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Risk scores are widely used for clinical decision making and commonly generated from logistic regression models. Machine-learning-based methods may work well for identifying important predictors, but such 'black box' variable selection limits interpretability, and variable importance evaluated from a single model can be biased. We propose a robust and interpretable variable selection approach using the recently developed Shapley variable importance cloud (ShapleyVIC) that accounts for variability across models. Our approach evaluates and visualizes overall variable contributions for in-depth inference and transparent variable selection, and filters out non-significant contributors to simplify model building steps. We derive an ensemble variable ranking from variable contributions, which is easily integrated with an automated and modularized risk score generator, AutoScore, for convenient implementation. In a study of early death or unplanned readmission, ShapleyVIC selected 6 of 41 candidate variables to create a well-performing model, which had similar performance to a 16-variable model from machine-learning-based ranking.

We study the evolution of preferences in a multi-population setting. Each individual has subjective preferences over potential outcomes, and chooses a best response based on his preferences and the information about the opponents' preferences. Individuals' realized fitnesses are given by material payoff functions. Following Dekel et al. (2007), we assume that individuals observe their opponents' preferences with some fixed probability $p$. We first derive necessary and sufficient conditions for stability for $p=1$ and $p=0$, and then check the robustness of our results against small perturbations on observability for the case of pure-strategy outcomes.

Remote screening of respiratory diseases has been widely studied as a non-invasive and early instrument for diagnosis purposes, especially in the pandemic. The respiratory sound classification task has been realized with numerous deep neural network (DNN) models due to their superior performance. However, in the high-stake medical domain where decisions can have significant consequences, it is desirable to develop interpretable models; thus, providing understandable reasons for physicians and patients. To address the issue, we propose a prototype learning framework, that jointly generates exemplar samples for explanation and integrates these samples into a layer of DNNs. The experimental results indicate that our method outperforms the state-of-the-art approaches on the largest public respiratory sound database.

Torsades de pointes (TdP) is an irregular heart rhythm characterized by faster beat rates and potentially could lead to sudden cardiac death. Much effort has been invested in understanding the drug-induced TdP in preclinical studies. However, a comprehensive statistical learning framework that can accurately predict the drug-induced TdP risk from preclinical data is still lacking. We proposed ordinal logistic regression and ordinal random forest models to predict low-, intermediate-, and high-risk drugs based on datasets generated from two experimental protocols. Leave-one-drug-out cross-validation, stratified bootstrap, and permutation predictor importance were applied to estimate and interpret the model performance under uncertainty. The potential outlier drugs identified by our models are consistent with their descriptions in the literature. Our method is accurate, interpretable, and thus useable as supplemental evidence in the drug safety assessment.

Risk evaluation to identify individuals who are at greater risk of cancer as a result of heritable pathogenic variants is a valuable component of individualized clinical management. Using principles of Mendelian genetics, Bayesian probability theory, and variant-specific knowledge, Mendelian models derive the probability of carrying a pathogenic variant and developing cancer in the future, based on family history. Existing Mendelian models are widely employed, but are generally limited to specific genes and syndromes. However, the upsurge of multi-gene panel germline testing has spurred the discovery of many new gene-cancer associations that are not presently accounted for in these models. We have developed PanelPRO, a flexible, efficient Mendelian risk prediction framework that can incorporate an arbitrary number of genes and cancers, overcoming the computational challenges that arise because of the increased model complexity. We implement an eleven-gene, eleven-cancer model, the largest Mendelian model created thus far, based on this framework. Using simulations and a clinical cohort with germline panel testing data, we evaluate model performance, validate the reverse-compatibility of our approach with existing Mendelian models, and illustrate its usage. Our implementation is freely available for research use in the PanelPRO R package.

The rapid progress in clinical data management systems and artificial intelligence approaches enable the era of personalized medicine. Intensive care units (ICUs) are the ideal clinical research environment for such development because they collect many clinical data and are highly computerized environments. We designed a retrospective clinical study on a prospective ICU database using clinical natural language to help in the early diagnosis of heart failure in critically ill children. The methodology consisted of empirical experiments of a learning algorithm to learn the hidden interpretation and presentation of the French clinical note data. This study included 1386 patients' clinical notes with 5444 single lines of notes. There were 1941 positive cases (36 % of total) and 3503 negative cases classified by two independent physicians using a standardized approach. The multilayer perceptron neural network outperforms other discriminative and generative classifiers. Consequently, the proposed framework yields an overall classification performance with 89 % accuracy, 88 % recall, and 89 % precision. This study successfully applied learning representation and machine learning algorithms to detect heart failure from clinical natural language in a single French institution. Further work is needed to use the same methodology in other institutions and other languages.

To provide a survey on the existing tasks and models in Machine Reading Comprehension (MRC), this report reviews: 1) the dataset collection and performance evaluation of some representative simple-reasoning and complex-reasoning MRC tasks; 2) the architecture designs, attention mechanisms, and performance-boosting approaches for developing neural-network-based MRC models; 3) some recently proposed transfer learning approaches to incorporating text-style knowledge contained in external corpora into the neural networks of MRC models; 4) some recently proposed knowledge base encoding approaches to incorporating graph-style knowledge contained in external knowledge bases into the neural networks of MRC models. Besides, according to what has been achieved and what are still deficient, this report also proposes some open problems for the future research.

Predictive models of student success in Massive Open Online Courses (MOOCs) are a critical component of effective content personalization and adaptive interventions. In this article we review the state of the art in predictive models of student success in MOOCs and present a categorization of MOOC research according to the predictors (features), prediction (outcomes), and underlying theoretical model. We critically survey work across each category, providing data on the raw data source, feature engineering, statistical model, evaluation method, prediction architecture, and other aspects of these experiments. Such a review is particularly useful given the rapid expansion of predictive modeling research in MOOCs since the emergence of major MOOC platforms in 2012. This survey reveals several key methodological gaps, which include extensive filtering of experimental subpopulations, ineffective student model evaluation, and the use of experimental data which would be unavailable for real-world student success prediction and intervention, which is the ultimate goal of such models. Finally, we highlight opportunities for future research, which include temporal modeling, research bridging predictive and explanatory student models, work which contributes to learning theory, and evaluating long-term learner success in MOOCs.

Surgical data science is a new research field that aims to observe all aspects of the patient treatment process in order to provide the right assistance at the right time. Due to the breakthrough successes of deep learning-based solutions for automatic image annotation, the availability of reference annotations for algorithm training is becoming a major bottleneck in the field. The purpose of this paper was to investigate the concept of self-supervised learning to address this issue. Our approach is guided by the hypothesis that unlabeled video data can be used to learn a representation of the target domain that boosts the performance of state-of-the-art machine learning algorithms when used for pre-training. Core of the method is an auxiliary task based on raw endoscopic video data of the target domain that is used to initialize the convolutional neural network (CNN) for the target task. In this paper, we propose the re-colorization of medical images with a generative adversarial network (GAN)-based architecture as auxiliary task. A variant of the method involves a second pre-training step based on labeled data for the target task from a related domain. We validate both variants using medical instrument segmentation as target task. The proposed approach can be used to radically reduce the manual annotation effort involved in training CNNs. Compared to the baseline approach of generating annotated data from scratch, our method decreases exploratively the number of labeled images by up to 75% without sacrificing performance. Our method also outperforms alternative methods for CNN pre-training, such as pre-training on publicly available non-medical or medical data using the target task (in this instance: segmentation). As it makes efficient use of available (non-)public and (un-)labeled data, the approach has the potential to become a valuable tool for CNN (pre-)training.

Tumor growth is associated with cell invasion and mass-effect, which are traditionally formulated by mathematical models, namely reaction-diffusion equations and biomechanics. Such models can be personalized based on clinical measurements to build the predictive models for tumor growth. In this paper, we investigate the possibility of using deep convolutional neural networks (ConvNets) to directly represent and learn the cell invasion and mass-effect, and to predict the subsequent involvement regions of a tumor. The invasion network learns the cell invasion from information related to metabolic rate, cell density and tumor boundary derived from multimodal imaging data. The expansion network models the mass-effect from the growing motion of tumor mass. We also study different architectures that fuse the invasion and expansion networks, in order to exploit the inherent correlations among them. Our network can easily be trained on population data and personalized to a target patient, unlike most previous mathematical modeling methods that fail to incorporate population data. Quantitative experiments on a pancreatic tumor data set show that the proposed method substantially outperforms a state-of-the-art mathematical model-based approach in both accuracy and efficiency, and that the information captured by each of the two subnetworks are complementary.