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BackgroundPhysical activity can confer diverse benefits on cancer survivors. Unfortunately, many cancer survivors are not sufficiently active. The efficacy of physical activity interventions for this population may be increased by grounding them in Self-Determination Theory (SDT). Combining game design elements with wearable technologies may be a useful and scalable approach to targeting SDT constructs to promote cancer survivors’ physical activity. ObjectiveThe primary aim of this study is to evaluate the feasibility and acceptability of Steps2Health, a physical activity intervention for cancer survivors. It also aims to investigate the effects of the intervention on motivation, physical activity, and step count. MethodsWe randomized 78 insufficiently active cancer survivors to an experimental or comparison group. All participants received a physical activity tracker. The experimental group participants also received a set sequence of multimedia messaging service messages that were triggered in real time by meeting predetermined cumulative step count totals. Messages presented information about a virtual journey and included photographs and vivid descriptions of locations to increase autonomous motivation. Additional messages targeted perceptions of relatedness (eg, role modeling) and competence (eg, facilitating mastery experiences). We administered pre- and postintervention surveys and conducted 15 individual interviews to evaluate the intervention. We performed directed content analysis of qualitative data and conducted mixed effects linear modeling to investigate participants’ changes in motivation, self-reported physical activity, and device-measured step counts. ResultsThere was minimal loss to follow-up (3/78, 4%), the device wear rate was high (2548/3044, 83.71% of days), and technical problems with messaging based on real-time step counts were limited. Our qualitative data analysis revealed 3 overarching themes: accessibility, autonomous motivation, and relatedness. Participants successfully navigated the technological aspects and game design elements of the intervention. Participants found messages targeting autonomous motivation and competence or self-efficacy to be enjoyable and compelling, but one feasibility criterion for participant engagement (response rate to text messages) was not met. Messages targeting relatedness were less highly rated than the messages targeting autonomous motivation and competence or self-efficacy. During the intervention, both groups increased their motivation for physical activity (B=0.16; 95% CI 0.01 to 0.30; P=.04; d=0.49), and assignment to the experimental group was associated with increased self-reported leisure activity score (B=10.78; 95% CI 3.54 to 18.02; P=.005; d=0.64). The experimental group had greater increases in daily step counts over time (B=322.08; 95% CI 54.01 to 590.15; P=.02; d=0.28). ConclusionsThis study supports the feasibility of using real-time game design elements to target SDT constructs and increase cancer survivors’ physical activity. Overall, our findings support the acceptability of the Steps2Health intervention, but fostering active participant engagement and targeting relatedness may present additional challenges. Steps2Health may help cancer survivors increase their physical activity levels.

BackgroundCancer survivors are at an elevated risk for several negative health outcomes, but physical activity (PA) can decrease those risks. Unfortunately, adherence to PA recommendations among survivors is low. Fitness mobile apps have been shown to facilitate the adoption of PA in the general population, but there are limited apps specifically designed for cancer survivors. This population has unique needs and barriers to PA, and most existing PA apps do not address these issues. Moreover, incorporating user preferences has been identified as an important priority for technology-based PA interventions, but at present there is limited literature that serves to establish these preferences in cancer survivors. This is especially problematic given the high cost of app development and because the majority of downloaded apps fail to engage users over the long term. ObjectiveThe aim of this study was to take a qualitative approach to provide practical insight regarding this population’s preferences for the features and messages of an app to increase PA. MethodsA total of 35 cancer survivors each attended 2 focus groups; a moderator presented slide shows on potential app features and messages and asked open-ended questions to elicit participant preferences. All sessions were audio recorded and transcribed verbatim. Three reviewers independently conducted thematic content analysis on all transcripts, then organized and consolidated findings to identify salient themes. ResultsParticipants (mean age 63.7, SD 10.8, years) were mostly female (24/35, 69%) and mostly white (25/35, 71%). Participants generally had access to technology and were receptive to engaging with an app to increase PA. Themes identified included preferences for (1) a casual, concise, and positive tone, (2) tools for personal goal attainment, (3) a prescription for PA, and (4) an experience that is tailored to the user. Participants reported wanting extensive background data collection with low data entry burden and to have a trustworthy source translate their personal data into individualized PA recommendations. They expressed a desire for app functions that could facilitate goal achievement and articulated a preference for a more private social experience. Finally, results indicated that PA goals might be best established in the context of personally held priorities and values. ConclusionsMany of the desired features identified are compatible with both empirically supported methods of behavior change and the relative strengths of an app as a delivery vehicle for behavioral intervention. Participating cancer survivors’ preferences contrasted with many current standard practices for mobile app development, including value-based rather than numeric goals, private socialization in small groups rather than sharing with broader social networks, and interpretation of PA data rather than merely providing numerical data. Taken together, these insights may help increase the acceptability of theory-based mHealth PA interventions in cancer survivors.

There is considerable interest in screening ultralarge chemical libraries for ligand discovery, both empirically and computationally1-4. Efforts have focused on readily synthesizable molecules, inevitably leaving many chemotypes unexplored. Here we investigate structure-based docking of a bespoke virtual library of tetrahydropyridines-a scaffold that is poorly sampled by a general billion-molecule virtual library but is well suited to many aminergic G-protein-coupled receptors. Using three inputs, each with diverse available derivatives, a one pot C-H alkenylation, electrocyclization and reduction provides the tetrahydropyridine core with up to six sites of derivatization5-7. Docking a virtual library of 75 million tetrahydropyridines against a model of the serotonin 5-HT2A receptor (5-HT2AR) led to the synthesis and testing of 17 initial molecules. Four of these molecules had low-micromolar activities against either the 5-HT2A or the 5-HT2B receptors. Structure-based optimization led to the 5-HT2AR agonists (R)-69 and (R)-70, with half-maximal effective concentration values of 41 nM and 110 nM, respectively, and unusual signalling kinetics that differ from psychedelic 5-HT2AR agonists. Cryo-electron microscopy structural analysis confirmed the predicted binding mode to 5-HT2AR. The favourable physical properties of these new agonists conferred high brain permeability, enabling mouse behavioural assays. Notably, neither had psychedelic activity, in contrast to classic 5-HT2AR agonists, whereas both had potent antidepressant activity in mouse models and had the same efficacy as antidepressants such as fluoxetine at as low as 1/40th of the dose. Prospects for using bespoke virtual libraries to sample pharmacologically relevant chemical space will be considered.