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Oct 1

Evolving Diagnostic Agents in a Virtual Clinical Environment

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

TFP: Temporally Conditioned Memory-Fusion Policies for Visuomotor Learning

Vision--Language--Action (VLA) policies such as π_{0.5} and OpenVLA perform well on many manipulation tasks, but they are often reactive: the next action is predicted from the current observation, instruction, and proprioceptive state. This assumption breaks down in stage-dependent manipulation, where visually similar states may require different actions depending on latent task progress and previous interaction outcomes. We argue that such tasks require not only memory, but dynamics-aware belief updates: the policy should preserve task progress during stable or occluded phases and revise its belief near contact, release, or subgoal transitions. We introduce Temporally Conditioned Memory-Fusion Policies (TFP), a lightweight memory-action framework for VLA backbones. TFP maintains an episode-local task-progress belief with Liquid Time-Constant dynamics and injects the updated belief directly into the flow-matching action decoder through adaptive modulation. This lets temporally accumulated context shape the generated action chunk, rather than serving only as passive history context. With a 3.3B-parameter model, TFP improves the average success rate from \(96.9\%\) to \(98.75\%\) on LIBERO and from \(91.4\%\) to \(93.77\%\) on LIBERO-plus. On the memory-focused MIKASA ShellGameTouch diagnostic, TFP achieves success up to \(75.0\%\). Mechanistic analyses show that write-gain changes near manipulation events are about \(6\times\) larger than far non-event phases, and hidden-state interventions show that the belief causally modulates generated action chunks. These results suggest that compact, event-sensitive memory dynamics can improve VLA policies under occlusion, visual perturbation, and stage-dependent task structure.

  • 9 authors
·
Jul 8

EventVLA: Event-Driven Visual Evidence Memory for Long-Horizon Vision-Language-Action Policies

Memory remains a critical bottleneck for long-horizon robotic manipulation, as standard Vision-Language-Action (VLA) policies often fail when task-relevant cues become occluded or unobservable over time. While existing memory-augmented methods utilize historical context, they either suffer from severe information bottlenecks, incur high latency via decoupled dual systems, or rely on unselective buffers that accumulate massive visual redundancies. To address these limitations, we introduce EventVLA, an end-to-end framework founded on the concept of sparse visual evidence memory that comprises two core components: foundational visual anchors to retain initial and short-term contexts, and a dynamic Keyframe Evidence Memory (KEM) module. Specifically, KEM directly predicts future keyframe probabilities from the VLA's latent embeddings to autonomously capture and store sparse, task-critical visual events. This foresight-driven mechanism empowers the policy to dynamically evaluate the future causal utility of current observations, preserving transient visual evidence before it becomes unobservable. Furthermore, we propose RoboTwin-MeM, a diagnostic benchmark specifically designed to evaluate non-Markovian manipulation tasks with interactive visual evidence. Extensive evaluations show that across 17 memory-requiring simulation tasks and 4 real-world bimanual tasks, EventVLA achieves an average success rate improvement of +40% over state-of-the-art memory-augmented VLAs.

MEMOBench: A Process Level Memory Benchmark for Robotic Manipulation

Robotic manipulation often requires acting on information that is no longer visible, yet Vision-Language-Action policies are usually evaluated when the current observation largely determines the next action. Existing robotic memory benchmarks expose this gap, but they still rely mainly on final task success and therefore conflate forgetting with manipulation failure. We present MEMOBench, a benchmark for process level memory evaluation in robotic manipulation. MEMOBench includes 30 history dependent tasks, 1{,}500 expert demonstrations, and 4{,}200 executable checkpoint instances from 84 templates. Each checkpoint pairs coarse to fine language with a simulator predicate and labels one memory operation: Storage, Update, or Compression. These annotations define Memory Storage Rate, Memory Update Rate, and Memory Compression Rate, which measure memory fidelity alongside task success. Across standard and memory augmented VLA policies, the strongest memory module baseline reaches only 31.9\% average success rate, and high storage often coexists with weak update and compression. Checkpoint language also supervises semantic, contrastive, and framewise memory alignment objectives, yielding modest gains across different memory operations. MEMOBench provides a diagnostic evaluation suite and training supervision for memory grounded robotic policies. The project page is available at https://github.com/Collab-Gen/MEMOBench.

  • 9 authors
·
Sep 6

Causal Judge Evaluation: Calibrated Surrogate Metrics for LLM Systems

LLM-as-judge evaluation has become the de facto standard for scaling model assessment, but the practice is statistically unsound: uncalibrated scores can invert preferences, naive confidence intervals on uncalibrated scores achieve near-0% coverage, and importance-weighted estimators collapse under limited overlap despite high effective sample size (ESS). We introduce Causal Judge Evaluation (CJE), a framework that fixes all three failures. On n=4,961 Chatbot Arena prompts (after filtering from 5k), CJE achieves 99% pairwise ranking accuracy at full sample size (94% averaged across configurations), matching oracle quality, at 14x lower cost (for ranking 5 policies) by calibrating a 16x cheaper judge on just 5% oracle labels (~250 labels). CJE combines three components: (i) AutoCal-R, reward calibration via mean-preserving isotonic regression; (ii) SIMCal-W, weight stabilization via stacking of S-monotone candidates; and (iii) Oracle-Uncertainty Aware (OUA) inference that propagates calibration uncertainty into confidence intervals. We formalize the Coverage-Limited Efficiency (CLE) diagnostic, which explains why IPS-style estimators fail even when ESS exceeds 90%: the logger rarely visits regions where target policies concentrate. Key findings: SNIPS inverts rankings even with reward calibration (38% pairwise, negative Kendall's tau) due to weight instability; calibrated IPS remains near-random (47%) despite weight stabilization, consistent with CLE; OUA improves coverage from near-0% to ~86% (Direct) and ~96% (stacked-DR), where naive intervals severely under-cover.

  • 1 authors
·
Dec 11, 2025 2

SC3-Eval: Evaluating Robot Foundation Models via Self-Consistent Video Generation

Evaluating generalist robot manipulation policies in the real world is expensive, slow, and difficult to scale. Action-conditioned video world models offer a scalable alternative by simulating policy rollouts. Autoregressive rollouts accumulate compounding errors, observations across multiple camera views must remain mutually consistent, and the evaluator must generalize to policies whose behaviors lie outside the training distribution. We address these challenges with SC3-Eval, a self-consistent video generation recipe that adapts a pre-trained video foundation model into an accurate policy evaluator by enforcing three complementary forms of consistency. First, forward-inverse dynamics consistency jointly trains the model to predict frames from actions and to recover actions from frames, anchoring generated rollouts to a physically plausible action manifold and counteracting the drift a forward-only model cannot penalize. Second, cross-view consistency trains the model to inpaint each camera view from the other, keeping the multi-camera observation coherent over long rollouts without any explicit memory mechanism. Third, test-time consistency reuses the inverse dynamics mode at inference as a per-action-chunk uncertainty signal that terminates rollouts whose generated frames drift away from the requested actions. We also demonstrate SC3-Eval rollouts reproduce the failure modes that policies exhibit in real-world rollouts, supporting fine-grained diagnostic comparison rather than aggregate ranking alone. Across seven real-world vision-language-action policies, SC3-Eval attains a closed-loop Pearson correlation of 0.929 and MMRV of 0.119, outperforming three strong prior video-model-based baselines, and generalizes to new tasks.

  • 12 authors
·
Jun 16

Unmasking the Illusion of Embodied Reasoning in Vision-Language-Action Models

Recent Vision-Language-Action (VLA) models report impressive success rates on standard robotic benchmarks, fueling optimism about general-purpose physical intelligence. However, recent evidence suggests a systematic misalignment between standard benchmark success and true embodied reasoning, raising the question of whether these high scores reflect genuine cognitive capability. To address this gap, we introduce BeTTER, a diagnostic Benchmark for Testing True Embodied Reasoning in robotic policies. BeTTER applies targeted causal interventions (e.g., spatial layout shifts, temporal extrapolation) while enforcing kinematic isolation to explicitly decouple high-level reasoning failures from low-level execution limits. Through systematic evaluation, we reveal that state-of-the-art VLAs catastrophically fail in dynamic scenarios, exhibiting severe lexical-kinematic shortcuts, behavioral inertia, and semantic feature collapse. Crucially, our mechanistic analysis traces these symptoms to fundamental architectural bottlenecks - such as capacity compression and myopic downsampling - which systematically degrade the model's foundational semantic representation. We demonstrate that highly static evaluation protocols effectively mask this degradation by allowing optimization to overfit to sensorimotor priors. Supported by real-world robotic validation, our findings confirm that this representational breakdown is not a simulation artifact, highlighting the critical need for future VLA paradigms to resolve the structural tension between high-frequency control and high-level reasoning.

  • 6 authors
·
Apr 19

Your Agents Are Aging Too: Agent Lifespan Engineering for Deployed Systems

Long-lived AI agents are increasingly deployed as persistent operational systems, yet they are still evaluated like freshly initialized models. Day-one benchmarks miss a basic systems question: how long does an agent remain reliable after deployment? Even when model weights are frozen, an agent's effective state keeps changing as it compresses interaction history, retrieves from a growing memory store, revises facts after updates, and undergoes routine maintenance. Reliability therefore becomes a lifespan property of the full agent harness, not only a snapshot property of the base model. We introduce AgingBench, a longitudinal reliability benchmark for agent lifespan engineering: measuring not only whether deployed agents degrade, but what form the degradation takes and where repair should target. AgingBench organizes agent aging into four mechanisms: compression aging, interference aging, revision aging, and maintenance aging. To diagnose these failures, AgingBench uses temporal dependency graphs and paired counterfactual probes that produce diagnostic profiles for the write, retrieval, and utilization stages of the memory pipeline. Across 7 scenarios, 14 models, multiple memory policies, and both runner-controlled and autonomous agents, over ~400 runs spanning 8 - 200 sessions show that agent aging is not one-dimensional: behavioral tests can remain clean while factual precision decays; derived-state tracking can collapse sharply within a single model; and the same wrong answer can require different repairs depending on what the diagnostic profile points to. These results suggest that reliable agent deployment requires lifespan evaluation, mechanism-level diagnosis, and stage-targeted repair, not only stronger day-one models.

  • 8 authors
·
May 24 2

Diagnostic Accuracy of Computed Tomography for Identifying Hospitalization in Patients with Suspected COVID-19

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.

  • 8 authors
·
Jul 30, 2020

RAD: Towards Trustworthy Retrieval-Augmented Multi-modal Clinical 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.

Fudan-University Fudan University
·
Sep 24, 2025

Exploring the Inquiry-Diagnosis Relationship with Advanced Patient Simulators

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

  • 10 authors
·
Jan 16, 2025 4

OLIVES Dataset: Ophthalmic Labels for Investigating Visual Eye Semantics

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.

  • 6 authors
·
Sep 22, 2022

PulseMind: A Multi-Modal Medical Model for Real-World Clinical Diagnosis

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

  • 12 authors
·
Jan 12

An Explainable Diagnostic Framework for Neurodegenerative Dementias via Reinforcement-Optimized LLM Reasoning

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.

  • 6 authors
·
May 26, 2025 2

Automatic Differential Diagnosis using Transformer-Based Multi-Label Sequence Classification

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.

  • 3 authors
·
Aug 28, 2024 1

DR.BENCH: Diagnostic Reasoning Benchmark for Clinical Natural Language Processing

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.

  • 7 authors
·
Sep 29, 2022

Domain constraints improve risk prediction when outcome data is missing

Machine learning models are often trained to predict the outcome resulting from a human decision. For example, if a doctor decides to test a patient for disease, will the patient test positive? A challenge is that historical decision-making determines whether the outcome is observed: we only observe test outcomes for patients doctors historically tested. Untested patients, for whom outcomes are unobserved, may differ from tested patients along observed and unobserved dimensions. We propose a Bayesian model class which captures this setting. The purpose of the model is to accurately estimate risk for both tested and untested patients. Estimating this model is challenging due to the wide range of possibilities for untested patients. To address this, we propose two domain constraints which are plausible in health settings: a prevalence constraint, where the overall disease prevalence is known, and an expertise constraint, where the human decision-maker deviates from purely risk-based decision-making only along a constrained feature set. We show theoretically and on synthetic data that domain constraints improve parameter inference. We apply our model to a case study of cancer risk prediction, showing that the model's inferred risk predicts cancer diagnoses, its inferred testing policy captures known public health policies, and it can identify suboptimalities in test allocation. Though our case study is in healthcare, our analysis reveals a general class of domain constraints which can improve model estimation in many settings.

  • 3 authors
·
Dec 6, 2023

LungNoduleAgent: A Collaborative Multi-Agent System for Precision Diagnosis of Lung Nodules

Diagnosing lung cancer typically involves physicians identifying lung nodules in Computed tomography (CT) scans and generating diagnostic reports based on their morphological features and medical expertise. Although advancements have been made in using multimodal large language models for analyzing lung CT scans, challenges remain in accurately describing nodule morphology and incorporating medical expertise. These limitations affect the reliability and effectiveness of these models in clinical settings. Collaborative multi-agent systems offer a promising strategy for achieving a balance between generality and precision in medical applications, yet their potential in pathology has not been thoroughly explored. To bridge these gaps, we introduce LungNoduleAgent, an innovative collaborative multi-agent system specifically designed for analyzing lung CT scans. LungNoduleAgent streamlines the diagnostic process into sequential components, improving precision in describing nodules and grading malignancy through three primary modules. The first module, the Nodule Spotter, coordinates clinical detection models to accurately identify nodules. The second module, the Radiologist, integrates localized image description techniques to produce comprehensive CT reports. Finally, the Doctor Agent System performs malignancy reasoning by using images and CT reports, supported by a pathology knowledge base and a multi-agent system framework. Extensive testing on two private datasets and the public LIDC-IDRI dataset indicates that LungNoduleAgent surpasses mainstream vision-language models, agent systems, and advanced expert models. These results highlight the importance of region-level semantic alignment and multi-agent collaboration in diagnosing nodules. LungNoduleAgent stands out as a promising foundational tool for supporting clinical analyses of lung nodules.

  • 10 authors
·
Nov 25, 2025

DiagnosisArena: Benchmarking Diagnostic Reasoning for Large Language Models

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.

  • 8 authors
·
May 20, 2025

Sequential Diagnosis with Language Models

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.

  • 15 authors
·
Jun 27, 2025

End-to-End Agentic RAG System Training for Traceable Diagnostic Reasoning

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

  • 10 authors
·
Aug 21, 2025 2

DDXPlus: A New Dataset For Automatic Medical Diagnosis

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.

  • 5 authors
·
May 18, 2022

MedExAgent: Training LLM Agents to Ask, Examine, and Diagnose in Noisy Clinical Environments

Real-world clinical diagnosis is a complex process in which the doctor is required to obtain information from both interaction with the patient and conducting medical exams. Additionally, the doctor needs to adapt to different patient personas, as well as noisy and incomplete information that can happen at any time during the process. However, existing benchmarks for medical LLMs and methods for automatic diagnosis largely simplify this process by reducing it to single-turn question answering, noise-free conversations, or sequential exam making, etc., ignoring the interactive and uncertain nature of clinical diagnosis. In this paper, we aim to address this gap by formalizing clinical diagnosis as a Partially Observable Markov Decision Process (POMDP) with three action types: questioning the patient, ordering medical exams as tool calls, and issuing a diagnosis. We also introduce a systematic noise model comprising seven patient noise types and three exam noise types. Using our proposed environment, we train an effective diagnosis agent, MedExAgent, through a two-stage pipeline that first performs supervised finetuning on synthetic conversations structured after the Calgary-Cambridge model for clinical interviews, and then applies DAPO to optimize a composite reward capturing diagnostic accuracy, tool call quality, and exam cost including financial cost and patient discomfort. Through extensive experiments and ablation studies, we demonstrate that MedExAgent achieves diagnostic performance comparable to larger models while maintaining cost-efficient examination strategies.

  • 5 authors
·
May 7

Gender-Dependent Diagnostic Substitution in LLM Medical Triage: Same Symptoms, Unequal Urgency

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.

  • 1 authors
·
Jun 1

Crowdsourcing Dermatology Images with Google Search Ads: Creating a Real-World Skin Condition Dataset

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.

  • 20 authors
·
Feb 28, 2024

CasiMedicos-Arg: A Medical Question Answering Dataset Annotated with Explanatory Argumentative Structures

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

  • 6 authors
·
Oct 7, 2024

Worse than Random? An Embarrassingly Simple Probing Evaluation of Large Multimodal Models in Medical VQA

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

  • 4 authors
·
May 30, 2024

Learning neuroimaging models from health system-scale data

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.

  • 21 authors
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Sep 23, 2025

Automated speech- and text-based classification of neuropsychiatric conditions in a multidiagnostic setting

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.

  • 11 authors
·
Jan 13, 2023

Exploration of Interpretability Techniques for Deep COVID-19 Classification using Chest X-ray Images

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

  • 13 authors
·
Jun 3, 2020

Progress Note Understanding -- Assessment and Plan Reasoning: Overview of the 2022 N2C2 Track 3 Shared Task

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

  • 6 authors
·
Mar 14, 2023

AgentClinic: a multimodal agent benchmark to evaluate AI in simulated clinical environments

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

  • 6 authors
·
May 13, 2024

Teaching LLMs Brazilian Healthcare: Injecting Knowledge from Official Clinical Guidelines

Brazil's Unified Health System (SUS) relies on official clinical guidelines that define diagnostic criteria, treatments, dosages, and monitoring procedures for over 200 million citizens. Yet current LLMs perform poorly on this guideline-specific knowledge, and no benchmark evaluates clinical recall grounded in Brazilian Portuguese protocols. We address this gap by adapting Qwen2.5-14B-Instruct to the Brazilian clinical domain. From 178 official guidelines (~5.4M tokens), we generate ~70M tokens of synthetic data in three formats -- rephrases, wiki-style articles, and question-answer pairs -- using four generator LLMs. We then apply continual pre-training followed by Group Relative Policy Optimization (GRPO). We introduce HealthBench-BR, with 1,780 balanced true/false clinical assertions, and PCDT-QA, with 890 open-ended clinical questions scored by an LLM judge. Our best model achieves 83.9% on HealthBench-BR and 85.4% on PCDT-QA, outperforming GPT-5.2, Claude Sonnet 4.6, Gemini 3.1 Pro, and Google AI Overview's web-grounded RAG despite having only 14B parameters. Ablations show that generator diversity and reinforcement learning are critical to these gains. We release all datasets, benchmarks, and model weights to support reproducible clinical NLP research for Brazilian Portuguese. Code, data, and model weights are available at https://github.com/hugoabonizio/clinical-protocols-br

  • 4 authors
·
Apr 30

Towards Conversational Diagnostic AI

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

  • 25 authors
·
Jan 10, 2024

Right Prediction, Wrong Reasoning: Uncovering LLM Misalignment in RA Disease Diagnosis

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

  • 7 authors
·
Apr 9, 2025

ViDi: Descriptive Visual Data Clustering as Radiologist Assistant in COVID-19 Streamline Diagnostic

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

  • 3 authors
·
Nov 30, 2020

MEDDxAgent: A Unified Modular Agent Framework for Explainable Automatic Differential Diagnosis

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.

  • 6 authors
·
Feb 26, 2025

PromptMRG: Diagnosis-Driven Prompts for Medical Report Generation

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.

  • 4 authors
·
Aug 24, 2023

Med-OPD: Improving Medical Vision-Language Models via Evidence-Aware On-Policy Distillation

Medical Vision-Language Models (Med-VLMs) require reliable reasoning from fine-grained visual evidence, yet existing models can produce plausible clinical answers by relying on language priors or medical templates rather than truly attending to diagnosis-critical regions. On-Policy Distillation (OPD) offers dense token-level supervision on student-generated trajectories and provides a privacy-compatible means of capability transfer without requiring the redistribution of raw patient data. However, standard OPD uniformly distills all tokens, causing sparse evidence-dependent tokens to be diluted by abundant clinical narrative tokens. Inspired by the success of OPD in the large language model community, we propose Med-OPD, to our knowledge the first unified post-training framework that integrates on-policy distillation with medical evidence-aware supervision for Med-VLMs. We introduce Medical Evidence Advantage (MEA), a teacher-grounded counterfactual signal that uses an answer-aware hint to focus teacher scoring on evidence supporting the target diagnosis, and measures each token's dependence on medical visual evidence by comparing teacher likelihoods under the original and evidence-degraded imaging modalities. Based on MEA, Med-OPD redistributes the distillation signal at both the token and trajectory levels, emphasizing diagnosis-critical tokens and evidence-reliant rollouts. Experiments on OmniMedVQA subsets show that Med-OPD consistently outperforms SFT and standard OPD across CT, MRI, Disease Diagnosis, and Lesion Grading. These results demonstrate that evidence-aware distillation can better strengthen medical VLMs' reliance on key visual evidence and improve reliable multimodal medical reasoning. The source code and data is publicly available at: https://github.com/yunhang8658/MedOPD.git

  • 6 authors
·
Jul 13

RareLens: Towards End-to-End Rare Disease Care via Aligning Divergent Large Language Model Reasoning

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.

  • 27 authors
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Jul 24

MedRAG: Enhancing Retrieval-augmented Generation with Knowledge Graph-Elicited Reasoning for Healthcare Copilot

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

  • 4 authors
·
Feb 6, 2025

Medical World Model: Generative Simulation of Tumor Evolution for Treatment Planning

Providing effective treatment and making informed clinical decisions are essential goals of modern medicine and clinical care. We are interested in simulating disease dynamics for clinical decision-making, leveraging recent advances in large generative models. To this end, we introduce the Medical World Model (MeWM), the first world model in medicine that visually predicts future disease states based on clinical decisions. MeWM comprises (i) vision-language models to serve as policy models, and (ii) tumor generative models as dynamics models. The policy model generates action plans, such as clinical treatments, while the dynamics model simulates tumor progression or regression under given treatment conditions. Building on this, we propose the inverse dynamics model that applies survival analysis to the simulated post-treatment tumor, enabling the evaluation of treatment efficacy and the selection of the optimal clinical action plan. As a result, the proposed MeWM simulates disease dynamics by synthesizing post-treatment tumors, with state-of-the-art specificity in Turing tests evaluated by radiologists. Simultaneously, its inverse dynamics model outperforms medical-specialized GPTs in optimizing individualized treatment protocols across all metrics. Notably, MeWM improves clinical decision-making for interventional physicians, boosting F1-score in selecting the optimal TACE protocol by 13%, paving the way for future integration of medical world models as the second readers.

  • 11 authors
·
Jun 2, 2025 2

LingxiDiagBench: A Multi-Agent Framework for Benchmarking LLMs in Chinese Psychiatric Consultation and Diagnosis

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.

Lyncia Lyncia
·
Jun 10 2

Medical-VLBERT: Medical Visual Language BERT for COVID-19 CT Report Generation With Alternate Learning

Medical imaging technologies, including computed tomography (CT) or chest X-Ray (CXR), are largely employed to facilitate the diagnosis of the COVID-19. Since manual report writing is usually too time-consuming, a more intelligent auxiliary medical system that could generate medical reports automatically and immediately is urgently needed. In this article, we propose to use the medical visual language BERT (Medical-VLBERT) model to identify the abnormality on the COVID-19 scans and generate the medical report automatically based on the detected lesion regions. To produce more accurate medical reports and minimize the visual-and-linguistic differences, this model adopts an alternate learning strategy with two procedures that are knowledge pretraining and transferring. To be more precise, the knowledge pretraining procedure is to memorize the knowledge from medical texts, while the transferring procedure is to utilize the acquired knowledge for professional medical sentences generations through observations of medical images. In practice, for automatic medical report generation on the COVID-19 cases, we constructed a dataset of 368 medical findings in Chinese and 1104 chest CT scans from The First Affiliated Hospital of Jinan University, Guangzhou, China, and The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China. Besides, to alleviate the insufficiency of the COVID-19 training samples, our model was first trained on the large-scale Chinese CX-CHR dataset and then transferred to the COVID-19 CT dataset for further fine-tuning. The experimental results showed that Medical-VLBERT achieved state-of-the-art performances on terminology prediction and report generation with the Chinese COVID-19 CT dataset and the CX-CHR dataset. The Chinese COVID-19 CT dataset is available at https://covid19ct.github.io/.

  • 11 authors
·
Aug 17, 2021

MedS^3: Towards Medical Small Language Models with Self-Evolved Slow Thinking

Medical language models (MLMs) have become pivotal in advancing medical natural language processing. However, prior models that rely on pre-training or supervised fine-tuning often exhibit low data efficiency and limited practicality in real-world clinical applications. While OpenAIs O1 highlights test-time scaling in mathematics, attempts to replicate this approach in medicine typically distill responses from GPT-series models to open-source models, focusing primarily on multiple-choice tasks. This strategy, though straightforward, neglects critical concerns like data privacy and realistic deployment in clinical settings. In this work, we present a deployable, small-scale medical language model, \mone, designed for long-chain reasoning in clinical tasks using a self-evolution paradigm. Starting with a seed dataset of around 8,000 instances spanning five domains and 16 datasets, we prompt a base policy model to perform Monte Carlo Tree Search (MCTS) to construct verifiable reasoning chains. Each reasoning step is assigned an evolution rollout value, allowing verified trajectories to train the policy model and the reward model. During inference, the policy model generates multiple responses, and the reward model selects the one with the highest reward score. Experiments on eleven evaluation datasets demonstrate that \mone outperforms prior open-source models by 2 points, with the addition of the reward model further boosting performance (sim13 points), surpassing GPT-4o-mini. Code and data are available at https://github.com/pixas/MedSSS.

  • 6 authors
·
Jan 21, 2025

RareBench: Can LLMs Serve as Rare Diseases Specialists?

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.

  • 6 authors
·
Feb 9, 2024

Towards Accurate Differential Diagnosis with Large Language Models

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.

  • 28 authors
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Nov 30, 2023 1

Evaluating AI systems under uncertain ground truth: a case study in dermatology

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.

  • 20 authors
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Jul 5, 2023

A deep learning system for differential diagnosis of skin diseases

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.

  • 22 authors
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Sep 11, 2019

Policy Gradient-Driven Noise Mask

Deep learning classifiers face significant challenges when dealing with heterogeneous multi-modal and multi-organ biomedical datasets. The low-level feature distinguishability limited to imaging-modality hinders the classifiers' ability to learn high-level semantic relationships, resulting in sub-optimal performance. To address this issue, image augmentation strategies are employed as regularization techniques. While additive noise input during network training is a well-established augmentation as regularization method, modern pipelines often favor more robust techniques such as dropout and weight decay. This preference stems from the observation that combining these established techniques with noise input can adversely affect model performance. In this study, we propose a novel pretraining pipeline that learns to generate conditional noise mask specifically tailored to improve performance on multi-modal and multi-organ datasets. As a reinforcement learning algorithm, our approach employs a dual-component system comprising a very light-weight policy network that learns to sample conditional noise using a differentiable beta distribution as well as a classifier network. The policy network is trained using the reinforce algorithm to generate image-specific noise masks that regularize the classifier during pretraining. A key aspect is that the policy network's role is limited to obtaining an intermediate (or heated) model before fine-tuning. During inference, the policy network is omitted, allowing direct comparison between the baseline and noise-regularized models. We conducted experiments and related analyses on RadImageNet datasets. Results demonstrate that fine-tuning the intermediate models consistently outperforms conventional training algorithms on both classification and generalization to unseen concept tasks.

  • 2 authors
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Apr 29, 2024

Xplainer: From X-Ray Observations to Explainable Zero-Shot Diagnosis

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

  • 6 authors
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Mar 23, 2023

Rare Disease Differential Diagnosis with Large Language Models at Scale: From Abdominal Actinomycosis to Wilson's Disease

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).

  • 3 authors
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Feb 20, 2025 2

EarlyDx: An Admission-Anchored Benchmark for Open-Ended Generation of Evidence-Supported ED-Encounter Diagnoses

Clinical diagnosis at hospital admission must be made rapidly from limited, incomplete evidence. Existing diagnosis-prediction benchmarks are poorly suited to this setting: they restrict prediction to closed code sets, exclude free-text notes, and supervise with discharge diagnoses that incorporate the full inpatient course. We introduce EarlyDx, a large-scale benchmark for open-ended early diagnosis, built from 154,834 emergency department encounters in MIMIC-IV. Each encounter is restricted to records available at admission time t_0 and supervised by the diagnoses recorded during the ED encounter rather than at discharge. An LLM auditor further verifies every free-text label as supported, partially supported, or unsupported by that evidence; the primary evaluation scores only fully supported labels. Under a semantic LLM-as-judge protocol, no evaluated system --- frontier general, medical-specialized, or in-domain post-trained --- synthesizes admission-time evidence reliably. Zero-shot models score largely by extraction, recovering only 3-31% of diagnoses that must be inferred rather than read from the record; post-training raises inference-dependent recall to 56%, but a sizeable margin remains, and on time-critical conditions no system attains a clinician's balance of sensitivity and precision. We release the full construction and evaluation pipeline at here.

  • 8 authors
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Jul 29

Robust and Interpretable Medical Image Classifiers via Concept Bottleneck Models

Medical image classification is a critical problem for healthcare, with the potential to alleviate the workload of doctors and facilitate diagnoses of patients. However, two challenges arise when deploying deep learning models to real-world healthcare applications. First, neural models tend to learn spurious correlations instead of desired features, which could fall short when generalizing to new domains (e.g., patients with different ages). Second, these black-box models lack interpretability. When making diagnostic predictions, it is important to understand why a model makes a decision for trustworthy and safety considerations. In this paper, to address these two limitations, we propose a new paradigm to build robust and interpretable medical image classifiers with natural language concepts. Specifically, we first query clinical concepts from GPT-4, then transform latent image features into explicit concepts with a vision-language model. We systematically evaluate our method on eight medical image classification datasets to verify its effectiveness. On challenging datasets with strong confounding factors, our method can mitigate spurious correlations thus substantially outperform standard visual encoders and other baselines. Finally, we show how classification with a small number of concepts brings a level of interpretability for understanding model decisions through case studies in real medical data.

  • 11 authors
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Oct 4, 2023

Sycophants in the Courtroom: Are LLMs Fragile to Juridical Authority and Evolving Legal Standards?

In medicine, claims remain valid when supported by empirical evidence grounded in stable biological reality. In law, by contrast, truth is contingent, defined by jurisdiction, temporal validity, and the hierarchy of authoritative sources. The recent success of large language models (LLMs) on medical licensing examinations has encouraged an expectation of comparable legal competence. This analogy, however, obscures a critical distinction between domains. Unlike in medicine, legal performance often depends less on inference than on determining when external authority is applicable, valid, and non-contradictory. We introduce a comparative diagnostic framework evaluating legal reasoning against medical baselines along four axes (knowledge recall, grounding, confidence, and robustness), uncovering a sharp domain asymmetry when applied to a new benchmark that encodes temporal validity and normative relationships. While medical LLMs reliably benefit from verified sources, legal LLMs struggle to assess when retrieved citations are useful or misleading, exhibiting overconfidence in perturbed contexts and sensitivity to superficial formatting cues. Increased model scale amplifies this tendency, revealing that stronger instruction following can coincide with weaker resistance to authoritative perturbations. These findings show that LLMs treat law as unstructured text rather than binding precedent, while revealing a tendency to over-trust authoritative but false information when external references conflict with a model's internal knowledge.

  • 6 authors
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Aug 9

POCOVID-Net: Automatic Detection of COVID-19 From a New Lung Ultrasound Imaging Dataset (POCUS)

With the rapid development of COVID-19 into a global pandemic, there is an ever more urgent need for cheap, fast and reliable tools that can assist physicians in diagnosing COVID-19. Medical imaging such as CT can take a key role in complementing conventional diagnostic tools from molecular biology, and, using deep learning techniques, several automatic systems were demonstrated promising performances using CT or X-ray data. Here, we advocate a more prominent role of point-of-care ultrasound imaging to guide COVID-19 detection. Ultrasound is non-invasive and ubiquitous in medical facilities around the globe. Our contribution is threefold. First, we gather a lung ultrasound (POCUS) dataset consisting of 1103 images (654 COVID-19, 277 bacterial pneumonia and 172 healthy controls), sampled from 64 videos. This dataset was assembled from various online sources, processed specifically for deep learning models and is intended to serve as a starting point for an open-access initiative. Second, we train a deep convolutional neural network (POCOVID-Net) on this 3-class dataset and achieve an accuracy of 89% and, by a majority vote, a video accuracy of 92% . For detecting COVID-19 in particular, the model performs with a sensitivity of 0.96, a specificity of 0.79 and F1-score of 0.92 in a 5-fold cross validation. Third, we provide an open-access web service (POCOVIDScreen) that is available at: https://pocovidscreen.org. The website deploys the predictive model, allowing to perform predictions on ultrasound lung images. In addition, it grants medical staff the option to (bulk) upload their own screenings in order to contribute to the growing public database of pathological lung ultrasound images. Dataset and code are available from: https://github.com/jannisborn/covid19_pocus_ultrasound. NOTE: This preprint is superseded by our paper in Applied Sciences: https://doi.org/10.3390/app11020672

  • 7 authors
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Apr 25, 2020

Pathology-CoT: Learning Visual Chain-of-Thought Agent from Expert Whole Slide Image Diagnosis Behavior

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

zhihuanglab Zhi Huang Lab
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Oct 6, 2025 2

MedCaseReasoning: Evaluating and learning diagnostic reasoning from clinical case reports

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

  • 10 authors
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May 16, 2025 2

Private, fair and accurate: Training large-scale, privacy-preserving AI models in medical imaging

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.

  • 9 authors
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Feb 3, 2023

Beyond True or False: Retrieval-Augmented Hierarchical Analysis of Nuanced Claims

Claims made by individuals or entities are oftentimes nuanced and cannot be clearly labeled as entirely "true" or "false" -- as is frequently the case with scientific and political claims. However, a claim (e.g., "vaccine A is better than vaccine B") can be dissected into its integral aspects and sub-aspects (e.g., efficacy, safety, distribution), which are individually easier to validate. This enables a more comprehensive, structured response that provides a well-rounded perspective on a given problem while also allowing the reader to prioritize specific angles of interest within the claim (e.g., safety towards children). Thus, we propose ClaimSpect, a retrieval-augmented generation-based framework for automatically constructing a hierarchy of aspects typically considered when addressing a claim and enriching them with corpus-specific perspectives. This structure hierarchically partitions an input corpus to retrieve relevant segments, which assist in discovering new sub-aspects. Moreover, these segments enable the discovery of varying perspectives towards an aspect of the claim (e.g., support, neutral, or oppose) and their respective prevalence (e.g., "how many biomedical papers believe vaccine A is more transportable than B?"). We apply ClaimSpect to a wide variety of real-world scientific and political claims featured in our constructed dataset, showcasing its robustness and accuracy in deconstructing a nuanced claim and representing perspectives within a corpus. Through real-world case studies and human evaluation, we validate its effectiveness over multiple baselines.

  • 3 authors
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Jun 12, 2025 2

Cross-Modal Clinical Knowledge Integration for Mammography Report Generation

Breast cancer is a major global health concern, and mammography screening plays a central role in early detection. The large volume of screening examinations creates a substantial workload for radiologists, making accurate and consistent report generation a critical clinical challenge. Existing automated mammography report generation methods primarily focus on direct visual-to-text mapping, while overlooking the structured clinical reasoning process followed by radiologists in real-world practice. To address this limitation, we propose MammoRG, a mammography report generation framework that explicitly simulates the clinical reporting workflow by following the BI-RADS guideline and incorporating prior clinical knowledge to produce diagnostic reports. Specifically, MammoRG adopts a two-stage training framework. In the first stage, the model learns to integrate clinically relevant prior knowledge from a patient's four-view mammograms through classification-based supervision. In the second stage, a terminology-aware supervised fine-tuning strategy is introduced to model mammography-specific clinical terms as atomic semantic units, enabling the generation of high-quality reports with improved clinical consistency. To facilitate clinical efficacy evaluation of generated reports, we further develop MammoRGTool, a dedicated mammography report parsing tool that extracts structured clinical information from free-text reports. Extensive experiments demonstrate that MammoRG consistently outperforms existing methods across multiple clinical efficacy metrics, particularly in diagnosis-related BI-RADS F1, where it surpasses the second-best model by 2.73%, 2.04%, 1.90%, and 3.27% on the internal, external 1, external 2, and VinDr-Mammo datasets, respectively.

  • 10 authors
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May 28