Daily Papers

Linguistic expressions of emotions such as depression, anxiety, and trauma-related states are pervasive in clinical notes, counseling dialogues, and online mental health communities, and accurate recognition of these emotions is essential for clinical triage, risk assessment, and timely intervention. Although large language models (LLMs) have demonstrated strong generalization ability in emotion analysis tasks, their diagnostic reliability in high-stakes, context-intensive medical settings remains highly sensitive to prompt design. Moreover, existing methods face two key challenges: emotional comorbidity, in which multiple intertwined emotional states complicate prediction, and inefficient exploration of clinically relevant cues. To address these challenges, we propose APOLO (Automated Prompt Optimization for Linguistic Emotion Diagnosis), a framework that systematically explores a broader and finer-grained prompt space to improve diagnostic efficiency and robustness. APOLO formulates instruction refinement as a Partially Observable Markov Decision Process and adopts a multi-agent collaboration mechanism involving Planner, Teacher, Critic, Student, and Target roles. Within this closed-loop framework, the Planner defines an optimization trajectory, while the Teacher-Critic-Student agents iteratively refine prompts to enhance reasoning stability and effectiveness, and the Target agent determines whether to continue optimization based on performance evaluation. Experimental results show that APOLO consistently improves diagnostic accuracy and robustness across domain-specific and stratified benchmarks, demonstrating a scalable and generalizable paradigm for trustworthy LLM applications in mental healthcare.

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

Melanoma is the most lethal subtype of skin cancer, and early and accurate detection of this disease can greatly improve patients' outcomes. Although machine learning models, especially convolutional neural networks (CNNs), have shown great potential in automating melanoma classification, their diagnostic reliability still suffers due to inconsistent focus on lesion areas. In this study, we analyze the relationship between lesion attention and diagnostic performance, involving masked images, bounding box detection, and transfer learning. We used multiple explainability and sensitivity analysis approaches to investigate how well models aligned their attention with lesion areas and how this alignment correlated with precision, recall, and F1-score. Results showed that models with a higher focus on lesion areas achieved better diagnostic performance, suggesting the potential of interpretable AI in medical diagnostics. This study provides a foundation for developing more accurate and trustworthy melanoma classification models in the future.

Imaging markers of cerebral small vessel disease provide valuable information on brain health, but their manual assessment is time-consuming and hampered by substantial intra- and interrater variability. Automated rating may benefit biomedical research, as well as clinical assessment, but diagnostic reliability of existing algorithms is unknown. Here, we present the results of the VAscular Lesions DetectiOn and Segmentation (Where is VALDO?) challenge that was run as a satellite event at the international conference on Medical Image Computing and Computer Aided Intervention (MICCAI) 2021. This challenge aimed to promote the development of methods for automated detection and segmentation of small and sparse imaging markers of cerebral small vessel disease, namely enlarged perivascular spaces (EPVS) (Task 1), cerebral microbleeds (Task 2) and lacunes of presumed vascular origin (Task 3) while leveraging weak and noisy labels. Overall, 12 teams participated in the challenge proposing solutions for one or more tasks (4 for Task 1 - EPVS, 9 for Task 2 - Microbleeds and 6 for Task 3 - Lacunes). Multi-cohort data was used in both training and evaluation. Results showed a large variability in performance both across teams and across tasks, with promising results notably for Task 1 - EPVS and Task 2 - Microbleeds and not practically useful results yet for Task 3 - Lacunes. It also highlighted the performance inconsistency across cases that may deter use at an individual level, while still proving useful at a population level.

In order to minimize the generalization error in neural networks, a novel technique to identify overfitting phenomena when training the learner is formally introduced. This enables support of a reliable and trustworthy early stopping condition, thus improving the predictive power of that type of modeling. Our proposal exploits the correlation over time in a collection of online indicators, namely characteristic functions for indicating if a set of hypotheses are met, associated with a range of independent stopping conditions built from a canary judgment to evaluate the presence of overfitting. That way, we provide a formal basis for decision making in terms of interrupting the learning process. As opposed to previous approaches focused on a single criterion, we take advantage of subsidiarities between independent assessments, thus seeking both a wider operating range and greater diagnostic reliability. With a view to illustrating the effectiveness of the halting condition described, we choose to work in the sphere of natural language processing, an operational continuum increasingly based on machine learning. As a case study, we focus on parser generation, one of the most demanding and complex tasks in the domain. The selection of cross-validation as a canary function enables an actual comparison with the most representative early stopping conditions based on overfitting identification, pointing to a promising start toward an optimal bias and variance control.

Understanding uncertainty in chain-of-thought reasoning is critical for reliable deployment of large language models. In this work, we propose a simple yet effective diagnostic approach based on trajectory shape rather than scalar magnitude. We show that this signal is practical, interpretable, and inexpensive to obtain in black-box settings, while remaining robust across models and datasets. Through extensive ablations and cross-domain replications, we demonstrate its utility for selective prediction and triage. Our findings offer a generalizable insight into uncertainty dynamics in reasoning tasks, with particular focus on numeric and discrete-answer settings.

The integration of quantum machine learning with classical deep learning offers promising avenues for medical image analysis by mapping data into high-dimensional Hilbert spaces. However, effectively unifying these distinct paradigms remains challenging due to common optimization asymmetries. In this paper, a novel hybrid quantum-classical architecture for breast cancer diagnosis based on a dual-branch feature-extraction pipeline is proposed. Our framework extracts and unifies complementary representations from classical models and quantum circuits, exploring both trainable and deterministic (non-trainable) quantum paradigms. To integrate these embeddings, three progressive feature fusion strategies are introduced: Static Hybrid Fusion (SHF) for offline extraction, Dynamic Hybrid Fusion (DHF) for end-to-end co-adaptation, and a novel Temperature-Scaled Hybrid Fusion (TSHF). The TSHF strategy incorporates a learnable scalar, inspired by multimodal learning, that dynamically balances hybrid gradient dynamics and resolves optimization bottlenecks. Empirical validation on the BreastMNIST dataset confirms our hypothesis that unifying diverse feature representations creates a richer data context. The TSHF strategy, specifically when pairing a ResNet backbone with a trainable quantum circuit, achieved a peak accuracy of 87.82%, F1-score of 91.77%, and an AUC-ROC of 89.08%, outperforming purely classical baselines. These results demonstrate that the proposed hybrid framework improves classification accuracy and threshold reliability, providing a stable, high-performance architecture for the clinical deployment of quantum-enhanced diagnostic tools.

Large language models (LLMs) are increasingly used in healthcare, but their reliability is heavily influenced by user-driven factors such as question phrasing and the completeness of clinical information. In this study, we examined how misinformation framing, source authority, model persona, and omission of key clinical details affect the diagnostic accuracy and reliability of LLM outputs. We conducted two experiments: one introducing misleading external opinions with varying assertiveness (perturbation test), and another removing specific categories of patient information (ablation test). Using public datasets (MedQA and Medbullets), we evaluated proprietary models (GPT-4o, Claude 3.5 Sonnet, Claude 3.5 Haiku, Gemini 1.5 Pro, Gemini 1.5 Flash) and open-source models (LLaMA 3 8B, LLaMA 3 Med42 8B, DeepSeek R1 8B). All models were vulnerable to user-driven misinformation, with proprietary models especially affected by definitive and authoritative language. Assertive tone had the greatest negative impact on accuracy. In the ablation test, omitting physical exam findings and lab results caused the most significant performance drop. Although proprietary models had higher baseline accuracy, their performance declined sharply under misinformation. These results highlight the need for well-structured prompts and complete clinical context. Users should avoid authoritative framing of misinformation and provide full clinical details, especially for complex cases.

Multi-agent systems powered by large language models (LLMs) are transforming enterprise automation, yet systematic evaluation methodologies for assessing tool-use reliability remain underdeveloped. We introduce a comprehensive diagnostic framework that leverages big data analytics to evaluate procedural reliability in intelligent agent systems, addressing critical needs for SME-centric deployment in privacy-sensitive environments. Our approach features a 12-category error taxonomy capturing failure modes across tool initialization, parameter handling, execution, and result interpretation. Through systematic evaluation of 1,980 deterministic test instances spanning both open-weight models (Qwen2.5 series, Functionary) and proprietary alternatives (GPT-4, Claude 3.5/3.7) across diverse edge hardware configurations, we identify actionable reliability thresholds for production deployment. Our analysis reveals that procedural reliability, particularly tool initialization failures, constitutes the primary bottleneck for smaller models, while qwen2.5:32b achieves flawless performance matching GPT-4.1. The framework demonstrates that mid-sized models (qwen2.5:14b) offer practical accuracy-efficiency trade-offs on commodity hardware (96.6\% success rate, 7.3 s latency), enabling cost-effective intelligent agent deployment for resource-constrained organizations. This work establishes foundational infrastructure for systematic reliability evaluation of tool-augmented multi-agent AI systems.

While LLM-as-a-Judge is widely used in automated evaluation, existing validation practices primarily operate at the level of observed outputs, offering limited insight into whether LLM judges themselves function as stable and reliable measurement instruments. To address this limitation, we introduce a two-phase diagnostic framework for assessing reliability of LLM-as-a-Judge, grounded in Item Response Theory (IRT). The framework adopts Graded Response Model (GRM) of IRT and formalizes reliability along two complementary dimensions: (1) intrinsic consistency, defined as the stability of measurement behavior under prompt variations, and (2) human alignment, capturing correspondence with human quality assessments. We empirically examine diverse LLM judges with this framework, and show that leveraging IRT-GRM yields interpretable signals for diagnosing judgments systematically. These signals provide practical guidance for verifying reliablity of LLM-as-a-Judge and identifying potential causes of unreliability.

As large language models (LLMs) are increasingly applied to real-world legal tasks, evaluating the reliability of their open-ended legal responses has become essential. These tasks require context-sensitive answers and allow little room for error, motivating fine-grained and diagnostic evaluation that can identify specific sources of response quality failures. We introduce LexRubric, a rubric-based benchmark for evaluating open-ended Chinese legal tasks. LexRubric contains 649 instances from legal consultation and judicial examination, which reflect both everyday legal needs and professional legal reasoning and cover 14 legal scenarios. It further includes 12,337 expert-written atomic scoring criteria organized under a unified six-dimensional framework, enabling accurate evaluation and diagnostic analysis across tasks and evaluation dimensions. To validate the reliability of the evaluation, we test multiple judge models and compare model-based judgments with human judgments. We further evaluate 18 recent general and legal-domain LLMs on LexRubric. Results show that different models exhibit distinct capability profiles, and that open-ended legal question remains challenging for current LLMs. Data is available at: https://github.com/foggpoy/LexRubric.

Large language models (LLMs) are increasingly integrated into legal drafting and research workflows, where incorrect citations or fabricated precedents can cause serious professional harm. Existing legal benchmarks largely emphasize statutory reasoning, contract understanding, or general legal question answering, but they do not directly study a central common-law failure mode: when asked to provide case authorities without external grounding, models may return plausible-looking but incorrect citations or cases. We introduce LegalCiteBench, a benchmark for studying closed-book citation recovery, citation verification, and case matching in legal language models. LegalCiteBench contains approximately 24K evaluation instances constructed from 1,000 real U.S. judicial opinions from the Case Law Access Project. The benchmark covers five citation-centric tasks: citation retrieval, citation completion, citation error detection, case matching, and case verification and correction. Across 21 LLMs, exact citation recovery remains highly challenging in this closed-book setting: even the strongest models score below 7/100 on citation retrieval and completion. Within the evaluated models, scale and legal-domain pretraining provide limited gains and do not resolve this difficulty. Models also frequently provide concrete but incorrect or low-overlap authorities under our evaluation protocol, with Misleading Answer Rates (MAR) exceeding 94% for 20 of 21 evaluated models on retrieval-heavy tasks. A prompt-only abstention experiment shows that explicit uncertainty instructions reduce some confident fabrication but do not improve citation correctness. LegalCiteBench is intended as a diagnostic framework for studying authority generation failures, verification behavior, and abstention when external grounding is absent, incomplete, or bypassed.

While current Computer Use Agent (CUA) benchmarks measure task completion effectively, they provide limited assessment of enterprise deployment readiness, emphasizing functional correctness over the operational reliability required for production systems. We present UI-CUBE (UiPath Computer Use BEnchmark), a systematic benchmark comprising 226 tasks across two difficulty tiers designed to expose fundamental architectural limitations in current CUAs. Our evaluation covers simple UI interactions (136 tasks) and complex workflows including copy-paste tasks (50 tasks) and enterprise application scenarios (40 tasks), with systematic interface variation coverage, multi-resolution testing and automated validation of task success through the application state. Evaluation of five state-of-the-art models reveals a sharp capability cliff rather than gradual performance degradation. Simple UI interactions achieve 67-85% success rates (compared to 97.9% human performance), but complex workflows drop precipitously to 9-19%. Human evaluators with no prior application experience achieve only 61.2% on complex tasks despite near-perfect performance on simple tasks, establishing realistic performance ceilings. This discontinuous performance pattern -- where agents achieve 68-87% of human performance on simple tasks but only 15-32% on complex workflows -- indicates fundamental architectural limitations in memory management, hierarchical planning, and state coordination rather than incremental capability gaps addressable through better training or prompting. UI-CUBE functions as an enterprise-readiness diagnostic, revealing that while current CUAs can manipulate individual interface elements, they cannot yet function as reliable workflow automation tools. These findings provide architectural insights essential for developing production-ready CUAs capable of managing complex, multi-step enterprise processes.

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

Large language models (LLMs) are increasingly explored for clinical decision support, yet most evaluations are conducted in English, leaving their reliability in other languages uncertain. Here we evaluate the impact of prompting language on diagnostic reasoning and final diagnosis accuracy by comparing English and French performance across five LLMs (o3, DeepSeek-R1, GPT-4-Turbo, Llama-3.1-405B-Instruct, and BioMistral-7B). A total of 180 clinical vignettes covering 16 medical specialties were assessed by two physicians using an 18-point scale evaluating both diagnosis accuracy and reasoning quality. Four of the five models performed better in English (mean difference 0.37-0.91, adjusted p < 0.05), with the gap spanning multiple aspects of reasoning, including differential diagnosis, logical structure, and internal validity. o3 was the only model showing no overall language effect. These findings demonstrate that prompting language remains a critical determinant of LLM clinical performance, with implications for equitable linguistico-cultural deployment worldwide.

Medical phrase grounding is crucial for identifying relevant regions in medical images based on phrase queries, facilitating accurate image analysis and diagnosis. However, current methods rely on manual extraction of key phrases from medical reports, reducing efficiency and increasing the workload for clinicians. Additionally, the lack of model confidence estimation limits clinical trust and usability. In this paper, we introduce a novel task called Medical Report Grounding (MRG), which aims to directly identify diagnostic phrases and their corresponding grounding boxes from medical reports in an end-to-end manner. To address this challenge, we propose uMedGround, a robust and reliable framework that leverages a multimodal large language model to predict diagnostic phrases by embedding a unique token, <BOX>, into the vocabulary to enhance detection capabilities. A vision encoder-decoder processes the embedded token and input image to generate grounding boxes. Critically, uMedGround incorporates an uncertainty-aware prediction model, significantly improving the robustness and reliability of grounding predictions. Experimental results demonstrate that uMedGround outperforms state-of-the-art medical phrase grounding methods and fine-tuned large visual-language models, validating its effectiveness and reliability. This study represents a pioneering exploration of the MRG task, marking the first-ever endeavor in this domain. Additionally, we demonstrate the applicability of uMedGround in medical visual question answering and class-based localization tasks, where it highlights visual evidence aligned with key diagnostic phrases, supporting clinicians in interpreting various types of textual inputs, including free-text reports, visual question answering queries, and class labels.

Most reported gains on agentic-LLM clinical benchmarks are often attributed to prompt engineering, yet our results suggest that larger improvements can come from architectural and engine-level design. We present MDIA, a Multi-agent Diagnostic Intelligence Agent implemented as a 7-node specialty-routed clinical reasoning graph, on the full HealthBench Professional benchmark (n = 525), on a non-fine-tuned LLM. MDIA achieves 0.6272 under OpenAI's GPT-5.4-2026-03-05, which is +3.72 pp above the performance of OpenAI's ChatGPT for Clinicians. The experimental work shows that performance lift is attributable to system architecture: specialty routing, multi-turn context preservation, drug-state safety gating, site-filtered search, length-aware synthesis, and engine-level reliability. These findings support the view that agentic clinical benchmark performance is shaped both by the underlying foundation model and the orchestration architecture. Nevertheless, we also noticed notable differences when using other models as a grader; in particular, when using Gemini 2.5 Pro, MDIA scored 0.6585, which suggests that the choice of grader is a source of variability. Robust evaluation of LLMs would therefore require assessment across several independent grader models.

Explainable Artificial Intelligence (XAI) techniques, such as Gradient-weighted Class Activation Mapping (Grad-CAM), have become indispensable for visualizing the reasoning process of deep neural networks in medical image analysis. Despite their popularity, the faithfulness and reliability of these heatmap-based explanations remain under scrutiny. This study critically investigates whether Grad-CAM truly represents the internal decision-making of deep models trained for lung cancer image classification. Using the publicly available IQ-OTH/NCCD dataset, we evaluate five representative architectures: ResNet-50, ResNet-101, DenseNet-161, EfficientNet-B0, and ViT-Base-Patch16-224, to explore model-dependent variations in Grad-CAM interpretability. We introduce a quantitative evaluation framework that combines localization accuracy, perturbation-based faithfulness, and explanation consistency to assess Grad-CAM reliability across architectures. Experimental findings reveal that while Grad-CAM effectively highlights salient tumor regions in most convolutional networks, its interpretive fidelity significantly degrades for Vision Transformer models due to non-local attention behavior. Furthermore, cross-model comparisons indicate substantial variability in saliency localization, implying that Grad-CAM explanations may not always correspond to the true diagnostic evidence used by the networks. This work exposes critical limitations of current saliency-based XAI approaches in medical imaging and emphasizes the need for model-aware interpretability methods that are both computationally sound and clinically meaningful. Our findings aim to inspire a more cautious and rigorous adoption of visual explanation tools in medical AI, urging the community to rethink what it truly means to "trust" a model's explanation.

Electroencephalography (EEG) is a cornerstone of brain-computer interfaces and clinical neuroscience, yet deep learning models are typically trained and evaluated under a single, unreported preprocessing pipeline. We formalize preprocessing choices as a counterfactual intervention space and show that EEG predictions are surprisingly unstable under this space: across six datasets spanning four paradigms, up to 42% of trial-level predictions flip when only the preprocessing changes, a variability that standard uncertainty methods do not explicitly quantify because they condition on a fixed preprocessing pipeline. We provide three tools to make this instability measurable, decomposable, and reducible. First, a Walsh-Hadamard decomposition of the 2^7 pipeline space reveals that sensitivity is near-additive in practice under the binary intervention design, enabling efficient step-by-step optimization. Second, we introduce Preprocessing Uncertainty (PU), a per-trial diagnostic that captures a dimension of instability complementary to model-based confidence. Third, we study Normalized Adaptive PGI (NA-PGI), a graph-structured regularizer that exploits the compositional structure of preprocessing interventions as one mitigation strategy with clear scope conditions.

Manipulation understanding requires reliable relational evidence, such as contact, support, containment, motion coupling, grasp, release, and active-hand involvement. Although these visual predicates are widely used in event-chain, graph-based, and neuro-symbolic models, their reliability under visual degradation is rarely analyzed directly. This paper introduces a predicate-level reliability framework for robust manipulation understanding under blur, occlusion, illumination change, low resolution, frame dropping, and detection noise. The framework defines a structured predicate vocabulary, confidence-aware predicate estimation, and reliability metrics for predicate preservation, degradation sensitivity, temporal consistency, confidence-weighted stability, and downstream impact. Experiments on controlled manipulation videos and public egocentric or bimanual datasets, including VISOR/EPIC-KITCHENS, H2O, and ARCTIC, show that predicate failures are structured rather than uniform. Static spatial predicates remain comparatively robust, whereas contact-sensitive, dynamic, and derived predicates such as grasp and release are more fragile. Under severe degradation, detection noise, occlusion, and frame dropping cause the strongest reliability losses. Downstream analysis shows that degraded predicates reduce manipulation-understanding accuracy from 0.89 to 0.58, while removing confidence weighting under moderate degradation reduces accuracy from 0.74 to 0.64. These results show that predicate reliability provides a diagnostic layer between visual perception and structured manipulation reasoning.

We introduce AIBrix, a cloud-native, open-source framework designed to optimize and simplify large-scale LLM deployment in cloud environments. Unlike traditional cloud-native stacks, AIBrix follows a co-design philosophy, ensuring every layer of the infrastructure is purpose-built for seamless integration with inference engines like vLLM. AIBrix introduces several key innovations to reduce inference costs and enhance performance including high-density LoRA management for dynamic adapter scheduling, LLM-specific autoscalers, and prefix-aware, load-aware routing. To further improve efficiency, AIBrix incorporates a distributed KV cache, boosting token reuse across nodes, leading to a 50% increase in throughput and a 70% reduction in inference latency. AIBrix also supports unified AI runtime which streamlines model management while maintaining vendor-agnostic engine compatibility. For large-scale multi-node inference, AIBrix employs hybrid orchestration -- leveraging Kubernetes for coarse-grained scheduling and Ray for fine-grained execution -- to balance efficiency and flexibility. Additionally, an SLO-driven GPU optimizer dynamically adjusts resource allocations, optimizing heterogeneous serving to maximize cost efficiency while maintaining service guarantees. Finally, AIBrix enhances system reliability with AI accelerator diagnostic tools, enabling automated failure detection and mock-up testing to improve fault resilience. AIBrix is available at https://github.com/vllm-project/aibrix.

Large Language Models (LLMs) achieve strong performance on diverse tasks but often exhibit cognitive inertia, struggling to follow instructions that conflict with the standardized patterns learned during supervised fine-tuning (SFT). To evaluate this limitation, we propose Inverse IFEval, a benchmark that measures models Counter-intuitive Abilitytheir capacity to override training-induced biases and comply with adversarial instructions. Inverse IFEval introduces eight types of such challenges, including Question Correction, Intentional Textual Flaws, Code without Comments, and Counterfactual Answering. Using a human-in-the-loop pipeline, we construct a dataset of 1012 high-quality Chinese and English questions across 23 domains, evaluated under an optimized LLM-as-a-Judge framework. Experiments on existing leading LLMs demonstrate the necessity of our proposed Inverse IFEval benchmark. Our findings emphasize that future alignment efforts should not only pursue fluency and factual correctness but also account for adaptability under unconventional contexts. We hope that Inverse IFEval serves as both a diagnostic tool and a foundation for developing methods that mitigate cognitive inertia, reduce overfitting to narrow patterns, and ultimately enhance the instruction-following reliability of LLMs in diverse and unpredictable real-world scenarios.

AI agents are rapidly advancing from passive language models to autonomous systems executing complex, multi-step tasks. Yet their overconfidence in failure remains a fundamental barrier to deployment in high-stakes settings. Existing calibration methods, built for static single-turn outputs, cannot address the unique challenges of agentic systems, such as compounding errors along trajectories, uncertainty from external tools, and opaque failure modes. To address these challenges, we introduce, for the first time, the problem of Agentic Confidence Calibration and propose Holistic Trajectory Calibration (HTC), a novel diagnostic framework that extracts rich process-level features ranging from macro dynamics to micro stability across an agent's entire trajectory. Powered by a simple, interpretable model, HTC consistently surpasses strong baselines in both calibration and discrimination, across eight benchmarks, multiple LLMs, and diverse agent frameworks. Beyond performance, HTC delivers three essential advances: it provides interpretability by revealing the signals behind failure, enables transferability by applying across domains without retraining, and achieves generalization through a General Agent Calibrator (GAC) that achieves the best calibration (lowest ECE) on the out-of-domain GAIA benchmark. Together, these contributions establish a new process-centric paradigm for confidence calibration, providing a framework for diagnosing and enhancing the reliability of AI agents.

We develop a statistical procedure to detect lookahead bias in economic forecasts generated by large language models (LLMs). Using a date-only recall query for a firm-date pair, we estimate the probability that the LLM has internalized information about the realized outcome, a statistic we term Lookahead Propensity (LAP). LAP is materially positive throughout the in-sample period and collapses essentially to zero right after the training-data cutoff. We show that a positive interaction between LAP and the LLM forecast in an accuracy regression indicates lookahead-bias contamination, and apply the test to two forecasting tasks: news headlines predicting stock returns and earnings call transcripts predicting capital expenditures. In both applications, the LLM forecast's predictive power is amplified on high-LAP firm-date pairs, and the interaction loses significance on post-training-cutoff samples. Our test provides a cost-efficient, diagnostic tool for assessing the validity and reliability of LLM-generated forecasts.

Ensuring the safety of large language models (LLMs) is critical for responsible deployment, yet existing evaluations often prioritize performance over identifying failure modes. We introduce Phare, a multilingual diagnostic framework to probe and evaluate LLM behavior across three critical dimensions: hallucination and reliability, social biases, and harmful content generation. Our evaluation of 17 state-of-the-art LLMs reveals patterns of systematic vulnerabilities across all safety dimensions, including sycophancy, prompt sensitivity, and stereotype reproduction. By highlighting these specific failure modes rather than simply ranking models, Phare provides researchers and practitioners with actionable insights to build more robust, aligned, and trustworthy language systems.

The escalating complexity of modern software imposes an unsustainable operational burden on Site Reliability Engineering (SRE) teams, demanding AI-driven automation that can emulate expert diagnostic reasoning. Existing solutions, from traditional AI methods to general-purpose multi-agent systems, fall short: they either lack deep causal reasoning or are not tailored for the specialized, investigative workflows unique to SRE. To address this gap, we present OpenDerisk, a specialized, open-source multi-agent framework architected for SRE. OpenDerisk integrates a diagnostic-native collaboration model, a pluggable reasoning engine, a knowledge engine, and a standardized protocol (MCP) to enable specialist agents to collectively solve complex, multi-domain problems. Our comprehensive evaluation demonstrates that OpenDerisk significantly outperforms state-of-the-art baselines in both accuracy and efficiency. This effectiveness is validated by its large-scale production deployment at Ant Group, where it serves over 3,000 daily users across diverse scenarios, confirming its industrial-grade scalability and practical impact. OpenDerisk is open source and available at https://github.com/derisk-ai/OpenDerisk/

Immunohistochemistry (IHC) provides information on protein expression in tissue sections and is commonly used to support pathology diagnosis and disease triage. While AI models for H\&E-stained slides show promise, their applicability to IHC is limited due to domain-specific variations. Here we introduce HPA10M, a dataset that contains 10,495,672 IHC images from the Human Protein Atlas with comprehensive metadata included, and encompasses 45 normal tissue types and 20 major cancer types. Based on HPA10M, we trained iSight, a multi-task learning framework for automated IHC staining assessment. iSight combines visual features from whole-slide images with tissue metadata through a token-level attention mechanism, simultaneously predicting staining intensity, location, quantity, tissue type, and malignancy status. On held-out data, iSight achieved 85.5\% accuracy for location, 76.6\% for intensity, and 75.7\% for quantity, outperforming fine-tuned foundation models (PLIP, CONCH) by 2.5--10.2\%. In addition, iSight demonstrates well-calibrated predictions with expected calibration errors of 0.0150-0.0408. Furthermore, in a user study with eight pathologists evaluating 200 images from two datasets, iSight outperformed initial pathologist assessments on the held-out HPA dataset (79\% vs 68\% for location, 70\% vs 57\% for intensity, 68\% vs 52\% for quantity). Inter-pathologist agreement also improved after AI assistance in both held-out HPA (Cohen's κ increased from 0.63 to 0.70) and Stanford TMAD datasets (from 0.74 to 0.76), suggesting expert--AI co-assessment can improve IHC interpretation. This work establishes a foundation for AI systems that can improve IHC diagnostic accuracy and highlights the potential for integrating iSight into clinical workflows to enhance the consistency and reliability of IHC assessment.

Clinical decision-making in radiology increasingly benefits from artificial intelligence (AI), particularly through large language models (LLMs). However, traditional retrieval-augmented generation (RAG) systems for radiology question answering (QA) typically rely on single-step retrieval, limiting their ability to handle complex clinical reasoning tasks. Here we propose radiology Retrieval and Reasoning (RaR), a multi-step retrieval and reasoning framework designed to improve diagnostic accuracy, factual consistency, and clinical reliability of LLMs in radiology question answering. We evaluated 25 LLMs spanning diverse architectures, parameter scales (0.5B to >670B), and training paradigms (general-purpose, reasoning-optimized, clinically fine-tuned), using 104 expert-curated radiology questions from previously established RSNA-RadioQA and ExtendedQA datasets. To assess generalizability, we additionally tested on an unseen internal dataset of 65 real-world radiology board examination questions. RaR significantly improved mean diagnostic accuracy over zero-shot prompting and conventional online RAG. The greatest gains occurred in small-scale models, while very large models (>200B parameters) demonstrated minimal changes (<2% improvement). Additionally, RaR retrieval reduced hallucinations (mean 9.4%) and retrieved clinically relevant context in 46% of cases, substantially aiding factual grounding. Even clinically fine-tuned models showed gains from RaR (e.g., MedGemma-27B), indicating that retrieval remains beneficial despite embedded domain knowledge. These results highlight the potential of RaR to enhance factuality and diagnostic accuracy in radiology QA, warranting future studies to validate their clinical utility. All datasets, code, and the full RaR framework are publicly available to support open research and clinical translation.

Precision agriculture relies heavily on accurate image analysis for crop disease identification and treatment recommendation, yet existing vision-language models (VLMs) often underperform in specialized agricultural domains. This work presents a domain-aware framework for agricultural image processing that combines prompt-based expert evaluation with self-consistency mechanisms to enhance VLM reliability in precision agriculture applications. We introduce two key innovations: (1) a prompt-based evaluation protocol that configures a language model as an expert plant pathologist for scalable assessment of image analysis outputs, and (2) a cosine-consistency self-voting mechanism that generates multiple candidate responses from agricultural images and selects the most semantically coherent diagnosis using domain-adapted embeddings. Applied to maize leaf disease identification from field images using a fine-tuned PaliGemma model, our approach improves diagnostic accuracy from 82.2\% to 87.8\%, symptom analysis from 38.9\% to 52.2\%, and treatment recommendation from 27.8\% to 43.3\% compared to standard greedy decoding. The system remains compact enough for deployment on mobile devices, supporting real-time agricultural decision-making in resource-constrained environments. These results demonstrate significant potential for AI-driven precision agriculture tools that can operate reliably in diverse field conditions.

Clinical decision-support systems are expert systems whose recommendations clinicians act on directly, yet they are usually cleared on one aggregate accuracy number from a held-out test set. That number says nothing about input reliability under encoding shifts, subgroup gaps, threshold sensitivity, or operational feasibility. We present RISED, a pre-deployment evaluation framework operationalising five dimensions (Reliability, Inclusivity, Sensitivity, Equity, Deployability) through BCa bootstrap 95% confidence intervals, literature-grounded thresholds, and Holm-Bonferroni-corrected PASS / FAIL / INCONCLUSIVE verdicts; Equity is a proxy-dependence diagnostic rather than a gating test. Applied to seven cohorts spanning 35 years (n from 303 to 99,492), RISED surfaces failures invisible to AUROC: on Diabetes 130, Reliability passes by three orders of magnitude (PSS = 0.0004) while Inclusivity (AUC parity gap = 0.262) and Sensitivity (max threshold-flip rate 49.1%) fail decisively; both NHIS cohorts reproduce this. NHANES 2021-2023, with a complete feature profile, achieves INCONCLUSIVE verdicts; BRFSS 2024 produces the suite's most severe Sensitivity failure (max threshold-flip rate 64.2%) after instrument rotation removed hypertension and cholesterol. The pattern recurs on credit- and income-prediction cohorts, confirming domain-agnosticity; a multi-model check shows the failures are data-driven, not model-specific. RISED ships as an open-source Python package complementing TRIPOD+AI, FUTURE-AI, and Fairlearn with the structured numerical evidence those standards require but do not prescribe.

Large Language Models (LLMs) have demonstrated impressive generative capabilities across diverse tasks but remain susceptible to hallucinations, confidently generated yet factually incorrect outputs. We introduce a reference-free, token-level hallucination detection framework that leverages the variance in token log-probabilities across multiple stochastic generations. Unlike prior methods that require ground-truth references or sentence-level verification, our approach is model-agnostic, interpretable, and suited for real-time or post-hoc analysis. We evaluate our method on unanswerable question prompts from the SQuAD v2 dataset and benchmark across three autoregressive models of varying scales: GPT-Neo 125M, Falcon 1B, and Mistral 7B. Through both quantitative metrics and visual diagnostics, we show that token-level variance reliably highlights instability in model outputs and correlates with hallucination patterns. Our framework is lightweight, reproducible, and adaptable to multiple domains, offering a valuable diagnostic tool for analyzing generative reliability in LLMs.

Optical Coherence Tomography Angiography (OCTA) and its derived en-face projections provide high-resolution visualization of the retinal and choroidal vasculature, which is critical for the rapid and accurate diagnosis of retinal diseases. However, acquiring high-quality OCTA images is challenging due to motion sensitivity and the high costs associated with software modifications for conventional OCT devices. Moreover, current deep learning methods for OCT-to-OCTA translation often overlook the vascular differences across retinal layers and struggle to reconstruct the intricate, dense vascular details necessary for reliable diagnosis. To overcome these limitations, we propose XOCT, a novel deep learning framework that integrates Cross-Dimensional Supervision (CDS) with a Multi-Scale Feature Fusion (MSFF) network for layer-aware vascular reconstruction. Our CDS module leverages 2D layer-wise en-face projections, generated via segmentation-weighted z-axis averaging, as supervisory signals to compel the network to learn distinct representations for each retinal layer through fine-grained, targeted guidance. Meanwhile, the MSFF module enhances vessel delineation through multi-scale feature extraction combined with a channel reweighting strategy, effectively capturing vascular details at multiple spatial scales. Our experiments on the OCTA-500 dataset demonstrate XOCT's improvements, especially for the en-face projections which are significant for clinical evaluation of retinal pathologies, underscoring its potential to enhance OCTA accessibility, reliability, and diagnostic value for ophthalmic disease detection and monitoring. The code is available at https://github.com/uci-cbcl/XOCT.

Large language model (LLM) agents now execute long, tool-using tasks where final outcome checks can arrive too late for intervention. Online warning requires lightweight prefix monitors over heterogeneous traces, but hand-authored event schemas are brittle and deployment-time LLM judging is costly. We introduce PrefixGuard, a trace-to-monitor framework with an offline StepView induction step followed by supervised monitor training. StepView induces deterministic typed-step adapters from raw trace samples, and the monitor learns an event abstraction and prefix-risk scorer from terminal outcomes. Across WebArena, τ^2-Bench, SkillsBench, and TerminalBench, the strongest PrefixGuard monitors reach 0.900/0.710/0.533/0.557 AUPRC. Using the strongest backend within each representation, they improve over raw-text controls by an average of +0.137 AUPRC. LLM judges remain substantially weaker under the same prefix-warning protocol. We also derive an observability ceiling on score-based area under the precision-recall curve (AUPRC) that separates monitor error from failures lacking evidence in the observed prefix. For finite-state audit, post-hoc deterministic finite automaton (DFA) extraction remains compact on WebArena and τ^2-Bench (29 and 20 states) but expands to 151 and 187 states on SkillsBench and TerminalBench. Finally, first-alert diagnostics show that strong ranking does not imply deployment utility: WebArena ranks well yet fails to support low-false-alarm alerts, whereas τ^2-Bench and TerminalBench retain more actionable early alerts. Together, these results position PrefixGuard as a practical monitor-synthesis recipe with explicit diagnostics for when prefix warnings translate into actionable interventions.

Tool use has become central to modern LLM agents, yet interface design is rarely isolated as an experimental variable. This paper studies whether schema based tool contracts and structured validation diagnostics improve reliability under strict interaction budgets. We evaluate three conditions that preserve identical tool semantics and information content: free form documentation, JSON Schema specifications, and JSON Schema with structured diagnostics. We implement a deterministic software engineering sandbox with logs, metrics, configurations, and repository tasks, and evaluate a fully crossed pilot with one open local model, three seeds, three interface conditions, and four budgets. We report end task success, interface misuse, execution failures, semantic misuse, recovery behavior, and overhead. In this pilot, success remains zero across conditions, while schema conditions reduce interface misuse but not semantic misuse. The evidence supports a precise interpretation that interface formalization improves contract adherence, but semantic action quality and timeout sensitive tasks remain dominant bottlenecks under constrained local inference.

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.

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

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.

Vision Language Models (VLMs) are increasingly used for tasks like medical report generation and visual question answering. However, fluent diagnostic text does not guarantee safe visual understanding. In clinical practice, interpretation begins with pre-diagnostic sanity checks: verifying that the input is valid to read (correct modality and anatomy, plausible viewpoint and orientation, and no obvious integrity violations). Existing benchmarks largely assume this step is solved, and therefore miss a critical failure mode: a model can produce plausible narratives even when the input is inconsistent or invalid. We introduce MedObvious, a 1,880-task benchmark that isolates input validation as a set-level consistency capability over small multi-panel image sets: the model must identify whether any panel violates expected coherence. MedObvious spans five progressive tiers, from basic orientation/modality mismatches to clinically motivated anatomy/viewpoint verification and triage-style cues, and includes five evaluation formats to test robustness across interfaces. Evaluating 17 different VLMs, we find that sanity checking remains unreliable: several models hallucinate anomalies on normal (negative-control) inputs, performance degrades when scaling to larger image sets, and measured accuracy varies substantially between multiple-choice and open-ended settings. These results show that pre-diagnostic verification remains unsolved for medical VLMs and should be treated as a distinct, safety-critical capability before deployment.

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.

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.

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.

Agentic retrieval-augmented reasoning pipelines are increasingly used to structure how large language models (LLMs) incorporate external evidence in clinical decision support. These systems iteratively retrieve curated domain knowledge and synthesize it into structured reports before answer selection. Although such pipelines can improve performance, their impact on reliability under model variability remains unclear. In real-world deployment, heterogeneous models may align, diverge, or synchronize errors in ways not captured by accuracy. We evaluated 34 LLMs on 169 expert-curated publicly available radiology questions, comparing zero-shot inference with a radiology-specific multi-step agentic retrieval condition in which all models received identical structured evidence reports derived from curated radiology knowledge. Agentic inference reduced inter-model decision dispersion (median entropy 0.48 vs. 0.13) and increased robustness of correctness across models (mean 0.74 vs. 0.81). Majority consensus also increased overall (P<0.001). Consensus strength and robust correctness remained correlated under both strategies (ho=0.88 for zero-shot; ho=0.87 for agentic), although high agreement did not guarantee correctness. Response verbosity showed no meaningful association with correctness. Among 572 incorrect outputs, 72% were associated with moderate or high clinically assessed severity, although inter-rater agreement was low (appa=0.02). Agentic retrieval therefore was associated with more concentrated decision distributions, stronger consensus, and higher cross-model robustness of correctness. These findings suggest that evaluating agentic systems through accuracy or agreement alone may not always be sufficient, and that complementary analyses of stability, cross-model robustness, and potential clinical impact are needed to characterize reliability under model variability.

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.

Seeking health-related advice on the internet has become a common practice in the digital era. Determining the trustworthiness of medical claims found online and finding appropriate evidence for this information is increasingly challenging. Fact-checking has emerged as an approach to assess the veracity of factual claims using evidence from credible knowledge sources. To help advance the automation of this task, in this paper, we introduce a novel dataset of 750 health-related claims, labeled for veracity by medical experts and backed with evidence from appropriate clinical studies. We provide an analysis of the dataset, highlighting its characteristics and challenges. The dataset can be used for Machine Learning tasks related to automated fact-checking such as evidence retrieval, veracity prediction, and explanation generation. For this purpose, we provide baseline models based on different approaches, examine their performance, and discuss the findings.

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.

Users typically engage with LLMs interactively, yet most existing benchmarks evaluate them in a static, single-turn format, posing reliability concerns in interactive scenarios. We identify a key obstacle towards reliability: LLMs are trained to answer any question, even with incomplete context or insufficient knowledge. In this paper, we propose to change the static paradigm to an interactive one, develop systems that proactively ask questions to gather more information and respond reliably, and introduce an benchmark - MediQ - to evaluate question-asking ability in LLMs. MediQ simulates clinical interactions consisting of a Patient System and an adaptive Expert System; with potentially incomplete initial information, the Expert refrains from making diagnostic decisions when unconfident, and instead elicits missing details via follow-up questions. We provide a pipeline to convert single-turn medical benchmarks into an interactive format. Our results show that directly prompting state-of-the-art LLMs to ask questions degrades performance, indicating that adapting LLMs to proactive information-seeking settings is nontrivial. We experiment with abstention strategies to better estimate model confidence and decide when to ask questions, improving diagnostic accuracy by 22.3%; however, performance still lags compared to an (unrealistic in practice) upper bound with complete information upfront. Further analyses show improved interactive performance with filtering irrelevant contexts and reformatting conversations. Overall, we introduce a novel problem towards LLM reliability, an interactive MediQ benchmark and a novel question-asking system, and highlight directions to extend LLMs' information-seeking abilities in critical domains.

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.

Artificial intelligence holds great promise for expanding access to expert medical knowledge and reasoning. However, most evaluations of language models rely on static vignettes and multiple-choice questions that fail to reflect the complexity and nuance of evidence-based medicine in real-world settings. In clinical practice, physicians iteratively formulate and revise diagnostic hypotheses, adapting each subsequent question and test to what they've just learned, and weigh the evolving evidence before committing to a final diagnosis. To emulate this iterative process, we introduce the Sequential Diagnosis Benchmark, which transforms 304 diagnostically challenging New England Journal of Medicine clinicopathological conference (NEJM-CPC) cases into stepwise diagnostic encounters. A physician or AI begins with a short case abstract and must iteratively request additional details from a gatekeeper model that reveals findings only when explicitly queried. Performance is assessed not just by diagnostic accuracy but also by the cost of physician visits and tests performed. We also present the MAI Diagnostic Orchestrator (MAI-DxO), a model-agnostic orchestrator that simulates a panel of physicians, proposes likely differential diagnoses and strategically selects high-value, cost-effective tests. When paired with OpenAI's o3 model, MAI-DxO achieves 80% diagnostic accuracy--four times higher than the 20% average of generalist physicians. MAI-DxO also reduces diagnostic costs by 20% compared to physicians, and 70% compared to off-the-shelf o3. When configured for maximum accuracy, MAI-DxO achieves 85.5% accuracy. These performance gains with MAI-DxO generalize across models from the OpenAI, Gemini, Claude, Grok, DeepSeek, and Llama families. We highlight how AI systems, when guided to think iteratively and act judiciously, can advance diagnostic precision and cost-effectiveness in clinical care.

Across medical specialties, clinical practice is anchored in evidence-based guidelines that codify best studied diagnostic and treatment pathways. These pathways routinely fall short for the long tail of real-world care not covered by guidelines. Most medical large language models (LLMs), however, are trained to encode common, guideline-focused medical knowledge in their parameters. Current evaluations test models primarily on recalling and reasoning with this memorized content, often in multiple-choice settings. Given the fundamental importance of evidence-based reasoning in medicine, it is neither feasible nor reliable to depend on memorization in practice. To address this gap, we introduce OGCaReBench, a free-form retrieval-focused benchmark aimed at evaluating LLMs at answering clinical questions that require going beyond typical guidelines. Extracted from published medical case reports and validated by medical experts, OGCaReBench contains long-form clinical questions requiring free-text answers, providing a systematic framework for assessing open-ended medical reasoning in rare, case-based scenarios. Our experiments reveal that even the best-performing baseline (GPT-5.2) correctly answers only 56% of our benchmark with specialized models only reaching 42%. Augmenting models with retrieved medical articles improves this performance to up to 82% (using GPT-5.2) highlighting the importance of evidence-grounding for real-world medical reasoning tasks. This work thus establishes a foundation for benchmarking and advancing both general-purpose and medical LLMs to produce reliable answers in challenging clinical contexts.

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.

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

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

The potential of Multimodal Large Language Models (MLLMs) in domain of medical imaging raise the demands of systematic and rigorous evaluation frameworks that are aligned with the real-world medical imaging practice. Existing practices that report single or coarse-grained metrics are lack the granularity required for specialized clinical support and fail to assess the reliability of reasoning mechanisms. To address this, we propose a paradigm shift toward multidimensional, fine-grained and in-depth evaluation. Based on a two-stage systematic construction pipeline designed for this paradigm, we instantiate it with MedRCube. We benchmark 33 MLLMs, Lingshu-32B achieve top-tier performance. Crucially, MedRCube exposes a series of pronounced insights inaccessible under prior evaluation settings. Furthermore, we introduce a credibility evaluation subset to quantify reasoning credibility, uncover a highly significant positive association between shortcut behavior and diagnostic task performance, raising concerns for clinically trustworthy deployment. The resources of this work can be found at https://github.com/F1mc/MedRCube.

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

Previous research on radiology report generation has made significant progress in terms of increasing the clinical accuracy of generated reports. In this paper, we emphasize another crucial quality that it should possess, i.e., inter-report consistency, which refers to the capability of generating consistent reports for semantically equivalent radiographs. This quality is even of greater significance than the overall report accuracy in terms of ensuring the system's credibility, as a system prone to providing conflicting results would severely erode users' trust. Regrettably, existing approaches struggle to maintain inter-report consistency, exhibiting biases towards common patterns and susceptibility to lesion variants. To address this issue, we propose ICON, which improves the inter-report consistency of radiology report generation. Aiming at enhancing the system's ability to capture the similarities in semantically equivalent lesions, our approach involves first extracting lesions from input images and examining their characteristics. Then, we introduce a lesion-aware mix-up augmentation technique to ensure that the representations of the semantically equivalent lesions align with the same attributes, by linearly interpolating them during the training phase. Extensive experiments on three publicly available chest X-ray datasets verify the effectiveness of our approach, both in terms of improving the consistency and accuracy of the generated reports.

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

Developing reliable AI systems to assist human clinicians in multi-modal medical diagnosis has long been a key objective for researchers. Recently, Multi-modal Large Language Models (MLLMs) have gained significant attention and achieved success across various domains. With strong reasoning capabilities and the ability to perform diverse tasks based on user instructions, they hold great potential for enhancing medical diagnosis. However, directly applying MLLMs to the medical domain still presents challenges. They lack detailed perception of visual inputs, limiting their ability to perform quantitative image analysis, which is crucial for medical diagnostics. Additionally, MLLMs often exhibit hallucinations and inconsistencies in reasoning, whereas clinical diagnoses must adhere strictly to established criteria. To address these challenges, we propose MedAgent-Pro, an evidence-based reasoning agentic system designed to achieve reliable, explainable, and precise medical diagnoses. This is accomplished through a hierarchical workflow: at the task level, knowledge-based reasoning generate reliable diagnostic plans for specific diseases following retrieved clinical criteria. While at the case level, multiple tool agents process multi-modal inputs, analyze different indicators according to the plan, and provide a final diagnosis based on both quantitative and qualitative evidence. Comprehensive experiments on both 2D and 3D medical diagnosis tasks demonstrate the superiority and effectiveness of MedAgent-Pro, while case studies further highlight its reliability and interpretability. The code is available at https://github.com/jinlab-imvr/MedAgent-Pro.

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.

Evaluating the reliability of news sources is a routine task for journalists and organizations committed to acquiring and disseminating accurate information. Recent research has shown that predicting sources' reliability represents an important first-prior step in addressing additional challenges such as fake news detection and fact-checking. In this paper, we introduce a novel approach for source reliability estimation that leverages reinforcement learning strategies for estimating the reliability degree of news sources. Contrary to previous research, our proposed approach models the problem as the estimation of a reliability degree, and not a reliability label, based on how all the news media sources interact with each other on the Web. We validated the effectiveness of our method on a news media reliability dataset that is an order of magnitude larger than comparable existing datasets. Results show that the estimated reliability degrees strongly correlates with journalists-provided scores (Spearman=0.80) and can effectively predict reliability labels (macro-avg. F_1 score=81.05). We release our implementation and dataset, aiming to provide a valuable resource for the NLP community working on information verification.

Single-prompt accuracy is the dominant way to benchmark language models, but it can miss reliability failures that matter. We evaluate a 15-model open-weight corpus, with the main reliability analyses focused on 10 instruct models across five classification and reasoning benchmarks under five prompt variants each, measuring accuracy, token-probability calibration, verbal-confidence calibration, verbal parse rate, and prompt-perturbation spread for every (model x dataset x variant) cell. We find three broad results. First, evaluation design can materially change the conclusion. Switching Expected Calibration Error (ECE) token from a raw to a label-set-normalised definition changes per-cell calibration by a mean absolute 0.149. More strikingly, pairing a chain-of-thought prompt with a first-character evaluator on ARC-Challenge reduces apparent accuracy by 72-88% across all five primary models; two independent repair procedures recover 93.8% and 102.7% of the lost performance, indicating an evaluator-side rather than model-side failure. Second, confidence signals are fragile. On MMLU-Pro, every primary model verbally reports confidence substantially above both its accuracy and its token-probability confidence on the same rows, and verbal parse rate can collapse for a single model on a single prompt variant. Third, prompt robustness does not track parameter count reliably. Across 10 instruct models, the correlation between model size and prompt-perturbation spread ranges from -0.244 to 0.474 across benchmarks. Taken together, these results show that reliability conclusions for small language models depend not only on the model being evaluated, but also on the evaluation pipeline used to measure it. We argue that calibration definitions, evaluator logic, verbal parseability, and prompt robustness should be reported explicitly when making reliability claims.

Recent progress in multimodal large language models (MLLMs) has demonstrated promising performance on medical benchmarks and in preliminary trials as clinical assistants. Yet, our pilot audit of diagnostic cases uncovers a critical failure mode: instability in early evidence interpretation precedes hallucination, creating branching reasoning trajectories that cascade into globally inconsistent conclusions. This highlights the need for clinical reasoning agents that constrain stochasticity and hallucination while producing auditable decision flows. We introduce MedMMV, a controllable multimodal multi-agent framework for reliable and verifiable clinical reasoning. MedMMV stabilizes reasoning through diversified short rollouts, grounds intermediate steps in a structured evidence graph under the supervision of a Hallucination Detector, and aggregates candidate paths with a Combined Uncertainty scorer. On six medical benchmarks, MedMMV improves accuracy by up to 12.7% and, more critically, demonstrates superior reliability. Blind physician evaluations confirm that MedMMV substantially increases reasoning truthfulness without sacrificing informational content. By controlling instability through a verifiable, multi-agent process, our framework provides a robust path toward deploying trustworthy AI systems in high-stakes domains like clinical decision support.

We develop and evaluate a data-driven approach for detecting unusual (anomalous) patient-management decisions using past patient cases stored in electronic health records (EHRs). Our hypothesis is that a patient-management decision that is unusual with respect to past patient care may be due to an error and that it is worthwhile to generate an alert if such a decision is encountered. We evaluate this hypothesis using data obtained from EHRs of 4486 post-cardiac surgical patients and a subset of 222 alerts generated from the data. We base the evaluation on the opinions of a panel of experts. The results of the study support our hypothesis that the outlier-based alerting can lead to promising true alert rates. We observed true alert rates that ranged from 25\% to 66\% for a variety of patient-management actions, with 66\% corresponding to the strongest outliers.

Background: Agent skills are increasingly deployed as modular, reusable capability units in AI agent systems. Medical research agent skills require safeguards beyond general-purpose evaluation, including scientific integrity, methodological validity, reproducibility, and boundary safety. This study developed and preliminarily evaluated a domain-specific audit framework for medical research agent skills, with a focus on reliability against expert review. Methods: We developed MedSkillAudit (skill-auditor@1.0), a layered framework assessing skill release readiness before deployment. We evaluated 75 skills across five medical research categories (15 per category). Two experts independently assigned a quality score (0-100), an ordinal release disposition (Production Ready / Limited Release / Beta Only / Reject), and a high-risk failure flag. System-expert agreement was quantified using ICC(2,1) and linearly weighted Cohen's kappa, benchmarked against the human inter-rater baseline. Results: The mean consensus quality score was 72.4 (SD = 13.0); 57.3% of skills fell below the Limited Release threshold. MedSkillAudit achieved ICC(2,1) = 0.449 (95% CI: 0.250-0.610), exceeding the human inter-rater ICC of 0.300. System-consensus score divergence (SD = 9.5) was smaller than inter-expert divergence (SD = 12.4), with no directional bias (Wilcoxon p = 0.613). Protocol Design showed the strongest category-level agreement (ICC = 0.551); Academic Writing showed a negative ICC (-0.567), reflecting a structural rubric-expert mismatch. Conclusions: Domain-specific pre-deployment audit may provide a practical foundation for governing medical research agent skills, complementing general-purpose quality checks with structured audit workflows tailored to scientific use cases.

Medical coding translates clinical documentation into standardized codes for billing, research, and public health, but manual coding is time-consuming and error-prone. Existing automation efforts rely on small datasets that poorly represent real-world patient heterogeneity. We trained a language model on 5.8 million electronic health records from 1.8 million patients across nearly all specialties in Eastern Denmark (2006--2016) to predict ICD-10 codes from clinical notes, medications, and laboratory results. Evaluated on 270,000 held-out patients, the model achieved a micro F1 of 71.8% and a top-10 recall of 95.5%. Performance varied by specialty (F1: 53--91%), with higher scores in specialties with well-defined diagnostic criteria. Codes appearing predominantly as secondary diagnoses had markedly lower F1 scores. For three such codes (suicide-related behaviors, weight disorders, and hypertension), the model identified thousands of uncoded cases, of which 76-86% were confirmed valid upon manual review, suggesting systematic under-coding rather than model error. These findings suggest under-coding of secondary diagnoses in Eastern Denmark during this period, with potential implications for epidemiological research, public health surveillance, and understanding of multimorbidity. Similar time constraints and reimbursement structures in other healthcare systems suggest this may not be isolated to this dataset. The model can automate coding for approximately 50% of cases and provide accurate suggestions for most others, and may offer a practical solution to help capture missed secondary conditions.

Radiology report evaluation is essential for advancing automated report generation. Natural language generation metrics have limited clinical relevance. Clinical efficacy (CE) metrics evaluate important medical findings, but focus mainly on presence and cover only a limited set of entities. Due to heavy reliance on manual annotations, it is difficult for CE metrics to extend clinical entities or attributes. In clinical practice, radiology reports serve as a medium for information transfer. Clinicians use them to perform downstream diagnostic tasks without directly inspecting images. Based on this insight, we propose ReportQA, a clinical-related and flexible radiology report evaluation framework, supporting detailed quantitative analysis of radiology report generation systems. We first collect datasets covering multiple imaging modalities and anatomical regions. We then construct knowledge trees of clinical entities and attributes with radiologist guidance, and use large language models (LLMs) to extract structured information from raw reports. Next, we generate QA pairs from predefined templates and apply quality control through self-filtering and report-based filtering. During evaluation, the report is treated as context, and an LLM acts as a judge model to answer the QA pairs. Based on the resulting QA accuracy, we introduce QAScore metric. Compared with existing metrics, QAScore shows better alignment with radiologist judgments. Experiments on multiple state-of-the-art vision-language models reveal that current report-based inference paradigms struggle to learn fine-grained clinical representations and exhibit strong negative prior biases. In contrast, question-driven inference provides a more effective alternative. For reproducibility and extensibility, we release the knowledge trees, structured reports, and QA pairs, along with the pipeline code for QA construction and evaluation.

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

With the emergence of large-scale vision language models (VLM), it is now possible to produce realistic-looking radiology reports for chest X-ray images. However, their clinical translation has been hampered by the factual errors and hallucinations in the produced descriptions during inference. In this paper, we present a novel phrase-grounded fact-checking model (FC model) that detects errors in findings and their indicated locations in automatically generated chest radiology reports. Specifically, we simulate the errors in reports through a large synthetic dataset derived by perturbing findings and their locations in ground truth reports to form real and fake findings-location pairs with images. A new multi-label cross-modal contrastive regression network is then trained on this dataset. We present results demonstrating the robustness of our method in terms of accuracy of finding veracity prediction and localization on multiple X-ray datasets. We also show its effectiveness for error detection in reports of SOTA report generators on multiple datasets achieving a concordance correlation coefficient of 0.997 with ground truth-based verification, thus pointing to its utility during clinical inference in radiology workflows.

Quantitative tools are increasingly appealing for decision support in healthcare, driven by the growing capabilities of advanced AI systems. However, understanding the predictive uncertainties surrounding a tool's output is crucial for decision-makers to ensure reliable and transparent decisions. In this paper, we present a case study on pulmonary nodule detection for lung cancer screening, enhancing an advanced detection model with an uncertainty quantification technique called conformal risk control (CRC). We demonstrate that prediction sets with conformal guarantees are attractive measures of predictive uncertainty in the safety-critical healthcare domain, allowing end-users to achieve arbitrary validity by trading off false positives and providing formal statistical guarantees on model performance. Among ground-truth nodules annotated by at least three radiologists, our model achieves a sensitivity that is competitive with that generally achieved by individual radiologists, with a slight increase in false positives. Furthermore, we illustrate the risks of using off-the-shelve prediction models when faced with ontological uncertainty, such as when radiologists disagree on what constitutes the ground truth on pulmonary nodules.

Neural networks have shown remarkable performance in computer vision, but their deployment in numerous scientific and technical fields is challenging due to their black-box nature. Scientists and practitioners need to evaluate the reliability of a decision, i.e., to know simultaneously if a model relies on the relevant features and whether these features are robust to image corruptions. Existing attribution methods aim to provide human-understandable explanations by highlighting important regions in the image domain, but fail to fully characterize a decision process's reliability. To bridge this gap, we introduce the Wavelet sCale Attribution Method (WCAM), a generalization of attribution from the pixel domain to the space-scale domain using wavelet transforms. Attribution in the wavelet domain reveals where {\it and} on what scales the model focuses, thus enabling us to assess whether a decision is reliable.

We develop an algorithm which exceeds the performance of board certified cardiologists in detecting a wide range of heart arrhythmias from electrocardiograms recorded with a single-lead wearable monitor. We build a dataset with more than 500 times the number of unique patients than previously studied corpora. On this dataset, we train a 34-layer convolutional neural network which maps a sequence of ECG samples to a sequence of rhythm classes. Committees of board-certified cardiologists annotate a gold standard test set on which we compare the performance of our model to that of 6 other individual cardiologists. We exceed the average cardiologist performance in both recall (sensitivity) and precision (positive predictive value).

Chest X-ray (CXR) radiology report generation (RRG) models have shown rapid progress, yet their clinical utility remains uncertain due to limited evaluation by radiologists. We present CXRMate-2, a state-of-the-art CXR RRG model that integrates structured multimodal conditioning and reinforcement learning with a composite reward for semantic alignment with radiologist reports. Across the MIMIC-CXR, CheXpert Plus, and ReXgradient datasets, CXRMate-2 achieves statistically significant improvements over strong benchmarks, including gains of 11.2% and 24.4% in GREEN and RadGraph-XL, respectively, on MIMIC-CXR relative to MedGemma 1.5 (4B). To directly compare CXRMate-2 against radiologist reporting, we conduct a blinded, randomised qualitative retrospective evaluation. Three consultant radiologists compare generated and radiologist reports across 120 studies from the MIMIC-CXR test set. Generated reports were deemed acceptable (defined as preferred or rated equally to radiologist reports) in 45% of ratings, with no statistically significant difference in preference rates between radiologist reports and acceptable generated reports for seven of the eight analysed findings. Preference for radiologist reports was driven primarily by higher recall, while generated reports were often preferred for readability. Together, these results suggest a credible pathway to clinically acceptable CXR RRG. Improvements in recall, alongside better detection of subtle findings (e.g., pulmonary congestion), are likely sufficient to achieve non-inferiority to radiologist reporting. With these targeted advances, CXR RRG systems may be ready for prospective evaluation in assistive roles within radiologist-led workflows.

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

This study investigates GPT-4's assessment of its performance in healthcare applications. A simple prompting technique was used to prompt the LLM with questions taken from the United States Medical Licensing Examination (USMLE) questionnaire and it was tasked to evaluate its confidence score before posing the question and after asking the question. The questionnaire was categorized into two groups-questions with feedback (WF) and questions with no feedback(NF) post-question. The model was asked to provide absolute and relative confidence scores before and after each question. The experimental findings were analyzed using statistical tools to study the variability of confidence in WF and NF groups. Additionally, a sequential analysis was conducted to observe the performance variation for the WF and NF groups. Results indicate that feedback influences relative confidence but doesn't consistently increase or decrease it. Understanding the performance of LLM is paramount in exploring its utility in sensitive areas like healthcare. This study contributes to the ongoing discourse on the reliability of AI, particularly of LLMs like GPT-4, within healthcare, offering insights into how feedback mechanisms might be optimized to enhance AI-assisted medical education and decision support.

Providing high quality explanations for AI predictions based on machine learning is a challenging and complex task. To work well it requires, among other factors: selecting a proper level of generality/specificity of the explanation; considering assumptions about the familiarity of the explanation beneficiary with the AI task under consideration; referring to specific elements that have contributed to the decision; making use of additional knowledge (e.g. expert evidence) which might not be part of the prediction process; and providing evidence supporting negative hypothesis. Finally, the system needs to formulate the explanation in a clearly interpretable, and possibly convincing, way. Given these considerations, ANTIDOTE fosters an integrated vision of explainable AI, where low-level characteristics of the deep learning process are combined with higher level schemes proper of the human argumentation capacity. ANTIDOTE will exploit cross-disciplinary competences in deep learning and argumentation to support a broader and innovative view of explainable AI, where the need for high-quality explanations for clinical cases deliberation is critical. As a first result of the project, we publish the Antidote CasiMedicos dataset to facilitate research on explainable AI in general, and argumentation in the medical domain in particular.

Lung cancer is the deadliest type of cancer worldwide and late detection is the major factor for the low survival rate of patients. Low dose computed tomography has been suggested as a potential screening tool but manual screening is costly, time-consuming and prone to variability. This has fueled the development of automatic methods for the detection, segmentation and characterisation of pulmonary nodules but its application to clinical routine is challenging. In this study, a new database for the development and testing of pulmonary nodule computer-aided strategies is presented which intends to complement current databases by giving additional focus to radiologist variability and local clinical reality. State-of-the-art nodule detection, segmentation and characterization methods are tested and compared to manual annotations as well as collaborative strategies combining multiple radiologists and radiologists and computer-aided systems. It is shown that state-of-the-art methodologies can determine a patient's follow-up recommendation as accurately as a radiologist, though the nodule detection method used shows decreased performance in this database.

Motion artefacts in magnetic resonance brain images can have a strong impact on diagnostic confidence. The assessment of MR image quality is fundamental before proceeding with the clinical diagnosis. Motion artefacts can alter the delineation of structures such as the brain, lesions or tumours and may require a repeat scan. Otherwise, an inaccurate (e.g. correct pathology but wrong severity) or incorrect diagnosis (e.g. wrong pathology) may occur. "Image quality assessment" as a fast, automated step right after scanning can assist in deciding if the acquired images are diagnostically sufficient. An automated image quality assessment based on the structural similarity index (SSIM) regression through a residual neural network is proposed in this work. Additionally, a classification into different groups - by subdividing with SSIM ranges - is evaluated. Importantly, this method predicts SSIM values of an input image in the absence of a reference ground truth image. The networks were able to detect motion artefacts, and the best performance for the regression and classification task has always been achieved with ResNet-18 with contrast augmentation. The mean and standard deviation of residuals' distribution were mu=-0.0009 and sigma=0.0139, respectively. Whilst for the classification task in 3, 5 and 10 classes, the best accuracies were 97, 95 and 89\%, respectively. The results show that the proposed method could be a tool for supporting neuro-radiologists and radiographers in evaluating image quality quickly.

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.

Qualitative research faces a critical reliability challenge: traditional inter-rater agreement methods require multiple human coders, are time-intensive, and often yield moderate consistency. We present a multi-perspective validation framework for LLM-based thematic analysis that combines ensemble validation with dual reliability metrics: Cohen's Kappa (κ) for inter-rater agreement and cosine similarity for semantic consistency. Our framework enables configurable analysis parameters (1-6 seeds, temperature 0.0-2.0), supports custom prompt structures with variable substitution, and provides consensus theme extraction across any JSON format. As proof-of-concept, we evaluate three leading LLMs (Gemini 2.5 Pro, GPT-4o, Claude 3.5 Sonnet) on a psychedelic art therapy interview transcript, conducting six independent runs per model. Results demonstrate Gemini achieves highest reliability (κ= 0.907, cosine=95.3%), followed by GPT-4o (κ= 0.853, cosine=92.6%) and Claude (κ= 0.842, cosine=92.1%). All three models achieve a high agreement (κ> 0.80), validating the multi-run ensemble approach. The framework successfully extracts consensus themes across runs, with Gemini identifying 6 consensus themes (50-83% consistency), GPT-4o identifying 5 themes, and Claude 4 themes. Our open-source implementation provides researchers with transparent reliability metrics, flexible configuration, and structure-agnostic consensus extraction, establishing methodological foundations for reliable AI-assisted qualitative research.

Users increasingly rely on Large Language Models (LLMs) for Deep Research, using them to synthesize diverse sources into structured reports that support understanding and action. In this context, the practical reliability of such reports hinges on logical quality: whether the report's claims and arguments are explicitly supported and can be trusted as a basis for downstream use, rather than merely appearing fluent or informative. However, current evaluation frameworks largely overlook this requirement. To bridge this gap, we introduce ReportLogic, a benchmark that quantifies report-level logical quality through a reader-centric lens of auditability. Specifically, ReportLogic adopts a hierarchical taxonomy that evaluates whether readers can (1) trace an on-topic report structure with a unified analytical arc (Macro-Logic), (2) understand the progression with necessary context (Expositional-Logic), and (3) verify conclusions via explicit claim--support (Structural-Logic). Based on this taxonomy, we construct a human-annotated rubric-guided dataset and train an open-source LogicJudge for scalable evaluation. We further evaluate judge robustness via adversarial attacks, showing that off-the-shelf LLM judges are frequently influenced by superficial cues (e.g., verbosity), and reasoning modes can mask broken support relations. Overall, our results provide actionable guidance for building more robust logic evaluators and improving the logical reliability of LLM-generated reports.

LLM confidence signals are used for abstention, routing, and safety-critical decisions. No standard practice exists for checking whether a confidence signal carries item-level information before building on it. We transfer the validity screening principle from clinical personality assessment (PAI, MMPI-3) as a portable protocol for benchmark-based LLM confidence data. The protocol specifies three core indices (L, Fp, RBS), a structural indicator (TRIN), and an item-sensitivity statistic, computed from a single 2x2 contingency table. A three-tier classification system (Invalid, Indeterminate, Valid) draws on four clinical traditions. Validated on 20 frontier LLMs across 524 items, four models are classified Invalid, two Indeterminate. Valid-profile models show mean r = .18 (15/16 significant). Invalid-profile models show mean r = -.20 (d = 2.48). Cross-benchmark validation on 18 models using MMLU with verbalized confidence and on external data from Yang et al. (2024) confirms the screen transfers across benchmarks and probe formats. All data and code: https://github.com/synthiumjp/validity-scaling-llm

Sycophancy in LLMs is documented across 70+ papers, but expert agreement on construct boundaries remains low (ICC=.184; Ye et al., 2026). The construct fragments because behavioral classification depends on which surface form is privileged. We adopt a materials-science framing: conversation as test specimen under load, LLM-model as material charge, pushback as progressive load, stance-flip as material failure. We characterize this failure across three loading cases (debate n=1000; false-presuppositions n=3400; ethical-setting n=3400; 10-17 material charges per case; 7800 specimens total) using 14 turn-level axis-measurements spanning velocity, damage accumulation, frame-drift, brittleness, and direction stability, plus three speaker-resolved axes from an independent pipeline. The measurements are Hooke-coupled (σ= E cdot varepsilon analog) and reproduce across loading cases with effects up to |r_{rb}| = 0.35 on debate; the sign structure adds a second pattern: the ethical-setting case inverts the velocity and accumulation blocks. Variance composition partitions into two profiles: debate is charge-dominated (brittle-fracture-like: the material grade decides), false-presuppositions and ethical-setting are topic-dominated (creep-like: the load decides); the ratios (2.03 vs 0.13/0.17) are estimator-dependent, for debate even in direction. Cross-judge reliability (GPT-4o vs Haiku 4.5) shows debate scoring is judge-robust (Cohen's κ= 0.88) while false-presupposition scoring is judge-sensitive (κ= 0.36) -- a caveat single-judge benchmarks must report. This is the methodological move Ye et al.'s diagnosis calls for: a multi-axis characterization that does not depend on which surface form of the construct one privileges.

Rare diseases affect hundreds of millions worldwide, yet diagnosis often spans years. Convectional pipelines decouple noisy evidence extraction from downstream inferential diagnosis, and general/medical large language models (LLMs) face scarce real world electronic health records (EHRs), stale domain knowledge, and hallucinations. We assemble a large, domain specialized clinical corpus and a clinician validated reasoning set, and develop RareSeek R1 via staged instruction tuning, chain of thought learning, and graph grounded retrieval. Across multicenter EHR narratives and public benchmarks, RareSeek R1 attains state of the art accuracy, robust generalization, and stability under noisy or overlapping phenotypes. Augmented retrieval yields the largest gains when narratives pair with prioritized variants by resolving ambiguity and aligning candidates to mechanisms. Human studies show performance on par with experienced physicians and consistent gains in assistive use. Notably, transparent reasoning highlights decisive non phenotypic evidence (median 23.1%, such as imaging, interventions, functional tests) underpinning many correct diagnoses. This work advances a narrative first, knowledge integrated reasoning paradigm that shortens the diagnostic odyssey and enables auditable, clinically translatable decision support.

Chest X-Ray (CXR) report generation is a promising approach to improving the efficiency of CXR interpretation. However, a significant increase in diagnostic accuracy is required before that can be realised. Motivated by this, we propose a framework that is more inline with a radiologist's workflow by considering longitudinal data. Here, the decoder is additionally conditioned on the report from the subject's previous imaging study via a prompt. We also propose a new reward for reinforcement learning based on CXR-BERT, which computes the similarity between reports. We conduct experiments on the MIMIC-CXR dataset. The results indicate that longitudinal data improves CXR report generation. CXR-BERT is also shown to be a promising alternative to the current state-of-the-art reward based on RadGraph. This investigation indicates that longitudinal CXR report generation can offer a substantial increase in diagnostic accuracy. Our Hugging Face model is available at: https://huggingface.co/aehrc/cxrmate and code is available at: https://github.com/aehrc/cxrmate.

Introduction: Electronic health records (EHR) are a critical medium through which patient stigmatization is perpetuated among healthcare teams. Methods: We identified linguistic features of doubt markers and stigmatizing labels in MIMIC-III EHR via expanded lexicon matching and supervised learning classifiers. Predictors of rates of linguistic features were assessed using Poisson regression models. Results: We found higher rates of stigmatizing labels per chart among patients who were Black or African American (RR: 1.16), patients with Medicare/Medicaid or government-run insurance (RR: 2.46), self-pay (RR: 2.12), and patients with a variety of stigmatizing disease and mental health conditions. Patterns among doubt markers were similar, though male patients had higher rates of doubt markers (RR: 1.25). We found increased stigmatizing labels used by nurses (RR: 1.40), and social workers (RR: 2.25), with similar patterns of doubt markers. Discussion: Stigmatizing language occurred at higher rates among historically stigmatized patients, perpetuated by multiple provider types.

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

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

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."

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.

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.

Knowledge Graph (KG) plays a crucial role in Medical Report Generation (MRG) because it reveals the relations among diseases and thus can be utilized to guide the generation process. However, constructing a comprehensive KG is labor-intensive and its applications on the MRG process are under-explored. In this study, we establish a complete KG on chest X-ray imaging that includes 137 types of diseases and abnormalities. Based on this KG, we find that the current MRG data sets exhibit a long-tailed problem in disease distribution. To mitigate this problem, we introduce a novel augmentation strategy that enhances the representation of disease types in the tail-end of the distribution. We further design a two-stage MRG approach, where a classifier is first trained to detect whether the input images exhibit any abnormalities. The classified images are then independently fed into two transformer-based generators, namely, ``disease-specific generator" and ``disease-free generator" to generate the corresponding reports. To enhance the clinical evaluation of whether the generated reports correctly describe the diseases appearing in the input image, we propose diverse sensitivity (DS), a new metric that checks whether generated diseases match ground truth and measures the diversity of all generated diseases. Results show that the proposed two-stage generation framework and augmentation strategies improve DS by a considerable margin, indicating a notable reduction in the long-tailed problem associated with under-represented diseases.

As LLM-powered agents have been used for high-stakes decision-making, such as clinical diagnosis, it becomes critical to develop reliable verification of their decisions to facilitate trustworthy deployment. Yet, existing verifiers usually underperform owing to a lack of domain knowledge and limited calibration. To address this, we establish GLEAN, an agent verification framework with Guideline-grounded Evidence Accumulation that compiles expert-curated protocols into trajectory-informed, well-calibrated correctness signals. GLEAN evaluates the step-wise alignment with domain guidelines and aggregates multi-guideline ratings into surrogate features, which are accumulated along the trajectory and calibrated into correctness probabilities using Bayesian logistic regression. Moreover, the estimated uncertainty triggers active verification, which selectively collects additional evidence for uncertain cases via expanding guideline coverage and performing differential checks. We empirically validate GLEAN with agentic clinical diagnosis across three diseases from the MIMIC-IV dataset, surpassing the best baseline by 12% in AUROC and 50% in Brier score reduction, which confirms the effectiveness in both discrimination and calibration. In addition, the expert study with clinicians recognizes GLEAN's utility in practice.

Given a black-box AI system and a task, at what confidence level can a practitioner trust the system's output? We answer with a reliability level -- a single number per system-task pair, derived from self-consistency sampling and conformal calibration, that serves as a black-box deployment gate with exact, finite-sample, distribution-free guarantees. Self-consistency sampling reduces uncertainty exponentially; conformal calibration guarantees correctness within 1/(n+1) of the target level, regardless of the system's errors -- made transparently visible through larger answer sets for harder questions. Weaker models earn lower reliability levels (not accuracy -- see Definition 2.4): GPT-4.1 earns 94.6% on GSM8K and 96.8% on TruthfulQA, while GPT-4.1-nano earns 89.8% on GSM8K and 66.5% on MMLU. We validate across five benchmarks, five models from three families, and both synthetic and real data. Conditional coverage on solvable items exceeds 0.93 across all configurations; sequential stopping reduces API costs by around 50%.

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.

Commonly used evaluation measures including Recall, Precision, F-Measure and Rand Accuracy are biased and should not be used without clear understanding of the biases, and corresponding identification of chance or base case levels of the statistic. Using these measures a system that performs worse in the objective sense of Informedness, can appear to perform better under any of these commonly used measures. We discuss several concepts and measures that reflect the probability that prediction is informed versus chance. Informedness and introduce Markedness as a dual measure for the probability that prediction is marked versus chance. Finally we demonstrate elegant connections between the concepts of Informedness, Markedness, Correlation and Significance as well as their intuitive relationships with Recall and Precision, and outline the extension from the dichotomous case to the general multi-class case.

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

Rationale: Computer aided detection (CAD) algorithms for Pulmonary Embolism (PE) algorithms have been shown to increase radiologists' sensitivity with a small increase in specificity. However, CAD for PE has not been adopted into clinical practice, likely because of the high number of false positives current CAD software produces. Objective: To generate a database of annotated computed tomography pulmonary angiographies, use it to compare the sensitivity and false positive rate of current algorithms and to develop new methods that improve such metrics. Methods: 91 Computed tomography pulmonary angiography scans were annotated by at least one radiologist by segmenting all pulmonary emboli visible on the study. 20 annotated CTPAs were open to the public in the form of a medical image analysis challenge. 20 more were kept for evaluation purposes. 51 were made available post-challenge. 8 submissions, 6 of them novel, were evaluated on the 20 evaluation CTPAs. Performance was measured as per embolus sensitivity vs. false positives per scan curve. Results: The best algorithms achieved a per-embolus sensitivity of 75% at 2 false positives per scan (fps) or of 70% at 1 fps, outperforming the state of the art. Deep learning approaches outperformed traditional machine learning ones, and their performance improved with the number of training cases. Significance: Through this work and challenge we have improved the state-of-the art of computer aided detection algorithms for pulmonary embolism. An open database and an evaluation benchmark for such algorithms have been generated, easing the development of further improvements. Implications on clinical practice will need further research.

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

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.

While Large Language Models (LLMs) can generate fluent and convincing responses, they are not necessarily correct. This is especially apparent in the popular decompose-then-verify factuality evaluation pipeline, where LLMs evaluate generations by decomposing the generations into individual, valid claims. Factuality evaluation is especially important for medical answers, since incorrect medical information could seriously harm the patient. However, existing factuality systems are a poor match for the medical domain, as they are typically only evaluated on objective, entity-centric, formulaic texts such as biographies and historical topics. This differs from condition-dependent, conversational, hypothetical, sentence-structure diverse, and subjective medical answers, which makes decomposition into valid facts challenging. We propose MedScore, a new pipeline to decompose medical answers into condition-aware valid facts and verify against in-domain corpora. Our method extracts up to three times more valid facts than existing methods, reducing hallucination and vague references, and retaining condition-dependency in facts. The resulting factuality score substantially varies by decomposition method, verification corpus, and used backbone LLM, highlighting the importance of customizing each step for reliable factuality evaluation by using our generalizable and modularized pipeline for domain adaptation.

Handwritten STEM exams capture open-ended reasoning and diagrams, but manual grading is slow and difficult to scale. We present an end-to-end workflow for grading scanned handwritten engineering quizzes with multimodal large language models (LLMs) that preserves the standard exam process (A4 paper, unconstrained student handwriting). The lecturer provides only a handwritten reference solution (100%) and a short set of grading rules; the reference is converted into a text-only summary that conditions grading without exposing the reference scan. Reliability is achieved through a multi-stage design with a format/presence check to prevent grading blank answers, an ensemble of independent graders, supervisor aggregation, and rigid templates with deterministic validation to produce auditable, machine-parseable reports. We evaluate the frozen pipeline in a clean-room protocol on a held-out real course quiz in Slovenian, including hand-drawn circuit schematics. With state-of-the-art backends (GPT-5.2 and Gemini-3 Pro), the full pipeline achieves approx8-point mean absolute difference to lecturer grades with low bias and an estimated manual-review trigger rate of approx17% at D_{max}=40. Ablations show that trivial prompting and removing the reference solution substantially degrade accuracy and introduce systematic over-grading, confirming that structured prompting and reference grounding are essential.

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.

Reliable epidemiological reasoning requires synthesizing study evidence to infer disease burden, transmission dynamics, and intervention effects at the population level. Existing medical question answering benchmarks primarily emphasize clinical knowledge or patient-level reasoning, yet few systematically evaluate evidence-grounded epidemiological inference. We present EpiQAL, the first diagnostic benchmark for epidemiological question answering across diverse diseases, comprising three subsets built from open-access literature. The subsets respectively evaluate text-grounded factual recall, multi-step inference linking document evidence with epidemiological principles, and conclusion reconstruction with the Discussion section withheld. Construction combines expert-designed taxonomy guidance, multi-model verification, and retrieval-based difficulty control. Experiments on ten open models reveal that current LLMs show limited performance on epidemiological reasoning, with multi-step inference posing the greatest challenge. Model rankings shift across subsets, and scale alone does not predict success. Chain-of-Thought prompting benefits multi-step inference but yields mixed results elsewhere. EpiQAL provides fine-grained diagnostic signals for evidence grounding, inferential reasoning, and conclusion reconstruction.

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

Radiological imaging is central to diagnosis, treatment planning, and clinical decision-making. Vision-language foundation models have spurred interest in automated radiology report generation (RRG), but safe deployment requires reliable clinical evaluation of generated reports. Existing metrics often rely on surface-level similarity or behave as black boxes, lacking interpretability. We introduce ICARE (Interpretable and Clinically-grounded Agent-based Report Evaluation), an interpretable evaluation framework leveraging large language model agents and dynamic multiple-choice question answering (MCQA). Two agents, each with either the ground-truth or generated report, generate clinically meaningful questions and quiz each other. Agreement on answers captures preservation and consistency of findings, serving as interpretable proxies for clinical precision and recall. By linking scores to question-answer pairs, ICARE enables transparent, and interpretable assessment. Clinician studies show ICARE aligns significantly more with expert judgment than prior metrics. Perturbation analyses confirm sensitivity to clinical content and reproducibility, while model comparisons reveal interpretable error patterns.

Specialized clinical AI assistants are rapidly entering medical practice, often framed as safer or more reliable than general-purpose large language models (LLMs). Yet, unlike frontier models, these clinical tools are rarely subjected to independent, quantitative evaluation, creating a critical evidence gap despite their growing influence on diagnosis, triage, and guideline interpretation. We assessed two widely deployed clinical AI systems (OpenEvidence and UpToDate Expert AI) against three state-of-the-art generalist LLMs (GPT-5, Gemini 3 Pro, and Claude Sonnet 4.5) using a 1,000-item mini-benchmark combining MedQA (medical knowledge) and HealthBench (clinician-alignment) tasks. Generalist models consistently outperformed clinical tools, with GPT-5 achieving the highest scores, while OpenEvidence and UpToDate demonstrated deficits in completeness, communication quality, context awareness, and systems-based safety reasoning. These findings reveal that tools marketed for clinical decision support may often lag behind frontier LLMs, underscoring the urgent need for transparent, independent evaluation before deployment in patient-facing workflows.

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.

Objective: Question answering (QA) systems have the potential to improve the quality of clinical care by providing health professionals with the latest and most relevant evidence. However, QA systems have not been widely adopted. This systematic review aims to characterize current medical QA systems, assess their suitability for healthcare, and identify areas of improvement. Materials and methods: We searched PubMed, IEEE Xplore, ACM Digital Library, ACL Anthology and forward and backward citations on 7th February 2023. We included peer-reviewed journal and conference papers describing the design and evaluation of biomedical QA systems. Two reviewers screened titles, abstracts, and full-text articles. We conducted a narrative synthesis and risk of bias assessment for each study. We assessed the utility of biomedical QA systems. Results: We included 79 studies and identified themes, including question realism, answer reliability, answer utility, clinical specialism, systems, usability, and evaluation methods. Clinicians' questions used to train and evaluate QA systems were restricted to certain sources, types and complexity levels. No system communicated confidence levels in the answers or sources. Many studies suffered from high risks of bias and applicability concerns. Only 8 studies completely satisfied any criterion for clinical utility, and only 7 reported user evaluations. Most systems were built with limited input from clinicians. Discussion: While machine learning methods have led to increased accuracy, most studies imperfectly reflected real-world healthcare information needs. Key research priorities include developing more realistic healthcare QA datasets and considering the reliability of answer sources, rather than merely focusing on accuracy.

Ensuring the quality and integrity of medical images is crucial for maintaining diagnostic accuracy in deep learning-based Computer-Aided Diagnosis and Computer-Aided Detection (CAD) systems. Covariate shifts are subtle variations in the data distribution caused by different imaging devices or settings and can severely degrade model performance, similar to the effects of adversarial attacks. Therefore, it is vital to have a lightweight and fast method to assess the quality of these images prior to using CAD models. AdverX-Ray addresses this need by serving as an image-quality assessment layer, designed to detect covariate shifts effectively. This Adversarial Variational Autoencoder prioritizes the discriminator's role, using the suboptimal outputs of the generator as negative samples to fine-tune the discriminator's ability to identify high-frequency artifacts. Images generated by adversarial networks often exhibit severe high-frequency artifacts, guiding the discriminator to focus excessively on these components. This makes the discriminator ideal for this approach. Trained on patches from X-ray images of specific machine models, AdverX-Ray can evaluate whether a scan matches the training distribution, or if a scan from the same machine is captured under different settings. Extensive comparisons with various OOD detection methods show that AdverX-Ray significantly outperforms existing techniques, achieving a 96.2% average AUROC using only 64 random patches from an X-ray. Its lightweight and fast architecture makes it suitable for real-time applications, enhancing the reliability of medical imaging systems. The code and pretrained models are publicly available.

In the age of open and free information, a concerning trend of reliance on AI is emerging. However, existing AI tools struggle to evaluate the credibility of information and to justify their assessments. Hence, there is a growing need for systems that can help users evaluate the trustworthiness of online information. Although major search engines incorporate AI features, they often lack clear reliability indicators. We present TrueGL, a model that makes trustworthy search results more accessible. The model is a fine-tuned version of IBM's Granite-1B, trained on the custom dataset and integrated into a search engine with a reliability scoring system. We evaluate the system using prompt engineering and assigning each statement a continuous reliability score from 0.1 to 1, then instructing the model to return a textual explanation alongside the score. Each model's predicted scores are measured against real scores using standard evaluation metrics. TrueGL consistently outperforms other small-scale LLMs and rule-based approaches across all experiments on key evaluation metrics, including MAE, RMSE, and R2. The model's high accuracy, broad content coverage, and ease of use make trustworthy information more accessible and help reduce the spread of false or misleading content online. Our code is publicly available at https://github.com/AlgazinovAleksandr/TrueGL, and our model is publicly released at https://huggingface.co/JoydeepC/trueGL.

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

Integrating large language models (LLMs) like DeepSeek R1 into healthcare requires rigorous evaluation of their reasoning alignment with clinical expertise. This study assesses DeepSeek R1's medical reasoning against expert patterns using 100 MedQA clinical cases. The model achieved 93% diagnostic accuracy, demonstrating systematic clinical judgment through differential diagnosis, guideline-based treatment selection, and integration of patient-specific factors. However, error analysis of seven incorrect cases revealed persistent limitations: anchoring bias, challenges reconciling conflicting data, insufficient exploration of alternatives, overthinking, knowledge gaps, and premature prioritization of definitive treatment over intermediate care. Crucially, reasoning length correlated with accuracy - shorter responses (<5,000 characters) were more reliable, suggesting extended explanations may signal uncertainty or rationalization of errors. While DeepSeek R1 exhibits foundational clinical reasoning capabilities, recurring flaws highlight critical areas for refinement, including bias mitigation, knowledge updates, and structured reasoning frameworks. These findings underscore LLMs' potential to augment medical decision-making through artificial reasoning but emphasize the need for domain-specific validation, interpretability safeguards, and confidence metrics (e.g., response length thresholds) to ensure reliability in real-world applications.

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.

We develop and evaluate a data-driven approach for detecting unusual (anomalous) patient-management actions using past patient cases stored in an electronic health record (EHR) system. Our hypothesis is that patient-management actions that are unusual with respect to past patients may be due to a potential error and that it is worthwhile to raise an alert if such a condition is encountered. We evaluate this hypothesis using data obtained from the electronic health records of 4,486 post-cardiac surgical patients. We base the evaluation on the opinions of a panel of experts. The results support that anomaly-based alerting can have reasonably low false alert rates and that stronger anomalies are correlated with higher alert rates.

We present VinDr-CXR-VQA, a large-scale chest X-ray dataset for explainable Medical Visual Question Answering (Med-VQA) with spatial grounding. The dataset contains 17,597 question-answer pairs across 4,394 images, each annotated with radiologist-verified bounding boxes and clinical reasoning explanations. Our question taxonomy spans six diagnostic types-Where, What, Is there, How many, Which, and Yes/No-capturing diverse clinical intents. To improve reliability, we construct a balanced distribution of 41.7% positive and 58.3% negative samples, mitigating hallucinations in normal cases. Benchmarking with MedGemma-4B-it demonstrates improved performance (F1 = 0.624, +11.8% over baseline) while enabling lesion localization. VinDr-CXR-VQA aims to advance reproducible and clinically grounded Med-VQA research. The dataset and evaluation tools are publicly available at huggingface.co/datasets/Dangindev/VinDR-CXR-VQA.

Rubric-based evaluation is widely used in LLM benchmarks and training pipelines for open-ended, less verifiable tasks. While prior work has demonstrated the effectiveness of rubrics using downstream signals such as reinforcement learning outcomes, there remains no principled way to diagnose how a rubric itself fails from such aggregated or downstream signals alone. To address this gap, we introduce RIFT: RubrIc Failure mode Taxonomy, a taxonomy for systematically characterizing failure modes in rubric composition and design. RIFT consists of eight failure modes organized into three high-level categories: Reliability Failures, Content Validity Failures, and Consequential Validity Failures. RIFT is developed using grounded theory by iteratively annotating rubrics drawn from five diverse data sources spanning general instruction following, code generation, creative writing, and expert-level deep research, until no new failure modes are identified. We evaluate the consistency of the taxonomy by measuring agreement among independent human annotators, observing fair agreement overall (87% pairwise agreement and 0.64 average Cohen's kappa). Finally, to support scalable diagnosis, we propose automated rubric quality metrics and show that they align with human failure-mode annotations, achieving up to 0.925 F1.

System log anomaly detection is critical for maintaining the reliability of large-scale software systems, yet traditional methods struggle with the heterogeneous and evolving nature of modern log data. Recent advances in Large Language Models (LLMs) offer promising new approaches to log understanding, but a systematic comparison of LLM-based methods against established techniques remains lacking. In this paper, we present a comprehensive benchmark study evaluating both LLM-based and traditional approaches for log anomaly detection across four widely-used public datasets: HDFS, BGL, Thunderbird, and Spirit. We evaluate three categories of methods: (1) classical log parsers (Drain, Spell, AEL) combined with machine learning classifiers, (2) fine-tuned transformer models (BERT, RoBERTa), and (3) prompt-based LLM approaches (GPT-3.5, GPT-4, LLaMA-3) in zero-shot and few-shot settings. Our experiments reveal that while fine-tuned transformers achieve the highest F1-scores (0.96-0.99), prompt-based LLMs demonstrate remarkablezero-shot capabilities (F1: 0.82-0.91) without requiring any labeled training data -- a significant advantage for real-world deployment where labeled anomalies are scarce. We further analyze the cost-accuracy trade-offs, latency characteristics, and failure modes of each approach. Our findings provide actionable guidelines for practitioners choosing log anomaly detection methods based on their specific constraints regarding accuracy, latency, cost, and label availability. All code and experimental configurations are publicly available to facilitate reproducibility.

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.

BACKGROUND: Radiology reports are typically written in a free-text format, making clinical information difficult to extract and use. Recently the adoption of structured reporting (SR) has been recommended by various medical societies thanks to the advantages it offers, e.g. standardization, completeness and information retrieval. We propose a pipeline to extract information from free-text radiology reports, that fits with the items of the reference SR registry proposed by a national society of interventional and medical radiology, focusing on CT staging of patients with lymphoma. METHODS: Our work aims to leverage the potential of Natural Language Processing (NLP) and Transformer-based models to deal with automatic SR registry filling. With the availability of 174 radiology reports, we investigate a rule-free generative Question Answering approach based on a domain-specific version of T5 (IT5). Two strategies (batch-truncation and ex-post combination) are implemented to comply with the model's context length limitations. Performance is evaluated in terms of strict accuracy, F1, and format accuracy, and compared with the widely used GPT-3.5 Large Language Model. A 5-point Likert scale questionnaire is used to collect human-expert feedback on the similarity between medical annotations and generated answers. RESULTS: The combination of fine-tuning and batch splitting allows IT5 to achieve notable results; it performs on par with GPT-3.5 albeit its size being a thousand times smaller in terms of parameters. Human-based assessment scores show a high correlation (Spearman's correlation coefficients>0.88, p-values<0.001) with AI performance metrics (F1) and confirm the superior ability of LLMs (i.e., GPT-3.5, 175B of parameters) in generating plausible human-like statements.

Medical Imaging (MI) datasets are fundamental to artificial intelligence in healthcare. The accuracy, robustness, and fairness of diagnostic algorithms depend on the data (and its quality) used to train and evaluate the models. MI datasets used to be proprietary, but have become increasingly available to the public, including on community-contributed platforms (CCPs) like Kaggle or HuggingFace. While open data is important to enhance the redistribution of data's public value, we find that the current CCP governance model fails to uphold the quality needed and recommended practices for sharing, documenting, and evaluating datasets. In this paper, we conduct an analysis of publicly available machine learning datasets on CCPs, discussing datasets' context, and identifying limitations and gaps in the current CCP landscape. We highlight differences between MI and computer vision datasets, particularly in the potentially harmful downstream effects from poor adoption of recommended dataset management practices. We compare the analyzed datasets across several dimensions, including data sharing, data documentation, and maintenance. We find vague licenses, lack of persistent identifiers and storage, duplicates, and missing metadata, with differences between the platforms. Our research contributes to efforts in responsible data curation and AI algorithms for healthcare.

We investigate whether large language models produce different medical triage recommendations for identical neurological symptoms when only the patient's stated gender and age vary. Using three model families--Gemini 3.5 Flash, Claude Sonnet 4.6, and GPT-5.4-mini--we present a standardized symptom profile (persistent headache, blurred vision, morning nausea, visual disturbances) across seven demographic conditions: three age groups (25, 38, 65) x two genders (male, female), plus a gender-unspecified baseline (n = 30 per condition per model, 630 total trials). We find a stark, systemic gender-dependent triage disparity: young women receive significantly lower emergency room (ER) referral rates than age-matched men (Gemini: 0% vs. 23.3%; Claude: 6.7% vs. 96.7%; GPT: 6.7% vs. 66.7%, all p < 0.001). The disparity disappears at age 65 for all models. The primary mechanism is diagnostic substitution: the models anchor on a gender-associated diagnosis, preferentially classifying young women with Idiopathic Intracranial Hypertension (IIH)--a condition epidemiologically linked to women of childbearing age--while diagnosing men with generic increased intracranial pressure with space-occupying lesions in the differential. This diagnostic closure routes female patients to lower-urgency care (outpatient doctor appointments) despite comparable severity ratings (7-9/10). Our findings demonstrate that clinical LLMs replicate documented human clinical biases by using epidemiological priors to suppress triage urgency, suggesting that AI triage engines must decouple urgency assessment from probabilistic diagnostic priors. We release all code, prompts, and raw results.