Daily Papers

The rapid development of Large Language Models (LLMs) for healthcare applications has spurred calls for holistic evaluation beyond frequently-cited benchmarks like USMLE, to better reflect real-world performance. While real-world assessments are valuable indicators of utility, they often lag behind the pace of LLM evolution, likely rendering findings obsolete upon deployment. This temporal disconnect necessitates a comprehensive upfront evaluation that can guide model selection for specific clinical applications. We introduce MEDIC, a framework assessing LLMs across five critical dimensions of clinical competence: medical reasoning, ethics and bias, data and language understanding, in-context learning, and clinical safety. MEDIC features a novel cross-examination framework quantifying LLM performance across areas like coverage and hallucination detection, without requiring reference outputs. We apply MEDIC to evaluate LLMs on medical question-answering, safety, summarization, note generation, and other tasks. Our results show performance disparities across model sizes, baseline vs medically finetuned models, and have implications on model selection for applications requiring specific model strengths, such as low hallucination or lower cost of inference. MEDIC's multifaceted evaluation reveals these performance trade-offs, bridging the gap between theoretical capabilities and practical implementation in healthcare settings, ensuring that the most promising models are identified and adapted for diverse healthcare applications.

Brain-Computer Interface (BCI) systems allow users to perform actions by translating their brain activity into commands. Such systems usually need a training phase, consisting in training a classification algorithm to discriminate between mental states using specific features from the recorded signals. This phase of feature selection and training is crucial for BCI performance and presents specific constraints to be met in a clinical context, such as post-stroke rehabilitation. In this paper, we present HappyFeat, a software making Motor Imagery (MI) based BCI experiments easier, by gathering all necessary manipulations and analysis in a single convenient GUI and via automation of experiment or analysis parameters. The resulting workflow allows for effortlessly selecting the best features, helping to achieve good BCI performance in time-constrained environments. Alternative features based on Functional Connectivity can be used and compared or combined with Power Spectral Density, allowing a network-oriented approach. We then give details of HappyFeat's main mechanisms, and a review of its performances in typical use cases. We also show that it can be used as an efficient tool for comparing different metrics extracted from the signals, to train the classification algorithm. To this end, we show a comparison between the commonly-used Power Spectral Density and network metrics based on Functional Connectivity. HappyFeat is available as an open-source project which can be freely downloaded on GitHub.

Artificial intelligence (AI) that can effectively learn ultrasound representations by integrating multi-source data holds significant promise for advancing clinical care. However, the scarcity of large labeled datasets in real-world clinical environments and the limited generalizability of task-specific models have hindered the development of generalizable clinical AI models for ultrasound applications. In this study, we present EchoCare, a novel ultrasound foundation model for generalist clinical use, developed via self-supervised learning on our curated, publicly available, large-scale dataset EchoCareData. EchoCareData comprises 4.5 million ultrasound images, sourced from over 23 countries across 5 continents and acquired via a diverse range of distinct imaging devices, thus encompassing global cohorts that are multi-center, multi-device, and multi-ethnic. Unlike prior studies that adopt off-the-shelf vision foundation model architectures, we introduce a hierarchical classifier into EchoCare to enable joint learning of pixel-level and representation-level features, capturing both global anatomical contexts and local ultrasound characteristics. With minimal training, EchoCare outperforms state-of-the-art comparison models across 10 representative ultrasound benchmarks of varying diagnostic difficulties, spanning disease diagnosis, lesion segmentation, organ detection, landmark prediction, quantitative regression, imaging enhancement and report generation. The code and pretrained model are publicly released, rendering EchoCare accessible for fine-tuning and local adaptation, supporting extensibility to additional applications. EchoCare provides a fully open and generalizable foundation model to boost the development of AI technologies for diverse clinical ultrasound applications.

Large language models (LLMs) such as GPT-4o and o1 have demonstrated strong performance on clinical natural language processing (NLP) tasks across multiple medical benchmarks. Nonetheless, two high-impact NLP tasks - structured tabular reporting from nurse dictations and medical order extraction from doctor-patient consultations - remain underexplored due to data scarcity and sensitivity, despite active industry efforts. Practical solutions to these real-world clinical tasks can significantly reduce the documentation burden on healthcare providers, allowing greater focus on patient care. In this paper, we investigate these two challenging tasks using private and open-source clinical datasets, evaluating the performance of both open- and closed-weight LLMs, and analyzing their respective strengths and limitations. Furthermore, we propose an agentic pipeline for generating realistic, non-sensitive nurse dictations, enabling structured extraction of clinical observations. To support further research in both areas, we release SYNUR and SIMORD, the first open-source datasets for nurse observation extraction and medical order extraction.

Foundation Models (FMs) trained on Electronic Health Records (EHRs) have achieved state-of-the-art results on numerous clinical prediction tasks. However, most existing EHR FMs have context windows of <1k tokens. This prevents them from modeling full patient EHRs which can exceed 10k's of events. Recent advancements in subquadratic long-context architectures (e.g., Mamba) offer a promising solution. However, their application to EHR data has not been well-studied. We address this gap by presenting the first systematic evaluation of the effect of context length on modeling EHR data. We find that longer context models improve predictive performance -- our Mamba-based model surpasses the prior state-of-the-art on 9/14 tasks on the EHRSHOT prediction benchmark. For clinical applications, however, model performance alone is insufficient -- robustness to the unique properties of EHR is crucial. Thus, we also evaluate models across three previously underexplored properties of EHR data: (1) the prevalence of "copy-forwarded" diagnoses which creates artificial repetition of tokens within EHR sequences; (2) the irregular time intervals between EHR events which can lead to a wide range of timespans within a context window; and (3) the natural increase in disease complexity over time which makes later tokens in the EHR harder to predict than earlier ones. Stratifying our EHRSHOT results, we find that higher levels of each property correlate negatively with model performance, but that longer context models are more robust to more extreme levels of these properties. Our work highlights the potential for using long-context architectures to model EHR data, and offers a case study for identifying new challenges in modeling sequential data motivated by domains outside of natural language. We release our models and code at: https://github.com/som-shahlab/long_context_clues

Medical vision-and-language models (MVLMs) have attracted substantial interest due to their capability to offer a natural language interface for interpreting complex medical data. Their applications are versatile and have the potential to improve diagnostic accuracy and decision-making for individual patients while also contributing to enhanced public health monitoring, disease surveillance, and policy-making through more efficient analysis of large data sets. MVLMS integrate natural language processing with medical images to enable a more comprehensive and contextual understanding of medical images alongside their corresponding textual information. Unlike general vision-and-language models trained on diverse, non-specialized datasets, MVLMs are purpose-built for the medical domain, automatically extracting and interpreting critical information from medical images and textual reports to support clinical decision-making. Popular clinical applications of MVLMs include automated medical report generation, medical visual question answering, medical multimodal segmentation, diagnosis and prognosis and medical image-text retrieval. Here, we provide a comprehensive overview of MVLMs and the various medical tasks to which they have been applied. We conduct a detailed analysis of various vision-and-language model architectures, focusing on their distinct strategies for cross-modal integration/exploitation of medical visual and textual features. We also examine the datasets used for these tasks and compare the performance of different models based on standardized evaluation metrics. Furthermore, we highlight potential challenges and summarize future research trends and directions. The full collection of papers and codes is available at: https://github.com/YtongXie/Medical-Vision-and-Language-Tasks-and-Methodologies-A-Survey.

Purpose: In radiology, large language models (LLMs), including ChatGPT, have recently gained attention, and their utility is being rapidly evaluated. However, concerns have emerged regarding their reliability in clinical applications due to limitations such as hallucinations and insufficient referencing. To address these issues, we focus on the latest technology, retrieval-augmented generation (RAG), which enables LLMs to reference reliable external knowledge (REK). Specifically, this study examines the utility and reliability of a recently released RAG-equipped LLM (RAG-LLM), NotebookLM, for staging lung cancer. Materials and methods: We summarized the current lung cancer staging guideline in Japan and provided this as REK to NotebookLM. We then tasked NotebookLM with staging 100 fictional lung cancer cases based on CT findings and evaluated its accuracy. For comparison, we performed the same task using a gold-standard LLM, GPT-4 Omni (GPT-4o), both with and without the REK. Results: NotebookLM achieved 86% diagnostic accuracy in the lung cancer staging experiment, outperforming GPT-4o, which recorded 39% accuracy with the REK and 25% without it. Moreover, NotebookLM demonstrated 95% accuracy in searching reference locations within the REK. Conclusion: NotebookLM successfully performed lung cancer staging by utilizing the REK, demonstrating superior performance compared to GPT-4o. Additionally, it provided highly accurate reference locations within the REK, allowing radiologists to efficiently evaluate the reliability of NotebookLM's responses and detect possible hallucinations. Overall, this study highlights the potential of NotebookLM, a RAG-LLM, in image diagnosis.

Pre-trained transformers are often fine-tuned to aid clinical decision-making using limited clinical notes. Model interpretability is crucial, especially in high-stakes domains like medicine, to establish trust and ensure safety, which requires human engagement. We introduce SUFO, a systematic framework that enhances interpretability of fine-tuned transformer feature spaces. SUFO utilizes a range of analytic and visualization techniques, including Supervised probing, Unsupervised similarity analysis, Feature dynamics, and Outlier analysis to address key questions about model trust and interpretability. We conduct a case study investigating the impact of pre-training data where we focus on real-world pathology classification tasks, and validate our findings on MedNLI. We evaluate five 110M-sized pre-trained transformer models, categorized into general-domain (BERT, TNLR), mixed-domain (BioBERT, Clinical BioBERT), and domain-specific (PubMedBERT) groups. Our SUFO analyses reveal that: (1) while PubMedBERT, the domain-specific model, contains valuable information for fine-tuning, it can overfit to minority classes when class imbalances exist. In contrast, mixed-domain models exhibit greater resistance to overfitting, suggesting potential improvements in domain-specific model robustness; (2) in-domain pre-training accelerates feature disambiguation during fine-tuning; and (3) feature spaces undergo significant sparsification during this process, enabling clinicians to identify common outlier modes among fine-tuned models as demonstrated in this paper. These findings showcase the utility of SUFO in enhancing trust and safety when using transformers in medicine, and we believe SUFO can aid practitioners in evaluating fine-tuned language models for other applications in medicine and in more critical domains.

The emergence of vision-language models has transformed medical AI, enabling unprecedented advances in diagnostic capability and clinical applications. However, progress in dermatology has lagged behind other medical domains due to the lack of standard image-text pairs. Existing dermatological datasets are limited in both scale and depth, offering only single-label annotations across a narrow range of diseases instead of rich textual descriptions, and lacking the crucial clinical context needed for real-world applications. To address these limitations, we present Derm1M, the first large-scale vision-language dataset for dermatology, comprising 1,029,761 image-text pairs. Built from diverse educational resources and structured around a standard ontology collaboratively developed by experts, Derm1M provides comprehensive coverage for over 390 skin conditions across four hierarchical levels and 130 clinical concepts with rich contextual information such as medical history, symptoms, and skin tone. To demonstrate Derm1M potential in advancing both AI research and clinical application, we pretrained a series of CLIP-like models, collectively called DermLIP, on this dataset. The DermLIP family significantly outperforms state-of-the-art foundation models on eight diverse datasets across multiple tasks, including zero-shot skin disease classification, clinical and artifacts concept identification, few-shot/full-shot learning, and cross-modal retrieval. Our dataset and code will be public.

Large Language Models (LLMs) have demonstrated significant potential in transforming clinical applications. In this study, we investigate the efficacy of four techniques in adapting LLMs for clinical use-cases: continuous pretraining, instruct fine-tuning, NEFTune, and prompt engineering. We employ these methods on Mistral 7B and Mixtral 8x7B models, leveraging a large-scale clinical pretraining dataset of 50 billion tokens and an instruct fine-tuning dataset of 500 million tokens. Our evaluation across various clinical tasks reveals the impact of each technique. While continuous pretraining beyond 250 billion tokens yields marginal improvements on its own, it establishes a strong foundation for instruct fine-tuning. Notably, NEFTune, designed primarily to enhance generation quality, surprisingly demonstrates additional gains on our benchmark. Complex prompt engineering methods further enhance performance. These findings show the importance of tailoring fine-tuning strategies and exploring innovative techniques to optimize LLM performance in the clinical domain.

Large Language Models (LLMs) hold great promise to revolutionize current clinical systems for their superior capacities on medical text processing tasks and medical licensing exams. Meanwhile, traditional ML models such as SVM and XGBoost have still been mainly adopted in clinical prediction tasks. An emerging question is Can LLMs beat traditional ML models in clinical prediction? Thus, we build a new benchmark ClinicalBench to comprehensively study the clinical predictive modeling capacities of both general-purpose and medical LLMs, and compare them with traditional ML models. ClinicalBench embraces three common clinical prediction tasks, two databases, 14 general-purpose LLMs, 8 medical LLMs, and 11 traditional ML models. Through extensive empirical investigation, we discover that both general-purpose and medical LLMs, even with different model scales, diverse prompting or fine-tuning strategies, still cannot beat traditional ML models in clinical prediction yet, shedding light on their potential deficiency in clinical reasoning and decision-making. We call for caution when practitioners adopt LLMs in clinical applications. ClinicalBench can be utilized to bridge the gap between LLMs' development for healthcare and real-world clinical practice.

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.

Large language models (LLMs) have demonstrated impressive capabilities in natural language understanding and generation, but the quality bar for medical and clinical applications is high. Today, attempts to assess models' clinical knowledge typically rely on automated evaluations on limited benchmarks. There is no standard to evaluate model predictions and reasoning across a breadth of tasks. To address this, we present MultiMedQA, a benchmark combining six existing open question answering datasets spanning professional medical exams, research, and consumer queries; and HealthSearchQA, a new free-response dataset of medical questions searched online. We propose a framework for human evaluation of model answers along multiple axes including factuality, precision, possible harm, and bias. In addition, we evaluate PaLM (a 540-billion parameter LLM) and its instruction-tuned variant, Flan-PaLM, on MultiMedQA. Using a combination of prompting strategies, Flan-PaLM achieves state-of-the-art accuracy on every MultiMedQA multiple-choice dataset (MedQA, MedMCQA, PubMedQA, MMLU clinical topics), including 67.6% accuracy on MedQA (US Medical License Exam questions), surpassing prior state-of-the-art by over 17%. However, human evaluation reveals key gaps in Flan-PaLM responses. To resolve this we introduce instruction prompt tuning, a parameter-efficient approach for aligning LLMs to new domains using a few exemplars. The resulting model, Med-PaLM, performs encouragingly, but remains inferior to clinicians. We show that comprehension, recall of knowledge, and medical reasoning improve with model scale and instruction prompt tuning, suggesting the potential utility of LLMs in medicine. Our human evaluations reveal important limitations of today's models, reinforcing the importance of both evaluation frameworks and method development in creating safe, helpful LLM models for clinical applications.

Large Language Models (LLMs) have shown the potential to significantly contribute to patient care, diagnostics, and administrative processes. Emerging biomedical LLMs address healthcare-specific challenges, including privacy demands and computational constraints. However, evaluation of these models has primarily been limited to non-clinical tasks, which do not reflect the complexity of practical clinical applications. Additionally, there has been no thorough comparison between biomedical and general-domain LLMs for clinical tasks. To fill this gap, we present the Clinical Language Understanding Evaluation (CLUE), a benchmark tailored to evaluate LLMs on real-world clinical tasks. CLUE includes two novel datasets derived from MIMIC IV discharge letters and four existing tasks designed to test the practical applicability of LLMs in healthcare settings. Our evaluation covers several biomedical and general domain LLMs, providing insights into their clinical performance and applicability. CLUE represents a step towards a standardized approach to evaluating and developing LLMs in healthcare to align future model development with the real-world needs of clinical application. We publish our evaluation and data generation scripts: https://github.com/dadaamin/CLUE

Background: Recent advancements in large language models (LLMs) offer potential benefits in healthcare, particularly in processing extensive patient records. However, existing benchmarks do not fully assess LLMs' capability in handling real-world, lengthy clinical data. Methods: We present the LongHealth benchmark, comprising 20 detailed fictional patient cases across various diseases, with each case containing 5,090 to 6,754 words. The benchmark challenges LLMs with 400 multiple-choice questions in three categories: information extraction, negation, and sorting, challenging LLMs to extract and interpret information from large clinical documents. Results: We evaluated nine open-source LLMs with a minimum of 16,000 tokens and also included OpenAI's proprietary and cost-efficient GPT-3.5 Turbo for comparison. The highest accuracy was observed for Mixtral-8x7B-Instruct-v0.1, particularly in tasks focused on information retrieval from single and multiple patient documents. However, all models struggled significantly in tasks requiring the identification of missing information, highlighting a critical area for improvement in clinical data interpretation. Conclusion: While LLMs show considerable potential for processing long clinical documents, their current accuracy levels are insufficient for reliable clinical use, especially in scenarios requiring the identification of missing information. The LongHealth benchmark provides a more realistic assessment of LLMs in a healthcare setting and highlights the need for further model refinement for safe and effective clinical application. We make the benchmark and evaluation code publicly available.

Adapting pretrained language models to novel domains, such as clinical applications, traditionally involves retraining their entire set of parameters. Parameter-Efficient Fine-Tuning (PEFT) techniques for fine-tuning language models significantly reduce computational requirements by selectively fine-tuning small subsets of parameters. In this study, we propose a two-step PEFT framework and evaluate it in the clinical domain. Our approach combines a specialised PEFT adapter layer designed for clinical domain adaptation with another adapter specialised for downstream tasks. We evaluate the framework on multiple clinical outcome prediction datasets, comparing it to clinically trained language models. Our framework achieves a better AUROC score averaged across all clinical downstream tasks compared to clinical language models. In particular, we observe large improvements of 4-5% AUROC in large-scale multilabel classification tasks, such as diagnoses and procedures classification. To our knowledge, this study is the first to provide an extensive empirical analysis of the interplay between PEFT techniques and domain adaptation in an important real-world domain of clinical applications.

Recent advancements in reasoning-enhanced large language models (LLMs), such as DeepSeek-R1 and OpenAI-o3, have demonstrated significant progress. However, their application in professional medical contexts remains underexplored, particularly in evaluating the quality of their reasoning processes alongside final outputs. Here, we introduce MedR-Bench, a benchmarking dataset of 1,453 structured patient cases, annotated with reasoning references derived from clinical case reports. Spanning 13 body systems and 10 specialties, it includes both common and rare diseases. To comprehensively evaluate LLM performance, we propose a framework encompassing three critical examination recommendation, diagnostic decision-making, and treatment planning, simulating the entire patient care journey. To assess reasoning quality, we present the Reasoning Evaluator, a novel automated system that objectively scores free-text reasoning responses based on efficiency, actuality, and completeness using dynamic cross-referencing and evidence checks. Using this benchmark, we evaluate five state-of-the-art reasoning LLMs, including DeepSeek-R1, OpenAI-o3-mini, and Gemini-2.0-Flash Thinking, etc. Our results show that current LLMs achieve over 85% accuracy in relatively simple diagnostic tasks when provided with sufficient examination results. However, performance declines in more complex tasks, such as examination recommendation and treatment planning. While reasoning outputs are generally reliable, with factuality scores exceeding 90%, critical reasoning steps are frequently missed. These findings underscore both the progress and limitations of clinical LLMs. Notably, open-source models like DeepSeek-R1 are narrowing the gap with proprietary systems, highlighting their potential to drive accessible and equitable advancements in healthcare.

Purpose: Accurate segmentation of clinical target volumes (CTV) and organs-at-risk is crucial for optimizing gynecologic brachytherapy (GYN-BT) treatment planning. However, anatomical variability, low soft-tissue contrast in CT imaging, and limited annotated datasets pose significant challenges. This study presents GynBTNet, a novel multi-stage learning framework designed to enhance segmentation performance through self-supervised pretraining and hierarchical fine-tuning strategies. Methods: GynBTNet employs a three-stage training strategy: (1) self-supervised pretraining on large-scale CT datasets using sparse submanifold convolution to capture robust anatomical representations, (2) supervised fine-tuning on a comprehensive multi-organ segmentation dataset to refine feature extraction, and (3) task-specific fine-tuning on a dedicated GYN-BT dataset to optimize segmentation performance for clinical applications. The model was evaluated against state-of-the-art methods using the Dice Similarity Coefficient (DSC), 95th percentile Hausdorff Distance (HD95), and Average Surface Distance (ASD). Results: Our GynBTNet achieved superior segmentation performance, significantly outperforming nnU-Net and Swin-UNETR. Notably, it yielded a DSC of 0.837 +/- 0.068 for CTV, 0.940 +/- 0.052 for the bladder, 0.842 +/- 0.070 for the rectum, and 0.871 +/- 0.047 for the uterus, with reduced HD95 and ASD compared to baseline models. Self-supervised pretraining led to consistent performance improvements, particularly for structures with complex boundaries. However, segmentation of the sigmoid colon remained challenging, likely due to anatomical ambiguities and inter-patient variability. Statistical significance analysis confirmed that GynBTNet's improvements were significant compared to baseline models.

Automated interpretation of electrocardiograms (ECG) has garnered significant attention with the advancements in machine learning methodologies. Despite the growing interest, most current studies focus solely on classification or regression tasks, which overlook a crucial aspect of clinical cardio-disease diagnosis: the diagnostic report generated by experienced human clinicians. In this paper, we introduce a novel approach to ECG interpretation, leveraging recent breakthroughs in Large Language Models (LLMs) and Vision-Transformer (ViT) models. Rather than treating ECG diagnosis as a classification or regression task, we propose an alternative method of automatically identifying the most similar clinical cases based on the input ECG data. Also, since interpreting ECG as images is more affordable and accessible, we process ECG as encoded images and adopt a vision-language learning paradigm to jointly learn vision-language alignment between encoded ECG images and ECG diagnosis reports. Encoding ECG into images can result in an efficient ECG retrieval system, which will be highly practical and useful in clinical applications. More importantly, our findings could serve as a crucial resource for providing diagnostic services in underdeveloped regions.

Deep Learning (DL) has the potential to optimize machine learning in both the scientific and clinical communities. However, greater expertise is required to develop DL algorithms, and the variability of implementations hinders their reproducibility, translation, and deployment. Here we present the community-driven Generally Nuanced Deep Learning Framework (GaNDLF), with the goal of lowering these barriers. GaNDLF makes the mechanism of DL development, training, and inference more stable, reproducible, interpretable, and scalable, without requiring an extensive technical background. GaNDLF aims to provide an end-to-end solution for all DL-related tasks in computational precision medicine. We demonstrate the ability of GaNDLF to analyze both radiology and histology images, with built-in support for k-fold cross-validation, data augmentation, multiple modalities and output classes. Our quantitative performance evaluation on numerous use cases, anatomies, and computational tasks supports GaNDLF as a robust application framework for deployment in clinical workflows.

Medical imaging provides critical evidence for clinical diagnosis, treatment planning, and surgical decisions, yet most existing imaging models are narrowly focused and require multiple specialized networks, limiting their generalization. Although large-scale language and multimodal models exhibit strong reasoning and multi-task capabilities, real-world clinical applications demand precise visual grounding, multimodal integration, and chain-of-thought reasoning. We introduce Citrus-V, a multimodal medical foundation model that combines image analysis with textual reasoning. The model integrates detection, segmentation, and multimodal chain-of-thought reasoning, enabling pixel-level lesion localization, structured report generation, and physician-like diagnostic inference in a single framework. We propose a novel multimodal training approach and release a curated open-source data suite covering reasoning, detection, segmentation, and document understanding tasks. Evaluations demonstrate that Citrus-V outperforms existing open-source medical models and expert-level imaging systems across multiple benchmarks, delivering a unified pipeline from visual grounding to clinical reasoning and supporting precise lesion quantification, automated reporting, and reliable second opinions.

The proliferation of Large Language Models (LLMs) in medicine has enabled impressive capabilities, yet a critical gap remains in their ability to perform systematic, transparent, and verifiable reasoning, a cornerstone of clinical practice. This has catalyzed a shift from single-step answer generation to the development of LLMs explicitly designed for medical reasoning. This paper provides the first systematic review of this emerging field. We propose a taxonomy of reasoning enhancement techniques, categorized into training-time strategies (e.g., supervised fine-tuning, reinforcement learning) and test-time mechanisms (e.g., prompt engineering, multi-agent systems). We analyze how these techniques are applied across different data modalities (text, image, code) and in key clinical applications such as diagnosis, education, and treatment planning. Furthermore, we survey the evolution of evaluation benchmarks from simple accuracy metrics to sophisticated assessments of reasoning quality and visual interpretability. Based on an analysis of 60 seminal studies from 2022-2025, we conclude by identifying critical challenges, including the faithfulness-plausibility gap and the need for native multimodal reasoning, and outlining future directions toward building efficient, robust, and sociotechnically responsible medical AI.

Most current medical vision language models struggle to jointly generate diagnostic text and pixel-level segmentation masks in response to complex visual questions. This represents a major limitation towards clinical application, as assistive systems that fail to provide both modalities simultaneously offer limited value to medical practitioners. To alleviate this limitation, we first introduce RadDiagSeg-D, a dataset combining abnormality detection, diagnosis, and multi-target segmentation into a unified and hierarchical task. RadDiagSeg-D covers multiple imaging modalities and is precisely designed to support the development of models that produce descriptive text and corresponding segmentation masks in tandem. Subsequently, we leverage the dataset to propose a novel vision-language model, RadDiagSeg-M, capable of joint abnormality detection, diagnosis, and flexible segmentation. RadDiagSeg-M provides highly informative and clinically useful outputs, effectively addressing the need to enrich contextual information for assistive diagnosis. Finally, we benchmark RadDiagSeg-M and showcase its strong performance across all components involved in the task of multi-target text-and-mask generation, establishing a robust and competitive baseline.

Scoliosis, a prevalent condition characterized by abnormal spinal curvature leading to deformity, requires precise assessment methods for effective diagnosis and management. The Cobb angle is a widely used scoliosis quantification method that measures the degree of curvature between the tilted vertebrae. Yet, manual measuring of Cobb angles is time-consuming and labor-intensive, fraught with significant interobserver and intraobserver variability. To address these challenges and the lack of interpretability found in certain existing automated methods, we have created fully automated software that not only precisely measures the Cobb angle but also provides clear visualizations of these measurements. This software integrates deep neural network-based spine region detection and segmentation, spine centerline identification, pinpointing the most significantly tilted vertebrae, and direct visualization of Cobb angles on the original images. Upon comparison with the assessments of 7 expert readers, our algorithm exhibited a mean deviation in Cobb angle measurements of 4.17 degrees, notably surpassing the manual approach's average intra-reader discrepancy of 5.16 degrees. The algorithm also achieved intra-class correlation coefficients (ICC) exceeding 0.96 and Pearson correlation coefficients above 0.944, reflecting robust agreement with expert assessments and superior measurement reliability. Through the comprehensive reader study and statistical analysis, we believe this algorithm not only ensures a higher consensus with expert readers but also enhances interpretability and reproducibility during assessments. It holds significant promise for clinical application, potentially aiding physicians in more accurate scoliosis assessment and diagnosis, thereby improving patient care.

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.

Accurate vessel segmentation is critical for clinical applications such as disease diagnosis and surgical planning, yet remains challenging due to thin, branching structures and low texture contrast. While foundation models like the Segment Anything Model (SAM) have shown promise in generic segmentation, they perform sub-optimally on vascular structures. In this work, we present VesSAM, a powerful and efficient framework tailored for 2D vessel segmentation. VesSAM integrates (1) a convolutional adapter to enhance local texture features, (2) a multi-prompt encoder that fuses anatomical prompts, including skeletons, bifurcation points, and segment midpoints, via hierarchical cross-attention, and (3) a lightweight mask decoder to reduce jagged artifacts. We also introduce an automated pipeline to generate structured multi-prompt annotations, and curate a diverse benchmark dataset spanning 8 datasets across 5 imaging modalities. Experimental results demonstrate that VesSAM consistently outperforms state-of-the-art PEFT-based SAM variants by over 10% Dice and 13% IoU, and achieves competitive performance compared to fully fine-tuned methods, with significantly fewer parameters. VesSAM also generalizes well to out-of-distribution (OoD) settings, outperforming all baselines in average OoD Dice and IoU.

The COVID-19 pandemic has posed a heavy burden to the healthcare system worldwide and caused huge social disruption and economic loss. Many deep learning models have been proposed to conduct clinical predictive tasks such as mortality prediction for COVID-19 patients in intensive care units using Electronic Health Record (EHR) data. Despite their initial success in certain clinical applications, there is currently a lack of benchmarking results to achieve a fair comparison so that we can select the optimal model for clinical use. Furthermore, there is a discrepancy between the formulation of traditional prediction tasks and real-world clinical practice in intensive care. To fill these gaps, we propose two clinical prediction tasks, Outcome-specific length-of-stay prediction and Early mortality prediction for COVID-19 patients in intensive care units. The two tasks are adapted from the naive length-of-stay and mortality prediction tasks to accommodate the clinical practice for COVID-19 patients. We propose fair, detailed, open-source data-preprocessing pipelines and evaluate 17 state-of-the-art predictive models on two tasks, including 5 machine learning models, 6 basic deep learning models and 6 deep learning predictive models specifically designed for EHR data. We provide benchmarking results using data from two real-world COVID-19 EHR datasets. One dataset is publicly available without needing any inquiry and another dataset can be accessed on request. We provide fair, reproducible benchmarking results for two tasks. We deploy all experiment results and models on an online platform. We also allow clinicians and researchers to upload their data to the platform and get quick prediction results using our trained models. We hope our efforts can further facilitate deep learning and machine learning research for COVID-19 predictive modeling.

Artificial intelligence has significantly advanced healthcare, particularly through large language models (LLMs) that excel in medical question answering benchmarks. However, their real-world clinical application remains limited due to the complexities of doctor-patient interactions. To address this, we introduce AI Hospital, a multi-agent framework simulating dynamic medical interactions between Doctor as player and NPCs including Patient, Examiner, Chief Physician. This setup allows for realistic assessments of LLMs in clinical scenarios. We develop the Multi-View Medical Evaluation (MVME) benchmark, utilizing high-quality Chinese medical records and NPCs to evaluate LLMs' performance in symptom collection, examination recommendations, and diagnoses. Additionally, a dispute resolution collaborative mechanism is proposed to enhance diagnostic accuracy through iterative discussions. Despite improvements, current LLMs exhibit significant performance gaps in multi-turn interactions compared to one-step approaches. Our findings highlight the need for further research to bridge these gaps and improve LLMs' clinical diagnostic capabilities. Our data, code, and experimental results are all open-sourced at https://github.com/LibertFan/AI_Hospital.

Universal medical image segmentation models have emerged as a promising paradigm due to their strong generalizability across diverse tasks, showing great potential for a wide range of clinical applications. This potential has been partly driven by the success of general-purpose vision models such as the Segment Anything Model (SAM), which has inspired the development of various fine-tuned variants for medical segmentation tasks. However, fine-tuned variants like MedSAM are trained on comparatively limited medical imaging data that often suffers from heterogeneity, scarce annotations, and distributional shifts. These challenges limit their ability to generalize across a wide range of medical segmentation tasks. In this regard, we propose MedSAMix, a training-free model merging method that integrates the strengths of both generalist models (e.g., SAM) and specialist models (e.g., MedSAM) for medical image segmentation. In contrast to traditional model merging approaches that rely on manual configuration and often result in suboptimal outcomes, we propose a zero-order optimization method to automatically discover optimal layer-wise merging solutions. Furthermore, for clinical applications, we develop two regimes to meet the demand of domain-specificity and generalizability in different scenarios by single-task optimization and multi-objective optimization respectively. Extensive evaluations on 25 medical segmentation tasks demonstrate that MedSAMix effectively mitigates model bias and consistently improves performance in both domain-specific accuracy and generalization, achieving improvements of 6.67% on specialized tasks and 4.37% on multi-task evaluations.

X-ray imaging is a rapid and cost-effective tool for visualizing internal human anatomy. While multi-view X-ray imaging provides complementary information that enhances diagnosis, intervention, and education, acquiring images from multiple angles increases radiation exposure and complicates clinical workflows. To address these challenges, we propose a novel view-conditioned diffusion model for synthesizing multi-view X-ray images from a single view. Unlike prior methods, which are limited in angular range, resolution, and image quality, our approach leverages the Diffusion Transformer to preserve fine details and employs a weak-to-strong training strategy for stable high-resolution image generation. Experimental results demonstrate that our method generates higher-resolution outputs with improved control over viewing angles. This capability has significant implications not only for clinical applications but also for medical education and data extension, enabling the creation of diverse, high-quality datasets for training and analysis. Our code is available at https://github.com/xiechun298/SV-DRR.

In this paper, we present the VMSE U-Net and VM-Unet CBAM+ model, two cutting-edge deep learning architectures designed to enhance medical image segmentation. Our approach integrates Squeeze-and-Excitation (SE) and Convolutional Block Attention Module (CBAM) techniques into the traditional VM U-Net framework, significantly improving segmentation accuracy, feature localization, and computational efficiency. Both models show superior performance compared to the baseline VM-Unet across multiple datasets. Notably, VMSEUnet achieves the highest accuracy, IoU, precision, and recall while maintaining low loss values. It also exhibits exceptional computational efficiency with faster inference times and lower memory usage on both GPU and CPU. Overall, the study suggests that the enhanced architecture VMSE-Unet is a valuable tool for medical image analysis. These findings highlight its potential for real-world clinical applications, emphasizing the importance of further research to optimize accuracy, robustness, and computational efficiency.

Objective: This study aims to evaluate and compare the performance of two Japanese language models-conventional Bidirectional Encoder Representations from Transformers (BERT) and the newer ModernBERT-in classifying findings from chest CT reports, with a focus on tokenization efficiency, processing time, and classification performance. Methods: We conducted a retrospective study using the CT-RATE-JPN dataset containing 22,778 training reports and 150 test reports. Both models were fine-tuned for multi-label classification of 18 common chest CT conditions. The training data was split in 18,222:4,556 for training and validation. Performance was evaluated using F1 scores for each condition and exact match accuracy across all 18 labels. Results: ModernBERT demonstrated superior tokenization efficiency, requiring 24.0% fewer tokens per document (258.1 vs. 339.6) compared to BERT Base. This translated to significant performance improvements, with ModernBERT completing training in 1877.67 seconds versus BERT's 3090.54 seconds (39% reduction). ModernBERT processed 38.82 samples per second during training (1.65x faster) and 139.90 samples per second during inference (1.66x faster). Despite these efficiency gains, classification performance remained comparable, with ModernBERT achieving superior F1 scores in 8 conditions, while BERT performed better in 4 conditions. Overall exact match accuracy was slightly higher for ModernBERT (74.67% vs. 72.67%), though this difference was not statistically significant (p=0.6291). Conclusion: ModernBERT offers substantial improvements in tokenization efficiency and training speed without sacrificing classification performance. These results suggest that ModernBERT is a promising candidate for clinical applications in Japanese radiology reports analysis.

Nanorobots are a promising development in targeted drug delivery and the treatment of neurological disorders, with potential for crossing the blood-brain barrier (BBB). These small devices leverage advancements in nanotechnology and bioengineering for precise navigation and targeted payload delivery, particularly for conditions like brain tumors, Alzheimer's disease, and Parkinson's disease. Recent progress in artificial intelligence (AI) and machine learning (ML) has improved the navigation and effectiveness of nanorobots, allowing them to detect and interact with cancer cells through biomarker analysis. This study presents a new reinforcement learning (RL) framework for optimizing nanorobot navigation in complex biological environments, focusing on cancer cell detection by analyzing the concentration gradients of surrounding biomarkers. We utilize a computer simulation model to explore the behavior of nanorobots in a three-dimensional space with cancer cells and biological barriers. The proposed method uses Q-learning to refine movement strategies based on real-time biomarker concentration data, enabling nanorobots to autonomously navigate to cancerous tissues for targeted drug delivery. This research lays the groundwork for future laboratory experiments and clinical applications, with implications for personalized medicine and less invasive cancer treatments. The integration of intelligent nanorobots could revolutionize therapeutic strategies, reducing side effects and enhancing treatment effectiveness for cancer patients. Further research will investigate the practical deployment of these technologies in medical settings, aiming to unlock the full potential of nanorobotics in healthcare.

Large language models (LLMs) have recently demonstrated their potential in clinical applications, providing valuable medical knowledge and advice. For example, a large dialog LLM like ChatGPT has successfully passed part of the US medical licensing exam. However, LLMs currently have difficulty processing images, making it challenging to interpret information from medical images, which are rich in information that supports clinical decisions. On the other hand, computer-aided diagnosis (CAD) networks for medical images have seen significant success in the medical field by using advanced deep-learning algorithms to support clinical decision-making. This paper presents a method for integrating LLMs into medical-image CAD networks. The proposed framework uses LLMs to enhance the output of multiple CAD networks, such as diagnosis networks, lesion segmentation networks, and report generation networks, by summarizing and reorganizing the information presented in natural language text format. The goal is to merge the strengths of LLMs' medical domain knowledge and logical reasoning with the vision understanding capability of existing medical-image CAD models to create a more user-friendly and understandable system for patients compared to conventional CAD systems. In the future, LLM's medical knowledge can be also used to improve the performance of vision-based medical-image CAD models.

Recent artificial intelligence (AI) systems have reached milestones in "grand challenges" ranging from Go to protein-folding. The capability to retrieve medical knowledge, reason over it, and answer medical questions comparably to physicians has long been viewed as one such grand challenge. Large language models (LLMs) have catalyzed significant progress in medical question answering; Med-PaLM was the first model to exceed a "passing" score in US Medical Licensing Examination (USMLE) style questions with a score of 67.2% on the MedQA dataset. However, this and other prior work suggested significant room for improvement, especially when models' answers were compared to clinicians' answers. Here we present Med-PaLM 2, which bridges these gaps by leveraging a combination of base LLM improvements (PaLM 2), medical domain finetuning, and prompting strategies including a novel ensemble refinement approach. Med-PaLM 2 scored up to 86.5% on the MedQA dataset, improving upon Med-PaLM by over 19% and setting a new state-of-the-art. We also observed performance approaching or exceeding state-of-the-art across MedMCQA, PubMedQA, and MMLU clinical topics datasets. We performed detailed human evaluations on long-form questions along multiple axes relevant to clinical applications. In pairwise comparative ranking of 1066 consumer medical questions, physicians preferred Med-PaLM 2 answers to those produced by physicians on eight of nine axes pertaining to clinical utility (p < 0.001). We also observed significant improvements compared to Med-PaLM on every evaluation axis (p < 0.001) on newly introduced datasets of 240 long-form "adversarial" questions to probe LLM limitations. While further studies are necessary to validate the efficacy of these models in real-world settings, these results highlight rapid progress towards physician-level performance in medical question answering.

Cell instance segmentation is a fundamental task in digital pathology with broad clinical applications. Recently, vision foundation models, which are predominantly based on Vision Transformers (ViTs), have achieved remarkable success in pathology image analysis. However, their improvements in cell instance segmentation remain limited. A key challenge arises from the tokenization process in ViTs, which substantially reduces the spatial resolution of input images, leading to suboptimal segmentation quality, especially for small and densely packed cells. To address this problem, we propose CellVTA (Cell Vision Transformer with Adapter), a novel method that improves the performance of vision foundation models for cell instance segmentation by incorporating a CNN-based adapter module. This adapter extracts high-resolution spatial information from input images and injects it into the ViT through a cross-attention mechanism. Our method preserves the core architecture of ViT, ensuring seamless integration with pretrained foundation models. Extensive experiments show that CellVTA achieves 0.538 mPQ on the CoNIC dataset and 0.506 mPQ on the PanNuke dataset, which significantly outperforms the state-of-the-art cell segmentation methods. Ablation studies confirm the superiority of our approach over other fine-tuning strategies, including decoder-only fine-tuning and full fine-tuning. Our code and models are publicly available at https://github.com/JieZheng-ShanghaiTech/CellVTA.

Optical coherence tomography (OCT) is a non-invasive imaging technique with extensive clinical applications in ophthalmology. OCT enables the visualization of the retinal layers, playing a vital role in the early detection and monitoring of retinal diseases. OCT uses the principle of light wave interference to create detailed images of the retinal microstructures, making it a valuable tool for diagnosing ocular conditions. This work presents an open-access OCT dataset (OCTDL) comprising over 1600 high-resolution OCT images labeled according to disease group and retinal pathology. The dataset consists of OCT records of patients with Age-related Macular Degeneration (AMD), Diabetic Macular Edema (DME), Epiretinal Membrane (ERM), Retinal Artery Occlusion (RAO), Retinal Vein Occlusion (RVO), and Vitreomacular Interface Disease (VID). The images were acquired with an Optovue Avanti RTVue XR using raster scanning protocols with dynamic scan length and image resolution. Each retinal b-scan was acquired by centering on the fovea and interpreted and cataloged by an experienced retinal specialist. In this work, we applied Deep Learning classification techniques to this new open-access dataset.

Nucleus instance segmentation in histology images is crucial for a broad spectrum of clinical applications. Current dominant algorithms rely on regression of nuclear proxy maps. Distinguishing nucleus instances from the estimated maps requires carefully curated post-processing, which is error-prone and parameter-sensitive. Recently, the Segment Anything Model (SAM) has earned huge attention in medical image segmentation, owing to its impressive generalization ability and promptable property. Nevertheless, its potential on nucleus instance segmentation remains largely underexplored. In this paper, we present a novel prompt-driven framework that consists of a nucleus prompter and SAM for automatic nucleus instance segmentation. Specifically, the prompter learns to generate a unique point prompt for each nucleus while the SAM is fine-tuned to output the corresponding mask for the prompted nucleus. Furthermore, we propose the inclusion of adjacent nuclei as negative prompts to enhance the model's capability to identify overlapping nuclei. Without complicated post-processing, our proposed method sets a new state-of-the-art performance on three challenging benchmarks. Code is available at github.com/windygoo/PromptNucSeg

Closed-loop brain stimulation refers to capturing neurophysiological measures such as electroencephalography (EEG), quickly identifying neural events of interest, and producing auditory, magnetic or electrical stimulation so as to interact with brain processes precisely. It is a promising new method for fundamental neuroscience and perhaps for clinical applications such as restoring degraded memory function; however, existing tools are expensive, cumbersome, and offer limited experimental flexibility. In this article, we propose the Portiloop, a deep learning-based, portable and low-cost closed-loop stimulation system able to target specific brain oscillations. We first document open-hardware implementations that can be constructed from commercially available components. We also provide a fast, lightweight neural network model and an exploration algorithm that automatically optimizes the model hyperparameters to the desired brain oscillation. Finally, we validate the technology on a challenging test case of real-time sleep spindle detection, with results comparable to off-line expert performance on the Massive Online Data Annotation spindle dataset (MODA; group consensus). Software and plans are available to the community as an open science initiative to encourage further development and advance closed-loop neuroscience research.

Electrocardiogram (ECG) serves as the primary non-invasive diagnostic tool for cardiac conditions monitoring, are crucial in assisting clinicians. Recent studies have concentrated on classifying cardiac conditions using ECG data but have overlooked ECG report generation, which is not only time-consuming but also requires clinical expertise. To automate ECG report generation and ensure its versatility, we propose the Multimodal ECG Instruction Tuning (MEIT) framework, the first attempt to tackle ECG report generation with LLMs and multimodal instructions. To facilitate future research, we establish a benchmark to evaluate MEIT with various LLMs backbones across two large-scale ECG datasets. Our approach uniquely aligns the representations of the ECG signal and the report, and we conduct extensive experiments to benchmark MEIT with nine open source LLMs, using more than 800,000 ECG reports. MEIT's results underscore the superior performance of instruction-tuned LLMs, showcasing their proficiency in quality report generation, zero-shot capabilities, and resilience to signal perturbation. These findings emphasize the efficacy of our MEIT framework and its potential for real-world clinical application.

Checklists are simple decision aids that are often used to promote safety and reliability in clinical applications. In this paper, we present a method to learn checklists for clinical decision support. We represent predictive checklists as discrete linear classifiers with binary features and unit weights. We then learn globally optimal predictive checklists from data by solving an integer programming problem. Our method allows users to customize checklists to obey complex constraints, including constraints to enforce group fairness and to binarize real-valued features at training time. In addition, it pairs models with an optimality gap that can inform model development and determine the feasibility of learning sufficiently accurate checklists on a given dataset. We pair our method with specialized techniques that speed up its ability to train a predictive checklist that performs well and has a small optimality gap. We benchmark the performance of our method on seven clinical classification problems, and demonstrate its practical benefits by training a short-form checklist for PTSD screening. Our results show that our method can fit simple predictive checklists that perform well and that can easily be customized to obey a rich class of custom constraints.

Foundation models pre-trained on large-scale natural image datasets offer a powerful paradigm for medical image segmentation. However, effectively transferring their learned representations for precise clinical applications remains a challenge. In this work, we propose Dino U-Net, a novel encoder-decoder architecture designed to exploit the high-fidelity dense features of the DINOv3 vision foundation model. Our architecture introduces an encoder built upon a frozen DINOv3 backbone, which employs a specialized adapter to fuse the model's rich semantic features with low-level spatial details. To preserve the quality of these representations during dimensionality reduction, we design a new fidelity-aware projection module (FAPM) that effectively refines and projects the features for the decoder. We conducted extensive experiments on seven diverse public medical image segmentation datasets. Our results show that Dino U-Net achieves state-of-the-art performance, consistently outperforming previous methods across various imaging modalities. Our framework proves to be highly scalable, with segmentation accuracy consistently improving as the backbone model size increases up to the 7-billion-parameter variant. The findings demonstrate that leveraging the superior, dense-pretrained features from a general-purpose foundation model provides a highly effective and parameter-efficient approach to advance the accuracy of medical image segmentation. The code is available at https://github.com/yifangao112/DinoUNet.

Large language models (LLMs) have been applied to tasks in healthcare, ranging from medical exam questions to responding to patient questions. With increasing institutional partnerships between companies producing LLMs and healthcare systems, real world clinical application is coming closer to reality. As these models gain traction, it is essential for healthcare practitioners to understand what LLMs are, their development, their current and potential applications, and the associated pitfalls when utilized in medicine. This review and accompanying tutorial aim to give an overview of these topics to aid healthcare practitioners in understanding the rapidly changing landscape of LLMs as applied to medicine.

Medical image segmentation is fundamental for biomedical discovery. Existing methods lack generalizability and demand extensive, time-consuming manual annotation for new clinical application. Here, we propose MedSAM-3, a text promptable medical segmentation model for medical image and video segmentation. By fine-tuning the Segment Anything Model (SAM) 3 architecture on medical images paired with semantic conceptual labels, our MedSAM-3 enables medical Promptable Concept Segmentation (PCS), allowing precise targeting of anatomical structures via open-vocabulary text descriptions rather than solely geometric prompts. We further introduce the MedSAM-3 Agent, a framework that integrates Multimodal Large Language Models (MLLMs) to perform complex reasoning and iterative refinement in an agent-in-the-loop workflow. Comprehensive experiments across diverse medical imaging modalities, including X-ray, MRI, Ultrasound, CT, and video, demonstrate that our approach significantly outperforms existing specialist and foundation models. We will release our code and model at https://github.com/Joey-S-Liu/MedSAM3.

As large language models (LLMs) advance in conversational and reasoning capabilities, their practical application in healthcare has become a critical research focus. However, there is a notable gap between the performance of medical LLMs on static benchmarks such as USMLE and their utility in real-world clinical decision-making. This discrepancy arises because traditional exams fail to capture the dynamic, interactive nature of medical consultations. To address this challenge, we introduce a novel dynamic verification framework that moves beyond static answer verifier, establishing a large-scale, high-fidelity interactive reinforcement learning system. Our framework comprises two key components: a Patient Simulator that creates realistic clinical environments using de-identified medical records, and a Clinical Rubrics Generator that dynamically produces multi-dimensional evaluation metrics. Building on this foundation, we develop Baichuan-M2, a 32B-parameter medical augmented reasoning model trained through a multi-stage reinforcement learning strategy with an improved Group Relative Policy Optimization (GRPO) algorithm. Evaluated on HealthBench, Baichuan-M2 outperforms all other open-source models and most advanced closed-source counterparts, achieving a score above 32 on the challenging HealthBench Hard benchmark-previously exceeded only by GPT-5. Our work demonstrates that robust dynamic verifier system is essential for aligning LLM capabilities with practical clinical applications, establishing a new Pareto front in the performance-parameter trade-off for medical AI deployment.

Medicine, by its nature, is a multifaceted domain that requires the synthesis of information across various modalities. Medical generative vision-language models (VLMs) make a first step in this direction and promise many exciting clinical applications. However, existing models typically have to be fine-tuned on sizeable down-stream datasets, which poses a significant limitation as in many medical applications data is scarce, necessitating models that are capable of learning from few examples in real-time. Here we propose Med-Flamingo, a multimodal few-shot learner adapted to the medical domain. Based on OpenFlamingo-9B, we continue pre-training on paired and interleaved medical image-text data from publications and textbooks. Med-Flamingo unlocks few-shot generative medical visual question answering (VQA) abilities, which we evaluate on several datasets including a novel challenging open-ended VQA dataset of visual USMLE-style problems. Furthermore, we conduct the first human evaluation for generative medical VQA where physicians review the problems and blinded generations in an interactive app. Med-Flamingo improves performance in generative medical VQA by up to 20\% in clinician's rating and firstly enables multimodal medical few-shot adaptations, such as rationale generation. We release our model, code, and evaluation app under https://github.com/snap-stanford/med-flamingo.

The segmentation of cell nuclei in tissue images stained with the blood dye hematoxylin and eosin (H&E) is essential for various clinical applications and analyses. Due to the complex characteristics of cellular morphology, a large receptive field is considered crucial for generating high-quality segmentation. However, previous methods face challenges in achieving a balance between the receptive field and computational burden. To address this issue, we propose LKCell, a high-accuracy and efficient cell segmentation method. Its core insight lies in unleashing the potential of large convolution kernels to achieve computationally efficient large receptive fields. Specifically, (1) We transfer pre-trained large convolution kernel models to the medical domain for the first time, demonstrating their effectiveness in cell segmentation. (2) We analyze the redundancy of previous methods and design a new segmentation decoder based on large convolution kernels. It achieves higher performance while significantly reducing the number of parameters. We evaluate our method on the most challenging benchmark and achieve state-of-the-art results (0.5080 mPQ) in cell nuclei instance segmentation with only 21.6% FLOPs compared with the previous leading method. Our source code and models are available at https://github.com/hustvl/LKCell.

Visual grounding is essential for precise perception and reasoning in multimodal large language models (MLLMs), especially in medical imaging domains. While existing medical visual grounding benchmarks primarily focus on single-image scenarios, real-world clinical applications often involve sequential images, where accurate lesion localization across different modalities and temporal tracking of disease progression (e.g., pre- vs. post-treatment comparison) require fine-grained cross-image semantic alignment and context-aware reasoning. To remedy the underrepresentation of image sequences in existing medical visual grounding benchmarks, we propose MedSG-Bench, the first benchmark tailored for Medical Image Sequences Grounding. It comprises eight VQA-style tasks, formulated into two paradigms of the grounding tasks, including 1) Image Difference Grounding, which focuses on detecting change regions across images, and 2) Image Consistency Grounding, which emphasizes detection of consistent or shared semantics across sequential images. MedSG-Bench covers 76 public datasets, 10 medical imaging modalities, and a wide spectrum of anatomical structures and diseases, totaling 9,630 question-answer pairs. We benchmark both general-purpose MLLMs (e.g., Qwen2.5-VL) and medical-domain specialized MLLMs (e.g., HuatuoGPT-vision), observing that even the advanced models exhibit substantial limitations in medical sequential grounding tasks. To advance this field, we construct MedSG-188K, a large-scale instruction-tuning dataset tailored for sequential visual grounding, and further develop MedSeq-Grounder, an MLLM designed to facilitate future research on fine-grained understanding across medical sequential images. The benchmark, dataset, and model are available at https://huggingface.co/MedSG-Bench

There is a lack of benchmarks for evaluating large language models (LLMs) in long-form medical question answering (QA). Most existing medical QA evaluation benchmarks focus on automatic metrics and multiple-choice questions. While valuable, these benchmarks fail to fully capture or assess the complexities of real-world clinical applications where LLMs are being deployed. Furthermore, existing studies on evaluating long-form answer generation in medical QA are primarily closed-source, lacking access to human medical expert annotations, which makes it difficult to reproduce results and enhance existing baselines. In this work, we introduce a new publicly available benchmark featuring real-world consumer medical questions with long-form answer evaluations annotated by medical doctors. We performed pairwise comparisons of responses from various open and closed-source medical and general-purpose LLMs based on criteria such as correctness, helpfulness, harmfulness, and bias. Additionally, we performed a comprehensive LLM-as-a-judge analysis to study the alignment between human judgments and LLMs. Our preliminary results highlight the strong potential of open LLMs in medical QA compared to leading closed models. Code & Data: https://github.com/lavita-ai/medical-eval-sphere

Observing and analyzing children's social behaviors is crucial for the early diagnosis of Autism Spectrum Disorders (ASD). This work focuses on automatically detecting ASD using computer vision techniques and large language models (LLMs). Existing methods typically rely on supervised learning. However, the scarcity of ASD diagnostic datasets and the lack of interpretability in diagnostic results significantly limits its clinical application. To address these challenges, we introduce a novel unsupervised approach based on script-centric behavior understanding. Our pipeline converts video content into scripts that describe the behavior of characters, leveraging the generalizability of large language models to detect ASD in a zero-shot or few-shot manner. Specifically, we propose a scripts transcription module for multimodal behavior data textualization and a domain prompts module to bridge LLMs. Our method achieves an accuracy of 92.00\% in diagnosing ASD in children with an average age of 24 months, surpassing the performance of supervised learning methods by 3.58\% absolutely. Extensive experiments confirm the effectiveness of our approach and suggest its potential for advancing ASD research through LLMs.

The label scarcity problem is the main challenge that hinders the wide application of deep learning systems in automatic cardiovascular diseases (CVDs) detection using electrocardiography (ECG). Tuning pre-trained models alleviates this problem by transferring knowledge learned from large datasets to downstream small datasets. However, bottlenecks in computational efficiency and detection performance limit its clinical applications. It is difficult to improve the detection performance without significantly sacrificing the computational efficiency during model training. Here, we propose a computation-efficient semi-supervised learning paradigm (CE-SSL) for robust and computation-efficient CVDs detection using ECG. It enables a robust adaptation of pre-trained models on downstream datasets with limited supervision and high computational efficiency. First, a random-deactivation technique is developed to achieve robust and fast low-rank adaptation of pre-trained weights. Subsequently, we propose a one-shot rank allocation module to determine the optimal ranks for the update matrices of the pre-trained weights. Finally, a lightweight semi-supervised learning pipeline is introduced to enhance model performance by leveraging labeled and unlabeled data with high computational efficiency. Extensive experiments on four downstream datasets demonstrate that CE-SSL not only outperforms the state-of-the-art methods in multi-label CVDs detection but also consumes fewer GPU footprints, training time, and parameter storage space. As such, this paradigm provides an effective solution for achieving high computational efficiency and robust detection performance in the clinical applications of pre-trained models under limited supervision. Code and Supplementary Materials are available at https://github.com/KAZABANA/CE-SSL

The Circle of Willis (CoW) is an important network of arteries connecting major circulations of the brain. Its vascular architecture is believed to affect the risk, severity, and clinical outcome of serious neurovascular diseases. However, characterizing the highly variable CoW anatomy is still a manual and time-consuming expert task. The CoW is usually imaged by two non-invasive angiographic imaging modalities, magnetic resonance angiography (MRA) and computed tomography angiography (CTA), but there exist limited datasets with annotations on CoW anatomy, especially for CTA. Therefore, we organized the TopCoW challenge with the release of an annotated CoW dataset. The TopCoW dataset is the first public dataset with voxel-level annotations for 13 CoW vessel components, enabled by virtual reality technology. It is also the first large dataset using 200 pairs of MRA and CTA from the same patients. As part of the benchmark, we invited submissions worldwide and attracted over 250 registered participants from six continents. The submissions were evaluated on both internal and external test datasets of 226 scans from over five centers. The top performing teams achieved over 90% Dice scores at segmenting the CoW components, over 80% F1 scores at detecting key CoW components, and over 70% balanced accuracy at classifying CoW variants for nearly all test sets. The best algorithms also showed clinical potential in classifying fetal-type posterior cerebral artery and locating aneurysms with CoW anatomy. TopCoW demonstrated the utility and versatility of CoW segmentation algorithms for a wide range of downstream clinical applications with explainability. The annotated datasets and best performing algorithms have been released as public Zenodo records to foster further methodological development and clinical tool building.

Gaussian processes (GPs) are popular nonparametric statistical models for learning unknown functions and quantifying the spatiotemporal uncertainty in data. Recent works have extended GPs to model scalar and vector quantities distributed over non-Euclidean domains, including smooth manifolds appearing in numerous fields such as computer vision, dynamical systems, and neuroscience. However, these approaches assume that the manifold underlying the data is known, limiting their practical utility. We introduce RVGP, a generalisation of GPs for learning vector signals over latent Riemannian manifolds. Our method uses positional encoding with eigenfunctions of the connection Laplacian, associated with the tangent bundle, readily derived from common graph-based approximation of data. We demonstrate that RVGP possesses global regularity over the manifold, which allows it to super-resolve and inpaint vector fields while preserving singularities. Furthermore, we use RVGP to reconstruct high-density neural dynamics derived from low-density EEG recordings in healthy individuals and Alzheimer's patients. We show that vector field singularities are important disease markers and that their reconstruction leads to a comparable classification accuracy of disease states to high-density recordings. Thus, our method overcomes a significant practical limitation in experimental and clinical applications.

The integration of Computer-Assisted Diagnosis (CAD) with Large Language Models (LLMs) holds great potential in clinical applications, specifically in the roles of virtual family doctors and clinic assistants. However, current works in this field are plagued by limitations, specifically a restricted scope of applicable image domains and the provision of unreliable medical advice. This restricts their overall processing capabilities. Furthermore, the mismatch in writing style between LLMs and radiologists undermines their practical usefulness. To tackle these challenges, we introduce ChatCAD+, which is designed to be universal and reliable. It is capable of handling medical images from diverse domains and leveraging up-to-date information from reputable medical websites to provide reliable medical advice. Additionally, it incorporates a template retrieval system that improves report generation performance via exemplar reports. This approach ensures greater consistency with the expertise of human professionals. The source code is available at https://github.com/zhaozh10/ChatCAD.

It is widely accepted that information derived from analyzing speech (the acoustic signal) and language production (words and sentences) serves as a useful window into the health of an individual's cognitive ability. In fact, most neuropsychological testing batteries have a component related to speech and language where clinicians elicit speech from patients for subjective evaluation across a broad set of dimensions. With advances in speech signal processing and natural language processing, there has been recent interest in developing tools to detect more subtle changes in cognitive-linguistic function. This work relies on extracting a set of features from recorded and transcribed speech for objective assessments of speech and language, early diagnosis of neurological disease, and tracking of disease after diagnosis. With an emphasis on cognitive and thought disorders, in this paper we provide a review of existing speech and language features used in this domain, discuss their clinical application, and highlight their advantages and disadvantages. Broadly speaking, the review is split into two categories: language features based on natural language processing and speech features based on speech signal processing. Within each category, we consider features that aim to measure complementary dimensions of cognitive-linguistics, including language diversity, syntactic complexity, semantic coherence, and timing. We conclude the review with a proposal of new research directions to further advance the field.

Electrocardiograms (ECGs) play a vital role in monitoring cardiac health and diagnosing heart diseases. However, traditional deep learning approaches for ECG analysis rely heavily on large-scale manual annotations, which are both time-consuming and resource-intensive to obtain. To overcome this limitation, self-supervised learning (SSL) has emerged as a promising alternative, enabling the extraction of robust ECG representations that can be efficiently transferred to various downstream tasks. While previous studies have explored SSL for ECG pretraining and multi-modal ECG-language alignment, they often fail to capture the multi-scale nature of ECG signals. As a result, these methods struggle to learn generalized representations due to their inability to model the hierarchical structure of ECG data. To address this gap, we introduce MELP, a novel Multi-scale ECG-Language Pretraining (MELP) model that fully leverages hierarchical supervision from ECG-text pairs. MELP first pretrains a cardiology-specific language model to enhance its understanding of clinical text. It then applies three levels of cross-modal supervision-at the token, beat, and rhythm levels-to align ECG signals with textual reports, capturing structured information across different time scales. We evaluate MELP on three public ECG datasets across multiple tasks, including zero-shot ECG classification, linear probing, and transfer learning. Experimental results demonstrate that MELP outperforms existing SSL methods, underscoring its effectiveness and adaptability across diverse clinical applications. Our code is available at https://github.com/HKU-MedAI/MELP.

Medical image segmentation poses challenges due to domain gaps, data modality variations, and dependency on domain knowledge or experts, especially for low- and middle-income countries (LMICs). Whereas for humans, given a few exemplars (with corresponding labels), we are able to segment different medical images even without exten-sive domain-specific clinical training. In addition, current SAM-based medical segmentation models use fine-grained visual prompts, such as the bounding rectangle generated from manually annotated target segmentation mask, as the bounding box (bbox) prompt during the testing phase. However, in actual clinical scenarios, no such precise prior knowledge is available. Our experimental results also reveal that previous models nearly fail to predict when given coarser bbox prompts. Considering these issues, in this paper, we introduce a domain-aware selective adaptation approach to adapt the general knowledge learned from a large model trained with natural images to the corresponding medical domains/modalities, with access to only a few (e.g. less than 5) exemplars. Our method mitigates the aforementioned limitations, providing an efficient and LMICs-friendly solution. Extensive experimental analysis showcases the effectiveness of our approach, offering potential advancements in healthcare diagnostics and clinical applications in LMICs.

Generating accurate 3D reconstructions from endoscopic video is a promising avenue for longitudinal radiation-free analysis of sinus anatomy and surgical outcomes. Several methods for monocular reconstruction have been proposed, yielding visually pleasant 3D anatomical structures by retrieving relative camera poses with structure-from-motion-type algorithms and fusion of monocular depth estimates. However, due to the complex properties of the underlying algorithms and endoscopic scenes, the reconstruction pipeline may perform poorly or fail unexpectedly. Further, acquiring medical data conveys additional challenges, presenting difficulties in quantitatively benchmarking these models, understanding failure cases, and identifying critical components that contribute to their precision. In this work, we perform a quantitative analysis of a self-supervised approach for sinus reconstruction using endoscopic sequences paired with optical tracking and high-resolution computed tomography acquired from nine ex-vivo specimens. Our results show that the generated reconstructions are in high agreement with the anatomy, yielding an average point-to-mesh error of 0.91 mm between reconstructions and CT segmentations. However, in a point-to-point matching scenario, relevant for endoscope tracking and navigation, we found average target registration errors of 6.58 mm. We identified that pose and depth estimation inaccuracies contribute equally to this error and that locally consistent sequences with shorter trajectories generate more accurate reconstructions. These results suggest that achieving global consistency between relative camera poses and estimated depths with the anatomy is essential. In doing so, we can ensure proper synergy between all components of the pipeline for improved reconstructions that will facilitate clinical application of this innovative technology.

Non-ideal measurement computed tomography (NICT), which sacrifices optimal imaging standards for new advantages in CT imaging, is expanding the clinical application scope of CT images. However, with the reduction of imaging standards, the image quality has also been reduced, extremely limiting the clinical acceptability. Although numerous studies have demonstrated the feasibility of deep learning for the NICT enhancement in specific scenarios, their high data cost and limited generalizability have become large obstacles. The recent research on the foundation model has brought new opportunities for building a universal NICT enhancement model - bridging the image quality degradation with minimal data cost. However, owing to the challenges in the collection of large pre-training datasets and the compatibility of data variation, no success has been reported. In this paper, we propose a multi-scale integrated Transformer AMPlifier (TAMP), the first imaging foundation model for universal NICT enhancement. It has been pre-trained on a large-scale physical-driven simulation dataset with 3.6 million NICT-ICT image pairs, and is able to directly generalize to the NICT enhancement tasks with various non-ideal settings and body regions. Via the adaptation with few data, it can further achieve professional performance in real-world specific scenarios. Our extensive experiments have demonstrated that the proposed TAMP has significant potential for promoting the exploration and application of NICT and serving a wider range of medical scenarios.

When developing deep neural networks for segmenting intraoperative ultrasound images, several practical issues are encountered frequently, such as the presence of ultrasound frames that do not contain regions of interest and the high variance in ground-truth labels. In this study, we evaluate the utility of a pre-screening classification network prior to the segmentation network. Experimental results demonstrate that such a classifier, minimising frame classification errors, was able to directly impact the number of false positive and false negative frames. Importantly, the segmentation accuracy on the classifier-selected frames, that would be segmented, remains comparable to or better than those from standalone segmentation networks. Interestingly, the efficacy of the pre-screening classifier was affected by the sampling methods for training labels from multiple observers, a seemingly independent problem. We show experimentally that a previously proposed approach, combining random sampling and consensus labels, may need to be adapted to perform well in our application. Furthermore, this work aims to share practical experience in developing a machine learning application that assists highly variable interventional imaging for prostate cancer patients, to present robust and reproducible open-source implementations, and to report a set of comprehensive results and analysis comparing these practical, yet important, options in a real-world clinical application.

Improving performance on complex tasks and enabling interpretable decision making in large language models (LLMs), especially for clinical applications, requires effective reasoning. Yet this remains challenging without supervised fine-tuning (SFT) on costly chain-of-thought (CoT) data distilled from closed-source models (e.g., GPT-4o). In this work, we present AlphaMed, the first medical LLM to show that reasoning capability can emerge purely through reinforcement learning (RL), using minimalist rule-based rewards on public multiple-choice QA datasets, without relying on SFT or distilled CoT data. AlphaMed achieves state-of-the-art results on six medical QA benchmarks, outperforming models trained with conventional SFT+RL pipelines. On challenging benchmarks (e.g., MedXpert), AlphaMed even surpasses larger or closed-source models such as DeepSeek-V3-671B and Claude-3.5-Sonnet. To understand the factors behind this success, we conduct a comprehensive data-centric analysis guided by three questions: (i) Can minimalist rule-based RL incentivize reasoning without distilled CoT supervision? (ii) How do dataset quantity and diversity impact reasoning? (iii) How does question difficulty shape the emergence and generalization of reasoning? Our findings show that dataset informativeness is a key driver of reasoning performance, and that minimalist RL on informative, multiple-choice QA data is effective at inducing reasoning without CoT supervision. We also observe divergent trends across benchmarks, underscoring limitations in current evaluation and the need for more challenging, reasoning-oriented medical QA benchmarks.

Graph neural networks (GNNs) have achieved state-of-the-art results in computer vision and medical image classification tasks by capturing structural dependencies across data instances. However, their decision-making remains largely opaque, limiting their trustworthiness in high-stakes clinical applications where interpretability is essential. Existing explainability techniques for GNNs are typically post-hoc and global, offering limited insight into individual node decisions or local reasoning. We introduce X-Node, a self-explaining GNN framework in which each node generates its own explanation as part of the prediction process. For every node, we construct a structured context vector encoding interpretable cues such as degree, centrality, clustering, feature saliency, and label agreement within its local topology. A lightweight Reasoner module maps this context into a compact explanation vector, which serves three purposes: (1) reconstructing the node's latent embedding via a decoder to enforce faithfulness, (2) generating a natural language explanation using a pre-trained LLM (e.g., Grok or Gemini), and (3) guiding the GNN itself via a "text-injection" mechanism that feeds explanations back into the message-passing pipeline. We evaluate X-Node on two graph datasets derived from MedMNIST and MorphoMNIST, integrating it with GCN, GAT, and GIN backbones. Our results show that X-Node maintains competitive classification accuracy while producing faithful, per-node explanations. Repository: https://github.com/basiralab/X-Node.

Ultrasound imaging has become the preferred imaging modality for early cancer screening due to its advantages of non-ionizing radiation, low cost, and real-time imaging capabilities. However, conventional ultrasound diagnosis heavily relies on physician expertise, presenting challenges of high subjectivity and low diagnostic efficiency. Vision-language models (VLMs) offer promising solutions for this issue, but existing general-purpose models demonstrate limited knowledge in ultrasound medical tasks, with poor generalization in multi-organ lesion recognition and low efficiency across multi-task diagnostics. To address these limitations, we propose EchoVLM, a vision-language model specifically designed for ultrasound medical imaging. The model employs a Mixture of Experts (MoE) architecture trained on data spanning seven anatomical regions. This design enables the model to perform multiple tasks, including ultrasound report generation, diagnosis and visual question-answering (VQA). The experimental results demonstrated that EchoVLM achieved significant improvements of 10.15 and 4.77 points in BLEU-1 scores and ROUGE-1 scores respectively compared to Qwen2-VL on the ultrasound report generation task. These findings suggest that EchoVLM has substantial potential to enhance diagnostic accuracy in ultrasound imaging, thereby providing a viable technical solution for future clinical applications. Source code and model weights are available at https://github.com/Asunatan/EchoVLM.

Remarkable strides in computational pathology have been made in the task-agnostic foundation model that advances the performance of a wide array of downstream clinical tasks. Despite the promising performance, there are still several challenges. First, prior works have resorted to either vision-only or image-caption data, disregarding pathology reports with more clinically authentic information from pathologists and gene expression profiles which respectively offer distinct knowledge for versatile clinical applications. Second, the current progress in pathology FMs predominantly concentrates on the patch level, where the restricted context of patch-level pretraining fails to capture whole-slide patterns. Even recent slide-level FMs still struggle to provide whole-slide context for patch representation. In this study, for the first time, we develop a pathology foundation model incorporating three levels of modalities: pathology slides, pathology reports, and gene expression data, which resulted in 26,169 slide-level modality pairs from 10,275 patients across 32 cancer types, amounting to over 116 million pathological patch images. To leverage these data for CPath, we propose a novel whole-slide pretraining paradigm that injects the multimodal whole-slide context into the patch representation, called Multimodal Self-TAught PRetraining (mSTAR). The proposed paradigm revolutionizes the pretraining workflow for CPath, enabling the pathology FM to acquire the whole-slide context. To the best of our knowledge, this is the first attempt to incorporate three modalities at the whole-slide context for enhancing pathology FMs. To systematically evaluate the capabilities of mSTAR, we built the largest spectrum of oncological benchmark, spanning 7 categories of oncological applications in 15 types of 97 practical oncological tasks.

In this paper, a multi-scale visual transformer model, referred as GasHis-Transformer, is proposed for Gastric Histopathological Image Detection (GHID), which enables the automatic global detection of gastric cancer images. GasHis-Transformer model consists of two key modules designed to extract global and local information using a position-encoded transformer model and a convolutional neural network with local convolution, respectively. A publicly available hematoxylin and eosin (H&E) stained gastric histopathological image dataset is used in the experiment. Furthermore, a Dropconnect based lightweight network is proposed to reduce the model size and training time of GasHis-Transformer for clinical applications with improved confidence. Moreover, a series of contrast and extended experiments verify the robustness, extensibility and stability of GasHis-Transformer. In conclusion, GasHis-Transformer demonstrates high global detection performance and shows its significant potential in GHID task.

Lung diseases remain a critical global health concern, and it's crucial to have accurate and quick ways to diagnose them. This work focuses on classifying different lung diseases into five groups: viral pneumonia, bacterial pneumonia, COVID, tuberculosis, and normal lungs. Employing advanced deep learning techniques, we explore a diverse range of models including CNN, hybrid models, ensembles, transformers, and Big Transfer. The research encompasses comprehensive methodologies such as hyperparameter tuning, stratified k-fold cross-validation, and transfer learning with fine-tuning.Remarkably, our findings reveal that the Xception model, fine-tuned through 5-fold cross-validation, achieves the highest accuracy of 96.21\%. This success shows that our methods work well in accurately identifying different lung diseases. The exploration of explainable artificial intelligence (XAI) methodologies further enhances our understanding of the decision-making processes employed by these models, contributing to increased trust in their clinical applications.

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.

The increasing prevalence of thyroid cancer globally has led to the development of various computer-aided detection methods. Accurate segmentation of thyroid nodules is a critical first step in the development of AI-assisted clinical decision support systems. This study focuses on instance segmentation of thyroid nodules using YOLOv5 algorithms on ultrasound images. We evaluated multiple YOLOv5 variants (Nano, Small, Medium, Large, and XLarge) across two dataset versions, with and without doppler images. The YOLOv5-Large algorithm achieved the highest performance with a dice score of 91\% and mAP of 0.87 on the dataset including doppler images. Notably, our results demonstrate that doppler images, typically excluded by physicians, can significantly improve segmentation performance. The YOLOv5-Small model achieved 79\% dice score when doppler images were excluded, while including them improved performance across all model variants. These findings suggest that instance segmentation with YOLOv5 provides an effective real-time approach for thyroid nodule detection, with potential clinical applications in automated diagnostic systems.

Multimodal Large Language Models (MLLMs) have demonstrated remarkable effectiveness in various general-domain scenarios, such as visual question answering and image captioning. Recently, researchers have increasingly focused on empowering MLLMs with medical conversational abilities, which hold significant promise for clinical applications. However, medical data presents unique challenges due to its heterogeneous nature -- encompassing diverse modalities including 2D images, 3D volumetric scans, and temporal video sequences. The substantial domain gap and data format inconsistencies across these modalities have hindered the development of unified medical MLLMs. To address these challenges, we propose Fleming-VL, a unified end-to-end framework for comprehensive medical visual understanding across heterogeneous modalities. Fleming-VL tackles this problem from a data-centric perspective through three key strategies: (1) scaling up pretraining by integrating long-context data from both natural and medical-specific domains; (2) complementing fine-tuning with rare medical data, including holistic video analysis and underrepresented 2D modalities such as ultrasound and dermoscopy images; (3) extending existing evaluation frameworks to incorporate 3D volumetric and video understanding benchmarks. Through supervised fine-tuning (SFT) and group relative policy optimization (GRPO), we develop Fleming-VL in multiple model scales. Extensive experiments demonstrate that Fleming-VL achieves state-of-the-art performance across multiple benchmarks, including medical VQA, video QA, and 3D medical image understanding. We publicly release Fleming-VL to promote transparent, reproducible, and auditable progress in medical AI.

Tear film break-up (TFBU) analysis is critical for diagnosing dry eye syndrome, but automated TFBU segmentation remains challenging due to the lack of annotated datasets and integrated solutions. This paper introduces the Tear Film Multi-task (TFM) Dataset, the first comprehensive dataset for multi-task tear film analysis, comprising 15 high-resolution videos (totaling 6,247 frames) annotated with three vision tasks: frame-level classification ('clear', 'closed', 'broken', 'blur'), Placido Ring detection, and pixel-wise TFBU area segmentation. Leveraging this dataset, we first propose TF-Net, a novel and efficient baseline segmentation model. TF-Net incorporates a MobileOne-mini backbone with re-parameterization techniques and an enhanced feature pyramid network to achieve a favorable balance between accuracy and computational efficiency for real-time clinical applications. We further establish benchmark performance on the TFM segmentation subset by comparing TF-Net against several state-of-the-art medical image segmentation models. Furthermore, we design TF-Collab, a novel integrated real-time pipeline that synergistically leverages models trained on all three tasks of the TFM dataset. By sequentially orchestrating frame classification for BUT determination, pupil region localization for input standardization, and TFBU segmentation, TF-Collab fully automates the analysis. Experimental results demonstrate the effectiveness of the proposed TF-Net and TF-Collab, providing a foundation for future research in ocular surface diagnostics. Our code and the TFM datasets are available at https://github.com/glory-wan/TF-Net

Ensuring the safety and reliability of large language models (LLMs) in clinical practice is critical to prevent patient harm and promote trustworthy healthcare applications of AI. However, LLMs are advancing so rapidly that static safety benchmarks often become obsolete upon publication, yielding only an incomplete and sometimes misleading picture of model trustworthiness. We demonstrate that a Dynamic, Automatic, and Systematic (DAS) red-teaming framework that continuously stress-tests LLMs can reveal significant weaknesses of current LLMs across four safety-critical domains: robustness, privacy, bias/fairness, and hallucination. A suite of adversarial agents is applied to autonomously mutate test cases, identify/evolve unsafe-triggering strategies, and evaluate responses, uncovering vulnerabilities in real time without human intervention. Applying DAS to 15 proprietary and open-source LLMs revealed a stark contrast between static benchmark performance and vulnerability under adversarial pressure. Despite a median MedQA accuracy exceeding 80\%, 94\% of previously correct answers failed our dynamic robustness tests. We observed similarly high failure rates across other domains: privacy leaks were elicited in 86\% of scenarios, cognitive-bias priming altered clinical recommendations in 81\% of fairness tests, and we identified hallucination rates exceeding 66\% in widely used models. Such profound residual risks are incompatible with routine clinical practice. By converting red-teaming from a static checklist into a dynamic stress-test audit, DAS red-teaming offers the surveillance that hospitals/regulators/technology vendors require as LLMs become embedded in patient chatbots, decision-support dashboards, and broader healthcare workflows. Our framework delivers an evolvable, scalable, and reliable safeguard for the next generation of medical AI.

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.

Chromosome analysis is vital for diagnosing genetic disorders and guiding cancer therapy decisions through the identification of somatic clonal aberrations. However, developing an AI model are hindered by the overwhelming complexity and diversity of chromosomal abnormalities, requiring extensive annotation efforts, while automated methods remain task-specific and lack generalizability due to the scarcity of comprehensive datasets spanning diverse resource conditions. Here, we introduce CHROMA, a foundation model for cytogenomics, designed to overcome these challenges by learning generalizable representations of chromosomal abnormalities. Pre-trained on over 84,000 specimens (~4 million chromosomal images) via self-supervised learning, CHROMA outperforms other methods across all types of abnormalities, even when trained on fewer labelled data and more imbalanced datasets. By facilitating comprehensive mapping of instability and clonal leisons across various aberration types, CHROMA offers a scalable and generalizable solution for reliable and automated clinical analysis, reducing the annotation workload for experts and advancing precision oncology through the early detection of rare genomic abnormalities, enabling broad clinical AI applications and making advanced genomic analysis more accessible.

Traditional Chinese Medicine (TCM) has seen increasing adoption in healthcare, with specialized Large Language Models (LLMs) emerging to support clinical applications. A fundamental requirement for these models is accurate identification of TCM drug ingredients. In this paper, we evaluate how general and TCM-specialized LLMs perform when identifying ingredients of Chinese drugs. Our systematic analysis reveals consistent failure patterns: models often interpret drug names literally, overuse common herbs regardless of relevance, and exhibit erratic behaviors when faced with unfamiliar formulations. LLMs also fail to understand the verification task. These findings demonstrate that current LLMs rely primarily on drug names rather than possessing systematic pharmacological knowledge. To address these limitations, we propose a Retrieval Augmented Generation (RAG) approach focused on ingredient names. Experiments across 220 TCM formulations show our method significantly improves accuracy from approximately 50% to 82% in ingredient verification tasks. Our work highlights critical weaknesses in current TCM-specific LLMs and offers a practical solution for enhancing their clinical reliability.

While recent multimodal large language models (MLLMs) have advanced automated ECG interpretation, they still face two key limitations: (1) insufficient multimodal synergy between time series signals and visual ECG representations, and (2) limited explainability in linking diagnoses to granular waveform evidence. We introduce GEM, the first MLLM unifying ECG time series, 12-lead ECG images and text for grounded and clinician-aligned ECG interpretation. GEM enables feature-grounded analysis, evidence-driven reasoning, and a clinician-like diagnostic process through three core innovations: a dual-encoder framework extracting complementary time series and image features, cross-modal alignment for effective multimodal understanding, and knowledge-guided instruction generation for generating high-granularity grounding data (ECG-Grounding) linking diagnoses to measurable parameters (e.g., QRS/PR Intervals). Additionally, we propose the Grounded ECG Understanding task, a clinically motivated benchmark designed to comprehensively assess the MLLM's capability in grounded ECG understanding. Experimental results on both existing and our proposed benchmarks show GEM significantly improves predictive performance (CSN 7.4% uparrow), explainability (22.7% uparrow), and grounding (24.8% uparrow), making it more suitable for real-world clinical applications. GitHub repository: https://github.com/lanxiang1017/GEM.git

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

Deformable image registration is crucial for aligning medical images in a non-linear fashion across different modalities, allowing for precise spatial correspondence between varying anatomical structures. This paper presents NestedMorph, a novel network utilizing a Nested Attention Fusion approach to improve intra-subject deformable registration between T1-weighted (T1w) MRI and diffusion MRI (dMRI) data. NestedMorph integrates high-resolution spatial details from an encoder with semantic information from a decoder using a multi-scale framework, enhancing both local and global feature extraction. Our model notably outperforms existing methods, including CNN-based approaches like VoxelMorph, MIDIR, and CycleMorph, as well as Transformer-based models such as TransMorph and ViT-V-Net, and traditional techniques like NiftyReg and SyN. Evaluations on the HCP dataset demonstrate that NestedMorph achieves superior performance across key metrics, including SSIM, HD95, and SDlogJ, with the highest SSIM of 0.89, and the lowest HD95 of 2.5 and SDlogJ of 0.22. These results highlight NestedMorph's ability to capture both local and global image features effectively, leading to superior registration performance. The promising outcomes of this study underscore NestedMorph's potential to significantly advance deformable medical image registration, providing a robust framework for future research and clinical applications. The source code and our implementation are available at: https://bit.ly/3zdVqcg

Accurate segmentation of tumors in PET/CT images is important in computer-aided diagnosis and treatment of cancer. The key issue of such a segmentation problem lies in the effective integration of complementary information from PET and CT images. However, the quality of PET and CT images varies widely in clinical settings, which leads to uncertainty in the modality information extracted by networks. To take the uncertainty into account in multi-modal information fusion, this paper proposes a novel Multi-modal Evidential Fusion Network (MEFN) comprising a Cross-Modal Feature Learning (CFL) module and a Multi-modal Trusted Fusion (MTF) module. The CFL module reduces the domain gap upon modality conversion and highlights common tumor features, thereby alleviating the needs of the segmentation module to handle modality specificity. The MTF module utilizes mutual attention mechanisms and an uncertainty calibrator to fuse modality features based on modality uncertainty and then fuse the segmentation results under the guidance of Dempster-Shafer Theory. Besides, a new uncertainty perceptual loss is introduced to force the model focusing on uncertain features and hence improve its ability to extract trusted modality information. Extensive comparative experiments are conducted on two publicly available PET/CT datasets to evaluate the performance of our proposed method whose results demonstrate that our MEFN significantly outperforms state-of-the-art methods with improvements of 2.15% and 3.23% in DSC scores on the AutoPET dataset and the Hecktor dataset, respectively. More importantly, our model can provide radiologists with credible uncertainty of the segmentation results for their decision in accepting or rejecting the automatic segmentation results, which is particularly important for clinical applications. Our code will be available at https://github.com/QPaws/MEFN.

Large language models (LLMs) have received much attention and shown their potential in digital health, while their application in mental health is subject to ongoing debate. This systematic review aims to summarize and characterize the use of LLMs in mental health by investigating the strengths and limitations of the latest work in LLMs and discusses the challenges and opportunities for early screening, digital interventions, and other clinical applications in mental health. Following PRISMA guidelines, we examined English articles from PubMed, DBLP Computer Science Bibliography, and IEEE Xplore, published between 1 January 2017, and 1 September 2023, focusing on mental health and LLMs. The review analyzed 32 articles, including mental health analysis using social media datasets (n=13), mental health chatbots (n=10), and other mental health applications (n=9). Findings reveal LLMs' effectiveness in mental health issue detection and the enhancement of telepsychological services through personalised healthcare. Nonetheless, risks like text inconsistencies, hallucinatory content, and the lack of an ethical framework raise concerns about their clinical use. Despite these challenges, the advancement of LLMs underscores their potential as innovative clinical tools, necessitating further research and development. The review emphasizes that LLMs should complement, not replace, professional mental health services.

Estimating the shape and motion state of the myocardium is essential in diagnosing cardiovascular diseases.However, cine magnetic resonance (CMR) imaging is dominated by 2D slices, whose large slice spacing challenges inter-slice shape reconstruction and motion acquisition.To address this problem, we propose a 4D reconstruction method that decouples motion and shape, which can predict the inter-/intra- shape and motion estimation from a given sparse point cloud sequence obtained from limited slices. Our framework comprises a neural motion model and an end-diastolic (ED) shape model. The implicit ED shape model can learn a continuous boundary and encourage the motion model to predict without the supervision of ground truth deformation, and the motion model enables canonical input of the shape model by deforming any point from any phase to the ED phase. Additionally, the constructed ED-space enables pre-training of the shape model, thereby guiding the motion model and addressing the issue of data scarcity. We propose the first 4D myocardial dataset as we know and verify our method on the proposed, public, and cross-modal datasets, showing superior reconstruction performance and enabling various clinical applications.

Electronic health records (EHR) contain narrative notes that provide extensive details on the medical condition and management of patients. Natural language processing (NLP) of clinical notes can use observed frequencies of clinical terms as predictive features for downstream applications such as clinical decision making and patient trajectory prediction. However, due to the vast number of highly similar and related clinical concepts, a more effective modeling strategy is to represent clinical terms as semantic embeddings via representation learning and use the low dimensional embeddings as feature vectors for predictive modeling. To achieve efficient representation, fine-tuning pretrained language models with biomedical knowledge graphs may generate better embeddings for biomedical terms than those from standard language models alone. These embeddings can effectively discriminate synonymous pairs of from those that are unrelated. However, they often fail to capture different degrees of similarity or relatedness for concepts that are hierarchical in nature. To overcome this limitation, we propose HiPrBERT, a novel biomedical term representation model trained on additionally complied data that contains hierarchical structures for various biomedical terms. We modify an existing contrastive loss function to extract information from these hierarchies. Our numerical experiments demonstrate that HiPrBERT effectively learns the pair-wise distance from hierarchical information, resulting in a substantially more informative embeddings for further biomedical applications

Despite being self-supervised, protein language models have shown remarkable performance in fundamental biological tasks such as predicting impact of genetic variation on protein structure and function. The effectiveness of these models on diverse set of tasks suggests that they learn meaningful representations of fitness landscape that can be useful for downstream clinical applications. Here, we interrogate the use of these language models in characterizing known pathogenic mutations in curated, medically actionable genes through an exhaustive search of putative compensatory mutations on each variant's genetic background. Systematic analysis of the predicted effects of these compensatory mutations reveal unappreciated structural features of proteins that are missed by other structure predictors like AlphaFold. While deep mutational scan experiments provide an unbiased estimate of the mutational landscape, we encourage the community to generate and curate rescue mutation experiments to inform the design of more sophisticated co-masking strategies and leverage large language models more effectively for downstream clinical prediction tasks.

With the rapid development of artificial intelligence (AI) in medical image processing, deep learning in color fundus photography (CFP) analysis is also evolving. Although there are some open-source, labeled datasets of CFPs in the ophthalmology community, large-scale datasets for screening only have labels of disease categories, and datasets with annotations of fundus structures are usually small in size. In addition, labeling standards are not uniform across datasets, and there is no clear information on the acquisition device. Here we release a multi-annotation, multi-quality, and multi-device color fundus image dataset for glaucoma analysis on an original challenge -- Retinal Fundus Glaucoma Challenge 2nd Edition (REFUGE2). The REFUGE2 dataset contains 2000 color fundus images with annotations of glaucoma classification, optic disc/cup segmentation, as well as fovea localization. Meanwhile, the REFUGE2 challenge sets three sub-tasks of automatic glaucoma diagnosis and fundus structure analysis and provides an online evaluation framework. Based on the characteristics of multi-device and multi-quality data, some methods with strong generalizations are provided in the challenge to make the predictions more robust. This shows that REFUGE2 brings attention to the characteristics of real-world multi-domain data, bridging the gap between scientific research and clinical application.

Recently, deep convolutional neural networks have achieved great success for medical image segmentation. However, unlike segmentation of natural images, most medical images such as MRI and CT are volumetric data. In order to make full use of volumetric information, 3D CNNs are widely used. However, 3D CNNs suffer from higher inference time and computation cost, which hinders their further clinical applications. Additionally, with the increased number of parameters, the risk of overfitting is higher, especially for medical images where data and annotations are expensive to acquire. To issue this problem, many 2.5D segmentation methods have been proposed to make use of volumetric spatial information with less computation cost. Despite these works lead to improvements on a variety of segmentation tasks, to the best of our knowledge, there has not previously been a large-scale empirical comparison of these methods. In this paper, we aim to present a review of the latest developments of 2.5D methods for volumetric medical image segmentation. Additionally, to compare the performance and effectiveness of these methods, we provide an empirical study of these methods on three representative segmentation tasks involving different modalities and targets. Our experimental results highlight that 3D CNNs may not always be the best choice. Despite all these 2.5D methods can bring performance gains to 2D baseline, not all the methods hold the benefits on different datasets. We hope the results and conclusions of our study will prove useful for the community on exploring and developing efficient volumetric medical image segmentation methods.

The emerging area of computational pathology (CPath) is ripe ground for the application of deep learning (DL) methods to healthcare due to the sheer volume of raw pixel data in whole-slide images (WSIs) of cancerous tissue slides. However, it is imperative for the DL algorithms relying on nuclei-level details to be able to cope with data from `the clinical wild', which tends to be quite challenging. We study, and extend recently released PanNuke dataset consisting of ~200,000 nuclei categorized into 5 clinically important classes for the challenging tasks of segmenting and classifying nuclei in WSIs. Previous pan-cancer datasets consisted of only up to 9 different tissues and up to 21,000 unlabeled nuclei and just over 24,000 labeled nuclei with segmentation masks. PanNuke consists of 19 different tissue types that have been semi-automatically annotated and quality controlled by clinical pathologists, leading to a dataset with statistics similar to the clinical wild and with minimal selection bias. We study the performance of segmentation and classification models when applied to the proposed dataset and demonstrate the application of models trained on PanNuke to whole-slide images. We provide comprehensive statistics about the dataset and outline recommendations and research directions to address the limitations of existing DL tools when applied to real-world CPath applications.

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.

Large language models offer transformative potential for healthcare, yet their responsible and equitable development depends critically on a deeper understanding of how training data characteristics influence model behavior, including the potential for bias. Current practices in dataset curation and bias assessment often lack the necessary transparency, creating an urgent need for comprehensive evaluation frameworks to foster trust and guide improvements. In this study, we present an in-depth analysis of potential downstream biases in clinical language models, with a focus on differential opioid prescription tendencies across diverse demographic groups, such as ethnicity, gender, and age. As part of this investigation, we introduce HC4: Healthcare Comprehensive Commons Corpus, a novel and extensively curated pretraining dataset exceeding 89 billion tokens. Our evaluation leverages both established general benchmarks and a novel, healthcare-specific methodology, offering crucial insights to support fairness and safety in clinical AI applications.

Large Language Models (LLMs) such as GPT & Llama have demonstrated significant achievements in summarization tasks but struggle with factual inaccuracies, a critical issue in clinical NLP applications where errors could lead to serious consequences. To counter the high costs and limited availability of expert-annotated data for factual alignment, this study introduces an innovative pipeline that utilizes >100B parameter GPT variants like GPT-3.5 & GPT-4 to act as synthetic experts to generate high-quality synthetics feedback aimed at enhancing factual consistency in clinical note summarization. Our research primarily focuses on edit feedback generated by these synthetic feedback experts without additional human annotations, mirroring and optimizing the practical scenario in which medical professionals refine AI system outputs. Although such 100B+ parameter GPT variants have proven to demonstrate expertise in various clinical NLP tasks, such as the Medical Licensing Examination, there is scant research on their capacity to act as synthetic feedback experts and deliver expert-level edit feedback for improving the generation quality of weaker (<10B parameter) LLMs like GPT-2 (1.5B) & Llama 2 (7B) in clinical domain. So in this work, we leverage 100B+ GPT variants to act as synthetic feedback experts offering expert-level edit feedback, that is used to reduce hallucinations and align weaker (<10B parameter) LLMs with medical facts using two distinct alignment algorithms (DPO & SALT), endeavoring to narrow the divide between AI-generated content and factual accuracy. This highlights the substantial potential of LLM-based synthetic edits in enhancing the alignment of clinical factuality.

This study investigates the feasibility and performance of federated learning (FL) for multi-label ICD code classification using clinical notes from the MIMIC-IV dataset. Unlike previous approaches that rely on centralized training or fine-tuned large language models, we propose a lightweight and scalable pipeline combining frozen text embeddings with simple multilayer perceptron (MLP) classifiers. This design offers a privacy-preserving and deployment-efficient alternative for clinical NLP applications, particularly suited to distributed healthcare settings. Extensive experiments across both centralized and federated configurations were conducted, testing six publicly available embedding models from Massive Text Embedding Benchmark leaderboard and three MLP classifier architectures under two medical coding (ICD-9 and ICD-10). Additionally, ablation studies over ten random stratified splits assess performance stability. Results show that embedding quality substantially outweighs classifier complexity in determining predictive performance, and that federated learning can closely match centralized results in idealized conditions. While the models are orders of magnitude smaller than state-of-the-art architectures and achieved competitive micro and macro F1 scores, limitations remain including the lack of end-to-end training and the simplified FL assumptions. Nevertheless, this work demonstrates a viable way toward scalable, privacy-conscious medical coding systems and offers a step toward for future research into federated, domain-adaptive clinical AI.

In natural language processing applied to the clinical domain, utilizing large language models has emerged as a promising avenue for error detection and correction on clinical notes, a knowledge-intensive task for which annotated data is scarce. This paper presents MedReAct'N'MedReFlex, which leverages a suite of four LLM-based medical agents. The MedReAct agent initiates the process by observing, analyzing, and taking action, generating trajectories to guide the search to target a potential error in the clinical notes. Subsequently, the MedEval agent employs five evaluators to assess the targeted error and the proposed correction. In cases where MedReAct's actions prove insufficient, the MedReFlex agent intervenes, engaging in reflective analysis and proposing alternative strategies. Finally, the MedFinalParser agent formats the final output, preserving the original style while ensuring the integrity of the error correction process. One core component of our method is our RAG pipeline based on our ClinicalCorp corpora. Among other well-known sources containing clinical guidelines and information, we preprocess and release the open-source MedWiki dataset for clinical RAG application. Our results demonstrate the central role of our RAG approach with ClinicalCorp leveraged through the MedReAct'N'MedReFlex framework. It achieved the ninth rank on the MEDIQA-CORR 2024 final leaderboard.

Clinical Natural Language Processing (NLP) has become an emerging technology in healthcare that leverages a large amount of free-text data in electronic health records (EHRs) to improve patient care, support clinical decisions, and facilitate clinical and translational science research. Recently, deep learning has achieved state-of-the-art performance in many clinical NLP tasks. However, training deep learning models usually requires large annotated datasets, which are normally not publicly available and can be time-consuming to build in clinical domains. Working with smaller annotated datasets is typical in clinical NLP and therefore, ensuring that deep learning models perform well is crucial for the models to be used in real-world applications. A widely adopted approach is fine-tuning existing Pre-trained Language Models (PLMs), but these attempts fall short when the training dataset contains only a few annotated samples. Few-Shot Learning (FSL) has recently been investigated to tackle this problem. Siamese Neural Network (SNN) has been widely utilized as an FSL approach in computer vision, but has not been studied well in NLP. Furthermore, the literature on its applications in clinical domains is scarce. In this paper, we propose two SNN-based FSL approaches for clinical NLP, including Pre-Trained SNN (PT-SNN) and SNN with Second-Order Embeddings (SOE-SNN). We evaluated the proposed approaches on two clinical tasks, namely clinical text classification and clinical named entity recognition. We tested three few-shot settings including 4-shot, 8-shot, and 16-shot learning. Both clinical NLP tasks were benchmarked using three PLMs, including BERT,BioBERT, and BioClinicalBERT. The experimental results verified the effectiveness of the proposed SNN-based FSL approaches in both NLP tasks.

Large-language models have recently demonstrated impressive zero-shot capabilities in a variety of natural language tasks such as summarization, dialogue generation, and question-answering. Despite many promising applications in clinical medicine, adoption of these models in real-world settings has been largely limited by their tendency to generate incorrect and sometimes even toxic statements. In this study, we develop Almanac, a large language model framework augmented with retrieval capabilities for medical guideline and treatment recommendations. Performance on a novel dataset of clinical scenarios (n = 130) evaluated by a panel of 5 board-certified and resident physicians demonstrates significant increases in factuality (mean of 18% at p-value < 0.05) across all specialties, with improvements in completeness and safety. Our results demonstrate the potential for large language models to be effective tools in the clinical decision-making process, while also emphasizing the importance of careful testing and deployment to mitigate their shortcomings.

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.

In this paper, a 3D-RegNet-based neural network is proposed for diagnosing the physical condition of patients with coronavirus (Covid-19) infection. In the application of clinical medicine, lung CT images are utilized by practitioners to determine whether a patient is infected with coronavirus. However, there are some laybacks can be considered regarding to this diagnostic method, such as time consuming and low accuracy. As a relatively large organ of human body, important spatial features would be lost if the lungs were diagnosed utilizing two dimensional slice image. Therefore, in this paper, a deep learning model with 3D image was designed. The 3D image as input data was comprised of two-dimensional pulmonary image sequence and from which relevant coronavirus infection 3D features were extracted and classified. The results show that the test set of the 3D model, the result: f1 score of 0.8379 and AUC value of 0.8807 have been achieved.

Medical image synthesis is an important topic for both clinical and research applications. Recently, diffusion models have become a leading approach in this area. Despite their strengths, many existing methods struggle with (1) limited generalizability that only work for specific body regions or voxel spacings, (2) slow inference, which is a common issue for diffusion models, and (3) weak alignment with input conditions, which is a critical issue for medical imaging. MAISI, a previously proposed framework, addresses generalizability issues but still suffers from slow inference and limited condition consistency. In this work, we present MAISI-v2, the first accelerated 3D medical image synthesis framework that integrates rectified flow to enable fast and high quality generation. To further enhance condition fidelity, we introduce a novel region-specific contrastive loss to enhance the sensitivity to region of interest. Our experiments show that MAISI-v2 can achieve SOTA image quality with 33 times acceleration for latent diffusion model. We also conducted a downstream segmentation experiment to show that the synthetic images can be used for data augmentation. We release our code, training details, model weights, and a GUI demo to facilitate reproducibility and promote further development within the community.

Accurate and efficient 3D segmentation is essential for both clinical and research applications. While foundation models like SAM have revolutionized interactive segmentation, their 2D design and domain shift limitations make them ill-suited for 3D medical images. Current adaptations address some of these challenges but remain limited, either lacking volumetric awareness, offering restricted interactivity, or supporting only a small set of structures and modalities. Usability also remains a challenge, as current tools are rarely integrated into established imaging platforms and often rely on cumbersome web-based interfaces with restricted functionality. We introduce nnInteractive, the first comprehensive 3D interactive open-set segmentation method. It supports diverse prompts-including points, scribbles, boxes, and a novel lasso prompt-while leveraging intuitive 2D interactions to generate full 3D segmentations. Trained on 120+ diverse volumetric 3D datasets (CT, MRI, PET, 3D Microscopy, etc.), nnInteractive sets a new state-of-the-art in accuracy, adaptability, and usability. Crucially, it is the first method integrated into widely used image viewers (e.g., Napari, MITK), ensuring broad accessibility for real-world clinical and research applications. Extensive benchmarking demonstrates that nnInteractive far surpasses existing methods, setting a new standard for AI-driven interactive 3D segmentation. nnInteractive is publicly available: https://github.com/MIC-DKFZ/napari-nninteractive (Napari plugin), https://www.mitk.org/MITK-nnInteractive (MITK integration), https://github.com/MIC-DKFZ/nnInteractive (Python backend).

Throughout the course of my Ph.D., I have been designing the user experience (UX) of various machine learning (ML) systems. In this workshop, I share two projects as case studies in which people engage with ML in much more complicated and nuanced ways than the technical HCML work might assume. The first case study describes how cardiology teams in three hospitals used a clinical decision-support system that helps them decide whether and when to implant an artificial heart to a heart failure patient. I demonstrate that physicians cannot draw on their decision-making experience by seeing only patient data on paper. They are also confused by some fundamental premises upon which ML operates. For example, physicians asked: Are ML predictions made based on clinicians' best efforts? Is it ethical to make decisions based on previous patients' collective outcomes? In the second case study, my collaborators and I designed an intelligent text editor, with the goal of improving authors' writing experience with NLP (Natural Language Processing) technologies. We prototyped a number of generative functionalities where the system provides phrase-or-sentence-level writing suggestions upon user request. When writing with the prototype, however, authors shared that they need to "see where the sentence is going two paragraphs later" in order to decide whether the suggestion aligns with their writing; Some even considered adopting machine suggestions as plagiarism, therefore "is simply wrong". By sharing these unexpected and intriguing responses from these real-world ML users, I hope to start a discussion about such previously-unknown complexities and nuances of -- as the workshop proposal states -- "putting ML at the service of people in a way that is accessible, useful, and trustworthy to all".

High-resolution (HR) magnetic resonance imaging (MRI) is crucial for many clinical and research applications. However, achieving it remains costly and constrained by technical trade-offs and experimental limitations. Super-resolution (SR) presents a promising computational approach to overcome these challenges by generating HR images from more affordable low-resolution (LR) scans, potentially improving diagnostic accuracy and efficiency without requiring additional hardware. This survey reviews recent advances in MRI SR techniques, with a focus on deep learning (DL) approaches. It examines DL-based MRI SR methods from the perspectives of computer vision, computational imaging, inverse problems, and MR physics, covering theoretical foundations, architectural designs, learning strategies, benchmark datasets, and performance metrics. We propose a systematic taxonomy to categorize these methods and present an in-depth study of both established and emerging SR techniques applicable to MRI, considering unique challenges in clinical and research contexts. We also highlight open challenges and directions that the community needs to address. Additionally, we provide a collection of essential open-access resources, tools, and tutorials, available on our GitHub: https://github.com/mkhateri/Awesome-MRI-Super-Resolution. IEEE keywords: MRI, Super-Resolution, Deep Learning, Computational Imaging, Inverse Problem, Survey.

Image registration is fundamental in medical imaging, enabling precise alignment of anatomical structures for diagnosis, treatment planning, image-guided treatment or longitudinal monitoring. This work introduces IMPACT (Image Metric with Pretrained model-Agnostic Comparison for Transmodality registration), a generic semantic similarity metric designed for seamless integration into diverse image registration frameworks (such as Elastix and Voxelmorph). It compares deep learning-based features extracted from medical images without requiring task-specific training, ensuring broad applicability across various modalities. By leveraging the features of the large-scale pretrained TotalSegmentator models and the ability to integrate Segment Anything Model (SAM) and other large-scale segmentation networks, this approach offers significant advantages. It provides robust, scalable, and efficient solutions for multimodal image registration. The IMPACT loss was evaluated on five challenging registration tasks involving thoracic CT/CBCT, and pelvic MR/CT datasets. Quantitative metrics, such as Target Registration Error and Dice Similarity Coefficient, demonstrated significant improvements in anatomical alignment compared to baseline methods. Qualitative analyses further confirmed the increased robustness of the proposed metric in the face of noise, artifacts, and modality variations. IMPACT's versatility and efficiency make it a valuable tool for advancing registration performance in clinical and research applications, addressing critical challenges in multimodal medical imaging.

Large Language Models (LLMs) have great potential in the field of health care, yet they face great challenges in adapting to rapidly evolving medical knowledge. This can lead to outdated or contradictory treatment suggestions. This study investigated how LLMs respond to evolving clinical guidelines, focusing on concept drift and internal inconsistencies. We developed the DriftMedQA benchmark to simulate guideline evolution and assessed the temporal reliability of various LLMs. Our evaluation of seven state-of-the-art models across 4,290 scenarios demonstrated difficulties in rejecting outdated recommendations and frequently endorsing conflicting guidance. Additionally, we explored two mitigation strategies: Retrieval-Augmented Generation and preference fine-tuning via Direct Preference Optimization. While each method improved model performance, their combination led to the most consistent and reliable results. These findings underscore the need to improve LLM robustness to temporal shifts to ensure more dependable applications in clinical practice.

In this study, we present seg2med, an advanced medical image synthesis framework that uses Denoising Diffusion Probabilistic Models (DDPM) to generate high-quality synthetic medical images conditioned on anatomical masks from TotalSegmentator. The framework synthesizes CT and MR images from segmentation masks derived from real patient data and XCAT digital phantoms, achieving a Structural Similarity Index Measure (SSIM) of 0.94 +/- 0.02 for CT and 0.89 +/- 0.04 for MR images compared to ground-truth images of real patients. It also achieves a Feature Similarity Index Measure (FSIM) of 0.78 +/- 0.04 for CT images from XCAT. The generative quality is further supported by a Fr\'echet Inception Distance (FID) of 3.62 for CT image generation. Additionally, seg2med can generate paired CT and MR images with consistent anatomical structures and convert images between CT and MR modalities, achieving SSIM values of 0.91 +/- 0.03 for MR-to-CT and 0.77 +/- 0.04 for CT-to-MR conversion. Despite the limitations of incomplete anatomical details in segmentation masks, the framework shows strong performance in cross-modality synthesis and multimodal imaging. seg2med also demonstrates high anatomical fidelity in CT synthesis, achieving a mean Dice coefficient greater than 0.90 for 11 abdominal organs and greater than 0.80 for 34 organs out of 59 in 58 test cases. The highest Dice of 0.96 +/- 0.01 was recorded for the right scapula. Leveraging the TotalSegmentator toolkit, seg2med enables segmentation mask generation across diverse datasets, supporting applications in clinical imaging, data augmentation, multimodal synthesis, and diagnostic algorithm development.

The emerging trend of advancing generalist artificial intelligence, such as GPTv4 and Gemini, has reshaped the landscape of research (academia and industry) in machine learning and many other research areas. However, domain-specific applications of such foundation models (e.g., in medicine) remain untouched or often at their very early stages. It will require an individual set of transfer learning and model adaptation techniques by further expanding and injecting these models with domain knowledge and data. The development of such technologies could be largely accelerated if the bundle of data, algorithms, and pre-trained foundation models were gathered together and open-sourced in an organized manner. In this work, we present OpenMEDLab, an open-source platform for multi-modality foundation models. It encapsulates not only solutions of pioneering attempts in prompting and fine-tuning large language and vision models for frontline clinical and bioinformatic applications but also building domain-specific foundation models with large-scale multi-modal medical data. Importantly, it opens access to a group of pre-trained foundation models for various medical image modalities, clinical text, protein engineering, etc. Inspiring and competitive results are also demonstrated for each collected approach and model in a variety of benchmarks for downstream tasks. We welcome researchers in the field of medical artificial intelligence to continuously contribute cutting-edge methods and models to OpenMEDLab, which can be accessed via https://github.com/openmedlab.

Linking clinical narratives to standardized vocabularies and coding systems is a key component of unlocking the information in medical text for analysis. However, many domains of medical concepts lack well-developed terminologies that can support effective coding of medical text. We present a framework for developing natural language processing (NLP) technologies for automated coding of under-studied types of medical information, and demonstrate its applicability via a case study on physical mobility function. Mobility is a component of many health measures, from post-acute care and surgical outcomes to chronic frailty and disability, and is coded in the International Classification of Functioning, Disability, and Health (ICF). However, mobility and other types of functional activity remain under-studied in medical informatics, and neither the ICF nor commonly-used medical terminologies capture functional status terminology in practice. We investigated two data-driven paradigms, classification and candidate selection, to link narrative observations of mobility to standardized ICF codes, using a dataset of clinical narratives from physical therapy encounters. Recent advances in language modeling and word embedding were used as features for established machine learning models and a novel deep learning approach, achieving a macro F-1 score of 84% on linking mobility activity reports to ICF codes. Both classification and candidate selection approaches present distinct strengths for automated coding in under-studied domains, and we highlight that the combination of (i) a small annotated data set; (ii) expert definitions of codes of interest; and (iii) a representative text corpus is sufficient to produce high-performing automated coding systems. This study has implications for the ongoing growth of NLP tools for a variety of specialized applications in clinical care and 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.

The integration of multimodal data including pathology images and gene profiles is widely applied in precise survival prediction. Despite recent advances in multimodal survival models, collecting complete modalities for multimodal fusion still poses a significant challenge, hindering their application in clinical settings. Current approaches tackling incomplete modalities often fall short, as they typically compensate for only a limited part of the knowledge of missing modalities. To address this issue, we propose a Distilled Prompt Learning framework (DisPro) to utilize the strong robustness of Large Language Models (LLMs) to missing modalities, which employs two-stage prompting for compensation of comprehensive information for missing modalities. In the first stage, Unimodal Prompting (UniPro) distills the knowledge distribution of each modality, preparing for supplementing modality-specific knowledge of the missing modality in the subsequent stage. In the second stage, Multimodal Prompting (MultiPro) leverages available modalities as prompts for LLMs to infer the missing modality, which provides modality-common information. Simultaneously, the unimodal knowledge acquired in the first stage is injected into multimodal inference to compensate for the modality-specific knowledge of the missing modality. Extensive experiments covering various missing scenarios demonstrated the superiority of the proposed method. The code is available at https://github.com/Innse/DisPro.

Cervical disc herniation (CDH) is a prevalent musculoskeletal disorder that significantly impacts health and requires labor-intensive analysis from experts. Despite advancements in automated detection of medical imaging, two significant challenges hinder the real-world application of these methods. First, the computational complexity and resource demands present a significant gap for real-time application. Second, noise in MRI reduces the effectiveness of existing methods by distorting feature extraction. To address these challenges, we propose three key contributions: Firstly, we introduced MedDet, which leverages the multi-teacher single-student knowledge distillation for model compression and efficiency, meanwhile integrating generative adversarial training to enhance performance. Additionally, we customize the second-order nmODE to improve the model's resistance to noise in MRI. Lastly, we conducted comprehensive experiments on the CDH-1848 dataset, achieving up to a 5% improvement in mAP compared to previous methods. Our approach also delivers over 5 times faster inference speed, with approximately 67.8% reduction in parameters and 36.9% reduction in FLOPs compared to the teacher model. These advancements significantly enhance the performance and efficiency of automated CDH detection, demonstrating promising potential for future application in clinical practice. See project website https://steve-zeyu-zhang.github.io/MedDet

Phrase grounding, i.e., mapping natural language phrases to specific image regions, holds significant potential for disease localization in medical imaging through clinical reports. While current state-of-the-art methods rely on discriminative, self-supervised contrastive models, we demonstrate that generative text-to-image diffusion models, leveraging cross-attention maps, can achieve superior zero-shot phrase grounding performance. Contrary to prior assumptions, we show that fine-tuning diffusion models with a frozen, domain-specific language model, such as CXR-BERT, substantially outperforms domain-agnostic counterparts. This setup achieves remarkable improvements, with mIoU scores doubling those of current discriminative methods. These findings highlight the underexplored potential of generative models for phrase grounding tasks. To further enhance performance, we introduce Bimodal Bias Merging (BBM), a novel post-processing technique that aligns text and image biases to identify regions of high certainty. BBM refines cross-attention maps, achieving even greater localization accuracy. Our results establish generative approaches as a more effective paradigm for phrase grounding in the medical imaging domain, paving the way for more robust and interpretable applications in clinical practice. The source code and model weights are available at https://github.com/Felix-012/generate_to_ground.

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

Like other fields of Traditional Medicines, Unani Medicines have been found as an effective medical practice for ages. It is still widely used in the subcontinent, particularly in Pakistan and India. However, Unani Medicines Practitioners are lacking modern IT applications in their everyday clinical practices. An Online Clinical Decision Support System may address this challenge to assist apprentice Unani Medicines practitioners in their diagnostic processes. The proposed system provides a web-based interface to enter the patient's symptoms, which are then automatically analyzed by our system to generate a list of probable diseases. The system allows practitioners to choose the most likely disease and inform patients about the associated treatment options remotely. The system consists of three modules: an Online Clinical Decision Support System, an Artificial Intelligence Inference Engine, and a comprehensive Unani Medicines Database. The system employs advanced AI techniques such as Decision Trees, Deep Learning, and Natural Language Processing. For system development, the project team used a technology stack that includes React, FastAPI, and MySQL. Data and functionality of the application is exposed using APIs for integration and extension with similar domain applications. The novelty of the project is that it addresses the challenge of diagnosing diseases accurately and efficiently in the context of Unani Medicines principles. By leveraging the power of technology, the proposed Clinical Decision Support System has the potential to ease access to healthcare services and information, reduce cost, boost practitioner and patient satisfaction, improve speed and accuracy of the diagnostic process, and provide effective treatments remotely. The application will be useful for Unani Medicines Practitioners, Patients, Government Drug Regulators, Software Developers, and Medical Researchers.

Since radiology reports needed for clinical practice and research are written and stored in free-text narrations, extraction of relative information for further analysis is difficult. In these circumstances, natural language processing (NLP) techniques can facilitate automatic information extraction and transformation of free-text formats to structured data. In recent years, deep learning (DL)-based models have been adapted for NLP experiments with promising results. Despite the significant potential of DL models based on artificial neural networks (ANN) and convolutional neural networks (CNN), the models face some limitations to implement in clinical practice. Transformers, another new DL architecture, have been increasingly applied to improve the process. Therefore, in this study, we propose a transformer-based fine-grained named entity recognition (NER) architecture for clinical information extraction. We collected 88 abdominopelvic sonography reports in free-text formats and annotated them based on our developed information schema. The text-to-text transfer transformer model (T5) and Scifive, a pre-trained domain-specific adaptation of the T5 model, were applied for fine-tuning to extract entities and relations and transform the input into a structured format. Our transformer-based model in this study outperformed previously applied approaches such as ANN and CNN models based on ROUGE-1, ROUGE-2, ROUGE-L, and BLEU scores of 0.816, 0.668, 0.528, and 0.743, respectively, while providing an interpretable structured report.

Large Language Models (LLMs) have revolutionized natural language processing through their state of art reasoning capabilities. This paper explores the convergence of LLM reasoning techniques and feature generation for machine learning tasks. We examine four key reasoning approaches: Chain of Thought, Tree of Thoughts, Retrieval-Augmented Generation, and Thought Space Exploration. Our analysis reveals how these approaches can be used to identify effective feature generation rules without having to manually specify search spaces. The paper categorizes LLM-based feature generation methods across various domains including finance, healthcare, and text analytics. LLMs can extract key information from clinical notes and radiology reports in healthcare, by enabling more efficient data utilization. In finance, LLMs facilitate text generation, summarization, and entity extraction from complex documents. We analyze evaluation methodologies for assessing feature quality and downstream performance, with particular attention to OCTree's decision tree reasoning approach that provides language-based feedback for iterative improvements. Current challenges include hallucination, computational efficiency, and domain adaptation. As of March 2025, emerging approaches include inference-time compute scaling, reinforcement learning, and supervised fine-tuning with model distillation. Future directions point toward multimodal feature generation, self-improving systems, and neuro-symbolic approaches. This paper provides a detailed overview of an emerging field that promises to automate and enhance feature engineering through language model reasoning.

Medical applications of machine learning (ML) have experienced a surge in popularity in recent years. The intensive care unit (ICU) is a natural habitat for ML given the abundance of available data from electronic health records. Models have been proposed to address numerous ICU prediction tasks like the early detection of complications. While authors frequently report state-of-the-art performance, it is challenging to verify claims of superiority. Datasets and code are not always published, and cohort definitions, preprocessing pipelines, and training setups are difficult to reproduce. This work introduces Yet Another ICU Benchmark (YAIB), a modular framework that allows researchers to define reproducible and comparable clinical ML experiments; we offer an end-to-end solution from cohort definition to model evaluation. The framework natively supports most open-access ICU datasets (MIMIC III/IV, eICU, HiRID, AUMCdb) and is easily adaptable to future ICU datasets. Combined with a transparent preprocessing pipeline and extensible training code for multiple ML and deep learning models, YAIB enables unified model development. Our benchmark comes with five predefined established prediction tasks (mortality, acute kidney injury, sepsis, kidney function, and length of stay) developed in collaboration with clinicians. Adding further tasks is straightforward by design. Using YAIB, we demonstrate that the choice of dataset, cohort definition, and preprocessing have a major impact on the prediction performance - often more so than model class - indicating an urgent need for YAIB as a holistic benchmarking tool. We provide our work to the clinical ML community to accelerate method development and enable real-world clinical implementations. Software Repository: https://github.com/rvandewater/YAIB.

The absence of transparency and explainability hinders the clinical adoption of Machine learning (ML) algorithms. Although various methods of explainable artificial intelligence (XAI) have been suggested, there is a lack of literature that delves into their practicality and assesses them based on criteria that could foster trust in clinical environments. To address this gap this study evaluates two popular XAI methods used for explaining predictive models in the healthcare context in terms of whether they (i) generate domain-appropriate representation, i.e. coherent with respect to the application task, (ii) impact clinical workflow and (iii) are consistent. To that end, explanations generated at the cohort and patient levels were analysed. The paper reports the first benchmarking of the XAI methods applied to risk prediction models obtained by evaluating the concordance between generated explanations and the trigger of a future clinical deterioration episode recorded by the data collection system. We carried out an analysis using two Electronic Medical Records (EMR) datasets sourced from Australian major hospitals. The findings underscore the limitations of state-of-the-art XAI methods in the clinical context and their potential benefits. We discuss these limitations and contribute to the theoretical development of trustworthy XAI solutions where clinical decision support guides the choice of intervention by suggesting the pattern or drivers for clinical deterioration in the future.

Large Language Models (LLMs) demonstrate remarkable versatility in various NLP tasks but encounter distinct challenges in biomedical due to the complexities of language and data scarcity. This paper investigates LLMs application in the biomedical domain by exploring strategies to enhance their performance for the NER task. Our study reveals the importance of meticulously designed prompts in the biomedical. Strategic selection of in-context examples yields a marked improvement, offering ~15-20\% increase in F1 score across all benchmark datasets for biomedical few-shot NER. Additionally, our results indicate that integrating external biomedical knowledge via prompting strategies can enhance the proficiency of general-purpose LLMs to meet the specialized needs of biomedical NER. Leveraging a medical knowledge base, our proposed method, DiRAG, inspired by Retrieval-Augmented Generation (RAG), can boost the zero-shot F1 score of LLMs for biomedical NER. Code is released at https://github.com/masoud-monajati/LLM_Bio_NER

In many real-world applications, deployed models encounter inputs that differ from the data seen during training. Out-of-distribution detection identifies whether an input stems from an unseen distribution, while open-world recognition flags such inputs to ensure the system remains robust as ever-emerging, previously unknown categories appear and must be addressed without retraining. Foundation and vision-language models are pre-trained on large and diverse datasets with the expectation of broad generalization across domains, including medical imaging. However, benchmarking these models on test sets with only a few common outlier types silently collapses the evaluation back to a closed-set problem, masking failures on rare or truly novel conditions encountered in clinical use. We therefore present NOVA, a challenging, real-life evaluation-only benchmark of sim900 brain MRI scans that span 281 rare pathologies and heterogeneous acquisition protocols. Each case includes rich clinical narratives and double-blinded expert bounding-box annotations. Together, these enable joint assessment of anomaly localisation, visual captioning, and diagnostic reasoning. Because NOVA is never used for training, it serves as an extreme stress-test of out-of-distribution generalisation: models must bridge a distribution gap both in sample appearance and in semantic space. Baseline results with leading vision-language models (GPT-4o, Gemini 2.0 Flash, and Qwen2.5-VL-72B) reveal substantial performance drops across all tasks, establishing NOVA as a rigorous testbed for advancing models that can detect, localize, and reason about truly unknown anomalies.

Given a stationary state-space model that relates a sequence of hidden states and corresponding measurements or observations, Bayesian filtering provides a principled statistical framework for inferring the posterior distribution of the current state given all measurements up to the present time. For example, the Apollo lunar module implemented a Kalman filter to infer its location from a sequence of earth-based radar measurements and land safely on the moon. To perform Bayesian filtering, we require a measurement model that describes the conditional distribution of each observation given state. The Kalman filter takes this measurement model to be linear, Gaussian. Here we show how a nonlinear, Gaussian approximation to the distribution of state given observation can be used in conjunction with Bayes' rule to build a nonlinear, non-Gaussian measurement model. The resulting approach, called the Discriminative Kalman Filter (DKF), retains fast closed-form updates for the posterior. We argue there are many cases where the distribution of state given measurement is better-approximated as Gaussian, especially when the dimensionality of measurements far exceeds that of states and the Bernstein-von Mises theorem applies. Online neural decoding for brain-computer interfaces provides a motivating example, where filtering incorporates increasingly detailed measurements of neural activity to provide users control over external devices. Within the BrainGate2 clinical trial, the DKF successfully enabled three volunteers with quadriplegia to control an on-screen cursor in real-time using mental imagery alone. Participant "T9" used the DKF to type out messages on a tablet PC.

Large Language Models (LLMs) present immense potential in the medical field, yet concerns over data privacy, regulatory compliance, and model stability restrict their widespread adoption. Although the distillation of high-performing closed-source LLMs has proven effective for general tasks, their application in healthcare is limited due to reduced domain knowledge and remnants of alignment behavior hindering clinical tasks. To address these challenges, we propose Dialogue-Based Knowledge Encoding (DBKE). DBKE enhances models' implicit knowledge base and primes them for conversational recall, augmenting their conversational capabilities and enabling a soft alignment for subsequent use cases. By transforming dense academic source text into synthetic dialogue, DBKE broadens the model's knowledge base and enables a soft alignment that guides downstream behaviours. We present Clinical Camel, an open-source, healthcare-focused conversational model, to showcase the effectiveness of DBKE. Clinical Camel outperforms GPT-3.5 on the United States Medical Licensing Examination (USMLE) Step 1 and Step 3 with scores of 53.2 % and 58.2 %, respectively, compared to GPT-3.5's scores of 36.1 % and 55.7 %. Clinical Camel adeptly handles multi-stage clinical case problems, provides adaptive counseling, and generates clinical notes. However, it is prone to hallucinations, which pose a significant obstacle in safety-critical settings. The performance of Clinical Camel underscores the importance of continued research and development of open-source models for the safe and effective integration of LLMs in healthcare settings.

Large language models (LLMs) hold great promise for medical applications and are evolving rapidly, with new models being released at an accelerated pace. However, current evaluations of LLMs in clinical contexts remain limited. Most existing benchmarks rely on medical exam-style questions or PubMed-derived text, failing to capture the complexity of real-world electronic health record (EHR) data. Others focus narrowly on specific application scenarios, limiting their generalizability across broader clinical use. To address this gap, we present BRIDGE, a comprehensive multilingual benchmark comprising 87 tasks sourced from real-world clinical data sources across nine languages. We systematically evaluated 52 state-of-the-art LLMs (including DeepSeek-R1, GPT-4o, Gemini, and Llama 4) under various inference strategies. With a total of 13,572 experiments, our results reveal substantial performance variation across model sizes, languages, natural language processing tasks, and clinical specialties. Notably, we demonstrate that open-source LLMs can achieve performance comparable to proprietary models, while medically fine-tuned LLMs based on older architectures often underperform versus updated general-purpose models. The BRIDGE and its corresponding leaderboard serve as a foundational resource and a unique reference for the development and evaluation of new LLMs in real-world clinical text understanding.

Objective: To transform heterogeneous clinical data from electronic health records into clinically meaningful constructed features using data driven method that rely, in part, on temporal relations among data. Materials and Methods: The clinically meaningful representations of medical concepts and patients are the key for health analytic applications. Most of existing approaches directly construct features mapped to raw data (e.g., ICD or CPT codes), or utilize some ontology mapping such as SNOMED codes. However, none of the existing approaches leverage EHR data directly for learning such concept representation. We propose a new way to represent heterogeneous medical concepts (e.g., diagnoses, medications and procedures) based on co-occurrence patterns in longitudinal electronic health records. The intuition behind the method is to map medical concepts that are co-occuring closely in time to similar concept vectors so that their distance will be small. We also derive a simple method to construct patient vectors from the related medical concept vectors. Results: For qualitative evaluation, we study similar medical concepts across diagnosis, medication and procedure. In quantitative evaluation, our proposed representation significantly improves the predictive modeling performance for onset of heart failure (HF), where classification methods (e.g. logistic regression, neural network, support vector machine and K-nearest neighbors) achieve up to 23% improvement in area under the ROC curve (AUC) using this proposed representation. Conclusion: We proposed an effective method for patient and medical concept representation learning. The resulting representation can map relevant concepts together and also improves predictive modeling performance.

Deep Learning has revolutionized various fields, including Computer Vision, Natural Language Processing, as well as Biomedical research. Within the field of neuroscience, specifically in electrophysiological neuroimaging, researchers are starting to explore leveraging deep learning to make predictions on their data without extensive feature engineering. The availability of large-scale datasets is a crucial aspect of allowing the experimentation of Deep Learning models. We are publishing the first large-scale clinical EEG dataset that simplifies data access and management for Deep Learning. This dataset contains eyes-closed EEG data prepared from a collection of 1,574 juvenile participants from the Healthy Brain Network. We demonstrate a use case integrating this framework, and discuss why providing such neuroinformatics infrastructure to the community is critical for future scientific discoveries.