Daily Papers

Emerging personal AI agents are moving toward persistent, multi-source memory. This creates an evaluation problem: systems must decide how to use conflicting or incomplete evidence; they cannot just retrieve facts from one clean history. Existing benchmarks rarely show whether an error came from the evidence given to a method or from the method's conflict-resolution step. We study this as selective QA over conflicting multi-source personal memory: systems answer based on conflicting, sometimes incomplete sources, or abstain when evidence is insufficient. We develop a benchmark containing 18 question templates across 8 reasoning types, 480 personas, 4 random seeds, and 34,560 instances, with controlled source distortions and deterministic ground truth. We evaluate the performance of baselines without access to any source, access to a single source, structured fusion methods, and frontier LLMs. The best trained fusion resolver reaches 80.3% accuracy, while the strongest prompt-only LLM baseline reaches 70.0%. With abstention, the same resolver reaches 85.3% selective accuracy at 78.3% coverage and the best LLM reaches 71.0% selective accuracy at 95.4% coverage. Different models have different strengths across reasoning types. We release the data, code, cached model outputs, and data-generating process for reuse.

Continuous episodic memory is a core capability for autonomous agents operating in dynamic, real-world environments, yet current streaming video benchmarks provide limited tools for diagnosing what models remember and for how long. We introduce Egostream, a diagnostic benchmark for streaming episodic memory evaluation in egocentric vision. \egostream organizes 2,250 curated questions along seven cognitive dimensions: detail, spatial, temporal, event, social, causal, and prospective memory. We introduce the Answer Validity Window (AVW), which specifies the temporal span an answer remains valid as the observed scene evolves. This allows us to expand the questions into 8,528 recall-conditioned evaluations, enabling controlled testing from instant to ultra-long-term recall while separating genuine model forgetting from natural world-state changes. We rigorously establish baseline performance through a unified streaming MLLM framework that compares several state-of-the-art memory-management mechanisms, covering sliding windows, attention sinks, KV-cache pruning, merging, and offloading. Experiments within a unified Qwen3-VL backbone reveal that comparable aggregate accuracies mask starkly different memory profiles. For instance, token pruning preserves fine-grained details and temporal structure significantly better than token merging, while quantized offloading rescues ultra-long-term recall. Ultimately, all mechanisms operate well below real-time (>1s per frame), and top performing methods ceil at about 45% accuracy, exposing critical gaps in current architectures. Egostream provides the diagnostic testbed needed to close these gaps. Project website, news and updates at: https://saroo25.github.io/Egostream/

Vision-language models (VLMs) excel on visual question answering and multimodal reasoning benchmarks. Yet their capability on ultra-resolution images - where critical evidence is tiny, subtle, spatially distant, or distributed - remains unclear. Existing evaluations largely report final-answer accuracy, offering limited insight into whether models acquire and integrate the necessary visual evidence. We introduce UltraVR, a diagnostic benchmark for evidence-grounded visual reasoning over ultra-resolution images. UltraVR spans four high-value scenarios: CCTV surveillance, remote sensing (RS), whole-slide image (WSI) pathology, and industrial anomaly detection (AD). These domains pose complementary challenges: fine-grained object grounding in crowded CCTV scenes, long-range spatial comparison in RS, multi-scale evidence navigation in WSI, and subtle irregularity detection in repetitive industrial layouts. Beyond standard QA triples, each instance includes a structured ground-truth chain of thought with step-level questions, intermediate answers, and reasoning labels. These labels decompose reasoning into evidence grounding, local perception, quantification, evidence integration, and decision inference, enabling process-level diagnosis over black-box scoring. Using UltraVR, we evaluate frontier VLMs and show that current models remain far from reliable on ultra-resolution reasoning. Importantly, the structured annotations allow us to localize failures across the visual-to-decision pipeline: errors concentrate in evidence grounding and local perception, while downstream inference often recovers when intermediate visual facts are supplied. These findings demonstrate UltraVR as a diagnostic testbed for measuring not only whether VLMs answer correctly, but where their ultra-resolution reasoning process breaks.

Recent advances in agentic Large Language Models (LLMs) have positioned them as generalist planners capable of reasoning and acting across diverse tasks. However, existing agent benchmarks largely focus on symbolic or weakly grounded environments, leaving their performance in physics-constrained real-world domains underexplored. We introduce AstroReason-Bench, a comprehensive benchmark for evaluating agentic planning in Space Planning Problems (SPP), a family of high-stakes problems with heterogeneous objectives, strict physical constraints, and long-horizon decision-making. AstroReason-Bench integrates multiple scheduling regimes, including ground station communication and agile Earth observation, and provides a unified agent-oriented interaction protocol. Evaluating on a range of state-of-the-art open- and closed-source agentic LLM systems, we find that current agents substantially underperform specialized solvers, highlighting key limitations of generalist planning under realistic constraints. AstroReason-Bench offers a challenging and diagnostic testbed for future agentic research.

Equation discovery from data is a core challenge in machine learning for science, requiring the recovery of concise symbolic expressions that govern complex physical and geometric phenomena. Recent approaches with large language models (LLMs) show promise in symbolic regression, but their success often hinges on memorized formulas or overly simplified functional forms. Existing benchmarks exacerbate this limitation: they focus on scalar functions, ignore domain grounding, and rely on brittle string-matching based metrics that fail to capture scientific equivalence. We introduce SurfaceBench, first comprehensive benchmark for symbolic surface discovery. SurfaceBench comprises 183 tasks across 15 categories of symbolic complexity, spanning explicit, implicit, and parametric equation representation forms. Each task includes ground-truth equations, variable semantics, and synthetically sampled three dimensional data. Unlike prior SR datasets, our tasks reflect surface-level structure, resist LLM memorization through novel symbolic compositions, and are grounded in scientific domains such as fluid dynamics, robotics, electromagnetics, and geometry. To evaluate equation discovery quality, we pair symbolic checks with geometry-aware metrics such as Chamfer and Hausdorff distances, capturing both algebraic fidelity and spatial reconstruction accuracy. Our experiments reveal that state-of-the-art frameworks, while occasionally successful on specific families, struggle to generalize across representation types and surface complexities. SurfaceBench thus establishes a challenging and diagnostic testbed that bridges symbolic reasoning with geometric reconstruction, enabling principled benchmarking of progress in compositional generalization, data-driven scientific induction, and geometry-aware reasoning with LLMs. We release the code here: https://github.com/Sanchit-404/surfacebench

While recent text-guided video editing models excel at elementary tasks (e.g., style transfer, object insertion), real-world user requests are highly compositional. A single prompt often demands multiple coupled edits, such as modifying subjects, actions, and camera views, while strictly preserving unrelated spatiotemporal content. Existing benchmarks, heavily constrained by isolated edits and coarse global metrics, fail to diagnose how models handle such complex workflows. To address this gap, we introduce CoVEBench, a compositional video editing benchmark comprising 416 curated source videos, 626 multi-point editing instructions, and 9,990 fine-grained checklist items. Covering diverse editing dimensions, CoVEBench evaluates models via MLLM-judged instruction compliance and video fidelity, alongside automated metrics for video quality. Extensive experiments reveal that compositional editing remains a profound challenge: current models frequently omit edits, violate preservation constraints, or introduce artifacts when handling multiple operations simultaneously. CoVEBench provides a challenging, diagnostic testbed to advance video editing toward realistic user workflows.

While large audio language models (LALMs) have achieved remarkable progress in audio processing at the second- or minute-level scale, understanding hour-level audio remains a fundamental bottleneck. Existing benchmarks predominantly rely on short clips or artificially concatenated segments, failing to faithfully assess LALM capacity for long-range information comprehension in real-world scenarios such as podcasts and lengthy speeches. To address this gap, we introduce VoiceGiraffe, a novel benchmark designed to rigorously evaluate LALMs across diverse real-world scenarios, modalities, and languages under long-context settings. It comprises 1500 curated triplets structured into a dual-level taxonomy of single-hop perception and multi-hop reasoning. We evaluate a broad suite of open-source and proprietary LALMs against human performance. Results underscore three fundamental findings. First, VoiceGiraffe remains highly challenging and far from saturation. Second, we show that no single inference paradigm universally dominates. The E2E inference benefits models with native long-context audio understanding, cascaded caption aggregation stabilizes small models overwhelmed by hour-scale audio, and reasoning-enhanced cascading with external LLM helps weaker models but can bottleneck stronger proprietary systems. Third, we reveal long-range memory persistence as a key bottleneck. LALMs are better at answering questions that require connecting salient causal cues than those requiring sustained tracking of sparse events across long audio, whereas humans show the opposite pattern. These findings position VoiceGiraffe as a challenging and diagnostic testbed for long-form audio understanding, highlighting the need for LALMs with persistent memory and robust long-range aggregation.

Visual entity tracking is an innate cognitive ability in humans, yet it remains a critical bottleneck for Vision-Language Models (VLMs). This deficit is often obscured in existing video benchmarks by visual shortcuts. We introduce VET-Bench, a synthetic diagnostic testbed featuring visually identical objects that necessitate tracking exclusively through spatiotemporal continuity. Our experiments reveal that current state-of-the-art VLMs perform at or near chance level on VET-Bench, exposing a fundamental limitation: an over-reliance on static frame-level features and a failure to maintain entity representations over time. We provide a theoretical analysis drawing connections to the state-tracking problem, proving that fixed-depth transformer-based VLMs are fundamentally limited in tracking indistinguishable objects without intermediate supervision due to expressivity constraints. To address this, we propose Spatiotemporal Grounded Chain-of-Thought (SGCoT): generating object trajectories as explicit intermediate states. Leveraging Molmo2's object tracking ability, we elicit SGCoT reasoning by fine-tuning on synthesized text-only data for alignment. Our method achieves state-of-the-art accuracy exceeding 90% on VET-Bench, demonstrating that VLMs can reliably solve the video shell-game task end-to-end without external tools. Our code and data are available at https://vetbench.github.io .

Recovering editable CAD programs from images or 3D observations is central to AI-assisted design, but progress is difficult to measure because existing evaluations are fragmented across datasets, modalities, and metrics. We introduce CADBench, a unified benchmark for multimodal CAD program generation. CADBench contains 18,000 evaluation samples spanning six benchmark families derived from DeepCAD, Fusion 360, ABC, MCB, and Objaverse; five input modalities including clean meshes, noisy meshes, single-view renders, photorealistic renders, and multi-view renders; and six metrics covering geometric fidelity, executability, and program compactness. STEP-based families are stratified by B-rep face count and all families are diversity-sampled to support controlled analysis across complexity and object variation. We benchmark eleven CAD-specialized and general-purpose vision-language systems, generating more than 1.4 million CAD programs. Under idealized inputs, specialized mesh-to-CAD models substantially outperform code-generating VLMs, which remain far from reliable CAD program reconstruction. CADBench further reveals three recurring failure modes: reconstruction quality degrades with geometric complexity, CAD-specialized models can be brittle under modality shift, and model rankings change across metrics. Together, these results position CADBench as a diagnostic testbed for measuring progress in editable 3D reconstruction and multimodal CAD understanding. The benchmark is publicly available at https://huggingface.co/datasets/DeCoDELab/CADBench.

Large language models often produce hallucinated answers that violate prompt-level constraints. A key diagnostic question is whether these failures reflect missing knowledge, or whether the model has the relevant information but follows the wrong inference path. We study this phenomenon as inference misalignment: a mismatch between the answer supported by the prompt and the answer favored by statistically salient latent associations. We formalize this view with a latent key-task model, in which pretraining-frequency imbalance can cause a shortcut path to dominate the constraint-sensitive path and induce positive inference loss. The framework predicts two failure modes: task-retrieval bias in entity disambiguation and key-selection bias in action choice. We introduce TrapQA, a controlled diagnostic testbed with two components. ScientistQA tests disambiguation among similar scientists with supplementary factual probes, while Real-Life Constrained QA tests everyday constraint following under salient shortcuts. Our results show that hallucination can arise from biased latent inference rather than absent knowledge alone.

Speculative decoding accelerates LLM inference, but SOTA hidden-state-based drafters suffer from long-range decay: draft accuracy degrades as the speculative step increases. Existing work attributes this decay to train-inference mismatch and proposes test-time training (TTT) as a remedy, yet we observe that long-range decay persists even in TTT-trained drafters. We revisit long-range decay from the perspective of context information preservation. In hidden-state reuse, we argue the target hidden state acts as a biased context compression: it aggregates historical token information according to the attention query at the current position, yielding a compact representation optimized for immediate next-token prediction. This compression can suppress information less relevant to the current query but important for later speculative steps. In contrast, the target model's KV cache serves as an explicit context, retaining the complete set of token-wise KV representations. We therefore posit the KV-Reuse Hypothesis: allowing the draft model to reuse the target KV cache can provide richer signals for long-horizon drafting. To test this hypothesis, we introduce KVShot, a diagnostic framework that compares three reuse paradigms: hidden-only, KV-only, and hybrid. Extensive evaluations on Qwen3-8B show that KV-Reuse improves long-range acceptance, although end-to-end speedups remain marginal under current training pipelines. Our analysis identifies two key structural bottlenecks: shallow drafters struggle to estimate target queries accurately, and draft-side KV projections receive sparse gradient signals. These findings suggest that realizing the full potential of KV-aware decoding requires moving beyond TTT toward block-wise training paradigms. By exposing these bottlenecks, KVShot provides a foundational diagnostic testbed and a clear roadmap for designing next-generation inference architectures.

Next-generation AI must manage vast personal data, diverse tools, and multi-step reasoning, yet most benchmarks remain context-free and single-turn. We present ASTRA-bench (Assistant Skills in Tool-use, Reasoning \& Action-planning), a benchmark that uniquely unifies time-evolving personal context with an interactive toolbox and complex user intents. Our event-driven pipeline generates 2,413 scenarios across four protagonists, grounded in longitudinal life events and annotated by referential, functional, and informational complexity. Evaluation of state-of-the-art models (e.g., Claude-4.5-Opus, DeepSeek-V3.2) reveals significant performance degradation under high-complexity conditions, with argument generation emerging as the primary bottleneck. These findings expose critical limitations in current agents' ability to ground reasoning within messy personal context and orchestrate reliable multi-step plans. We release ASTRA-bench with a full execution environment and evaluation scripts to provide a diagnostic testbed for developing truly context-aware AI assistants.

Audio-visual generation is rapidly advancing from short clips to minute-long content, while existing evaluation protocols remain largely confined to short-form settings. Existing benchmarks primarily focus on 5--10 second text-conditioned generation and rarely support unified evaluation across text, image, and video conditioning modalities. Moreover, they provide limited insight into how identity consistency, narrative coherence, and audio-visual alignment degrade over extended temporal horizons. To bridge this gap, we introduce LongAV-Compass, a systematic benchmark for minute-long audio-visual generation. LongAV-Compass contains 284 curated test cases spanning text-to-audio-video (T2AV), image-to-audio-video (I2AV), and video-to-audio-video (V2AV), organized by application scenario and generation complexity. The benchmark combines taxonomy-guided benchmark construction with a unified evaluation framework that integrates MLLM-assisted assessment with complementary perceptual and multimodal metrics, including DINO-v2, ArcFace, CLIP, and ImageBind. The framework evaluates more than 20 fine-grained dimensions covering within-segment quality, cross-segment consistency, global narrative coherence, semantic alignment, and audio-visual synchronization. Through experiments on 11 representative models together with human-alignment validation, LongAV-Compass provides a diagnostic testbed for analyzing the limitations of current systems in sustaining coherent, semantically aligned, and temporally consistent minute-scale audio-visual generation across diverse input modalities.

Text-to-Audio-Video (T2AV) generation aims to synthesize temporally coherent video and semantically synchronized audio from natural language, yet its evaluation remains fragmented, often relying on unimodal metrics or narrowly scoped benchmarks that fail to capture cross-modal alignment, instruction following, and perceptual realism under complex prompts. To address this limitation, we present T2AV-Compass, a unified benchmark for comprehensive evaluation of T2AV systems, consisting of 500 diverse and complex prompts constructed via a taxonomy-driven pipeline to ensure semantic richness and physical plausibility. Besides, T2AV-Compass introduces a dual-level evaluation framework that integrates objective signal-level metrics for video quality, audio quality, and cross-modal alignment with a subjective MLLM-as-a-Judge protocol for instruction following and realism assessment. Extensive evaluation of 11 representative T2AVsystems reveals that even the strongest models fall substantially short of human-level realism and cross-modal consistency, with persistent failures in audio realism, fine-grained synchronization, instruction following, etc. These results indicate significant improvement room for future models and highlight the value of T2AV-Compass as a challenging and diagnostic testbed for advancing text-to-audio-video generation.

Video-based numerical reasoning provides a premier arena for testing whether Vision-Language Models (VLMs) truly "understand" real-world dynamics, as accurate numerical deduction necessitates a profound grasp of temporal events, object permanence, and compositional logic beyond superficial pattern matching. However, existing benchmarks are often confined to narrow domains, such as repetitive athletic motions, or treat simple counting merely as a superficial regression task, failing to assess multi-step numerical logic within the inherent complexity of real-world multimedia content. We introduce VidNum-1.4K, a comprehensive VideoQA benchmark comprising 1,379 strictly human-annotated video-question pairs designed to evaluate genuine numerical reasoning across highly diverse environments, encompassing object, action, and event quantification. The VidNum-1.4K is uniquely structured into a three-level hierarchy that evolves from direct visual perception to video-based compositional numerical reasoning, requiring models to perform arithmetic operations, comparisons, and logical deductions grounded in temporal evidence. Our evaluations across a diverse suite of state-of-the-art VLMs reveal a striking reasoning gap: while the Gemini-3.1-pro barely reaches a 60% accuracy threshold, representative open-source families struggle heavily in the 25%--45% range. These findings demonstrate that current VLMs still lack a stable "internal world model", positioning VidNum-1.4K as a demanding diagnostic testbed for the next generation of numerical video intelligence.

Pretrained Multimodal Large Language Models (MLLMs) are increasingly deployed in medical AI systems for clinical reasoning, diagnosis support, and report generation. However, their training on sensitive patient data raises critical privacy and compliance challenges under regulations such as HIPAA and GDPR, which enforce the "right to be forgotten". Unlearning, the process of tuning models to selectively remove the influence of specific training data points, offers a potential solution, yet its effectiveness in complex medical settings remains underexplored. To systematically study this, we introduce MedForget, a Hierarchy-Aware Multimodal Unlearning Testbed with explicit retain and forget splits and evaluation sets containing rephrased variants. MedForget models hospital data as a nested hierarchy (Institution -> Patient -> Study -> Section), enabling fine-grained assessment across eight organizational levels. The benchmark contains 3840 multimodal (image, question, answer) instances, each hierarchy level having a dedicated unlearning target, reflecting distinct unlearning challenges. Experiments with four SOTA unlearning methods on three tasks (generation, classification, cloze) show that existing methods struggle to achieve complete, hierarchy-aware forgetting without reducing diagnostic performance. To test whether unlearning truly deletes hierarchical pathways, we introduce a reconstruction attack that progressively adds hierarchical level context to prompts. Models unlearned at a coarse granularity show strong resistance, while fine-grained unlearning leaves models vulnerable to such reconstruction. MedForget provides a practical, HIPAA-aligned testbed for building compliant medical AI systems.

Recent interest in multimodal large language models (MLLMs) raises a central question: can they reason over dynamic visual evidence rather than merely recognize objects or events in individual frames? This ability, which we refer to as video temporal-logical reasoning, requires models to maintain, update, and compose evidence as visual states evolve across frames. Existing video benchmarks often conflate this capability with scene complexity, static recognition, or uncontrolled temporal variation. To isolate this capability, we introduce Video-MME-Logical, a controlled benchmark organized around five temporal-logical operations: state tracking, sequential counting, temporal ordering, dynamic spatiality, and structural composition. The benchmark contains 25 fine-grained task categories generated with controlled object states, transitions, temporal dependencies, and logical compositions. It enables difficulty-controlled final-answer evaluation by varying temporal horizon and reasoning complexity, and supports intermediate-state diagnostics by verifying whether models recover the required logical reasoning trace before producing the final answer. Experiments with state-of-the-art MLLMs reveal a substantial human-model gap, especially as temporal-logical complexity increases. Supervised fine-tuning on up to 500K generated samples improves performance but remains insufficient to close the reasoning gap, positioning Video-MME-Logical as a scalable testbed for analyzing and improving temporal-logical reasoning in MLLMs.

Continuous perception, the ability to integrate visual observations over time in a continuous stream fashion, is essential for robust real-world understanding, yet remains largely untested in current multimodal models. We introduce CP-Bench, a minimal and fully controlled benchmark designed to isolate this capability using an extremely simple task: counting identical cubes in a synthetic scene while the camera moves and only reveals subsets of objects at any moment. Despite the simplicity of the setting, we find that state-of-the-art open-source and commercial models, including Qwen-3-VL, InternVL3, GPT-5, and Gemini-3-Pro, fail dramatically. A static-camera control variant confirms that the failure arises not from object recognition but from an inability to accumulate evidence across time. Further experiments show that neither higher sampling FPS, perception- or spatial-enhanced models, nor finetuning with additional videos leads to meaningful cross-temporal generalization. Our results reveal a fundamental limitation in modern multimodal architectures and training paradigms. CP-Bench provides a simple yet powerful diagnostic tool and establishes a clean testbed for developing models capable of genuine time-consistent visual reasoning.

Spoken query retrieval is an important interaction mode in modern information retrieval. However, existing evaluation datasets are often limited to simple queries under constrained noise conditions, making them inadequate for assessing the robustness of spoken query retrieval systems under complex acoustic perturbations. To address this limitation, we present SQuTR, a robustness benchmark for spoken query retrieval that includes a large-scale dataset and a unified evaluation protocol. SQuTR aggregates 37,317 unique queries from six commonly used English and Chinese text retrieval datasets, spanning multiple domains and diverse query types. We synthesize speech using voice profiles from 200 real speakers and mix 17 categories of real-world environmental noise under controlled SNR levels, enabling reproducible robustness evaluation from quiet to highly noisy conditions. Under the unified protocol, we conduct large-scale evaluations on representative cascaded and end-to-end retrieval systems. Experimental results show that retrieval performance decreases as noise increases, with substantially different drops across systems. Even large-scale retrieval models struggle under extreme noise, indicating that robustness remains a critical bottleneck. Overall, SQuTR provides a reproducible testbed for benchmarking and diagnostic analysis, and facilitates future research on robustness in spoken query to text retrieval.

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

Clinical diagnosis is critical in medical practice, typically requiring a continuous and evolving process that includes primary diagnosis, differential diagnosis, and final diagnosis. However, most existing clinical diagnostic tasks are single-step processes, which does not align with the complex multi-step diagnostic procedures found in real-world clinical settings. In this paper, we propose a multi-step diagnostic task and annotate a clinical diagnostic dataset (MSDiagnosis). This dataset includes primary diagnosis, differential diagnosis, and final diagnosis questions. Additionally, we propose a novel and effective framework. This framework combines forward inference, backward inference, reflection, and refinement, enabling the LLM to self-evaluate and adjust its diagnostic results. To assess the effectiveness of our proposed method, we design and conduct extensive experiments. The experimental results demonstrate the effectiveness of the proposed method. We also provide a comprehensive experimental analysis and suggest future research directions for this task.

This paper introduces a new testbed CLIFT (Clinical Shift) for the clinical domain Question-answering task. The testbed includes 7.5k high-quality question answering samples to provide a diverse and reliable benchmark. We performed a comprehensive experimental study and evaluated several QA deep-learning models under the proposed testbed. Despite impressive results on the original test set, the performance degrades when applied to new test sets, which shows the distribution shift. Our findings emphasize the need for and the potential for increasing the robustness of clinical domain models under distributional shifts. The testbed offers one way to track progress in that direction. It also highlights the necessity of adopting evaluation metrics that consider robustness to natural distribution shifts. We plan to expand the corpus by adding more samples and model results. The full paper and the updated benchmark are available at github.com/openlifescience-ai/clift

Pre-trained neural language models give high performance on natural language inference (NLI) tasks. But whether they actually understand the meaning of the processed sequences remains unclear. We propose a new diagnostics test suite which allows to assess whether a dataset constitutes a good testbed for evaluating the models' meaning understanding capabilities. We specifically apply controlled corruption transformations to widely used benchmarks (MNLI and ANLI), which involve removing entire word classes and often lead to non-sensical sentence pairs. If model accuracy on the corrupted data remains high, then the dataset is likely to contain statistical biases and artefacts that guide prediction. Inversely, a large decrease in model accuracy indicates that the original dataset provides a proper challenge to the models' reasoning capabilities. Hence, our proposed controls can serve as a crash test for developing high quality data for NLI tasks.

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.

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.

In this work, we introduce MedAgentSim, an open-source simulated clinical environment with doctor, patient, and measurement agents designed to evaluate and enhance LLM performance in dynamic diagnostic settings. Unlike prior approaches, our framework requires doctor agents to actively engage with patients through multi-turn conversations, requesting relevant medical examinations (e.g., temperature, blood pressure, ECG) and imaging results (e.g., MRI, X-ray) from a measurement agent to mimic the real-world diagnostic process. Additionally, we incorporate self improvement mechanisms that allow models to iteratively refine their diagnostic strategies. We enhance LLM performance in our simulated setting by integrating multi-agent discussions, chain-of-thought reasoning, and experience-based knowledge retrieval, facilitating progressive learning as doctor agents interact with more patients. We also introduce an evaluation benchmark for assessing the LLM's ability to engage in dynamic, context-aware diagnostic interactions. While MedAgentSim is fully automated, it also supports a user-controlled mode, enabling human interaction with either the doctor or patient agent. Comprehensive evaluations in various simulated diagnostic scenarios demonstrate the effectiveness of our approach. Our code, simulation tool, and benchmark are available at https://medagentsim.netlify.app/.

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.

Large language models (LLMs) are increasingly envisioned as decision-support tools in clinical practice, yet safe clinical reasoning demands integrating heterogeneous knowledge bases -- trials, primary studies, regulatory documents, and cost data -- under strict accuracy constraints. Existing evaluations often rely on synthetic prompts, reduce the task to single-hop factoid queries, or conflate reasoning with open-ended generation, leaving their real-world utility unclear. To close this gap, we present MedBrowseComp, the first benchmark that systematically tests an agent's ability to reliably retrieve and synthesize multi-hop medical facts from live, domain-specific knowledge bases. MedBrowseComp contains more than 1,000 human-curated questions that mirror clinical scenarios where practitioners must reconcile fragmented or conflicting information to reach an up-to-date conclusion. Applying MedBrowseComp to frontier agentic systems reveals performance shortfalls as low as ten percent, exposing a critical gap between current LLM capabilities and the rigor demanded in clinical settings. MedBrowseComp therefore offers a clear testbed for reliable medical information seeking and sets concrete goals for future model and toolchain upgrades. You can visit our project page at: https://moreirap12.github.io/mbc-browse-app/

Automated clinical diagnosis remains a core challenge in medical AI, which usually requires models to integrate multi-modal data and reason across complex, case-specific contexts. Although recent methods have advanced medical report generation (MRG) and visual question answering (VQA) with medical vision-language models (VLMs), these methods, however, predominantly operate under a sample-isolated inference paradigm, as such processing cases independently without access to longitudinal electronic health records (EHRs) or structurally related patient examples. This paradigm limits reasoning to image-derived information alone, which ignores external complementary medical evidence for potentially more accurate diagnosis. To overcome this limitation, we propose HyperWalker, a Deep Diagnosis framework that reformulates clinical reasoning via dynamic hypergraphs and test-time training. First, we construct a dynamic hypergraph, termed iBrochure, to model the structural heterogeneity of EHR data and implicit high-order associations among multimodal clinical information. Within this hypergraph, a reinforcement learning agent, Walker, navigates to and identifies optimal diagnostic paths. To ensure comprehensive coverage of diverse clinical characteristics in test samples, we incorporate a linger mechanism, a multi-hop orthogonal retrieval strategy that iteratively selects clinically complementary neighborhood cases reflecting distinct clinical attributes. Experiments on MRG with MIMIC and medical VQA on EHRXQA demonstrate that HyperWalker achieves state-of-the-art performance. Code is available at: https://github.com/Bean-Young/HyperWalker

The integration of Artificial Intelligence (AI), especially Large Language Models (LLMs), into the clinical diagnosis process offers significant potential to improve the efficiency and accessibility of medical care. While LLMs have shown some promise in the medical domain, their application in clinical diagnosis remains underexplored, especially in real-world clinical practice, where highly sophisticated, patient-specific decisions need to be made. Current evaluations of LLMs in this field are often narrow in scope, focusing on specific diseases or specialties and employing simplified diagnostic tasks. To bridge this gap, we introduce CliBench, a novel benchmark developed from the MIMIC IV dataset, offering a comprehensive and realistic assessment of LLMs' capabilities in clinical diagnosis. This benchmark not only covers diagnoses from a diverse range of medical cases across various specialties but also incorporates tasks of clinical significance: treatment procedure identification, lab test ordering and medication prescriptions. Supported by structured output ontologies, CliBench enables a precise and multi-granular evaluation, offering an in-depth understanding of LLM's capability on diverse clinical tasks of desired granularity. We conduct a zero-shot evaluation of leading LLMs to assess their proficiency in clinical decision-making. Our preliminary results shed light on the potential and limitations of current LLMs in clinical settings, providing valuable insights for future advancements in LLM-powered healthcare.

Given the dominance of dense retrievers that do not generalize well beyond their training dataset distributions, domain-specific test sets are essential in evaluating retrieval. There are few test datasets for retrieval systems intended for use by healthcare providers in a point-of-care setting. To fill this gap we have collaborated with medical professionals to create CURE, an ad-hoc retrieval test dataset for passage ranking with 2000 queries spanning 10 medical domains with a monolingual (English) and two cross-lingual (French/Spanish -> English) conditions. In this paper, we describe how CURE was constructed and provide baseline results to showcase its effectiveness as an evaluation tool. CURE is published with a Creative Commons Attribution Non Commercial 4.0 license and can be accessed on Hugging Face.

Scientific research based on multimodal clinical data (including medical imaging) requires coordinating clinical, radiological, programming, and biostatistical expertise, a fragmented process that bottlenecks discovery. We present VERITAS (Verifiable Epistemic Reasoning for Image-Derived Hypothesis Testing via Agentic Systems), a clinical co-scientist: a multi-agent system that autonomously tests natural-language hypotheses and produces a fully auditable evidence trail, tracing every conclusion through executable outputs from analysis plan to segmentation masks to statistical code to final verdict. Unlike prior AI-scientist systems, which mainly operate on tabular or text data, VERITAS grounds autonomous discovery directly in medical images. It decomposes the workflow into four phases handled by role-specialized agents, and introduces an epistemic evidence label framework that mechanically classifies outcomes as Supported, Refuted, Underpowered, or Invalid by jointly evaluating significance, effect direction, and study power. This distinction is critical in medical imaging, where non-significant results often reflect insufficient sample size rather than absent effects. We construct a tiered benchmark of 64 hypotheses spanning six complexity levels across cardiac and brain glioma MRI datasets. VERITAS reaches 81.4% verdict accuracy with frontier models and 71.2% with locally-hosted open-weight models (8-30B), outperforming all single-model baselines in both classes. It also produces the highest rate of independently verifiable statistical outputs (86.6%), so even its failures remain diagnosable through artifact inspection. Structured multi-agent decomposition thus substitutes for model scale while preserving the verifiability that scientific discovery demands. We release code, hypothesis bank, and evaluation pipeline at https://github.com/LucZot/veritas.

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.

Traditionally, AI research in medical diagnosis has largely centered on image analysis. While this has led to notable advancements, the absence of patient-reported symptoms continues to hinder diagnostic accuracy. To address this, we propose a Pre-Consultation Dialogue Framework (PCDF) that mimics real-world diagnostic procedures, where doctors iteratively query patients before reaching a conclusion. Specifically, we simulate diagnostic dialogues between two vision-language models (VLMs): a DocVLM, which generates follow-up questions based on the image and dialogue history, and a PatientVLM, which responds using a symptom profile derived from the ground-truth diagnosis. We additionally conducted a small-scale clinical validation of the synthetic symptoms generated by our framework, with licensed clinicians confirming their clinical relevance, symptom coverage, and overall realism. These findings indicate that the resulting DocVLM-PatientVLM interactions form coherent, multi-turn consultations paired with images and diagnoses, which we then use to fine-tune the DocVLM. This dialogue-based supervision leads to substantial gains over image-only training, highlighting the value of realistic symptom elicitation for diagnosis.

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.

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

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

Robust benchmarks are crucial for evaluating Multimodal Large Language Models (MLLMs). Yet we find that models can ace many multimodal benchmarks without strong visual understanding, instead exploiting biases, linguistic priors, and superficial patterns. This is especially problematic for vision-centric benchmarks that are meant to require visual inputs. We adopt a diagnostic principle for benchmark design: if a benchmark can be gamed, it will be. Designers should therefore try to ``game'' their own benchmarks first, using diagnostic and debiasing procedures to systematically identify and mitigate non-visual biases. Effective diagnosis requires directly ``training on the test set'' -- probing the released test set for its intrinsic, exploitable patterns. We operationalize this standard with two components. First, we diagnose benchmark susceptibility using a ``Test-set Stress-Test'' (TsT) methodology. Our primary diagnostic tool involves fine-tuning a powerful Large Language Model via k-fold cross-validation on exclusively the non-visual, textual inputs of the test set to reveal shortcut performance and assign each sample a bias score s(x). We complement this with a lightweight Random Forest-based diagnostic operating on hand-crafted features for fast, interpretable auditing. Second, we debias benchmarks by filtering high-bias samples using an ``Iterative Bias Pruning'' (IBP) procedure. Applying this framework to four benchmarks -- VSI-Bench, CV-Bench, MMMU, and VideoMME -- we uncover pervasive non-visual biases. As a case study, we apply our full framework to create VSI-Bench-Debiased, demonstrating reduced non-visual solvability and a wider vision-blind performance gap than the original.

Automated test generation holds great promise for alleviating the burdens of manual test creation. However, existing search-based techniques compromise on test readability, while LLM-based approaches are prohibitively expensive in practice. We present TestForge, an agentic unit testing framework designed to cost-effectively generate high-quality test suites for real-world code. Our key insight is to reframe LLM-based test generation as an iterative process. TestForge thus begins with tests generated via zero-shot prompting, and then continuously refines those tests based on feedback from test executions and coverage reports. We evaluate TestForge on TestGenEval, a real world unit test generation benchmark sourced from 11 large scale open source repositories; we show that TestForge achieves a pass@1 rate of 84.3%, 44.4% line coverage and 33.8% mutation score on average, outperforming prior classical approaches and a one-iteration LLM-based baseline. TestForge produces more natural and understandable tests compared to state-of-the-art search-based techniques, and offers substantial cost savings over LLM-based techniques (at $0.63 per file). Finally, we release a version of TestGenEval integrated with the OpenHands platform, a popular open-source framework featuring a diverse set of software engineering agents and agentic benchmarks, for future extension and development.

Leaf-lesion segmentation is topology-sensitive: small merges, splits, or false holes can be biologically meaningful descriptors of biochemical pathways, yet they are weakly penalized by standard pixel-wise losses in Euclidean latents. I explore HyperTopo-Adapters, a lightweight, parameter-efficient head trained on top of a frozen vision encoder, which embeds features on a product manifold -- hyperbolic + Euclidean + spherical (H + E + S) -- to encourage hierarchical separation (H), local linear detail (E), and global closure (S). A topology prior complements Dice/BCE in two forms: (i) persistent-homology (PH) distance for evaluation and selection, and (ii) a differentiable surrogate that combines a soft Euler-characteristic match with total variation regularization for stable training. I introduce warm-ups for both the hyperbolic contrastive term and the topology prior, per-sample evaluation of structure-aware metrics (Boundary-F1, Betti errors, PD distance), and a min-PD within top-K Dice rule for checkpoint selection. On a Kaggle leaf-lesion dataset (N=2,940), early results show consistent gains in boundary and topology metrics (reducing Delta beta_1 hole error by 9%) while Dice/IoU remain competitive. The study is diagnostic by design: I report controlled ablations (curvature learning, latent dimensions, contrastive temperature, surrogate settings), and ongoing tests varying encoder strength (ResNet-50, DeepLabV3, DINOv2/v3), input resolution, PH weight, and partial unfreezing of late blocks. The contribution is an open, reproducible train/eval suite (available at https://github.com/ChimdiWalter/HyperTopo-Adapters) that isolates geometric/topological priors and surfaces failure modes to guide stronger, topology-preserving architectures.

This paper presents a Patherea, a framework for point-based cell detection and classification that provides a complete solution for developing and evaluating state-of-the-art approaches. We introduce a large-scale dataset collected to directly replicate a clinical workflow for Ki-67 proliferation index estimation and use it to develop an efficient point-based approach that directly predicts point-based predictions, without the need for intermediate representations. The proposed approach effectively utilizes point proposal candidates with the hybrid Hungarian matching strategy and a flexible architecture that enables the usage of various backbones and (pre)training strategies. We report state-of-the-art results on existing public datasets - Lizard, BRCA-M2C, BCData, and the newly proposed Patherea dataset. We show that the performance on existing public datasets is saturated and that the newly proposed Patherea dataset represents a significantly harder challenge for the recently proposed approaches. We also demonstrate the effectiveness of recently proposed pathology foundational models that our proposed approach can natively utilize and benefit from. We also revisit the evaluation protocol that is used in the broader field of cell detection and classification and identify the erroneous calculation of performance metrics. Patherea provides a benchmarking utility that addresses the identified issues and enables a fair comparison of different approaches. The dataset and the code will be publicly released upon acceptance.

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

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

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.

Multimodal clinical models are usually judged on accuracy with every modality present, but deployment removes modalities; an echocardiogram is often unavailable where an ECG is routine. Two questions then matter beyond the size of the accuracy loss: which modality was responsible, and whether the model fails loudly or silently once that modality is dropped. The distinction is per-example and modality-level, and is separate from post-hoc feature attribution (e.g. SHAP). Models are replaced often; the evaluation that answers these questions is reused. We present a model-agnostic modality-failure framework: given N modality embeddings, any mask-aware probe, and labels, it returns a per-example failure taxonomy, a per-modality complementarity matrix that attributes error to modalities, and a loud-vs-silent dropout profile separating monitorable failures from those that pass unflagged far from the decision boundary, using only deployment-observable signals. We release it as a small, unit-tested harness and validate it against planted ground truth. Across seeds it recovers that planted modality dominance and complementary subset, reports per-modality loud-vs-silent rates, and scales to a three-modality complementarity matrix; because the planted structure is known by construction, this validates recovery of per-example attribution rather than clinical performance. We then instantiate the framework on frozen EchoJEPA and HuBERT-ECG embeddings for LVEF and the EF <= 40% HFrEF gate over a paired MIMIC-IV cohort, where on the held-out test split (n = 245) dropping echo nearly doubles error. The narrow echo-to-ECG overlap that bounds cohort size is itself a deployment finding for cardiac foundation models. All of our work can be found at https://github.com/criticaldata/PRIMED-AI.

The field of medical diagnosis has undergone a significant transformation with the advent of large language models (LLMs), yet the challenges of interpretability within these models remain largely unaddressed. This study introduces Chain-of-Diagnosis (CoD) to enhance the interpretability of LLM-based medical diagnostics. CoD transforms the diagnostic process into a diagnostic chain that mirrors a physician's thought process, providing a transparent reasoning pathway. Additionally, CoD outputs the disease confidence distribution to ensure transparency in decision-making. This interpretability makes model diagnostics controllable and aids in identifying critical symptoms for inquiry through the entropy reduction of confidences. With CoD, we developed DiagnosisGPT, capable of diagnosing 9604 diseases. Experimental results demonstrate that DiagnosisGPT outperforms other LLMs on diagnostic benchmarks. Moreover, DiagnosisGPT provides interpretability while ensuring controllability in diagnostic rigor.

Clinical trial matching is the task of identifying trials for which patients may be potentially eligible. Typically, this task is labor-intensive and requires detailed verification of patient electronic health records (EHRs) against the stringent inclusion and exclusion criteria of clinical trials. This process is manual, time-intensive, and challenging to scale up, resulting in many patients missing out on potential therapeutic options. Recent advancements in Large Language Models (LLMs) have made automating patient-trial matching possible, as shown in multiple concurrent research studies. However, the current approaches are confined to constrained, often synthetic datasets that do not adequately mirror the complexities encountered in real-world medical data. In this study, we present the first, end-to-end large-scale empirical evaluation of clinical trial matching using real-world EHRs. Our study showcases the capability of LLMs to accurately match patients with appropriate clinical trials. We perform experiments with proprietary LLMs, including GPT-4 and GPT-3.5, as well as our custom fine-tuned model called OncoLLM and show that OncoLLM, despite its significantly smaller size, not only outperforms GPT-3.5 but also matches the performance of qualified medical doctors. All experiments were carried out on real-world EHRs that include clinical notes and available clinical trials from a single cancer center in the United States.

Synthetic Data Generation (SDG) based on Artificial Intelligence (AI) can transform the way clinical medicine is delivered by overcoming privacy barriers that currently render clinical data sharing difficult. This is the key to accelerating the development of digital tools contributing to enhanced patient safety. Such tools include robust data-driven clinical decision support systems, and example-based digital training tools that will enable healthcare professionals to improve their diagnostic performance for enhanced patient safety. This study focuses on the clinical evaluation of medical SDG, with a proof-of-concept investigation on diagnosing Inflammatory Bowel Disease (IBD) using Wireless Capsule Endoscopy (WCE) images. Its scientific contributions include a) a novel protocol for the systematic Clinical Evaluation of Medical Image Synthesis (CEMIS); b) a novel variational autoencoder-based model for the generation of high-resolution synthetic WCE images; and c) a comprehensive evaluation of the synthetic images using the CEMIS protocol by 10 international WCE specialists, in terms of image quality, diversity, and realism, as well as their utility for clinical decision-making. The results show that TIDE-II generates clinically plausible, very realistic WCE images, of improved quality compared to relevant state-of-the-art generative models. Concludingly, CEMIS can serve as a reference for future research on medical image-generation techniques, while the adaptation/extension of the architecture of TIDE-II to other imaging domains can be promising.

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.

Currently, evaluating vision-language models (VLMs) in medical imaging tasks oversimplifies clinical reality by relying on pre-selected 2D images that demand significant manual labor to curate. This setup misses the core challenge of realworld diagnostics: a true clinical agent must actively navigate full 3D volumes across multiple sequences or modalities to gather evidence and ultimately support a final decision. To address this, we propose MEDOPENCLAW, an auditable runtime designed to let VLMs operate dynamically within standard medical tools or viewers (e.g., 3D Slicer). On top of this runtime, we introduce MEDFLOWBENCH, a full-study medical imaging benchmark covering multi-sequence brain MRI and lung CT/PET. It systematically evaluates medical agentic capabilities across viewer-only, tool-use, and open-method tracks. Initial results reveal a critical insight: while state-of-the-art LLMs/VLMs (e.g., Gemini 3.1 Pro and GPT-5.4) can successfully navigate the viewer to solve basic study-level tasks, their performance paradoxically degrades when given access to professional support tools due to a lack of precise spatial grounding. By bridging the gap between static-image perception and interactive clinical workflows, MEDOPENCLAW and MEDFLOWBENCH establish a reproducible foundation for developing auditable, full-study medical imaging agents.

Large language models (LLMs) trained with next-word-prediction have achieved success as clinical foundation models. Representations from these language backbones yield strong linear probe performance across biomedical tasks, suggesting that patient semantics emerge from next-token prediction at scale. However, this paradigm treats patients as a document to be summarized rather than a dynamical system to be simulated; a patient's trajectory emerges from their state evolving under interventions and time, requiring models that simulate dynamics rather than predict tokens. To address this, we introduce SMB-Structure, a world model for structured EHR that grounds a joint-embedding prediction architecture (JEPA) with next-token prediction (SFT). SFT grounds our model to reconstruct future patient states in token space, while JEPA predicts those futures in latent space from the initial patient representation alone, forcing trajectory dynamics to be encoded before the next state is observed. We validate across two large-scale cohorts: Memorial Sloan Kettering (23,319 oncology patients; 323,000+ patient-years) and INSPECT (19,402 pulmonary embolism patients). Using a linear probe evaluated at multiple points along the disease trajectory, we demonstrate that our training paradigm learns embeddings that capture disease dynamics not recoverable by autoregressive baselines, enabling SMB-Structure to achieve competitive performance on complex tasks characterized by high patient heterogeneity. Model weights are available at https://huggingface.co/standardmodelbio/SMB-v1-1.7B-Structure.

Most medical multimodal benchmarks focus on static tasks such as image question answering, report generation, and plain-language rewriting. Patient education is more demanding: systems must identify relevant evidence across images, show patients where to look, explain findings in accessible language, and handle confusion or distress. Yet most patient education work remains text-only, even though combined image-and-text explanations may better support understanding. We introduce MedImageEdu, a benchmark for multi-turn, evidence-grounded radiology patient education. Each case provides a radiology report with report text and case images. A DoctorAgent interacts with a PatientAgent, conditioned on a hidden profile that captures factors such as education level, health literacy, and personality. When a patient question would benefit from visual support, the DoctorAgent can issue drawing instructions grounded in the report, case images, and the current question to a benchmark-provided drawing tool. The tool returns image(s), after which the DoctorAgent produces a final multimodal response consisting of the image(s) and a grounded plain-language explanation. MedImageEdu contains 150 cases from three sources and evaluates both the consultation process and the final multimodal response along five dimensions: Consultation, Safety and Scope, Language Quality, Drawing Quality, and Image-Text Response Quality. Across representative open- and closed-source vision-language model agents, we find three consistent gaps: fluent language often outpaces faithful visual grounding, safety is the weakest dimension across disease categories, and emotionally tense interactions are harder than low education or low health literacy. MedImageEdu provides a controlled testbed for assessing whether multimodal agents can teach from evidence rather than merely answer from text.

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

Future short or long-term space missions require a new generation of monitoring and diagnostic systems due to communication impasses as well as limitations in specialized crew and equipment. Machine learning supported diagnostic systems present a viable solution for medical and technical applications. We discuss challenges and applicability of such systems in light of upcoming missions and outline an example use case for a next-generation medical diagnostic system for future space operations. Additionally, we present approach recommendations and constraints for the successful generation and use of machine learning models aboard a spacecraft.

The scaling laws and extraordinary performance of large foundation models motivate the development and utilization of such models in biomedicine. However, despite early promising results on some biomedical benchmarks, there are still major challenges that need to be addressed before these models can be used in real-world clinics. Frontier general-domain models such as GPT-4V still have significant performance gaps in multimodal biomedical applications. More importantly, less-acknowledged pragmatic issues, including accessibility, model cost, and tedious manual evaluation make it hard for clinicians to use state-of-the-art large models directly on private patient data. Here, we explore training open-source small multimodal models (SMMs) to bridge competency gaps for unmet clinical needs in radiology. To maximize data efficiency, we adopt a modular approach by incorporating state-of-the-art pre-trained models for image and text modalities, and focusing on training a lightweight adapter to ground each modality to the text embedding space, as exemplified by LLaVA-Med. For training, we assemble a large dataset of over 697 thousand radiology image-text pairs. For evaluation, we propose CheXprompt, a GPT-4-based metric for factuality evaluation, and demonstrate its parity with expert evaluation. For best practice, we conduct a systematic ablation study on various choices in data engineering and multimodal training. The resulting LlaVA-Rad (7B) model attains state-of-the-art results on standard radiology tasks such as report generation and cross-modal retrieval, even outperforming much larger models such as GPT-4V and Med-PaLM M (84B). The inference of LlaVA-Rad is fast and can be performed on a single V100 GPU in private settings, offering a promising state-of-the-art tool for real-world clinical applications.

How can we use AI to discover a new state of the art for a scientific problem? Prior work in test-time scaling, such as AlphaEvolve, performs search by prompting a frozen LLM. We perform reinforcement learning at test time, so the LLM can continue to train, but now with experience specific to the test problem. This form of continual learning is quite special, because its goal is to produce one great solution rather than many good ones on average, and to solve this very problem rather than generalize to other problems. Therefore, our learning objective and search subroutine are designed to prioritize the most promising solutions. We call this method Test-Time Training to Discover (TTT-Discover). Following prior work, we focus on problems with continuous rewards. We report results for every problem we attempted, across mathematics, GPU kernel engineering, algorithm design, and biology. TTT-Discover sets the new state of the art in almost all of them: (i) Erdős' minimum overlap problem and an autocorrelation inequality; (ii) a GPUMode kernel competition (up to 2times faster than prior art); (iii) past AtCoder algorithm competitions; and (iv) denoising problem in single-cell analysis. Our solutions are reviewed by experts or the organizers. All our results are achieved with an open model, OpenAI gpt-oss-120b, and can be reproduced with our publicly available code, in contrast to previous best results that required closed frontier models. Our test-time training runs are performed using Tinker, an API by Thinking Machines, with a cost of only a few hundred dollars per problem.

Clinical diagnosis prediction models, when provided with a patient's medical history, aim to detect potential diseases early, facilitating timely intervention and improving prognostic outcomes. However, the inherent scarcity of patient data and large disease candidate space often pose challenges in developing satisfactory models for this intricate task. The exploration of leveraging Large Language Models (LLMs) for encapsulating clinical decision processes has been limited. We introduce MERA, a clinical diagnosis prediction model that bridges pertaining natural language knowledge with medical practice. We apply hierarchical contrastive learning on a disease candidate ranking list to alleviate the large decision space issue. With concept memorization through fine-tuning, we bridge the natural language clinical knowledge with medical codes. Experimental results on MIMIC-III and IV datasets show that MERA achieves the state-of-the-art diagnosis prediction performance and dramatically elevates the diagnosis prediction capabilities of generative LMs.

Explaining deep learning models is essential for clinical integration of medical image analysis systems. A good explanation highlights if a model depends on spurious features that undermines generalization and harms a subset of patients or, conversely, may present novel biological insights. Although techniques like GradCAM can identify influential features, they are measurement tools that do not themselves form an explanation. We propose a human-machine-VLM interaction system tailored to explaining classifiers in computational pathology, including multi-instance learning for whole-slide images. Our proof of concept comprises (1) an AI-integrated slide viewer to run sliding-window experiments to test claims of an explanation, and (2) quantification of an explanation's predictiveness using general-purpose vision-language models. The results demonstrate that this allows us to qualitatively test claims of explanations and can quantifiably distinguish competing explanations. This offers a practical path from explainable AI to explained AI in digital pathology and beyond. Code and prompts are available at https://github.com/nki-ai/x2x.

Large Language Models (LLMs) have demonstrated significant enhancements in instruction-following abilities through instruction tuning, achieving notable performances across various tasks. Previous research has focused on fine-tuning medical domain-specific LLMs using an extensive array of medical-specific data, incorporating millions of pieces of biomedical literature to augment their medical capabilities. However, existing medical instruction-tuned LLMs have been constrained by the limited scope of tasks and instructions available, restricting the efficacy of instruction tuning and adversely affecting performance in the general domain. In this paper, we fine-tune LLaMA-series models using 52k diverse, machine-generated, medical instruction-following data, MedInstruct-52k, resulting in the model AlpaCare. Comprehensive experimental results on both general and medical-specific domain free-form instruction evaluations showcase AlpaCare's strong medical proficiency and generalizability compared to previous instruction-tuned models in both medical and general domains. We provide public access to our MedInstruct-52k dataset and a clinician-crafted free-form instruction test set, MedInstruct-test, along with our codebase, to foster further research and development. Our project page is available at https://github.com/XZhang97666/AlpaCare.

To generate evidence regarding the safety and efficacy of artificial intelligence (AI) enabled medical devices, AI models need to be evaluated on a diverse population of patient cases, some of which may not be readily available. We propose an evaluation approach for testing medical imaging AI models that relies on in silico imaging pipelines in which stochastic digital models of human anatomy (in object space) with and without pathology are imaged using a digital replica imaging acquisition system to generate realistic synthetic image datasets. Here, we release M-SYNTH, a dataset of cohorts with four breast fibroglandular density distributions imaged at different exposure levels using Monte Carlo x-ray simulations with the publicly available Virtual Imaging Clinical Trial for Regulatory Evaluation (VICTRE) toolkit. We utilize the synthetic dataset to analyze AI model performance and find that model performance decreases with increasing breast density and increases with higher mass density, as expected. As exposure levels decrease, AI model performance drops with the highest performance achieved at exposure levels lower than the nominal recommended dose for the breast type.

Timely and accurate lymphoma diagnosis is essential for guiding cancer treatment. Standard diagnostic practice combines hematoxylin and eosin (HE)-stained whole slide images with immunohistochemistry, flow cytometry, and molecular genetic tests to determine lymphoma subtypes, a process requiring costly equipment, skilled personnel, and causing treatment delays. Deep learning methods could assist pathologists by extracting diagnostic information from routinely available HE-stained slides, yet comprehensive benchmarks for lymphoma subtyping on multicenter data are lacking. In this work, we present the first multicenter lymphoma benchmarking dataset covering four common lymphoma subtypes and healthy control tissue. We systematically evaluate five publicly available pathology foundation models (H-optimus-1, H0-mini, Virchow2, UNI2, Titan) combined with attention-based (AB-MIL) and transformer-based (TransMIL) multiple instance learning aggregators across three magnifications (10x, 20x, 40x). On in-distribution test sets, models achieve multiclass balanced accuracies exceeding 80% across all magnifications, with all foundation models performing similarly and both aggregation methods showing comparable results. The magnification study reveals that 40x resolution is sufficient, with no performance gains from higher resolutions or cross-magnification aggregation. However, on out-of-distribution test sets, performance drops substantially to around 60%, highlighting significant generalization challenges. To advance the field, larger multicenter studies covering additional rare lymphoma subtypes are needed. We provide an automated benchmarking pipeline to facilitate such future research.

Recent advances in reasoning with large language models (LLMs)has shown remarkable reasoning capabilities in domains such as mathematics and coding, yet their application to clinical diagnosis remains underexplored. Here, we introduce ClinicalGPT-R1, a reasoning enhanced generalist large language model for disease diagnosis. Trained on a dataset of 20,000 real-world clinical records, ClinicalGPT-R1 leverages diverse training strategies to enhance diagnostic reasoning. To benchmark performance, we curated MedBench-Hard, a challenging dataset spanning seven major medical specialties and representative diseases. Experimental results demonstrate that ClinicalGPT-R1 outperforms GPT-4o in Chinese diagnostic tasks and achieves comparable performance to GPT-4 in English settings. This comparative study effectively validates the superior performance of ClinicalGPT-R1 in disease diagnosis tasks. Resources are available at https://github.com/medfound/medfound.

We present WBCBench 2026, an ISBI challenge and benchmark for automated WBC classification designed to stress-test algorithms under three key difficulties: (i) severe class imbalance across 13 morphologically fine-grained WBC classes, (ii) strict patient-level separation between training, validation and test sets, and (iii) synthetic scanner- and setting-induced domain shift via controlled noise, blur and illumination perturbations. All images are single-site microscopic blood smear acquisitions with standardised staining and expert hematopathologist annotations. This paper reviews the challenge and summarises the proposed solutions and final outcomes. The benchmark is organised into two phases. Phase 1 provides a pristine training set. Phase 2 introduces degraded images with split-specific severity distributions for train, validation and test, emulating a realistic shift between development and deployment conditions. We specify a standardised submission schema, open-source evaluator, and macro-averaged F1 score as the primary ranking metric.

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.

We introduce iTRIALSPACE, a programmable evaluation framework for controlled assessment of lung CT models. Standard benchmarks are static retrospective collections that entangle lesion size, lobe prevalence, anatomy, and acquisition context, making it difficult to determine what structurally drives model accuracy. iTRIALSPACE addresses this limitation by composing real clinical CTs and lesion profiles into controlled virtual lesion trials through a four-stage pipeline: multidataset nodule profiling, explicit trial specification, anatomy-aware mask insertion, and ControlNet-conditioned CT synthesis. The framework is built on a unified 54-attribute nodule-profile dataset spanning 13,140 annotated nodules from seven public CT sources and instantiated as 13 trial modes. We evaluate iTRIALSPACE in a 55,469-sample Virtual Lesion Study spanning three medical VLMs, four spatialguidance conditions, and three clinical tasks. Across all 13 modes, the synthetic substrate remains within the real-to-real FID baseline, and synthetic performance rankings transfer strongly to real clinical data (ρ = 0.93, p < 10^{-15}). Controlled trial modes expose findings unavailable to fixed-distribution benchmarks, including shortcut-driven size prediction collapse under lobe-equalized sampling and hostto-donor variance ratios of 8.9x and 3.3x in twin-cross analysis. These results position iTRIALSPACE as an auditable evaluation infrastructure for controlled, falsifiable testing beyond static retrospective benchmarks.

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.

Large language models (LLMs) show promise for clinical reasoning and decision support, but evaluation in realistic, electronic health record-congruent settings remains limited. Existing benchmarks often rely on static datasets or unstructured inputs that do not reflect the structured, interoperable data formats used in clinical systems. We introduce a pipeline for generating clinically realistic HL7 FHIR R4 bundles from unstructured text, enabling controllable evaluation of clinical decision support systems. The pipeline combines staged LLM generation with terminology-grounded validation and repair to reduce hallucinated codes and enforce structural and semantic consistency. Applying this approach to MedCaseReasoning, we construct MedCase-Structured, a synthetic dataset aligned with clinician-authored diagnostic cases, achieving valid FHIR generation for 82.5% of cases. Evaluation on MedCase-Structured reveals consistently lower diagnostic accuracy for LLMs on structured FHIR inputs than with plain text, highlighting the importance of deployment-aligned benchmarking.

Randomized controlled trials (RCTs) are the benchmark for causal inference, yet field implementation can deviate. We here present a remote audit - a design-based, preregistrable diagnostic that uses only pre-treatment satellite imagery to test whether assignment is independent of local conditions. The conditional randomization test of the remote audit evaluates whether treatment assignment is more predictable from pre-treatment satellite features than expected under the experiment's registered mechanism, providing a finite-sample valid, design-based diagnostic that requires no parametric assumptions. The procedure is finite-sample valid, honors blocks and clusters, and controls multiplicity across image models and resolutions via a max-statistic. We illustrate with two RCTs: Uganda's Youth Opportunities Program, where the audit corroborates randomization and flags selection and missing-data risks; and a school-based trial in Bangladesh, where assignment is highly predictable from pre-treatment features relative to the stated design, consistent with independent concerns about irregularities. Remote audits complement balance tests, lower early-stage costs, and enable rapid design checks when baseline surveys are expensive or infeasible.

This paper proposes one of the first clinical applications of multimodal large language models (LLMs) as an assistant for radiologists to check errors in their reports. We created an evaluation dataset from two real-world radiology datasets (MIMIC-CXR and IU-Xray), with 1,000 subsampled reports each. A subset of original reports was modified to contain synthetic errors by introducing various type of mistakes. The evaluation contained two difficulty levels: SIMPLE for binary error-checking and COMPLEX for identifying error types. LLaVA (Large Language and Visual Assistant) variant models, including our instruction-tuned model, were used for the evaluation. Additionally, a domain expert evaluation was conducted on a small test set. At the SIMPLE level, the LLaVA v1.5 model outperformed other publicly available models. Instruction tuning significantly enhanced performance by 47.4% and 25.4% on MIMIC-CXR and IU-Xray data, respectively. The model also surpassed the domain experts accuracy in the MIMIC-CXR dataset by 1.67%. Notably, among the subsets (N=21) of the test set where a clinician did not achieve the correct conclusion, the LLaVA ensemble mode correctly identified 71.4% of these cases. This study marks a promising step toward utilizing multi-modal LLMs to enhance diagnostic accuracy in radiology. The ensemble model demonstrated comparable performance to clinicians, even capturing errors overlooked by humans. Nevertheless, future work is needed to improve the model ability to identify the types of inconsistency.

The rapid progress of multimodal large language models (MLLMs) has led to increasing interest in agent-based systems. While most prior work in medical imaging concentrates on automating routine clinical workflows, we study an underexplored yet clinically significant setting: distinguishing visually hard-to-separate diseases in a zero-shot setting. We benchmark representative agents on two imaging-only proxy diagnostic tasks, (1) melanoma vs. atypical nevus and (2) pulmonary edema vs. pneumonia, where visual features are highly confounded despite substantial differences in clinical management. We introduce a multi-agent framework based on contrastive adjudication. Experimental results show improved diagnostic performance (an 11-percentage-point gain in accuracy on dermoscopy data) and reduced unsupported claims on qualitative samples, although overall performance remains insufficient for clinical deployment. We acknowledge the inherent uncertainty in human annotations and the absence of clinical context, which further limit the translation to real-world settings. Within this controlled setting, this pilot study provides preliminary insights into zero-shot agent performance in visually confounded scenarios.

Context: Test-driven development (TDD) is a widely employed software development practice that involves developing test cases based on requirements prior to writing the code. Although various methods for automated test case generation have been proposed, they are not specifically tailored for TDD, where requirements instead of code serve as input. Objective: In this paper, we introduce a text-to-testcase generation approach based on a large language model (GPT-3.5) that is fine-tuned on our curated dataset with an effective prompt design. Method: Our approach involves enhancing the capabilities of basic GPT-3.5 for text-to-testcase generation task that is fine-tuned on our curated dataset with an effective prompting design. We evaluated the effectiveness of our approach using a span of five large-scale open-source software projects. Results: Our approach generated 7k test cases for open source projects, achieving 78.5% syntactic correctness, 67.09% requirement alignment, and 61.7% code coverage, which substantially outperforms all other LLMs (basic GPT-3.5, Bloom, and CodeT5). In addition, our ablation study demonstrates the substantial performance improvement of the fine-tuning and prompting components of the GPT-3.5 model. Conclusions: These findings lead us to conclude that fine-tuning and prompting should be considered in the future when building a language model for the text-to-testcase generation task

The increasing use of tools and solutions based on Large Language Models (LLMs) for various tasks in the medical domain has become a prominent trend. Their use in this highly critical and sensitive domain has thus raised important questions about their robustness, especially in response to variations in input, and the reliability of the generated outputs. This study addresses these questions by constructing a textual dataset based on the ICD-10-CM code descriptions, widely used in US hospitals and containing many clinical terms, and their easily reproducible rephrasing. We then benchmarked existing embedding models, either generalist or specialized in the clinical domain, in a semantic search task where the goal was to correctly match the rephrased text to the original description. Our results showed that generalist models performed better than clinical models, suggesting that existing clinical specialized models are more sensitive to small changes in input that confuse them. The highlighted problem of specialized models may be due to the fact that they have not been trained on sufficient data, and in particular on datasets that are not diverse enough to have a reliable global language understanding, which is still necessary for accurate handling of medical documents.

Tool-augmented large language models (LLMs) are rapidly being integrated into real-world applications. Due to the lack of benchmarks, the community still needs to fully understand the hallucination issues within these models. To address this challenge, we introduce a comprehensive diagnostic benchmark, ToolBH. Specifically, we assess the LLM's hallucinations through two perspectives: depth and breadth. In terms of depth, we propose a multi-level diagnostic process, including (1) solvability detection, (2) solution planning, and (3) missing-tool analysis. For breadth, we consider three scenarios based on the characteristics of the toolset: missing necessary tools, potential tools, and limited functionality tools. Furthermore, we developed seven tasks and collected 700 evaluation samples through multiple rounds of manual annotation. The results show the significant challenges presented by the ToolBH benchmark. The current advanced models Gemini-1.5-Pro and GPT-4o only achieve a total score of 45.3 and 37.0, respectively, on a scale of 100. In this benchmark, larger model parameters do not guarantee better performance; the training data and response strategies also play a crucial role in tool-enhanced LLM scenarios. Our diagnostic analysis indicates that the primary reason for model errors lies in assessing task solvability. Additionally, open-weight models suffer from performance drops with verbose replies, whereas proprietary models excel with longer reasoning.

Software testing is a critical, yet resource-intensive phase of the software development lifecycle. Over the years, various automated tools have been developed to aid in this process. Search-based approaches typically achieve high coverage but produce tests with low readability, whereas large language model (LLM)-based methods generate more human-readable tests but often suffer from low coverage and compilability. While the majority of research efforts have focused on improving test coverage and readability, little attention has been paid to enhancing the robustness of bug detection, particularly in exposing corner cases and vulnerable execution paths. To address this gap, we propose AdverTest, a novel adversarial framework for LLM-powered test case generation. AdverTest comprises two interacting agents: a test case generation agent (T) and a mutant generation agent (M). These agents engage in an adversarial loop, where M persistently creates new mutants "hacking" the blind spots of T's current test suite, while T iteratively refines its test cases to "kill" the challenging mutants produced by M. This interaction loop is guided by both coverage and mutation scores, enabling the system to co-evolve toward both high test coverage and bug detection capability. Experimental results in the Defects4J dataset show that our approach improves fault detection rates by 8.56% over the best existing LLM-based methods and by 63.30% over EvoSuite, while also improving line and branch coverage.

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

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

Deep convolutional neural networks (CNNs) are the current state-of-the-art for digital analysis of histopathological images. The large size of whole-slide microscopy images (WSIs) requires advanced memory handling to read, display and process these images. There are several open-source platforms for working with WSIs, but few support deployment of CNN models. These applications use third-party solutions for inference, making them less user-friendly and unsuitable for high-performance image analysis. To make deployment of CNNs user-friendly and feasible on low-end machines, we have developed a new platform, FastPathology, using the FAST framework and C++. It minimizes memory usage for reading and processing WSIs, deployment of CNN models, and real-time interactive visualization of results. Runtime experiments were conducted on four different use cases, using different architectures, inference engines, hardware configurations and operating systems. Memory usage for reading, visualizing, zooming and panning a WSI were measured, using FastPathology and three existing platforms. FastPathology performed similarly in terms of memory to the other C++ based application, while using considerably less than the two Java-based platforms. The choice of neural network model, inference engine, hardware and processors influenced runtime considerably. Thus, FastPathology includes all steps needed for efficient visualization and processing of WSIs in a single application, including inference of CNNs with real-time display of the results. Source code, binary releases and test data can be found online on GitHub at https://github.com/SINTEFMedtek/FAST-Pathology/.

The emergence of large-scale multi-modal generative models has drastically advanced artificial intelligence, introducing unprecedented levels of performance and functionality. However, optimizing these models remains challenging due to historically isolated paths of model-centric and data-centric developments, leading to suboptimal outcomes and inefficient resource utilization. In response, we present a novel sandbox suite tailored for integrated data-model co-development. This sandbox provides a comprehensive experimental platform, enabling rapid iteration and insight-driven refinement of both data and models. Our proposed "Probe-Analyze-Refine" workflow, validated through applications on state-of-the-art LLaVA-like and DiT based models, yields significant performance boosts, such as topping the VBench leaderboard. We also uncover fruitful insights gleaned from exhaustive benchmarks, shedding light on the critical interplay between data quality, diversity, and model behavior. With the hope of fostering deeper understanding and future progress in multi-modal data and generative modeling, our codes, datasets, and models are maintained and accessible at https://github.com/modelscope/data-juicer/blob/main/docs/Sandbox.md.

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.

We introduce InternAgent-1.5, a unified system designed for end-to-end scientific discovery across computational and empirical domains. The system is built on a structured architecture composed of three coordinated subsystems for generation, verification, and evolution. These subsystems are supported by foundational capabilities for deep research, solution optimization, and long horizon memory. The architecture allows InternAgent-1.5 to operate continuously across extended discovery cycles while maintaining coherent and improving behavior. It also enables the system to coordinate computational modeling and laboratory experimentation within a single unified system. We evaluate InternAgent-1.5 on scientific reasoning benchmarks such as GAIA, HLE, GPQA, and FrontierScience, and the system achieves leading performance that demonstrates strong foundational capabilities. Beyond these benchmarks, we further assess two categories of discovery tasks. In algorithm discovery tasks, InternAgent-1.5 autonomously designs competitive methods for core machine learning problems. In empirical discovery tasks, it executes complete computational or wet lab experiments and produces scientific findings in earth, life, biological, and physical domains. Overall, these results show that InternAgent-1.5 provides a general and scalable framework for autonomous scientific discovery.

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.

We introduce Kvasir-VQA, an extended dataset derived from the HyperKvasir and Kvasir-Instrument datasets, augmented with question-and-answer annotations to facilitate advanced machine learning tasks in Gastrointestinal (GI) diagnostics. This dataset comprises 6,500 annotated images spanning various GI tract conditions and surgical instruments, and it supports multiple question types including yes/no, choice, location, and numerical count. The dataset is intended for applications such as image captioning, Visual Question Answering (VQA), text-based generation of synthetic medical images, object detection, and classification. Our experiments demonstrate the dataset's effectiveness in training models for three selected tasks, showcasing significant applications in medical image analysis and diagnostics. We also present evaluation metrics for each task, highlighting the usability and versatility of our dataset. The dataset and supporting artifacts are available at https://datasets.simula.no/kvasir-vqa.

Traditional metrics for Medical Report Generation (MRG) predominantly rely on surface-level n-gram overlap, which fails to capture clinical factual accuracy and often overlooks catastrophic diagnostic errors. We address this fundamental limitation by proposing AtomiMed, a universal, modality-agnostic evaluation framework that decomposes complex medical narratives into a standardized, multi-level hierarchy of Atomic Clinical Facts, encompassing Disease-level entities and Attribute-level descriptors, including location, morphology, and severity. By implementing an Agentic Cross-Verification loop between ground-truth and predicted reports, AtomiMed simulates a multi-radiologist peer-review process to verify clinical consistency, thus enabling the decoupled assessment of diagnostic detection and descriptive accuracy. To facilitate standardized evaluation, we introduce MRGEvalKit, an open-source toolkit for automated hierarchical extraction, and curate OmniMRG-Bench, a comprehensive multi-modal benchmark covering X-ray, CT, MRI, and Ultrasound. Extensive experiments on multiple expert-annotated reader studies demonstrate that AtomiMed achieves significantly higher correlation with human radiologist judgment compared to traditional and model-based metrics. Our code are release at https://github.com/Venn2336/MRGEvalkit

Large Language Models (LLMs) have impressive capabilities, but are prone to outputting falsehoods. Recent work has developed techniques for inferring whether a LLM is telling the truth by training probes on the LLM's internal activations. However, this line of work is controversial, with some authors pointing out failures of these probes to generalize in basic ways, among other conceptual issues. In this work, we use high-quality datasets of simple true/false statements to study in detail the structure of LLM representations of truth, drawing on three lines of evidence: 1. Visualizations of LLM true/false statement representations, which reveal clear linear structure. 2. Transfer experiments in which probes trained on one dataset generalize to different datasets. 3. Causal evidence obtained by surgically intervening in a LLM's forward pass, causing it to treat false statements as true and vice versa. Overall, we present evidence that at sufficient scale, LLMs linearly represent the truth or falsehood of factual statements. We also show that simple difference-in-mean probes generalize as well as other probing techniques while identifying directions which are more causally implicated in model outputs.

We introduce RadEval, a unified, open-source framework for evaluating radiology texts. RadEval consolidates a diverse range of metrics, from classic n-gram overlap (BLEU, ROUGE) and contextual measures (BERTScore) to clinical concept-based scores (F1CheXbert, F1RadGraph, RaTEScore, SRR-BERT, TemporalEntityF1) and advanced LLM-based evaluators (GREEN). We refine and standardize implementations, extend GREEN to support multiple imaging modalities with a more lightweight model, and pretrain a domain-specific radiology encoder, demonstrating strong zero-shot retrieval performance. We also release a richly annotated expert dataset with over 450 clinically significant error labels and show how different metrics correlate with radiologist judgment. Finally, RadEval provides statistical testing tools and baseline model evaluations across multiple publicly available datasets, facilitating reproducibility and robust benchmarking in radiology report generation.

Clinical AI development has traditionally followed a collaborative paradigm that depends on close interaction between clinicians and specialized AI teams. This paradigm imposes a practical challenge: clinicians must repeatedly communicate and refine their requirements with AI developers before those requirements can be translated into executable model development. This iterative process is time-consuming, and even after repeated discussion, misalignment may still exist because the two sides do not fully share each other's expertise. However, autonomous coding agents may change this paradigm, raising the possibility that clinicians could develop clinical AI models independently through natural-language interaction alone. In this study, we present such an autonomous prototype for clinician-driven clinical AI development. We evaluated the system on five clinical tasks spanning dermoscopic lesion classification, melanoma-versus-nevus triage, wrist-fracture detection (including a weakly supervised variant with only 5% bounding-box annotations), and debiased pneumothorax classification on chest radiographs. Across these settings, the system consistently developed models from clinician requests and achieved promising performance. Notably, in a debiased pneumothorax classification task on chest radiographs, where chest drains can act as a major confounder, the system successfully mitigated shortcut learning and nearly halved the model's reliance on chest drains. These findings provide proof of concept that autonomous coding agents may help shift clinical AI development toward a more clinician-driven paradigm, reducing the communication overhead and dependence on specialized AI developers. Although further validation and robustness assessment are needed, this study suggests a promising path toward making clinical AI development more accessible.

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.

LLM agents often retry after external validation rejects a candidate, but the interface between validation and the next model call remains underspecified. We introduce VeriHarness, a code-controlled agent loop in which models generate candidates while external validators control acceptance, budgets, and traces. We use it to compare raw diagnostics with feedback that identifies the failure location, observed value, and admissible alternatives. Across 50 paired TextWorld games under a four-call cap, feedback containing all three fields raises terminal success from 14/50 to 36/50 for Qwen2.5-Coder-14B (+44 percentage points) and from 8/50 to 29/50 for Llama-3.1-8B (+42 points). Ablations locate most of the gain in the admissible alternatives: feedback containing only the location and observed value remains near the raw diagnostic baseline. Presenting the complete repair information in prose instead of a keyed JSON record yields nearly the same success, providing no evidence that JSON syntax itself improves repair. The ordering persists across the tested call budgets and one sampled-decoding setting.

In this paper, we critically evaluate the capabilities of the state-of-the-art multimodal large language model, i.e., GPT-4 with Vision (GPT-4V), on Visual Question Answering (VQA) task. Our experiments thoroughly assess GPT-4V's proficiency in answering questions paired with images using both pathology and radiology datasets from 11 modalities (e.g. Microscopy, Dermoscopy, X-ray, CT, etc.) and fifteen objects of interests (brain, liver, lung, etc.). Our datasets encompass a comprehensive range of medical inquiries, including sixteen distinct question types. Throughout our evaluations, we devised textual prompts for GPT-4V, directing it to synergize visual and textual information. The experiments with accuracy score conclude that the current version of GPT-4V is not recommended for real-world diagnostics due to its unreliable and suboptimal accuracy in responding to diagnostic medical questions. In addition, we delineate seven unique facets of GPT-4V's behavior in medical VQA, highlighting its constraints within this complex arena. The complete details of our evaluation cases are accessible at https://github.com/ZhilingYan/GPT4V-Medical-Report.

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

In this article, we describe the design and implementation of a publicly accessible dermatology image analysis benchmark challenge. The goal of the challenge is to sup- port research and development of algorithms for automated diagnosis of melanoma, a lethal form of skin cancer, from dermoscopic images. The challenge was divided into sub-challenges for each task involved in image analysis, including lesion segmentation, dermoscopic feature detection within a lesion, and classification of melanoma. Training data included 900 images. A separate test dataset of 379 images was provided to measure resultant performance of systems developed with the training data. Ground truth for both training and test sets was generated by a panel of dermoscopic experts. In total, there were 79 submissions from a group of 38 participants, making this the largest standardized and comparative study for melanoma diagnosis in dermoscopic images to date. While the official challenge duration and ranking of participants has concluded, the datasets remain available for further research and development.

Current evaluation protocols for Vision-Language Models (VLMs) in Radiology Report Generation (RRG) rely on report-level metrics that measure lexical overlap or aggregate clinical correctness. However, such metrics do not test whether individual diagnostic statements stem from the actual pathological evidence visible in the image. This allows models to achieve competitive scores by exploiting learned priors or spurious correlations, a failure mode we refer to as vision shortcut. We introduce SHOVIR, a benchmark for evaluating vision shortcut behavior in RRG. SHOVIR extends two spatially annotated chest X-ray datasets, MIMIC-CXR and PadChest-GR, with per-box CheXpert labels, and defines image-level and disease-level occlusion experiments that contrast baseline performance on clean images against localized, region-specific perturbations. Comparing predictions across these conditions isolates two failure modes at the disease-class level: direct shortcuts, where a finding persists after its visual evidence is removed, and contextual shortcuts, where detection degrades once co-occurring pathologies are occluded despite the target region remaining intact. Benchmarking eight state-of-the-art VLMs, we find that shortcut behavior varies substantially across architectures and datasets. Models achieving the highest baseline report quality do not necessarily rank highest in spatial grounding, revealing that clinically fluent generation can coexist with shallow reliance on visual evidence. These findings expose a blind spot in current RRG evaluation and motivate region-aware assessment protocols.

Biomedical text embeddings have primarily been developed using research literature from PubMed, yet clinical cardiology practice relies heavily on procedural knowledge and specialized terminology found in comprehensive textbooks rather than research abstracts. This research practice gap limits the effectiveness of existing embedding models for clinical applications incardiology. This study trained CardioEmbed, a domain-specialized embedding model based on Qwen3-Embedding-8B, using contrastive learning on a curated corpus of seven comprehensive cardiology textbooks totaling approximately 150,000 sentences after deduplication. The model employs InfoNCE loss with in-batch negatives and achieves 99.60% retrieval accuracy on cardiac-specific semantic retrieval tasks, a +15.94 percentage point improvement over MedTE, the current state-of-the-art medical embedding model. On MTEB medical benchmarks, the model obtained BIOSSES 0.77 Spearman and SciFact 0.61 NDCG@10, indicating competitive performance on related biomedical domains. Domain-specialized training on comprehensive clinical textbooks yields near-perfect cardiology retrieval (99.60% Acc@1), improving over MedTE by +15.94 percentage points.

Clinical trial matching is a key process in health delivery and discovery. In practice, it is plagued by overwhelming unstructured data and unscalable manual processing. In this paper, we conduct a systematic study on scaling clinical trial matching using large language models (LLMs), with oncology as the focus area. Our study is grounded in a clinical trial matching system currently in test deployment at a large U.S. health network. Initial findings are promising: out of box, cutting-edge LLMs, such as GPT-4, can already structure elaborate eligibility criteria of clinical trials and extract complex matching logic (e.g., nested AND/OR/NOT). While still far from perfect, LLMs substantially outperform prior strong baselines and may serve as a preliminary solution to help triage patient-trial candidates with humans in the loop. Our study also reveals a few significant growth areas for applying LLMs to end-to-end clinical trial matching, such as context limitation and accuracy, especially in structuring patient information from longitudinal medical records.

In this study, we present MedS-Bench, a comprehensive benchmark designed to evaluate the performance of large language models (LLMs) in clinical contexts. Unlike existing benchmarks that focus on multiple-choice question answering, MedS-Bench spans 11 high-level clinical tasks, including clinical report summarization, treatment recommendations, diagnosis, named entity recognition, and medical concept explanation, among others. We evaluated six leading LLMs, e.g., MEDITRON, Mistral, InternLM 2, Llama 3, GPT-4, and Claude-3.5 using few-shot prompting, and found that even the most sophisticated models struggle with these complex tasks. To address these limitations, we developed MedS-Ins, a large-scale instruction tuning dataset for medicine. MedS-Ins comprises 58 medically oriented language corpora, totaling 13.5 million samples across 122 tasks. To demonstrate the dataset's utility, we conducted a proof-of-concept experiment by performing instruction tuning on a lightweight, open-source medical language model. The resulting model, MMedIns-Llama 3, significantly outperformed existing models across nearly all clinical tasks. To promote further advancements in the application of LLMs to clinical challenges, we have made the MedS-Ins dataset fully accessible and invite the research community to contribute to its expansion.Additionally, we have launched a dynamic leaderboard for MedS-Bench, which we plan to regularly update the test set to track progress and enhance the adaptation of general LLMs to the medical domain. Leaderboard: https://henrychur.github.io/MedS-Bench/. Github: https://github.com/MAGIC-AI4Med/MedS-Ins.

In clinical practice, electrocardiography (ECG) remains the gold standard for cardiac monitoring, providing crucial insights for diagnosing a wide range of cardiovascular diseases (CVDs). However, its reliance on specialized equipment and trained personnel limits feasibility for continuous routine monitoring. Photoplethysmography (PPG) offers accessible, continuous monitoring but lacks definitive electrophysiological information, preventing conclusive diagnosis. Generative models present a promising approach to translate PPG into clinically valuable ECG signals, yet current methods face substantial challenges, including the misalignment of physiological semantics in generative models and the complexity of modeling in high-dimensional signals. To this end, we propose PPGFlowECG, a two-stage framework that aligns PPG and ECG in a shared latent space via the CardioAlign Encoder and employs latent rectified flow to generate ECGs with high fidelity and interpretability. To the best of our knowledge, this is the first study to experiment on MCMED, a newly released clinical-grade dataset comprising over 10 million paired PPG-ECG samples from more than 118,000 emergency department visits with expert-labeled cardiovascular disease annotations. Results demonstrate the effectiveness of our method for PPG-to-ECG translation and cardiovascular disease detection. Moreover, cardiologist-led evaluations confirm that the synthesized ECGs achieve high fidelity and improve diagnostic reliability, underscoring our method's potential for real-world cardiovascular screening.

Medical conversational AI (AI) plays a pivotal role in the development of safer and more effective medical dialogue systems. However, existing benchmarks and evaluation frameworks for assessing the information-gathering and diagnostic reasoning abilities of medical large language models (LLMs) have not been rigorously evaluated. To address these gaps, we present MedDialogRubrics, a novel benchmark comprising 5,200 synthetically constructed patient cases and over 60,000 fine-grained evaluation rubrics generated by LLMs and subsequently refined by clinical experts, specifically designed to assess the multi-turn diagnostic capabilities of LLM. Our framework employs a multi-agent system to synthesize realistic patient records and chief complaints from underlying disease knowledge without accessing real-world electronic health records, thereby mitigating privacy and data-governance concerns. We design a robust Patient Agent that is limited to a set of atomic medical facts and augmented with a dynamic guidance mechanism that continuously detects and corrects hallucinations throughout the dialogue, ensuring internal coherence and clinical plausibility of the simulated cases. Furthermore, we propose a structured LLM-based and expert-annotated rubric-generation pipeline that retrieves Evidence-Based Medicine (EBM) guidelines and utilizes the reject sampling to derive a prioritized set of rubric items ("must-ask" items) for each case. We perform a comprehensive evaluation of state-of-the-art models and demonstrate that, across multiple assessment dimensions, current models face substantial challenges. Our results indicate that improving medical dialogue will require advances in dialogue management architectures, not just incremental tuning of the base-model.

Recent progress in Large Vision-Language Models (LVLMs) has enabled promising applications in medical tasks, such as report generation and visual question answering. However, existing benchmarks focus mainly on the final diagnostic answer, offering limited insight into whether models engage in clinically meaningful reasoning. To address this, we present CheXStruct and CXReasonBench, a structured pipeline and benchmark built on the publicly available MIMIC-CXR-JPG dataset. CheXStruct automatically derives a sequence of intermediate reasoning steps directly from chest X-rays, such as segmenting anatomical regions, deriving anatomical landmarks and diagnostic measurements, computing diagnostic indices, and applying clinical thresholds. CXReasonBench leverages this pipeline to evaluate whether models can perform clinically valid reasoning steps and to what extent they can learn from structured guidance, enabling fine-grained and transparent assessment of diagnostic reasoning. The benchmark comprises 18,988 QA pairs across 12 diagnostic tasks and 1,200 cases, each paired with up to 4 visual inputs, and supports multi-path, multi-stage evaluation including visual grounding via anatomical region selection and diagnostic measurements. Even the strongest of 10 evaluated LVLMs struggle with structured reasoning and generalization, often failing to link abstract knowledge with anatomically grounded visual interpretation. The code is available at https://github.com/ttumyche/CXReasonBench

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

Large Vision-Language Models (LVLMs) are increasingly being explored for applications in telemedicine, yet their ability to engage with diverse patient behaviors remains underexplored. We introduce 3MDBench (Medical Multimodal Multi-agent Dialogue Benchmark), an open-source evaluation framework designed to assess LLM-driven medical consultations. Unlike existing benchmarks, 3MDBench simulates real-world patient variability by incorporating four temperament-driven Patient Agents and an Assessor Agent that evaluates diagnostic accuracy and dialogue quality. The benchmark integrates textual and image-based patient data across 34 common diagnoses, mirroring real-world telemedicine interactions. Under different diagnostic strategies, we evaluate state-of-the-art LVLMs. Our findings demonstrate that incorporating dialogue improves the F1 score from 50.4 to 54.2 compared to non-dialogue settings, underscoring the value of context-driven, information-seeking questioning. Additionally, we demonstrate that multimodal inputs enhance diagnostic efficiency. Image-supported models outperform text-only counterparts by raising the diagnostic F1 score from 52.8 to 54.2 in a similar dialogue setting. Finally, we suggest an approach that improves the diagnostic F1-score to 70.3 by training the CNN model on the diagnosis prediction task and incorporating its top-3 predictions into the LVLM context. 3MDBench provides a reproducible and extendable evaluation framework for AI-driven medical assistants. It offers insights into how patient temperament, dialogue strategies, and multimodal reasoning influence diagnosis quality. By addressing real-world complexities in telemedicine, our benchmark paves the way for more empathetic, reliable, and context-aware AI-driven healthcare solutions. The source code of our benchmark is publicly available: https://github.com/univanxx/3mdbench

Electrocardiograms (ECGs) are non-invasive diagnostic tools crucial for detecting cardiac arrhythmic diseases in clinical practice. While ECG Self-supervised Learning (eSSL) methods show promise in representation learning from unannotated ECG data, they often overlook the clinical knowledge that can be found in reports. This oversight and the requirement for annotated samples for downstream tasks limit eSSL's versatility. In this work, we address these issues with the Multimodal ECG Representation Learning (MERL}) framework. Through multimodal learning on ECG records and associated reports, MERL is capable of performing zero-shot ECG classification with text prompts, eliminating the need for training data in downstream tasks. At test time, we propose the Clinical Knowledge Enhanced Prompt Engineering (CKEPE) approach, which uses Large Language Models (LLMs) to exploit external expert-verified clinical knowledge databases, generating more descriptive prompts and reducing hallucinations in LLM-generated content to boost zero-shot classification. Based on MERL, we perform the first benchmark across six public ECG datasets, showing the superior performance of MERL compared against eSSL methods. Notably, MERL achieves an average AUC score of 75.2% in zero-shot classification (without training data), 3.2% higher than linear probed eSSL methods with 10\% annotated training data, averaged across all six datasets. Code and models are available at https://github.com/cheliu-computation/MERL

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

Large language models (LLMs) have made remarkable progress in code generation, but competitive programming remains a challenge. Recent training-based methods have improved code generation by using reinforcement learning (RL) with execution feedback. The more recent framework CURE further incorporates test generation into the training process, jointly training a Coder and a Tester within a single model. At inference time, the Coder generates many candidate programs, and the Tester generates tests from the problem description. The candidate who passes the most of the generated tests is selected as the final answer. However, CURE has two critical limitations. First, the Tester never reads any candidate code, so its tests often fail to expose implementation-specific bugs. Second, the Coder generates every candidate from scratch and never learns to fix a buggy program based on a failed test. To address these limitations, we propose FixAudit, which approaches competitive code generation from a new perspective: starting from a single initial candidate, it iteratively improves the candidate through a targeted test-and-repair debugging cycle. The framework trains one shared model with two specialized roles through four stages: the Fixer, which repairs the current candidate based on a failing test, and the Auditor, which reads the candidate code to generate new tests that expose its remaining bugs. We evaluate FixAudit on three benchmarks: APPS, CodeContests, and xCodeEval. Applied to a 7B model, the framework surpasses the average performance of the larger 32B baseline within the same model family under the zero-shot setting. Compared to strong baselines built on the same 7B base model, FixAudit improves average Pass@1 by 35.1% to 36.8% and average AvgPassRatio by 7.1% to 24.5%.

This paper presents a data-driven, task-specific paradigm for experimental design, to shorten acquisition time, reduce costs, and accelerate the deployment of imaging devices. Current approaches in experimental design focus on model-parameter estimation and require specification of a particular model, whereas in imaging, other tasks may drive the design. Furthermore, such approaches often lead to intractable optimization problems in real-world imaging applications. Here we present a new paradigm for experimental design that simultaneously optimizes the design (set of image channels) and trains a machine-learning model to execute a user-specified image-analysis task. The approach obtains data densely-sampled over the measurement space (many image channels) for a small number of acquisitions, then identifies a subset of channels of prespecified size that best supports the task. We propose a method: TADRED for TAsk-DRiven Experimental Design in imaging, to identify the most informative channel-subset whilst simultaneously training a network to execute the task given the subset. Experiments demonstrate the potential of TADRED in diverse imaging applications: several clinically-relevant tasks in magnetic resonance imaging; and remote sensing and physiological applications of hyperspectral imaging. Results show substantial improvement over classical experimental design, two recent application-specific methods within the new paradigm, and state-of-the-art approaches in supervised feature selection. We anticipate further applications of our approach. Code is available: https://github.com/sbb-gh/experimental-design-multichannel

Recent advances in generative medical models are constrained by modality-specific scenarios that hinder the integration of complementary evidence from imaging, pathology, and clinical notes. This fragmentation limits their evolution into foundation models that can learn and reason across the full spectrum of biomedical data. We propose MeDiM, the first medical discrete diffusion model that learns shared distributions across modalities without modality-specific components. MeDiM unifies multiple generative tasks: translating between images and text, and jointly producing image-report pairs across domains in response to prompts. Built on a discrete diffusion framework, MeDiM bridges vision and language representations through a shared probabilistic space. To enable unified and flexible medical generation, we employ a multimodal large language model (MLLM) as the diffusion backbone, leveraging its prior knowledge and cross-modal reasoning. Two key designs are introduced: (1) removing the causal attention mask for bidirectional context, and (2) injecting continuous timestep embeddings for diffusion awareness. Experiments demonstrate high-fidelity medical generation (FID 16.60 on MIMIC-CXR and FID 24.19 on PathGen) and accurate report generation (METEOR 0.2650 and 0.2580). Jointly generated image-report pairs further enhance downstream performance (plus6.43 percent BLEU-1, plus18.57 percent BLEU-2, plus31.58 percent BLEU-3, plus4.80 percent METEOR), showing that MeDiM supports coherent and clinically grounded multimodal outputs.

The rapid advancement of large-scale vision-language models has showcased remarkable capabilities across various tasks. However, the lack of extensive and high-quality image-text data in medicine has greatly hindered the development of large-scale medical vision-language models. In this work, we present a diagnosis-guided bootstrapping strategy that exploits both image and label information to construct vision-language datasets. Based on the constructed dataset, we developed MedDr, a generalist foundation model for healthcare capable of handling diverse medical data modalities, including radiology, pathology, dermatology, retinography, and endoscopy. Moreover, during inference, we propose a simple but effective retrieval-augmented medical diagnosis strategy, which enhances the model's generalization ability. Extensive experiments on visual question answering, medical report generation, and medical image diagnosis demonstrate the superiority of our method.

Large Language Models (LLMs) and Retrieval-Augmented Generation (RAG) systems are increasingly integrated into clinical workflows; however, prompt injection attacks can steer these systems toward clinically unsafe or misleading outputs. We introduce the Medical Prompt Injection Benchmark (MPIB), a dataset-and-benchmark suite for evaluating clinical safety under both direct prompt injection and indirect, RAG-mediated injection across clinically grounded tasks. MPIB emphasizes outcome-level risk via the Clinical Harm Event Rate (CHER), which measures high-severity clinical harm events under a clinically grounded taxonomy, and reports CHER alongside Attack Success Rate (ASR) to disentangle instruction compliance from downstream patient risk. The benchmark comprises 9,697 curated instances constructed through multi-stage quality gates and clinical safety linting. Evaluating MPIB across a diverse set of baseline LLMs and defense configurations, we find that ASR and CHER can diverge substantially, and that robustness depends critically on whether adversarial instructions appear in the user query or in retrieved context. We release MPIB with evaluation code, adversarial baselines, and comprehensive documentation to support reproducible and systematic research on clinical prompt injection. Code and data are available at GitHub (code) and Hugging Face (data).

Recently, given the docstring for the target problem and the target function signature, large language models (LLMs) have been used not only to generate source code, but also to generate test cases, consisting of test inputs and assertions (e.g., in the form of checking an actual output against the expected output). However, as shown by our empirical study on assertions generated by four LLMs for the HumanEval benchmark, over 62% of the generated assertions are incorrect (i.e., failed on the ground-truth problem solution). To detect incorrect assertions (given the docstring and the target function signature along with a sample of example inputs and outputs), in this paper, we propose a new approach named DeCon to effectively detect incorrect assertions via LLM-generated postconditions for the target problem (a postcondition is a predicate that must always be true just after the execution of the ground-truth problem solution). Our approach requires a small set of I/O examples (i.e., a sample of example inputs and outputs) for the target problem (e.g., the I/O examples included in the docstring for a target problem in HumanEval). We use the given I/O examples to filter out those LLM-generated postconditions that are violated by at least one given I/O example. We then use the remaining postconditions to detect incorrect assertions as those assertions that violate at least one remaining postcondition. Experimental results show that DeCon can detect averagely more than 64% (63% and 65.5% detected by GPT-3.5 and GPT-4, respectively) incorrect assertions generated by four state-of-the-art LLMs, and DeCon can also improve the effectiveness of these LLMs in code generation by 4% in terms of Pass@1. In addition, although DeCon might filter out correct assertions, the fault-finding ability of the remaining correct assertions decreases only slightly.

Current Large Language Models (LLMs) exhibit significant limitations, notably in structured, interpretable, and verifiable medical reasoning, alongside practical deployment challenges related to computational resources and data privacy. This report focused on the development of WiNGPT-3.0, the 32-billion parameter LLMs, engineered with the objective of enhancing its capacity for medical reasoning and exploring its potential for effective integration within healthcare IT infrastructures. The broader aim is to advance towards clinically applicable models. The approach involved a multi-stage training pipeline tailored for general, medical, and clinical reasoning. This pipeline incorporated supervised fine-tuning (SFT) and reinforcement learning (RL), leveraging curated Long Chain-of-Thought (CoT) datasets, auxiliary reward models, and an evidence-based diagnostic chain simulation. WiNGPT-3.0 demonstrated strong performance: specific model variants achieved scores of 66.6 on MedCalc and 87.1 on MedQA-USMLE. Furthermore, targeted training improved performance on a clinical reasoning task from a baseline score of 58.1 to 62.5. These findings suggest that reinforcement learning, even when applied with a limited dataset of only a few thousand examples, can enhance medical reasoning accuracy. Crucially, this demonstration of RL's efficacy with limited data and computation paves the way for more trustworthy and practically deployable LLMs within clinical workflows and health information infrastructures.

Laboratory test results are an important and generally high dimensional component of a patient's Electronic Health Record (EHR). We train embedding representations (via Word2Vec and GloVe) for LOINC codes of laboratory tests from the EHRs of about 80,000 patients at a cancer center. To include information about lab test outcomes, we also train embeddings on the concatenation of a LOINC code with a symbol indicating normality or abnormality of the result. We observe several clinically meaningful similarities among LOINC embeddings trained over our data. For the embeddings of the concatenation of LOINCs with abnormality codes, we evaluate the performance for mortality prediction tasks and the ability to preserve ordinality properties: i.e. a lab test with normal outcome should be more similar to an abnormal one than to the a very abnormal one.

Clinical trials are fundamental in developing new drugs, medical devices, and treatments. However, they are often time-consuming and have low success rates. Although there have been initial attempts to create large language models (LLMs) for clinical trial design and patient-trial matching, these models remain task-specific and not adaptable to diverse clinical trial tasks. To address this challenge, we propose a clinical trial foundation model named Panacea, designed to handle multiple tasks, including trial search, trial summarization, trial design, and patient-trial matching. We also assemble a large-scale dataset, named TrialAlign, of 793,279 trial documents and 1,113,207 trial-related scientific papers, to infuse clinical knowledge into the model by pre-training. We further curate TrialInstruct, which has 200,866 of instruction data for fine-tuning. These resources enable Panacea to be widely applicable for a range of clinical trial tasks based on user requirements. We evaluated Panacea on a new benchmark, named TrialPanorama, which covers eight clinical trial tasks. Our method performed the best on seven of the eight tasks compared to six cutting-edge generic or medicine-specific LLMs. Specifically, Panacea showed great potential to collaborate with human experts in crafting the design of eligibility criteria, study arms, and outcome measures, in multi-round conversations. In addition, Panacea achieved 14.42% improvement in patient-trial matching, 41.78% to 52.02% improvement in trial search, and consistently ranked at the top for five aspects of trial summarization. Our approach demonstrates the effectiveness of Panacea in clinical trials and establishes a comprehensive resource, including training data, model, and benchmark, for developing clinical trial foundation models, paving the path for AI-based clinical trial development.

Large language models (LLMs) are increasingly proposed as clinical agents, yet static, single-turn benchmarks cannot capture how a model dynamically delivers care across an encounter: gathering information, planning treatment, and adapting longitudinal management across successive patient states. Medical education has long addressed an analogous challenge through standardized patients (SPs): trained actors who consistently portray clinical cases, enabling realistic practice and objective, scripted assessment. Here we introduce MedSP1000, an SP-derived interactive benchmark for clinical-agent evaluation, including 1,638 SP cases with 24,602 trajectory-level peer-reviewed rubrics. MedSP1000 converts peer-reviewed SP teaching cases into executable scenarios with defined SP case scripts, clinical environment contexts, and human-validated structured rubric. In each simulation evaluation run, a clinical agent interacts in closed loop with a patient agent and an environment controller, and its behaviour is scored throughout the encounter against expert criteria specified in the original materials. Applying MedSP1000 to a range of general-purpose and medically specialized LLMs, we find that performance on static benchmarks does not reliably translate to such educational scenarios. The best-performing model, GPT-5.5, completes only 60.4% of expert-defined rubric items, whereas the strongest medically specialized model reaches 40.0%; increasing test-time compute produces no measurable gain. These results suggest that current LLMs, including agentic systems tuned for medicine, are not yet reliable enough to be safely integrated into actual clinical practice. More broadly, MedSP1000 shows how process-level, SP-style evaluation can reveal clinically relevant failure modes that single-turn benchmarks miss.

Developing accurate machine learning models for oncology requires large-scale, high-quality multimodal datasets. However, creating such datasets remains challenging due to the complexity and heterogeneity of medical data. To address this challenge, we introduce HoneyBee, a scalable modular framework for building multimodal oncology datasets that leverages foundational models to generate representative embeddings. HoneyBee integrates various data modalities, including clinical records, imaging data, and patient outcomes. It employs data preprocessing techniques and transformer-based architectures to generate embeddings that capture the essential features and relationships within the raw medical data. The generated embeddings are stored in a structured format using Hugging Face datasets and PyTorch dataloaders for accessibility. Vector databases enable efficient querying and retrieval for machine learning applications. We demonstrate the effectiveness of HoneyBee through experiments assessing the quality and representativeness of the embeddings. The framework is designed to be extensible to other medical domains and aims to accelerate oncology research by providing high-quality, machine learning-ready datasets. HoneyBee is an ongoing open-source effort, and the code, datasets, and models are available at the project repository.

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.

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.

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

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

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.

Synthetic medical data generation has opened up new possibilities in the healthcare domain, offering a powerful tool for simulating clinical scenarios, enhancing diagnostic and treatment quality, gaining granular medical knowledge, and accelerating the development of unbiased algorithms. In this context, we present a novel approach called ViewXGen, designed to overcome the limitations of existing methods that rely on general domain pipelines using only radiology reports to generate frontal-view chest X-rays. Our approach takes into consideration the diverse view positions found in the dataset, enabling the generation of chest X-rays with specific views, which marks a significant advancement in the field. To achieve this, we introduce a set of specially designed tokens for each view position, tailoring the generation process to the user's preferences. Furthermore, we leverage multi-view chest X-rays as input, incorporating valuable information from different views within the same study. This integration rectifies potential errors and contributes to faithfully capturing abnormal findings in chest X-ray generation. To validate the effectiveness of our approach, we conducted statistical analyses, evaluating its performance in a clinical efficacy metric on the MIMIC-CXR dataset. Also, human evaluation demonstrates the remarkable capabilities of ViewXGen, particularly in producing realistic view-specific X-rays that closely resemble the original images.

Vision-language foundation models (VLMs) show promise for diverse imaging tasks but often underperform on medical benchmarks. Prior efforts to improve performance include model finetuning, which requires large domain-specific datasets and significant compute, or manual prompt engineering, which is hard to generalize and often inaccessible to medical institutions seeking to deploy these tools. These challenges motivate interest in approaches that draw on a model's embedded knowledge while abstracting away dependence on human-designed prompts to enable scalable, weight-agnostic performance improvements. To explore this, we adapt the Declarative Self-improving Python (DSPy) framework for structured automated prompt optimization in medical vision-language systems through a comprehensive, formal evaluation. We implement prompting pipelines for five medical imaging tasks across radiology, gastroenterology, and dermatology, evaluating 10 open-source VLMs with four prompt optimization techniques. Optimized pipelines achieved a median relative improvement of 53% over zero-shot prompting baselines, with the largest gains ranging from 300% to 3,400% on tasks where zero-shot performance is low. These results highlight the substantial potential of applying automated prompt optimization to medical AI systems, demonstrating significant gains for vision-based applications requiring accurate clinical image interpretation. By reducing dependence on prompt design to elicit intended outputs, these techniques allow clinicians to focus on patient care and clinical decision-making. Furthermore, our experiments offer scalability and preserve data privacy, demonstrating performance improvement on open-source VLMs. We publicly release our evaluation pipelines to support reproducible research on specialized medical tasks, available at https://github.com/DaneshjouLab/prompt-triage-lab.