Developing a Multimodal Monitoring System for Geriatric Depression: A Feasibility Study.

The Internet of Medical Things is promising for monitoring depression symptoms. Therefore, it is necessary to develop multimodal monitoring systems tailored for elderly individuals with high feasibility and usability for further research and practice. This study comprised two phases: (1) methodological development of the system; and (2) system validation to evaluate its feasibility. We developed a system that includes a smartphone for facial and verbal expressions, a smartwatch for activity and heart rate monitoring, and an ecological momentary assessment application. A sample of 21 older Koreans aged 65 years and more was recruited from a community center. The 4-week data were collected for each participant (n = 19) using self-report questionnaires, wearable devices, and interviews and were analyzed using mixed methods. The depressive group (n = 6) indicated lower user acceptance relative to the nondepressive group (n = 13). Both groups experienced positive emotions, had regular life patterns, increased their self-interest, and stated that a system could disturb their daily activities. However, they were interested in learning new technologies and actively monitored their mental health status. Our multimodal monitoring system shows potential as a feasible and useful measure for acquiring mental health information about geriatric depression.

Allosteric Mutant IDH1 Inhibitors Reveal Mechanisms for IDH1 Mutant and Isoform Selectivity.

Oncogenic IDH1 and IDH2 mutations contribute to cancer via production of R-2-hydroxyglutarate (2-HG). Here, we characterize two structurally distinct mutant- and isoform-selective IDH1 inhibitors that inhibit 2-HG production. Both bind to an allosteric pocket on IDH1, yet shape it differently, highlighting the plasticity of this site. Oncogenic IDH1R132H mutation destabilizes an IDH1 "regulatory segment," which otherwise restricts compound access to the allosteric pocket. Regulatory segment destabilization in wild-type IDH1 promotes inhibitor binding, suggesting that destabilization is critical for mutant selectivity. We also report crystal structures of oncogenic IDH2 mutant isoforms, highlighting the fact that the analogous segment of IDH2 is not similarly destabilized. This intrinsic stability of IDH2 may contribute to observed inhibitor IDH1 isoform selectivity. Moreover, discrete residues in the IDH1 allosteric pocket that differ from IDH2 may also guide IDH1 isoform selectivity. These data provide a deeper understanding of how IDH1 inhibitors achieve mutant and isoform selectivity.