The high-level architecture of our simulator is illustrated in Figure 1 of Section 4. Additional details (with references to objects in the source code) are provided below. Simulations were run in Python 3.8 on an Intel(R) Xeon(R) CPU E5-2667 One direction is to extend the feature description of the ads (beyond topic) to include features that reflect ad quality and location. Baseline parameters are: µ = 0 . The resulting cohort errors are consistent with Figure 1 of Section 5.1. For the fully informative prior, the agent is completely certain of users' cohorts for Lastly, for the uninformative prior, revelation of a user's cookie does not inform the The agent's ability to distinguish users based on their responses depends on the similarities of affinities across users in different cohorts.

How does a user's consent decision influence

As regulatory agencies increasingly recognise real-world evidence as a complement to traditional clinical trial data, interest has grown in applying Bayesian methods across both interventional and observational research (Boulanger and Carlin (2021). A central objective in many clinical investigations is the delineation of patient subgroups that exhibit comparable disease-related characteristics (He, Belouali, Patricoski, Lehmann, Ball, Anagnostou, Kreimeyer, and Botsis (2023)). Electronic Health Records (EHR) have become an important resource for such phenotypic analyses (Hripcsak and Albers (2013)). Bayesian approaches to patient phenotyping in clinical observational studies have been limited by the computational challenges associated with applying the Markov Chain Monte Carlo (MCMC) approach to real-world data. Hubbard, Huang, Harton, Oganisian, Choi, Utidjian, Eneli, Bailey, and Chen (2019) proposed a Bayes latent class model that could be used in a general context for observational studies that use EHR data. They consider the common clinical context where gold-standard phenotype information, such as genetic and laboratory data, is not fully available. A general model of this form has high potential applicability for use in clinical decision support across disease areas for both primary and secondary clinical databases. Latent Class Analysis (LCA) is widely used when we want to identify patient phenotypes or subgroups given multivariate data (Lanza and Rhoades (2013)). A challenge in clinical LCA is the prevalence of mixed data, where we may have combinations of continuous, nominal, ordinal and count data.

Transcatheter Aortic Valve Replacement (TAVR) has emerged as a minimally invasive treatment option for patients with severe aortic stenosis, a life-threatening cardiovascular condition. Multiple transcatheter heart valves (THV) have been approved for use in TAVR, but current guidelines regarding valve type prescription remain an active topic of debate. We propose a data-driven clinical support tool to identify the optimal valve type with the objective of minimizing the risk of permanent pacemaker implantation (PPI), a predominant postoperative complication. We synthesize a novel dataset that combines U.S. and Greek patient populations and integrates three distinct data sources (patient demographics, computed tomography scans, echocardiograms) while harmonizing differences in each country's record system. We introduce a leaf-level analysis to leverage population heterogeneity and avoid benchmarking against uncertain counterfactual risk estimates. The final prescriptive model shows a reduction in PPI rates of 26% and 16% compared with the current standard of care in our internal U.S. population and external Greek validation cohort, respectively. To the best of our knowledge, this work represents the first unified, personalized prescription strategy for THV selection in TAVR.

Few-shot learning (FSL) mitigates data scarcity in cardiac MRI segmentation but typically relies on semi-supervised techniques sensitive to domain shifts and validation bias, restricting zero-shot generalizability. We propose PathCo-LatticE, a fully supervised FSL framework that replaces unlabeled data with pathology-guided synthetic supervision. First, our Virtual Patient Engine models continuous latent disease trajectories from sparse clinical anchors, using generative modeling to synthesize physiologically plausible, fully labeled 3D cohorts. Second, Self-Reinforcing Interleaved Validation (SIV) provides a leakage-free protocol that evaluates models online with progressively challenging synthetic samples, eliminating the need for real validation data. Finally, a dynamic Lattice-of-Experts (LoE) organizes specialized networks within a pathology-aware topology and activates the most relevant experts per input, enabling robust zero-shot generalization to unseen data without target-domain fine-tuning. We evaluated PathCo-LatticE in a strict out-of-distribution (OOD) setting, deriving all anchors and severity statistics from a single-source domain (ACDC) and performing zero-shot testing on the multi-center, multi-vendor M&Ms dataset. PathCo-LatticE outperforms four state-of-the-art FSL methods by 4.2-11% Dice starting from only 7 labeled anchors, and approaches fully supervised performance (within 1% Dice) with only 19 labeled anchors. The method shows superior harmonization across four vendors and generalization to unseen pathologies. [Code will be made publicly available].

The development of accessible screening tools for early cancer detection in dogs represents a significant challenge in veterinary medicine. Routine laboratory data offer a promising, low-cost source for such tools, but their utility is hampered by the non-specificity of individual biomarkers and the severe class imbalance inherent in screening populations. This study assesses the feasibility of cancer risk classification using the Golden Retriever Lifetime Study (GRLS) cohort under real-world constraints, including the grouping of diverse cancer types and the inclusion of post-diagnosis samples. A comprehensive benchmark evaluation was conducted, systematically comparing 126 analytical pipelines that comprised various machine learning models, feature selection methods, and data balancing techniques. Data were partitioned at the patient level to prevent leakage. The optimal model, a Logistic Regression classifier with class weighting and recursive feature elimination, demonstrated moderate ranking ability (AUROC = 0.815; 95% CI: 0.793-0.836) but poor clinical classification performance (F1-score = 0.25, Positive Predictive Value = 0.15). While a high Negative Predictive Value (0.98) was achieved, insufficient recall (0.79) precludes its use as a reliable rule-out test. Interpretability analysis with SHapley Additive exPlanations (SHAP) revealed that predictions were driven by non-specific features like age and markers of inflammation and anemia. It is concluded that while a statistically detectable cancer signal exists in routine lab data, it is too weak and confounded for clinically reliable discrimination from normal aging or other inflammatory conditions. This work establishes a critical performance ceiling for this data modality in isolation and underscores that meaningful progress in computational veterinary oncology will require integration of multi-modal data sources.

Early detection of cancer plays a key role in improving survival rates, but identifying reliable biomarkers from RNA-seq data is still a major challenge. The data are high-dimensional, and conventional statistical methods often fail to capture the complex relationships between genes. In this study, we introduce RGE-GCN (Recursive Gene Elimination with Graph Convolutional Networks), a framework that combines feature selection and classification in a single pipeline. Our approach builds a graph from gene expression profiles, uses a Graph Convolutional Network to classify cancer versus normal samples, and applies Integrated Gradients to highlight the most informative genes. By recursively removing less relevant genes, the model converges to a compact set of biomarkers that are both interpretable and predictive. We evaluated RGE-GCN on synthetic data as well as real-world RNA-seq cohorts of lung, kidney, and cervical cancers. Across all datasets, the method consistently achieved higher accuracy and F1-scores than standard tools such as DESeq2, edgeR, and limma-voom. Importantly, the selected genes aligned with well-known cancer pathways including PI3K-AKT, MAPK, SUMOylation, and immune regulation. These results suggest that RGE-GCN shows promise as a generalizable approach for RNA-seq based early cancer detection and biomarker discovery (https://rce-gcn.streamlit.app/ ).

Electronic health records (EHRs) support powerful clinical prediction models, but existing methods typically provide coarse, post hoc explanations that offer limited value for patient-level decision making. We introduce a knowledge graph (KG)-guided chain-of-thought (CoT) framework that generates clinically grounded and temporally consistent reasoning for visit-level disease prediction in MIMIC-III. ICD-9 codes are mapped to PrimeKG, from which disease-relevant nodes and multi-hop reasoning paths are extracted and used as scaffolds for CoT generation; only explanations whose conclusions match observed outcomes are retained. Lightweight LLaMA-3.1-Instruct-8B and Gemma-7B models are then fine-tuned on this supervision corpus. Across ten PrimeKG-mapped diseases and limited training cohorts (400 and 1000 cases), KG-guided models outperform strong classical baselines, achieving AUROC values of 0.66 to 0.70 and macro-AUPR values of 0.40 to 0.47. The models also transfer zero-shot to the CRADLE cohort, improving accuracy from approximately 0.40 to 0.51 up to 0.72 to 0.77. A blinded clinician evaluation shows consistent preference for KG-guided CoT explanations in clarity, relevance, and clinical correctness.

Deep unsupervised anomaly detection in brain magnetic resonance imaging offers a promising route to identify pathological deviations without requiring lesion-specific annotations. Yet, fragmented evaluations, heterogeneous datasets, and inconsistent metrics have hindered progress toward clinical translation. Here, we present a large-scale, multi-center benchmark of deep unsupervised anomaly detection for brain imaging. The training cohort comprised 2,976 T1 and 2,972 T2-weighted scans from healthy individuals across six scanners, with ages ranging from 6 to 89 years. Validation used 92 scans to tune hyperparameters and estimate unbiased thresholds. Testing encompassed 2,221 T1w and 1,262 T2w scans spanning healthy datasets and diverse clinical cohorts. Across all algorithms, the Dice-based segmentation performance varied between 0.03 and 0.65, indicating substantial variability. To assess robustness, we systematically evaluated the impact of different scanners, lesion types and sizes, as well as demographics (age, sex). Reconstruction-based methods, particularly diffusion-inspired approaches, achieved the strongest lesion segmentation performance, while feature-based methods showed greater robustness under distributional shifts. However, systematic biases, such as scanner-related effects, were observed for the majority of algorithms, including that small and low-contrast lesions were missed more often, and that false positives varied with age and sex. Increasing healthy training data yields only modest gains, underscoring that current unsupervised anomaly detection frameworks are limited algorithmically rather than by data availability. Our benchmark establishes a transparent foundation for future research and highlights priorities for clinical translation, including image native pretraining, principled deviation measures, fairness-aware modeling, and robust domain adaptation.

MRI-based brain age estimation models aim to assess a subject's biological brain age based on information, such as neuroanatomical features. Various factors, including neurodegenerative diseases, can accelerate brain aging and measuring this phenomena could serve as a potential biomarker for clinical applications. While deep learning (DL)-based regression has recently attracted major attention, existing approaches often fail to capture the continuous nature of neuromorphological changes, potentially resulting in sub-optimal feature representation and results. To address this, we propose to use supervised contrastive learning with the recent Rank-N-Contrast (RNC) loss to estimate brain age based on widely used T1w structural MRI for the first time and leverage Grad-RAM to visually explain regression results. Experiments show that our proposed method achieves a mean absolute error (MAE) of 4.27 years and an $R^2$ of 0.93 with a limited dataset of training samples, significantly outperforming conventional deep regression with the same ResNet backbone while performing better or comparably with the state-of-the-art methods with significantly larger training data. Furthermore, Grad-RAM revealed more nuanced features related to age regression with the RNC loss than conventional deep regression. As an exploratory study, we employed the proposed method to estimate the gap between the biological and chronological brain ages in Alzheimer's Disease and Parkinson's disease patients, and revealed the correlation between the brain age gap and disease severity, demonstrating its potential as a biomarker in neurodegenerative disorders.