Daily Papers

Dermatological diagnosis represents a complex multimodal challenge that requires integrating visual features with specialized clinical knowledge. While vision-language pretraining (VLP) has advanced medical AI, its effectiveness in dermatology is limited by text length constraints and the lack of structured texts. In this paper, we introduce MAKE, a Multi-Aspect Knowledge-Enhanced vision-language pretraining framework for zero-shot dermatological tasks. Recognizing that comprehensive dermatological descriptions require multiple knowledge aspects that exceed standard text constraints, our framework introduces: (1) a multi-aspect contrastive learning strategy that decomposes clinical narratives into knowledge-enhanced sub-texts through large language models, (2) a fine-grained alignment mechanism that connects subcaptions with diagnostically relevant image features, and (3) a diagnosis-guided weighting scheme that adaptively prioritizes different sub-captions based on clinical significance prior. Through pretraining on 403,563 dermatological image-text pairs collected from education resources, MAKE significantly outperforms state-of-the-art VLP models on eight datasets across zero-shot skin disease classification, concept annotation, and cross-modal retrieval tasks. Our code will be made publicly available at https: //github.com/SiyuanYan1/MAKE.

Clinical diagnosis is a highly specialized discipline requiring both domain expertise and strict adherence to rigorous guidelines. While current AI-driven medical research predominantly focuses on knowledge graphs or natural text pretraining paradigms to incorporate medical knowledge, these approaches primarily rely on implicitly encoded knowledge within model parameters, neglecting task-specific knowledge required by diverse downstream tasks. To address this limitation, we propose Retrieval-Augmented Diagnosis (RAD), a novel framework that explicitly injects external knowledge into multimodal models directly on downstream tasks. Specifically, RAD operates through three key mechanisms: retrieval and refinement of disease-centered knowledge from multiple medical sources, a guideline-enhanced contrastive loss that constrains the latent distance between multi-modal features and guideline knowledge, and the dual transformer decoder that employs guidelines as queries to steer cross-modal fusion, aligning the models with clinical diagnostic workflows from guideline acquisition to feature extraction and decision-making. Moreover, recognizing the lack of quantitative evaluation of interpretability for multimodal diagnostic models, we introduce a set of criteria to assess the interpretability from both image and text perspectives. Extensive evaluations across four datasets with different anatomies demonstrate RAD's generalizability, achieving state-of-the-art performance. Furthermore, RAD enables the model to concentrate more precisely on abnormal regions and critical indicators, ensuring evidence-based, trustworthy diagnosis. Our code is available at https://github.com/tdlhl/RAD.

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

Weighting methods in causal inference have been widely used to achieve a desirable level of covariate balancing. However, the existing weighting methods have desirable theoretical properties only when a certain model, either the propensity score or outcome regression model, is correctly specified. In addition, the corresponding estimators do not behave well for finite samples due to large variance even when the model is correctly specified. In this paper, we consider to use the integral probability metric (IPM), which is a metric between two probability measures, for covariate balancing. Optimal weights are determined so that weighted empirical distributions for the treated and control groups have the smallest IPM value for a given set of discriminators. We prove that the corresponding estimator can be consistent without correctly specifying any model (neither the propensity score nor the outcome regression model). In addition, we empirically show that our proposed method outperforms existing weighting methods with large margins for finite samples.

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

The differential diagnosis of neurodegenerative dementias is a challenging clinical task, mainly because of the overlap in symptom presentation and the similarity of patterns observed in structural neuroimaging. To improve diagnostic efficiency and accuracy, deep learning-based methods such as Convolutional Neural Networks and Vision Transformers have been proposed for the automatic classification of brain MRIs. However, despite their strong predictive performance, these models find limited clinical utility due to their opaque decision making. In this work, we propose a framework that integrates two core components to enhance diagnostic transparency. First, we introduce a modular pipeline for converting 3D T1-weighted brain MRIs into textual radiology reports. Second, we explore the potential of modern Large Language Models (LLMs) to assist clinicians in the differential diagnosis between Frontotemporal dementia subtypes, Alzheimer's disease, and normal aging based on the generated reports. To bridge the gap between predictive accuracy and explainability, we employ reinforcement learning to incentivize diagnostic reasoning in LLMs. Without requiring supervised reasoning traces or distillation from larger models, our approach enables the emergence of structured diagnostic rationales grounded in neuroimaging findings. Unlike post-hoc explainability methods that retrospectively justify model decisions, our framework generates diagnostic rationales as part of the inference process-producing causally grounded explanations that inform and guide the model's decision-making process. In doing so, our framework matches the diagnostic performance of existing deep learning methods while offering rationales that support its diagnostic conclusions.

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

Automatic medical report generation (MRG) is of great research value as it has the potential to relieve radiologists from the heavy burden of report writing. Despite recent advancements, accurate MRG remains challenging due to the need for precise clinical understanding and the identification of clinical findings. Moreover, the imbalanced distribution of diseases makes the challenge even more pronounced, as rare diseases are underrepresented in training data, making their diagnostic performance unreliable. To address these challenges, we propose diagnosis-driven prompts for medical report generation (PromptMRG), a novel framework that aims to improve the diagnostic accuracy of MRG with the guidance of diagnosis-aware prompts. Specifically, PromptMRG is based on encoder-decoder architecture with an extra disease classification branch. When generating reports, the diagnostic results from the classification branch are converted into token prompts to explicitly guide the generation process. To further improve the diagnostic accuracy, we design cross-modal feature enhancement, which retrieves similar reports from the database to assist the diagnosis of a query image by leveraging the knowledge from a pre-trained CLIP. Moreover, the disease imbalanced issue is addressed by applying an adaptive logit-adjusted loss to the classification branch based on the individual learning status of each disease, which overcomes the barrier of text decoder's inability to manipulate disease distributions. Experiments on two MRG benchmarks show the effectiveness of the proposed method, where it obtains state-of-the-art clinical efficacy performance on both datasets.

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

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

Current medical language models, adapted from large language models (LLMs), typically predict ICD code-based diagnosis from electronic health records (EHRs) because these labels are readily available. However, ICD codes do not capture the nuanced, context-rich reasoning clinicians use for diagnosis. Clinicians synthesize diverse patient data and reference clinical practice guidelines (CPGs) to make evidence-based decisions. This misalignment limits the clinical utility of existing models. We introduce GARMLE-G, a Generation-Augmented Retrieval framework that grounds medical language model outputs in authoritative CPGs. Unlike conventional Retrieval-Augmented Generation based approaches, GARMLE-G enables hallucination-free outputs by directly retrieving authoritative guideline content without relying on model-generated text. It (1) integrates LLM predictions with EHR data to create semantically rich queries, (2) retrieves relevant CPG knowledge snippets via embedding similarity, and (3) fuses guideline content with model output to generate clinically aligned recommendations. A prototype system for hypertension diagnosis was developed and evaluated on multiple metrics, demonstrating superior retrieval precision, semantic relevance, and clinical guideline adherence compared to RAG-based baselines, while maintaining a lightweight architecture suitable for localized healthcare deployment. This work provides a scalable, low-cost, and hallucination-free method for grounding medical language models in evidence-based clinical practice, with strong potential for broader clinical deployment.

Post-training quantization is a key technique for reducing the memory and inference latency of large language models by quantizing weights and activations without requiring retraining. However, existing methods either (1) fail to account for the varying importance of hidden features to the end loss or, when incorporating end loss, (2) neglect the critical interactions between model weights. To address these limitations, we propose GuidedQuant, a novel quantization approach that integrates gradient information from the end loss into the quantization objective while preserving cross-weight dependencies within output channels. GuidedQuant consistently boosts the performance of state-of-the-art quantization methods across weight-only scalar, weight-only vector, and weight-and-activation quantization. Additionally, we introduce a novel non-uniform scalar quantization algorithm, which is guaranteed to monotonically decrease the quantization objective value, and outperforms existing methods in this category. We release the code at https://github.com/snu-mllab/GuidedQuant.

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.

Recently computer-aided diagnosis has demonstrated promising performance, effectively alleviating the workload of clinicians. However, the inherent sample imbalance among different diseases leads algorithms biased to the majority categories, leading to poor performance for rare categories. Existing works formulated this challenge as a long-tailed problem and attempted to tackle it by decoupling the feature representation and classification. Yet, due to the imbalanced distribution and limited samples from tail classes, these works are prone to biased representation learning and insufficient classifier calibration. To tackle these problems, we propose a new Long-tailed Medical Diagnosis (LMD) framework for balanced medical image classification on long-tailed datasets. In the initial stage, we develop a Relation-aware Representation Learning (RRL) scheme to boost the representation ability by encouraging the encoder to capture intrinsic semantic features through different data augmentations. In the subsequent stage, we propose an Iterative Classifier Calibration (ICC) scheme to calibrate the classifier iteratively. This is achieved by generating a large number of balanced virtual features and fine-tuning the encoder using an Expectation-Maximization manner. The proposed ICC compensates for minority categories to facilitate unbiased classifier optimization while maintaining the diagnostic knowledge in majority classes. Comprehensive experiments on three public long-tailed medical datasets demonstrate that our LMD framework significantly surpasses state-of-the-art approaches. The source code can be accessed at https://github.com/peterlipan/LMD.

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

Classifier-Free Guidance (CFG) enhances the quality and condition adherence of text-to-image diffusion models. It operates by combining the conditional and unconditional predictions using a fixed weight. However, recent works vary the weights throughout the diffusion process, reporting superior results but without providing any rationale or analysis. By conducting comprehensive experiments, this paper provides insights into CFG weight schedulers. Our findings suggest that simple, monotonically increasing weight schedulers consistently lead to improved performances, requiring merely a single line of code. In addition, more complex parametrized schedulers can be optimized for further improvement, but do not generalize across different models and tasks.

Cardiovascular diseases (CVDs) remain the leading cause of mortality globally, and echocardiography is critical for diagnosis of both common and congenital cardiac conditions. However, echocardiographic data for certain pathologies are scarce, hindering the development of robust automated diagnosis models. In this work, we propose Echo-Path, a novel generative framework to produce echocardiogram videos conditioned on specific cardiac pathologies. Echo-Path can synthesize realistic ultrasound video sequences that exhibit targeted abnormalities, focusing here on atrial septal defect (ASD) and pulmonary arterial hypertension (PAH). Our approach introduces a pathology-conditioning mechanism into a state-of-the-art echo video generator, allowing the model to learn and control disease-specific structural and motion patterns in the heart. Quantitative evaluation demonstrates that the synthetic videos achieve low distribution distances, indicating high visual fidelity. Clinically, the generated echoes exhibit plausible pathology markers. Furthermore, classifiers trained on our synthetic data generalize well to real data and, when used to augment real training sets, it improves downstream diagnosis of ASD and PAH by 7\% and 8\% respectively. Code, weights and dataset are available here https://github.com/Marshall-mk/EchoPathv1

Medical images and radiology reports are crucial for diagnosing medical conditions, highlighting the importance of quantitative analysis for clinical decision-making. However, the diversity and cross-source heterogeneity of these data challenge the generalizability of current data-mining methods. Multimodal large language models (MLLMs) have recently transformed many domains, significantly affecting the medical field. Notably, Gemini-Vision-series (Gemini) and GPT-4-series (GPT-4) models have epitomized a paradigm shift in Artificial General Intelligence (AGI) for computer vision, showcasing their potential in the biomedical domain. In this study, we evaluated the performance of the Gemini, GPT-4, and 4 popular large models for an exhaustive evaluation across 14 medical imaging datasets, including 5 medical imaging categories (dermatology, radiology, dentistry, ophthalmology, and endoscopy), and 3 radiology report datasets. The investigated tasks encompass disease classification, lesion segmentation, anatomical localization, disease diagnosis, report generation, and lesion detection. Our experimental results demonstrated that Gemini-series models excelled in report generation and lesion detection but faces challenges in disease classification and anatomical localization. Conversely, GPT-series models exhibited proficiency in lesion segmentation and anatomical localization but encountered difficulties in disease diagnosis and lesion detection. Additionally, both the Gemini series and GPT series contain models that have demonstrated commendable generation efficiency. While both models hold promise in reducing physician workload, alleviating pressure on limited healthcare resources, and fostering collaboration between clinical practitioners and artificial intelligence technologies, substantial enhancements and comprehensive validations remain imperative before clinical deployment.

Depression poses significant challenges to patients and healthcare organizations, necessitating efficient assessment methods. Existing paradigms typically focus on a patient-doctor way that overlooks multi-role interactions, such as family involvement in the evaluation and caregiving process. Moreover, current automatic depression detection (ADD) methods usually model depression detection as a classification or regression task, lacking interpretability for the decision-making process. To address these issues, we developed InterMind, a doctor-patient-family interactive depression assessment system empowered by large language models (LLMs). Our system enables patients and families to contribute descriptions, generates assistive diagnostic reports for doctors, and provides actionable insights, improving diagnostic precision and efficiency. To enhance LLMs' performance in psychological counseling and diagnostic interpretability, we integrate retrieval-augmented generation (RAG) and chain-of-thoughts (CoT) techniques for data augmentation, which mitigates the hallucination issue of LLMs in specific scenarios after instruction fine-tuning. Quantitative experiments and professional assessments by clinicians validate the effectiveness of our system.

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

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.

Large language models (LLMs) have shown remarkable capability in numerous tasks and applications. However, fine-tuning LLMs using high-quality datasets under external supervision remains prohibitively expensive. In response, LLM self-improvement approaches have been vibrantly developed recently. The typical paradigm of LLM self-improvement involves training LLM on self-generated data, part of which may be detrimental and should be filtered out due to the unstable data quality. While current works primarily employs filtering strategies based on answer correctness, in this paper, we demonstrate that filtering out correct but with high distribution shift extent (DSE) samples could also benefit the results of self-improvement. Given that the actual sample distribution is usually inaccessible, we propose a new metric called DS weight to approximate DSE, inspired by the Importance Weighting methods. Consequently, we integrate DS weight with self-consistency to comprehensively filter the self-generated samples and fine-tune the language model. Experiments show that with only a tiny valid set (up to 5\% size of the training set) to compute DS weight, our approach can notably promote the reasoning ability of current LLM self-improvement methods. The resulting performance is on par with methods that rely on external supervision from pre-trained reward models.

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

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

In observational studies, balancing covariates in different treatment groups is essential to estimate treatment effects. One of the most commonly used methods for such purposes is weighting. The performance of this class of methods usually depends on strong regularity conditions for the underlying model, which might not hold in practice. In this paper, we investigate weighting methods from a functional estimation perspective and argue that the weights needed for covariate balancing could differ from those needed for treatment effects estimation under low regularity conditions. Motivated by this observation, we introduce a new framework of weighting that directly targets the treatment effects estimation. Unlike existing methods, the resulting estimator for a treatment effect under this new framework is a simple kernel-based U-statistic after applying a data-driven transformation to the observed covariates. We characterize the theoretical properties of the new estimators of treatment effects under a nonparametric setting and show that they are able to work robustly under low regularity conditions. The new framework is also applied to several numerical examples to demonstrate its practical merits.

Metric space magnitude, an active field of research in algebraic topology, is a scalar quantity that summarizes the effective number of distinct points that live in a general metric space. The {\em weighting vector} is a closely-related concept that captures, in a nontrivial way, much of the underlying geometry of the original metric space. Recent work has demonstrated that when the metric space is Euclidean, the weighting vector serves as an effective tool for boundary detection. We recast this result and show the weighting vector may be viewed as a solution to a kernelized SVM. As one consequence, we apply this new insight to the task of outlier detection, and we demonstrate performance that is competitive or exceeds performance of state-of-the-art techniques on benchmark data sets. Under mild assumptions, we show the weighting vector, which has computational cost of matrix inversion, can be efficiently approximated in linear time. We show how nearest neighbor methods can approximate solutions to the minimization problems defined by SVMs.

Spine disorders affect 619 million people globally and are a leading cause of disability, yet AI-assisted diagnosis remains limited by the lack of level-aware, multimodal datasets. Clinical decision-making for spine disorders requires sophisticated reasoning across X-ray, CT, and MRI at specific vertebral levels. However, progress has been constrained by the absence of traceable, clinically-grounded instruction data and standardized, spine-specific benchmarks. To address this, we introduce SpineMed, an ecosystem co-designed with practicing spine surgeons. It features SpineMed-450k, the first large-scale dataset explicitly designed for vertebral-level reasoning across imaging modalities with over 450,000 instruction instances, and SpineBench, a clinically-grounded evaluation framework. SpineMed-450k is curated from diverse sources, including textbooks, guidelines, open datasets, and ~1,000 de-identified hospital cases, using a clinician-in-the-loop pipeline with a two-stage LLM generation method (draft and revision) to ensure high-quality, traceable data for question-answering, multi-turn consultations, and report generation. SpineBench evaluates models on clinically salient axes, including level identification, pathology assessment, and surgical planning. Our comprehensive evaluation of several recently advanced large vision-language models (LVLMs) on SpineBench reveals systematic weaknesses in fine-grained, level-specific reasoning. In contrast, our model fine-tuned on SpineMed-450k demonstrates consistent and significant improvements across all tasks. Clinician assessments confirm the diagnostic clarity and practical utility of our model's outputs.

In modern recommendation systems, the standard pipeline involves training machine learning models on historical data to predict user behaviors and improve recommendations continuously. However, these data training loops can introduce interference in A/B tests, where data generated by control and treatment algorithms, potentially with different distributions, are combined. To address these challenges, we introduce a novel approach called weighted training. This approach entails training a model to predict the probability of each data point appearing in either the treatment or control data and subsequently applying weighted losses during model training. We demonstrate that this approach achieves the least variance among all estimators that do not cause shifts in the training distributions. Through simulation studies, we demonstrate the lower bias and variance of our approach compared to other methods.

Accurate segmentation of Multiple Sclerosis (MS) lesions in longitudinal MRI scans is crucial for monitoring disease progression and treatment efficacy. Although changes across time are taken into account when assessing images in clinical practice, most existing deep learning methods treat scans from different timepoints separately. Among studies utilizing longitudinal images, a simple channel-wise concatenation is the primary albeit suboptimal method employed to integrate timepoints. We introduce a novel approach that explicitly incorporates temporal differences between baseline and follow-up scans through a unique architectural inductive bias called Difference Weighting Block. It merges features from two timepoints, emphasizing changes between scans. We achieve superior scores in lesion segmentation (Dice Score, Hausdorff distance) as well as lesion detection (lesion-level F_1 score) as compared to state-of-the-art longitudinal and single timepoint models across two datasets. Our code is made publicly available at www.github.com/MIC-DKFZ/Longitudinal-Difference-Weighting.

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

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

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

The emergence of groundbreaking large language models capable of performing complex reasoning tasks holds significant promise for addressing various scientific challenges, including those arising in complex clinical scenarios. To enable their safe and effective deployment in real-world healthcare settings, it is urgently necessary to benchmark the diagnostic capabilities of current models systematically. Given the limitations of existing medical benchmarks in evaluating advanced diagnostic reasoning, we present DiagnosisArena, a comprehensive and challenging benchmark designed to rigorously assess professional-level diagnostic competence. DiagnosisArena consists of 1,113 pairs of segmented patient cases and corresponding diagnoses, spanning 28 medical specialties, deriving from clinical case reports published in 10 top-tier medical journals. The benchmark is developed through a meticulous construction pipeline, involving multiple rounds of screening and review by both AI systems and human experts, with thorough checks conducted to prevent data leakage. Our study reveals that even the most advanced reasoning models, o3-mini, o1, and DeepSeek-R1, achieve only 45.82%, 31.09%, and 17.79% accuracy, respectively. This finding highlights a significant generalization bottleneck in current large language models when faced with clinical diagnostic reasoning challenges. Through DiagnosisArena, we aim to drive further advancements in AIs diagnostic reasoning capabilities, enabling more effective solutions for real-world clinical diagnostic challenges. We provide the benchmark and evaluation tools for further research and development https://github.com/SPIRAL-MED/DiagnosisArena.

Differential Diagnosis (DDx) is a fundamental yet complex aspect of clinical decision-making, in which physicians iteratively refine a ranked list of possible diseases based on symptoms, antecedents, and medical knowledge. While recent advances in large language models (LLMs) have shown promise in supporting DDx, existing approaches face key limitations, including single-dataset evaluations, isolated optimization of components, unrealistic assumptions about complete patient profiles, and single-attempt diagnosis. We introduce a Modular Explainable DDx Agent (MEDDxAgent) framework designed for interactive DDx, where diagnostic reasoning evolves through iterative learning, rather than assuming a complete patient profile is accessible. MEDDxAgent integrates three modular components: (1) an orchestrator (DDxDriver), (2) a history taking simulator, and (3) two specialized agents for knowledge retrieval and diagnosis strategy. To ensure robust evaluation, we introduce a comprehensive DDx benchmark covering respiratory, skin, and rare diseases. We analyze single-turn diagnostic approaches and demonstrate the importance of iterative refinement when patient profiles are not available at the outset. Our broad evaluation demonstrates that MEDDxAgent achieves over 10% accuracy improvements in interactive DDx across both large and small LLMs, while offering critical explainability into its diagnostic reasoning process.

Online medical service provides patients convenient access to doctors, but effectively ranking doctors based on specific medical needs remains challenging. Current ranking approaches typically lack the interpretability crucial for patient trust and informed decision-making. Additionally, the scarcity of standardized benchmarks and labeled data for supervised learning impedes progress in expertise-aware doctor ranking. To address these challenges, we propose an explainable ranking framework for doctor ranking powered by large language models in a zero-shot setting. Our framework dynamically generates disease-specific ranking criteria to guide the large language model in assessing doctor relevance with transparency and consistency. It further enhances interpretability by generating step-by-step rationales for its ranking decisions, improving the overall explainability of the information retrieval process. To support rigorous evaluation, we built and released DrRank, a novel expertise-driven dataset comprising 38 disease-treatment pairs and 4,325 doctor profiles. On this benchmark, our framework significantly outperforms the strongest baseline by +6.45 NDCG@10. Comprehensive analyses also show our framework is fair across disease types, patient gender, and geographic regions. Furthermore, verification by medical experts confirms the reliability and interpretability of our approach, reinforcing its potential for trustworthy, real-world doctor recommendation. To demonstrate its broader applicability, we validate our framework on two datasets from BEIR benchmark, where it again achieves superior performance. The code and associated data are available at: https://github.com/YangLab-BUPT/DrRank.

For safety, medical AI systems undergo thorough evaluations before deployment, validating their predictions against a ground truth which is assumed to be fixed and certain. However, this ground truth is often curated in the form of differential diagnoses. While a single differential diagnosis reflects the uncertainty in one expert assessment, multiple experts introduce another layer of uncertainty through disagreement. Both forms of uncertainty are ignored in standard evaluation which aggregates these differential diagnoses to a single label. In this paper, we show that ignoring uncertainty leads to overly optimistic estimates of model performance, therefore underestimating risk associated with particular diagnostic decisions. To this end, we propose a statistical aggregation approach, where we infer a distribution on probabilities of underlying medical condition candidates themselves, based on observed annotations. This formulation naturally accounts for the potential disagreements between different experts, as well as uncertainty stemming from individual differential diagnoses, capturing the entire ground truth uncertainty. Our approach boils down to generating multiple samples of medical condition probabilities, then evaluating and averaging performance metrics based on these sampled probabilities. In skin condition classification, we find that a large portion of the dataset exhibits significant ground truth uncertainty and standard evaluation severely over-estimates performance without providing uncertainty estimates. In contrast, our framework provides uncertainty estimates on common metrics of interest such as top-k accuracy and average overlap, showing that performance can change multiple percentage points. We conclude that, while assuming a crisp ground truth can be acceptable for many AI applications, a more nuanced evaluation protocol should be utilized in medical diagnosis.

Radiologists play a crucial role by translating medical images into medical reports. However, the field faces staffing shortages and increasing workloads. While automated approaches using vision-language models (VLMs) show promise as assistants, they require exceptionally high accuracy. Most current VLMs in radiology rely solely on supervised fine-tuning (SFT). Meanwhile, in the general domain, additional preference fine-tuning has become standard practice. The challenge in radiology lies in the prohibitive cost of obtaining radiologist feedback. We propose a scalable automated preference alignment technique for VLMs in radiology, focusing on chest X-ray (CXR) report generation. Our method leverages publicly available datasets with an LLM-as-a-Judge mechanism, eliminating the need for additional expert radiologist feedback. We evaluate and benchmark five direct alignment algorithms (DAAs). Our results show up to a 57.4% improvement in average GREEN scores, a LLM-based metric for evaluating CXR reports, and a 9.2% increase in an average across six metrics (domain specific and general), compared to the SFT baseline. We study reward overoptimization via length exploitation, with reports lengthening by up to 3.2x. To assess a potential alignment tax, we benchmark on six additional diverse tasks, finding no significant degradations. A reader study involving four board-certified radiologists indicates win rates of up to 0.62 over the SFT baseline, while significantly penalizing verbosity. Our analysis provides actionable insights for the development of VLMs in high-stakes fields like radiology.

Federated learning (FL) has been a promising approach in the field of medical imaging in recent years. A critical problem in FL, specifically in medical scenarios is to have a more accurate shared model which is robust to noisy and out-of distribution clients. In this work, we tackle the problem of statistical heterogeneity in data for FL which is highly plausible in medical data where for example the data comes from different sites with different scanner settings. We propose IDA (Inverse Distance Aggregation), a novel adaptive weighting approach for clients based on meta-information which handles unbalanced and non-iid data. We extensively analyze and evaluate our method against the well-known FL approach, Federated Averaging as a baseline.

Human-interpretable predictions are essential for deploying AI in medical imaging, yet most interpretable-by-design (IBD) frameworks require concept annotations for training data, which are costly and impractical to obtain in clinical contexts. Recent attempts to bypass annotation, such as zero-shot vision-language models or concept-generation frameworks, struggle to capture domain-specific medical features, leading to poor reliability. In this paper, we propose a novel Prior-guided Concept Predictor (PCP), a weakly supervised framework that enables concept answer prediction without explicit supervision or reliance on language models. PCP leverages class-level concept priors as weak supervision and incorporates a refinement mechanism with KL divergence and entropy regularization to align predictions with clinical reasoning. Experiments on PH2 (dermoscopy) and WBCatt (hematology) show that PCP improves concept-level F1-score by over 33% compared to zero-shot baselines, while delivering competitive classification performance on four medical datasets (PH2, WBCatt, HAM10000, and CXR4) relative to fully supervised concept bottleneck models (CBMs) and V-IP.

Generalist Large Language Models (LLMs), such as GPT-4, have shown considerable promise in various domains, including medical diagnosis. Rare diseases, affecting approximately 300 million people worldwide, often have unsatisfactory clinical diagnosis rates primarily due to a lack of experienced physicians and the complexity of differentiating among many rare diseases. In this context, recent news such as "ChatGPT correctly diagnosed a 4-year-old's rare disease after 17 doctors failed" underscore LLMs' potential, yet underexplored, role in clinically diagnosing rare diseases. To bridge this research gap, we introduce RareBench, a pioneering benchmark designed to systematically evaluate the capabilities of LLMs on 4 critical dimensions within the realm of rare diseases. Meanwhile, we have compiled the largest open-source dataset on rare disease patients, establishing a benchmark for future studies in this domain. To facilitate differential diagnosis of rare diseases, we develop a dynamic few-shot prompt methodology, leveraging a comprehensive rare disease knowledge graph synthesized from multiple knowledge bases, significantly enhancing LLMs' diagnostic performance. Moreover, we present an exhaustive comparative study of GPT-4's diagnostic capabilities against those of specialist physicians. Our experimental findings underscore the promising potential of integrating LLMs into the clinical diagnostic process for rare diseases. This paves the way for exciting possibilities in future advancements in this field.

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

Recent advancements in Large Language Models (LLMs) have drawn increasing attention since the learned embeddings pretrained on large-scale datasets have shown powerful ability in various downstream applications. However, whether the learned knowledge by LLMs can be transferred to clinical cardiology remains unknown. In this work, we aim to bridge this gap by transferring the knowledge of LLMs to clinical Electrocardiography (ECG). We propose an approach for cardiovascular disease diagnosis and automatic ECG diagnosis report generation. We also introduce an additional loss function by Optimal Transport (OT) to align the distribution between ECG and language embedding. The learned embeddings are evaluated on two downstream tasks: (1) automatic ECG diagnosis report generation, and (2) zero-shot cardiovascular disease detection. Our approach is able to generate high-quality cardiac diagnosis reports and also achieves competitive zero-shot classification performance even compared with supervised baselines, which proves the feasibility of transferring knowledge from LLMs to the cardiac domain.

Current vision-language models (VLMs) in medicine are primarily designed for categorical question answering (e.g., "Is this normal or abnormal?") or qualitative descriptive tasks. However, clinical decision-making often relies on quantitative assessments, such as measuring the size of a tumor or the angle of a joint, from which physicians draw their own diagnostic conclusions. This quantitative reasoning capability remains underexplored and poorly supported in existing VLMs. In this work, we introduce MedVision, a large-scale dataset and benchmark specifically designed to evaluate and improve VLMs on quantitative medical image analysis. MedVision spans 22 public datasets covering diverse anatomies and modalities, with 30.8 million image-annotation pairs. We focus on three representative quantitative tasks: (1) detection of anatomical structures and abnormalities, (2) tumor/lesion (T/L) size estimation, and (3) angle/distance (A/D) measurement. Our benchmarks show that current off-the-shelf VLMs perform poorly on these tasks. However, with supervised fine-tuning on MedVision, we significantly enhance their performance across detection, T/L estimation, and A/D measurement, demonstrating reduced error rates and improved precision. This work provides a foundation for developing VLMs with robust quantitative reasoning capabilities in medical imaging. Code and data are available at https://medvision-vlm.github.io.

Supervised learning is often affected by a covariate shift in which the marginal distributions of instances (covariates x) of training and testing samples p_tr(x) and p_te(x) are different but the label conditionals coincide. Existing approaches address such covariate shift by either using the ratio p_te(x)/p_tr(x) to weight training samples (reweighted methods) or using the ratio p_tr(x)/p_te(x) to weight testing samples (robust methods). However, the performance of such approaches can be poor under support mismatch or when the above ratios take large values. We propose a minimax risk classification (MRC) approach for covariate shift adaptation that avoids such limitations by weighting both training and testing samples. In addition, we develop effective techniques that obtain both sets of weights and generalize the conventional kernel mean matching method. We provide novel generalization bounds for our method that show a significant increase in the effective sample size compared with reweighted methods. The proposed method also achieves enhanced classification performance in both synthetic and empirical experiments.

Diffusion models have demonstrated compelling generation quality by optimizing the variational lower bound through a simple denoising score matching loss. In this paper, we provide theoretical evidence that the prevailing practice of using a constant loss weight strategy in diffusion models leads to biased estimation during the training phase. Simply optimizing the denoising network to predict Gaussian noise with constant weighting may hinder precise estimations of original images. To address the issue, we propose an elegant and effective weighting strategy grounded in the theoretically unbiased principle. Moreover, we conduct a comprehensive and systematic exploration to dissect the inherent bias problem deriving from constant weighting loss from the perspectives of its existence, impact and reasons. These analyses are expected to advance our understanding and demystify the inner workings of diffusion models. Through empirical evaluation, we demonstrate that our proposed debiased estimation method significantly enhances sample quality without the reliance on complex techniques, and exhibits improved efficiency compared to the baseline method both in training and sampling processes.

People with diabetes are at risk of developing an eye disease called diabetic retinopathy (DR). This disease occurs when high blood glucose levels cause damage to blood vessels in the retina. Computer-aided DR diagnosis is a promising tool for early detection of DR and severity grading, due to the great success of deep learning. However, most current DR diagnosis systems do not achieve satisfactory performance or interpretability for ophthalmologists, due to the lack of training data with consistent and fine-grained annotations. To address this problem, we construct a large fine-grained annotated DR dataset containing 2,842 images (FGADR). This dataset has 1,842 images with pixel-level DR-related lesion annotations, and 1,000 images with image-level labels graded by six board-certified ophthalmologists with intra-rater consistency. The proposed dataset will enable extensive studies on DR diagnosis. We set up three benchmark tasks for evaluation: 1. DR lesion segmentation; 2. DR grading by joint classification and segmentation; 3. Transfer learning for ocular multi-disease identification. Moreover, a novel inductive transfer learning method is introduced for the third task. Extensive experiments using different state-of-the-art methods are conducted on our FGADR dataset, which can serve as baselines for future research.

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.

Rare diseases, including Inborn Errors of Metabolism (IEM), pose significant diagnostic challenges. Case reports serve as key but computationally underutilized resources to inform diagnosis. Clinical dense information extraction refers to organizing medical information into structured predefined categories. Large Language Models (LLMs) may enable scalable information extraction from case reports but are rarely evaluated for this task. We introduce CaseReportBench, an expert-annotated dataset for dense information extraction of case reports, focusing on IEMs. Using this dataset, we assess various models and prompting strategies, introducing novel approaches such as category-specific prompting and subheading-filtered data integration. Zero-shot chain-of-thought prompting offers little advantage over standard zero-shot prompting. Category-specific prompting improves alignment with the benchmark. The open-source model Qwen2.5-7B outperforms GPT-4o for this task. Our clinician evaluations show that LLMs can extract clinically relevant details from case reports, supporting rare disease diagnosis and management. We also highlight areas for improvement, such as LLMs' limitations in recognizing negative findings important for differential diagnosis. This work advances LLM-driven clinical natural language processing and paves the way for scalable medical AI applications.

There has been a rapidly growing interest in Automatic Symptom Detection (ASD) and Automatic Diagnosis (AD) systems in the machine learning research literature, aiming to assist doctors in telemedicine services. These systems are designed to interact with patients, collect evidence about their symptoms and relevant antecedents, and possibly make predictions about the underlying diseases. Doctors would review the interactions, including the evidence and the predictions, collect if necessary additional information from patients, before deciding on next steps. Despite recent progress in this area, an important piece of doctors' interactions with patients is missing in the design of these systems, namely the differential diagnosis. Its absence is largely due to the lack of datasets that include such information for models to train on. In this work, we present a large-scale synthetic dataset of roughly 1.3 million patients that includes a differential diagnosis, along with the ground truth pathology, symptoms and antecedents for each patient. Unlike existing datasets which only contain binary symptoms and antecedents, this dataset also contains categorical and multi-choice symptoms and antecedents useful for efficient data collection. Moreover, some symptoms are organized in a hierarchy, making it possible to design systems able to interact with patients in a logical way. As a proof-of-concept, we extend two existing AD and ASD systems to incorporate the differential diagnosis, and provide empirical evidence that using differentials as training signals is essential for the efficiency of such systems or for helping doctors better understand the reasoning of those systems.

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

As deep learning models gain attraction in medical data, ensuring transparent and trustworthy decision-making is essential. In skin cancer diagnosis, while advancements in lesion detection and classification have improved accuracy, the black-box nature of these methods poses challenges in understanding their decision processes, leading to trust issues among physicians. This study leverages the CLIP (Contrastive Language-Image Pretraining) model, trained on different skin lesion datasets, to capture meaningful relationships between visual features and diagnostic criteria terms. To further enhance transparency, we propose a method called MedGrad E-CLIP, which builds on gradient-based E-CLIP by incorporating a weighted entropy mechanism designed for complex medical imaging like skin lesions. This approach highlights critical image regions linked to specific diagnostic descriptions. The developed integrated pipeline not only classifies skin lesions by matching corresponding descriptions but also adds an essential layer of explainability developed especially for medical data. By visually explaining how different features in an image relates to diagnostic criteria, this approach demonstrates the potential of advanced vision-language models in medical image analysis, ultimately improving transparency, robustness, and trust in AI-driven diagnostic systems.

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

Building upon our previous investigations of O1 replication (Part 1: Journey Learning [Qin et al., 2024] and Part 2: Distillation [Huang et al., 2024]), this work explores the potential of inference-time scaling in large language models (LLMs) for medical reasoning tasks, ranging from diagnostic decision-making to treatment planning. Through extensive experiments on medical benchmarks of varying complexity (MedQA, Medbullets, and JAMA Clinical Challenges), our investigation reveals several key insights: (1) Increasing inference time does lead to improved performance. With a modest training set of 500 samples, our model yields substantial performance improvements of 6%-11%. (2) Task complexity directly correlates with the required length of reasoning chains, confirming the necessity of extended thought processes for challenging problems. (3) The differential diagnoses generated by our model adhere to the principles of the hypothetico-deductive method, producing a list of potential conditions that may explain a patient's symptoms and systematically narrowing these possibilities by evaluating the evidence. These findings demonstrate the promising synergy between inference-time scaling and journey learning in advancing LLMs' real-world clinical reasoning capabilities.

Pulmonary Hypertension (PH) is a severe disease characterized by an elevated pulmonary artery pressure. The gold standard for PH diagnosis is measurement of mean Pulmonary Artery Pressure (mPAP) during an invasive Right Heart Catheterization. In this paper, we investigate noninvasive approach to PH detection utilizing Magnetic Resonance Imaging, Computer Models and Machine Learning. We show using the ablation study, that physics-informed feature engineering based on models of blood circulation increases the performance of Gradient Boosting Decision Trees-based algorithms for classification of PH and regression of values of mPAP. We compare results of regression (with thresholding of estimated mPAP) and classification and demonstrate that metrics achieved in both experiments are comparable. The predicted mPAP values are more informative to the physicians than the probability of PH returned by classification models. They provide the intuitive explanation of the outcome of the machine learning model (clinicians are accustomed to the mPAP metric, contrary to the PH probability).

In domain adaptation, maximum mean discrepancy (MMD) has been widely adopted as a discrepancy metric between the distributions of source and target domains. However, existing MMD-based domain adaptation methods generally ignore the changes of class prior distributions, i.e., class weight bias across domains. This remains an open problem but ubiquitous for domain adaptation, which can be caused by changes in sample selection criteria and application scenarios. We show that MMD cannot account for class weight bias and results in degraded domain adaptation performance. To address this issue, a weighted MMD model is proposed in this paper. Specifically, we introduce class-specific auxiliary weights into the original MMD for exploiting the class prior probability on source and target domains, whose challenge lies in the fact that the class label in target domain is unavailable. To account for it, our proposed weighted MMD model is defined by introducing an auxiliary weight for each class in the source domain, and a classification EM algorithm is suggested by alternating between assigning the pseudo-labels, estimating auxiliary weights and updating model parameters. Extensive experiments demonstrate the superiority of our weighted MMD over conventional MMD for domain adaptation.

As the global burden of Alzheimer's disease (AD) continues to grow, early and accurate detection has become increasingly critical, especially in regions with limited access to advanced diagnostic tools. We propose BRAINS (Biomedical Retrieval-Augmented Intelligence for Neurodegeneration Screening) to address this challenge. This novel system harnesses the powerful reasoning capabilities of Large Language Models (LLMs) for Alzheimer's detection and monitoring. BRAINS features a dual-module architecture: a cognitive diagnostic module and a case-retrieval module. The Diagnostic Module utilizes LLMs fine-tuned on cognitive and neuroimaging datasets -- including MMSE, CDR scores, and brain volume metrics -- to perform structured assessments of Alzheimer's risk. Meanwhile, the Case Retrieval Module encodes patient profiles into latent representations and retrieves similar cases from a curated knowledge base. These auxiliary cases are fused with the input profile via a Case Fusion Layer to enhance contextual understanding. The combined representation is then processed with clinical prompts for inference. Evaluations on real-world datasets demonstrate BRAINS effectiveness in classifying disease severity and identifying early signs of cognitive decline. This system not only shows strong potential as an assistive tool for scalable, explainable, and early-stage Alzheimer's disease detection, but also offers hope for future applications in the field.

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

Large language models (LLMs) have demonstrated impressive capabilities in disease diagnosis. However, their effectiveness in identifying rarer diseases, which are inherently more challenging to diagnose, remains an open question. Rare disease performance is critical with the increasing use of LLMs in healthcare settings. This is especially true if a primary care physician needs to make a rarer prognosis from only a patient conversation so that they can take the appropriate next step. To that end, several clinical decision support systems are designed to support providers in rare disease identification. Yet their utility is limited due to their lack of knowledge of common disorders and difficulty of use. In this paper, we propose RareScale to combine the knowledge LLMs with expert systems. We use jointly use an expert system and LLM to simulate rare disease chats. This data is used to train a rare disease candidate predictor model. Candidates from this smaller model are then used as additional inputs to black-box LLM to make the final differential diagnosis. Thus, RareScale allows for a balance between rare and common diagnoses. We present results on over 575 rare diseases, beginning with Abdominal Actinomycosis and ending with Wilson's Disease. Our approach significantly improves the baseline performance of black-box LLMs by over 17% in Top-5 accuracy. We also find that our candidate generation performance is high (e.g. 88.8% on gpt-4o generated chats).

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 emergence of vision-language models (VLMs) has opened new possibilities for clinical reasoning and has shown promising performance in dermatological diagnosis. However, their trustworthiness and clinical utility are often limited by three major factors: (1) Data heterogeneity, where diverse datasets lack consistent diagnostic labels and clinical concept annotations; (2) Absence of grounded diagnostic rationales, leading to a scarcity of reliable reasoning supervision; and (3) Limited scalability and generalization, as models trained on small, densely annotated datasets struggle to transfer nuanced reasoning to large, sparsely-annotated ones. To address these limitations, we propose SkinR1, a novel dermatological VLM that combines deep, textbook-based reasoning with the broad generalization capabilities of reinforcement learning (RL). SkinR1 systematically resolves the key challenges through a unified, end-to-end framework. First, we design a textbook-based reasoning generator that synthesizes high-fidelity, hierarchy-aware, and differential-diagnosis (DDx)-informed trajectories, providing reliable expert-level supervision. Second, we leverage the constructed trajectories for supervised fine-tuning (SFT) empowering the model with grounded reasoning ability. Third, we develop a novel RL paradigm that, by incorporating the hierarchical structure of diseases, effectively transfers these grounded reasoning patterns to large-scale, sparse data. Extensive experiments on multiple dermatology datasets demonstrate that SkinR1 achieves superior diagnostic accuracy. The ablation study demonstrates the importance of the reasoning foundation instilled by SFT.

Identifying disease phenotypes from electronic health records (EHRs) is critical for numerous secondary uses. Manually encoding physician knowledge into rules is particularly challenging for rare diseases due to inadequate EHR coding, necessitating review of clinical notes. Large language models (LLMs) offer promise in text understanding but may not efficiently handle real-world clinical documentation. We propose a zero-shot LLM-based method enriched by retrieval-augmented generation and MapReduce, which pre-identifies disease-related text snippets to be used in parallel as queries for the LLM to establish diagnosis. We show that this method as applied to pulmonary hypertension (PH), a rare disease characterized by elevated arterial pressures in the lungs, significantly outperforms physician logic rules (F_1 score of 0.62 vs. 0.75). This method has the potential to enhance rare disease cohort identification, expanding the scope of robust clinical research and care gap identification.

Relation classification models are conventionally evaluated using only a single measure, e.g., micro-F1, macro-F1 or AUC. In this work, we analyze weighting schemes, such as micro and macro, for imbalanced datasets. We introduce a framework for weighting schemes, where existing schemes are extremes, and two new intermediate schemes. We show that reporting results of different weighting schemes better highlights strengths and weaknesses of a model.

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

Pathology diagnosis based on EEG signals and decoding brain activity holds immense importance in understanding neurological disorders. With the advancement of artificial intelligence methods and machine learning techniques, the potential for accurate data-driven diagnoses and effective treatments has grown significantly. However, applying machine learning algorithms to real-world datasets presents diverse challenges at multiple levels. The scarcity of labelled data, especially in low regime scenarios with limited availability of real patient cohorts due to high costs of recruitment, underscores the vital deployment of scaling and transfer learning techniques. In this study, we explore a real-world pathology classification task to highlight the effectiveness of data and model scaling and cross-dataset knowledge transfer. As such, we observe varying performance improvements through data scaling, indicating the need for careful evaluation and labelling. Additionally, we identify the challenges of possible negative transfer and emphasize the significance of some key components to overcome distribution shifts and potential spurious correlations and achieve positive transfer. We see improvement in the performance of the target model on the target (NMT) datasets by using the knowledge from the source dataset (TUAB) when a low amount of labelled data was available. Our findings indicate a small and generic model (e.g. ShallowNet) performs well on a single dataset, however, a larger model (e.g. TCN) performs better on transfer and learning from a larger and diverse dataset.

Automatic medical report generation (MRG), which possesses significant research value as it can aid radiologists in clinical diagnosis and report composition, has garnered increasing attention. Despite recent progress, generating accurate reports remains arduous due to the requirement for precise clinical comprehension and disease diagnosis inference. Furthermore, owing to the limited accessibility of medical data and the imbalanced distribution of diseases, the underrepresentation of rare diseases in training data makes large-scale medical visual language models (LVLMs) prone to hallucinations, such as omissions or fabrications, severely undermining diagnostic performance and further intensifying the challenges for MRG in practice. In this study, to effectively mitigate hallucinations in medical report generation, we propose a chain-of-medical-thought approach (CoMT), which intends to imitate the cognitive process of human doctors by decomposing diagnostic procedures. The radiological features with different importance are structured into fine-grained medical thought chains to enhance the inferential ability during diagnosis, thereby alleviating hallucination problems and enhancing the diagnostic accuracy of MRG. The code and dataset have been released at https://github.com/FRENKIE-CHIANG/CoMT.

Hepatocellular carcinoma is the most spread primary liver cancer across the world (sim80\% of the liver tumors). The gold standard for HCC diagnosis is liver biopsy. However, in the clinical routine, expert radiologists provide a visual diagnosis by interpreting hepatic CT-scans according to a standardized protocol, the LI-RADS, which uses five radiological criteria with an associated decision tree. In this paper, we propose an automatic approach to predict histology-proven HCC from CT images in order to reduce radiologists' inter-variability. We first show that standard deep learning methods fail to accurately predict HCC from CT-scans on a challenging database, and propose a two-step approach inspired by the LI-RADS system to improve the performance. We achieve improvements from 6 to 18 points of AUC with respect to deep learning baselines trained with different architectures. We also provide clinical validation of our method, achieving results that outperform non-expert radiologists and are on par with expert ones.

Clinical machine learning research and AI driven clinical decision support models rely on clinically accurate labels. Manually extracting these labels with the help of clinical specialists is often time-consuming and expensive. This study tests the feasibility of automatic span- and document-level diagnosis extraction from unstructured Dutch echocardiogram reports. We included 115,692 unstructured echocardiogram reports from the UMCU a large university hospital in the Netherlands. A randomly selected subset was manually annotated for the occurrence and severity of eleven commonly described cardiac characteristics. We developed and tested several automatic labelling techniques at both span and document levels, using weighted and macro F1-score, precision, and recall for performance evaluation. We compared the performance of span labelling against document labelling methods, which included both direct document classifiers and indirect document classifiers that rely on span classification results. The SpanCategorizer and MedRoBERTa.nl models outperformed all other span and document classifiers, respectively. The weighted F1-score varied between characteristics, ranging from 0.60 to 0.93 in SpanCategorizer and 0.96 to 0.98 in MedRoBERTa.nl. Direct document classification was superior to indirect document classification using span classifiers. SetFit achieved competitive document classification performance using only 10\% of the training data. Utilizing a reduced label set yielded near-perfect document classification results. We recommend using our published SpanCategorizer and MedRoBERTa.nl models for span- and document-level diagnosis extraction from Dutch echocardiography reports. For settings with limited training data, SetFit may be a promising alternative for document classification.

Weight oscillation is an undesirable side effect of quantization-aware training, in which quantized weights frequently jump between two quantized levels, resulting in training instability and a sub-optimal final model. We discover that the learnable scaling factor, a widely-used de facto setting in quantization aggravates weight oscillation. In this study, we investigate the connection between the learnable scaling factor and quantized weight oscillation and use ViT as a case driver to illustrate the findings and remedies. In addition, we also found that the interdependence between quantized weights in query and key of a self-attention layer makes ViT vulnerable to oscillation. We, therefore, propose three techniques accordingly: statistical weight quantization (rm StatsQ) to improve quantization robustness compared to the prevalent learnable-scale-based method; confidence-guided annealing (rm CGA) that freezes the weights with high confidence and calms the oscillating weights; and query-key reparameterization (rm QKR) to resolve the query-key intertwined oscillation and mitigate the resulting gradient misestimation. Extensive experiments demonstrate that these proposed techniques successfully abate weight oscillation and consistently achieve substantial accuracy improvement on ImageNet. Specifically, our 2-bit DeiT-T/DeiT-S algorithms outperform the previous state-of-the-art by 9.8% and 7.7%, respectively. Code and models are available at: https://github.com/nbasyl/OFQ.

The recent surge of foundation models in computer vision and natural language processing opens up perspectives in utilizing multi-modal clinical data to train large models with strong generalizability. Yet pathological image datasets often lack biomedical text annotation and enrichment. Guiding data-efficient image diagnosis from the use of biomedical text knowledge becomes a substantial interest. In this paper, we propose to Connect Image and Text Embeddings (CITE) to enhance pathological image classification. CITE injects text insights gained from language models pre-trained with a broad range of biomedical texts, leading to adapt foundation models towards pathological image understanding. Through extensive experiments on the PatchGastric stomach tumor pathological image dataset, we demonstrate that CITE achieves leading performance compared with various baselines especially when training data is scarce. CITE offers insights into leveraging in-domain text knowledge to reinforce data-efficient pathological image classification. Code is available at https://github.com/Yunkun-Zhang/CITE.

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

Medical decision-making requires integrating diverse medical information, from imaging to clinical narratives. These medical modalities are often acquired in a many-to-many manner. However, current medical vision-language pretraining models (Med-VLPMs) fail to directly account for this many-to-many mapping in their model training and embeddings. To address this, we present Probabilistic Modality-Enhanced Diagnosis (ProbMED), a multimodal Med-VLPM that employs probabilistic contrastive learning to model distributions over embeddings rather than deterministic estimates. ProbMED aligns four distinct modalities -- chest X-rays, electrocardiograms, echocardiograms, and clinical text -- into a unified probabilistic embedding space. We use InfoNCE loss with Hellinger distance to integrate inter-modality distributions. We introduce a probabilistic synthetic sampling loss that captures modality-specific mean and variance to improve intra-modality binding. Extensive experiments across 13 medical datasets demonstrate that our model outperforms current Med-VLPMs in cross-modality retrieval, zero-shot, and few-shot classification. We also demonstrate the robust integration of multiple modalities for prognostication, showing improved intra- and inter-medical modality binding.

Rare diseases collectively affect over 300 million individuals worldwide, yet timely and accurate diagnosis remains a pervasive challenge. This is largely due to their clinical heterogeneity, low individual prevalence, and the limited familiarity most clinicians have with rare conditions. Here, we introduce DeepRare, the first rare disease diagnosis agentic system powered by a large language model (LLM), capable of processing heterogeneous clinical inputs. The system generates ranked diagnostic hypotheses for rare diseases, each accompanied by a transparent chain of reasoning that links intermediate analytic steps to verifiable medical evidence. DeepRare comprises three key components: a central host with a long-term memory module; specialized agent servers responsible for domain-specific analytical tasks integrating over 40 specialized tools and web-scale, up-to-date medical knowledge sources, ensuring access to the most current clinical information. This modular and scalable design enables complex diagnostic reasoning while maintaining traceability and adaptability. We evaluate DeepRare on eight datasets. The system demonstrates exceptional diagnostic performance among 2,919 diseases, achieving 100% accuracy for 1013 diseases. In HPO-based evaluations, DeepRare significantly outperforms other 15 methods, like traditional bioinformatics diagnostic tools, LLMs, and other agentic systems, achieving an average Recall@1 score of 57.18% and surpassing the second-best method (Reasoning LLM) by a substantial margin of 23.79 percentage points. For multi-modal input scenarios, DeepRare achieves 70.60% at Recall@1 compared to Exomiser's 53.20% in 109 cases. Manual verification of reasoning chains by clinical experts achieves 95.40% agreements. Furthermore, the DeepRare system has been implemented as a user-friendly web application http://raredx.cn/doctor.

Guidance is a crucial technique for extracting the best performance out of image-generating diffusion models. Traditionally, a constant guidance weight has been applied throughout the sampling chain of an image. We show that guidance is clearly harmful toward the beginning of the chain (high noise levels), largely unnecessary toward the end (low noise levels), and only beneficial in the middle. We thus restrict it to a specific range of noise levels, improving both the inference speed and result quality. This limited guidance interval improves the record FID in ImageNet-512 significantly, from 1.81 to 1.40. We show that it is quantitatively and qualitatively beneficial across different sampler parameters, network architectures, and datasets, including the large-scale setting of Stable Diffusion XL. We thus suggest exposing the guidance interval as a hyperparameter in all diffusion models that use guidance.

As opposed to evaluating computation and logic-based reasoning, current benchmarks for evaluating large language models (LLMs) in medicine are primarily focused on question-answering involving domain knowledge and descriptive reasoning. While such qualitative capabilities are vital to medical diagnosis, in real-world scenarios, doctors frequently use clinical calculators that follow quantitative equations and rule-based reasoning paradigms for evidence-based decision support. To this end, we propose MedCalc-Bench, a first-of-its-kind dataset focused on evaluating the medical calculation capability of LLMs. MedCalc-Bench contains an evaluation set of over 1000 manually reviewed instances from 55 different medical calculation tasks. Each instance in MedCalc-Bench consists of a patient note, a question requesting to compute a specific medical value, a ground truth answer, and a step-by-step explanation showing how the answer is obtained. While our evaluation results show the potential of LLMs in this area, none of them are effective enough for clinical settings. Common issues include extracting the incorrect entities, not using the correct equation or rules for a calculation task, or incorrectly performing the arithmetic for the computation. We hope our study highlights the quantitative knowledge and reasoning gaps in LLMs within medical settings, encouraging future improvements of LLMs for various clinical calculation tasks.

Automatic radiology report generation is booming due to its huge application potential for the healthcare industry. However, existing computer vision and natural language processing approaches to tackle this problem are limited in two aspects. First, when extracting image features, most of them neglect multi-view reasoning in vision and model single-view structure of medical images, such as space-view or channel-view. However, clinicians rely on multi-view imaging information for comprehensive judgment in daily clinical diagnosis. Second, when generating reports, they overlook context reasoning with multi-modal information and focus on pure textual optimization utilizing retrieval-based methods. We aim to address these two issues by proposing a model that better simulates clinicians' perspectives and generates more accurate reports. Given the above limitation in feature extraction, we propose a Globally-intensive Attention (GIA) module in the medical image encoder to simulate and integrate multi-view vision perception. GIA aims to learn three types of vision perception: depth view, space view, and pixel view. On the other hand, to address the above problem in report generation, we explore how to involve multi-modal signals to generate precisely matched reports, i.e., how to integrate previously predicted words with region-aware visual content in next word prediction. Specifically, we design a Visual Knowledge-guided Decoder (VKGD), which can adaptively consider how much the model needs to rely on visual information and previously predicted text to assist next word prediction. Hence, our final Intensive Vision-guided Network (IVGN) framework includes a GIA-guided Visual Encoder and the VKGD. Experiments on two commonly-used datasets IU X-Ray and MIMIC-CXR demonstrate the superior ability of our method compared with other state-of-the-art approaches.

Automatic disease diagnosis has become increasingly valuable in clinical practice. The advent of large language models (LLMs) has catalyzed a paradigm shift in artificial intelligence, with growing evidence supporting the efficacy of LLMs in diagnostic tasks. Despite the increasing attention in this field, a holistic view is still lacking. Many critical aspects remain unclear, such as the diseases and clinical data to which LLMs have been applied, the LLM techniques employed, and the evaluation methods used. In this article, we perform a comprehensive review of LLM-based methods for disease diagnosis. Our review examines the existing literature across various dimensions, including disease types and associated clinical specialties, clinical data, LLM techniques, and evaluation methods. Additionally, we offer recommendations for applying and evaluating LLMs for diagnostic tasks. Furthermore, we assess the limitations of current research and discuss future directions. To our knowledge, this is the first comprehensive review for LLM-based disease diagnosis.

Assessing scientific claims requires identifying, extracting, and reasoning with multimodal data expressed in information-rich figures in scientific literature. Despite the large body of work in scientific QA, figure captioning, and other multimodal reasoning tasks over chart-based data, there are no readily usable multimodal benchmarks that directly test claim verification abilities. To remedy this gap, we introduce a new benchmark MuSciClaims accompanied by diagnostics tasks. We automatically extract supported claims from scientific articles, which we manually perturb to produce contradicted claims. The perturbations are designed to test for a specific set of claim verification capabilities. We also introduce a suite of diagnostic tasks that help understand model failures. Our results show most vision-language models are poor (~0.3-0.5 F1), with even the best model only achieving 0.72 F1. They are also biased towards judging claims as supported, likely misunderstanding nuanced perturbations within the claims. Our diagnostics show models are bad at localizing correct evidence within figures, struggle with aggregating information across modalities, and often fail to understand basic components of the figure.

Automated model selection is often proposed to users to choose which machine learning model (or method) to apply to a given regression task. In this paper, we show that combining different regression models can yield better results than selecting a single ('best') regression model, and outline an efficient method that obtains optimally weighted convex linear combination from a heterogeneous set of regression models. More specifically, in this paper, a heuristic weight optimization, used in a preceding conference paper, is replaced by an exact optimization algorithm using convex quadratic programming. We prove convexity of the quadratic programming formulation for the straightforward formulation and for a formulation with weighted data points. The novel weight optimization is not only (more) exact but also more efficient. The methods we develop in this paper are implemented and made available via github-open source. They can be executed on commonly available hardware and offer a transparent and easy to interpret interface. The results indicate that the approach outperforms model selection methods on a range of data sets, including data sets with mixed variable type from drug discovery applications.

This paper explores the task of radiology report generation, which aims at generating free-text descriptions for a set of radiographs. One significant challenge of this task is how to correctly maintain the consistency between the images and the lengthy report. Previous research explored solving this issue through planning-based methods, which generate reports only based on high-level plans. However, these plans usually only contain the major observations from the radiographs (e.g., lung opacity), lacking much necessary information, such as the observation characteristics and preliminary clinical diagnoses. To address this problem, the system should also take the image information into account together with the textual plan and perform stronger reasoning during the generation process. In this paper, we propose an observation-guided radiology report generation framework (ORGAN). It first produces an observation plan and then feeds both the plan and radiographs for report generation, where an observation graph and a tree reasoning mechanism are adopted to precisely enrich the plan information by capturing the multi-formats of each observation. Experimental results demonstrate that our framework outperforms previous state-of-the-art methods regarding text quality and clinical efficacy

Medical imaging plays a pivotal role in modern healthcare, with computed tomography pulmonary angiography (CTPA) being a critical tool for diagnosing pulmonary embolism and other thoracic conditions. However, the complexity of interpreting CTPA scans and generating accurate radiology reports remains a significant challenge. This paper introduces Abn-BLIP (Abnormality-aligned Bootstrapping Language-Image Pretraining), an advanced diagnosis model designed to align abnormal findings to generate the accuracy and comprehensiveness of radiology reports. By leveraging learnable queries and cross-modal attention mechanisms, our model demonstrates superior performance in detecting abnormalities, reducing missed findings, and generating structured reports compared to existing methods. Our experiments show that Abn-BLIP outperforms state-of-the-art medical vision-language models and 3D report generation methods in both accuracy and clinical relevance. These results highlight the potential of integrating multimodal learning strategies for improving radiology reporting. The source code is available at https://github.com/zzs95/abn-blip.

The objective of Radiology Report Generation (RRG) is to automatically generate coherent textual analyses of diseases based on radiological images, thereby alleviating the workload of radiologists. Current AI-based methods for RRG primarily focus on modifications to the encoder-decoder model architecture. To advance these approaches, this paper introduces an Organ-Regional Information Driven (ORID) framework which can effectively integrate multi-modal information and reduce the influence of noise from unrelated organs. Specifically, based on the LLaVA-Med, we first construct an RRG-related instruction dataset to improve organ-regional diagnosis description ability and get the LLaVA-Med-RRG. After that, we propose an organ-based cross-modal fusion module to effectively combine the information from the organ-regional diagnosis description and radiology image. To further reduce the influence of noise from unrelated organs on the radiology report generation, we introduce an organ importance coefficient analysis module, which leverages Graph Neural Network (GNN) to examine the interconnections of the cross-modal information of each organ region. Extensive experiments an1d comparisons with state-of-the-art methods across various evaluation metrics demonstrate the superior performance of our proposed method.

Deep learning (DL) has proven highly effective for ultrasound-based computer-aided diagnosis (CAD) of breast cancers. In an automaticCAD system, lesion detection is critical for the following diagnosis. However, existing DL-based methods generally require voluminous manually-annotated region of interest (ROI) labels and class labels to train both the lesion detection and diagnosis models. In clinical practice, the ROI labels, i.e. ground truths, may not always be optimal for the classification task due to individual experience of sonologists, resulting in the issue of coarse annotation that limits the diagnosis performance of a CAD model. To address this issue, a novel Two-Stage Detection and Diagnosis Network (TSDDNet) is proposed based on weakly supervised learning to enhance diagnostic accuracy of the ultrasound-based CAD for breast cancers. In particular, all the ROI-level labels are considered as coarse labels in the first training stage, and then a candidate selection mechanism is designed to identify optimallesion areas for both the fully and partially annotated samples. It refines the current ROI-level labels in the fully annotated images and the detected ROIs in the partially annotated samples with a weakly supervised manner under the guidance of class labels. In the second training stage, a self-distillation strategy further is further proposed to integrate the detection network and classification network into a unified framework as the final CAD model for joint optimization, which then further improves the diagnosis performance. The proposed TSDDNet is evaluated on a B-mode ultrasound dataset, and the experimental results show that it achieves the best performance on both lesion detection and diagnosis tasks, suggesting promising application potential.

As machine learning tasks continue to evolve, the trend has been to gather larger datasets and train increasingly larger models. While this has led to advancements in accuracy, it has also escalated computational costs to unsustainable levels. Addressing this, our work aims to strike a delicate balance between computational efficiency and model accuracy, a persisting challenge in the field. We introduce a novel method that employs core subset selection for reweighting, effectively optimizing both computational time and model performance. By focusing on a strategically selected coreset, our approach offers a robust representation, as it efficiently minimizes the influence of outliers. The re-calibrated weights are then mapped back to and propagated across the entire dataset. Our experimental results substantiate the effectiveness of this approach, underscoring its potential as a scalable and precise solution for model training.

We introduce Cautious Weight Decay (CWD), a one-line, optimizer-agnostic modification that applies weight decay only to parameter coordinates whose signs align with the optimizer update. Unlike standard decoupled decay, which implicitly optimizes a regularized or constrained objective, CWD preserves the original loss and admits a bilevel interpretation: it induces sliding-mode behavior upon reaching the stationary manifold, allowing it to search for locally Pareto-optimal stationary points of the unmodified objective. In practice, CWD is a drop-in change for optimizers such as AdamW, Lion, and Muon, requiring no new hyperparameters or additional tuning. For language model pre-training and ImageNet classification, CWD consistently improves final loss and accuracy at million- to billion-parameter scales.

Automated radiology report generation from chest X-ray (CXR) images has the potential to improve clinical efficiency and reduce radiologists' workload. However, most datasets, including the publicly available MIMIC-CXR and CheXpert Plus, consist entirely of free-form reports, which are inherently variable and unstructured. This variability poses challenges for both generation and evaluation: existing models struggle to produce consistent, clinically meaningful reports, and standard evaluation metrics fail to capture the nuances of radiological interpretation. To address this, we introduce Structured Radiology Report Generation (SRRG), a new task that reformulates free-text radiology reports into a standardized format, ensuring clarity, consistency, and structured clinical reporting. We create a novel dataset by restructuring reports using large language models (LLMs) following strict structured reporting desiderata. Additionally, we introduce SRR-BERT, a fine-grained disease classification model trained on 55 labels, enabling more precise and clinically informed evaluation of structured reports. To assess report quality, we propose F1-SRR-BERT, a metric that leverages SRR-BERT's hierarchical disease taxonomy to bridge the gap between free-text variability and structured clinical reporting. We validate our dataset through a reader study conducted by five board-certified radiologists and extensive benchmarking experiments.

The meaningful use of electronic health records (EHR) continues to progress in the digital era with clinical decision support systems augmented by artificial intelligence. A priority in improving provider experience is to overcome information overload and reduce the cognitive burden so fewer medical errors and cognitive biases are introduced during patient care. One major type of medical error is diagnostic error due to systematic or predictable errors in judgment that rely on heuristics. The potential for clinical natural language processing (cNLP) to model diagnostic reasoning in humans with forward reasoning from data to diagnosis and potentially reduce the cognitive burden and medical error has not been investigated. Existing tasks to advance the science in cNLP have largely focused on information extraction and named entity recognition through classification tasks. We introduce a novel suite of tasks coined as Diagnostic Reasoning Benchmarks, DR.BENCH, as a new benchmark for developing and evaluating cNLP models with clinical diagnostic reasoning ability. The suite includes six tasks from ten publicly available datasets addressing clinical text understanding, medical knowledge reasoning, and diagnosis generation. DR.BENCH is the first clinical suite of tasks designed to be a natural language generation framework to evaluate pre-trained language models. Experiments with state-of-the-art pre-trained generative language models using large general domain models and models that were continually trained on a medical corpus demonstrate opportunities for improvement when evaluated in DR. BENCH. We share DR. BENCH as a publicly available GitLab repository with a systematic approach to load and evaluate models for the cNLP community.

While large-scale training data is fundamental for developing capable large language models (LLMs), strategically selecting high-quality data has emerged as a critical approach to enhance training efficiency and reduce computational costs. Current data selection methodologies predominantly rely on static, training-agnostic criteria, failing to account for the dynamic model training and data interactions. In this paper, we propose a new Data Weighting Model (DWM) to adjust the weight of selected data within each batch to achieve a dynamic data utilization during LLM training. Specially, to better capture the dynamic data preference of the trained model, a bi-level optimization framework is implemented to update the weighting model. Our experiments demonstrate that DWM enhances the performance of models trained with randomly-selected data, and the learned weighting model can be transferred to enhance other data selection methods and models of different sizes. Moreover, we further analyze how a model's data preferences evolve throughout training, providing new insights into the data preference of the model during training.

Small sample sizes are common in many disciplines, which necessitates pooling roughly similar datasets across multiple institutions to study weak but relevant associations between images and disease outcomes. Such data often manifest shift/imbalance in covariates (i.e., secondary non-imaging data). Controlling for such nuisance variables is common within standard statistical analysis, but the ideas do not directly apply to overparameterized models. Consequently, recent work has shown how strategies from invariant representation learning provides a meaningful starting point, but the current repertoire of methods is limited to accounting for shifts/imbalances in just a couple of covariates at a time. In this paper, we show how viewing this problem from the perspective of Category theory provides a simple and effective solution that completely avoids elaborate multi-stage training pipelines that would otherwise be needed. We show the effectiveness of this approach via extensive experiments on real datasets. Further, we discuss how this style of formulation offers a unified perspective on at least 5+ distinct problem settings, from self-supervised learning to matching problems in 3D reconstruction.

Medical systematic reviews typically require assessing all the documents retrieved by a search. The reason is two-fold: the task aims for ``total recall''; and documents retrieved using Boolean search are an unordered set, and thus it is unclear how an assessor could examine only a subset. Screening prioritisation is the process of ranking the (unordered) set of retrieved documents, allowing assessors to begin the downstream processes of the systematic review creation earlier, leading to earlier completion of the review, or even avoiding screening documents ranked least relevant. Screening prioritisation requires highly effective ranking methods. Pre-trained language models are state-of-the-art on many IR tasks but have yet to be applied to systematic review screening prioritisation. In this paper, we apply several pre-trained language models to the systematic review document ranking task, both directly and fine-tuned. An empirical analysis compares how effective neural methods compare to traditional methods for this task. We also investigate different types of document representations for neural methods and their impact on ranking performance. Our results show that BERT-based rankers outperform the current state-of-the-art screening prioritisation methods. However, BERT rankers and existing methods can actually be complementary, and thus, further improvements may be achieved if used in conjunction.

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

Foodborne gastrointestinal (GI) illness is a common cause of ill health in the UK. However, many cases do not interact with the healthcare system, posing significant challenges for traditional surveillance methods. The growth of publicly available online restaurant reviews and advancements in large language models (LLMs) present potential opportunities to extend disease surveillance by identifying public reports of GI illness. In this study, we introduce a novel annotation schema, developed with experts in GI illness, applied to the Yelp Open Dataset of reviews. Our annotations extend beyond binary disease detection, to include detailed extraction of information on symptoms and foods. We evaluate the performance of open-weight LLMs across these three tasks: GI illness detection, symptom extraction, and food extraction. We compare this performance to RoBERTa-based classification models fine-tuned specifically for these tasks. Our results show that using prompt-based approaches, LLMs achieve micro-F1 scores of over 90% for all three of our tasks. Using prompting alone, we achieve micro-F1 scores that exceed those of smaller fine-tuned models. We further demonstrate the robustness of LLMs in GI illness detection across three bias-focused experiments. Our results suggest that publicly available review text and LLMs offer substantial potential for public health surveillance of GI illness by enabling highly effective extraction of key information. While LLMs appear to exhibit minimal bias in processing, the inherent limitations of restaurant review data highlight the need for cautious interpretation of results.

Osteoporotic vertebral compression fractures (VCFs) are prevalent in the elderly population, typically assessed on computed tomography (CT) scans by evaluating vertebral height loss. This assessment helps determine the fracture's impact on spinal stability and the need for surgical intervention. However, clinical data indicate that many VCFs exhibit irregular compression, complicating accurate diagnosis. While deep learning methods have shown promise in aiding VCFs screening, they often lack interpretability and sufficient sensitivity, limiting their clinical applicability. To address these challenges, we introduce a novel vertebra synthesis-height loss quantification-VCFs grading framework. Our proposed model, HealthiVert-GAN, utilizes a coarse-to-fine synthesis network designed to generate pseudo-healthy vertebral images that simulate the pre-fracture state of fractured vertebrae. This model integrates three auxiliary modules that leverage the morphology and height information of adjacent healthy vertebrae to ensure anatomical consistency. Additionally, we introduce the Relative Height Loss of Vertebrae (RHLV) as a quantification metric, which divides each vertebra into three sections to measure height loss between pre-fracture and post-fracture states, followed by fracture severity classification using a Support Vector Machine (SVM). Our approach achieves state-of-the-art classification performance on both the Verse2019 dataset and our private dataset, and it provides cross-sectional distribution maps of vertebral height loss. This practical tool enhances diagnostic sensitivity in clinical settings and assisting in surgical decision-making. Our code is available: https://github.com/zhibaishouheilab/HealthiVert-GAN.

Background: Reporting and Data Systems (RADS) standardize radiology risk communication but automated RADS assignment from narrative reports is challenging because of guideline complexity, output-format constraints, and limited benchmarking across RADS frameworks and model sizes. Purpose: To create RXL-RADSet, a radiologist-verified synthetic multi-RADS benchmark, and compare validity and accuracy of open-weight small language models (SLMs) with a proprietary model for RADS assignment. Materials and Methods: RXL-RADSet contains 1,600 synthetic radiology reports across 10 RADS (BI-RADS, CAD-RADS, GB-RADS, LI-RADS, Lung-RADS, NI-RADS, O-RADS, PI-RADS, TI-RADS, VI-RADS) and multiple modalities. Reports were generated by LLMs using scenario plans and simulated radiologist styles and underwent two-stage radiologist verification. We evaluated 41 quantized SLMs (12 families, 0.135-32B parameters) and GPT-5.2 under a fixed guided prompt. Primary endpoints were validity and accuracy; a secondary analysis compared guided versus zero-shot prompting. Results: Under guided prompting GPT-5.2 achieved 99.8% validity and 81.1% accuracy (1,600 predictions). Pooled SLMs (65,600 predictions) achieved 96.8% validity and 61.1% accuracy; top SLMs in the 20-32B range reached ~99% validity and mid-to-high 70% accuracy. Performance scaled with model size (inflection between <1B and >=10B) and declined with RADS complexity primarily due to classification difficulty rather than invalid outputs. Guided prompting improved validity (99.2% vs 96.7%) and accuracy (78.5% vs 69.6%) compared with zero-shot. Conclusion: RXL-RADSet provides a radiologist-verified multi-RADS benchmark; large SLMs (20-32B) can approach proprietary-model performance under guided prompting, but gaps remain for higher-complexity schemes.

Artificial intelligence has advanced in Medical Visual Question Answering (Med-VQA), but prevalent research tends to focus on the accuracy of the answers, often overlooking the reasoning paths and interpretability, which are crucial in clinical settings. Besides, current Med-VQA algorithms, typically reliant on singular models, lack the robustness needed for real-world medical diagnostics which usually require collaborative expert evaluation. To address these shortcomings, this paper presents MedCoT, a novel hierarchical expert verification reasoning chain method designed to enhance interpretability and accuracy in biomedical imaging inquiries. MedCoT is predicated on two principles: The necessity for explicit reasoning paths in Med-VQA and the requirement for multi-expert review to formulate accurate conclusions. The methodology involves an Initial Specialist proposing diagnostic rationales, followed by a Follow-up Specialist who validates these rationales, and finally, a consensus is reached through a vote among a sparse Mixture of Experts within the locally deployed Diagnostic Specialist, which then provides the definitive diagnosis. Experimental evaluations on four standard Med-VQA datasets demonstrate that MedCoT surpasses existing state-of-the-art approaches, providing significant improvements in performance and interpretability.

Identifying cirrhosis is key to correctly assess the health of the liver. However, the gold standard diagnosis of the cirrhosis needs a medical intervention to obtain the histological confirmation, e.g. the METAVIR score, as the radiological presentation can be equivocal. In this work, we propose to leverage transfer learning from large datasets annotated by radiologists, which we consider as a weak annotation, to predict the histological score available on a small annex dataset. To this end, we propose to compare different pretraining methods, namely weakly-supervised and self-supervised ones, to improve the prediction of the cirrhosis. Finally, we introduce a loss function combining both supervised and self-supervised frameworks for pretraining. This method outperforms the baseline classification of the METAVIR score, reaching an AUC of 0.84 and a balanced accuracy of 0.75, compared to 0.77 and 0.72 for a baseline classifier.

The mathematical problem-solving capabilities of large language models have become a focal point of research, with growing interests in leveraging self-generated reasoning paths as a promising way to refine and enhance these models. These paths capture step-by-step logical processes while requiring only the correct answer for supervision. The self-training method has been shown to be effective in reasoning tasks while eliminating the need for external models and manual annotations. However, optimizing the use of self-generated data for model training remains an open challenge. In this work, we propose Entropy-Based Adaptive Weighting for Self-Training (EAST), an adaptive weighting strategy designed to prioritize uncertain data during self-training. Specifically, EAST employs a mapping function with a tunable parameter that controls the sharpness of the weighting, assigning higher weights to data where the model exhibits greater uncertainty. This approach guides the model to focus on more informative and challenging examples, thereby enhancing its reasoning ability. We evaluate our approach on GSM8K and MATH benchmarks. Empirical results show that, while the vanilla method yields virtually no improvement (0%) on MATH, EAST achieves around a 1% gain over backbone model. On GSM8K, EAST attains a further 1-2% performance boost compared to the vanilla method.

Current medical retrieval benchmarks primarily emphasize lexical or shallow semantic similarity, overlooking the reasoning-intensive demands that are central to clinical decision-making. In practice, physicians often retrieve authoritative medical evidence to support diagnostic hypotheses. Such evidence typically aligns with an inferred diagnosis rather than the surface form of a patient's symptoms, leading to low lexical or semantic overlap between queries and relevant documents. To address this gap, we introduce R2MED, the first benchmark explicitly designed for reasoning-driven medical retrieval. It comprises 876 queries spanning three tasks: Q&A reference retrieval, clinical evidence retrieval, and clinical case retrieval. These tasks are drawn from five representative medical scenarios and twelve body systems, capturing the complexity and diversity of real-world medical information needs. We evaluate 15 widely-used retrieval systems on R2MED and find that even the best model achieves only 31.4 nDCG@10, demonstrating the benchmark's difficulty. Classical re-ranking and generation-augmented retrieval methods offer only modest improvements. Although large reasoning models improve performance via intermediate inference generation, the best results still peak at 41.4 nDCG@10. These findings underscore a substantial gap between current retrieval techniques and the reasoning demands of real clinical tasks. We release R2MED as a challenging benchmark to foster the development of next-generation medical retrieval systems with enhanced reasoning capabilities. Data and code are available at https://github.com/R2MED/R2MED

Conventional medical image segmentation methods have been found inadequate in facilitating physicians with the identification of specific lesions for diagnosis and treatment. Given the utility of text as an instructional format, we introduce a novel task termed Medical Image Referring Segmentation (MIRS), which requires segmenting specified lesions in images based on the given language expressions. Due to the varying object scales in medical images, MIRS demands robust vision-language modeling and comprehensive multi-scale interaction for precise localization and segmentation under linguistic guidance. However, existing medical image segmentation methods fall short in meeting these demands, resulting in insufficient segmentation accuracy. In response, we propose an approach named Language-guided Scale-aware MedSegmentor (LSMS), incorporating two appealing designs: (1)~a Scale-aware Vision-Language Attention module that leverages diverse convolutional kernels to acquire rich visual knowledge and interact closely with linguistic features, thereby enhancing lesion localization capability; (2)~a Full-Scale Decoder that globally models multi-modal features across various scales, capturing complementary information between scales to accurately outline lesion boundaries. Addressing the lack of suitable datasets for MIRS, we constructed a vision-language medical dataset called Reference Hepatic Lesion Segmentation (RefHL-Seg). This dataset comprises 2,283 abdominal CT slices from 231 cases, with corresponding textual annotations and segmentation masks for various liver lesions in images. We validated the performance of LSMS for MIRS and conventional medical image segmentation tasks across various datasets. Our LSMS consistently outperforms on all datasets with lower computational costs. The code and datasets will be released.

Multimodal large language models (MLLMs) have begun to demonstrate robust reasoning capabilities on general tasks, yet their application in the medical domain remains in its early stages. Constructing chain-of-thought (CoT) training data is essential for bolstering the reasoning abilities of medical MLLMs. However, existing approaches exhibit a deficiency in offering a comprehensive framework for searching and evaluating effective reasoning paths towards critical diagnosis. To address this challenge, we propose Mentor-Intern Collaborative Search (MICS), a novel reasoning-path searching scheme to generate rigorous and effective medical CoT data. MICS first leverages mentor models to initialize the reasoning, one step at a time, then prompts each intern model to continue the thinking along those initiated paths, and finally selects the optimal reasoning path according to the overall reasoning performance of multiple intern models. The reasoning performance is determined by an MICS-Score, which assesses the quality of generated reasoning paths. Eventually, we construct MMRP, a multi-task medical reasoning dataset with ranked difficulty, and Chiron-o1, a new medical MLLM devised via a curriculum learning strategy, with robust visual question-answering and generalizable reasoning capabilities. Extensive experiments demonstrate that Chiron-o1, trained on our CoT dataset constructed using MICS, achieves state-of-the-art performance across a list of medical visual question answering and reasoning benchmarks. Codes are available at GitHub - manglu097/Chiron-o1: Enhancing Step-by-Step and Verifiable Medical Reasoning in MLLMs

Estimating truncated density models is difficult, as these models have intractable normalising constants and hard to satisfy boundary conditions. Score matching can be adapted to solve the truncated density estimation problem, but requires a continuous weighting function which takes zero at the boundary and is positive elsewhere. Evaluation of such a weighting function (and its gradient) often requires a closed-form expression of the truncation boundary and finding a solution to a complicated optimisation problem. In this paper, we propose approximate Stein classes, which in turn leads to a relaxed Stein identity for truncated density estimation. We develop a novel discrepancy measure, truncated kernelised Stein discrepancy (TKSD), which does not require fixing a weighting function in advance, and can be evaluated using only samples on the boundary. We estimate a truncated density model by minimising the Lagrangian dual of TKSD. Finally, experiments show the accuracy of our method to be an improvement over previous works even without the explicit functional form of the boundary.

An ugly duckling is an obviously different skin lesion from surrounding lesions of an individual, and the ugly duckling sign is a criterion used to aid in the diagnosis of cutaneous melanoma by differentiating between highly suspicious and benign lesions. However, the appearance of pigmented lesions, can change drastically from one patient to another, resulting in difficulties in visual separation of ugly ducklings. Hence, we propose DMT-Quadruplet - a deep metric learning network to learn lesion features at two tiers - patient-level and lesion-level. We introduce a patient-specific quadruplet mining approach together with a tiered quadruplet network, to drive the network to learn more contextual information both globally and locally between the two tiers. We further incorporate a dynamic margin within the patient-specific mining to allow more useful quadruplets to be mined within individuals. Comprehensive experiments show that our proposed method outperforms traditional classifiers, achieving 54% higher sensitivity than a baseline ResNet18 CNN and 37% higher than a naive triplet network in classifying ugly duckling lesions. Visualisation of the data manifold in the metric space further illustrates that DMT-Quadruplet is capable of classifying ugly duckling lesions in both patient-specific and patient-agnostic manner successfully.

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.

Computer-aided diagnosis establishes methods for robust assessment of medical image-based examination. Image processing introduced a promising strategy to facilitate disease classification and detection while diminishing unnecessary expenses. In this paper, we propose a novel metastatic cancer image classification model based on DenseNet Block, which can effectively identify metastatic cancer in small image patches taken from larger digital pathology scans. We evaluate the proposed approach to the slightly modified version of the PatchCamelyon (PCam) benchmark dataset. The dataset is the slightly modified version of the PatchCamelyon (PCam) benchmark dataset provided by Kaggle competition, which packs the clinically-relevant task of metastasis detection into a straight-forward binary image classification task. The experiments indicated that our model outperformed other classical methods like Resnet34, Vgg19. Moreover, we also conducted data augmentation experiment and study the relationship between Batches processed and loss value during the training and validation process.

Developing models with robust group fairness properties is paramount, particularly in ethically sensitive domains such as medical diagnosis. Recent approaches to achieving fairness in machine learning require a substantial amount of training data and depend on model retraining, which may not be practical in real-world scenarios. To mitigate these challenges, we propose Bias-based Weight Masking Fine-Tuning (BMFT), a novel post-processing method that enhances the fairness of a trained model in significantly fewer epochs without requiring access to the original training data. BMFT produces a mask over model parameters, which efficiently identifies the weights contributing the most towards biased predictions. Furthermore, we propose a two-step debiasing strategy, wherein the feature extractor undergoes initial fine-tuning on the identified bias-influenced weights, succeeded by a fine-tuning phase on a reinitialised classification layer to uphold discriminative performance. Extensive experiments across four dermatological datasets and two sensitive attributes demonstrate that BMFT outperforms existing state-of-the-art (SOTA) techniques in both diagnostic accuracy and fairness metrics. Our findings underscore the efficacy and robustness of BMFT in advancing fairness across various out-of-distribution (OOD) settings. Our code is available at: https://github.com/vios-s/BMFT

Accurate coding of tumor diagnoses with ICD-10-GM and ICD-O-3 is essential for structured cancer documentation in Germany. Smaller open-weight LLMs are appealing for privacy-preserving automation but often struggle with coding accuracy in German-language contexts. This study investigates whether instruction-based fine-tuning on public datasets improves the coding accuracy of open-weight LLMs for German tumor diagnosis texts. The evaluation uses coded diagnoses from the local tumor documentation system as test data. In a systematic data quality assessment, the upper limit for ICD-10 coding performance was estimated at 60-79% for exact and 81-94% for partial (three-character codes only) derivation. As training data, over 500,000 question-answer pairs were created based on the ICD-10-GM, ICD-O-3, and OPS catalogues. Eight open-weight models from the Qwen, Llama, and Mistral families (7-70 B parameters) were fine-tuned. ICD-10-GM accuracy rose from 1.4-24% to 41-58%, and partial accuracy from 31-74% to 73-83%. The accuracy of ICD-O-3 topography coding also improved but started and remained considerably lower with an exact accuracy of 22-40% and a partial accuracy of 56-67% after fine-tuning. Malformed code outputs dropped to 0% for all models. Tumor-diagnosis recognition reached 99%. Accuracy correlated positively with model size, but gaps between small and large models narrowed after fine-tuning. The reasoning mode in Qwen3 generally yielded a lower performance than fine-tuning and was over 100 times slower. Our findings highlight the potential of leveraging public catalogues to build instruction datasets that improve LLMs in medical documentation tasks. The complete training dataset and the best-performing checkpoints of the fine-tuned models are available from https://huggingface.co/datasets/stefan-m-lenz/ICDOPS-QA-2024.

Recognition problems in long-tailed data, in which the sample size per class is heavily skewed, have gained importance because the distribution of the sample size per class in a dataset is generally exponential unless the sample size is intentionally adjusted. Various methods have been devised to address these problems. Recently, weight balancing, which combines well-known classical regularization techniques with two-stage training, has been proposed. Despite its simplicity, it is known for its high performance compared with existing methods devised in various ways. However, there is a lack of understanding as to why this method is effective for long-tailed data. In this study, we analyze weight balancing by focusing on neural collapse and the cone effect at each training stage and found that it can be decomposed into an increase in Fisher's discriminant ratio of the feature extractor caused by weight decay and cross entropy loss and implicit logit adjustment caused by weight decay and class-balanced loss. Our analysis enables the training method to be further simplified by reducing the number of training stages to one while increasing accuracy.

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.

Diffusion models have emerged as a formidable tool for training-free conditional generation.However, a key hurdle in inference-time guidance techniques is the need for compute-heavy backpropagation through the diffusion network for estimating the guidance direction. Moreover, these techniques often require handcrafted parameter tuning on a case-by-case basis. Although some recent works have introduced minimal compute methods for linear inverse problems, a generic lightweight guidance solution to both linear and non-linear guidance problems is still missing. To this end, we propose Dreamguider, a method that enables inference-time guidance without compute-heavy backpropagation through the diffusion network. The key idea is to regulate the gradient flow through a time-varying factor. Moreover, we propose an empirical guidance scale that works for a wide variety of tasks, hence removing the need for handcrafted parameter tuning. We further introduce an effective lightweight augmentation strategy that significantly boosts the performance during inference-time guidance. We present experiments using Dreamguider on multiple tasks across multiple datasets and models to show the effectiveness of the proposed modules. To facilitate further research, we will make the code public after the review process.

Selective Classification, wherein models can reject low-confidence predictions, promises reliable translation of machine-learning based classification systems to real-world scenarios such as clinical diagnostics. While current evaluation of these systems typically assumes fixed working points based on pre-defined rejection thresholds, methodological progress requires benchmarking the general performance of systems akin to the AUROC in standard classification. In this work, we define 5 requirements for multi-threshold metrics in selective classification regarding task alignment, interpretability, and flexibility, and show how current approaches fail to meet them. We propose the Area under the Generalized Risk Coverage curve (AUGRC), which meets all requirements and can be directly interpreted as the average risk of undetected failures. We empirically demonstrate the relevance of AUGRC on a comprehensive benchmark spanning 6 data sets and 13 confidence scoring functions. We find that the proposed metric substantially changes metric rankings on 5 out of the 6 data sets.

Robust validation metrics remain essential in contemporary deep learning, not only to detect overfitting and poor generalization, but also to monitor training dynamics. In the supervised classification setting, we investigate whether interactions between training data and model weights can yield such a metric that both tracks generalization during training and attributes performance to individual training samples. We introduce Gradient-Weight Alignment (GWA), quantifying the coherence between per-sample gradients and model weights. We show that effective learning corresponds to coherent alignment, while misalignment indicates deteriorating generalization. GWA is efficiently computable during training and reflects both sample-specific contributions and dataset-wide learning dynamics. Extensive experiments show that GWA accurately predicts optimal early stopping, enables principled model comparisons, and identifies influential training samples, providing a validation-set-free approach for model analysis directly from the training data.

Recent advances in reasoning-enhanced large language models (LLMs) and multimodal LLMs (MLLMs) have significantly improved performance in complex tasks, yet medical AI models often overlook the structured reasoning processes inherent in clinical practice. In this work, we present ChestX-Reasoner, a radiology diagnosis MLLM designed to leverage process supervision mined directly from clinical reports, reflecting the step-by-step reasoning followed by radiologists. We construct a large dataset by extracting and refining reasoning chains from routine radiology reports. Our two-stage training framework combines supervised fine-tuning and reinforcement learning guided by process rewards to better align model reasoning with clinical standards. We introduce RadRBench-CXR, a comprehensive benchmark featuring 59K visual question answering samples with 301K clinically validated reasoning steps, and propose RadRScore, a metric evaluating reasoning factuality, completeness, and effectiveness. ChestX-Reasoner outperforms existing medical and general-domain MLLMs in both diagnostic accuracy and reasoning ability, achieving 16%, 5.9%, and 18% improvements in reasoning ability compared to the best medical MLLM, the best general MLLM, and its base model, respectively, as well as 3.3%, 24%, and 27% improvements in outcome accuracy. All resources are open-sourced to facilitate further research in medical reasoning MLLMs.

In recent years, automated radiology report generation has experienced significant growth. This paper introduces MRScore, an automatic evaluation metric tailored for radiology report generation by leveraging Large Language Models (LLMs). Conventional NLG (natural language generation) metrics like BLEU are inadequate for accurately assessing the generated radiology reports, as systematically demonstrated by our observations within this paper. To address this challenge, we collaborated with radiologists to develop a framework that guides LLMs for radiology report evaluation, ensuring alignment with human analysis. Our framework includes two key components: i) utilizing GPT to generate large amounts of training data, i.e., reports with different qualities, and ii) pairing GPT-generated reports as accepted and rejected samples and training LLMs to produce MRScore as the model reward. Our experiments demonstrate MRScore's higher correlation with human judgments and superior performance in model selection compared to traditional metrics. Our code and datasets will be available on GitHub.

Given a set of dissimilarity measurements amongst data points, determining what metric representation is most "consistent" with the input measurements or the metric that best captures the relevant geometric features of the data is a key step in many machine learning algorithms. Existing methods are restricted to specific kinds of metrics or small problem sizes because of the large number of metric constraints in such problems. In this paper, we provide an active set algorithm, Project and Forget, that uses Bregman projections, to solve metric constrained problems with many (possibly exponentially) inequality constraints. We provide a theoretical analysis of Project and Forget and prove that our algorithm converges to the global optimal solution and that the L_2 distance of the current iterate to the optimal solution decays asymptotically at an exponential rate. We demonstrate that using our method we can solve large problem instances of three types of metric constrained problems: general weight correlation clustering, metric nearness, and metric learning; in each case, out-performing the state of the art methods with respect to CPU times and problem sizes.

Users of social platforms often perceive these sites as supportive spaces to post about their mental health issues. Those conversations contain important traces about individuals' health risks. Recently, researchers have exploited this online information to construct mental health detection models, which aim to identify users at risk on platforms like Twitter, Reddit or Facebook. Most of these models are centred on achieving good classification results, ignoring the explainability and interpretability of the decisions. Recent research has pointed out the importance of using clinical markers, such as the use of symptoms, to improve trust in the computational models by health professionals. In this paper, we propose using transformer-based architectures to detect and explain the appearance of depressive symptom markers in the users' writings. We present two approaches: i) train a model to classify, and another one to explain the classifier's decision separately and ii) unify the two tasks simultaneously using a single model. Additionally, for this latter manner, we also investigated the performance of recent conversational LLMs when using in-context learning. Our natural language explanations enable clinicians to interpret the models' decisions based on validated symptoms, enhancing trust in the automated process. We evaluate our approach using recent symptom-based datasets, employing both offline and expert-in-the-loop metrics to assess the quality of the explanations generated by our models. The experimental results show that it is possible to achieve good classification results while generating interpretable symptom-based explanations.

Evaluating radiology reports is a challenging problem as factual correctness is extremely important due to the need for accurate medical communication about medical images. Existing automatic evaluation metrics either suffer from failing to consider factual correctness (e.g., BLEU and ROUGE) or are limited in their interpretability (e.g., F1CheXpert and F1RadGraph). In this paper, we introduce GREEN (Generative Radiology Report Evaluation and Error Notation), a radiology report generation metric that leverages the natural language understanding of language models to identify and explain clinically significant errors in candidate reports, both quantitatively and qualitatively. Compared to current metrics, GREEN offers: 1) a score aligned with expert preferences, 2) human interpretable explanations of clinically significant errors, enabling feedback loops with end-users, and 3) a lightweight open-source method that reaches the performance of commercial counterparts. We validate our GREEN metric by comparing it to GPT-4, as well as to error counts of 6 experts and preferences of 2 experts. Our method demonstrates not only higher correlation with expert error counts, but simultaneously higher alignment with expert preferences when compared to previous approaches."

Tissue phenotyping is a fundamental task in learning objective characterizations of histopathologic biomarkers within the tumor-immune microenvironment in cancer pathology. However, whole-slide imaging (WSI) is a complex computer vision in which: 1) WSIs have enormous image resolutions with precludes large-scale pixel-level efforts in data curation, and 2) diversity of morphological phenotypes results in inter- and intra-observer variability in tissue labeling. To address these limitations, current efforts have proposed using pretrained image encoders (transfer learning from ImageNet, self-supervised pretraining) in extracting morphological features from pathology, but have not been extensively validated. In this work, we conduct a search for good representations in pathology by training a variety of self-supervised models with validation on a variety of weakly-supervised and patch-level tasks. Our key finding is in discovering that Vision Transformers using DINO-based knowledge distillation are able to learn data-efficient and interpretable features in histology images wherein the different attention heads learn distinct morphological phenotypes. We make evaluation code and pretrained weights publicly-available at: https://github.com/Richarizardd/Self-Supervised-ViT-Path.

In this article, we introduce a novel normalization technique for neural network weight matrices, which we term weight conditioning. This approach aims to narrow the gap between the smallest and largest singular values of the weight matrices, resulting in better-conditioned matrices. The inspiration for this technique partially derives from numerical linear algebra, where well-conditioned matrices are known to facilitate stronger convergence results for iterative solvers. We provide a theoretical foundation demonstrating that our normalization technique smoothens the loss landscape, thereby enhancing convergence of stochastic gradient descent algorithms. Empirically, we validate our normalization across various neural network architectures, including Convolutional Neural Networks (CNNs), Vision Transformers (ViT), Neural Radiance Fields (NeRF), and 3D shape modeling. Our findings indicate that our normalization method is not only competitive but also outperforms existing weight normalization techniques from the literature.

Medical question-answering (QA) is a critical task for evaluating how effectively large language models (LLMs) encode clinical knowledge and assessing their potential applications in medicine. Despite showing promise on multiple-choice tests, LLMs frequently struggle with open-ended medical questions, producing responses with dangerous hallucinations or lacking comprehensive coverage of critical aspects. Existing approaches attempt to address these challenges through domain-specific fine-tuning, but this proves resource-intensive and difficult to scale across models. To improve the comprehensiveness and factuality of medical responses, we propose a novel approach utilizing structured medical reasoning. Our method guides LLMs through an seven-step cognitive process inspired by clinical diagnosis, enabling more accurate and complete answers without additional training. Experiments on the MedLFQA benchmark demonstrate that our approach achieves the highest Factuality Score of 85.8, surpassing fine-tuned models. Notably, this improvement transfers to smaller models, highlighting the method's efficiency and scalability. Our code and datasets are available.

Osteoporosis is a widespread and chronic metabolic bone disease that often remains undiagnosed and untreated due to limited access to bone mineral density (BMD) tests like Dual-energy X-ray absorptiometry (DXA). In response to this challenge, current advancements are pivoting towards detecting osteoporosis by examining alternative indicators from peripheral bone areas, with the goal of increasing screening rates without added expenses or time. In this paper, we present a method to predict osteoporosis using hand and wrist X-ray images, which are both widely accessible and affordable, though their link to DXA-based data is not thoroughly explored. Initially, our method segments the ulnar, radius, and metacarpal bones using a foundational model for image segmentation. Then, we use a self-supervised learning approach to extract meaningful representations without the need for explicit labels, and move on to classify osteoporosis in a supervised manner. Our method is evaluated on a dataset with 192 individuals, cross-referencing their verified osteoporosis conditions against the standard DXA test. With a notable classification score (AUC=0.83), our model represents a pioneering effort in leveraging vision-based techniques for osteoporosis identification from the peripheral skeleton sites.

Pre-training lays the foundation for recent successes in radiograph analysis supported by deep learning. It learns transferable image representations by conducting large-scale fully-supervised or self-supervised learning on a source domain. However, supervised pre-training requires a complex and labor intensive two-stage human-assisted annotation process while self-supervised learning cannot compete with the supervised paradigm. To tackle these issues, we propose a cross-supervised methodology named REviewing FreE-text Reports for Supervision (REFERS), which acquires free supervision signals from original radiology reports accompanying the radiographs. The proposed approach employs a vision transformer and is designed to learn joint representations from multiple views within every patient study. REFERS outperforms its transfer learning and self-supervised learning counterparts on 4 well-known X-ray datasets under extremely limited supervision. Moreover, REFERS even surpasses methods based on a source domain of radiographs with human-assisted structured labels. Thus REFERS has the potential to replace canonical pre-training methodologies.