Daily Papers

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

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.

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.

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.

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/

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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

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

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.

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.

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.

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.

Medical Visual Language Models have shown great potential in various healthcare applications, including medical image captioning and diagnostic assistance. However, most existing models rely on text-based instructions, limiting their usability in real-world clinical environments especially in scenarios such as surgery, text-based interaction is often impractical for physicians. In addition, current medical image analysis models typically lack comprehensive reasoning behind their predictions, which reduces their reliability for clinical decision-making. Given that medical diagnosis errors can have life-changing consequences, there is a critical need for interpretable and rational medical assistance. To address these challenges, we introduce an end-to-end speech-driven medical VLM, SilVar-Med, a multimodal medical image assistant that integrates speech interaction with VLMs, pioneering the task of voice-based communication for medical image analysis. In addition, we focus on the interpretation of the reasoning behind each prediction of medical abnormalities with a proposed reasoning dataset. Through extensive experiments, we demonstrate a proof-of-concept study for reasoning-driven medical image interpretation with end-to-end speech interaction. We believe this work will advance the field of medical AI by fostering more transparent, interactive, and clinically viable diagnostic support systems. Our code and dataset are publicly available at SiVar-Med.

Global healthcare providers are exploring use of large language models (LLMs) to provide medical advice to the public. LLMs now achieve nearly perfect scores on medical licensing exams, but this does not necessarily translate to accurate performance in real-world settings. We tested if LLMs can assist members of the public in identifying underlying conditions and choosing a course of action (disposition) in ten medical scenarios in a controlled study with 1,298 participants. Participants were randomly assigned to receive assistance from an LLM (GPT-4o, Llama 3, Command R+) or a source of their choice (control). Tested alone, LLMs complete the scenarios accurately, correctly identifying conditions in 94.9% of cases and disposition in 56.3% on average. However, participants using the same LLMs identified relevant conditions in less than 34.5% of cases and disposition in less than 44.2%, both no better than the control group. We identify user interactions as a challenge to the deployment of LLMs for medical advice. Standard benchmarks for medical knowledge and simulated patient interactions do not predict the failures we find with human participants. Moving forward, we recommend systematic human user testing to evaluate interactive capabilities prior to public deployments in healthcare.

This work describes the development and real-world deployment of a deep learning-based AI system for evaluating canine and feline radiographs across a broad range of findings and abnormalities. We describe a new semi-supervised learning approach that combines NLP-derived labels with self-supervised training leveraging more than 2.5 million x-ray images. Finally we describe the clinical deployment of the model including system architecture, real-time performance evaluation and data drift detection.

We introduce CheXGenBench, a rigorous and multifaceted evaluation framework for synthetic chest radiograph generation that simultaneously assesses fidelity, privacy risks, and clinical utility across state-of-the-art text-to-image generative models. Despite rapid advancements in generative AI for real-world imagery, medical domain evaluations have been hindered by methodological inconsistencies, outdated architectural comparisons, and disconnected assessment criteria that rarely address the practical clinical value of synthetic samples. CheXGenBench overcomes these limitations through standardised data partitioning and a unified evaluation protocol comprising over 20 quantitative metrics that systematically analyse generation quality, potential privacy vulnerabilities, and downstream clinical applicability across 11 leading text-to-image architectures. Our results reveal critical inefficiencies in the existing evaluation protocols, particularly in assessing generative fidelity, leading to inconsistent and uninformative comparisons. Our framework establishes a standardised benchmark for the medical AI community, enabling objective and reproducible comparisons while facilitating seamless integration of both existing and future generative models. Additionally, we release a high-quality, synthetic dataset, SynthCheX-75K, comprising 75K radiographs generated by the top-performing model (Sana 0.6B) in our benchmark to support further research in this critical domain. Through CheXGenBench, we establish a new state-of-the-art and release our framework, models, and SynthCheX-75K dataset at https://raman1121.github.io/CheXGenBench/

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

Run-time steering strategies like Medprompt are valuable for guiding large language models (LLMs) to top performance on challenging tasks. Medprompt demonstrates that a general LLM can be focused to deliver state-of-the-art performance on specialized domains like medicine by using a prompt to elicit a run-time strategy involving chain of thought reasoning and ensembling. OpenAI's o1-preview model represents a new paradigm, where a model is designed to do run-time reasoning before generating final responses. We seek to understand the behavior of o1-preview on a diverse set of medical challenge problem benchmarks. Following on the Medprompt study with GPT-4, we systematically evaluate the o1-preview model across various medical benchmarks. Notably, even without prompting techniques, o1-preview largely outperforms the GPT-4 series with Medprompt. We further systematically study the efficacy of classic prompt engineering strategies, as represented by Medprompt, within the new paradigm of reasoning models. We found that few-shot prompting hinders o1's performance, suggesting that in-context learning may no longer be an effective steering approach for reasoning-native models. While ensembling remains viable, it is resource-intensive and requires careful cost-performance optimization. Our cost and accuracy analysis across run-time strategies reveals a Pareto frontier, with GPT-4o representing a more affordable option and o1-preview achieving state-of-the-art performance at higher cost. Although o1-preview offers top performance, GPT-4o with steering strategies like Medprompt retains value in specific contexts. Moreover, we note that the o1-preview model has reached near-saturation on many existing medical benchmarks, underscoring the need for new, challenging benchmarks. We close with reflections on general directions for inference-time computation with LLMs.

When it comes to deploying deep vision models, the behavior of these systems must be explicable to ensure confidence in their reliability and fairness. A common approach to evaluate deep learning models is to build a labeled test set with attributes of interest and assess how well it performs. However, creating a balanced test set (i.e., one that is uniformly sampled over all the important traits) is often time-consuming, expensive, and prone to mistakes. The question we try to address is: can we evaluate the sensitivity of deep learning models to arbitrary visual attributes without an annotated test set? This paper argues the case that Zero-shot Model Diagnosis (ZOOM) is possible without the need for a test set nor labeling. To avoid the need for test sets, our system relies on a generative model and CLIP. The key idea is enabling the user to select a set of prompts (relevant to the problem) and our system will automatically search for semantic counterfactual images (i.e., synthesized images that flip the prediction in the case of a binary classifier) using the generative model. We evaluate several visual tasks (classification, key-point detection, and segmentation) in multiple visual domains to demonstrate the viability of our methodology. Extensive experiments demonstrate that our method is capable of producing counterfactual images and offering sensitivity analysis for model diagnosis without the need for a test set.

Recent advancements in artificial intelligence (AI) have precipitated significant breakthroughs in healthcare, particularly in refining diagnostic procedures. However, previous studies have often been constrained to limited functionalities. This study introduces MiniGPT-Med, a vision-language model derived from large-scale language models and tailored for medical applications. MiniGPT-Med demonstrates remarkable versatility across various imaging modalities, including X-rays, CT scans, and MRIs, enhancing its utility. The model is capable of performing tasks such as medical report generation, visual question answering (VQA), and disease identification within medical imagery. Its integrated processing of both image and textual clinical data markedly improves diagnostic accuracy. Our empirical assessments confirm MiniGPT-Med's superior performance in disease grounding, medical report generation, and VQA benchmarks, representing a significant step towards reducing the gap in assisting radiology practice. Furthermore, it achieves state-of-the-art performance on medical report generation, higher than the previous best model by 19\% accuracy. MiniGPT-Med promises to become a general interface for radiology diagnoses, enhancing diagnostic efficiency across a wide range of medical imaging applications.

Medical imaging is essential in modern radiotherapy, supporting diagnosis, treatment planning, and monitoring. Synthetic imaging, particularly synthetic computed tomography (sCT), is gaining traction in radiotherapy. The SynthRAD2025 dataset and Grand Challenge promote advancements in sCT generation by providing a benchmarking platform for algorithms using cone-beam CT (CBCT) and magnetic resonance imaging (MRI). The dataset includes 2362 cases: 890 MRI-CT and 1472 CBCT-CT pairs from head-and-neck, thoracic, and abdominal cancer patients treated at five European university medical centers (UMC Groningen, UMC Utrecht, Radboud UMC, LMU University Hospital Munich, and University Hospital of Cologne). Data were acquired with diverse scanners and protocols. Pre-processing, including rigid and deformable image registration, ensures high-quality, modality-aligned images. Extensive quality assurance validates image consistency and usability. All imaging data is provided in MetaImage (.mha) format, ensuring compatibility with medical image processing tools. Metadata, including acquisition parameters and registration details, is available in structured CSV files. To maintain dataset integrity, SynthRAD2025 is divided into training (65%), validation (10%), and test (25%) sets. The dataset is accessible at https://doi.org/10.5281/zenodo.14918089 under the SynthRAD2025 collection. This dataset supports benchmarking and the development of synthetic imaging techniques for radiotherapy applications. Use cases include sCT generation for MRI-only and MR-guided photon/proton therapy, CBCT-based dose calculations, and adaptive radiotherapy workflows. By integrating diverse acquisition settings, SynthRAD2025 fosters robust, generalizable image synthesis algorithms, advancing personalized cancer care and adaptive radiotherapy.

Purpose: Medical imaging has become increasingly important in diagnosing and treating oncological patients, particularly in radiotherapy. Recent advances in synthetic computed tomography (sCT) generation have increased interest in public challenges to provide data and evaluation metrics for comparing different approaches openly. This paper describes a dataset of brain and pelvis computed tomography (CT) images with rigidly registered CBCT and MRI images to facilitate the development and evaluation of sCT generation for radiotherapy planning. Acquisition and validation methods: The dataset consists of CT, CBCT, and MRI of 540 brains and 540 pelvic radiotherapy patients from three Dutch university medical centers. Subjects' ages ranged from 3 to 93 years, with a mean age of 60. Various scanner models and acquisition settings were used across patients from the three data-providing centers. Details are available in CSV files provided with the datasets. Data format and usage notes: The data is available on Zenodo (https://doi.org/10.5281/zenodo.7260705) under the SynthRAD2023 collection. The images for each subject are available in nifti format. Potential applications: This dataset will enable the evaluation and development of image synthesis algorithms for radiotherapy purposes on a realistic multi-center dataset with varying acquisition protocols. Synthetic CT generation has numerous applications in radiation therapy, including diagnosis, treatment planning, treatment monitoring, and surgical planning.

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

Medical benchmark datasets significantly contribute to developing Large Language Models (LLMs) for medical knowledge extraction, diagnosis, summarization, and other uses. Yet, current benchmarks are mainly derived from exam questions given to medical students or cases described in the medical literature, lacking the complexity of real-world patient cases that deviate from classic textbook abstractions. These include rare diseases, uncommon presentations of common diseases, and unexpected treatment responses. Here, we construct Clinically Uncommon Patient Cases and Diagnosis Dataset (CUPCase) based on 3,562 real-world case reports from BMC, including diagnoses in open-ended textual format and as multiple-choice options with distractors. Using this dataset, we evaluate the ability of state-of-the-art LLMs, including both general-purpose and Clinical LLMs, to identify and correctly diagnose a patient case, and test models' performance when only partial information about cases is available. Our findings show that general-purpose GPT-4o attains the best performance in both the multiple-choice task (average accuracy of 87.9%) and the open-ended task (BERTScore F1 of 0.764), outperforming several LLMs with a focus on the medical domain such as Meditron-70B and MedLM-Large. Moreover, GPT-4o was able to maintain 87% and 88% of its performance with only the first 20% of tokens of the case presentation in multiple-choice and free text, respectively, highlighting the potential of LLMs to aid in early diagnosis in real-world cases. CUPCase expands our ability to evaluate LLMs for clinical decision support in an open and reproducible manner.

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

Synthesizing clinical evidence largely relies on systematic reviews of clinical trials and retrospective analyses from medical literature. However, the rapid expansion of publications presents challenges in efficiently identifying, summarizing, and updating clinical evidence. Here, we introduce TrialMind, a generative artificial intelligence (AI) pipeline for facilitating human-AI collaboration in three crucial tasks for evidence synthesis: study search, screening, and data extraction. To assess its performance, we chose published systematic reviews to build the benchmark dataset, named TrialReviewBench, which contains 100 systematic reviews and the associated 2,220 clinical studies. Our results show that TrialMind excels across all three tasks. In study search, it generates diverse and comprehensive search queries to achieve high recall rates (Ours 0.711-0.834 v.s. Human baseline 0.138-0.232). For study screening, TrialMind surpasses traditional embedding-based methods by 30% to 160%. In data extraction, it outperforms a GPT-4 baseline by 29.6% to 61.5%. We further conducted user studies to confirm its practical utility. Compared to manual efforts, human-AI collaboration using TrialMind yielded a 71.4% recall lift and 44.2% time savings in study screening and a 23.5% accuracy lift and 63.4% time savings in data extraction. Additionally, when comparing synthesized clinical evidence presented in forest plots, medical experts favored TrialMind's outputs over GPT-4's outputs in 62.5% to 100% of cases. These findings show the promise of LLM-based approaches like TrialMind to accelerate clinical evidence synthesis via streamlining study search, screening, and data extraction from medical literature, with exceptional performance improvement when working with human experts.

Surgical site infection (SSI) is one of the most common and costly healthcare-associated infections and and surgical wound care remains a significant clinical challenge in preventing SSIs and improving patient outcomes. While recent studies have explored the use of deep learning for preliminary surgical wound screening, progress has been hindered by concerns over data privacy and the high costs associated with expert annotation. Currently, no publicly available dataset or benchmark encompasses various types of surgical wounds, resulting in the absence of an open-source Surgical-Wound screening tool. To address this gap: (1) we present SurgWound, the first open-source dataset featuring a diverse array of surgical wound types. It contains 697 surgical wound images annotated by 3 professional surgeons with eight fine-grained clinical attributes. (2) Based on SurgWound, we introduce the first benchmark for surgical wound diagnosis, which includes visual question answering (VQA) and report generation tasks to comprehensively evaluate model performance. (3) Furthermore, we propose a three-stage learning framework, WoundQwen, for surgical wound diagnosis. In the first stage, we employ five independent MLLMs to accurately predict specific surgical wound characteristics. In the second stage, these predictions serve as additional knowledge inputs to two MLLMs responsible for diagnosing outcomes, which assess infection risk and guide subsequent interventions. In the third stage, we train a MLLM that integrates the diagnostic results from the previous two stages to produce a comprehensive report. This three-stage framework can analyze detailed surgical wound characteristics and provide subsequent instructions to patients based on surgical images, paving the way for personalized wound care, timely intervention, and improved patient outcomes.

The rapid increase of computed tomography (CT) scans and their time-consuming manual analysis have created an urgent need for robust automated analysis techniques in clinical settings. These aim to assist radiologists and help them managing their growing workload. Existing methods typically generate entire reports directly from 3D CT images, without explicitly focusing on observed abnormalities. This unguided approach often results in repetitive content or incomplete reports, failing to prioritize anomaly-specific descriptions. We propose a new anomaly-guided report generation model, which first predicts abnormalities and then generates targeted descriptions for each. Evaluation on a public dataset demonstrates significant improvements in report quality and clinical relevance. We extend our work by conducting an ablation study to demonstrate its effectiveness.

Early detection of gastric cancer, a leading cause of cancer-related mortality worldwide, remains hampered by the limitations of current diagnostic technologies, leading to high rates of misdiagnosis and missed diagnoses. To address these challenges, we propose an integrated system that synergizes advanced hardware and software technologies to balance speed-accuracy. Our study introduces the One Class Twin Cross Learning (OCT-X) algorithm. Leveraging a novel fast double-threshold grid search strategy (FDT-GS) and a patch-based deep fully convolutional network, OCT-X maximizes diagnostic accuracy through real-time data processing and seamless lesion surveillance. The hardware component includes an all-in-one point-of-care testing (POCT) device with high-resolution imaging sensors, real-time data processing, and wireless connectivity, facilitated by the NI CompactDAQ and LabVIEW software. Our integrated system achieved an unprecedented diagnostic accuracy of 99.70%, significantly outperforming existing models by up to 4.47%, and demonstrated a 10% improvement in multirate adaptability. These findings underscore the potential of OCT-X as well as the integrated system in clinical diagnostics, offering a path toward more accurate, efficient, and less invasive early gastric cancer detection. Future research will explore broader applications, further advancing oncological diagnostics. Code is available at https://github.com/liu37972/Multirate-Location-on-OCT-X-Learning.git.

A key strength of managed runtimes over hardware is the ability to gain detailed insight into the dynamic execution of programs with instrumentation. Analyses such as code coverage, execution frequency, tracing, and debugging, are all made easier in a virtual setting. As a portable, low-level bytecode, WebAssembly offers inexpensive in-process sandboxing with high performance. Yet to date, Wasm engines have not offered much insight into executing programs, supporting at best bytecode-level stepping and basic source maps, but no instrumentation capabilities. In this paper, we show the first non-intrusive dynamic instrumentation system for WebAssembly in the open-source Wizard Research Engine. Our innovative design offers a flexible, complete hierarchy of instrumentation primitives that support building high-level, complex analyses in terms of low-level, programmable probes. In contrast to emulation or machine code instrumentation, injecting probes at the bytecode level increases expressiveness and vastly simplifies the implementation by reusing the engine's JIT compiler, interpreter, and deoptimization mechanism rather than building new ones. Wizard supports both dynamic instrumentation insertion and removal while providing consistency guarantees, which is key to composing multiple analyses without interference. We detail a fully-featured implementation in a high-performance multi-tier Wasm engine, show novel optimizations specifically designed to minimize instrumentation overhead, and evaluate performance characteristics under load from various analyses. This design is well-suited for production engine adoption as probes can be implemented to have no impact on production performance when not in use.

In recent years, there is strong emphasis on mining medical data using machine learning techniques. A common problem is to obtain a noiseless set of textual documents, with a relevant content for the research question, and developing a Question Answering (QA) model for a specific medical field. The purpose of this paper is to present a new methodology for building a medical dataset and obtain a QA model for analysis of symptoms and impact on daily life for a specific disease domain. The ``Mental Health'' forum was used, a forum dedicated to people suffering from schizophrenia and different mental disorders. Relevant posts of active users, who regularly participate, were extrapolated providing a new method of obtaining low-bias content and without privacy issues. Furthermore, it is shown how to pre-process the dataset to convert it into a QA dataset. The Bidirectional Encoder Representations from Transformers (BERT), DistilBERT, RoBERTa, and BioBERT models were fine-tuned and evaluated via F1-Score, Exact Match, Precision and Recall. Accurate empirical experiments demonstrated the effectiveness of the proposed method for obtaining an accurate dataset for QA model implementation. By fine-tuning the BioBERT QA model, we achieved an F1 score of 0.885, showing a considerable improvement and outperforming the state-of-the-art model for mental disorders domain.

In this work, we develop an open-source surgical simulation environment that includes a realistic model obtained by MRI-scanning a physical phantom, for the purpose of training and evaluating a Learning from Demonstration (LfD) algorithm for autonomous suturing. The LfD algorithm utilizes Dynamic Movement Primitives (DMP) and Locally Weighted Regression (LWR), but focuses on the needle trajectory, rather than the instruments, to obtain better generality with respect to needle grasps. We conduct a user study to collect multiple suturing demonstrations and perform a comprehensive analysis of the ability of the LfD algorithm to generalize from a demonstration at one location in one phantom to different locations in the same phantom and to a different phantom. Our results indicate good generalization, on the order of 91.5%, when learning from more experienced subjects, indicating the need to integrate skill assessment in the future.

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

Medical diagnostic applications require models that can process multimodal medical inputs (images, patient histories, lab results) and generate diverse outputs including both textual reports and visual content (annotations, segmentation masks, and images). Despite this need, existing medical AI systems disrupt this unified process: medical image understanding models interpret images but cannot generate visual outputs, while medical image generation models synthesize images but cannot provide textual explanations. This leads to gaps in data representation, feature integration, and task-level multimodal capabilities. To this end, we propose a multi-level framework that draws inspiration from diagnostic workflows through the Observation-Knowledge-Analysis (OKA) paradigm. Specifically, at the observation level, we construct UniMed-5M, a dataset comprising over 5.6M samples that reformat diverse unimodal data into multimodal pairs for foundational observation. At the knowledge level, we propose Progressive Curriculum Learning that systematically introduces medical multimodal knowledge. At the analysis level, we introduce UniMedVL, the first medical unified multimodal model for the simultaneous analysis of image understanding and generation tasks within a single architecture. UniMedVL achieves superior performance on five medical image understanding benchmarks, while matching specialized models in generation quality across eight medical imaging modalities. Crucially, our unified architecture enables bidirectional knowledge sharing: generation tasks enhance visual understanding features, demonstrating that integrating traditionally separate capabilities within a single medical framework unlocks improvements across diverse medical vision-language tasks. Code is available at https://github.com/uni-medical/UniMedVL.

Test-time scaling has emerged as a powerful technique for enhancing the reasoning capabilities of large language models. However, its effectiveness in medical reasoning remains uncertain, as the medical domain fundamentally differs from mathematical tasks in terms of knowledge representation and decision-making processes. In this paper, we provide the first comprehensive investigation of test-time scaling for medical reasoning and present m1, a simple yet effective approach that increases a model's medical reasoning capability at inference. Our evaluation across diverse medical tasks demonstrates that test-time scaling consistently enhances medical reasoning, enabling lightweight fine-tuned models under 10B parameters to establish new state-of-the-art performance, while our 32B model rivals previous 70B-scale medical LLMs. However, we identify an optimal reasoning token budget of approximately 4K, beyond which performance may degrade due to overthinking. Budget forcing, which extends test-time computation through iterative prompts, helps models double-check answers but does not necessarily improve the overall medical QA performance and, in some cases, even introduces errors into previously correct responses. Our case-by-case analysis identifies insufficient medical knowledge as a key bottleneck that prevents further performance gains through test-time scaling. We find that increasing data scale, improving data quality, and expanding model capacity consistently enhance medical knowledge grounding, enabling continued performance improvements, particularly on challenging medical benchmarks where smaller models reach saturation. These findings underscore fundamental differences between medical and mathematical reasoning in LLMs, highlighting that enriched medical knowledge, other than increased reasoning depth alone, is essential for realizing the benefits of test-time scaling.

Hypothesis ranking is a crucial component of automated scientific discovery, particularly in natural sciences where wet-lab experiments are costly and throughput-limited. Existing approaches focus on pre-experiment ranking, relying solely on large language model's internal reasoning without incorporating empirical outcomes from experiments. We introduce the task of experiment-guided ranking, which aims to prioritize candidate hypotheses based on the results of previously tested ones. However, developing such strategies is challenging due to the impracticality of repeatedly conducting real experiments in natural science domains. To address this, we propose a simulator grounded in three domain-informed assumptions, modeling hypothesis performance as a function of similarity to a known ground truth hypothesis, perturbed by noise. We curate a dataset of 124 chemistry hypotheses with experimentally reported outcomes to validate the simulator. Building on this simulator, we develop a pseudo experiment-guided ranking method that clusters hypotheses by shared functional characteristics and prioritizes candidates based on insights derived from simulated experimental feedback. Experiments show that our method outperforms pre-experiment baselines and strong ablations.

Lung cancer remains the leading cause of cancer-related mortality worldwide, and early detection through low-dose computed tomography (LDCT) has shown significant promise in reducing death rates. With the growing integration of artificial intelligence (AI) into medical imaging, the development and evaluation of robust AI models require access to large, well-annotated datasets. In this study, we introduce the utility of Duke Lung Cancer Screening (DLCS) Dataset, the largest open-access LDCT dataset with over 2,000 scans and 3,000 expert-verified nodules. We benchmark deep learning models for both 3D nodule detection and lung cancer classification across internal and external datasets including LUNA16, LUNA25, and NLST-3D+. For detection, we develop two MONAI-based RetinaNet models (DLCSDmD and LUNA16-mD), evaluated using the Competition Performance Metric (CPM). For classification, we compare five models, including state-of-the-art pretrained models (Models Genesis, Med3D), a selfsupervised foundation model (FMCB), a randomly initialized ResNet50, and proposed a novel Strategic Warm-Start++ (SWS++) model. SWS++ uses curated candidate patches to pretrain a classification backbone within the same detection pipeline, enabling task-relevant feature learning. Our models demonstrated strong generalizability, with SWS++ achieving comparable or superior performance to existing foundational models across multiple datasets (AUC: 0.71 to 0.90). All code, models, and data are publicly released to promote reproducibility and collaboration. This work establishes a standardized benchmarking resource for lung cancer AI research, supporting future efforts in model development, validation, and clinical translation.

Large Language Models (LLMs) have shown remarkable success in supporting a wide range of knowledge-intensive tasks. In specialized domains, there is growing interest in leveraging LLMs to assist subject matter experts with domain-specific challenges. However, deploying LLMs as SaaS solutions raises data privacy concerns, while many open-source models demand significant computational resources for effective domain adaptation and deployment. A promising alternative is to develop smaller, domain-specialized LLMs, though this approach is often constrained by the lack of high-quality domain-specific training data. In this work, we address these limitations by presenting a cost-efficient and scalable training pipeline that combines guided synthetic data generation from a small seed corpus with bottom-up domain data curation. Our pipeline integrates Domain-Adaptive Pretraining (DAPT), Domain-specific Supervised Fine-tuning (DSFT), and Direct Preference Optimization (DPO) to train effective small-scale models for specialized use cases. We demonstrate this approach through DiagnosticSLM, a 3B-parameter domain-specific model tailored for fault diagnosis, root cause analysis, and repair recommendation in industrial settings. To evaluate model performance, we introduce four domain-specific benchmarks: multiple-choice questions (DiagnosticMCQ), question answering (DiagnosticQA), sentence completion (DiagnosticComp), and summarization (DiagnosticSum). DiagnosticSLM achieves up to 25% accuracy improvement over open-source models of comparable or larger size (2B-9B) on the MCQ task, while also outperforming or matching them in other tasks, demonstrating effective domain-specific reasoning and generalization capabilities.

Medical imaging plays a significant role in clinical practice of medical diagnosis, where the text reports of the images are essential in understanding them and facilitating later treatments. By generating the reports automatically, it is beneficial to help lighten the burden of radiologists and significantly promote clinical automation, which already attracts much attention in applying artificial intelligence to medical domain. Previous studies mainly follow the encoder-decoder paradigm and focus on the aspect of text generation, with few studies considering the importance of cross-modal mappings and explicitly exploit such mappings to facilitate radiology report generation. In this paper, we propose a cross-modal memory networks (CMN) to enhance the encoder-decoder framework for radiology report generation, where a shared memory is designed to record the alignment between images and texts so as to facilitate the interaction and generation across modalities. Experimental results illustrate the effectiveness of our proposed model, where state-of-the-art performance is achieved on two widely used benchmark datasets, i.e., IU X-Ray and MIMIC-CXR. Further analyses also prove that our model is able to better align information from radiology images and texts so as to help generating more accurate reports in terms of clinical indicators.

Large Language Models (LLMs) and multi-agent systems have shown impressive capabilities in natural language tasks but face challenges in clinical trial applications, primarily due to limited access to external knowledge. Recognizing the potential of advanced clinical trial tools that aggregate and predict based on the latest medical data, we propose an integrated solution to enhance their accessibility and utility. We introduce Clinical Agent System (ClinicalAgent), a clinical multi-agent system designed for clinical trial tasks, leveraging GPT-4, multi-agent architectures, LEAST-TO-MOST, and ReAct reasoning technology. This integration not only boosts LLM performance in clinical contexts but also introduces novel functionalities. The proposed method achieves competitive predictive performance in clinical trial outcome prediction (0.7908 PR-AUC), obtaining a 0.3326 improvement over the standard prompt Method. Publicly available code can be found at https://anonymous.4open.science/r/ClinicalAgent-6671.

Semantic medical image segmentation is a crucial part of both scientific research and clinical care. With enough labelled data, deep learning models can be trained to accurately automate specific medical image segmentation tasks. However, manually segmenting images to create training data is highly labor intensive. In this paper, we present ScribblePrompt, an interactive segmentation framework for medical imaging that enables human annotators to segment unseen structures using scribbles, clicks, and bounding boxes. Scribbles are an intuitive and effective form of user interaction for complex tasks, however most existing methods focus on click-based interactions. We introduce algorithms for simulating realistic scribbles that enable training models that are amenable to multiple types of interaction. To achieve generalization to new tasks, we train on a diverse collection of 65 open-access biomedical datasets -- using both real and synthetic labels. We test ScribblePrompt on multiple network architectures and unseen datasets, and demonstrate that it can be used in real-time on a single CPU. We evaluate ScribblePrompt using manually-collected scribbles, simulated interactions, and a user study. ScribblePrompt outperforms existing methods in all our evaluations. In the user study, ScribblePrompt reduced annotation time by 28% while improving Dice by 15% compared to existing methods. We showcase ScribblePrompt in an online demo and provide code at https://scribbleprompt.csail.mit.edu

Radiology reports contain rich clinical information that can be used to train imaging models without relying on costly manual annotation. However, existing approaches face critical limitations: rule-based methods struggle with linguistic variability, supervised models require large annotated datasets, and recent LLM-based systems depend on closed-source or resource-intensive models that are unsuitable for clinical use. Moreover, current solutions are largely restricted to English and single-modality, single-taxonomy datasets. We introduce MOSAIC, a multilingual, taxonomy-agnostic, and computationally efficient approach for radiological report classification. Built on a compact open-access language model (MedGemma-4B), MOSAIC supports both zero-/few-shot prompting and lightweight fine-tuning, enabling deployment on consumer-grade GPUs. We evaluate MOSAIC across seven datasets in English, Spanish, French, and Danish, spanning multiple imaging modalities and label taxonomies. The model achieves a mean macro F1 score of 88 across five chest X-ray datasets, approaching or exceeding expert-level performance, while requiring only 24 GB of GPU memory. With data augmentation, as few as 80 annotated samples are sufficient to reach a weighted F1 score of 82 on Danish reports, compared to 86 with the full 1600-sample training set. MOSAIC offers a practical alternative to large or proprietary LLMs in clinical settings. Code and models are open-source. We invite the community to evaluate and extend MOSAIC on new languages, taxonomies, and modalities.

Recruiting patients to participate in clinical trials can be challenging and time-consuming. Usually, participation in a clinical trial is initiated by a healthcare professional and proposed to the patient. Promoting clinical trials directly to patients via online recruitment might help to reach them more efficiently. In this study, we address the case where a patient is initiating their own recruitment process and wants to determine whether they are eligible for a given clinical trial, using their own language to describe their medical profile. To study whether this creates difficulties in the patient trial matching process, we design a new dataset and task, Natural Language Inference for Patient Recruitment (NLI4PR), in which patient language profiles must be matched to clinical trials. We create it by adapting the TREC 2022 Clinical Trial Track dataset, which provides patients' medical profiles, and rephrasing them manually using patient language. We also use the associated clinical trial reports where the patients are either eligible or excluded. We prompt several open-source Large Language Models on our task and achieve from 56.5 to 71.8 of F1 score using patient language, against 64.7 to 73.1 for the same task using medical language. When using patient language, we observe only a small loss in performance for the best model, suggesting that having the patient as a starting point could be adopted to help recruit patients for clinical trials. The corpus and code bases are all freely available on our Github and HuggingFace repositories.

The need for improved diagnostic methods in ophthalmology is acute, especially in the underdeveloped regions with limited access to specialists and advanced equipment. Therefore, we introduce VisionUnite, a novel vision-language foundation model for ophthalmology enhanced with clinical knowledge. VisionUnite has been pretrained on an extensive dataset comprising 1.24 million image-text pairs, and further refined using our proposed MMFundus dataset, which includes 296,379 high-quality fundus image-text pairs and 889,137 simulated doctor-patient dialogue instances. Our experiments indicate that VisionUnite outperforms existing generative foundation models such as GPT-4V and Gemini Pro. It also demonstrates diagnostic capabilities comparable to junior ophthalmologists. VisionUnite performs well in various clinical scenarios including open-ended multi-disease diagnosis, clinical explanation, and patient interaction, making it a highly versatile tool for initial ophthalmic disease screening. VisionUnite can also serve as an educational aid for junior ophthalmologists, accelerating their acquisition of knowledge regarding both common and underrepresented ophthalmic conditions. VisionUnite represents a significant advancement in ophthalmology, with broad implications for diagnostics, medical education, and understanding of disease mechanisms. The source code is at https://github.com/HUANGLIZI/VisionUnite.

Medical imaging is frequently used in clinical practice and trials for diagnosis and treatment. Writing imaging reports is time-consuming and can be error-prone for inexperienced radiologists. Therefore, automatically generating radiology reports is highly desired to lighten the workload of radiologists and accordingly promote clinical automation, which is an essential task to apply artificial intelligence to the medical domain. In this paper, we propose to generate radiology reports with memory-driven Transformer, where a relational memory is designed to record key information of the generation process and a memory-driven conditional layer normalization is applied to incorporating the memory into the decoder of Transformer. Experimental results on two prevailing radiology report datasets, IU X-Ray and MIMIC-CXR, show that our proposed approach outperforms previous models with respect to both language generation metrics and clinical evaluations. Particularly, this is the first work reporting the generation results on MIMIC-CXR to the best of our knowledge. Further analyses also demonstrate that our approach is able to generate long reports with necessary medical terms as well as meaningful image-text attention mappings.

Patient recruitment is challenging for clinical trials. We introduce TrialGPT, an end-to-end framework for zero-shot patient-to-trial matching with large language models. TrialGPT comprises three modules: it first performs large-scale filtering to retrieve candidate trials (TrialGPT-Retrieval); then predicts criterion-level patient eligibility (TrialGPT-Matching); and finally generates trial-level scores (TrialGPT-Ranking). We evaluate TrialGPT on three cohorts of 183 synthetic patients with over 75,000 trial annotations. TrialGPT-Retrieval can recall over 90% of relevant trials using less than 6% of the initial collection. Manual evaluations on 1,015 patient-criterion pairs show that TrialGPT-Matching achieves an accuracy of 87.3% with faithful explanations, close to the expert performance. The TrialGPT-Ranking scores are highly correlated with human judgments and outperform the best-competing models by 43.8% in ranking and excluding trials. Furthermore, our user study reveals that TrialGPT can reduce the screening time by 42.6% in patient recruitment. Overall, these results have demonstrated promising opportunities for patient-to-trial matching with TrialGPT.

Scientific discovery relies on scientists generating novel hypotheses that undergo rigorous experimental validation. To augment this process, we introduce an AI co-scientist, a multi-agent system built on Gemini 2.0. The AI co-scientist is intended to help uncover new, original knowledge and to formulate demonstrably novel research hypotheses and proposals, building upon prior evidence and aligned to scientist-provided research objectives and guidance. The system's design incorporates a generate, debate, and evolve approach to hypothesis generation, inspired by the scientific method and accelerated by scaling test-time compute. Key contributions include: (1) a multi-agent architecture with an asynchronous task execution framework for flexible compute scaling; (2) a tournament evolution process for self-improving hypotheses generation. Automated evaluations show continued benefits of test-time compute, improving hypothesis quality. While general purpose, we focus development and validation in three biomedical areas: drug repurposing, novel target discovery, and explaining mechanisms of bacterial evolution and anti-microbial resistance. For drug repurposing, the system proposes candidates with promising validation findings, including candidates for acute myeloid leukemia that show tumor inhibition in vitro at clinically applicable concentrations. For novel target discovery, the AI co-scientist proposed new epigenetic targets for liver fibrosis, validated by anti-fibrotic activity and liver cell regeneration in human hepatic organoids. Finally, the AI co-scientist recapitulated unpublished experimental results via a parallel in silico discovery of a novel gene transfer mechanism in bacterial evolution. These results, detailed in separate, co-timed reports, demonstrate the potential to augment biomedical and scientific discovery and usher an era of AI empowered scientists.

Test case generation is an important activity, yet a time-consuming and laborious task. Recently, AthenaTest -- a deep learning approach for generating unit test cases -- is proposed. However, AthenaTest can generate less than one-fifth of the test cases correctly, due to a lack of assertion knowledge and test signature verification. In this paper, we propose A3Test, a DL-based test case generation approach that is augmented by assertion knowledge with a mechanism to verify naming consistency and test signatures. A3Test leverages the domain adaptation principles where the goal is to adapt the existing knowledge from an assertion generation task to the test case generation task. We also introduce a verification approach to verify naming consistency and test signatures. Through an evaluation of 5,278 focal methods from the Defects4j dataset, we find that our A3Test (1) achieves 147% more correct test cases and 15% more method coverage, with a lower number of generated test cases than AthenaTest; (2) still outperforms the existing pre-trained models for the test case generation task; (3) contributes substantially to performance improvement via our own proposed assertion pre-training and the verification components; (4) is 97.2% much faster while being more accurate than AthenaTest.

Accurate and interpretable multi-disease diagnosis remains a critical challenge in medical research, particularly when leveraging heterogeneous multimodal medical data. Current approaches often rely on single-modal data, limiting their ability to comprehensively understand complex diseases. To address this, we propose MedTVT-R1, a novel Multimodal Large Language Model (MLLM) framework designed to integrate clinical multimodal data for reasoning and diagnosing multiple diseases. We construct MedTVT-QA, a curated instruction dataset that provides question-answer pairs for physiological-level interpretations and disease-level diagnoses with a Chain of Evidence approach. MedTVT-R1 incorporates a modality perception layer to capture inter-modal dependencies and adaptively weight modality contributions. Additionally, we employ Group Relative Policy Optimization (GRPO)-based Reinforcement Fine-Tuning with a Jaccard Reward function to enhance diagnostic reasoning. Experimental results demonstrate MedTVT-R1's superiority in multimodal feature utilization and multi-disease diagnosis, offering significant potential for clinical applications such as diagnostic report generation and comorbidity reasoning. The dataset and code are available at https://github.com/keke-nice/MedTVT-R1.

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

Automated diagnostic systems (ADS) have shown significant potential in the early detection of polyps during endoscopic examinations, thereby reducing the incidence of colorectal cancer. However, due to high annotation costs and strict privacy concerns, acquiring high-quality endoscopic images poses a considerable challenge in the development of ADS. Despite recent advancements in generating synthetic images for dataset expansion, existing endoscopic image generation algorithms failed to accurately generate the details of polyp boundary regions and typically required medical priors to specify plausible locations and shapes of polyps, which limited the realism and diversity of the generated images. To address these limitations, we present Polyp-Gen, the first full-automatic diffusion-based endoscopic image generation framework. Specifically, we devise a spatial-aware diffusion training scheme with a lesion-guided loss to enhance the structural context of polyp boundary regions. Moreover, to capture medical priors for the localization of potential polyp areas, we introduce a hierarchical retrieval-based sampling strategy to match similar fine-grained spatial features. In this way, our Polyp-Gen can generate realistic and diverse endoscopic images for building reliable ADS. Extensive experiments demonstrate the state-of-the-art generation quality, and the synthetic images can improve the downstream polyp detection task. Additionally, our Polyp-Gen has shown remarkable zero-shot generalizability on other datasets. The source code is available at https://github.com/CUHK-AIM-Group/Polyp-Gen.

Medical care follows complex clinical pathways that extend beyond isolated physician-patient encounters, emphasizing decision-making and transitions between different stages. Current benchmarks focusing on static exams or isolated dialogues inadequately evaluate large language models (LLMs) in dynamic clinical scenarios. We introduce CP-Env, a controllable agentic hospital environment designed to evaluate LLMs across end-to-end clinical pathways. CP-Env simulates a hospital ecosystem with patient and physician agents, constructing scenarios ranging from triage and specialist consultation to diagnostic testing and multidisciplinary team meetings for agent interaction. Following real hospital adaptive flow of healthcare, it enables branching, long-horizon task execution. We propose a three-tiered evaluation framework encompassing Clinical Efficacy, Process Competency, and Professional Ethics. Results reveal that most models struggle with pathway complexity, exhibiting hallucinations and losing critical diagnostic details. Interestingly, excessive reasoning steps can sometimes prove counterproductive, while top models tend to exhibit reduced tool dependency through internalized knowledge. CP-Env advances medical AI agents development through comprehensive end-to-end clinical evaluation. We provide the benchmark and evaluation tools for further research and development at https://github.com/SPIRAL-MED/CP_ENV.

Language promptable X-ray image segmentation would enable greater flexibility for human-in-the-loop workflows in diagnostic and interventional precision medicine. Prior efforts have contributed task-specific models capable of solving problems within a narrow scope, but expanding to broader use requires additional data, annotations, and training time. Recently, language-aligned foundation models (LFMs) -- machine learning models trained on large amounts of highly variable image and text data thus enabling broad applicability -- have emerged as promising tools for automated image analysis. Existing foundation models for medical image analysis focus on scenarios and modalities where large, richly annotated datasets are available. However, the X-ray imaging modality features highly variable image appearance and applications, from diagnostic chest X-rays to interventional fluoroscopy, with varying availability of data. To pave the way toward an LFM for comprehensive and language-aligned analysis of arbitrary medical X-ray images, we introduce FluoroSAM, a language-promptable variant of the Segment Anything Model, trained from scratch on 3M synthetic X-ray images from a wide variety of human anatomies, imaging geometries, and viewing angles. These include pseudo-ground truth masks for 128 organ types and 464 tools with associated text descriptions. FluoroSAM is capable of segmenting myriad anatomical structures and tools based on natural language prompts, thanks to the novel incorporation of vector quantization (VQ) of text embeddings in the training process. We demonstrate FluoroSAM's performance quantitatively on real X-ray images and showcase on several applications how FluoroSAM is a key enabler for rich human-machine interaction in the X-ray image acquisition and analysis context. Code is available at https://github.com/arcadelab/fluorosam.

Pre-trained language models like ChatGPT have significantly improved code generation. As these models scale up, there is an increasing need for the output to handle more intricate tasks. Moreover, in bioinformatics, generating functional programs poses additional notable challenges due to the amount of domain knowledge, the need for complicated data operations, and intricate functional dependencies between the operations. Here, we present BioCoder, a benchmark developed to evaluate existing pre-trained models in generating bioinformatics code. In relation to function-code generation, BioCoder covers potential package dependencies, class declarations, and global variables. It incorporates 1026 functions and 1243 methods in Python and Java from GitHub and 253 examples from the Rosalind Project. BioCoder incorporates a fuzz-testing framework for evaluation, and we have applied it to evaluate many models including InCoder, CodeGen, CodeGen2, SantaCoder, StarCoder, StarCoder+, InstructCodeT5+, and ChatGPT. Our detailed analysis of these models emphasizes the importance of domain knowledge, pragmatic code generation, and contextual understanding. Our dataset, benchmark, Docker images, and scripts required for testing are all available at https://github.com/gersteinlab/biocoder.

Large language models (LLMs) integrated into agent-driven workflows hold immense promise for healthcare, yet a significant gap exists between their potential and practical implementation within clinical settings. To address this, we present a practitioner-oriented field manual for deploying generative agents that use electronic health record (EHR) data. This guide is informed by our experience deploying the "irAE-Agent", an automated system to detect immune-related adverse events from clinical notes at Mass General Brigham, and by structured interviews with 21 clinicians, engineers, and informatics leaders involved in the project. Our analysis reveals a critical misalignment in clinical AI development: less than 20% of our effort was dedicated to prompt engineering and model development, while over 80% was consumed by the sociotechnical work of implementation. We distill this effort into five "heavy lifts": data integration, model validation, ensuring economic value, managing system drift, and governance. By providing actionable solutions for each of these challenges, this field manual shifts the focus from algorithmic development to the essential infrastructure and implementation work required to bridge the "valley of death" and successfully translate generative AI from pilot projects into routine clinical care.

Differential diagnosis is crucial for medicine as it helps healthcare providers systematically distinguish between conditions that share similar symptoms. This study assesses the impact of lab test results on differential diagnoses (DDx) made by large language models (LLMs). Clinical vignettes from 50 case reports from PubMed Central were created incorporating patient demographics, symptoms, and lab results. Five LLMs GPT-4, GPT-3.5, Llama-2-70b, Claude-2, and Mixtral-8x7B were tested to generate Top 10, Top 5, and Top 1 DDx with and without lab data. A comprehensive evaluation involving GPT-4, a knowledge graph, and clinicians was conducted. GPT-4 performed best, achieving 55% accuracy for Top 1 diagnoses and 60% for Top 10 with lab data, with lenient accuracy up to 80%. Lab results significantly improved accuracy, with GPT-4 and Mixtral excelling, though exact match rates were low. Lab tests, including liver function, metabolic/toxicology panels, and serology/immune tests, were generally interpreted correctly by LLMs for differential diagnosis.

Accurate diagnostic coding of medical notes is crucial for enhancing patient care, medical research, and error-free billing in healthcare organizations. Manual coding is a time-consuming task for providers, and diagnostic codes often exhibit low sensitivity and specificity, whereas the free text in medical notes can be a more precise description of a patients status. Thus, accurate automated diagnostic coding of medical notes has become critical for a learning healthcare system. Recent developments in long-document transformer architectures have enabled attention-based deep-learning models to adjudicate medical notes. In addition, contrastive loss functions have been used to jointly pre-train large language and image models with noisy labels. To further improve the automated adjudication of medical notes, we developed an approach based on i) models for ICD-10 diagnostic code sequences using a large real-world data set, ii) large language models for medical notes, and iii) contrastive pre-training to build an integrated model of both ICD-10 diagnostic codes and corresponding medical text. We demonstrate that a contrastive approach for pre-training improves performance over prior state-of-the-art models for the MIMIC-III-50, MIMIC-III-rare50, and MIMIC-III-full diagnostic coding tasks.

Objective: To allow efficient learning using the Recurrent Inference Machine (RIM) for image reconstruction whereas not being strictly dependent on the training data distribution so that unseen modalities and pathologies are still accurately recovered. Methods: Theoretically, the RIM learns to solve the inverse problem of accelerated-MRI reconstruction whereas being robust to variable imaging conditions. The efficiency and generalization capabilities with different training datasets were studied, as well as recurrent network units with decreasing complexity: the Gated Recurrent Unit (GRU), the Minimal Gated Unit (MGU), and the Independently Recurrent Neural Network (IndRNN), to reduce inference times. Validation was performed against Compressed Sensing (CS) and further assessed based on data unseen during training. A pathology study was conducted by reconstructing simulated white matter lesions and prospectively undersampled data of a Multiple Sclerosis patient. Results: Training on a single modality of 3T T_1-weighted brain data appeared sufficient to also reconstruct 7T T_{2}^*-weighted brain and 3T T_2-weighted knee data. The IndRNN is an efficient recurrent unit, reducing inference time by 68\% compared to CS, whereas maintaining performance. The RIM was able to reconstruct lesions unseen during training more accurately than CS when trained on T_2-weighted knee data. Training on T_1-weighted brain data and on combined data slightly enhanced the signal compared to CS. Conclusion: The RIM is efficient when decreasing its complexity, which reduces the inference time, whereas still being able to reconstruct data and pathology that was unseen during training.

Multiple Instance Learning (MIL) is a sub-domain of classification problems with positive and negative labels and a "bag" of inputs, where the label is positive if and only if a positive element is contained within the bag, and otherwise is negative. Training in this context requires associating the bag-wide label to instance-level information, and implicitly contains a causal assumption and asymmetry to the task (i.e., you can't swap the labels without changing the semantics). MIL problems occur in healthcare (one malignant cell indicates cancer), cyber security (one malicious executable makes an infected computer), and many other tasks. In this work, we examine five of the most prominent deep-MIL models and find that none of them respects the standard MIL assumption. They are able to learn anti-correlated instances, i.e., defaulting to "positive" labels until seeing a negative counter-example, which should not be possible for a correct MIL model. We suspect that enhancements and other works derived from these models will share the same issue. In any context in which these models are being used, this creates the potential for learning incorrect models, which creates risk of operational failure. We identify and demonstrate this problem via a proposed "algorithmic unit test", where we create synthetic datasets that can be solved by a MIL respecting model, and which clearly reveal learning that violates MIL assumptions. The five evaluated methods each fail one or more of these tests. This provides a model-agnostic way to identify violations of modeling assumptions, which we hope will be useful for future development and evaluation of MIL models.

This paper presents a comprehensive evaluation of GPT-4V's capabilities across diverse medical imaging tasks, including Radiology Report Generation, Medical Visual Question Answering (VQA), and Visual Grounding. While prior efforts have explored GPT-4V's performance in medical image analysis, to the best of our knowledge, our study represents the first quantitative evaluation on publicly available benchmarks. Our findings highlight GPT-4V's potential in generating descriptive reports for chest X-ray images, particularly when guided by well-structured prompts. Meanwhile, its performance on the MIMIC-CXR dataset benchmark reveals areas for improvement in certain evaluation metrics, such as CIDEr. In the domain of Medical VQA, GPT-4V demonstrates proficiency in distinguishing between question types but falls short of the VQA-RAD benchmark in terms of accuracy. Furthermore, our analysis finds the limitations of conventional evaluation metrics like the BLEU scores, advocating for the development of more semantically robust assessment methods. In the field of Visual Grounding, GPT-4V exhibits preliminary promise in recognizing bounding boxes, but its precision is lacking, especially in identifying specific medical organs and signs. Our evaluation underscores the significant potential of GPT-4V in the medical imaging domain, while also emphasizing the need for targeted refinements to fully unlock its capabilities.