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
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.
Accurate segmentation of pulmonary vessels plays a very critical role in diagnosing and assessing various lung diseases. Currently, many automated algorithms are primarily targeted at CTPA (Computed Tomography Pulmonary Angiography) types of data. However, the segmentation precision of these methods is insufficient, and support for NCCT (Non-Contrast Computed Tomography) types of data is also a requirement in some clinical scenarios. In this study, we propose a 3D image segmentation algorithm for automated pulmonary vessel segmentation from both contrast-enhanced and non-contrast CT images. In the network, we designed a Vessel Lumen Structure Optimization Module (VLSOM), which extracts the centerline (Cl) of vessels and adjusts the weights based on the positional information and adds a Cl-Dice Loss to supervise the stability of the vessels structure. We used 427 sets of high-precision annotated CT data from multiple vendors and countries to train the model and achieved Cl-DICE, Cl-Recall, and Recall values of 0.892, 0.861, 0.924 for CTPA data and 0.925, 0.903, 0.949 for NCCT data. This shows that our model has achieved good performance in both accuracy and completeness of pulmonary
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
Accurate assessment of tissue perfusion is crucial in visceral surgery, especially during anastomosis. Currently, subjective visual judgment is commonly employed in clinical settings. Hyperspectral imaging (HSI) offers a non-invasive, quantitative alternative. However, HSI imaging lacks continuous integration into the clinical workflow. This study presents a hyperspectral light field system for intraoperative tissue oxygen saturation (SO2) analysis and visualization. We present a correlation method for determining SO2 saturation with low computational demands. We demonstrate clinical application, with our results aligning with the perfusion boundaries determined by the surgeon. We perform and compare continuous perfusion analysis using two hyperspectral cameras (Cubert S5, Cubert X20), achieving processing times of < 170 ms and < 400 ms, respectively. We discuss camera characteristics, system parameters, and the suitability for clinical use and real-time applications.
Standardization of data items collected in paediatric clinical trials is an important but challenging issue. The Clinical Data Interchange Standards Consortium (CDISC) data standards are well understood by the pharmaceutical industry but lack the implementation of some paediatric specific concepts. When a paediatric concept is absent within CDISC standards, companies and research institutions take multiple approaches in the collection of paediatric data, leading to different implementations of standards and potentially limited utility for reuse. To overcome these challenges, the conect4children consortium has developed a cross-cutting paediatric data dictionary (CCPDD). The dictionary was built over three phases - scoping (including a survey sent out to ten industrial and 34 academic partners to gauge interest), creation of a longlist and consensus building for the final set of terms. The dictionary was finalized during a workshop with attendees from academia, hospitals, industry and CDISC. The attendees held detailed discussions on each data item and participated in the final vote on the inclusion of the item in the CCPDD. Nine industrial and 34 academic partners responded to the
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.
Traditionally, studies in experimental physiology have been conducted in small groups of human participants, animal models or cell lines. Identifying optimal study designs that achieve sufficient power for drawing proper statistical inferences to detect group level effects with small sample sizes has been challenging. Moreover, average effects derived from traditional group-level inference do not necessarily apply to individual participants. Here, we introduce N-of-1 trials as an innovative study design that can be used to draw valid statistical inference about the effects of interventions on individual participants and can be aggregated across multiple study participants to provide population-level inferences more efficiently than standard group randomized trials. N-of-1 trials have been used since the late 1980s, but without large-scale adoption and with few applications in experimental physiology research settings. In this manuscript, we introduce the key components and design features of N-of-1 trials, describe statistical analysis and interpretations of the results, and describe some available digital tools to facilitate their use using examples from experimental physiology.
This paper describes our approach to the MEDIQA-CORR shared task, which involves error detection and correction in clinical notes curated by medical professionals. This task involves handling three subtasks: detecting the presence of errors, identifying the specific sentence containing the error, and correcting it. Through our work, we aim to assess the capabilities of Large Language Models (LLMs) trained on a vast corpora of internet data that contain both factual and unreliable information. We propose to comprehensively address all subtasks together, and suggest employing a unique prompt-based in-context learning strategy. We will evaluate its efficacy in this specialized task demanding a combination of general reasoning and medical knowledge. In medical systems where prediction errors can have grave consequences, we propose leveraging self-consistency and ensemble methods to enhance error correction and error detection performance.
Deep Learning (DL) has the potential to optimize machine learning in both the scientific and clinical communities. However, greater expertise is required to develop DL algorithms, and the variability of implementations hinders their reproducibility, translation, and deployment. Here we present the community-driven Generally Nuanced Deep Learning Framework (GaNDLF), with the goal of lowering these barriers. GaNDLF makes the mechanism of DL development, training, and inference more stable, reproducible, interpretable, and scalable, without requiring an extensive technical background. GaNDLF aims to provide an end-to-end solution for all DL-related tasks in computational precision medicine. We demonstrate the ability of GaNDLF to analyze both radiology and histology images, with built-in support for k-fold cross-validation, data augmentation, multiple modalities and output classes. Our quantitative performance evaluation on numerous use cases, anatomies, and computational tasks supports GaNDLF as a robust application framework for deployment in clinical workflows.
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
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
The increasing availability of unstructured clinical narratives in electronic health records (EHRs) has created new opportunities for automated disease characterization, cohort identification, and clinical decision support. However, modeling long, domain-specific clinical text remains challenging due to limited labeled data, severe class imbalance, and the high computational cost of adapting large pretrained language models. This study presents a GPT-based architecture for clinical text classification that adapts a pretrained decoder-only Transformer using a selective fine-tuning strategy. Rather than updating all model parameters, the majority of the GPT-2 backbone is frozen, and training is restricted to the final Transformer block, the final layer normalization, and a lightweight classification head. This approach substantially reduces the number of trainable parameters while preserving the representational capacity required to model complex clinical language. The proposed method is evaluated on radiology reports from the MIMIC-IV-Note dataset using uncertainty-aware CheXpert-style labels derived directly from report text. Experiments cover multiple problem formulations, includi
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
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
Temporal information extraction from unstructured text is essential for contextualizing events and deriving actionable insights, particularly in the medical domain. We address the task of extracting clinical events and their temporal relations using the well-studied I2B2 2012 Temporal Relations Challenge corpus. This task is inherently challenging due to complex clinical language, long documents, and sparse annotations. We introduce GRAPHTREX, a novel method integrating span-based entity-relation extraction, clinical large pre-trained language models (LPLMs), and Heterogeneous Graph Transformers (HGT) to capture local and global dependencies. Our HGT component facilitates information propagation across the document through innovative global landmarks that bridge distant entities. Our method improves the state-of-the-art with 5.5% improvement in the tempeval $F_1$ score over the previous best and up to 8.9% improvement on long-range relations, which presents a formidable challenge. We further demonstrate generalizability by establishing a strong baseline on the E3C corpus. This work not only advances temporal information extraction but also lays the groundwork for improved diagnosti
Defining the Inclusion/Exclusion (I/E) criteria of a trial is one of the most important steps during a trial design. Increasingly complex I/E criteria potentially create information imbalance and transparency issues between the people who design and run the trials and those who consume the information produced by the trials. In order to better understand and quantify the impact of a category of I/E criteria on observed treatment effects, a concept, named the Selection Induced Contrast Estimate (SICE) effect, is introduced and formulated in this paper. The SICE effect can exist in controlled clinical trials when treatment affects the correlation between a marker used for selection and the response of interest. This effect is demonstrated with both simulations and real clinical trial data. Although the statistical elements behind the SICE effect have been well studied, explicitly formulating and studying this effect can benefit several areas, including better transparency in I/E criteria, meta-analysis of multiple clinical trials, treatment effect interpretation in real-world medical practice, etc.
Objectives: Electronic health records (EHRs) are only a first step in capturing and utilizing health-related data - the challenge is turning that data into useful information. Furthermore, EHRs are increasingly likely to include data relating to patient outcomes, functionality such as clinical decision support, and genetic information as well, and, as such, can be seen as repositories of increasingly valuable information about patients' health conditions and responses to treatment over time. Methods: We describe a case study of 423 patients treated by Centerstone within Tennessee and Indiana in which we utilized electronic health record data to generate predictive algorithms of individual patient treatment response. Multiple models were constructed using predictor variables derived from clinical, financial and geographic data. Results: For the 423 patients, 101 deteriorated, 223 improved and in 99 there was no change in clinical condition. Based on modeling of various clinical indicators at baseline, the highest accuracy in predicting individual patient response ranged from 70-72% within the models tested. In terms of individual predictors, the Centerstone Assessment of Recovery Le
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