Microrandomized Trials: Developing Just-in-Time Adaptive Interventions for Better Public Health.

Just-in-time adaptive interventions (JITAIs) represent an intervention design that adapts the provision and type of support over time to an individual's changing status and contexts, intending to deliver the right support on the right occasion. As a novel strategy for delivering mobile health interventions, JITAIs have the potential to improve access to quality care in underserved communities and, thus, alleviate health disparities, a significant public health concern. Valid experimental designs and analysis methods are required to inform the development of JITAIs. Here, we briefly review the cutting-edge design of microrandomized trials (MRTs), covering both the classical MRT design and its outcome-adaptive counterpart. Associated statistical challenges related to the design and analysis of MRTs are also discussed. Two case studies are provided to illustrate the aforementioned concepts and designs throughout the article. We hope our work leads to better design and application of JITAIs, advancing public health research and practice. (Am J Public Health. 2023;113(1):60-69. https://doi.org/10.2105/AJPH.2022.307150).

The assessment of epigenetic diversity, differentiation, and structure in the 'Fuji' mutation line implicates roles of epigenetic modification in the occurrence of different mutant groups as well as spontaneous mutants.

The 'Fuji' line includes many varieties with a similar genetic background and consistent inducement factors with epigenetic occurrence, thus it may be considered an ideal candidate for epigenetic research. In this study, 91 bud mutations of 'Fuji' apple were used as the test materials. Using the genetic variation within 'Fuji' as the control, the characteristics of epigenetic variation at different levels in both varieties and mutant groups were examined. The results showed that: (1) the global genomic DNA methylation level of the 91 bud mutants of 'Fuji' ranged from 29.120%-45.084%, with an average of 35.910%. Internal cytosine methylation was the main DNA methylation pattern. Regarding the variation of methylation patterns of 'Fuji' mutants, the vast majority of loci maintained the original methylation pattern existed in 'Fuji'. CHG methylation variation was the main type of variation; (2) the variation in methylation patterns between the mutant groups was greater than that of methylation levels. Among these patterns, the variation in CHG methylation patterns (including CHG hypermethylation and CHG demethylation) was expected to be dominant. The observed variation in methylation levels was more important in the Color mutant group; however, the variation in methylation patterns was more obvious in both the early maturation and Spur mutant groups. Moreover, the range of variation in the Early-maturation group was much wider than that in the Spur mutant group; (3) epigenetic diversity and genetic diversity were both low between the mutant groups. In the 'Fuji' mutant groups, there was few correlation between genetic and epigenetic variation, and epigenetic differentiation resulted in more loci with moderate or greater differentiation; (4) the purifying selection seemed to play a major role in the differentiation of different groups of 'Fuji' mutants (65.618%), but epigenetic diversity selection still occurred at nearly 35% of loci. Sixteen epigenetic outlier loci were detected.