The ILHBN: challenges, opportunities, and solutions from harmonizing data under heterogeneous study designs, target populations, and measurement protocols.

The ILHBN is funded by the National Institutes of Health to collaboratively study the interactive dynamics of behavior, health, and the environment using Intensive Longitudinal Data (ILD) to (a) understand and intervene on behavior and health and (b) develop new analytic methods to innovate behavioral theories and interventions. The heterogenous study designs, populations, and measurement protocols adopted by the seven studies within the ILHBN created practical challenges, but also unprecedented opportunities to capitalize on data harmonization to provide comparable views of data from different studies, enhance the quality and utility of expensive and hard-won ILD, and amplify scientific yield. The purpose of this article is to provide a brief report of the challenges, opportunities, and solutions from some of the ILHBN's cross-study data harmonization efforts. We review the process through which harmonization challenges and opportunities motivated the development of tools and collection of metadata within the ILHBN. A variety of strategies have been adopted within the ILHBN to facilitate harmonization of ecological momentary assessment, location, accelerometer, and participant engagement data while preserving theory-driven heterogeneity and data privacy considerations. Several tools have been developed by the ILHBN to resolve challenges in integrating ILD across multiple data streams and time scales both within and across studies. Harmonization of distinct longitudinal measures, measurement tools, and sampling rates across studies is challenging, but also opens up new opportunities to address cross-cutting scientific themes of interest.

Health behavior changes, such as prevention of suicidal thoughts and behaviors, smoking, drug use, and alcohol use; and the promotion of mental health, sleep, and physical activities, and decreases in sedentary behavior, are difficult to sustain. The ILHBN is a cooperative agreement network funded jointly by seven participating units within the National Institutes of Health to collaboratively study how factors that occur in individuals' everyday life and in their natural environment influence the success of positive health behavior changes. This article discusses how information collected using smartphones, wearables, and other devices can provide helpful active and passive reflections of the participants' extent of risk and resources at the moment for an extended period of time. However, successful engagement and retention of participants also require tailored adaptations of study designs, measurement tools, measurement intervals, study span, and device choices that create hurdles in integrating (harmonizing) data from multiple studies. We describe some of the challenges, opportunities, and solutions that emerged from harmonizing intensive longitudinal data under heterogeneous study and participant characteristics within the ILHBN, and share some tools and recommendations to facilitate future data harmonization efforts.

Conditional MitoTimer reporter mice for assessment of mitochondrial structure, oxidative stress, and mitophagy.

Assessment of structural and functional changes of mitochondria is vital for biomedical research as mitochondria are the power plants essential for biological processes and tissue/organ functions. Others and we have developed a novel reporter gene, pMitoTimer, which codes for a redox sensitive mitochondrial targeted protein that switches from green fluorescence protein (GFP) to red fluorescent protein (DsRed) when oxidized. It has been shown in transfected cells, transgenic C. elegans and Drosophila m., as well as somatically transfected adult skeletal muscle that this reporter gene allows quantifiable assessment of mitochondrial structure, oxidative stress, and lysosomal targeting of mitochondria-containing autophagosomes. Here, we generated CAG-CAT-MitoTimer transgenic mice using a transgene containing MitoTimer downstream of LoxP-flanked bacterial chloramphenicol acetyltransferase (CAT) gene with stop codon under the control of the cytomegalovirus (CMV) enhancer fused to the chicken ß-actin promoter (CAG). When CAG-CAT-MitoTimer mice were crossbred with various tissue-specific (muscle, adipose tissue, kidney, and pancreatic tumor) or global Cre transgenic mice, the double transgenic offspring showed MitoTimer expression in tissue-specific or global manner. Lastly, we show that hindlimb ischemia-reperfusion caused early, transient increases of mitochondrial oxidative stress, mitochondrial fragmentation and lysosomal targeting of autophagosomes containing mitochondria as well as a later reduction of mitochondrial content in skeletal muscle along with mitochondrial oxidative stress in sciatic nerve. Thus, we have generated conditional MitoTimer mice and provided proof of principle evidence of their utility to simultaneously assess mitochondrial structure, oxidative stress, and mitophagy in vivo in a tissue-specific, controllable fashion.