Daily Papers

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.

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

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

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).

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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/.

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.

Automated radiology report generation (RRG) aims to produce detailed textual reports from clinical imaging, such as computed tomography (CT) scans, to improve the accuracy and efficiency of diagnosis and provision of management advice. RRG is complicated by two key challenges: (1) inherent complexity in extracting relevant information from imaging data under resource constraints, and (2) difficulty in objectively evaluating discrepancies between model-generated and expert-written reports. To address these challenges, we propose mu^2LLM, a textbf{mu}ltiscale textbf{mu}ltimodal large language models for RRG tasks. The novel {mu}^2Tokenizer, as an intermediate layer, integrates multi-modal features from the multiscale visual tokenizer and the text tokenizer, then enhances report generation quality through direct preference optimization (DPO), guided by GREEN-RedLlama. Experimental results on four large CT image-report medical datasetdemonstrate that our method outperforms existing approaches, highlighting the potential of our fine-tuned mu^2LLMs on limited data for RRG tasks.

Redshift drift effect, an observational probe that indenpendent of cosmological models, presents unique applications in specific cosmological epoch. By quantifying redshift drift signal , researchers can determine the rate of the Universe's accelerated expansion and impose constraints on cosmological models and parameters. This study evaluates the precision in cosmological parameters estimation derived from this signal via HI 21cm signal, that observed by the Square Kilometre Array (SKA) telescope, with spectral resolutions of 0.001 Hz and 0.002 Hz over an observational period of Delta T = 0.5 year, utilizing two established techniques: the canonical redshift drift and the differential redshift drift method. The primary objective of this project is to ascertain the rate of cosmic acceleration and establish a solid foundation for real-time cosmology. The results reveal that both the two methods impose highly precise constraints on cosmological parameters, with accuracy reaching the level of millimeter per second (mm/s) or better. However, the canonical method provides relatively less stringent compared to the differential approach. Furthermore, when solely constraining the matter density parameter Omega_m, the strategy can be adapted to the canonical method. Nonetheless, the differential method exhibits clear advantages when simultaneously constraining the matter density parameter Omega_m and the equation of state of dark energy. These findings validate SKA's capability in detecting redshift drift and refining observational cosmology and indicates the effect can offer superior diagnostic capabilities compared to other techniques, provided that appropriate observational equipment or sufficient observational time is employed.