among radiologists while showing more variable agreement patterns between human readers and AI models. ReXVQA establishes a new standard for evaluating generalist radiological AI systems, offering public leaderboards, fine-grained evaluation splits, structured explanations, and category-level breakdowns. This benchmark lays the foundation for next-generation AI systems capable of mimicking expert-level clinical reasoning beyond narrow pathology classification. Our dataset will be open-sourced at https://huggingface.co/datasets/rajpurkarlab/ReXVQA

Leading vision-language models (VLMs) are trained on general Internet content, overlooking scientific journals' rich, domain-specific knowledge. Training on specialty-specific literature could yield high-performance, task-specific tools, enabling generative AI to match generalist models in specialty publishing, educational, and clinical tasks. We created NeuroPubs, a multimodal dataset of 23,000 Neurosurgery Publications articles (134M words, 78K image-caption pairs). Using NeuroPubs, VLMs generated publication-ready graphical abstracts (70% of 100 abstracts) and board-style questions indistinguishable from human-written ones (54% of 89,587 questions). We used these questions to train CNS-Obsidian, a 34B-parameter VLM. In a blinded, randomized controlled trial, our model demonstrated non-inferiority to then state-of-the-art GPT-4o in neurosurgical differential diagnosis (clinical utility, 40.62% upvotes vs. 57.89%, p=0.1150; accuracy, 59.38% vs. 65.79%, p=0.3797). Our pilot study demonstrates how training generative AI models on specialty-specific journal content - without large-scale internet data - results in high-performance academic and clinical tools, enabling domain-tailored AI across diverse fields.

Large language models (LLMs) have demonstrated strong performance and rapid progress in a wide range of medical reasoning tasks. However, their sequential autoregressive decoding forces inherently parallel clinical reasoning, such as differential diagnosis, into a single linear reasoning path, limiting both efficiency and reliability for complex medical problems. To address this, we propose MedVerse, a reasoning framework for complex medical inference that reformulates medical reasoning as a parallelizable directed acyclic graph (DAG) process based on Petri net theory. The framework adopts a full-stack design across data, model architecture, and system execution. For data creation, we introduce the MedVerse Curator, an automated pipeline that synthesizes knowledge-grounded medical reasoning paths and transforms them into Petri net-structured representations. At the architectural level, we propose a topology-aware attention mechanism with adaptive position indices that supports parallel reasoning while preserving logical consistency. Systematically, we develop a customized inference engine that supports parallel execution without additional overhead. Empirical evaluations show that MedVerse improves strong general-purpose LLMs by up to 8.9%. Compared to specialized medical LLMs, MedVerse achieves comparable performance while delivering a 1.3x reduction in inference latency and a 1.7x increase in generation throughput, enabled by its parallel decoding capability.

Large language models (LLMs) are increasingly explored for clinical decision support, yet most evaluations are conducted in English, leaving their reliability in other languages uncertain. Here we evaluate the impact of prompting language on diagnostic reasoning and final diagnosis accuracy by comparing English and French performance across five LLMs (o3, DeepSeek-R1, GPT-4-Turbo, Llama-3.1-405B-Instruct, and BioMistral-7B). A total of 180 clinical vignettes covering 16 medical specialties were assessed by two physicians using an 18-point scale evaluating both diagnosis accuracy and reasoning quality. Four of the five models performed better in English (mean difference 0.37-0.91, adjusted p < 0.05), with the gap spanning multiple aspects of reasoning, including differential diagnosis, logical structure, and internal validity. o3 was the only model showing no overall language effect. These findings demonstrate that prompting language remains a critical determinant of LLM clinical performance, with implications for equitable linguistico-cultural deployment worldwide.

Listening to heart and lung sounds - auscultation - is one of the first and most fundamental steps in a clinical examination. Despite being fast and non-invasive, it demands years of experience to interpret subtle audio cues. Recent deep learning methods have made progress in automating cardiopulmonary sound analysis, yet most are restricted to simple classification and offer little clinical interpretability or decision support. We present StethoLM, the first audio-language model specialized for cardiopulmonary auscultation, capable of performing instruction-driven clinical tasks across the full spectrum of auscultation analysis. StethoLM integrates audio encoding with a medical language model backbone and is trained on StethoBench, a comprehensive benchmark comprising 77,027 instruction-response pairs synthesized from 16,125 labeled cardiopulmonary recordings spanning seven clinical task categories: binary classification, detection, reporting, reasoning, differential diagnosis, comparison, and location-based analysis. Through multi-stage training that combines supervised fine-tuning and direct preference optimization, StethoLM achieves substantial gains in performance and robustness on out-of-distribution data. Our work establishes a foundation for instruction-following AI systems in clinical auscultation.

As large language models (LLMs) become primary sources of health information for millions, their accuracy in women's health remains critically unexamined. We introduce the Women's Health Benchmark (WHB), the first benchmark evaluating LLM performance specifically in women's health. Our benchmark comprises 96 rigorously validated model stumps covering five medical specialties (obstetrics and gynecology, emergency medicine, primary care, oncology, and neurology), three query types (patient query, clinician query, and evidence/policy query), and eight error types (dosage/medication errors, missing critical information, outdated guidelines/treatment recommendations, incorrect treatment advice, incorrect factual information, missing/incorrect differential diagnosis, missed urgency, and inappropriate recommendations). We evaluated 13 state-of-the-art LLMs and revealed alarming gaps: current models show approximately 60\% failure rates on the women's health benchmark, with performance varying dramatically across specialties and error types. Notably, models universally struggle with "missed urgency" indicators, while newer models like GPT-5 show significant improvements in avoiding inappropriate recommendations. Our findings underscore that AI chatbots are not yet fully able of providing reliable advice in women's health.

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.

Developing a generalist radiology diagnosis system can greatly enhance clinical diagnostics. In this paper, we introduce RadDiag, a foundational model supporting 2D and 3D inputs across various modalities and anatomies, using a transformer-based fusion module for comprehensive disease diagnosis. Due to patient privacy concerns and the lack of large-scale radiology diagnosis datasets, we utilize high-quality, clinician-reviewed radiological images available online with diagnosis labels. Our dataset, RP3D-DiagDS, contains 40,936 cases with 195,010 scans covering 5,568 disorders (930 unique ICD-10-CM codes). Experimentally, our RadDiag achieves 95.14% AUC on internal evaluation with the knowledge-enhancement strategy. Additionally, RadDiag can be zero-shot applied or fine-tuned to external diagnosis datasets sourced from various hospitals, demonstrating state-of-the-art results. In conclusion, we show that publicly shared medical data on the Internet is a tremendous and valuable resource that can potentially support building a generalist AI for healthcare.

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

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

People with diabetes are at risk of developing an eye disease called diabetic retinopathy (DR). This disease occurs when high blood glucose levels cause damage to blood vessels in the retina. Computer-aided DR diagnosis is a promising tool for early detection of DR and severity grading, due to the great success of deep learning. However, most current DR diagnosis systems do not achieve satisfactory performance or interpretability for ophthalmologists, due to the lack of training data with consistent and fine-grained annotations. To address this problem, we construct a large fine-grained annotated DR dataset containing 2,842 images (FGADR). This dataset has 1,842 images with pixel-level DR-related lesion annotations, and 1,000 images with image-level labels graded by six board-certified ophthalmologists with intra-rater consistency. The proposed dataset will enable extensive studies on DR diagnosis. We set up three benchmark tasks for evaluation: 1. DR lesion segmentation; 2. DR grading by joint classification and segmentation; 3. Transfer learning for ocular multi-disease identification. Moreover, a novel inductive transfer learning method is introduced for the third task. Extensive experiments using different state-of-the-art methods are conducted on our FGADR dataset, which can serve as baselines for future research.

Medical coding translates clinical documentation into standardized codes for billing, research, and public health, but manual coding is time-consuming and error-prone. Existing automation efforts rely on small datasets that poorly represent real-world patient heterogeneity. We trained a language model on 5.8 million electronic health records from 1.8 million patients across nearly all specialties in Eastern Denmark (2006--2016) to predict ICD-10 codes from clinical notes, medications, and laboratory results. Evaluated on 270,000 held-out patients, the model achieved a micro F1 of 71.8% and a top-10 recall of 95.5%. Performance varied by specialty (F1: 53--91%), with higher scores in specialties with well-defined diagnostic criteria. Codes appearing predominantly as secondary diagnoses had markedly lower F1 scores. For three such codes (suicide-related behaviors, weight disorders, and hypertension), the model identified thousands of uncoded cases, of which 76-86% were confirmed valid upon manual review, suggesting systematic under-coding rather than model error. These findings suggest under-coding of secondary diagnoses in Eastern Denmark during this period, with potential implications for epidemiological research, public health surveillance, and understanding of multimorbidity. Similar time constraints and reimbursement structures in other healthcare systems suggest this may not be isolated to this dataset. The model can automate coding for approximately 50% of cases and provide accurate suggestions for most others, and may offer a practical solution to help capture missed secondary conditions.

Large Language Models (LLMs) are increasingly adopted across domains such as education, healthcare, and finance. In healthcare, LLMs support tasks including disease diagnosis, abnormality classification, and clinical decision-making. Among these, multi-abnormality classification of radiology reports is critical for clinical workflow automation and biomedical research. Leveraging strong natural language processing capabilities, LLMs enable efficient processing of unstructured medical text and reduce the administrative burden of manual report analysis. To improve performance, LLMs are often fine-tuned on private, institution-specific datasets such as radiology reports. However, this raises significant privacy concerns: LLMs may memorize training data and become vulnerable to data extraction attacks, while sharing fine-tuned models risks exposing sensitive patient information. Despite growing interest in LLMs for medical text classification, privacy-preserving fine-tuning for multi-abnormality classification remains underexplored. To address this gap, we propose a differentially private (DP) fine-tuning framework for multi-abnormality classification from free-text radiology reports. Our approach integrates differential privacy with Low-Rank Adaptation (LoRA) to efficiently fine-tune LLMs on sensitive clinical data while mitigating leakage risks. We further employ labels generated by a larger LLM to train smaller models, enabling efficient inference under strong privacy guarantees. Experiments on MIMIC-CXR and CT-RATE demonstrate the effectiveness of our DP-LoRA framework across varying privacy regimes. On MIMIC-CXR, our method achieves weighted F1-scores up to 0.89 under moderate privacy budgets, approaching non-private LoRA (0.90) and full fine-tuning (0.96), confirming that strong privacy can be achieved with only modest performance trade-offs.

AI agents are becoming increasingly capable of generating scientific code, but generating code is not the same as improving the algorithms behind it. For numerical solvers, execution feedback can expose poor performance, but rarely reveals its underlying cause and how to address it. We introduce Auto-Diagnosis and Skill Discovery (ADSD), a framework that links numerical diagnosis to reusable solver self-improvement. ADSD follows a diagnosis-first paradigm that first explains why a solver performs poorly, then uses this diagnosis to guide the discovery of appropriate numerical methods. The resulting knowledge is packaged into reusable solver skills, turning solver improvement from trial-and-error editing into a structured process of diagnosis, discovery, and implementation. Across four challenging numerical domains--power flow equation, AC optimal power flow control, stiff ordinary differential equations, and heterogeneous diffusion PDEs--ADSD consistently improves solver accuracy, robustness, and efficiency. On GOC-500 power flow, for example, ADSD reduces mean solver error by nearly 71times, with improvements further transferring to unseen grid topologies and operating regimes.

Speech pathology has impacts on communication abilities and quality of life. While deep learning-based models have shown potential in diagnosing these disorders, the use of sensitive data raises critical privacy concerns. Although differential privacy (DP) has been explored in the medical imaging domain, its application in pathological speech analysis remains largely unexplored despite the equally critical privacy concerns. To the best of our knowledge, this study is the first to investigate DP's impact on pathological speech data, focusing on the trade-offs between privacy, diagnostic accuracy, and fairness. Using a large, real-world dataset of 200 hours of recordings from 2,839 German-speaking participants, we observed a maximum accuracy reduction of 3.85% when training with DP with high privacy levels. To highlight real-world privacy risks, we demonstrated the vulnerability of non-private models to gradient inversion attacks, reconstructing identifiable speech samples and showcasing DP's effectiveness in mitigating these risks. To explore the potential generalizability across languages and disorders, we validated our approach on a dataset of Spanish-speaking Parkinson's disease patients, leveraging pretrained models from healthy English-speaking datasets, and demonstrated that careful pretraining on large-scale task-specific datasets can maintain favorable accuracy under DP constraints. A comprehensive fairness analysis revealed minimal gender bias at reasonable privacy levels but underscored the need for addressing age-related disparities. Our results establish that DP can balance privacy and utility in speech disorder detection, while highlighting unique challenges in privacy-fairness trade-offs for speech data. This provides a foundation for refining DP methodologies and improving fairness across diverse patient groups in real-world deployments.

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.

The DSM-1 was published in 1952, contains 128 diagnostic categories, described in 132 pages. The DSM-5 appeared in 2013, contains 541 diagnostic categories, described in 947 pages. The field of psychology is characterised by a steady proliferation of diagnostic models and subcategories, that seems to be inspired by the principle of "divide and inflate". This approach is in contrast with experimental evidence, which suggests on one hand that traumas of various kind are often present in the anamnesis of patients and, on the other, that the gene variants implicated are shared across a wide range of diagnoses. In this work I propose a holistic approach, built with tools borrowed from the field of Artificial Intelligence. My model is based on two pillars. The first one is trauma, which represents the attack to the mind, is psychological in nature and has its origin in the environment. The second pillar is dissociation, which represents the mind defence in both physiological and pathological conditions, and incorporates all other defence mechanisms. Damages to dissociation can be considered as another category of attacks, that are neurobiological in nature and can be of genetic or environmental origin. They include, among other factors, synaptic over-pruning, abuse of drugs and inflammation. These factors concur to weaken the defence, represented by the neural networks that implement the dissociation mechanism in the brain. The model is subsequently used to interpret five mental conditions: PTSD, complex PTSD, dissociative identity disorder, schizophrenia and bipolar disorder. Ideally, this is a first step towards building a model that aims to explain a wider range of psychopathological affections with a single theoretical framework. The last part is dedicated to sketching a new psychotherapy for psychological trauma.

Rare diseases affect hundreds of millions worldwide, yet diagnosis often spans years. Convectional pipelines decouple noisy evidence extraction from downstream inferential diagnosis, and general/medical large language models (LLMs) face scarce real world electronic health records (EHRs), stale domain knowledge, and hallucinations. We assemble a large, domain specialized clinical corpus and a clinician validated reasoning set, and develop RareSeek R1 via staged instruction tuning, chain of thought learning, and graph grounded retrieval. Across multicenter EHR narratives and public benchmarks, RareSeek R1 attains state of the art accuracy, robust generalization, and stability under noisy or overlapping phenotypes. Augmented retrieval yields the largest gains when narratives pair with prioritized variants by resolving ambiguity and aligning candidates to mechanisms. Human studies show performance on par with experienced physicians and consistent gains in assistive use. Notably, transparent reasoning highlights decisive non phenotypic evidence (median 23.1%, such as imaging, interventions, functional tests) underpinning many correct diagnoses. This work advances a narrative first, knowledge integrated reasoning paradigm that shortens the diagnostic odyssey and enables auditable, clinically translatable decision support.

We investigate whether large language models produce different medical triage recommendations for identical neurological symptoms when only the patient's stated gender and age vary. Using three model families--Gemini 3.5 Flash, Claude Sonnet 4.6, and GPT-5.4-mini--we present a standardized symptom profile (persistent headache, blurred vision, morning nausea, visual disturbances) across seven demographic conditions: three age groups (25, 38, 65) x two genders (male, female), plus a gender-unspecified baseline (n = 30 per condition per model, 630 total trials). We find a stark, systemic gender-dependent triage disparity: young women receive significantly lower emergency room (ER) referral rates than age-matched men (Gemini: 0% vs. 23.3%; Claude: 6.7% vs. 96.7%; GPT: 6.7% vs. 66.7%, all p < 0.001). The disparity disappears at age 65 for all models. The primary mechanism is diagnostic substitution: the models anchor on a gender-associated diagnosis, preferentially classifying young women with Idiopathic Intracranial Hypertension (IIH)--a condition epidemiologically linked to women of childbearing age--while diagnosing men with generic increased intracranial pressure with space-occupying lesions in the differential. This diagnostic closure routes female patients to lower-urgency care (outpatient doctor appointments) despite comparable severity ratings (7-9/10). Our findings demonstrate that clinical LLMs replicate documented human clinical biases by using epidemiological priors to suppress triage urgency, suggesting that AI triage engines must decouple urgency assessment from probabilistic diagnostic priors. We release all code, prompts, and raw results.

When asked to describe a medical image that was never attached, frontier vision-language models do not abstain: they confabulate a diagnosis. We show that this confabulation is not random. It is structured by who the patient is said to be. Across chest X-ray, brain MRI, and dermatology, Claude Opus-4.7, GPT-5.4, and Gemini-3.1-Pro are each queried with only a demographic descriptor and no image, and changing the descriptor systematically shifts the diagnosis returned. Claude concentrates sharply: a 65-year-old white man asking about a skin mole receives Melanoma in nearly every response, and a 32-year-old Black woman asking about her chest X-ray receives a Sarcoidosis diagnosis whose reasoning reads "suspected, based on demographics and classic pattern.'' GPT-5.4's effect is broader, fabricating across every demographic cell we test, most conspicuously naming Sarcoidosis for young Black patients on chest X-ray. Two structural findings sharpen the problem. A hedged regime appears in which the prose acknowledges the missing image while the structured diagnosis field nevertheless names a disease, a dissociation invisible to prose-only audits. And Claude's dermatology effect collapses entirely when 'skin mole' is swapped for 'skin lesion' while GPT-5.4's is preserved, indicating that mirage is a family of distinct failure modes rather than a single phenomenon. Trustworthy VLM deployment in clinical pipelines requires auditing the structured output channel directly, and probe-word sensitivity should be treated as a first-class evaluation dimension

Differential privacy (DP) is a key technique for protecting sensitive patient data in medical deep learning (DL). As clinical models grow more data-dependent, balancing privacy with utility and fairness has become a critical challenge. This scoping review synthesizes recent developments in applying DP to medical DL, with a particular focus on DP-SGD and alternative mechanisms across centralized and federated settings. Using a structured search strategy, we identified 74 studies published up to March 2025. Our analysis spans diverse data modalities, training setups, and downstream tasks, and highlights the tradeoffs between privacy guarantees, model accuracy, and subgroup fairness. We find that while DP-especially at strong privacy budgets-can preserve performance in well-structured imaging tasks, severe degradation often occurs under strict privacy, particularly in underrepresented or complex modalities. Furthermore, privacy-induced performance gaps disproportionately affect demographic subgroups, with fairness impacts varying by data type and task. A small subset of studies explicitly addresses these tradeoffs through subgroup analysis or fairness metrics, but most omit them entirely. Beyond DP-SGD, emerging approaches leverage alternative mechanisms, generative models, and hybrid federated designs, though reporting remains inconsistent. We conclude by outlining key gaps in fairness auditing, standardization, and evaluation protocols, offering guidance for future work toward equitable and clinically robust privacy-preserving DL systems in medicine.

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.

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

For the early identification, diagnosis, and treatment of mental health illnesses, the integration of deep learning (DL) and machine learning (ML) has started playing a significant role. By evaluating complex data from imaging, genetics, and behavioral assessments, these technologies have the potential to significantly improve clinical outcomes. However, they also present unique challenges related to data integration and ethical issues. This survey reviews the development of ML and DL methods for the early diagnosis and treatment of mental health issues. It examines a range of applications, with a particular emphasis on behavioral assessments, genetic and biomarker analysis, and medical imaging for diagnosing diseases like depression, bipolar disorder, and schizophrenia. Predictive modeling for illness progression is further discussed, focusing on the role of risk prediction models and longitudinal studies. Key findings highlight how ML and DL can improve diagnostic accuracy and treatment outcomes while addressing methodological inconsistencies, data integration challenges, and ethical concerns. The study emphasizes the importance of building real-time monitoring systems for individualized treatment, enhancing data fusion techniques, and fostering interdisciplinary collaboration. Future research should focus on overcoming these obstacles to ensure the valuable and ethical application of ML and DL in mental health services.

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.

Rare diseases collectively affect an estimated 3.5% to 5.9% of the population, yet more than 70% of patients are misdiagnosed and many endure years of evaluation before a diagnosis is reached, because early presentations are nonspecific and relevant expertise is scarce and unevenly distributed. Artificial intelligence could provide support, but existing systems address isolated stages of care, overwhelmingly diagnosis. They typically depend on the results of downstream investigations, and they treat the variability between models as noise to be eliminated. Here we present RareLens, a system that supports clinical decision-making across the entire rare disease trajectory by exploiting this variability. When heterogeneous large language models evaluate the same case, they generate divergent but complementary reasoning, which RareLens aligns and calibrates into a single convergent, actionable decision at each stage. Four coordinated modules perform primary-visit risk screening, diagnosis, treatment planning and prognosis. Developed and evaluated on RareBench, a real-world dataset of 157,525 cases spanning all 33 Orphanet categories and more than 7,000 conditions, RareLens outperformed every frontier model tested, including GPT-5, DeepSeek-R1, Claude-3.7-Sonnet and Gemini-2.5-Pro, at each stage. It achieved an area under the curve of 0.917 for screening and top-1 accuracies of 65.5% and 89.8% for diagnosis and treatment. In an external study spanning 1,287 cases and 23 physicians, autonomous RareLens and physicians assisted by RareLens both substantially outperformed unaided physicians. These findings indicate that aligning divergent model reasoning, rather than scaling a single model, offers a generalizable strategy for high-uncertainty clinical decision-making.

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

Mental health disorders are one of the most serious diseases in the world. Most people with such a disease lack access to adequate care, which highlights the importance of training models for the diagnosis and treatment of mental health disorders. However, in the mental health domain, privacy concerns limit the accessibility of personalized treatment data, making it challenging to build powerful models. In this paper, we introduce MentalArena, a self-play framework to train language models by generating domain-specific personalized data, where we obtain a better model capable of making a personalized diagnosis and treatment (as a therapist) and providing information (as a patient). To accurately model human-like mental health patients, we devise Symptom Encoder, which simulates a real patient from both cognition and behavior perspectives. To address intent bias during patient-therapist interactions, we propose Symptom Decoder to compare diagnosed symptoms with encoded symptoms, and dynamically manage the dialogue between patient and therapist according to the identified deviations. We evaluated MentalArena against 6 benchmarks, including biomedicalQA and mental health tasks, compared to 6 advanced models. Our models, fine-tuned on both GPT-3.5 and Llama-3-8b, significantly outperform their counterparts, including GPT-4o. We hope that our work can inspire future research on personalized care. Code is available in https://github.com/Scarelette/MentalArena/tree/main

Knowledge Graph (KG) plays a crucial role in Medical Report Generation (MRG) because it reveals the relations among diseases and thus can be utilized to guide the generation process. However, constructing a comprehensive KG is labor-intensive and its applications on the MRG process are under-explored. In this study, we establish a complete KG on chest X-ray imaging that includes 137 types of diseases and abnormalities. Based on this KG, we find that the current MRG data sets exhibit a long-tailed problem in disease distribution. To mitigate this problem, we introduce a novel augmentation strategy that enhances the representation of disease types in the tail-end of the distribution. We further design a two-stage MRG approach, where a classifier is first trained to detect whether the input images exhibit any abnormalities. The classified images are then independently fed into two transformer-based generators, namely, ``disease-specific generator" and ``disease-free generator" to generate the corresponding reports. To enhance the clinical evaluation of whether the generated reports correctly describe the diseases appearing in the input image, we propose diverse sensitivity (DS), a new metric that checks whether generated diseases match ground truth and measures the diversity of all generated diseases. Results show that the proposed two-stage generation framework and augmentation strategies improve DS by a considerable margin, indicating a notable reduction in the long-tailed problem associated with under-represented diseases.

Despite the impressive capabilities of Large Language Models (LLMs) in general medical domains, questions remain about their performance in diagnosing rare diseases. To answer this question, we aim to assess the diagnostic performance of LLMs in rare diseases, and explore methods to enhance their effectiveness in this area. In this work, we introduce a rare disease question-answering (ReDis-QA) dataset to evaluate the performance of LLMs in diagnosing rare diseases. Specifically, we collected 1360 high-quality question-answer pairs within the ReDis-QA dataset, covering 205 rare diseases. Additionally, we annotated meta-data for each question, facilitating the extraction of subsets specific to any given disease and its property. Based on the ReDis-QA dataset, we benchmarked several open-source LLMs, revealing that diagnosing rare diseases remains a significant challenge for these models. To facilitate retrieval augmentation generation for rare disease diagnosis, we collect the first rare diseases corpus (ReCOP), sourced from the National Organization for Rare Disorders (NORD) database. Specifically, we split the report of each rare disease into multiple chunks, each representing a different property of the disease, including their overview, symptoms, causes, effects, related disorders, diagnosis, and standard therapies. This structure ensures that the information within each chunk aligns consistently with a question. Experiment results demonstrate that ReCOP can effectively improve the accuracy of LLMs on the ReDis-QA dataset by an average of 8%. Moreover, it significantly guides LLMs to generate trustworthy answers and explanations that can be traced back to existing literature.

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.

Rare diseases affect millions of individuals worldwide, yet timely diagnosis remains a major public health challenge due to scarcity of specialized clinical expertise. While large language models (LLMs) show promise to support rare disease diagnosis, current models are constrained by insufficient clinical deployability, limited clinically grounded evidence, and scarcity of training data. Here we present RaDaR (Rare Disease navigatoR), an open-source, compact reasoning LLM (32B parameters) for rare disease diagnosis. RaDaR was trained with 49,170 publicly available free-text cases and 104,666 synthetic cases with reasoning-enhanced training. RaDaR showed the strongest performance among evaluated open-source models, including the 671B DeepSeek-R1, across public benchmarks and four external validation centers. In a retrospective cohort, RaDaR prioritized the final diagnosis before documented clinical suspicion in 61.06 percent of cases, corresponding to a potential lead time of 1.87 months and 50.18 percent of the within-center interval. In a randomized physician-assistance trial, RaDaR assistance improved physicians' rare-disease diagnostic accuracy by 21.44 percentage points compared with internet search alone. Synthetic-data ablations suggested that phenotype-anchored narratives provide useful training signal for long-tail rare diseases, with a monotonic scaling trend within the tested data range. Together, RaDaR and its development and validation framework provide a deployable rare-disease reasoning model and a reproducible development framework for diagnostic AI under data scarcity.

Mental distress like depression and anxiety contribute to the largest proportion of the global burden of diseases. Automated diagnosis systems of such disorders, empowered by recent innovations in Artificial Intelligence, can pave the way to reduce the sufferings of the affected individuals. Development of such systems requires information-rich and balanced corpora. In this work, we introduce a novel mental distress analysis audio dataset DEPAC, labeled based on established thresholds on depression and anxiety standard screening tools. This large dataset comprises multiple speech tasks per individual, as well as relevant demographic information. Alongside, we present a feature set consisting of hand-curated acoustic and linguistic features, which were found effective in identifying signs of mental illnesses in human speech. Finally, we justify the quality and effectiveness of our proposed audio corpus and feature set in predicting depression severity by comparing the performance of baseline machine learning models built on this dataset with baseline models trained on other well-known depression corpora.

Background Major depressive disorder (MDD) is a leading cause of global disability, yet current diagnostic approaches often rely on subjective assessments and lack the ability to integrate multimodal clinical information. Large language models (LLMs) hold promise for enhancing diagnostic accuracy through advanced reasoning but face challenges in interpretability, hallucination, and reliance on synthetic data. Methods We developed MDD-Thinker, an LLM-based diagnostic framework that integrates supervised fine-tuning (SFT) with reinforcement learning (RL) to strengthen reasoning ability and interpretability. Using the UK Biobank dataset, we generated 40,000 reasoning samples, supplemented with 10,000 samples from publicly available mental health datasets. The model was fine-tuned on these reasoning corpora, and its diagnostic and reasoning performance was evaluated against machine learning, deep learning, and state-of-the-art LLM baselines. Findings MDD-Thinker achieved an accuracy of 0.8268 and F1-score of 0.8081, significantly outperforming traditional baselines such as SVM and MLP, as well as general-purpose LLMs. Incorporating both SFT and RL yielded the greatest improvements, with relative gains of 29.0% in accuracy, 38.1% in F1-score, and 34.8% in AUC. Moreover, the model demonstrated comparable reasoning performance compared to much larger LLMs, while maintaining computational efficiency. Interpretation This study presents the first reasoning-enhanced LLM framework for MDD diagnosis trained on large-scale real-world clinical data. By integrating SFT and RL, MDD-Thinker balances accuracy, interpretability, and efficiency, offering a scalable approach for intelligent psychiatric diagnostics. These findings suggest that reasoning-oriented LLMs can provide clinically reliable support for MDD detection and may inform broader applications in mental health care.

Mental health disorders represent a burgeoning global public health challenge. While Large Language Models (LLMs) have demonstrated potential in psychiatric assessment, their clinical utility is severely constrained by benchmarks that lack ecological validity and fine-grained diagnostic supervision. To bridge this gap, we introduce MentalDx Bench, the first benchmark dedicated to disorder-level psychiatric diagnosis within real-world clinical settings. Comprising 712 de-identified electronic health records annotated by board-certified psychiatrists under ICD-11 guidelines, the benchmark covers 76 disorders across 16 diagnostic categories. Evaluation of 18 LLMs reveals a critical paradigm misalignment: strong performance at coarse diagnostic categorization contrasts with systematic failure at disorder-level diagnosis, underscoring a gap between pattern-based modeling and clinical hypothetico-deductive reasoning. In response, we propose MentalSeek-Dx, a medical-specialized LLM trained to internalize this clinical reasoning process through supervised trajectory construction and curriculum-based reinforcement learning. Experiments on MentalDx Bench demonstrate that MentalSeek-Dx achieves state-of-the-art (SOTA) performance with only 14B parameters, establishing a clinically grounded framework for reliable psychiatric diagnosis.

Medical imaging artificial intelligence has achieved strong performance in isolated image interpretation, but remains poorly aligned with radiological practice, where diagnosis and follow-up rely on comparison across prior studies and analogous reference cases. Here we formulate radiological comparison as an entity-aware cross-image reasoning problem and introduce a framework that supports both reference-case retrieval and temporal comparative interpretation. We construct MedReCo-DB, a large-scale comparative imaging resource derived from routine image-report pairs, comprising more than 690,000 images from over 160,000 patients across eight institutions, four countries and seven imaging modalities. Reports are decomposed into anatomical structures, abnormal findings and pathological conditions to provide supervision for entity-conditioned retrieval and comparative visual question answering. Using this resource, we develop MedReCo, an entity-aware visual encoder for controllable retrieval of clinically analogous cases, and MedReCo-VLM, a vision--language extension for generative interpretation of interval change. Across internal, external and cross-center evaluations, MedReCo achieved the highest Recall@1 in all 12 internal retrieval settings and improved external retrieval by a mean of 6.0 percentage points. In clinically confusable differential groups, it consistently outperformed the strongest baselines. MedReCo-VLM achieved the best performance across all comparative generation evaluations and improved longitudinal follow-up accuracy by 14.5-46.5 percentage points on chest radiographs and 13.0-27.9 percentage points on CT. These findings suggest that entity-aware comparative reasoning can be learned from routine clinical data at scale and may provide a more clinically aligned foundation for medical imaging AI.

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/.

Introduction: Electronic health records (EHR) are a critical medium through which patient stigmatization is perpetuated among healthcare teams. Methods: We identified linguistic features of doubt markers and stigmatizing labels in MIMIC-III EHR via expanded lexicon matching and supervised learning classifiers. Predictors of rates of linguistic features were assessed using Poisson regression models. Results: We found higher rates of stigmatizing labels per chart among patients who were Black or African American (RR: 1.16), patients with Medicare/Medicaid or government-run insurance (RR: 2.46), self-pay (RR: 2.12), and patients with a variety of stigmatizing disease and mental health conditions. Patterns among doubt markers were similar, though male patients had higher rates of doubt markers (RR: 1.25). We found increased stigmatizing labels used by nurses (RR: 1.40), and social workers (RR: 2.25), with similar patterns of doubt markers. Discussion: Stigmatizing language occurred at higher rates among historically stigmatized patients, perpetuated by multiple provider types.

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 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 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.

Ever since the original algorithm by Nesterov (1983), the true nature of the acceleration phenomenon has remained elusive, with various interpretations of why the method is actually faster. The diagnosis of the algorithm through the lens of Ordinary Differential Equations (ODEs) and the corresponding dynamical system formulation to explain the underlying dynamics has a rich history. In the literature, the ODEs that explain algorithms are typically derived by considering the limiting case of the algorithm maps themselves, that is, an ODE formulation follows the development of an algorithm. This obfuscates the underlying higher order principles and thus provides little evidence of the working of the algorithm. Such has been the case with Nesterov algorithm and the various analogies used to describe the acceleration phenomena, viz, momentum associated with the rolling of a Heavy-Ball down a slope, Hessian damping etc. The main focus of our work is to ideate the genesis of the Nesterov algorithm from the viewpoint of dynamical systems leading to demystifying the mathematical rigour behind the algorithm. Instead of reverse engineering ODEs from discrete algorithms, this work explores tools from the recently developed control paradigm titled Passivity and Immersion approach and the Geometric Singular Perturbation theory which are applied to arrive at the formulation of a dynamical system that explains and models the acceleration phenomena. This perspective helps to gain insights into the various terms present and the sequence of steps used in Nesterovs accelerated algorithm for the smooth strongly convex and the convex case. The framework can also be extended to derive the acceleration achieved using the triple momentum method and provides justifications for the non-convergence to the optimal solution in the Heavy-Ball method.

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.

Background: General-purpose large language models that utilize both text and images have not been evaluated on a diverse array of challenging medical cases. Methods: Using 934 cases from the NEJM Image Challenge published between 2005 and 2023, we evaluated the accuracy of the recently released Generative Pre-trained Transformer 4 with Vision model (GPT-4V) compared to human respondents overall and stratified by question difficulty, image type, and skin tone. We further conducted a physician evaluation of GPT-4V on 69 NEJM clinicopathological conferences (CPCs). Analyses were conducted for models utilizing text alone, images alone, and both text and images. Results: GPT-4V achieved an overall accuracy of 61% (95% CI, 58 to 64%) compared to 49% (95% CI, 49 to 50%) for humans. GPT-4V outperformed humans at all levels of difficulty and disagreement, skin tones, and image types; the exception was radiographic images, where performance was equivalent between GPT-4V and human respondents. Longer, more informative captions were associated with improved performance for GPT-4V but similar performance for human respondents. GPT-4V included the correct diagnosis in its differential for 80% (95% CI, 68 to 88%) of CPCs when using text alone, compared to 58% (95% CI, 45 to 70%) of CPCs when using both images and text. Conclusions: GPT-4V outperformed human respondents on challenging medical cases and was able to synthesize information from both images and text, but performance deteriorated when images were added to highly informative text. Overall, our results suggest that multimodal AI models may be useful in medical diagnostic reasoning but that their accuracy may depend heavily on context.

In recent years, deep learning models have been extensively applied to biological data across various modalities. Discriminative deep learning models have excelled at classifying images into categories (e.g., healthy versus diseased, treated versus untreated). However, these models are often perceived as black boxes due to their complexity and lack of interpretability, limiting their application in real-world biological contexts. In biological research, explainability is essential: understanding classifier decisions and identifying subtle differences between conditions are critical for elucidating the effects of treatments, disease progression, and biological processes. To address this challenge, we propose DiffEx, a method for generating visually interpretable attributes to explain classifiers and identify microscopic cellular variations between different conditions. We demonstrate the effectiveness of DiffEx in explaining classifiers trained on natural and biological images. Furthermore, we use DiffEx to uncover phenotypic differences within microscopy datasets. By offering insights into cellular variations through classifier explanations, DiffEx has the potential to advance the understanding of diseases and aid drug discovery by identifying novel biomarkers.

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.

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

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

Skin diseases affect millions of people worldwide, across all ethnicities. Increasing diagnosis accessibility requires fair and accurate segmentation and classification of dermatology images. However, the scarcity of annotated medical images, especially for rare diseases and underrepresented skin tones, poses a challenge to the development of fair and accurate models. In this study, we introduce a Fair, Efficient, and Diverse Diffusion-based framework for skin lesion segmentation and malignancy classification. FEDD leverages semantically meaningful feature embeddings learned through a denoising diffusion probabilistic backbone and processes them via linear probes to achieve state-of-the-art performance on Diverse Dermatology Images (DDI). We achieve an improvement in intersection over union of 0.18, 0.13, 0.06, and 0.07 while using only 5%, 10%, 15%, and 20% labeled samples, respectively. Additionally, FEDD trained on 10% of DDI demonstrates malignancy classification accuracy of 81%, 14% higher compared to the state-of-the-art. We showcase high efficiency in data-constrained scenarios while providing fair performance for diverse skin tones and rare malignancy conditions. Our newly annotated DDI segmentation masks and training code can be found on https://github.com/hectorcarrion/fedd.

The clinical translation of dermatological AI is hindered by opaque reasoning and systematic performance disparities across skin tones. Here we present SkinGPT-R1, a multimodal large language model that integrates chain-of-thought diagnostic reasoning with a fairness-aware mixture-of-experts architecture for interpretable and equitable skin disease diagnosis. Through parameter-efficient adaptation of a frozen reasoning backbone, SkinGPT-R1 generates structured diagnostic reports comprising visual findings, differential reasoning, and final diagnosis. Across seven external datasets spanning diverse pathologies and imaging conditions, SkinGPT-R1 achieves state-of-the-art accuracy on six benchmarks, including 82.50\% on a challenging 40-class long-tail classification task (+19.30\% over leading baselines). Blinded evaluation by five board-certified dermatologists on 1,000 phenotypically balanced cases yields a mean score of 3.6 out of 5, with the highest ratings in safety (3.8) and reasoning coherence (3.6), indicating that the generated rationales are clinically safe, logically grounded, and suitable for supporting diagnostic decision-making. Critically, SkinGPT-R1 mitigates algorithmic bias across the full Fitzpatrick spectrum, achieving a robust worst-group performance of 41.40\% on the Fitz17k benchmark and a five-fold relative improvement in lower-bound accuracy on the DDI dataset compared to standard multimodal baselines. These results establish a framework for trustworthy, fair, and explainable AI-assisted dermatological diagnosis.

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.

Gastrointestinal (GI) diseases represent a clinically significant burden, necessitating precise diagnostic approaches to optimize patient outcomes. Conventional histopathological diagnosis suffers from limited reproducibility and diagnostic variability. To overcome these limitations, we develop Digepath, a specialized foundation model for GI pathology. Our framework introduces a dual-phase iterative optimization strategy combining pretraining with fine-screening, specifically designed to address the detection of sparsely distributed lesion areas in whole-slide images. Digepath is pretrained on over 353 million multi-scale images from 210,043 H&E-stained slides of GI diseases. It attains state-of-the-art performance on 33 out of 34 tasks related to GI pathology, including pathological diagnosis, protein expression status prediction, gene mutation prediction, and prognosis evaluation. We further translate the intelligent screening module for early GI cancer and achieve near-perfect 99.70% sensitivity across nine independent medical institutions. This work not only advances AI-driven precision pathology for GI diseases but also bridge critical gaps in histopathological practice.

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

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.

Learning disorders are neurological conditions that affect the brain's ability to interconnect communication areas. Dyslexic students experience problems with reading, memorizing, and exposing concepts; however the magnitude of these can be mitigated through both therapies and the creation of compensatory mechanisms. Several efforts have been made to mitigate these issues, leading to the creation of digital resources for students with specific learning disorders attending primary and secondary education levels. Conversely, a standard approach is still missed in higher education. The VRAIlexia project has been created to tackle this issue by proposing two different tools: a mobile application integrating virtual reality (VR) to collect data quickly and easily, and an artificial intelligencebased software (AI) to analyze the collected data for customizing the supporting methodology for each student. The first one has been created and is being distributed among dyslexic students in Higher Education Institutions, for the conduction of specific psychological and psychometric tests. The second tool applies specific artificial intelligence algorithms to the data gathered via the application and other surveys. These AI techniques have allowed us to identify the most relevant difficulties faced by the students' cohort. Our different models have obtained around 90\% mean accuracy for predicting the support tools and learning strategies.

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.

Neurological diseases are the leading global cause of disability, yet most lack disease-modifying treatments. We present PROTON, a heterogeneous graph transformer that generates testable hypotheses across molecular, organoid, and clinical systems. To evaluate PROTON, we apply it to Parkinson's disease (PD), bipolar disorder (BD), and Alzheimer's disease (AD). In PD, PROTON linked genetic risk loci to genes essential for dopaminergic neuron survival and predicted pesticides toxic to patient-derived neurons, including the insecticide endosulfan, which ranked within the top 1.29% of predictions. In silico screens performed by PROTON reproduced six genome-wide α-synuclein experiments, including a split-ubiquitin yeast two-hybrid system (normalized enrichment score [NES] = 2.30, FDR-adjusted p < 1 times 10^{-4}), an ascorbate peroxidase proximity labeling assay (NES = 2.16, FDR < 1 times 10^{-4}), and a high-depth targeted exome sequencing study in 496 synucleinopathy patients (NES = 2.13, FDR < 1 times 10^{-4}). In BD, PROTON predicted calcitriol as a candidate drug that reversed proteomic alterations observed in cortical organoids derived from BD patients. In AD, we evaluated PROTON predictions in health records from n = 610,524 patients at Mass General Brigham, confirming that five PROTON-predicted drugs were associated with reduced seven-year dementia risk (minimum hazard ratio = 0.63, 95% CI: 0.53-0.75, p < 1 times 10^{-7}). PROTON generated neurological hypotheses that were evaluated across molecular, organoid, and clinical systems, defining a path for AI-driven discovery in neurological disease.

A principal component analysis of the TCGA data for 15 cancer localizations unveils the following qualitative facts about tumors: 1) The state of a tissue in gene expression space may be described by a few variables. In particular, there is a single variable describing the progression from a normal tissue to a tumor. 2) Each cancer localization is characterized by a gene expression profile, in which genes have specific weights in the definition of the cancer state. There are no less than 2500 differentially-expressed genes, which lead to power-like tails in the expression distribution functions. 3) Tumors in different localizations share hundreds or even thousands of differentially expressed genes. There are 6 genes common to the 15 studied tumor localizations. 4) The tumor region is a kind of attractor. Tumors in advanced stages converge to this region independently of patient age or genetic variability. 5) There is a landscape of cancer in gene expression space with an approximate border separating normal tissues from tumors.

Pathology vision-language models (VLMs) have shown strong visual perception ability, but their robustness in the language domain remains poorly characterized. Existing pathology VLM benchmarks largely rely on canonical closed-set prompts or perturb only generic templates, treating language as a fixed evaluation component rather than a variable axis of model behavior. In clinical practice, however, diagnostic language varies across reports, institutions, and candidate diagnoses. We introduce PathLang, a language-centered and clinically grounded zero-shot benchmark. PathLang holds the underlying slides, ground-truth labels, and image-text evaluation direction fixed while systematically varying only the diagnostic language, so that performance differences reflect how a diagnosis is phrased rather than what is imaged. The language variation follows how pathologists actually rephrase diagnoses (terminology, specificity, and reporting style), and all prompts and candidate pools are validated by six board-certified pathologists. PathLang covers four task families: (1) zero-shot classification with image-text alignment analysis, (2) cross-modal retrieval, (3) paraphrase robustness, including semantic-equivalence paraphrases, length and reporting-style variation, and prompt ensembling, and (4) open-vocabulary diagnosis retrieval over four candidate pools with distinct forms of semantic competition. Across nine VLMs and five public datasets spanning four organs, we find that performance is highly sensitive to clinically equivalent paraphrases, varies substantially across forms of semantic competition, and that image-text alignment quality does not necessarily translate into inter-class separability. We release the prompt corpus, candidate pools, pre-computed text embeddings, and evaluation code at https://anonymous.4open.science/r/PathLang.

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.

In recent years, people from all over the world are suffering from one of the most severe diseases in history, known as Coronavirus disease 2019, COVID-19 for short. When the virus reaches the lungs, it has a higher probability to cause lung pneumonia and sepsis. X-ray image is a powerful tool in identifying the typical features of the infection for COVID-19 patients. The radiologists and pathologists observe that ground-glass opacity appears in the chest X-ray for infected patient cozzi2021ground, and it could be used as one of the criteria during the diagnosis process. In the past few years, deep learning has proven to be one of the most powerful methods in the field of image classification. Due to significant differences in Chest X-Ray between normal and infected people rousan2020chest, deep models could be used to identify the presence of the disease given a patient's Chest X-Ray. Many deep models are complex, and it evolves with lots of input parameters. Designers sometimes struggle with the tuning process for deep models, especially when they build up the model from scratch. Genetic Algorithm, inspired by the biological evolution process, plays a key role in solving such complex problems. In this paper, I proposed a genetic-based approach to optimize the Convolutional Neural Network(CNN) for the Chest X-Ray classification task.

Counterfactual medical image generation effectively addresses data scarcity and enhances the interpretability of medical images. However, due to the complex and diverse pathological features of medical images and the imbalanced class distribution in medical data, generating high-quality and diverse medical images from limited data is significantly challenging. Additionally, to fully leverage the information in limited data, such as anatomical structure information and generate more structurally stable medical images while avoiding distortion or inconsistency. In this paper, in order to enhance the clinical relevance of generated data and improve the interpretability of the model, we propose a novel medical image generation framework, which generates independent pathological and structural features based on causal disentanglement and utilizes text-guided modeling of pathological features to regulate the generation of counterfactual images. First, we achieve feature separation through causal disentanglement and analyze the interactions between features. Here, we introduce group supervision to ensure the independence of pathological and identity features. Second, we leverage a diffusion model guided by pathological findings to model pathological features, enabling the generation of diverse counterfactual images. Meanwhile, we enhance accuracy by leveraging a large language model to extract lesion severity and location from medical reports. Additionally, we improve the performance of the latent diffusion model on long-tailed categories through initial noise optimization.

Accurate dermatological diagnosis naturally necessitates equitable performance across diverse populations, yet a systematic lack of expertly annotated images, especially for underrepresented skin tones and rare diseases, impedes progress toward measurably fair methods. We introduce cgDDI (Controllable Generation of Diverse Dermatological Imagery), a hybrid framework that (1) synthesizes realistic healthy skin samples without disturbing other input properties, (2) maps single-sample rare lesions onto novel skin-tones and locations non-parametrically, and (3) allows for efficient parametric generation with as few as 10 training samples. The framework supports both human and automated segmentation masking, enabling scalability to datasets without pre-made lesion masks. We grow a 656-image dataset by more than 400x and validate across two datasets: biopsy-confirmed Diverse Dermatology Images (DDI) and expert-verified Fitzpatrick17k (F17k). On the DDI benchmark, we achieve malignancy classification accuracy of 86.4% under synthetic-only training and 90.9% state-of-the-art performance with real data fine-tuning, alongside leading fairness metrics. Cross-dataset experiments show +13.9% accuracy improvements on unseen F17k data despite minimal disease overlap. We openly release 266k+ synthetic images, code, and generative models to further support fairness research at https://github.com/hectorcarrion/ControllableGenDDI.

Breast cancer is a prevalent form of cancer among women, with over 1.5 million women being diagnosed each year. Unfortunately, the survival rates for breast cancer patients in certain third-world countries, like South Africa, are alarmingly low, with only 40% of diagnosed patients surviving beyond five years. The inadequate availability of resources, including qualified pathologists, delayed diagnoses, and ineffective therapy planning, contribute to this low survival rate. To address this pressing issue, medical specialists and researchers have turned to domain-specific AI approaches, specifically deep learning models, to develop end-to-end solutions that can be integrated into computer-aided diagnosis (CAD) systems. By improving the workflow of pathologists, these AI models have the potential to enhance the detection and diagnosis of breast cancer. This research focuses on evaluating the performance of various cutting-edge convolutional neural network (CNN) architectures in comparison to a relatively new model called the Vision Trans-former (ViT). The objective is to determine the superiority of these models in terms of their accuracy and effectiveness. The experimental results reveal that the ViT models outperform the other selected state-of-the-art CNN architectures, achieving an impressive accuracy rate of 95.15%. This study signifies a significant advancement in the field, as it explores the utilization of data augmentation and other relevant preprocessing techniques in conjunction with deep learning models for the detection and diagnosis of breast cancer using datasets of Breast Cancer Histopathological Image Classification.

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.

The medical domain is vast and diverse, with many existing embedding models focused on general healthcare applications. However, these models often struggle to capture a deep understanding of diseases due to their broad generalization across the entire medical field. To address this gap, I present DisEmbed, a disease-focused embedding model. DisEmbed is trained on a synthetic dataset specifically curated to include disease descriptions, symptoms, and disease-related Q\&A pairs, making it uniquely suited for disease-related tasks. For evaluation, I benchmarked DisEmbed against existing medical models using disease-specific datasets and the triplet evaluation method. My results demonstrate that DisEmbed outperforms other models, particularly in identifying disease-related contexts and distinguishing between similar diseases. This makes DisEmbed highly valuable for disease-specific use cases, including retrieval-augmented generation (RAG) tasks, where its performance is particularly robust.

Skin tone as a demographic bias and inconsistent human labeling poses challenges in dermatology AI. We take another angle to investigate color contrast's impact, beyond skin tones, on malignancy detection in skin disease datasets: We hypothesize that in addition to skin tones, the color difference between the lesion area and skin also plays a role in malignancy detection performance of dermatology AI models. To study this, we first propose a robust labeling method to quantify color contrast scores of each image and validate our method by showing small labeling variations. More importantly, applying our method to the only diverse-skin tone and pathologically-confirmed skin disease dataset DDI, yields DDI-CoCo Dataset, and we observe a performance gap between the high and low color difference groups. This disparity remains consistent across various state-of-the-art (SoTA) image classification models, which supports our hypothesis. Furthermore, we study the interaction between skin tone and color difference effects and suggest that color difference can be an additional reason behind model performance bias between skin tones. Our work provides a complementary angle to dermatology AI for improving skin disease detection.

Multiple Instance learning (MIL) models have been extensively used in pathology to predict biomarkers and risk-stratify patients from gigapixel-sized images. Machine learning problems in medical imaging often deal with rare diseases, making it important for these models to work in a label-imbalanced setting. In pathology images, there is another level of imbalance, where given a positively labeled Whole Slide Image (WSI), only a fraction of pixels within it contribute to the positive label. This compounds the severity of imbalance and makes imbalanced classification in pathology challenging. Furthermore, these imbalances can occur in out-of-distribution (OOD) datasets when the models are deployed in the real-world. We leverage the idea that decoupling feature and classifier learning can lead to improved decision boundaries for label imbalanced datasets. To this end, we investigate the integration of supervised contrastive learning with multiple instance learning (SC-MIL). Specifically, we propose a joint-training MIL framework in the presence of label imbalance that progressively transitions from learning bag-level representations to optimal classifier learning. We perform experiments with different imbalance settings for two well-studied problems in cancer pathology: subtyping of non-small cell lung cancer and subtyping of renal cell carcinoma. SC-MIL provides large and consistent improvements over other techniques on both in-distribution (ID) and OOD held-out sets across multiple imbalanced settings.

Automated methods have been widely used to identify and analyze mental health conditions (e.g., depression) from various sources of information, including social media. Yet, deployment of such models in real-world healthcare applications faces challenges including poor out-of-domain generalization and lack of trust in black box models. In this work, we propose approaches for depression detection that are constrained to different degrees by the presence of symptoms described in PHQ9, a questionnaire used by clinicians in the depression screening process. In dataset-transfer experiments on three social media datasets, we find that grounding the model in PHQ9's symptoms substantially improves its ability to generalize to out-of-distribution data compared to a standard BERT-based approach. Furthermore, this approach can still perform competitively on in-domain data. These results and our qualitative analyses suggest that grounding model predictions in clinically-relevant symptoms can improve generalizability while producing a model that is easier to inspect.

Skin cancer is one of the most threatening diseases worldwide. However, diagnosing skin cancer correctly is challenging. Recently, deep learning algorithms have emerged to achieve excellent performance on various tasks. Particularly, they have been applied to the skin disease diagnosis tasks. In this paper, we present a review on deep learning methods and their applications in skin disease diagnosis. We first present a brief introduction to skin diseases and image acquisition methods in dermatology, and list several publicly available skin datasets for training and testing algorithms. Then, we introduce the conception of deep learning and review popular deep learning architectures. Thereafter, popular deep learning frameworks facilitating the implementation of deep learning algorithms and performance evaluation metrics are presented. As an important part of this article, we then review the literature involving deep learning methods for skin disease diagnosis from several aspects according to the specific tasks. Additionally, we discuss the challenges faced in the area and suggest possible future research directions. The major purpose of this article is to provide a conceptual and systematically review of the recent works on skin disease diagnosis with deep learning. Given the popularity of deep learning, there remains great challenges in the area, as well as opportunities that we can explore in the future.

Prion diseases are rare, rapidly progressive, and fatal neurodegenerative disorders that remain difficult to diagnose, particularly in their early stages because of nonspecific clinical presentations. However, to our knowledge, there is no publicly available prion-disease-focused dataset designed to capture a broad range of clinically relevant entities from the biomedical literature. We introduce PrionNER, a manually annotated named entity recognition dataset for prion disease clinical information in PubMed abstracts. The current release comprises 317 abstracts, 2,943 sentences, and 6,955 text-bound entity annotations spanning 15 coarse-grained and 31 fine-grained clinically oriented entity types covering diseases, symptoms, diagnostics, findings, anatomy, treatments, and temporal and statistical evidence. Inter-annotator agreement reaches 81.78 exact-match F1, indicating strong annotation consistency. We benchmark supervised BERT baselines, W2NER, and zero-shot extractors on PrionNER. W2NER is the strongest supervised model, and Gemma-4-31B is the strongest zero-shot model, but the benchmark remains challenging, especially for structurally complex mentions and fine-grained clinically adjacent label distinctions. PrionNER provides a clinically grounded benchmark for prion-disease information extraction and supports research on rare-disease biomedical NLP under low-resource, fine-grained, and non-flat extraction conditions. The dataset, annotation guidelines, and evaluation scripts are available at https://github.com/daotuanan/PrionNER/.

Despite extensive standardization, diagnostic interviews for mental health disorders encompass substantial subjective judgment. Previous studies have demonstrated that EEG-based neural measures can function as reliable objective correlates of depression, or even predictors of depression and its course. However, their clinical utility has not been fully realized because of 1) the lack of automated ways to deal with the inherent noise associated with EEG data at scale, and 2) the lack of knowledge of which aspects of the EEG signal may be markers of a clinical disorder. Here we adapt an unsupervised pipeline from the recent deep representation learning literature to address these problems by 1) learning a disentangled representation using beta-VAE to denoise the signal, and 2) extracting interpretable features associated with a sparse set of clinical labels using a Symbol-Concept Association Network (SCAN). We demonstrate that our method is able to outperform the canonical hand-engineered baseline classification method on a number of factors, including participant age and depression diagnosis. Furthermore, our method recovers a representation that can be used to automatically extract denoised Event Related Potentials (ERPs) from novel, single EEG trajectories, and supports fast supervised re-mapping to various clinical labels, allowing clinicians to re-use a single EEG representation regardless of updates to the standardized diagnostic system. Finally, single factors of the learned disentangled representations often correspond to meaningful markers of clinical factors, as automatically detected by SCAN, allowing for human interpretability and post-hoc expert analysis of the recommendations made by the model.

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

Artificial intelligence (AI) models are increasingly used in the medical domain. However, as medical data is highly sensitive, special precautions to ensure its protection are required. The gold standard for privacy preservation is the introduction of differential privacy (DP) to model training. Prior work indicates that DP has negative implications on model accuracy and fairness, which are unacceptable in medicine and represent a main barrier to the widespread use of privacy-preserving techniques. In this work, we evaluated the effect of privacy-preserving training of AI models regarding accuracy and fairness compared to non-private training. For this, we used two datasets: (1) A large dataset (N=193,311) of high quality clinical chest radiographs, and (2) a dataset (N=1,625) of 3D abdominal computed tomography (CT) images, with the task of classifying the presence of pancreatic ductal adenocarcinoma (PDAC). Both were retrospectively collected and manually labeled by experienced radiologists. We then compared non-private deep convolutional neural networks (CNNs) and privacy-preserving (DP) models with respect to privacy-utility trade-offs measured as area under the receiver-operator-characteristic curve (AUROC), and privacy-fairness trade-offs, measured as Pearson's r or Statistical Parity Difference. We found that, while the privacy-preserving trainings yielded lower accuracy, they did largely not amplify discrimination against age, sex or co-morbidity. Our study shows that -- under the challenging realistic circumstances of a real-life clinical dataset -- the privacy-preserving training of diagnostic deep learning models is possible with excellent diagnostic accuracy and fairness.

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.

Large language models (LLMs) show promise in medical diagnosis, but real-world deployment remains challenging due to high-stakes clinical decisions and imperfect reasoning reliability. As a result, careful inspection of model behavior is essential for assessing whether diagnostic reasoning is reliable and clinically grounded. However, debugging medical LLMs remains difficult. First, developers often lack sufficient medical domain expertise to interpret model errors in clinically meaningful terms. Second, models can fail across a large and diverse set of instances involving different input types, tasks, and reasoning steps, making it challenging for developers to prioritize which errors deserve focused inspection. Third, developers struggle to identify recurring error patterns across cases, as existing debugging practices are largely instance-centric and rely on manual inspection of isolated failures. To address these challenges, we present VeriLLMed, a visual analytics system that integrates external biomedical knowledge to audit and debug medical LLM diagnostic reasoning. VeriLLMed transforms model outputs into comparable reasoning paths, constructs knowledge graph-grounded reference paths, and identifies three recurring classes of diagnosis errors: relation errors, branch errors, and missing errors. Case studies and expert evaluation demonstrate that VeriLLMed helps developers identify clinically implausible reasoning and generate actionable insights that can inform the improvement of medical LLMs.

Diabetic retinopathy (DR) is a prevalent complication of diabetes associated with a significant risk of vision loss. Timely identification is critical to curb vision impairment. Algorithms for DR staging from digital fundus images (DFIs) have been recently proposed. However, models often fail to generalize due to distribution shifts between the source domain on which the model was trained and the target domain where it is deployed. A common and particularly challenging shift is often encountered when the source- and target-domain supports do not fully overlap. In this research, we introduce DRStageNet, a deep learning model designed to mitigate this challenge. We used seven publicly available datasets, comprising a total of 93,534 DFIs that cover a variety of patient demographics, ethnicities, geographic origins and comorbidities. We fine-tune DINOv2, a pretrained model of self-supervised vision transformer, and implement a multi-source domain fine-tuning strategy to enhance generalization performance. We benchmark and demonstrate the superiority of our method to two state-of-the-art benchmarks, including a recently published foundation model. We adapted the grad-rollout method to our regression task in order to provide high-resolution explainability heatmaps. The error analysis showed that 59\% of the main errors had incorrect reference labels. DRStageNet is accessible at URL [upon acceptance of the manuscript].

The controversy of computed tomography (CT) use in COVID-19 screening is associated with ambiguous characteristics of chest CT as a diagnostic test. The reported values of CT sensitivity and specificity calculated using RT-PCR as a reference standard vary widely. The objective of this study was to reevaluate the diagnostic and prognostic value of CT using an alternative approach. This study included 973 symptomatic COVID-19 patients aged 42 pm 17 years, 56% females. We reviewed the disease dynamics between the initial and follow-up CT studies using a "CT0-4" grading system. Sensitivity and specificity were calculated as conditional probabilities that a patient's condition would improve or deteriorate relative to the initial CT study results. For the calculation of negative (NPV) and positive (PPV) predictive values, we estimated the COVID-19 prevalence in Moscow. We used several ARIMA and EST models with different parameters to fit the data on total cases of COVID-19 from March 6, 2020, to July 20, 2020, and forecast the incidence. The "CT0-4" grading scale demonstrated low sensitivity (28%) but high specificity (95%). The best statistical model for describing the pandemic in Moscow was ETS with multiplicative trend, error, and season type. According to our calculations, with the predicted prevalence of 2.1%, the values of NPV and PPV would be 98% and 10%, correspondingly. We associate the low sensitivity and PPV values with the small sample size of the patients with severe symptoms and non-optimal methodological setup for measuring these specific characteristics. The "CT0-4" grading scale was highly specific and predictive for identifying admissions to hospitals of COVID-19 patients. Despite the ambiguous accuracy, chest CT proved to be an effective practical tool for patient management during the pandemic, provided that the necessary infrastructure and human resources are available.