Daily Papers

Vision evaluations are typically done through multi-step processes. In most contemporary fields, experts analyze images using structured, evidence-based adaptive questioning. In plant pathology, botanists inspect leaf images, identify visual cues, infer diagnostic intent, and probe further with targeted questions that adapt to species, symptoms, and severity. This structured probing is crucial for accurate disease diagnosis and treatment formulation. Yet current vision-language models are evaluated on single-turn question answering. To address this gap, we introduce PlantInquiryVQA, a benchmark for studying multi-step, intent-driven visual reasoning in botanical diagnosis. We formalize a Chain of Inquiry framework modeling diagnostic trajectories as ordered question-answer sequences conditioned on grounded visual cues and explicit epistemic intent. We release a dataset of 24,950 expert-curated plant images and 138,068 question-answer pairs annotated with visual grounding, severity labels, and domain-specific reasoning templates. Evaluations on top-tier Multimodal Large Language Models reveal that while they describe visual symptoms adequately, they struggle with safe clinical reasoning and accurate diagnosis. Importantly, structured question-guided inquiry significantly improves diagnostic correctness, reduces hallucination, and increases reasoning efficiency. We hope PlantInquiryVQA serves as a foundational benchmark in advancing research to train diagnostic agents to reason like expert botanists rather than static classifiers.

Large language model (LLM) agents offer a promising data-driven approach to automating Site Reliability Engineering (SRE), yet their enterprise deployment is constrained by three challenges: restricted access to proprietary data, unsafe action execution under permission-governed environments, and the inability of closed systems to improve from failures. We present AOI (Autonomous Operations Intelligence), a trainable multi-agent framework formulating automated operations as a structured trajectory learning problem under security constraints. Our approach integrates three key components. First, a trainable diagnostic system applies Group Relative Policy Optimization (GRPO) to distill expert-level knowledge into locally deployed open-source models, enabling preference-based learning without exposing sensitive data. Second, a read-write separated execution architecture decomposes operational trajectories into observation, reasoning, and action phases, allowing safe learning while preventing unauthorized state mutation. Third, a Failure Trajectory Closed-Loop Evolver mines unsuccessful trajectories and converts them into corrective supervision signals, enabling continual data augmentation. Evaluated on the AIOpsLab benchmark, our contributions yield cumulative gains. (1) The AOI runtime alone achieves 66.3% best@5 success on all 86 tasks, outperforming the prior state-of-the-art (41.9%) by 24.4 points. (2) Adding Observer GRPO training, a locally deployed 14B model reaches 42.9% avg@1 on 63 held-out tasks with unseen fault types, surpassing Claude Sonnet 4.5. (3) The Evolver converts 37 failed trajectories into diagnostic guidance, improving end-to-end avg@5 by 4.8 points while reducing variance by 35%.

Code agents can autonomously resolve GitHub issues, yet when they fail, current evaluation provides no visibility into where or why. Metrics such as Pass@1 collapse an entire execution into a single binary outcome, making it difficult to identify where and why the agent went wrong. To address this limitation, we introduce TRAJEVAL, a diagnostic framework that decomposes agent trajectories into three interpretable stages: search (file localization), read (function comprehension), and edit (modification targeting). For each stage, we compute precision and recall by comparing against reference patches. Analyzing 16,758 trajectories across three agent architectures and seven models, we find universal inefficiencies (all agents examine approximately 22x more functions than necessary) yet distinct failure modes: GPT-5 locates relevant code but targets edits incorrectly, while Qwen-32B fails at file discovery entirely. We validate that these diagnostics are predictive, achieving model-level Pass@1 prediction within 0.87-2.1% MAE, and actionable: real-time feedback based on trajectory signals improves two state-of-the-art models by 2.2-4.6 percentage points while reducing costs by 20-31%. These results demonstrate that our framework not only provides a more fine-grained analysis of agent behavior, but also translates diagnostic signals into tangible performance gains. More broadly, TRAJEVAL transforms agent evaluation beyond outcome-based benchmarking toward mechanism-driven diagnosis of agent success and failure.

Long-horizon GUI agents are a key step toward real-world deployment, yet effective interaction memory under prevailing paradigms remains under-explored. Replaying full interaction sequences is redundant and amplifies noise, while summaries often erase dependency-critical information and traceability. We present AndroTMem, a diagnostic framework for anchored memory in long-horizon Android GUI agents. Its core benchmark, AndroTMem-Bench, comprises 1,069 tasks with 34,473 interaction steps (avg. 32.1 per task, max. 65). We evaluate agents with TCR (Task Complete Rate), focusing on tasks whose completion requires carrying forward critical intermediate state; AndroTMem-Bench is designed to enforce strong step-to-step causal dependencies, making sparse yet essential intermediate states decisive for downstream actions and centering interaction memory in evaluation. Across open- and closed-source GUI agents, we observe a consistent pattern: as interaction sequences grow longer, performance drops are driven mainly by within-task memory failures, not isolated perception errors or local action mistakes. Guided by this diagnosis, we propose Anchored State Memory (ASM), which represents interaction sequences as a compact set of causally linked intermediate-state anchors to enable subgoal-targeted retrieval and attribution-aware decision making. Across multiple settings and 12 evaluated GUI agents, ASM consistently outperforms full-sequence replay and summary-based baselines, improving TCR by 5%-30.16% and AMS by 4.93%-24.66%, indicating that anchored, structured memory effectively mitigates the interaction-memory bottleneck in long-horizon GUI tasks. The code, benchmark, and related resources are publicly available at [https://github.com/CVC2233/AndroTMem](https://github.com/CVC2233/AndroTMem).

The rise of AI agents introduces complex safety and security challenges arising from autonomous tool use and environmental interactions. Current guardrail models lack agentic risk awareness and transparency in risk diagnosis. To introduce an agentic guardrail that covers complex and numerous risky behaviors, we first propose a unified three-dimensional taxonomy that orthogonally categorizes agentic risks by their source (where), failure mode (how), and consequence (what). Guided by this structured and hierarchical taxonomy, we introduce a new fine-grained agentic safety benchmark (ATBench) and a Diagnostic Guardrail framework for agent safety and security (AgentDoG). AgentDoG provides fine-grained and contextual monitoring across agent trajectories. More Crucially, AgentDoG can diagnose the root causes of unsafe actions and seemingly safe but unreasonable actions, offering provenance and transparency beyond binary labels to facilitate effective agent alignment. AgentDoG variants are available in three sizes (4B, 7B, and 8B parameters) across Qwen and Llama model families. Extensive experimental results demonstrate that AgentDoG achieves state-of-the-art performance in agentic safety moderation in diverse and complex interactive scenarios. All models and datasets are openly released.

AI agents often fail in ways that are difficult to localize because executions are probabilistic, long-horizon, multi-agent, and mediated by noisy tool outputs. We address this gap by manually annotating failed agent runs and release a novel benchmark of 115 failed trajectories spanning structured API workflows, incident management, and open-ended web/file tasks. Each trajectory is annotated with a critical failure step and a category from a grounded-theory derived, cross-domain failure taxonomy. To mitigate the human cost of failure attribution, we present AGENTRX, an automated domain-agnostic diagnostic framework that pinpoints the critical failure step in a failed agent trajectory. It synthesizes constraints, evaluates them step-by-step, and produces an auditable validation log of constraint violations with associated evidence; an LLM-based judge uses this log to localize the critical step and category. Our framework improves step localization and failure attribution over existing baselines across three domains.

Retrieval-Augmented Generation (RAG) extends large language models (LLMs) beyond parametric knowledge, yet it is unclear when iterative retrieval-reasoning loops meaningfully outperform static RAG, particularly in scientific domains with multi-hop reasoning, sparse domain knowledge, and heterogeneous evidence. We provide the first controlled, mechanism-level diagnostic study of whether synchronized iterative retrieval and reasoning can surpass an idealized static upper bound (Gold Context) RAG. We benchmark eleven state-of-the-art LLMs under three regimes: (i) No Context, measuring reliance on parametric memory; (ii) Gold Context, where all oracle evidence is supplied at once; and (iii) Iterative RAG, a training-free controller that alternates retrieval, hypothesis refinement, and evidence-aware stopping. Using the chemistry-focused ChemKGMultiHopQA dataset, we isolate questions requiring genuine retrieval and analyze behavior with diagnostics spanning retrieval coverage gaps, anchor-carry drop, query quality, composition fidelity, and control calibration. Across models, Iterative RAG consistently outperforms Gold Context, with gains up to 25.6 percentage points, especially for non-reasoning fine-tuned models. Staged retrieval reduces late-hop failures, mitigates context overload, and enables dynamic correction of early hypothesis drift, but remaining failure modes include incomplete hop coverage, distractor latch trajectories, early stopping miscalibration, and high composition failure rates even with perfect retrieval. Overall, staged retrieval is often more influential than the mere presence of ideal evidence; we provide practical guidance for deploying and diagnosing RAG systems in specialized scientific settings and a foundation for more reliable, controllable iterative retrieval-reasoning frameworks.

Agent skills can remarkably improve task success rates by using human-written procedural documents, but their quality is difficult to assess without environment-grounded verification. Existing skill generation methods heavily rely on preference logs rather than direct environment interaction, often yielding negligible or even degraded gains. We identify that it is a fundamental timing bottleneck: robust skills should be posterior-based, distilled from empirical environment interaction rather than prior plans. In this study, we introduce the Posterior Distillation Index (PDI), a trajectory-level metric that quantifies how well a distilled skill is grounded in the task-environment evidence. To operationalize PDI, we present SPARK (Structured Pipelines for Autonomous Runnable tasKs and sKill generation) for preserving task execution evidence towards full trajectory-level analysis. SPARK generates environment-verified trajectories used to compute PDI, and it applies PDI as an online diagnostic and intervention signal to ensure posterior skill formation. Across 86 runnable tasks, SPARK-generated skills consistently surpass no-skill baselines and outperform human-written skills on student models (inference cost up to 1,000x cheaper than teacher models). These findings show that PDI-guided distillation produces efficient and transferable skills grounded in the task-environment interaction. We release our code at https://github.com/EtaYang10th/spark-skills .

Autoregressive language models (LMs) generate one token at a time, yet human reasoning operates over higher-level abstractions - sentences, propositions, and concepts. This contrast raises a central question- Can LMs likewise learn to reason over structured semantic units rather than raw token sequences? In this work, we investigate whether pretrained LMs can be lifted into such abstract reasoning spaces by building on their learned representations. We present a framework that adapts a pretrained token-level LM to operate in sentence space by autoregressively predicting continuous embeddings of next sentences. We explore two embedding paradigms inspired by classical representation learning: 1) semantic embeddings, learned via autoencoding to preserve surface meaning; and 2) contextual embeddings, trained via next-sentence prediction to encode anticipatory structure. We evaluate both under two inference regimes: Discretized, which decodes each predicted embedding into text before re-encoding; and Continuous, which reasons entirely in embedding space for improved efficiency. Across four domains - mathematics, logic, commonsense, and planning - contextual embeddings under continuous inference show competitive performance with Chain-of-Thought (CoT) while reducing inference-time FLOPs on average by half. We also present early signs of scalability and modular adaptation. Finally, to visualize latent trajectories, we introduce SentenceLens, a diagnostic tool that decodes intermediate model states into interpretable sentences. Together, our results indicate that pretrained LMs can effectively transition to abstract, structured reasoning within latent embedding spaces.

Effective LLM training depends on predictable scaling of key quantities -- such as final loss and optimal hyperparameters -- with model and dataset size. Qiu et al. (2025) recently showed that this predictability can extend beyond scalars: whole training loss curves can *collapse* onto a universal trajectory after a simple normalization. What remains unclear is whether this phenomenon persists for LLM families trained under *practical scaling recipes*, where width, depth, learning rate, batch size, and weight decay are scaled jointly. We show that it does: loss curves collapse across scales precisely when optimization hyperparameters are set optimally for the given data budget, in accordance with recent empirical scaling laws. Collapse therefore emerges as a signature of compute-efficient training. We demonstrate two applications at scale: (1) deviation-from-collapse provides a sensitive, early diagnostic of training pathologies, and (2) predictability of collapsed curves enables early stopping in large-scale hyperparameter tuning. Finally, we train a competitive LLM family, *Celerity*, using these insights, establishing collapse as an effective tool for developing efficient LLMs.

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.

Chain-of-thought (CoT) reasoning has advanced medical visual question answering (VQA), yet most existing CoT rationales are free-form and fail to capture the structured reasoning process clinicians actually follow. This work asks: Can traceable, multi-step reasoning supervision improve reasoning accuracy and the interpretability of Medical VQA? To this end, we introduce Step-CoT, a large-scale medical reasoning dataset with expert-curated, structured multi-step CoT aligned to clinical diagnostic workflows, implicitly grounding the model's reasoning in radiographic evidence. Step-CoT comprises more than 10K real clinical cases and 70K VQA pairs organized around diagnostic workflows, providing supervised intermediate steps that guide models to follow valid reasoning trajectories. To effectively learn from Step-CoT, we further introduce a teacher-student framework with a dynamic graph-structured focusing mechanism that prioritizes diagnostically informative steps while filtering out less relevant contexts. Our experiments show that using Step-CoT can improve reasoning accuracy and interpretability. Benchmark: github.com/hahaha111111/Step-CoT. Dataset Card: huggingface.co/datasets/fl-15o/Step-CoT

Large Language Models (LLMs) are converging towards a singular Artificial Hivemind, where shared Nature (pre-training priors) result in a profound collapse of distributional diversity, limiting the distinct perspectives necessary for creative exploration and scientific discovery. To address this, we propose to equip models with inference-time Nurture (individualized epistemic trajectories) using Epistemic Evolution paradigm, progressing through explore, internalize, and express. We instantiate this via PRISM (Pluralistic Reasoning via In-context Structure Modeling), a model-agnostic system that augments LLM with dynamic On-the-fly Epistemic Graphs. On three creativity benchmarks, PRISM achieves state-of-the-art novelty and significantly expands distributional diversity. Moreover, we evaluate the real-world utility via a challenging rare-disease diagnosis benchmark. Results demonstrate that PRISM successfully uncovers correct long-tail diagnoses that standard LLM miss, confirming that its divergence stems from meaningful exploration rather than incoherent noise. Overall, this work establishes a new paradigm for Pluralistic AI, moving beyond monolithic consensus toward a diverse ecosystem of unique cognitive individuals capable of collective, multi-perspective discovery.

Multimodal Large Language Models (MLLMs) show promise for medical applications, yet progress in dermatology lags due to limited training data, narrow task coverage, and lack of clinically-grounded supervision that mirrors expert diagnostic workflows. We present a comprehensive framework to address these gaps. First, we introduce DermoInstruct, a large-scale morphology-anchored instruction corpus comprising 211,243 images and 772,675 trajectories across five task formats, capturing the complete diagnostic pipeline from morphological observation and clinical reasoning to final diagnosis. Second, we establish DermoBench, a rigorous benchmark evaluating 11 tasks across four clinical axes: Morphology, Diagnosis, Reasoning, and Fairness, including a challenging subset of 3,600 expert-verified open-ended instances and human performance baselines. Third, we develop DermoGPT, a dermatology reasoning MLLM trained via supervised fine-tuning followed by our Morphologically-Anchored Visual-Inference-Consistent (MAVIC) reinforcement learning objective, which enforces consistency between visual observations and diagnostic conclusions. At inference, we deploy Confidence-Consistency Test-time adaptation (CCT) for robust predictions. Experiments show DermoGPT significantly outperforms 16 representative baselines across all axes, achieving state-of-the-art performance while substantially narrowing the human-AI gap. DermoInstruct, DermoBench and DermoGPT will be made publicly available at https://github.com/mendicant04/DermoGPT upon acceptance.

The National Comprehensive Cancer Network (NCCN) provides evidence-based guidelines for cancer treatment. Translating complex patient presentations into guideline-compliant treatment recommendations is time-intensive, requires specialized expertise, and is prone to error. Advances in large language model (LLM) capabilities promise to reduce the time required to generate treatment recommendations and improve accuracy. We present an LLM agent-based approach to automatically generate guideline-concordant treatment trajectories for patients with non-small cell lung cancer (NSCLC). Our contributions are threefold. First, we construct a novel longitudinal dataset of 121 cases of NSCLC patients that includes clinical encounters, diagnostic results, and medical histories, each expertly annotated with the corresponding NCCN guideline trajectories by board-certified oncologists. Second, we demonstrate that existing LLMs possess domain-specific knowledge that enables high-quality proxy benchmark generation for both model development and evaluation, achieving strong correlation (Spearman coefficient r=0.88, RMSE = 0.08) with expert-annotated benchmarks. Third, we develop a hybrid approach combining expensive human annotations with model consistency information to create both the agent framework that predicts the relevant guidelines for a patient, as well as a meta-classifier that verifies prediction accuracy with calibrated confidence scores for treatment recommendations (AUROC=0.800), a critical capability for communicating the accuracy of outputs, custom-tailoring tradeoffs in performance, and supporting regulatory compliance. This work establishes a framework for clinically viable LLM-based guideline adherence systems that balance accuracy, interpretability, and regulatory requirements while reducing annotation costs, providing a scalable pathway toward automated clinical decision support.

Despite extensive standardization, diagnostic interviews for mental health disorders encompass substantial subjective judgment. Previous studies have demonstrated that EEG-based neural measures can function as reliable objective correlates of depression, or even predictors of depression and its course. However, their clinical utility has not been fully realized because of 1) the lack of automated ways to deal with the inherent noise associated with EEG data at scale, and 2) the lack of knowledge of which aspects of the EEG signal may be markers of a clinical disorder. Here we adapt an unsupervised pipeline from the recent deep representation learning literature to address these problems by 1) learning a disentangled representation using beta-VAE to denoise the signal, and 2) extracting interpretable features associated with a sparse set of clinical labels using a Symbol-Concept Association Network (SCAN). We demonstrate that our method is able to outperform the canonical hand-engineered baseline classification method on a number of factors, including participant age and depression diagnosis. Furthermore, our method recovers a representation that can be used to automatically extract denoised Event Related Potentials (ERPs) from novel, single EEG trajectories, and supports fast supervised re-mapping to various clinical labels, allowing clinicians to re-use a single EEG representation regardless of updates to the standardized diagnostic system. Finally, single factors of the learned disentangled representations often correspond to meaningful markers of clinical factors, as automatically detected by SCAN, allowing for human interpretability and post-hoc expert analysis of the recommendations made by the model.

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.

Predicting disease trajectories from electronic health records (EHRs) is a complex task due to major challenges such as data non-stationarity, high granularity of medical codes, and integration of multimodal data. EHRs contain both structured data, such as diagnostic codes, and unstructured data, such as clinical notes, which hold essential information often overlooked. Current models, primarily based on structured data, struggle to capture the complete medical context of patients, resulting in a loss of valuable information. To address this issue, we propose an approach that integrates unstructured clinical notes into transformer-based deep learning models for sequential disease prediction. This integration enriches the representation of patients' medical histories, thereby improving the accuracy of diagnosis predictions. Experiments on MIMIC-IV datasets demonstrate that the proposed approach outperforms traditional models relying solely on structured data.

Counterfactual medical image generation enables clinicians to explore clinical hypotheses, such as predicting disease progression, facilitating their decision-making. While existing methods can generate visually plausible images from disease progression prompts, they produce silent predictions that lack interpretation to verify how the generation reflects the hypothesized progression -- a critical gap for medical applications that require traceable reasoning. In this paper, we propose Interpretable Counterfactual Generation (ICG), a novel task requiring the joint generation of counterfactual images that reflect the clinical hypothesis and interpretation texts that outline the visual changes induced by the hypothesis. To enable ICG, we present ICG-CXR, the first dataset pairing longitudinal medical images with hypothetical progression prompts and textual interpretations. We further introduce ProgEmu, an autoregressive model that unifies the generation of counterfactual images and textual interpretations. We demonstrate the superiority of ProgEmu in generating progression-aligned counterfactuals and interpretations, showing significant potential in enhancing clinical decision support and medical education. Project page: https://progemu.github.io.

Disease progression simulation is a crucial area of research that has significant implications for clinical diagnosis, prognosis, and treatment. One major challenge in this field is the lack of continuous medical imaging monitoring of individual patients over time. To address this issue, we develop a novel framework termed Progressive Image Editing (PIE) that enables controlled manipulation of disease-related image features, facilitating precise and realistic disease progression simulation. Specifically, we leverage recent advancements in text-to-image generative models to simulate disease progression accurately and personalize it for each patient. We theoretically analyze the iterative refining process in our framework as a gradient descent with an exponentially decayed learning rate. To validate our framework, we conduct experiments in three medical imaging domains. Our results demonstrate the superiority of PIE over existing methods such as Stable Diffusion Walk and Style-Based Manifold Extrapolation based on CLIP score (Realism) and Disease Classification Confidence (Alignment). Our user study collected feedback from 35 veteran physicians to assess the generated progressions. Remarkably, 76.2% of the feedback agrees with the fidelity of the generated progressions. To our best knowledge, PIE is the first of its kind to generate disease progression images meeting real-world standards. It is a promising tool for medical research and clinical practice, potentially allowing healthcare providers to model disease trajectories over time, predict future treatment responses, and improve patient outcomes.

Advances in medical imaging technologies have enabled the collection of longitudinal images, which involve repeated scanning of the same patients over time, to monitor disease progression. However, predictive modeling of such data remains challenging due to high dimensionality, irregular sampling, and data sparsity. To address these issues, we propose ImageFlowNet, a novel model designed to forecast disease trajectories from initial images while preserving spatial details. ImageFlowNet first learns multiscale joint representation spaces across patients and time points, then optimizes deterministic or stochastic flow fields within these spaces using a position-parameterized neural ODE/SDE framework. The model leverages a UNet architecture to create robust multiscale representations and mitigates data scarcity by combining knowledge from all patients. We provide theoretical insights that support our formulation of ODEs, and motivate our regularizations involving high-level visual features, latent space organization, and trajectory smoothness. We validate ImageFlowNet on three longitudinal medical image datasets depicting progression in geographic atrophy, multiple sclerosis, and glioblastoma, demonstrating its ability to effectively forecast disease progression and outperform existing methods. Our contributions include the development of ImageFlowNet, its theoretical underpinnings, and empirical validation on real-world datasets. The official implementation is available at https://github.com/KrishnaswamyLab/ImageFlowNet.

Deep neural networks are often applied to medical images to automate the problem of medical diagnosis. However, a more clinically relevant question that practitioners usually face is how to predict the future trajectory of a disease. Current methods for prognosis or disease trajectory forecasting often require domain knowledge and are complicated to apply. In this paper, we formulate the prognosis prediction problem as a one-to-many prediction problem. Inspired by a clinical decision-making process with two agents -- a radiologist and a general practitioner -- we predict prognosis with two transformer-based components that share information with each other. The first transformer in this framework aims to analyze the imaging data, and the second one leverages its internal states as inputs, also fusing them with auxiliary clinical data. The temporal nature of the problem is modeled within the transformer states, allowing us to treat the forecasting problem as a multi-task classification, for which we propose a novel loss. We show the effectiveness of our approach in predicting the development of structural knee osteoarthritis changes and forecasting Alzheimer's disease clinical status directly from raw multi-modal data. The proposed method outperforms multiple state-of-the-art baselines with respect to performance and calibration, both of which are needed for real-world applications. An open-source implementation of our method is made publicly available at https://github.com/Oulu-IMEDS/CLIMATv2.

Automating radiology report generation can significantly alleviate radiologists' workloads. Previous research has primarily focused on realizing highly concise observations while neglecting the precise attributes that determine the severity of diseases (e.g., small pleural effusion). Since incorrect attributes will lead to imprecise radiology reports, strengthening the generation process with precise attribute modeling becomes necessary. Additionally, the temporal information contained in the historical records, which is crucial in evaluating a patient's current condition (e.g., heart size is unchanged), has also been largely disregarded. To address these issues, we propose RECAP, which generates precise and accurate radiology reports via dynamic disease progression reasoning. Specifically, RECAP first predicts the observations and progressions (i.e., spatiotemporal information) given two consecutive radiographs. It then combines the historical records, spatiotemporal information, and radiographs for report generation, where a disease progression graph and dynamic progression reasoning mechanism are devised to accurately select the attributes of each observation and progression. Extensive experiments on two publicly available datasets demonstrate the effectiveness of our model.

In medical applications, deep learning methods are built to automate diagnostic tasks. However, a clinically relevant question that practitioners usually face, is how to predict the future trajectory of a disease (prognosis). Current methods for such a problem often require domain knowledge, and are complicated to apply. In this paper, we formulate the prognosis prediction problem as a one-to-many forecasting problem from multimodal data. Inspired by a clinical decision-making process with two agents -- a radiologist and a general practitioner, we model a prognosis prediction problem with two transformer-based components that share information between each other. The first block in this model aims to analyze the imaging data, and the second block leverages the internal representations of the first one as inputs, also fusing them with auxiliary patient data. We show the effectiveness of our method in predicting the development of structural knee osteoarthritis changes over time. Our results show that the proposed method outperforms the state-of-the-art baselines in terms of various performance metrics. In addition, we empirically show that the existence of the multi-agent transformers with depths of 2 is sufficient to achieve good performances. Our code is publicly available at https://github.com/MIPT-Oulu/CLIMAT.

Background: Electronic Health Records hold detailed longitudinal information about each patient's health status and general clinical history, a large portion of which is stored within the unstructured text. Existing approaches focus mostly on structured data and a subset of single-domain outcomes. We explore how temporal modelling of patients from free text and structured data, using deep generative transformers can be used to forecast a wide range of future disorders, substances, procedures or findings. Methods: We present Foresight, a novel transformer-based pipeline that uses named entity recognition and linking tools to convert document text into structured, coded concepts, followed by providing probabilistic forecasts for future medical events such as disorders, substances, procedures and findings. We processed the entire free-text portion from three different hospital datasets totalling 811336 patients covering both physical and mental health. Findings: On tests in two UK hospitals (King's College Hospital, South London and Maudsley) and the US MIMIC-III dataset precision@10 0.68, 0.76 and 0.88 was achieved for forecasting the next disorder in a patient timeline, while precision@10 of 0.80, 0.81 and 0.91 was achieved for forecasting the next biomedical concept. Foresight was also validated on 34 synthetic patient timelines by five clinicians and achieved relevancy of 97% for the top forecasted candidate disorder. As a generative model, it can forecast follow-on biomedical concepts for as many steps as required. Interpretation: Foresight is a general-purpose model for biomedical concept modelling that can be used for real-world risk forecasting, virtual trials and clinical research to study the progression of disorders, simulate interventions and counterfactuals, and educational purposes.

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

Multi-modal large language models (MM-LLMs) have shown strong performance in medical image understanding and clinical reasoning. Recent medical agent systems extend them with tool use and multi-agent collaboration, enabling complex decision-making. However, these systems rely almost entirely on frontier models (e.g., GPT), whose API-based deployment incurs high cost, high latency, and privacy risks that conflict with on-premise clinical requirements. We present Meissa, a lightweight 4B-parameter medical MM-LLM that brings agentic capability offline. Instead of imitating static answers, Meissa learns both when to engage external interaction (strategy selection) and how to execute multi-step interaction (strategy execution) by distilling structured trajectories from frontier models. Specifically, we propose: (1) Unified trajectory modeling: trajectories (reasoning and action traces) are represented within a single state-action-observation formalism, allowing one model to generalize across heterogeneous medical environments. (2) Three-tier stratified supervision: the model's own errors trigger progressive escalation from direct reasoning to tool-augmented and multi-agent interaction, explicitly learning difficulty-aware strategy selection. (3) Prospective-retrospective supervision: pairing exploratory forward traces with hindsight-rationalized execution traces enables stable learning of effective interaction policies. Trained on 40K curated trajectories, Meissa matches or exceeds proprietary frontier agents in 10 of 16 evaluation settings across 13 medical benchmarks spanning radiology, pathology, and clinical reasoning. Using over 25x fewer parameters than typical frontier models like Gemini-3, Meissa operates fully offline with 22x lower end-to-end latency compared to API-based deployment. Data, models, and environments are released at https://github.com/Schuture/Meissa.

The emergence of tool-calling-based agent systems introduces a more evidence-driven paradigm for pathology image analysis in contrast to the coarse-grained text-image diagnostic approaches. With the recent large-scale experimental adoption of spatial transcriptomics technologies, molecularly validated pathological diagnosis is becoming increasingly open and accessible. In this work, we propose LAMMI-Pathology (LVLM-Agent System for Molecularly Informed Medical Intelligence in Pathology), a scalable agent framework for domain-specific agent tool-calling. LAMMI-Pathology adopts a tool-centric, bottom-up architecture in which customized domain-adaptive tools serve as the foundation. These tools are clustered by domain style to form component agents, which are then coordinated through a top-level planner hierarchically, avoiding excessively long context lengths that could induce task drift. Based on that, we introduce a novel trajectory construction mechanism based on Atomic Execution Nodes (AENs), which serve as reliable and composable units for building semi-simulated reasoning trajectories that capture credible agent-tool interactions. Building on this foundation, we develop a trajectory-aware fine-tuning strategy that aligns the planner's decision-making process with these multi-step reasoning trajectories, thereby enhancing inference robustness in pathology understanding and its adaptive use of the customized toolset.

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

Clinical case reports encode temporal patient trajectories that are often underexploited by traditional machine learning methods relying on structured data. In this work, we introduce the forecasting problem from textual time series, where timestamped clinical findings -- extracted via an LLM-assisted annotation pipeline -- serve as the primary input for prediction. We systematically evaluate a diverse suite of models, including fine-tuned decoder-based large language models and encoder-based transformers, on tasks of event occurrence prediction, temporal ordering, and survival analysis. Our experiments reveal that encoder-based models consistently achieve higher F1 scores and superior temporal concordance for short- and long-horizon event forecasting, while fine-tuned masking approaches enhance ranking performance. In contrast, instruction-tuned decoder models demonstrate a relative advantage in survival analysis, especially in early prognosis settings. Our sensitivity analyses further demonstrate the importance of time ordering, which requires clinical time series construction, as compared to text ordering, the format of the text inputs that LLMs are classically trained on. This highlights the additional benefit that can be ascertained from time-ordered corpora, with implications for temporal tasks in the era of widespread LLM use.

Daily progress notes are common types in the electronic health record (EHR) where healthcare providers document the patient's daily progress and treatment plans. The EHR is designed to document all the care provided to patients, but it also enables note bloat with extraneous information that distracts from the diagnoses and treatment plans. Applications of natural language processing (NLP) in the EHR is a growing field with the majority of methods in information extraction. Few tasks use NLP methods for downstream diagnostic decision support. We introduced the 2022 National NLP Clinical Challenge (N2C2) Track 3: Progress Note Understanding - Assessment and Plan Reasoning as one step towards a new suite of tasks. The Assessment and Plan Reasoning task focuses on the most critical components of progress notes, Assessment and Plan subsections where health problems and diagnoses are contained. The goal of the task was to develop and evaluate NLP systems that automatically predict causal relations between the overall status of the patient contained in the Assessment section and its relation to each component of the Plan section which contains the diagnoses and treatment plans. The goal of the task was to identify and prioritize diagnoses as the first steps in diagnostic decision support to find the most relevant information in long documents like daily progress notes. We present the results of 2022 n2c2 Track 3 and provide a description of the data, evaluation, participation and system performance.

Longitudinal analysis has great potential to reveal developmental trajectories and monitor disease progression in medical imaging. This process relies on consistent and robust joint 4D segmentation. Traditional techniques are dependent on the similarity of images over time and the use of subject-specific priors to reduce random variation and improve the robustness and sensitivity of the overall longitudinal analysis. This is however slow and computationally intensive as subject-specific templates need to be rebuilt every time. The focus of this work to accelerate this analysis with the use of deep learning. The proposed approach is based on deep CNNs and incorporates semantic segmentation and provides a longitudinal relationship for the same subject. The proposed approach is based on deep CNNs and incorporates semantic segmentation and provides a longitudinal relationship for the same subject. The state of art using 3D patches as inputs to modified Unet provides results around {0.91 pm 0.5} Dice and using multi-view atlas in CNNs provide around the same results. In this work, different models are explored, each offers better accuracy and fast results while increasing the segmentation quality. These methods are evaluated on 135 scans from the EADC-ADNI Harmonized Hippocampus Protocol. Proposed CNN based segmentation approaches demonstrate how 2D segmentation using prior slices can provide similar results to 3D segmentation while maintaining good continuity in the 3D dimension and improved speed. Just using 2D modified sagittal slices provide us a better Dice and longitudinal analysis for a given subject. For the ADNI dataset, using the simple UNet CNN technique gives us {0.84 pm 0.5} and while using modified CNN techniques on the same input yields {0.89 pm 0.5}. Rate of atrophy and RMS error are calculated for several test cases using various methods and analyzed.

Longitudinal multimodal data, including electronic health records (EHR) and sequential chest X-rays (CXRs), is critical for modeling disease progression, yet remains underutilized due to two key challenges: (1) redundancy in consecutive CXR sequences, where static anatomical regions dominate over clinically-meaningful dynamics, and (2) temporal misalignment between sparse, irregular imaging and continuous EHR data. We introduce DiPro, a novel framework that addresses these challenges through region-aware disentanglement and multi-timescale alignment. First, we disentangle static (anatomy) and dynamic (pathology progression) features in sequential CXRs, prioritizing disease-relevant changes. Second, we hierarchically align these static and dynamic CXR features with asynchronous EHR data via local (pairwise interval-level) and global (full-sequence) synchronization to model coherent progression pathways. Extensive experiments on the MIMIC dataset demonstrate that DiPro could effectively extract temporal clinical dynamics and achieve state-of-the-art performance on both disease progression identification and general ICU prediction tasks.

Clinical diagnostic workups typically follow a modality escalation pathway: after initial clinical evaluation, clinicians begin with routine structural imaging (e.g., MRI), selectively add sequences such as FLAIR or T2 to refine the differential, and reserve molecular imaging (e.g., amyloid-PET) for cases that remain uncertain after standard evaluation. Consequently, patients are observed with heterogeneous and often incomplete modality subsets. However, most current AI models assume fixed data modalities as the model inputs. In this paper, we present BrainAnytime, a unified pretraining framework pretrained on 34,899 3D brain scans from five datasets that support brain image analysis under arbitrary modality availability spanning multi-sequence MRI and amyloid-PET. A single model accepts whatever imaging is available, from a lone T1 scan to a full multimodal workup. Pretraining learns structural-molecular correspondences between MRI and PET via cross-modal distillation (RCMD) and prioritizes disease-vulnerable anatomy via atlas-guided curriculum masking (PACM), all within a shared 3D masked autoencoder (Multi-MAE3D). Across four downstream tasks and five clinically motivated modality settings, BrainAnytime largely outperforms modality-specific models, missing-modality baselines, and large-scale brain MRI pretrained foundation models on most modality settings. Notably, it surpasses the strongest missing-modality baselines with relative improvements of 6.2% and 7.0% in average accuracy on CN vs. AD and CN vs. MCI classification, respectively. Code is available at https://github.com/SDH-Lab/BrainAnytime.

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

Large language model (LLM)-based agents increasingly rely on tool use to complete real-world tasks. While existing works evaluate the LLMs' tool use capability, they largely focus on the final answers yet overlook the detailed tool usage trajectory, i.e., whether tools are selected, parameterized, and ordered correctly. We introduce TRAJECT-Bench, a trajectory-aware benchmark to comprehensively evaluate LLMs' tool use capability through diverse tasks with fine-grained evaluation metrics. TRAJECT-Bench pairs high-fidelity, executable tools across practical domains with tasks grounded in production-style APIs, and synthesizes trajectories that vary in breadth (parallel calls) and depth (interdependent chains). Besides final accuracy, TRAJECT-Bench also reports trajectory-level diagnostics, including tool selection and argument correctness, and dependency/order satisfaction. Analyses reveal failure modes such as similar tool confusion and parameter-blind selection, and scaling behavior with tool diversity and trajectory length where the bottleneck of transiting from short to mid-length trajectories is revealed, offering actionable guidance for LLMs' tool use.

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.

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.

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.

Tool tracking in surgical videos is essential for advancing computer-assisted interventions, such as skill assessment, safety zone estimation, and human-machine collaboration. However, the lack of context-rich datasets limits AI applications in this field. Existing datasets rely on overly generic tracking formalizations that fail to capture surgical-specific dynamics, such as tools moving out of the camera's view or exiting the body. This results in less clinically relevant trajectories and a lack of flexibility for real-world surgical applications. Methods trained on these datasets often struggle with visual challenges such as smoke, reflection, and bleeding, further exposing the limitations of current approaches. We introduce CholecTrack20, a specialized dataset for multi-class, multi-tool tracking in surgical procedures. It redefines tracking formalization with three perspectives: (i) intraoperative, (ii) intracorporeal, and (iii) visibility, enabling adaptable and clinically meaningful tool trajectories. The dataset comprises 20 full-length surgical videos, annotated at 1 fps, yielding over 35K frames and 65K labeled tool instances. Annotations include spatial location, category, identity, operator, phase, and scene visual challenge. Benchmarking state-of-the-art methods on CholecTrack20 reveals significant performance gaps, with current approaches (< 45\% HOTA) failing to meet the accuracy required for clinical translation. These findings motivate the need for advanced and intuitive tracking algorithms and establish CholecTrack20 as a foundation for developing robust AI-driven surgical assistance systems.

Accurate prediction of major adverse cardiovascular events recurrence risk in acute myocardial infarction patients based on postoperative cardiac MRI and associated clinical notes is crucial for precision treatment and personalized intervention. Existing methods primarily focus on risk stratification capability while overlooking the need for intermediate robust reasoning and model interpretability in clinical practice. Moreover, end-to-end risk prediction using LLM/VLM faces significant challenges due to data limitations and modeling complexity. To bridge this gap, we propose CardioCoT, a novel two-stage hierarchical reasoning-enhanced survival analysis framework designed to enhance both model interpretability and predictive performance. In the first stage, we employ an evidence-augmented self-refinement mechanism to guide LLM/VLMs in generating robust hierarchical reasoning trajectories based on associated radiological findings. In the second stage, we integrate the reasoning trajectories with imaging data for risk model training and prediction. CardioCoT demonstrates superior performance in MACE recurrence risk prediction while providing interpretable reasoning processes, offering valuable insights for clinical decision-making.

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

Longitudinal health agents must reason across multi-source trajectories that combine continuous device streams, sparse clinical exams, and episodic life events - yet evaluating them is hard: real-world data cannot be released at scale, and temporally grounded attribution questions seldom admit definitive answers without structured ground truth. We present ESL-Bench, an event-driven synthesis framework and benchmark providing 100 synthetic users, each with a 1-5 year trajectory comprising a health profile, a multi-phase narrative plan, daily device measurements, periodic exam records, and an event log with explicit per-indicator impact parameters. Each indicator follows a baseline stochastic process driven by discrete events with sigmoid-onset, exponential-decay kernels under saturation and projection constraints; a hybrid pipeline delegates sparse semantic artifacts to LLM-based planning and dense indicator dynamics to algorithmic simulation with hard physiological bounds. Users are each paired with 100 evaluation queries across five dimensions - Lookup, Trend, Comparison, Anomaly, Explanation - stratified into Easy, Medium, and Hard tiers, with all ground-truth answers programmatically computable from the recorded event-indicator relationships. Evaluating 13 methods spanning LLMs with tools, DB-native agents, and memory-augmented RAG, we find that DB agents (48-58%) substantially outperform memory RAG baselines (30-38%), with the gap concentrated on Comparison and Explanation queries where multi-hop reasoning and evidence attribution are required.

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.

Identifying, tracking, and predicting wound heal-stage progression is a fundamental task towards proper diagnosis, effective treatment, facilitating healing, and reducing pain. Traditionally, a medical expert might observe a wound to determine the current healing state and recommend treatment. However, sourcing experts who can produce such a diagnosis solely from visual indicators can be difficult, time-consuming and expensive. In addition, lesions may take several weeks to undergo the healing process, demanding resources to monitor and diagnose continually. Automating this task can be challenging; datasets that follow wound progression from onset to maturation are small, rare, and often collected without computer vision in mind. To tackle these challenges, we introduce a self-supervised learning scheme composed of (a) learning embeddings of wound's temporal dynamics, (b) clustering for automatic stage discovery, and (c) fine-tuned classification. The proposed self-supervised and flexible learning framework is biologically inspired and trained on a small dataset with zero human labeling. The HealNet framework achieved high pre-text and downstream classification accuracy; when evaluated on held-out test data, HealNet achieved 97.7% pre-text accuracy and 90.62% heal-stage classification accuracy.

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

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

Foundation models (FMs) trained on electronic health records (EHRs) have shown strong performance on a range of clinical prediction tasks. However, adapting these models to local health systems remains challenging due to limited data availability and resource constraints. In this study, we investigated what these models learn and evaluated the transferability of an FM trained on MIMIC-IV to an institutional EHR dataset at the University of Chicago Medical Center. We assessed their ability to identify outlier patients and examined representation-space patient trajectories in relation to future clinical outcomes. We also evaluated the performance of supervised fine-tuned classifiers on both source and target datasets. Our findings offer insights into the adaptability of FMs across different healthcare systems, highlight considerations for their effective implementation, and provide an empirical analysis of the underlying factors that contribute to their predictive performance.

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.

Mental health disorders affect hundreds of millions globally, and the Web now serves as a primary medium for accessing support, information, and assessment. Large language models (LLMs) offer scalable and accessible assistance, yet their deployment in mental-health settings remains risky when their reasoning is incomplete, inconsistent, or ungrounded. Existing psychological LLMs emphasize emotional understanding or knowledge recall but overlook the step-wise, clinically aligned reasoning required for appraisal, diagnosis, intervention planning, abstraction, and verification. To address these issues, we introduce MentraSuite, a unified framework for advancing reliable mental-health reasoning. We propose MentraBench, a comprehensive benchmark spanning five core reasoning aspects, six tasks, and 13 datasets, evaluating both task performance and reasoning quality across five dimensions: conciseness, coherence, hallucination avoidance, task understanding, and internal consistency. We further present Mindora, a post-trained model optimized through a hybrid SFT-RL framework with an inconsistency-detection reward to enforce faithful and coherent reasoning. To support training, we construct high-quality trajectories using a novel reasoning trajectory generation strategy, that strategically filters difficult samples and applies a structured, consistency-oriented rewriting process to produce concise, readable, and well-balanced trajectories. Across 20 evaluated LLMs, Mindora achieves the highest average performance on MentraBench and shows remarkable performances in reasoning reliability, demonstrating its effectiveness for complex mental-health scenarios.

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.

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

In this work, we present LesionLocator, a framework for zero-shot longitudinal lesion tracking and segmentation in 3D medical imaging, establishing the first end-to-end model capable of 4D tracking with dense spatial prompts. Our model leverages an extensive dataset of 23,262 annotated medical scans, as well as synthesized longitudinal data across diverse lesion types. The diversity and scale of our dataset significantly enhances model generalizability to real-world medical imaging challenges and addresses key limitations in longitudinal data availability. LesionLocator outperforms all existing promptable models in lesion segmentation by nearly 10 dice points, reaching human-level performance, and achieves state-of-the-art results in lesion tracking, with superior lesion retrieval and segmentation accuracy. LesionLocator not only sets a new benchmark in universal promptable lesion segmentation and automated longitudinal lesion tracking but also provides the first open-access solution of its kind, releasing our synthetic 4D dataset and model to the community, empowering future advancements in medical imaging. Code is available at: www.github.com/MIC-DKFZ/LesionLocator

Long chain-of-thought (CoT) trajectories provide rich supervision signals for distilling reasoning from teacher to student LLMs. However, both prior work and our experiments show that trajectories from stronger teachers do not necessarily yield better students, highlighting the importance of data-student suitability in distillation. Existing methods assess suitability primarily through student likelihood, favoring trajectories that closely align with the model's current behavior but overlooking more informative ones. Addressing this, we propose Rank-Surprisal Ratio (RSR), a simple metric that captures both alignment and informativeness to assess the suitability of a reasoning trajectory. RSR is motivated by the observation that effective trajectories typically combine low absolute probability with relatively high-ranked tokens under the student model, balancing learning signal strength and behavioral alignment. Concretely, RSR is defined as the ratio of a trajectory's average token-wise rank to its average negative log-likelihood, and is straightforward to compute and interpret. Across five student models and reasoning trajectories from 11 diverse teachers, RSR strongly correlates with post-training performance (average Spearman 0.86), outperforming existing metrics. We further demonstrate its practical utility in both trajectory selection and teacher selection.

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.

Purpose. Patients with advanced cancer may undergo multiple lines of treatment, switching therapies as their disease progresses. Motivated by a study of metastatic prostate cancer, we develop a microsimulation framework to study therapy sequence. Methods. We propose a discrete-time state transition model to study two lines of anti-cancer therapy. Based on digitized published progression-free survival (PFS) and overall survival (OS) curves, we infer event types (progression or death), and estimate transition probabilities using cumulative incidence functions with competing risks. Our model incorporates within-patient dependence over time, such that response to first-line therapy informs subsequent event probabilities. Parameters governing the degree of within-patient dependence can be used to calibrate the model-based results to those of a target trial. We demonstrate these methods in a study of two therapy sequences for metastatic prostate cancer, where Docetaxel (DCT) and Abiraterone Acetate (AA) are both appropriate for use in either first or second line treatment. We assess costs, Quality-Adjusted Life Years (QALYs) and Incremental Cost Effectiveness Ratio (ICER) for two treatment strategies: DCT then AA vs AA then DCT. Results. Using digitized survival curves from relevant clinical trials, we identified 8.6-13.9% of PFS times that should be categorized as deaths, allowing for estimation of cumulative incidence functions. Models assuming within-patient independence overestimated OS time, corrected with our calibration approach. Correction resulted in meaningful changes in the difference in QALYs between treatment strategies (0.07 vs 0.15) and the ICER (-\76,836/QALY vs -21,030/QALY). Conclusions. Microsimulation models can be successfully used to study cost-effectiveness of therapy sequences, taking care to account correctly for within-patient dependence.

A crucial step within secondary analysis of electronic health records (EHRs) is to identify the patient cohort under investigation. While EHRs contain medical billing codes that aim to represent the conditions and treatments patients may have, much of the information is only present in the patient notes. Therefore, it is critical to develop robust algorithms to infer patients' conditions and treatments from their written notes. In this paper, we introduce a dataset for patient phenotyping, a task that is defined as the identification of whether a patient has a given medical condition (also referred to as clinical indication or phenotype) based on their patient note. Nursing Progress Notes and Discharge Summaries from the Intensive Care Unit of a large tertiary care hospital were manually annotated for the presence of several high-context phenotypes relevant to treatment and risk of re-hospitalization. This dataset contains 1102 Discharge Summaries and 1000 Nursing Progress Notes. Each Discharge Summary and Progress Note has been annotated by at least two expert human annotators (one clinical researcher and one resident physician). Annotated phenotypes include treatment non-adherence, chronic pain, advanced/metastatic cancer, as well as 10 other phenotypes. This dataset can be utilized for academic and industrial research in medicine and computer science, particularly within the field of medical natural language processing.

MRI is an indispensable clinical tool, offering a rich variety of tissue contrasts to support broad diagnostic and research applications. Clinical exams routinely acquire multiple structural sequences that provide complementary information for differential diagnosis, while research protocols often incorporate advanced functional, diffusion, spectroscopic, and relaxometry sequences to capture multidimensional insights into tissue structure and composition. However, these capabilities come at the cost of prolonged scan times, which reduce patient throughput, increase susceptibility to motion artifacts, and may require trade-offs in image quality or diagnostic scope. Over the last two decades, advances in image reconstruction algorithms--alongside improvements in hardware and pulse sequence design--have made it possible to accelerate acquisitions while preserving diagnostic quality. Central to this progress is the ability to incorporate prior information to regularize the solutions to the reconstruction problem. In this tutorial, we overview the basics of MRI reconstruction and highlight state-of-the-art approaches, beginning with classical methods that rely on explicit hand-crafted priors, and then turning to deep learning methods that leverage a combination of learned and crafted priors to further push the performance envelope. We also explore the translational aspects and eventual clinical implications of these methods. We conclude by discussing future directions to address remaining challenges in MRI reconstruction. The tutorial is accompanied by a Python toolbox (https://github.com/tutorial-MRI-recon/tutorial) to demonstrate select methods discussed in the article.

Chest X-ray imaging (CXR) is an important diagnostic tool used in hospitals to assess patient conditions and monitor changes over time. Generative models, specifically diffusion-based models, have shown promise in generating realistic synthetic X-rays. However, these models mainly focus on conditional generation using single-time-point data, i.e., typically CXRs taken at a specific time with their corresponding reports, limiting their clinical utility, particularly for capturing temporal changes. To address this limitation, we propose a novel framework, EHRXDiff, which predicts future CXR images by integrating previous CXRs with subsequent medical events, e.g., prescriptions, lab measures, etc. Our framework dynamically tracks and predicts disease progression based on a latent diffusion model, conditioned on the previous CXR image and a history of medical events. We comprehensively evaluate the performance of our framework across three key aspects, including clinical consistency, demographic consistency, and visual realism. We demonstrate that our framework generates high-quality, realistic future images that capture potential temporal changes, suggesting its potential for further development as a clinical simulation tool. This could offer valuable insights for patient monitoring and treatment planning in the medical field.

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.

Accurate differentiation of pseudoprogression (PsP) from True Progression (TP) following radiotherapy (RT) in glioblastoma (GBM) patients is crucial for optimal treatment planning. However, this task remains challenging due to the overlapping imaging characteristics of PsP and TP. This study therefore proposes a multimodal deep-learning approach utilizing complementary information from routine anatomical MR images, clinical parameters, and RT treatment planning information for improved predictive accuracy. The approach utilizes a self-supervised Vision Transformer (ViT) to encode multi-sequence MR brain volumes to effectively capture both global and local context from the high dimensional input. The encoder is trained in a self-supervised upstream task on unlabeled glioma MRI datasets from the open BraTS2021, UPenn-GBM, and UCSF-PDGM datasets to generate compact, clinically relevant representations from FLAIR and T1 post-contrast sequences. These encoded MR inputs are then integrated with clinical data and RT treatment planning information through guided cross-modal attention, improving progression classification accuracy. This work was developed using two datasets from different centers: the Burdenko Glioblastoma Progression Dataset (n = 59) for training and validation, and the GlioCMV progression dataset from the University Hospital Erlangen (UKER) (n = 20) for testing. The proposed method achieved an AUC of 75.3%, outperforming the current state-of-the-art data-driven approaches. Importantly, the proposed approach relies on readily available anatomical MRI sequences, clinical data, and RT treatment planning information, enhancing its clinical feasibility. The proposed approach addresses the challenge of limited data availability for PsP and TP differentiation and could allow for improved clinical decision-making and optimized treatment plans for GBM patients.

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

Alzheimer's disease (AD) is a degenerative brain disease impairing a person's ability to perform day to day activities. The clinical manifestations of Alzheimer's disease are characterized by heterogeneity in age, disease span, progression rate, impairment of memory and cognitive abilities. Due to these variabilities, personalized care and treatment planning, as well as patient counseling about their individual progression is limited. Recent developments in machine learning to detect hidden patterns in complex, multi-dimensional datasets provides significant opportunities to address this critical need. In this work, we use unsupervised and supervised machine learning approaches for subtype identification and prediction. We apply machine learning methods to the extensive clinical observations available at the Alzheimer's Disease Neuroimaging Initiative (ADNI) data set to identify patient subtypes and to predict disease progression. Our analysis depicts the progression space for the Alzheimer's disease into low, moderate and high disease progression zones. The proposed work will enable early detection and characterization of distinct disease subtypes based on clinical heterogeneity. We anticipate that our models will enable patient counseling, clinical trial design, and ultimately individualized clinical care.

For the early identification, diagnosis, and treatment of mental health illnesses, the integration of deep learning (DL) and machine learning (ML) has started playing a significant role. By evaluating complex data from imaging, genetics, and behavioral assessments, these technologies have the potential to significantly improve clinical outcomes. However, they also present unique challenges related to data integration and ethical issues. This survey reviews the development of ML and DL methods for the early diagnosis and treatment of mental health issues. It examines a range of applications, with a particular emphasis on behavioral assessments, genetic and biomarker analysis, and medical imaging for diagnosing diseases like depression, bipolar disorder, and schizophrenia. Predictive modeling for illness progression is further discussed, focusing on the role of risk prediction models and longitudinal studies. Key findings highlight how ML and DL can improve diagnostic accuracy and treatment outcomes while addressing methodological inconsistencies, data integration challenges, and ethical concerns. The study emphasizes the importance of building real-time monitoring systems for individualized treatment, enhancing data fusion techniques, and fostering interdisciplinary collaboration. Future research should focus on overcoming these obstacles to ensure the valuable and ethical application of ML and DL in mental health services.

Electronic Health Records (EHRs) contain rich temporal dynamics that conventional encoding approaches fail to adequately capture. While Large Language Models (LLMs) show promise for EHR modeling, they struggle to reason about sequential clinical events and temporal dependencies. We propose Next Event Prediction (NEP), a framework that enhances LLMs' temporal reasoning through autoregressive fine-tuning on clinical event sequences. By reformulating EHRs as timestamped event chains and predicting future medical events, NEP explicitly models disease progression patterns and causal relationships. Extensive evaluations across oncology survival prediction and clinical diagnosis tasks demonstrate NEP's superiority, outperforming specialized EHR models by 4.6% AUROC and general-purpose LLMs by 7.2% C-index in temporal reasoning tasks. Our analyses reveal dual benefits: state-of-the-art prediction accuracy combined with clinically interpretable attention patterns that align with known disease pathways.

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.

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.

Purpose: Magnetic resonance imaging (MRI) to visualize anatomical motion is becoming increasingly important when treating cancer patients with radiotherapy. Hybrid MRI-linear accelerator (MRI-linac) systems allow real-time motion management during irradiation. This paper presents a multi-institutional real-time MRI time series dataset from different MRI-linac vendors. The dataset is designed to support developing and evaluating real-time tumor localization (tracking) algorithms for MRI-guided radiotherapy within the TrackRAD2025 challenge (https://trackrad2025.grand-challenge.org/). Acquisition and validation methods: The dataset consists of sagittal 2D cine MRIs in 585 patients from six centers (3 Dutch, 1 German, 1 Australian, and 1 Chinese). Tumors in the thorax, abdomen, and pelvis acquired on two commercially available MRI-linacs (0.35 T and 1.5 T) were included. For 108 cases, irradiation targets or tracking surrogates were manually segmented on each temporal frame. The dataset was randomly split into a public training set of 527 cases (477 unlabeled and 50 labeled) and a private testing set of 58 cases (all labeled). Data Format and Usage Notes: The data is publicly available under the TrackRAD2025 collection: https://doi.org/10.57967/hf/4539. Both the images and segmentations for each patient are available in metadata format. Potential Applications: This novel clinical dataset will enable the development and evaluation of real-time tumor localization algorithms for MRI-guided radiotherapy. By enabling more accurate motion management and adaptive treatment strategies, this dataset has the potential to advance the field of radiotherapy significantly.

The life trajectories of notable people have been studied to pinpoint the times and places of significant events such as birth, death, education, marriage, competition, work, speeches, scientific discoveries, artistic achievements, and battles. Understanding how these individuals interact with others provides valuable insights for broader research into human dynamics. However, the scarcity of trajectory data in terms of volume, density, and inter-person interactions, limits relevant studies from being comprehensive and interactive. We mine millions of biography pages from Wikipedia and tackle the generalization problem stemming from the variety and heterogeneity of the trajectory descriptions. Our ensemble model COSMOS, which combines the idea of semi-supervised learning and contrastive learning, achieves an F1 score of 85.95%. For this task, we also create a hand-curated dataset, WikiLifeTrajectory, consisting of 8,852 (person, time, location) triplets as ground truth. Besides, we perform an empirical analysis on the trajectories of 8,272 historians to demonstrate the validity of the extracted results. To facilitate the research on trajectory extractions and help the analytical studies to construct grand narratives, we make our code, the million-level extracted trajectories, and the WikiLifeTrajectory dataset publicly available.

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

Radiotherapy often involves a prolonged treatment period. During this time, patients may experience organ motion due to breathing and other physiological factors. Predicting and modeling this motion before treatment is crucial for ensuring precise radiation delivery. However, existing pre-treatment organ motion prediction methods primarily rely on deformation analysis using principal component analysis (PCA), which is highly dependent on registration quality and struggles to capture periodic temporal dynamics for motion modeling.In this paper, we observe that organ motion prediction closely resembles an autoregressive process, a technique widely used in natural language processing (NLP). Autoregressive models predict the next token based on previous inputs, naturally aligning with our objective of predicting future organ motion phases. Building on this insight, we reformulate organ motion prediction as an autoregressive process to better capture patient-specific motion patterns. Specifically, we acquire 4D CT scans for each patient before treatment, with each sequence comprising multiple 3D CT phases. These phases are fed into the autoregressive model to predict future phases based on prior phase motion patterns. We evaluate our method on a real-world test set of 4D CT scans from 50 patients who underwent radiotherapy at our institution and a public dataset containing 4D CT scans from 20 patients (some with multiple scans), totaling over 1,300 3D CT phases. The performance in predicting the motion of the lung and heart surpasses existing benchmarks, demonstrating its effectiveness in capturing motion dynamics from CT images. These results highlight the potential of our method to improve pre-treatment planning in radiotherapy, enabling more precise and adaptive radiation delivery.

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.

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

Speech patterns have been identified as potential diagnostic markers for neuropsychiatric conditions. However, most studies only compare a single clinical group to healthy controls, whereas clinical practice often requires differentiating between multiple potential diagnoses (multiclass settings). To address this, we assembled a dataset of repeated recordings from 420 participants (67 with major depressive disorder, 106 with schizophrenia and 46 with autism, as well as matched controls), and tested the performance of a range of conventional machine learning models and advanced Transformer models on both binary and multiclass classification, based on voice and text features. While binary models performed comparably to previous research (F1 scores between 0.54-0.75 for autism spectrum disorder, ASD; 0.67-0.92 for major depressive disorder, MDD; and 0.71-0.83 for schizophrenia); when differentiating between multiple diagnostic groups performance decreased markedly (F1 scores between 0.35-0.44 for ASD, 0.57-0.75 for MDD, 0.15-0.66 for schizophrenia, and 0.38-0.52 macro F1). Combining voice and text-based models yielded increased performance, suggesting that they capture complementary diagnostic information. Our results indicate that models trained on binary classification may learn to rely on markers of generic differences between clinical and non-clinical populations, or markers of clinical features that overlap across conditions, rather than identifying markers specific to individual conditions. We provide recommendations for future research in the field, suggesting increased focus on developing larger transdiagnostic datasets that include more fine-grained clinical features, and that can support the development of models that better capture the complexity of neuropsychiatric conditions and naturalistic diagnostic assessment.

The long-term effects of Postacute Sequelae of SARS-CoV-2, known as PASC, pose a significant challenge to healthcare systems worldwide. Accurate identification of progression events, such as hospitalization and reinfection, is essential for effective patient management and resource allocation. However, traditional models trained on structured data struggle to capture the nuanced progression of PASC. In this study, we introduce the first publicly available cohort of 18 PASC patients, with text time series features based on Large Language Model Llama-3.1-70B-Instruct and clinical risk annotated by clinical expert. We propose an Active Attention Network to predict the clinical risk and identify progression events related to the risk. By integrating human expertise with active learning, we aim to enhance clinical risk prediction accuracy and enable progression events identification with fewer number of annotation. The ultimate goal is to improves patient care and decision-making for SARS-CoV-2 patient.

Large language models (LLMs) have recently showcased remarkable capabilities, spanning a wide range of tasks and applications, including those in the medical domain. Models like GPT-4 excel in medical question answering but may face challenges in the lack of interpretability when handling complex tasks in real clinical settings. We thus introduce the diagnostic reasoning dataset for clinical notes (DiReCT), aiming at evaluating the reasoning ability and interpretability of LLMs compared to human doctors. It contains 511 clinical notes, each meticulously annotated by physicians, detailing the diagnostic reasoning process from observations in a clinical note to the final diagnosis. Additionally, a diagnostic knowledge graph is provided to offer essential knowledge for reasoning, which may not be covered in the training data of existing LLMs. Evaluations of leading LLMs on DiReCT bring out a significant gap between their reasoning ability and that of human doctors, highlighting the critical need for models that can reason effectively in real-world clinical scenarios.

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

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

With the advent of Large Language Models (LLMs), medical artificial intelligence (AI) has experienced substantial technological progress and paradigm shifts, highlighting the potential of LLMs to streamline healthcare delivery and improve patient outcomes. Considering this rapid technical progress, in this survey, we trace the recent advances of Medical Large Language Models (Med-LLMs), including the background, key findings, and mainstream techniques, especially for the evolution from general-purpose models to medical-specialized applications. Firstly, we delve into the foundational technology of Med-LLMs, indicating how general models can be progressively adapted and refined for the complicated medical tasks. Secondly, the wide-ranging applications of Med-LLMs are investigated across various healthcare domains, as well as an up-to-date review of existing Med-LLMs. The transformative impact of these models on daily medical practice is evident through their ability to assist clinicians, educators, and patients. Recognizing the importance of responsible innovation, we discuss the challenges associated with ensuring fairness, accountability, privacy, and robustness. Ethical considerations, rigorous evaluation methodologies, and the establishment of regulatory frameworks are crucial for building trustworthiness in the real-world system. We emphasize the need for ongoing scrutiny and development to maintain high standards of safety and reliability. Finally, we anticipate possible future trajectories for Med-LLMs, identifying key avenues for prudent expansion. By consolidating these insights, our review aims to provide professionals and researchers with a thorough understanding of the strengths and limitations of Med-LLMs, fostering a balanced and ethical approach to their integration into the healthcare ecosystem.

User profiling and region analysis are two tasks of significant commercial value. However, in practical applications, modeling different features typically involves four main steps: data preparation, data processing, model establishment, evaluation, and optimization. This process is time-consuming and labor-intensive. Repeating this workflow for each feature results in abundant development time for tasks and a reduced overall volume of task development. Indeed, human mobility data contains a wealth of information. Several successful cases suggest that conducting in-depth analysis of population movement data could potentially yield meaningful profiles about users and areas. Nonetheless, most related works have not thoroughly utilized the semantic information within human mobility data and trained on a fixed number of the regions. To tap into the rich information within population movement, based on the perspective that Regions Are Who walk them, we propose a large spatiotemporal model based on trajectories (RAW). It possesses the following characteristics: 1) Tailored for trajectory data, introducing a GPT-like structure with a parameter count of up to 1B; 2) Introducing a spatiotemporal fine-tuning module, interpreting trajectories as collection of users to derive arbitrary region embedding. This framework allows rapid task development based on the large spatiotemporal model. We conducted extensive experiments to validate the effectiveness of our proposed large spatiotemporal model. It's evident that our proposed method, relying solely on human mobility data without additional features, exhibits a certain level of relevance in user profiling and region analysis. Moreover, our model showcases promising predictive capabilities in trajectory generation tasks based on the current state, offering the potential for further innovative work utilizing this large spatiotemporal model.

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.

We present a foundation model-derived method to identify highly informative tokens and events in electronic health records. Our approach considers incoming data in the entire context of a patient's hospitalization and so can flag anomalous events that rule-based approaches would consider within a normal range. We demonstrate that the events our model flags are significant for predicting downstream patient outcomes and that a fraction of events identified as carrying little information can safely be dropped. Additionally, we show how informativeness can help interpret the predictions of prognostic models trained on foundation model-derived representations.

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.

Automated radiology report generation offers an effective solution to alleviate radiologists' workload. However, most existing methods focus primarily on single or fixed-view images to model current disease conditions, which limits diagnostic accuracy and overlooks disease progression. Although some approaches utilize longitudinal data to track disease progression, they still rely on single images to analyze current visits. To address these issues, we propose enhanced contrastive learning with Multi-view Longitudinal data to facilitate chest X-ray Report Generation, named MLRG. Specifically, we introduce a multi-view longitudinal contrastive learning method that integrates spatial information from current multi-view images and temporal information from longitudinal data. This method also utilizes the inherent spatiotemporal information of radiology reports to supervise the pre-training of visual and textual representations. Subsequently, we present a tokenized absence encoding technique to flexibly handle missing patient-specific prior knowledge, allowing the model to produce more accurate radiology reports based on available prior knowledge. Extensive experiments on MIMIC-CXR, MIMIC-ABN, and Two-view CXR datasets demonstrate that our MLRG outperforms recent state-of-the-art methods, achieving a 2.3% BLEU-4 improvement on MIMIC-CXR, a 5.5% F1 score improvement on MIMIC-ABN, and a 2.7% F1 RadGraph improvement on Two-view CXR.

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.

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.

In computational pathology, understanding and generation have evolved along disparate paths: advanced understanding models already exhibit diagnostic-level competence, whereas generative models largely simulate pixels. Progress remains hindered by three coupled factors: the scarcity of large, high-quality image-text corpora; the lack of precise, fine-grained semantic control, which forces reliance on non-semantic cues; and terminological heterogeneity, where diverse phrasings for the same diagnostic concept impede reliable text conditioning. We introduce UniPath, a semantics-driven pathology image generation framework that leverages mature diagnostic understanding to enable controllable generation. UniPath implements Multi-Stream Control: a Raw-Text stream; a High-Level Semantics stream that uses learnable queries to a frozen pathology MLLM to distill paraphrase-robust Diagnostic Semantic Tokens and to expand prompts into diagnosis-aware attribute bundles; and a Prototype stream that affords component-level morphological control via a prototype bank. On the data front, we curate a 2.65M image-text corpus and a finely annotated, high-quality 68K subset to alleviate data scarcity. For a comprehensive assessment, we establish a four-tier evaluation hierarchy tailored to pathology. Extensive experiments demonstrate UniPath's SOTA performance, including a Patho-FID of 80.9 (51% better than the second-best) and fine-grained semantic control achieving 98.7% of the real-image. The meticulously curated datasets, complete source code, and pre-trained model weights developed in this study will be made openly accessible to the public.

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.

Identifying patient cohorts is fundamental to numerous healthcare tasks, including clinical trial recruitment and retrospective studies. Current cohort retrieval methods in healthcare organizations rely on automated queries of structured data combined with manual curation, which are time-consuming, labor-intensive, and often yield low-quality results. Recent advancements in large language models (LLMs) and information retrieval (IR) offer promising avenues to revolutionize these systems. Major challenges include managing extensive eligibility criteria and handling the longitudinal nature of unstructured Electronic Medical Records (EMRs) while ensuring that the solution remains cost-effective for real-world application. This paper introduces a new task, Automatic Cohort Retrieval (ACR), and evaluates the performance of LLMs and commercial, domain-specific neuro-symbolic approaches. We provide a benchmark task, a query dataset, an EMR dataset, and an evaluation framework. Our findings underscore the necessity for efficient, high-quality ACR systems capable of longitudinal reasoning across extensive patient databases.

Understanding causal narratives communicated in clinical notes can help make strides towards personalized healthcare. Extracted causal information from clinical notes can be combined with structured EHR data such as patients' demographics, diagnoses, and medications. This will enhance healthcare providers' ability to identify aspects of a patient's story communicated in the clinical notes and help make more informed decisions. In this work, we propose annotation guidelines, develop an annotated corpus and provide baseline scores to identify types and direction of causal relations between a pair of biomedical concepts in clinical notes; communicated implicitly or explicitly, identified either in a single sentence or across multiple sentences. We annotate a total of 2714 de-identified examples sampled from the 2018 n2c2 shared task dataset and train four different language model based architectures. Annotation based on our guidelines achieved a high inter-annotator agreement i.e. Fleiss' kappa (kappa) score of 0.72, and our model for identification of causal relations achieved a macro F1 score of 0.56 on the test data. The high inter-annotator agreement for clinical text shows the quality of our annotation guidelines while the provided baseline F1 score sets the direction for future research towards understanding narratives in clinical texts.

Alzheimer's Disease (AD) is marked by significant inter-individual variability in its progression, complicating accurate prognosis and personalized care planning. This heterogeneity underscores the critical need for predictive models capable of forecasting patient-specific disease trajectories. Artificial Intelligence (AI) offers powerful tools to address this challenge by analyzing complex, multi-modal, and longitudinal patient data. This paper provides a comprehensive survey of AI methodologies applied to personalized AD progression prediction. We review key approaches including state-space models for capturing temporal dynamics, deep learning techniques like Recurrent Neural Networks for sequence modeling, Graph Neural Networks (GNNs) for leveraging network structures, and the emerging concept of AI-driven digital twins for individualized simulation. Recognizing that data limitations often impede progress, we examine common challenges such as high dimensionality, missing data, and dataset imbalance. We further discuss AI-driven mitigation strategies, with a specific focus on synthetic data generation using Variational Autoencoders (VAEs) and Generative Adversarial Networks (GANs) to augment and balance datasets. The survey synthesizes the strengths and limitations of current approaches, emphasizing the trend towards multimodal integration and the persistent need for model interpretability and generalizability. Finally, we identify critical open challenges, including robust external validation, clinical integration, and ethical considerations, and outline promising future research directions such as hybrid models, causal inference, and federated learning. This review aims to consolidate current knowledge and guide future efforts in developing clinically relevant AI tools for personalized AD prognostication.

This work investigates the reproducibility of the paper 'Explaining RL decisions with trajectories'. The original paper introduces a novel approach in explainable reinforcement learning based on the attribution decisions of an agent to specific clusters of trajectories encountered during training. We verify the main claims from the paper, which state that (i) training on less trajectories induces a lower initial state value, (ii) trajectories in a cluster present similar high-level patterns, (iii) distant trajectories influence the decision of an agent, and (iv) humans correctly identify the attributed trajectories to the decision of the agent. We recover the environments used by the authors based on the partial original code they provided for one of the environments (Grid-World), and implemented the remaining from scratch (Seaquest, HalfCheetah, Breakout and Q*Bert). While we confirm that (i), (ii), and (iii) partially hold, we extend on the largely qualitative experiments from the authors by introducing a quantitative metric to further support (iii), and new experiments and visual results for (i). Moreover, we investigate the use of different clustering algorithms and encoder architectures to further support (ii). We could not support (iv), given the limited extent of the original experiments. We conclude that, while some of the claims can be supported, further investigations and experiments could be of interest. We recognise the novelty of the work from the authors and hope that our work paves the way for clearer and more transparent approaches.

Real-world clinical diagnosis is a complex process in which the doctor is required to obtain information from both interaction with the patient and conducting medical exams. Additionally, the doctor needs to adapt to different patient personas, as well as noisy and incomplete information that can happen at any time during the process. However, existing benchmarks for medical LLMs and methods for automatic diagnosis largely simplify this process by reducing it to single-turn question answering, noise-free conversations, or sequential exam making, etc., ignoring the interactive and uncertain nature of clinical diagnosis. In this paper, we aim to address this gap by formalizing clinical diagnosis as a Partially Observable Markov Decision Process (POMDP) with three action types: questioning the patient, ordering medical exams as tool calls, and issuing a diagnosis. We also introduce a systematic noise model comprising seven patient noise types and three exam noise types. Using our proposed environment, we train an effective diagnosis agent, MedExAgent, through a two-stage pipeline that first performs supervised finetuning on synthetic conversations structured after the Calgary-Cambridge model for clinical interviews, and then applies DAPO to optimize a composite reward capturing diagnostic accuracy, tool call quality, and exam cost including financial cost and patient discomfort. Through extensive experiments and ablation studies, we demonstrate that MedExAgent achieves diagnostic performance comparable to larger models while maintaining cost-efficient examination strategies.

Clinical diagnosis of the eye is performed over multifarious data modalities including scalar clinical labels, vectorized biomarkers, two-dimensional fundus images, and three-dimensional Optical Coherence Tomography (OCT) scans. Clinical practitioners use all available data modalities for diagnosing and treating eye diseases like Diabetic Retinopathy (DR) or Diabetic Macular Edema (DME). Enabling usage of machine learning algorithms within the ophthalmic medical domain requires research into the relationships and interactions between all relevant data over a treatment period. Existing datasets are limited in that they neither provide data nor consider the explicit relationship modeling between the data modalities. In this paper, we introduce the Ophthalmic Labels for Investigating Visual Eye Semantics (OLIVES) dataset that addresses the above limitation. This is the first OCT and near-IR fundus dataset that includes clinical labels, biomarker labels, disease labels, and time-series patient treatment information from associated clinical trials. The dataset consists of 1268 near-IR fundus images each with at least 49 OCT scans, and 16 biomarkers, along with 4 clinical labels and a disease diagnosis of DR or DME. In total, there are 96 eyes' data averaged over a period of at least two years with each eye treated for an average of 66 weeks and 7 injections. We benchmark the utility of OLIVES dataset for ophthalmic data as well as provide benchmarks and concrete research directions for core and emerging machine learning paradigms within medical image analysis.

We develop graph-based methods for semi-supervised learning based on label propagation on a data similarity graph. When data is abundant or arrive in a stream, the problems of computation and data storage arise for any graph-based method. We propose a fast approximate online algorithm that solves for the harmonic solution on an approximate graph. We show, both empirically and theoretically, that good behavior can be achieved by collapsing nearby points into a set of local representative points that minimize distortion. Moreover, we regularize the harmonic solution to achieve better stability properties. We also present graph-based methods for detecting conditional anomalies and apply them to the identification of unusual clinical actions in hospitals. Our hypothesis is that patient-management actions that are unusual with respect to the past patients may be due to errors and that it is worthwhile to raise an alert if such a condition is encountered. Conditional anomaly detection extends standard unconditional anomaly framework but also faces new problems known as fringe and isolated points. We devise novel nonparametric graph-based methods to tackle these problems. Our methods rely on graph connectivity analysis and soft harmonic solution. Finally, we conduct an extensive human evaluation study of our conditional anomaly methods by 15 experts in critical care.

Vision-Language Models (VLMs) are advancing computational pathology with superior visual understanding capabilities. However, current systems often reduce diagnosis to directly output conclusions without verifiable evidence-linked reasoning, which severely limits clinical trust and hinders expert error rectification. To address these barriers, we construct PathReasoner, the first large-scale dataset of whole-slide image (WSI) reasoning. Unlike previous work reliant on unverified distillation, we develop a rigorous knowledge-guided generation pipeline. By leveraging medical knowledge graphs, we explicitly align structured pathological findings and clinical reasoning with diagnoses, generating over 20K high-quality instructional samples. Based on the database, we propose PathReasoner-R1, which synergizes trajectory-masked supervised fine-tuning with reasoning-oriented reinforcement learning to instill structured chain-of-thought capabilities. To ensure medical rigor, we engineer a knowledge-aware multi-granular reward function incorporating an Entity Reward mechanism strictly aligned with knowledge graphs. This effectively guides the model to optimize for logical consistency rather than mere outcome matching, thereby enhancing robustness. Extensive experiments demonstrate that PathReasoner-R1 achieves state-of-the-art performance on both PathReasoner and public benchmarks across various image scales, equipping pathology models with transparent, clinically grounded reasoning capabilities. Dataset and code are available at https://github.com/cyclexfy/PathReasoner-R1.

Practitioners frequently aim to infer an unobserved population trajectory using sample snapshots at multiple time points. For instance, in single-cell sequencing, scientists would like to learn how gene expression evolves over time. But sequencing any cell destroys that cell. So we cannot access any cell's full trajectory, but we can access snapshot samples from many cells. Stochastic differential equations are commonly used to analyze systems with full individual-trajectory access; since here we have only sample snapshots, these methods are inapplicable. The deep learning community has recently explored using Schr\"odinger bridges (SBs) and their extensions to estimate these dynamics. However, these methods either (1) interpolate between just two time points or (2) require a single fixed reference dynamic within the SB, which is often just set to be Brownian motion. But learning piecewise from adjacent time points can fail to capture long-term dependencies. And practitioners are typically able to specify a model class for the reference dynamic but not the exact values of the parameters within it. So we propose a new method that (1) learns the unobserved trajectories from sample snapshots across multiple time points and (2) requires specification only of a class of reference dynamics, not a single fixed one. In particular, we suggest an iterative projection method inspired by Schr\"odinger bridges; we alternate between learning a piecewise SB on the unobserved trajectories and using the learned SB to refine our best guess for the dynamics within the reference class. We demonstrate the advantages of our method via a well-known simulated parametric model from ecology, simulated and real data from systems biology, and real motion-capture data.

Despite achieving high accuracy on medical benchmarks, LLMs exhibit the Einstellung Effect in clinical diagnosis--relying on statistical shortcuts rather than patient-specific evidence, causing misdiagnosis in atypical cases. Existing benchmarks fail to detect this critical failure mode. We introduce MedEinst, a counterfactual benchmark with 5,383 paired clinical cases across 49 diseases. Each pair contains a control case and a "trap" case with altered discriminative evidence that flips the diagnosis. We measure susceptibility via Bias Trap Rate--probability of misdiagnosing traps despite correctly diagnosing controls. Extensive Evaluation of 17 LLMs shows frontier models achieve high baseline accuracy but severe bias trap rates. Thus, we propose ECR-Agent, aligning LLM reasoning with Evidence-Based Medicine standard via two components: (1) Dynamic Causal Inference (DCI) performs structured reasoning through dual-pathway perception, dynamic causal graph reasoning across three levels (association, intervention, counterfactual), and evidence audit for final diagnosis; (2) Critic-Driven Graph and Memory Evolution (CGME) iteratively refines the system by storing validated reasoning paths in an exemplar base and consolidating disease-specific knowledge into evolving illness graphs. Source code is to be released.

The PI-CAI (Prostate Imaging: Cancer AI) challenge led to expert-level diagnostic algorithms for clinically significant prostate cancer detection. The algorithms receive biparametric MRI scans as input, which consist of T2-weighted and diffusion-weighted scans. These scans can be misaligned due to multiple factors in the scanning process. Image registration can alleviate this issue by predicting the deformation between the sequences. We investigate the effect of image registration on the diagnostic performance of AI-based prostate cancer diagnosis. First, the image registration algorithm, developed in MeVisLab, is analyzed using a dataset with paired lesion annotations. Second, the effect on diagnosis is evaluated by comparing case-level cancer diagnosis performance between using the original dataset, rigidly aligned diffusion-weighted scans, or deformably aligned diffusion-weighted scans. Rigid registration showed no improvement. Deformable registration demonstrated a substantial improvement in lesion overlap (+10% median Dice score) and a positive yet non-significant improvement in diagnostic performance (+0.3% AUROC, p=0.18). Our investigation shows that a substantial improvement in lesion alignment does not directly lead to a significant improvement in diagnostic performance. Qualitative analysis indicated that jointly developing image registration methods and diagnostic AI algorithms could enhance diagnostic accuracy and patient outcomes.

Deep learning based automated pathological diagnosis has markedly improved diagnostic efficiency and reduced variability between observers, yet its clinical adoption remains limited by opaque model decisions and a lack of traceable rationale. To address this, recent multimodal visual reasoning architectures provide a unified framework that generates segmentation masks at the pixel level alongside semantically aligned textual explanations. By localizing lesion regions and producing expert style diagnostic narratives, these models deliver the transparent and interpretable insights necessary for dependable AI assisted pathology. Building on these advancements, we propose PathMR, a cell-level Multimodal visual Reasoning framework for Pathological image analysis. Given a pathological image and a textual query, PathMR generates expert-level diagnostic explanations while simultaneously predicting cell distribution patterns. To benchmark its performance, we evaluated our approach on the publicly available PathGen dataset as well as on our newly developed GADVR dataset. Extensive experiments on these two datasets demonstrate that PathMR consistently outperforms state-of-the-art visual reasoning methods in text generation quality, segmentation accuracy, and cross-modal alignment. These results highlight the potential of PathMR for improving interpretability in AI-driven pathological diagnosis. The code will be publicly available in https://github.com/zhangye-zoe/PathMR.

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.

Surgical future prediction, driven by real-time AI analysis of surgical video, is critical for operating room safety and efficiency. It provides actionable insights into upcoming events, their timing, and risks-enabling better resource allocation, timely instrument readiness, and early warnings for complications (e.g., bleeding, bile duct injury). Despite this need, current surgical AI research focuses on understanding what is happening rather than predicting future events. Existing methods target specific tasks in isolation, lacking unified approaches that span both short-term (action triplets, events) and long-term horizons (remaining surgery duration, phase transitions). These methods rely on coarse-grained supervision while fine-grained surgical action triplets and steps remain underexplored. Furthermore, methods based only on future feature prediction struggle to generalize across different surgical contexts and procedures. We address these limits by reframing surgical future prediction as state-change learning. Rather than forecasting raw observations, our approach classifies state transitions between current and future timesteps. We introduce SurgFUTR, implementing this through a teacher-student architecture. Video clips are compressed into state representations via Sinkhorn-Knopp clustering; the teacher network learns from both current and future clips, while the student network predicts future states from current videos alone, guided by our Action Dynamics (ActDyn) module. We establish SFPBench with five prediction tasks spanning short-term (triplets, events) and long-term (remaining surgery duration, phase and step transitions) horizons. Experiments across four datasets and three procedures show consistent improvements. Cross-procedure transfer validates generalizability.

Vision-Language Models (VLMs) frequently "hallucinate" - generate plausible yet factually incorrect statements - posing a critical barrier to their trustworthy deployment. In this work, we propose a new paradigm for diagnosing hallucinations, recasting them from static output errors into dynamic pathologies of a model's computational cognition. Our framework is grounded in a normative principle of computational rationality, allowing us to model a VLM's generation as a dynamic cognitive trajectory. We design a suite of information-theoretic probes that project this trajectory onto an interpretable, low-dimensional Cognitive State Space. Our central discovery is a governing principle we term the geometric-information duality: a cognitive trajectory's geometric abnormality within this space is fundamentally equivalent to its high information-theoretic surprisal. Hallucination detection is counts as a geometric anomaly detection problem. Evaluated across diverse settings - from rigorous binary QA (POPE) and comprehensive reasoning (MME) to unconstrained open-ended captioning (MS-COCO) - our framework achieves state-of-the-art performance. Crucially, it operates with high efficiency under weak supervision and remains highly robust even when calibration data is heavily contaminated. This approach enables a causal attribution of failures, mapping observable errors to distinct pathological states: perceptual instability (measured by Perceptual Entropy), logical-causal failure (measured by Inferential Conflict), and decisional ambiguity (measured by Decision Entropy). Ultimately, this opens a path toward building AI systems whose reasoning is transparent, auditable, and diagnosable by design.

Predictive process monitoring is a process mining task aimed at forecasting information about a running process trace, such as the most correct next activity to be executed. In medical domains, predictive process monitoring can provide valuable decision support in atypical and nontrivial situations. Decision support and quality assessment in medicine cannot ignore domain knowledge, in order to be grounded on all the available information (which is not limited to data) and to be really acceptable by end users. In this paper, we propose a predictive process monitoring approach relying on the use of a {\em transformer}, a deep learning architecture based on the attention mechanism. A major contribution of our work lies in the incorporation of ontological domain-specific knowledge, carried out through a graph positional encoding technique. The paper presents and discusses the encouraging experimental result we are collecting in the domain of stroke management.

Positron emission tomography (PET) is a cornerstone of modern oncologic and neurologic imaging, distinguished by its unique ability to illuminate dynamic metabolic processes that transcend the anatomical focus of traditional imaging technologies. Radiology reports are essential for clinical decision making, yet their manual creation is labor-intensive and time-consuming. Recent advancements of vision-language models (VLMs) have shown strong potential in medical applications, presenting a promising avenue for automating report generation. However, existing applications of VLMs in the medical domain have predominantly focused on structural imaging modalities, while the unique characteristics of molecular PET imaging have largely been overlooked. To bridge the gap, we introduce PET2Rep, a large-scale comprehensive benchmark for evaluation of general and medical VLMs for radiology report generation for PET images. PET2Rep stands out as the first dedicated dataset for PET report generation with metabolic information, uniquely capturing whole-body image-report pairs that cover dozens of organs to fill the critical gap in existing benchmarks and mirror real-world clinical comprehensiveness. In addition to widely recognized natural language generation metrics, we introduce a series of clinical efficiency metrics to evaluate the quality of radiotracer uptake pattern description in key organs in generated reports. We conduct a head-to-head comparison of 30 cutting-edge general-purpose and medical-specialized VLMs. The results show that the current state-of-the-art VLMs perform poorly on PET report generation task, falling considerably short of fulfilling practical needs. Moreover, we identify several key insufficiency that need to be addressed to advance the development in medical applications.

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.

Chest Xray imaging is a widely used diagnostic tool in modern medicine, and its high utilization creates substantial workloads for radiologists. To alleviate this burden, vision language models are increasingly applied to automate Chest Xray radiology report generation (CXRRRG), aiming for clinically accurate descriptions while reducing manual effort. Conventional approaches, however, typically rely on single images, failing to capture the longitudinal context necessary for producing clinically faithful comparison statements. Recently, growing attention has been directed toward incorporating longitudinal data into CXR RRG, enabling models to leverage historical studies in ways that mirror radiologists diagnostic workflows. Nevertheless, existing surveys primarily address single image CXRRRG and offer limited guidance for longitudinal settings, leaving researchers without a systematic framework for model design. To address this gap, this survey provides the first comprehensive review of longitudinal radiology report generation (LRRG). Specifically, we examine dataset construction strategies, report generation architectures alongside longitudinally tailored designs, and evaluation protocols encompassing both longitudinal specific measures and widely used benchmarks. We further summarize LRRG methods performance, alongside analyses of different ablation studies, which collectively highlight the critical role of longitudinal information and architectural design choices in improving model performance. Finally, we summarize five major limitations of current research and outline promising directions for future development, aiming to lay a foundation for advancing this emerging field.

Generative models trained using self-supervision of tokenized electronic health record (EHR) timelines show promise for clinical outcome prediction. This is typically done using Monte Carlo simulation for future patient trajectories. However, existing approaches suffer from three key limitations: sparse estimate distributions that poorly differentiate patient risk levels, extreme computational costs, and high sampling variance. We propose two new estimators: the Sum of Conditional Outcome Probability Estimator (SCOPE) and Risk Estimation from Anticipated Conditional Hazards (REACH), that leverage next-token probability distributions discarded by standard Monte Carlo. We prove both estimators are unbiased and that REACH guarantees variance reduction over Monte Carlo sampling for any model and outcome. Empirically, on hospital mortality prediction in MIMIC-IV using the ETHOS-ARES framework, SCOPE and REACH match 100-sample Monte Carlo performance using only 10-11 samples (95% CI: [9,11]), representing a ~10x reduction in inference cost without degrading calibration. For ICU admission prediction, efficiency gains are more modest (~1.2x), which we attribute to the outcome's lower "spontaneity," a property we characterize theoretically and empirically. These methods substantially improve the feasibility of deploying generative EHR models in resource-constrained clinical settings.

Cell tracking is a subject of active research gathering great interest in medicine and biology. Positron emission tomography (PET) is well suited for tracking radio-labeled cells in vivo due to its exceptional sensitivity and whole-body capability. For validation, ground-truth data are desirable that realistically mimic the flow of cells in a clinical situation. This study develops a workflow (CeFloPS) for simulating moving radio-labeled cells in a human phantom. From the XCAT phantom, the blood vessels are reduced to nodal networks along which cells can move and distribute to organs and tissues. The movement is directed by the blood flow, which is calculated in each node using the Hagen-Pooiseuille equation and Kirchhoff's laws assuming laminar flow. Organs are voxelized and movement of cells from artery entry to vein exit is generated via a biased 3D random walk. The probabilities of cells moving or remaining in tissues are derived from rate constants of tracer kinetic-based compartment modeling. PET listmode data is generated using the Monte-Carlo simulation framework GATE based on the definition of a large-body PET scanner with cell paths as moving radioactive sources and the XCAT phantom providing attenuation data. From the flow simulation of 100,000 cells, 100 sample cells were further processed by GATE and listmode data was reconstructed into images for comparison. As demonstrated by comparisons of simulated and reconstructed cell distributions, CeFloPS is capable of simulating cell behavior in whole-body PET. It achieves this simulation in a way that is anatomically and physiologically reasonable, thereby providing valuable data for the development and validation of cell tracking algorithms.

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

Recently, intelligent analysis of lung nodules with the assistant of computer aided detection (CAD) techniques can improve the accuracy rate of lung cancer diagnosis. However, existing CAD systems and pulmonary datasets mainly focus on Computed Tomography (CT) images from one single period, while ignoring the cross spatio-temporal features associated with the progression of nodules contained in imaging data from various captured periods of lung cancer. If the evolution patterns of nodules across various periods in the patients' CT sequences can be explored, it will play a crucial role in guiding the precise screening identification of lung cancer. Therefore, a cross spatio-temporal lung nodule dataset with pathological information for nodule identification and diagnosis is constructed, which contains 328 CT sequences and 362 annotated nodules from 109 patients. This comprehensive database is intended to drive research in the field of CAD towards more practical and robust methods, and also contribute to the further exploration of precision medicine related field. To ensure patient confidentiality, we have removed sensitive information from the dataset.

In clinical radiology reports, doctors capture important information about the patient's health status. They convey their observations from raw medical imaging data about the inner structures of a patient. As such, formulating reports requires medical experts to possess wide-ranging knowledge about anatomical regions with their normal, healthy appearance as well as the ability to recognize abnormalities. This explicit grasp on both the patient's anatomy and their appearance is missing in current medical image-processing systems as annotations are especially difficult to gather. This renders the models to be narrow experts e.g. for identifying specific diseases. In this work, we recover this missing link by adding human anatomy into the mix and enable the association of content in medical reports to their occurrence in associated imagery (medical phrase grounding). To exploit anatomical structures in this scenario, we present a sophisticated automatic pipeline to gather and integrate human bodily structures from computed tomography datasets, which we incorporate in our PAXRay: A Projected dataset for the segmentation of Anatomical structures in X-Ray data. Our evaluation shows that methods that take advantage of anatomical information benefit heavily in visually grounding radiologists' findings, as our anatomical segmentations allow for up to absolute 50% better grounding results on the OpenI dataset as compared to commonly used region proposals. The PAXRay dataset is available at https://constantinseibold.github.io/paxray/.

Recent developments in Large Language Model (LLM)-based agents have shown impressive capabilities spanning multiple domains, exemplified by deep research systems that demonstrate superior performance on complex information-seeking and synthesis tasks. While general-purpose deep research agents have shown impressive capabilities, they struggle significantly with medical domain challenges, as evidenced by leading proprietary systems achieving limited accuracy on complex medical benchmarks. The key limitations are: (1) the model lacks sufficient dense medical knowledge for clinical reasoning, and (2) the framework is constrained by the absence of specialized retrieval tools tailored for medical contexts.We present a medical deep research agent that addresses these challenges through two core innovations. First, we develop a novel data synthesis framework using medical knowledge graphs, extracting the longest chains from subgraphs around rare medical entities to generate complex multi-hop question-answer pairs. Second, we integrate a custom-built private medical retrieval engine alongside general-purpose tools, enabling accurate medical information synthesis. Our approach generates 2100+ diverse trajectories across 12 medical specialties, each averaging 4.2 tool interactions.Through a two-stage training paradigm combining supervised fine-tuning and online reinforcement learning with composite rewards, our MedResearcher-R1-32B model demonstrates exceptional performance, establishing new state-of-the-art results on medical benchmarks while maintaining competitive performance on general deep research tasks. Our work demonstrates that strategic domain-specific innovations in architecture, tool design, and training data construction can enable smaller open-source models to outperform much larger proprietary systems in specialized domains.

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.

We present a labeled large-scale, high resolution chest x-ray dataset for the automated exploration of medical images along with their associated reports. This dataset includes more than 160,000 images obtained from 67,000 patients that were interpreted and reported by radiologists at Hospital San Juan Hospital (Spain) from 2009 to 2017, covering six different position views and additional information on image acquisition and patient demography. The reports were labeled with 174 different radiographic findings, 19 differential diagnoses and 104 anatomic locations organized as a hierarchical taxonomy and mapped onto standard Unified Medical Language System (UMLS) terminology. Of these reports, 27% were manually annotated by trained physicians and the remaining set was labeled using a supervised method based on a recurrent neural network with attention mechanisms. The labels generated were then validated in an independent test set achieving a 0.93 Micro-F1 score. To the best of our knowledge, this is one of the largest public chest x-ray database suitable for training supervised models concerning radiographs, and the first to contain radiographic reports in Spanish. The PadChest dataset can be downloaded from http://bimcv.cipf.es/bimcv-projects/padchest/.

LLMs for clinical decision support often fail under small but clinically meaningful input shifts such as masking a symptom or negating a finding, despite high performance on static benchmarks. These reasoning failures frequently go undetected by standard NLP metrics, which are insensitive to latent representation shifts that drive diagnosis instability. We propose a geometry-aware evaluation framework, LAPD (Latent Agentic Perturbation Diagnostics), which systematically probes the latent robustness of clinical LLMs under structured adversarial edits. Within this framework, we introduce Latent Diagnosis Flip Rate (LDFR), a model-agnostic diagnostic signal that captures representational instability when embeddings cross decision boundaries in PCA-reduced latent space. Clinical notes are generated using a structured prompting pipeline grounded in diagnostic reasoning, then perturbed along four axes: masking, negation, synonym replacement, and numeric variation to simulate common ambiguities and omissions. We compute LDFR across both foundation and clinical LLMs, finding that latent fragility emerges even under minimal surface-level changes. Finally, we validate our findings on 90 real clinical notes from the DiReCT benchmark (MIMIC-IV), confirming the generalizability of LDFR beyond synthetic settings. Our results reveal a persistent gap between surface robustness and semantic stability, underscoring the importance of geometry-aware auditing in safety-critical clinical AI.

During the radiotherapy treatment of patients with lung cancer, the radiation delivered to healthy tissue around the tumor needs to be minimized, which is difficult because of respiratory motion and the latency of linear accelerator systems. In the proposed study, we first use the Lucas-Kanade pyramidal optical flow algorithm to perform deformable image registration of chest computed tomography scan images of four patients with lung cancer. We then track three internal points close to the lung tumor based on the previously computed deformation field and predict their position with a recurrent neural network (RNN) trained using real-time recurrent learning (RTRL) and gradient clipping. The breathing data is quite regular, sampled at approximately 2.5Hz, and includes artificial drift in the spine direction. The amplitude of the motion of the tracked points ranged from 12.0mm to 22.7mm. Finally, we propose a simple method for recovering and predicting 3D tumor images from the tracked points and the initial tumor image based on a linear correspondence model and Nadaraya-Watson non-linear regression. The root-mean-square error, maximum error, and jitter corresponding to the RNN prediction on the test set were smaller than the same performance measures obtained with linear prediction and least mean squares (LMS). In particular, the maximum prediction error associated with the RNN, equal to 1.51mm, is respectively 16.1% and 5.0% lower than the maximum error associated with linear prediction and LMS. The average prediction time per time step with RTRL is equal to 119ms, which is less than the 400ms marker position sampling time. The tumor position in the predicted images appears visually correct, which is confirmed by the high mean cross-correlation between the original and predicted images, equal to 0.955.

This paper reports on the second "Throughput" phase of the Tracking Machine Learning (TrackML) challenge on the Codalab platform. As in the first "Accuracy" phase, the participants had to solve a difficult experimental problem linked to tracking accurately the trajectory of particles as e.g. created at the Large Hadron Collider (LHC): given O(10^5) points, the participants had to connect them into O(10^4) individual groups that represent the particle trajectories which are approximated helical. While in the first phase only the accuracy mattered, the goal of this second phase was a compromise between the accuracy and the speed of inference. Both were measured on the Codalab platform where the participants had to upload their software. The best three participants had solutions with good accuracy and speed an order of magnitude faster than the state of the art when the challenge was designed. Although the core algorithms were less diverse than in the first phase, a diversity of techniques have been used and are described in this paper. The performance of the algorithms are analysed in depth and lessons derived.

Across the world's coronavirus disease 2019 (COVID-19) hot spots, the need to streamline patient diagnosis and management has become more pressing than ever. As one of the main imaging tools, chest X-rays (CXRs) are common, fast, non-invasive, relatively cheap, and potentially bedside to monitor the progression of the disease. This paper describes the first public COVID-19 image data collection as well as a preliminary exploration of possible use cases for the data. This dataset currently contains hundreds of frontal view X-rays and is the largest public resource for COVID-19 image and prognostic data, making it a necessary resource to develop and evaluate tools to aid in the treatment of COVID-19. It was manually aggregated from publication figures as well as various web based repositories into a machine learning (ML) friendly format with accompanying dataloader code. We collected frontal and lateral view imagery and metadata such as the time since first symptoms, intensive care unit (ICU) status, survival status, intubation status, or hospital location. We present multiple possible use cases for the data such as predicting the need for the ICU, predicting patient survival, and understanding a patient's trajectory during treatment. Data can be accessed here: https://github.com/ieee8023/covid-chestxray-dataset

With the rapid development of artificial intelligence, large language models (LLMs) have shown promising capabilities in mimicking human-level language comprehension and reasoning. This has sparked significant interest in applying LLMs to enhance various aspects of healthcare, ranging from medical education to clinical decision support. However, medicine involves multifaceted data modalities and nuanced reasoning skills, presenting challenges for integrating LLMs. This paper provides a comprehensive review on the applications and implications of LLMs in medicine. It begins by examining the fundamental applications of general-purpose and specialized LLMs, demonstrating their utilities in knowledge retrieval, research support, clinical workflow automation, and diagnostic assistance. Recognizing the inherent multimodality of medicine, the review then focuses on multimodal LLMs, investigating their ability to process diverse data types like medical imaging and EHRs to augment diagnostic accuracy. To address LLMs' limitations regarding personalization and complex clinical reasoning, the paper explores the emerging development of LLM-powered autonomous agents for healthcare. Furthermore, it summarizes the evaluation methodologies for assessing LLMs' reliability and safety in medical contexts. Overall, this review offers an extensive analysis on the transformative potential of LLMs in modern medicine. It also highlights the pivotal need for continuous optimizations and ethical oversight before these models can be effectively integrated into clinical practice. Visit https://github.com/mingze-yuan/Awesome-LLM-Healthcare for an accompanying GitHub repository containing latest papers.