ASU Scholarship Showcase

Linnorm is a novel normalization and transformation method for the analysis of single cell RNA sequencing (scRNA-seq) data. Linnorm is developed to remove technical noises and simultaneously preserve biological variations in scRNA-seq data, such that existing statistical methods can be improved. Using real scRNA-seq data, we compared Linnorm with existing normalization methods, including NODES, SAMstrt, SCnorm, scran, DESeq and TMM. Linnorm shows advantages in speed, technical noise removal and preservation of cell heterogeneity, which can improve existing methods in the discovery of novel subtypes, pseudo-temporal ordering of cells, clustering analysis, etc. Linnorm also performs better than existing DEG analysis methods, including BASiCS, NODES, SAMstrt, Seurat and DESeq2, in false positive rate control and accuracy.

Contemporary human populations conform to ecogeographic predictions that animals will become more compact in cooler climates and less compact in warmer ones. However, it remains unclear to what extent this pattern reflects plastic responses to current environments or genetic differences among populations. Analyzing anthropometric surveys of 232,684 children and adults from across 80 ethnolinguistic groups in sub-Saharan Africa, Asia and the Americas, we confirm that body surface-to-volume correlates with contemporary temperature at magnitudes found in more latitudinally diverse samples (Adj. R² = 0.14-0.28). However, far more variation in body surface-to-volume is attributable to genetic population structure (Adj. R² = 0.50-0.74). Moreover, genetic population structure accounts for nearly all of the observed relationship between contemporary temperature and body surface-to-volume among children and adults. Indeed, after controlling for population structure, contemporary temperature accounts for no more than 4% of the variance in body form in these groups. This effect of genetic affinity on body form is also independent of other ecological variables, such as dominant mode of subsistence and household wealth per capita. These findings suggest that the observed fit of human body surface-to-volume with current climate in this sample reflects relatively large effects of existing genetic population structure of contemporary humans compared to plastic response to current environments.

Background: The transition from the home to college is a phase in which emerging adults shift toward more unhealthy eating and physical activity patterns, higher body mass indices, thus increasing risk of overweight/obesity. Currently, little is understood about how changing friendship networks shape weight gain behaviors. This paper describes the recruitment, data collection, and data analytic protocols for the SPARC (Social impact of Physical Activity and nutRition in College) study, a longitudinal examination of the mechanisms by which friends and friendship networks influence nutrition and physical activity behaviors and weight gain in the transition to college life.

Methods: The SPARC study aims to follow 1450 university freshmen from a large university over an academic year, collecting data on multiple aspects of friends and friendship networks. Integrating multiple types of data related to student lives, ecological momentary assessments (EMAs) are administered via a cell phone application, devilSPARC. EMAs collected in four 1-week periods (a total of 4 EMA waves) are integrated with linked data from web-based surveys and anthropometric measurements conducted at four times points (for a total of eight data collection periods including EMAs, separated by ~1 month). University databases will provide student card data, allowing integration of both time-dated data on food purchasing, use of physical activity venues, and geographical information system (GIS) locations of these activities relative to other students in their social networks.

Discussion: Findings are intended to guide the development of more effective interventions to enhance behaviors among college students that protect against weight gain during college.

Periodicities (repeating patterns) are observed in many human behaviors. Their strength may capture untapped patterns that incorporate sleep, sedentary, and active behaviors into a single metric indicative of better health. We present a framework to detect periodicities from longitudinal wrist-worn accelerometry data. GENEActiv accelerometer data were collected from 20 participants (17 men, 3 women, aged 35–65) continuously for 64.4±26.2 (range: 13.9 to 102.0) consecutive days. Cardiometabolic risk biomarkers and health-related quality of life metrics were assessed at baseline. Periodograms were constructed to determine patterns emergent from the accelerometer data. Periodicity strength was calculated using circular autocorrelations for time-lagged windows. The most notable periodicity was at 24 h, indicating a circadian rest-activity cycle; however, its strength varied significantly across participants. Periodicity strength was most consistently associated with LDL-cholesterol (r’s = 0.40–0.79, P’s < 0.05) and triglycerides (r’s = 0.68–0.86, P’s < 0.05) but also associated with hs-CRP and health-related quality of life, even after adjusting for demographics and self-rated physical activity and insomnia symptoms. Our framework demonstrates a new method for characterizing behavior patterns longitudinally which captures relationships between 24 h accelerometry data and health outcomes.

Background: Falls are a major public health concern in older adults. Recent fall prevention guidelines recommend the use of multifactorial fall prevention programs (FPPs) that include exercise for community-dwelling older adults; however, the availability of sustainable, community-based FPPs is limited.

Methods: We conducted a 24-week quasi-experimental study to evaluate the efficacy of a community-based, multifactorial FPP [Stay in Balance (SIB)] on dynamic and functional balance and muscular strength. The SIB program was delivered by allied health students and included a health education program focused on fall risk factors and a progressive exercise program emphasizing lower-extremity strength and balance. All participants initially received the 12-week SIB program, and participants were non-randomly assigned at baseline to either continue the SIB exercise program at home or as a center-based program for an additional 12 weeks. Adults aged 60 and older (n = 69) who were at-risk of falling (fall history or 2+ fall risk factors) were recruited to participate. Mixed effects repeated measures using Statistical Application Software Proc Mixed were used to examine group, time, and group-by-time effects on dynamic balance (8-Foot Up and Go), functional balance (Berg Balance Scale), and muscular strength (30 s chair stands and 30 s arm curls). Non-normally distributed outcome variables were log-transformed.

Results: After adjusting for age, gender, and body mass index, 8-Foot Up and Go scores, improved significantly over time [F_(2,173) = 8.92, p = 0.0; T0 − T2 diff = 1.2 (1.0)]. Berg Balance Scores [F_(2,173) = 29.0, p < 0.0001; T0 − T2 diff = 4.96 (0.72)], chair stands [F_(2,171) = 10.17, p < 0.0001; T0 − T2 diff = 3.1 (0.7)], and arm curls [F_(2,171) = 12.7, p < 0.02; T0 − T2 diff = 2.7 (0.6)] also all improved significantly over time. There were no significant group-by-time effects observed for any of the outcomes.

Conclusion: The SIB program improved dynamic and functional balance and muscular strength in older adults at-risk for falling. Our findings indicate continuing home-based strength and balance exercises at home after completion of a center-based FPP program may be an effective and feasible way to maintain improvements in balance and strength parameters.

Two distinct monocyte (Mo)/macrophage (Mp) subsets (Ly6C^low and Ly6C^hi) orchestrate cardiac recovery process following myocardial infarction (MI). Prostaglandin (PG) E₂ is involved in the Mo/Mp-mediated inflammatory response, however, the role of its receptors in Mos/Mps in cardiac healing remains to be determined. Here we show that pharmacological inhibition or gene ablation of the Ep3 receptor in mice suppresses accumulation of Ly6C^low Mos/Mps in infarcted hearts. Ep3 deletion in Mos/Mps markedly attenuates healing after MI by reducing neovascularization in peri-infarct zones. Ep3 deficiency diminishes CX3C chemokine receptor 1 (CX3CR1) expression and vascular endothelial growth factor (VEGF) secretion in Mos/Mps by suppressing TGFβ1 signaling and subsequently inhibits Ly6C^low Mos/Mps migration and angiogenesis. Targeted overexpression of Ep3 receptors in Mos/Mps improves wound healing by enhancing angiogenesis. Thus, the PGE₂/Ep3 axis promotes cardiac healing after MI by activating reparative Ly6C^low Mos/Mps, indicating that Ep3 receptor activation may be a promising therapeutic target for acute MI.

Modeling of transcriptional regulatory networks (TRNs) has been increasingly used to dissect the nature of gene regulation. Inference of regulatory relationships among transcription factors (TFs) and genes, especially among multiple TFs, is still challenging. In this study, we introduced an integrative method, LogicTRN, to decode TF–TF interactions that form TF logics in regulating target genes. By combining cis-regulatory logics and transcriptional kinetics into one single model framework, LogicTRN can naturally integrate dynamic gene expression data and TF-DNA-binding signals in order to identify the TF logics and to reconstruct the underlying TRNs. We evaluated the newly developed methodology using simulation, comparison and application studies, and the results not only show their consistence with existing knowledge, but also demonstrate its ability to accurately reconstruct TRNs in biological complex systems.

Mobile devices are a promising channel for delivering just-in-time guidance and support for improving key daily health behaviors. Despite an explosion of mobile phone applications aimed at physical activity and other health behaviors, few have been based on theoretically derived constructs and empirical evidence. Eighty adults ages 45 years and older who were insufficiently physically active, engaged in prolonged daily sitting, and were new to smartphone technology, participated in iterative design development and feasibility testing of three daily activity smartphone applications based on motivational frames drawn from behavioral science theory and evidence. An “analytically” framed custom application focused on personalized goal setting, self-monitoring, and active problem solving around barriers to behavior change. A “socially” framed custom application focused on social comparisons, norms, and support.

An “affectively” framed custom application focused on operant conditioning principles of reinforcement scheduling and emotional transference to an avatar, whose movements and behaviors reflected the physical activity and sedentary levels of the user. To explore the applications' initial efficacy in changing regular physical activity and leisure-time sitting, behavioral changes were assessed across eight weeks in 68 participants using the CHAMPS physical activity questionnaire and the Australian sedentary behavior questionnaire. User acceptability of and satisfaction with the applications was explored via a post-intervention user survey. The results indicated that the three applications were sufficiently robust to significantly improve regular moderate-to-vigorous intensity physical activity and decrease leisure-time sitting during the 8-week behavioral adoption period. Acceptability of the applications was confirmed in the post-intervention surveys for this sample of midlife and older adults new to smartphone technology. Preliminary data exploring sustained use of the applications across a longer time period yielded promising results. The results support further systematic investigation of the efficacy of the applications for changing these key health-promoting behaviors.

Background: Prior studies have shown that using uterotonics to augment or induce labor before arrival at comprehensive Emergency Obstetric and Neonatal Care (CEmONC) settings (henceforth, “outside uterotonics”) may contribute to perinatal mortality in low- and middle-income countries. We estimate its effect on perinatal mortality in rural Bangladesh.

Methods: Using hospital records (23986 singleton term births, Jan 1, 2009-Dec 31, 2015) from rural Bangladesh, we use a logistic regression model to estimate the increased risk of perinatal death from uterotonics administered outside a CEmONC facility.

Results: Among term births (≥37 weeks gestation), the risk of perinatal death adjusted for key confounders is significantly increased among women reporting uterotonic use outside of CEmONC (OR = 3 · 0, 95 % CI = 2 · 4,3 · 7). This increased risk is particularly high for fresh stillbirths (OR = 4 · 0, 95 % CI = 3 · 0,5 · 3) and intrapartum-related causes of early neonatal deaths (birth asphyxia) (OR = 3 · 1, 95 % CI = 2 · 2,4 · 5).

Conclusions: In this sample, outside uterotonic use was associated with substantially increased risk of fresh stillbirths, deaths due to birth asphyxia, and all perinatal deaths. In settings of high uterotonic use outside of controlled settings, substantial improvement in both stillbirth and early neonatal mortality may be made by reducing such use.