A comparative atlas of single-cell chromatin accessibility in the human brain.

Recent advances in single-cell transcriptomics have illuminated the diverse neuronal and glial cell types within the human brain. However, the regulatory programs governing cell identity and function remain unclear. Using a single-nucleus assay for transposase-accessible chromatin using sequencing (snATAC-seq), we explored open chromatin landscapes across 1.1 million cells in 42 brain regions from three adults. Integrating this data unveiled 107 distinct cell types and their specific utilization of 544,735 candidate cis-regulatory DNA elements (cCREs) in the human genome. Nearly a third of the cCREs demonstrated conservation and chromatin accessibility in the mouse brain cells. We reveal strong links between specific brain cell types and neuropsychiatric disorders including schizophrenia, bipolar disorder, Alzheimer's disease (AD), and major depression, and have developed deep learning models to predict the regulatory roles of noncoding risk variants in these disorders.

An RFX transcription factor regulates ciliogenesis in the closest living relatives of animals.

Cilia allowed our protistan ancestors to sense and explore their environment, avoid predation, and capture bacterial prey.1,2,3 Regulated ciliogenesis was likely critical for early animal evolution,2,4,5,6 and in modern animals, deploying cilia in the right cells at the right time is crucial for development and physiology. Two transcription factors, RFX and FoxJ1, coordinate ciliogenesis in animals7,8,9 but are absent from the genomes of many other ciliated eukaryotes, raising the question of how the regulation of ciliogenesis in animals evolved.10,11 By comparing the genomes of animals with those of their closest living relatives, the choanoflagellates, we found that the genome of their last common ancestor encoded at least three RFX paralogs and a FoxJ1 homolog. Disruption of the RFX homolog cRFXa in the model choanoflagellate Salpingoeca rosetta resulted in delayed cell proliferation and aberrant ciliogenesis, marked by the collapse and resorption of nascent cilia. In cRFXa mutants, ciliogenesis genes and foxJ1 were significantly downregulated. Moreover, the promoters of S. rosetta ciliary genes are enriched for DNA motifs matching those bound by the cRFXa protein in vitro. These findings suggest that an ancestral cRFXa homolog coordinated ciliogenesis in the progenitors of animals and choanoflagellates and that the selective deployment of the RFX regulatory module may have been necessary to differentiate ciliated from non-ciliated cell types during early animal evolution.

Following Insufficiently Active Adolescents: What Predicts Whether They Meet Adult Activity Guidelines When They Grow Up?

BACKGROUND: We investigated the percentage of insufficiently active adolescents who became young adults meeting moderate to vigorous physical activity (MVPA) guidelines. We also explored adolescent psychosocial and environmental factors that predicted MVPA guideline adherence in young adulthood. METHODS: Participants included N = 1001 adolescents (mean age = 14.1 y) reporting < 7 hours per week of MVPA and followed (8 y later) into young adulthood through Project EAT. We examined mean weekly hours of MVPA, MVPA change between adolescence and young adulthood, and the proportion of participants meeting MVPA guidelines in young adulthood. With sex-stratified logistic regression, we tested 11 adolescent psychosocial and environmental factors predicting meeting MVPA guidelines in young adulthood. RESULTS: Overall, 55% of insufficiently active adolescents became young adults meeting MVPA guidelines. On average, participants reported 3.0 hours per week of MVPA, which improved to 3.8 hours per week in young adulthood. Among female participants, higher MVPA in adolescence and stronger feelings of exercise compulsion predicted greater odds of meeting adult MVPA guidelines (odds ratioMVPA = 1.18; odds ratiocompulsion = 1.13). Among female and male participants, perceived friend support for activity in adolescence predicted greater odds of meeting adult MVPA guidelines (odds ratiofemale = 1.12; odds ratiomale = 1.26). CONCLUSIONS: Insufficiently active adolescents can later meet adult guidelines. Interventions that increase perceived friend support for activity may benefit individuals across development.

Sport and Physical Activity Among Transgender, Gender Diverse, and Questioning Adolescents.

PURPOSE: We compared rates of sport and physical activity (PA) of transgender and gender diverse adolescents and adolescents questioning their gender (TGDQ) with those of cisgender adolescents. Additionally, we tested for differences in sport and PA among TGDQ youth. METHODS: We used 2019 Minnesota Student Survey data (N = 125,375). We calculated descriptive statistics, then used chi-squares and one-way analyses of variance to test for differences in involvement in sports, PA lessons, and PA between TGDQ and cisgender adolescents. Then, we used the same tests to compare participation among all TGDQ adolescents, considering their gender identity and sex assigned at birth. RESULTS: Overall, TGDQ adolescents participated in sport and PA less than cisgender adolescents; TGD youth participated less than questioning youth. Within sex assigned at birth, participation varied by gender identity. DISCUSSION: TGDQ adolescents need support to participate in sport and PA. Adults should remain cognizant that sport restrictions could impair TGDQ adolescents' health.

Weight Status Among Minnesota Hispanic or Latino/a Youth: An Exploration of Protective Factors.

PURPOSE: Pediatric obesity disproportionately impacts Hispanic or Latino/a adolescents. Culturally appropriate family-based behavioral initiatives to improve weight status are warranted. The purpose of this research was to determine prevalence rates and identify protective factors associated with having overweight/obesity (body mass index ≥ 85th percentile) to inform Hispanic or Latino/a-targeted behavioral intervention development. DESIGN: Secondary data analyses of a population-based statewide survey. SETTING: Minnesota public high schools. PARTICIPANTS: Male (n = 2,644) and female (n = 2,798) Hispanic or Latino/a 9th and 11th graders (N = 5,442). MEASURES: Obesity-related behaviors (meeting fruit and vegetable [F&V] and physical activity [PA] recommendations), family caring, family country/region of origin, and weight status. ANALYSIS: Stepwise logistic regression models (F&V, PA), stratified by biological sex, were used to identify protective factors of overweight/obesity. RESULTS: The overall prevalence of meeting F&V and PA recommendations was 11.0% and 11.8%, respectively. Meeting F&V recommendations was not protective against overweight/obesity in either sex. Yet, males and females who met PA recommendations had significantly lower odds of having overweight/obesity (p < .05). In F&V and PA models, family caring was protective against overweight/obesity in females (p < .05), and family country/region of origin was protective against overweight/obesity in both sexes (p < .05). CONCLUSION: Findings illustrate a need for obesity prevention initiatives for Hispanic or Latino/a youth. More research is needed to understand the protective nature of family caring and country/region of origin.

Flipping the Script: An Initial Exploration of Flipped Learning as an Enhanced Alternative to Traditional Physical Education Lessons.

BACKGROUND: Physical activity (PA) is related to a variety of positive outcomes for youth and physical education (PE) represents a primary school-based environment where students can engage in moderate-to-vigorous physical activity (MVPA). Limitations exist in secondary schools with low socio-economic status, where MVPA engagement is generally below the recommended 50% of lesson time. Growing evidence suggests that using a flipped learning approach (FLA) may naturally enhance PE lessons as outlined by The Theory of Expanded, Extended, and Enhanced Opportunities for Youth Physical Activity Promotion. PURPOSE: The purpose of this study was to compare the impact of the FLA to traditional instruction on student MVPA, lesson context, and teacher involvement during middle school PE lessons. METHODS: Participants were 56 male students from two 7th-grade classes from a low-SES, suburban school. This study employed the System for Observing Fitness Instruction Time (SOFIT). Data were examined through descriptive statistics. Linear regression models were used to predict SOFIT outcomes as a function of FLA versus traditional instruction. RESULTS: Students in the FLA class spent significantly more class time in MVPA (p < 0.01). Regression models predicted participants in FLA classes would spend 55% more class time in MVPA (p < 0.01). After adjusting for covariates, models showed students in FLA classes would spend almost 18 more minutes in MVPA than students in traditional classes (p < 0.01). DISCUSSION/CONCLUSION: The FLA may be a practical lesson enhancement strategy to increase student MVPA and improve PE opportunities for students in low SES schools when compared to the use of traditional instruction. The results of this study demonstrated positive potential of using FLA in PE but should be considered within the context of their limitations. Further examination of the FLA is warranted.

Girls on the Run: Impact of a Physical Activity Youth Development Program on Psychosocial and Behavioral Outcomes.

PURPOSE: Girls on the Run is an after-school physical activity-based positive youth development program designed to enhance girls' social, psychological, and physical development. We evaluated the effectiveness of the program by employing a longitudinal design and mixed methods. METHODS: Girls (N = 203; aged 8-11 y) completed survey measures of positive youth development constructs (competence, confidence, connection, character, and caring), physical activity, and sedentary behavior prior to, at the end of, and 3 months after the season. Subsamples of girls, coaches, caregivers, and school personnel participated in focus groups. Coaches completed information about their team's community impact project and number of girls who completed the season-ending 5k. RESULTS: The full sample improved in confidence and connection, whereas girls who started below the preseason average showed the greatest gains from preseason to postseason on all measures, and scores were maintained or continued to improve at follow-up. All stakeholders in focus groups corroborated evidence of season-long improvement in social and emotional behaviors and health outcomes. Involvement in the community impact project contributed to girls' growth in character and empathy skills. CONCLUSION: Findings provide empirical evidence that Girls on the Run is effective in promoting positive youth development, including season-long and lasting change in competence, confidence, connection, character, caring, and physical activity, especially among girls who exhibited lower preseason scores than their peers.

Prehospital Acute ST-Elevation Myocardial Infarction Identification in San Diego: A Retrospective Analysis of the Effect of a New Software Algorithm.

BACKGROUND: A significant increase in false positive ST-elevation myocardial infarction (STEMI) electrocardiogram interpretations was noted after replacement of all of the City of San Diego's 110 monitor-defibrillator units with a new brand. These concerns were brought to the manufacturer and a revised interpretive algorithm was implemented. OBJECTIVES: This study evaluated the effects of a revised interpretation algorithm to identify STEMI when used by San Diego paramedics. METHODS: Data were reviewed 6 months before and 6 months after the introduction of a revised interpretation algorithm. True-positive and false-positive interpretations were identified. Factors contributing to an incorrect interpretation were assessed and patient demographics were collected. RESULTS: A total of 372 (234 preimplementation, 138 postimplementation) cases met inclusion criteria. There was a significant reduction in false positive STEMI (150 preimplementation, 40 postimplementation; p < 0.001) after implementation. The most common factors resulting in false positive before implementation were right bundle branch block, left bundle branch block, and atrial fibrillation. The new algorithm corrected for these misinterpretations with most postimplementation false positives attributed to benign early repolarization and poor data quality. Subsequent follow-up at 10 months showed maintenance of the observed reduction in false positives. CONCLUSIONS: This study shows that introducing a revised 12-lead interpretive algorithm resulted in a significant reduction in the number of false positive STEMI electrocardiogram interpretations in a large urban emergency medical services system. Rigorous testing and standardization of new interpretative software is recommended before introduction into a clinical setting to prevent issues resulting from inappropriate cardiac catheterization laboratory activations.

Subjective Cognitive Decline, Objective Cognition, and Depression in Older Hispanics Screened for Memory Impairment.

Subjective cognitive decline (SCD) is common in older adults and may be an early marker of future cognitive decline. Research suggest that SCD is more closely related to concurrent symptoms of depression than to objective cognitive performance in non-Hispanic Whites, but it is unknown whether the associations of SCD, cognition, and depression manifest differently in Hispanic older adults. We examined if SCD is associated with objective cognitive performance or with depression symptoms in 145 Hispanic individuals ages 60 or older referred by community health clinics for screening of cognitive complaints. All participants lived near the U.S.-Mexico border, spoke Spanish only, or were Spanish-English bilingual. Memory-only and global cognitive composites were created from scores on Spanish versions of several neuropsychological tests. The Geriatric Depression Scale (GDS) and a five-item SCD questionnaire developed by our group were also completed. Multiple regression analyses showed no significant associations between SCD and memory or global cognitive composite scores after adjusting for age, sex, education, and GDS score. In contrast, there was a significant association between GDS and SCD after adjusting for age, sex, education, global and memory composite scores. Findings suggest that SCD does not accurately reflect current cognitive status in older Hispanics who present to their primary care physician with cognitive complaints. Clinicians should interpret SCD in this population within the context of information about symptoms of depression. Longitudinal research is needed in older Hispanics to better characterize SCD in this population and to determine if it can predict future cognitive decline.