The competency of any intelligent agent is bounded by its formal account of the world in which it operates. Clinical AI lacks such an account. Existing frameworks address evaluation, regulation, or system design in isolation, without a shared model of the clinical world to connect them. We introduce the Clinical World Model, a framework that formalizes care as a tripartite interaction among Patient, Provider, and Ecosystem. To formalize how any agent, whether human or artificial, transforms information into clinical action, we develop parallel decision-making architectures for providers, patients, and AI agents, grounded in validated principles of clinical cognition. The Clinical AI Skill-Mix operationalizes competency through eight dimensions. Five define the clinical competency space (condition, phase, care setting, provider role, and task) and three specify how AI engages human reasoning (assigned authority, agent facing, and anchoring layer). The combinatorial product of these dimensions yields a space of billions of distinct competency coordinates. A central structural implication is that validation within one coordinate provides minimal evidence for performance in another, re
Brain structural MRI has been widely used to assess the future progression of cognitive impairment (CI). Previous learning-based studies usually suffer from the issue of small-sized labeled training data, while there exist a huge amount of structural MRIs in large-scale public databases. Intuitively, brain anatomical structures derived from these public MRIs (even without task-specific label information) can be used to boost CI progression trajectory prediction. However, previous studies seldom take advantage of such brain anatomy prior. To this end, this paper proposes a brain anatomy prior modeling (BAPM) framework to forecast the clinical progression of cognitive impairment with small-sized target MRIs by exploring anatomical brain structures. Specifically, the BAPM consists of a pretext model and a downstream model, with a shared brain anatomy-guided encoder to model brain anatomy prior explicitly. Besides the encoder, the pretext model also contains two decoders for two auxiliary tasks (i.e., MRI reconstruction and brain tissue segmentation), while the downstream model relies on a predictor for classification. The brain anatomy-guided encoder is pre-trained with the pretext mo
We introduce Clinical ModernBERT, a transformer based encoder pretrained on large scale biomedical literature, clinical notes, and medical ontologies, incorporating PubMed abstracts, MIMIC IV clinical data, and medical codes with their textual descriptions. Building on ModernBERT the current state of the art natural language text encoder featuring architectural upgrades such as rotary positional embeddings (RoPE), Flash Attention, and extended context length up to 8,192 tokens our model adapts these innovations specifically for biomedical and clinical domains. Clinical ModernBERT excels at producing semantically rich representations tailored for long context tasks. We validate this both by analyzing its pretrained weights and through empirical evaluation on a comprehensive suite of clinical NLP benchmarks.
Empiric antibiotic prescribing in high-risk clinical contexts often requires decision making under conditions of incomplete information, where inappropriate coverage or unjustified escalation may compromise safety and antimicrobial stewardship. While clinical decision-support systems have been proposed to assist in this process, many approaches lack explicit governance and evaluation mechanisms defining scope, abstention conditions, recommendation permissibility, and expected system behavior. This work specifies a governance and evaluation framework for deterministic clinical decision-support systems operating under explicitly constrained scope. Deterministic behavior is adopted to ensure that identical inputs yield identical outputs, supporting transparency, auditability, and conservative decision support in high-risk prescribing contexts. The framework treats governance as a first-class design component, separating clinical decision logic from rule-based mechanisms that determine whether a recommendation may be issued. Explicit abstention, deterministic stewardship constraints, and exclusion rules are formalized as core constructs. The framework defines an evaluation methodology
Introduction: Semantic search, which retrieves documents based on conceptual similarity rather than keyword matching, offers substantial advantages for retrieval of clinical information. However, deploying semantic search across entire health systems, comprising hundreds of millions of clinical notes, presents formidable engineering, cost, and governance challenges that have prevented adoption. Methods: We deployed a semantic search system at a large children's hospital indexing 166 million clinical notes (484 million vectors) from 1.68 million patients. The system uses instruction-tuned qwen3-embedding-0.6B embeddings, stores vectors in a managed database with storage-optimized indexing, maintains full-text metadata in a low-latency key-value store, and operates within a HIPAA-compliant governance framework. We evaluated the system through three experiments: optimization of embedding model and chunking strategy using a physician-authored benchmark dataset, characterization of full-scale performance (cost, latency, retrieval quality), and clinical utility assessment via comparison of chart abstraction efficiency across three tasks. Results: The system delivers sub-second query late
Clinical AI development has traditionally followed a collaborative paradigm that depends on close interaction between clinicians and specialized AI teams. This paradigm imposes a practical challenge: clinicians must repeatedly communicate and refine their requirements with AI developers before those requirements can be translated into executable model development. This iterative process is time-consuming, and even after repeated discussion, misalignment may still exist because the two sides do not fully share each other's expertise. However, autonomous coding agents may change this paradigm, raising the possibility that clinicians could develop clinical AI models independently through natural-language interaction alone. In this study, we present such an autonomous prototype for clinician-driven clinical AI development. We evaluated the system on five clinical tasks spanning dermoscopic lesion classification, melanoma-versus-nevus triage, wrist-fracture detection (including a weakly supervised variant with only 5% bounding-box annotations), and debiased pneumothorax classification on chest radiographs. Across these settings, the system consistently developed models from clinician re
We introduce SoftTiger, a clinical large language model (CLaM) designed as a foundation model for healthcare workflows. The narrative and unstructured nature of clinical notes is a major obstacle for healthcare intelligentization. We address a critical problem of structuring clinical notes into clinical data, according to international interoperability standards. We collect and annotate data for three subtasks, namely, international patient summary, clinical impression and medical encounter. We then supervised fine-tuned a state-of-the-art LLM using public and credentialed clinical data. The training is orchestrated in a way that the target model can first support basic clinical tasks such as abbreviation expansion and temporal information extraction, and then learn to perform more complex downstream clinical tasks. Moreover, we address several modeling challenges in the healthcare context, e.g., extra long context window. Our blind pairwise evaluation shows that SoftTiger outperforms other popular open-source models and GPT-3.5, comparable to Gemini-pro, with a mild gap from GPT-4. We believe that LLMs may become a step-stone towards healthcare digitalization and democratization.
We propose a hierarchically structured variational inference model for accurately disentangling observable evidence of disease (e.g. brain lesions or atrophy) from subject-specific anatomy in brain MRIs. With flexible, partially autoregressive priors, our model (1) addresses the subtle and fine-grained dependencies that typically exist between anatomical and pathological generating factors of an MRI to ensure the clinical validity of generated samples; (2) preserves and disentangles finer pathological details pertaining to a patient's disease state. Additionally, we experiment with an alternative training configuration where we provide supervision to a subset of latent units. It is shown that (1) a partially supervised latent space achieves a higher degree of disentanglement between evidence of disease and subject-specific anatomy; (2) when the prior is formulated with an autoregressive structure, knowledge from the supervision can propagate to the unsupervised latent units, resulting in more informative latent representations capable of modelling anatomy-pathology interdependencies.
Digital Twins hold great potential to personalize clinical patient care, provided the concept is translated to meet specific requirements emerging from established clinical workflows. We present a general and unspecialized Digital Twin design combining knowledge graphs and ensemble learning to reflect the entire patient's clinical journey and assist clinicians in their decision-making. Such a design is predictive, modular, evolving, informed, interpretable and explainable, thus opening broad clinical applications.
We evaluate the impact of large language model-based clinical decision support in live care. In partnership with Penda Health, a network of primary care clinics in Nairobi, Kenya, we studied AI Consult, a tool that serves as a safety net for clinicians by identifying potential documentation and clinical decision-making errors. AI Consult integrates into clinician workflows, activating only when needed and preserving clinician autonomy. We conducted a quality improvement study, comparing outcomes for 39,849 patient visits performed by clinicians with or without access to AI Consult across 15 clinics. Visits were rated by independent physicians to identify clinical errors. Clinicians with access to AI Consult made relatively fewer errors: 16% fewer diagnostic errors and 13% fewer treatment errors. In absolute terms, the introduction of AI Consult would avert diagnostic errors in 22,000 visits and treatment errors in 29,000 visits annually at Penda alone. In a survey of clinicians with AI Consult, all clinicians said that AI Consult improved the quality of care they delivered, with 75% saying the effect was "substantial". These results required a clinical workflow-aligned AI Consult i
This paper is dedicated to the design and evaluation of the first AMR parser tailored for clinical notes. Our objective was to facilitate the precise transformation of the clinical notes into structured AMR expressions, thereby enhancing the interpretability and usability of clinical text data at scale. Leveraging the colon cancer dataset from the Temporal Histories of Your Medical Events (THYME) corpus, we adapted a state-of-the-art AMR parser utilizing continuous training. Our approach incorporates data augmentation techniques to enhance the accuracy of AMR structure predictions. Notably, through this learning strategy, our parser achieved an impressive F1 score of 88% on the THYME corpus's colon cancer dataset. Moreover, our research delved into the efficacy of data required for domain adaptation within the realm of clinical notes, presenting domain adaptation data requirements for AMR parsing. This exploration not only underscores the parser's robust performance but also highlights its potential in facilitating a deeper understanding of clinical narratives through structured semantic representations.
Bioinformatics platforms have significantly changed clinical diagnostics by facilitating the analysis of genomic data, thereby advancing personalized medicine and improving patient care. This study examines the integration, usage patterns, challenges, and impact of the Galaxy platform within clinical diagnostics laboratories. We employed a convergent parallel mixed-methods design, collecting quantitative survey data and qualitative insights from structured interviews with fifteen participants across various clinical roles. The findings indicate a wide adoption of Galaxy, with participants expressing high satisfaction due to its user-friendly interface and notable improvements in workflow efficiency and diagnostic accuracy. Challenges such as data security and training needs were also identified, highlighting the platform's role in simplifying complex data analysis tasks. This study contributes to understanding the transformative potential of Galaxy in clinical practice and offers recommendations for optimizing its integration and functionality. These insights are crucial for advancing clinical diagnostics and enhancing patient outcomes.
Despite the plethora of AI-based algorithms developed for anomaly detection in radiology, subsequent integration into clinical setting is rarely evaluated. In this work, we assess the applicability and utility of an AI-based model for brain aneurysm detection comparing the performance of two readers with different levels of experience (2 and 13 years). We aim to answer the following questions: 1) Do the readers improve their performance when assisted by the AI algorithm? 2) How much does the AI algorithm impact routine clinical workflow? We reuse and enlarge our open-access, Time-Of-Flight Magnetic Resonance Angiography dataset (N=460). We use 360 subjects for training/validating our algorithm and 100 as unseen test set for the reading session. Even though our model reaches state-of-the-art results on the test set (sensitivity=74%, false positive rate=1.6), we show that neither the junior nor the senior reader significantly increase their sensitivity (p=0.59, p=1, respectively). In addition, we find that reading time for both readers is significantly higher in the "AI-assisted" setting than in the "Unassisted" (+15 seconds, on average; p=3x10^(-4) junior, p=3x10^(-5) senior). The c
Specialised pre-trained language models are becoming more frequent in NLP since they can potentially outperform models trained on generic texts. BioBERT and BioClinicalBERT are two examples of such models that have shown promise in medical NLP tasks. Many of these models are overparametrised and resource-intensive, but thanks to techniques like Knowledge Distillation (KD), it is possible to create smaller versions that perform almost as well as their larger counterparts. In this work, we specifically focus on development of compact language models for processing clinical texts (i.e. progress notes, discharge summaries etc). We developed a number of efficient lightweight clinical transformers using knowledge distillation and continual learning, with the number of parameters ranging from 15 million to 65 million. These models performed comparably to larger models such as BioBERT and ClinicalBioBERT and significantly outperformed other compact models trained on general or biomedical data. Our extensive evaluation was done across several standard datasets and covered a wide range of clinical text-mining tasks, including Natural Language Inference, Relation Extraction, Named Entity Reco
We present a semi-parametric generative model for predicting anatomy of a patient in subsequent scans following a single baseline image. Such predictive modeling promises to facilitate novel analyses in both voxel-level studies and longitudinal biomarker evaluation. We capture anatomical change through a combination of population-wide regression and a non-parametric model of the subject's health based on individual genetic and clinical indicators. In contrast to classical correlation and longitudinal analysis, we focus on predicting new observations from a single subject observation. We demonstrate prediction of follow-up anatomical scans in the ADNI cohort, and illustrate a novel analysis approach that compares a patient's scans to the predicted subject-specific healthy anatomical trajectory. The code is available at https://github.com/adalca/voxelorb.
Vision-Language-Action (VLA) models are driving a revolution in robotics, enabling machines to understand instructions and interact with the physical world. This field is exploding with new models and datasets, making it both exciting and challenging to keep pace with. This survey offers a clear and structured guide to the VLA landscape. We design it to follow the natural learning path of a researcher: we start with the basic Modules of any VLA model, trace the history through key Milestones, and then dive deep into the core Challenges that define recent research frontier. Our main contribution is a detailed breakdown of the five biggest challenges in: (1) Representation, (2) Execution, (3) Generalization, (4) Safety, and (5) Dataset and Evaluation. This structure mirrors the developmental roadmap of a generalist agent: establishing the fundamental perception-action loop, scaling capabilities across diverse embodiments and environments, and finally ensuring trustworthy deployment-all supported by the essential data infrastructure. For each of them, we review existing approaches and highlight future opportunities. We position this paper as both a foundational guide for newcomers and
Objective: Integrating EHR data with other resources is essential in rare disease research due to low disease prevalence. Such integration is dependent on the alignment of ontologies used for data annotation. The International Classification of Diseases (ICD) is used to annotate clinical diagnoses; the Human Phenotype Ontology (HPO) to annotate phenotypes. Although these ontologies overlap in biomedical entities described, the extent to which they are interoperable is unknown. We investigate how well aligned these ontologies are and whether such alignments facilitate EHR data integration. Materials and Methods: We conducted an empirical analysis of the coverage of mappings between ICD and HPO. We interpret this mapping coverage as a proxy for how easily clinical data can be integrated with research ontologies such as HPO. We quantify how exhaustively ICD codes are mapped to HPO by analyzing mappings in the UMLS Metathesaurus. We analyze the proportion of ICD codes mapped to HPO within a real-world EHR dataset. Results and Discussion: Our analysis revealed that only 2.2% of ICD codes have direct mappings to HPO in UMLS. Within our EHR dataset, less than 50% of ICD codes have mapping
Ophthalmologists have used fundus images to screen and diagnose eye diseases. However, different equipments and ophthalmologists pose large variations to the quality of fundus images. Low-quality (LQ) degraded fundus images easily lead to uncertainty in clinical screening and generally increase the risk of misdiagnosis. Thus, real fundus image restoration is worth studying. Unfortunately, real clinical benchmark has not been explored for this task so far. In this paper, we investigate the real clinical fundus image restoration problem. Firstly, We establish a clinical dataset, Real Fundus (RF), including 120 low- and high-quality (HQ) image pairs. Then we propose a novel Transformer-based Generative Adversarial Network (RFormer) to restore the real degradation of clinical fundus images. The key component in our network is the Window-based Self-Attention Block (WSAB) which captures non-local self-similarity and long-range dependencies. To produce more visually pleasant results, a Transformer-based discriminator is introduced. Extensive experiments on our clinical benchmark show that the proposed RFormer significantly outperforms the state-of-the-art (SOTA) methods. In addition, expe
Clinical trials are critical in advancing medical treatments but often suffer from immense time and financial burden. Advances in statistical methodologies and artificial intelligence (AI) present opportunities to address these inefficiencies. Here we introduce Prognostic Covariate-Adjusted Mixed Models for Repeated Measures (PROCOVA-MMRM) as an advantageous combination of prognostic covariate adjustment (PROCOVA) and Mixed Models for Repeated Measures (MMRM). PROCOVA-MMRM utilizes time-matched prognostic scores generated from AI models to enhance the precision of treatment effect estimators for longitudinal continuous outcomes, enabling reductions in sample size and enrollment times. We first provide a description of the background and implementation of PROCOVA-MMRM, followed by two case study reanalyses where we compare the performance of PROCOVA-MMRM versus the unadjusted MMRM. These reanalyses demonstrate significant improvements in statistical power and precision in clinical indications with unmet medical need, specifically Alzheimer's Disease (AD) and Amyotrophic Lateral Sclerosis (ALS). We also explore the potential for sample size reduction with the prospective implementati
Like other fields of Traditional Medicines, Unani Medicines have been found as an effective medical practice for ages. It is still widely used in the subcontinent, particularly in Pakistan and India. However, Unani Medicines Practitioners are lacking modern IT applications in their everyday clinical practices. An Online Clinical Decision Support System may address this challenge to assist apprentice Unani Medicines practitioners in their diagnostic processes. The proposed system provides a web-based interface to enter the patient's symptoms, which are then automatically analyzed by our system to generate a list of probable diseases. The system allows practitioners to choose the most likely disease and inform patients about the associated treatment options remotely. The system consists of three modules: an Online Clinical Decision Support System, an Artificial Intelligence Inference Engine, and a comprehensive Unani Medicines Database. The system employs advanced AI techniques such as Decision Trees, Deep Learning, and Natural Language Processing. For system development, the project team used a technology stack that includes React, FastAPI, and MySQL. Data and functionality of the a