Acute Myocardial Infarction (AMI), a common disease that can have serious consequences, occurs when myocardial blood flow stops due to occlusion of the coronary artery. Early and accurate prediction of AMI is critical for rapid prognosis and improved patient outcomes. Metabolomics, the study of small molecules within biological systems, is an effective tool used to discover biomarkers associated with many diseases. This study intended to construct a predictive model for AMI utilizing metabolomics data and an explainable machine learning approach called Explainable Boosting Machines (EBM). The EBM model was trained on a dataset of 102 prognostic metabolites gathered from 99 individuals, including 34 healthy controls and 65 AMI patients. After a comprehensive data preprocessing, 21 metabolites were determined as the candidate predictors to predict AMI. The EBM model displayed satisfactory performance in predicting AMI, with various classification performance metrics. The model\'s predictions were based on the combined effects of individual metabolites and their interactions. In this context, the results obtained in two different EBM modeling, including both only individual metabolite features and their interaction effects, were discussed. The most important predictors included creatinine, nicotinamide, and isocitrate. These metabolites are involved in different biological activities, such as energy metabolism, DNA repair, and cellular signaling. The results demonstrate the potential of the combination of metabolomics and the EBM model in constructing reliable and interpretable prediction outputs for AMI. The discussed metabolite biomarkers may assist in early diagnosis, risk assessment, and personalized treatment methods for AMI patients. This study successfully developed a pipeline incorporating extensive data preprocessing and the EBM model to identify potential metabolite biomarkers for predicting AMI. The EBM model, with its ability to incorporate interaction terms, demonstrated satisfactory classification performance and revealed significant metabolite interactions that could be valuable in assessing AMI risk. However, the results obtained from this study should be validated with studies to be carried out in larger and well-defined samples.

UNASSIGNED: The precise prediction of COVID-19 prognosis remains a clinical challenge. In this regard, early identification of severe cases facilitates the triage and management of COVID-19 cases. The present paper aims to explore the prognosis of COVID-19 patients based on routine laboratory tests taken when patients are admitted.
UNASSIGNED: A data set including 1455 COVID-19 patients (727 male, 728 female) and their routine laboratory tests conducted upon hospital admission, age, Intensive Care Unit (ICU) admission, and outcome were gathered. The data set was randomly split into the train (75% of the data) and test data set (25% of the data). The explainable boosting machine (EBM) and extreme gradient boosting (XGBoost) were used for predicting the mortality and ICU admission of COVID-19 cases. Also, feature importance was extracted using EBM and XGBoost.
UNASSIGNED: The EBM and XGBoost achieved 86.38% and 88.56% accuracy in the test data set, respectively. In addition, EBM and XGBoost predicted the ICU admission with an accuracy of 89.37%, and 79.29% in the test data set for COVID-19 patients, respectively. Also, obtained models indicated that aspartate transaminase (AST), lymphocyte, blood urea nitrogen (BUN), and age are the most significant predictors of COVID-19 mortality. Furthermore, the lymphocyte count, AST, and BUN level were the most significant ICU admission predictors of COVID-19 patients.
UNASSIGNED: The current study indicated that both EBM and XGBoost could predict the ICU admission and mortality of COVID-19 cases based on routine hematological and clinical chemistry evaluation at the time of admission. Also, based on the results, AST, lymphocyte count, and BUN levels could be used as early predictors of COVID-19 prognosis.

BACKGROUND: Predicting cognition decline in patients with mild cognitive impairment (MCI) is crucial for identifying high-risk individuals and implementing effective management. To improve predicting MCI-to-AD conversion, it is necessary to consider various factors using explainable machine learning (XAI) models which provide interpretability while maintaining predictive accuracy. This study used the Explainable Boosting Machine (EBM) model with multimodal features to predict the conversion of MCI to AD during different follow-up periods while providing interpretability.
METHODS: This retrospective case-control study is conducted with data obtained from the ADNI database, with records of 1042 MCI patients from 2006 to 2022 included. The exposures included in this study were MRI biomarkers, cognitive scores, demographics, and clinical features. The main outcome was AD conversion from aMCI during follow-up. The EBM model was utilized to predict aMCI converting to AD based on three feature combinations, obtaining interpretability while ensuring accuracy. Meanwhile, the interaction effect was considered in the model. The three feature combinations were compared in different follow-up periods with accuracy, sensitivity, specificity, and AUC-ROC. The global and local explanations are displayed by importance ranking and feature interpretability plots.
RESULTS: The five-years prediction accuracy reached 85% (AUC = 0.92) using both cognitive scores and MRI markers. Apart from accuracies, we obtained features\' importance in different follow-up periods. In early stage of AD, the MRI markers play a major role, while for middle-term, the cognitive scores are more important. Feature risk scoring plots demonstrated insightful nonlinear interactive associations between selected factors and outcome. In one-year prediction, lower right inferior temporal volume (<9000) is significantly associated with AD conversion. For two-year prediction, low left inferior temporal thickness (<2) is most critical. For three-year prediction, higher FAQ scores (>4) is the most important. During four-year prediction, APOE4 is the most critical. For five-year prediction, lower right entorhinal volume (<1000) is the most critical feature.
CONCLUSIONS: The established glass-box model EBMs with multimodal features demonstrated a superior ability with detailed interpretability in predicting AD conversion from MCI. Multi features with significant importance were identified. Further study may be of significance to determine whether the established prediction tool would improve clinical management for AD patients.

OBJECTIVE: To construct an inherent interpretability machine learning model as an explainable boosting machine model (EBM) for predicting one-year risk of death in patients with severe ischemic stroke.
METHODS: We randomly divided the data of 2369 eligible patients with severe ischemic stroke in the MIMIC-Ⅳ(2.0) database, who were admitted in ICU in 2008 to 2019, into a training dataset (80%) and a test dataset (20%), and assessed the prognosis of the patients using the EBM model. The prediction performance of the model was evaluated by calculating the area under the receiver operating characteristic (AUC) curve. The calibration curve and Brier score were used to evaluate the degree of calibration of the model, and a decision curve was generated to assess the net clinical benefit.
RESULTS: The EBM model constructed in this study had good discrimination power, calibration and net benefit, with an AUC of 0.857 (95% CI: 0.831-0.887) for predicting prognosis of severe ischemic stroke. Calibration curve analysis showed that the standard curve of the EBM model was the closest to the ideal curve. Decision curve analysis showed that the model had the greatest net benefit rate at the prediction probability threshold of 0.10 to 0.80. The top 5 independent predictive variables based on the EBM model were age, SOFA score, mean heart rate, mechanical ventilation, and mean respiratory rate, whose significance scores ranged from 0.179 to 0.370.
CONCLUSIONS: This EBM model has a good performance for predicting the risk of death within one year in patients with severe ischemic stroke and allows clinicians to better understand the contributing factors of the patients\' outcomes through the model interpretability.

OBJECTIVE: Prediction of survival in patients diagnosed with a brain tumour is challenging because of heterogeneous tumour behaviours and treatment response. Advances in machine learning have led to the development of clinical prognostic models, but due to the lack of model interpretability, integration into clinical practice is almost non-existent. In this retrospective study, we compare five classification models with varying degrees of interpretability for the prediction of brain tumour survival greater than one year following diagnosis.
METHODS: 1028 patients aged ≥16 years with a brain tumour diagnosis between April 2012 and April 2020 were included in our study. Three intrinsically interpretable \'glass box\' classifiers (Bayesian Rule Lists [BRL], Explainable Boosting Machine [EBM], and Logistic Regression [LR]), and two \'black box\' classifiers (Random Forest [RF] and Support Vector Machine [SVM]) were trained on electronic patients records for the prediction of one-year survival. All models were evaluated using balanced accuracy (BAC), F1-score, sensitivity, specificity, and receiver operating characteristics. Black box model interpretability and misclassified predictions were quantified using SHapley Additive exPlanations (SHAP) values and model feature importance was evaluated by clinical experts.
RESULTS: The RF model achieved the highest BAC of 78.9%, closely followed by SVM (77.7%), LR (77.5%) and EBM (77.1%). Across all models, age, diagnosis (tumour type), functional features, and first treatment were top contributors to the prediction of one year survival. We used EBM and SHAP to explain model misclassifications and investigated the role of feature interactions in prognosis.
CONCLUSIONS: Interpretable models are a natural choice for the domain of predictive medicine. Intrinsically interpretable models, such as EBMs, may provide an advantage over traditional clinical assessment of brain tumour prognosis by weighting potential risk factors and their interactions that may be unknown to clinicians. An agreement between model predictions and clinical knowledge is essential for establishing trust in the models decision making process, as well as trust that the model will make accurate predictions when applied to new data.

Scans without evidence of dopaminergic deficit (SWEDD) refers to patients who mimics motor and non-motor symptoms of Parkinson\'s disease (PD) but showing integrity of dopaminergic system. For this reason, the differential diagnosis between SWEDD and PD patients is often not possible in absence of dopamine imaging. Machine Learning (ML) showed optimal performance in automatically distinguishing these two diseases from clinical and imaging data. However, the most common applied ML algorithms provide high accuracy at expense of findings intelligibility. In this work, a novel ML glass-box model, the Explainable Boosting Machine (EBM), based on Generalized Additive Models plus interactions (GA2Ms), was employed to obtain interpretability in classifying PD and SWEDD while still providing optimal performance. Dataset (168 healthy controls, HC; 396 PD; 58 SWEDD) was obtained from PPMI database and consisted of 178 among clinical and imaging features. Six binary EBM classifiers were trained on feature space with (SBR) and without (noSBR) dopaminergic striatal specific binding ratio: HC-PDSBR, HC-SWEDDSBR, PD-SWEDDSBR and HC-PDnoSBR, HC-SWEDDnoSBR, PD-SWEDDnoSBR. Excellent AUC-ROC (1) was reached in classifying HC from PD and SWEDD, both with and without SBR, and by PD-SWEDDSBR (0.986), while PD-SWEDDnoSBR showed lower AUC-ROC (0.882). Apart from optimal accuracies, EBM algorithm was able to provide global and local explanations, revealing that the presence of pairwise interactions between UPSIT Booklet #1 and Epworth Sleepiness Scale item 3 (ESS3), MDS-UPDRS-III pronation-supination movements right hand (NP3PRSPR) and MDS-UPDRS-III rigidity left upper limb (NP3RIGLU) could provide good performance in predicting PD and SWEDD also without imaging features.