ABSTRACT
BACKGROUND: The use of health games is a promising strategy for educating and promoting healthy lifestyle behaviors among children. OBJECTIVE: We aimed to describe the design and development of a serious game, called HelperFriend, and evaluate its feasibility, acceptability, and preliminary effects in children in a pilot study. HelperFriend is a vicarious experiential video game designed to promote 3 lifestyle behaviors among young children: physical activity, healthy eating, and socioemotional wellness. METHODS: Participants aged 8 to 11 years were recruited from an elementary school and randomized to receive a healthy lifestyle behavior educational talk (control) or play six 30-minute sessions with HelperFriend (intervention). Assessments were conducted at baseline (T0) and after the intervention (ie, 4 weeks) (T1). The primary outcome was gain in knowledge. The secondary outcomes were intention to conduct healthy behaviors, dietary intake, and player satisfaction. RESULTS: Knowledge scores of intervention group participants increased from T0 to T1 for physical activity (t14=2.01, P=.03), healthy eating (t14=3.14, P=.003), and socioemotional wellness (t14=2.75, P=.008). In addition, from T0 to T1, the intervention group improved their intention to perform physical activity (t14=2.82, P=.006), healthy eating (t14=3.44, P=.002), and socioemotional wellness (t14=2.65, P=.009); and there was a reduction in their intake of 13 unhealthy foods. HelperFriend was well received by intervention group. CONCLUSIONS: HelperFriend appears to be feasible and acceptable for young children. In addition, this game seems to be a viable tool to help improve the knowledge, the intention to conduct healthy behaviors, and the dietary intake of children; however, a well-powered randomized controlled trial is needed to prove the efficacy of HelperFriend.
ABSTRACT
Somatic DNA hypomethylation and aneuploidy are hallmarks of cancer, and there is evidence for a causal relationship between them in knockout mice but not in human cancer. The non-mobile pericentromeric repetitive elements SST1 are hypomethylated in about 17% of human colorectal cancers (CRC) with some 5-7% exhibiting strong age-independent demethylation. We studied the frequency of genome doubling, a common event in solid tumors linked to aneuploidy, in randomly selected single cell clones of near-diploid LS174T human CRC cells differing in their level of SST1 demethylation. Near-diploid LS174T cells underwent frequent genome-doubling events generating near-tetraploid clones with lower levels of SST1 methylation. In primary CRC, strong SST1 hypomethylation was significantly associated with global genomic hypomethylation and mutations in TP53. This work uncovers the association of the naturally occurring demethylation of the SST1 pericentromeric repeat with the onset of spontaneous tetraploidization in human CRC cells in culture and with TP53 mutations in primary CRCs. Altogether, our findings provide further support for an oncogenic pathway linking somatic hypomethylation and genetic copy number alterations in a subset of human CRC.
ABSTRACT
BACKGROUND: Morphogenesis is a developmental process in which cells organize into shapes and patterns. Complex, non-linear and multi-factorial models with images as output are commonly used to study morphogenesis. It is difficult to understand the relation between the uncertainty in the input and the output of such 'black-box' models, giving rise to the need for sensitivity analysis tools. In this paper, we introduce a workflow for a global sensitivity analysis approach to study the impact of single parameters and the interactions between them on the output of morphogenesis models. RESULTS: To demonstrate the workflow, we used a published, well-studied model of vascular morphogenesis. The parameters of this cellular Potts model (CPM) represent cell properties and behaviors that drive the mechanisms of angiogenic sprouting. The global sensitivity analysis correctly identified the dominant parameters in the model, consistent with previous studies. Additionally, the analysis provided information on the relative impact of single parameters and of interactions between them. This is very relevant because interactions of parameters impede the experimental verification of the predicted effect of single parameters. The parameter interactions, although of low impact, provided also new insights in the mechanisms of in silico sprouting. Finally, the analysis indicated that the model could be reduced by one parameter. CONCLUSIONS: We propose global sensitivity analysis as an alternative approach to study the mechanisms of morphogenesis. Comparison of the ranking of the impact of the model parameters to knowledge derived from experimental data and from manipulation experiments can help to falsify models and to find the operand mechanisms in morphogenesis. The workflow is applicable to all 'black-box' models, including high-throughput in vitro models in which output measures are affected by a set of experimental perturbations.
