Statistical analysis was performed using GraphPad Prism software (version 9.1.1; GraphPad Software, La Jolla, CA, USA), R (version 3.6.3, R Core Team, 2021). Pearson correlation was used to compare plasma concentrations, ease of administration scores, AE burden and weight loss. Heatmaps were made using Heatmap.2 of the gplots package available in R [34 ]. In order to account for age-based variation in plasma concentrations and ease of administration scores, patients were divided into 3 age groups of approximately similar size (0 < age ≤ 3 years (6 patients), 3 < age ≤ 15 years (10 patients), and 15 < age ≤ 21 years (8 patients)) (Figure 1 B). The significance of observed differences between atovaquone and vehicle treated samples in vitro and in vivo was determined by repeated measures ANOVA to compare all samples at all tested time points. For in vivo survival analyses, Kaplan–Meier survival curves were generated and compared for significant differences by the log-rank test.
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