Passive sensing on mobile devices to improve mental health services with adolescent and young mothers in low-resource settings: the role of families in feasibility and acceptability.

BACKGROUND: Passive sensor data from mobile devices can shed light on daily activities, social behavior, and maternal-child interactions to improve maternal and child health services including mental healthcare. We assessed feasibility and acceptability of the Sensing Technologies for Maternal Depression Treatment in Low Resource Settings (StandStrong) platform. The StandStrong passive data collection platform was piloted with adolescent and young mothers, including mothers experiencing postpartum depression, in Nepal. METHODS: Mothers (15-25 years old) with infants (< 12 months old) were recruited in person from vaccination clinics in rural Nepal. They were provided with an Android smartphone and a Bluetooth beacon to collect data in four domains: the mother's location using the Global Positioning System (GPS), physical activity using the phone's accelerometer, auditory environment using episodic audio recording on the phone, and mother-infant proximity measured with the Bluetooth beacon attached to the infant's clothing. Feasibility and acceptability were evaluated based on the amount of passive sensing data collected compared to the total amount that could be collected in a 2-week period. Endline qualitative interviews were conducted to understand mothers' experiences and perceptions of passive data collection. RESULTS: Of the 782 women approached, 320 met eligibility criteria and 38 mothers (11 depressed, 27 non-depressed) were enrolled. 38 mothers (11 depressed, 27 non-depressed) were enrolled. Across all participants, 5,579 of the hour-long data collection windows had at least one audio recording [mean (M) = 57.4% of the total possible hour-long recording windows per participant; median (Mdn) = 62.6%], 5,001 activity readings (M = 50.6%; Mdn = 63.2%), 4,168 proximity readings (M = 41.1%; Mdn = 47.6%), and 3,482 GPS readings (M = 35.4%; Mdn = 39.2%). Feasibility challenges were phone battery charging, data usage exceeding prepaid limits, and burden of carrying mobile phones. Acceptability challenges were privacy concerns and lack of family involvement. Overall, families' understanding of passive sensing and families' awareness of potential benefits to mothers and infants were the major modifiable factors increasing acceptability and reducing gaps in data collection. CONCLUSION: Per sensor type, approximately half of the hour-long collection windows had at least one reading. Feasibility challenges for passive sensing on mobile devices can be addressed by providing alternative phone charging options, reverse billing for the app, and replacing mobile phones with smartwatches. Enhancing acceptability will require greater family involvement and improved communication regarding benefits of passive sensing for psychological interventions and other health services. Registration International Registered Report Identifier (IRRID): DERR1-10.2196/14734.

What Does Social Support Sound Like? Challenges and Opportunities for Using Passive Episodic Audio Collection to Assess the Social Environment.

Background: The social environment, comprised of social support, social burden, and quality of interactions, influences a range of health outcomes, including mental health. Passive audio data collection on mobile phones (e.g., episodic recording of the auditory environment without requiring any active input from the phone user) enables new opportunities to understand the social environment. We evaluated the use of passive audio collection on mobile phones as a window into the social environment while conducting a study of mental health among adolescent and young mothers in Nepal. Methods: We enrolled 23 adolescent and young mothers who first participated in qualitative interviews to describe their social support and identify sounds potentially associated with that support. Then, episodic recordings were collected for 2 weeks from the mothers using an app to record 30 s of audio every 15 min from 4 A.M. to 9 P.M. Audio data were processed and classified using a pretrained model. Each classification category was accompanied by an estimated accuracy score. Manual validation of the machine-predicted speech and non-speech categories was done for accuracy. Results: In qualitative interviews, mothers described a range of positive and negative social interactions and the sounds that accompanied these. Potential positive sounds included adult speech and laughter, infant babbling and laughter, and sounds from baby toys. Sounds characterizing negative stimuli included yelling, crying, screaming by adults and crying by infants. Sounds associated with social isolation included silence and TV or radio noises. Speech comprised 43% of all passively recorded audio clips (n = 7,725). Manual validation showed a 23% false positive rate and 62% false-negative rate for speech, demonstrating potential underestimation of speech exposure. Other common sounds were music and vehicular noises. Conclusions: Passively capturing audio has the potential to improve understanding of the social environment. However, a pre-trained model had the limited accuracy for identifying speech and lacked categories allowing distinction between positive and negative social interactions. To improve the contribution of passive audio collection to understanding the social environment, future work should improve the accuracy of audio categorization, code for constellations of sounds, and combine audio with other smartphone data collection such as location and activity.

ONC201 kills breast cancer cells in vitro by targeting mitochondria.

We report a novel mechanism of action of ONC201 as a mitochondria-targeting drug in cancer cells. ONC201 was originally identified as a small molecule that induces transcription of TNF-related apoptosis-inducing ligand (TRAIL) and subsequently kills cancer cells by activating TRAIL death receptors. In this study, we examined ONC201 toxicity on multiple human breast and endometrial cancer cell lines. ONC201 attenuated cell viability in all cancer cell lines tested. Unexpectedly, ONC201 toxicity was not dependent on either TRAIL receptors nor caspases. Time-lapse live cell imaging revealed that ONC201 induces cell membrane ballooning followed by rupture, distinct from the morphology of cells undergoing apoptosis. Further investigation found that ONC201 induces phosphorylation of AMP-dependent kinase and ATP loss. Cytotoxicity and ATP depletion were significantly enhanced in the absence of glucose, suggesting that ONC201 targets mitochondrial respiration. Further analysis indicated that ONC201 indirectly inhibits mitochondrial respiration. Confocal and electron microscopic analysis demonstrated that ONC201 triggers mitochondrial structural damage and functional impairment. Moreover, ONC201 decreased mitochondrial DNA (mtDNA). RNAseq analysis revealed that ONC201 suppresses expression of multiple mtDNA-encoded genes and nuclear-encoded mitochondrial genes involved in oxidative phosphorylation and other mitochondrial functions. Importantly, fumarate hydratase deficient cancer cells and multiple cancer cell lines with reduced amounts of mtDNA were resistant to ONC201. These results indicate that cells not dependent on mitochondrial respiration are ONC201-resistant. Our data demonstrate that ONC201 kills cancer cells by disrupting mitochondrial function and further suggests that cancer cells that are dependent on glycolysis will be resistant to ONC201.

AGE-RAGE signal generates a specific NF-κB RelA "barcode" that directs collagen I expression.

Advanced glycation end products (AGEs) are sugar-modified biomolecules that accumulate in the body with advancing age, and are implicated in the development of multiple age-associated structural and functional abnormities and diseases. It has been well documented that AGEs signal via their receptor RAGE to activate several cellular programs including NF-κB, leading to inflammation. A large number of stimuli can activate NF-κB; yet different stimuli, or the same stimulus for NF-κB in different cellular settings, produce a very different transcriptional landscape and physiological outcome. The NF-κB barcode hypothesis posits that cellular network dynamics generate signal-specific post-translational modifications, or a "barcode" to NF-κB, and that a signature "barcode" mediates a specific gene expression pattern. In the current study, we established that AGE-RAGE signaling results in NF-κB activation that directs collagen Ia1 and Ia2 expression. We further demonstrated that AGE-RAGE signal induces phosphorylation of RelA at three specific residues, T254, S311, and S536. These modifications are required for transcription of collagen I genes and are a consequence of cellular network dynamics. The increase of collagen content is a hallmark of arterial aging, and our work provides a potential mechanistic link between RAGE signaling, NF-κB activation, and aging-associated arterial alterations in structure and function.