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Scaling up Continuous-Time Markov Chains Helps Resolve Underspecification
Modeling the time evolution of discrete sets of items (e.g., genetic mutations) is a fundamental problem in many biomedical applications. We approach this problem through the lens of continuous-time Markov chains, and show that the resulting learning task is generally underspecified in the usual setting of cross-sectional data. We explore a perhaps surprising remedy: including a number of additional independent items can help determine time order, and hence resolve underspecifi-cation. This is in sharp contrast to the common practice of limiting the analysis to a small subset of relevant items, which is followed largely due to poor scaling of existing methods. To put our theoretical insight into practice, we develop an approximate likelihood maximization method for learning continuous-time Markov chains, which can scale to hundreds of items and is orders of magnitude faster than previous methods. We demonstrate the effectiveness of our approach on synthetic and real cancer data.
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Predicting Parkinson's Disease Progression Using Statistical and Neural Mixed Effects Models: Comparative Study on Longitudinal Biomarkers
Tong, Ran, Wang, Lanruo, Wang, Tong, Yan, Wei
Predicting Parkinson's Disease (PD) progression is crucial, and voice biomarkers offer a non-invasive method for tracking symptom severity (UPDRS scores) through telemonitoring. Analyzing this longitudinal data is challenging due to within-subject correlations and complex, nonlinear patient-specific progression patterns. This study benchmarks LMMs against two advanced hybrid approaches: the Generalized Neural Network Mixed Model (GNMM) (Mandel 2021), which embeds a neural network within a GLMM structure, and the Neural Mixed Effects (NME) model (Wortwein 2023), allowing nonlinear subject-specific parameters throughout the network. Using the Oxford Parkinson's telemonitoring voice dataset, we evaluate these models' performance in predicting Total UPDRS to offer practical guidance for PD research and clinical applications.
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PathCo-LatticE: Pathology-Constrained Lattice-Of Experts Framework for Fully-supervised Few-Shot Cardiac MRI Segmentation
Elbayumi, Mohamed, Elbaz, Mohammed S. M.
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].
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From Frustration to Fun: An Adaptive Problem-Solving Puzzle Game Powered by Genetic Algorithm
McConnell, Matthew, Zhao, Richard
This paper explores adaptive problem solving with a game designed to support the development of problem-solving skills. Using an adaptive, AI-powered puzzle game, our adaptive problem-solving system dynamically generates pathfinding-based puzzles using a genetic algorithm, tailoring the difficulty of each puzzle to individual players in an online real-time approach. A player-modeling system records user interactions and informs the generation of puzzles to approximate a target difficulty level based on various metrics of the player. By combining procedural content generation with online adaptive difficulty adjustment, the system aims to maintain engagement, mitigate frustration, and maintain an optimal level of challenge. A pilot user study investigates the effectiveness of this approach, comparing different types of adaptive difficulty systems and interpreting players' responses. This work lays the foundation for further research into emotionally informed player models, advanced AI techniques for adaptivity, and broader applications beyond gaming in educational settings.
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