Heterozygous Kmt2d loss diminishes enhancers to render medulloblastoma cells vulnerable to combinatory inhibition of lysine demethylation and oxidative phosphorylation.

The histone H3 lysine 4 (H3K4) methyltransferase KMT2D (also called MLL4) is one of the most frequently mutated epigenetic modifiers in medulloblastoma (MB) and other types of cancer. Notably, heterozygous loss of KMT2D is prevalent in MB and other cancer types. However, what role heterozygous KMT2D loss plays in tumorigenesis has not been well characterized. Here, we show that heterozygous Kmt2d loss highly promotes MB driven by heterozygous loss of the MB suppressor gene Ptch in mice. Heterozygous Kmt2d loss upregulated tumor-promoting programs, including oxidative phosphorylation and G-protein-coupled receptor signaling, in Ptch-mutant-driven MB genesis. Mechanistically, both downregulation of the transcription-repressive tumor suppressor gene NCOR2 by heterozygous Kmt2d loss and upregulation of the oncogene MycN by heterozygous Ptch loss increased the expression of tumor-promoting genes. Moreover, heterozygous Kmt2d loss extensively diminished enhancer signals (e.g., H3K27ac) and H3K4me3 signature, including those for tumor suppressor genes (e.g., Ncor2). Combinatory pharmacological inhibition of oxidative phosphorylation and the H3K4 demethylase LSD1 drastically reduced tumorigenicity of MB cells bearing heterozygous Kmt2d loss. These findings reveal the mechanistic basis underlying the MB-promoting effect of heterozygous KMT2D loss, provide a rationale for a therapeutic strategy for treatment of KMT2D-deficient MB, and have mechanistic implications for the molecular pathogenesis of other types of cancer bearing heterozygous KMT2D loss.

Technology-Facilitated Abuse Prevalence and Associations Among a Nationally Representative Sample of Young Men.

PURPOSE: We undertook a study to determine the prevalence and associations of technology-facilitated abuse (TFA)-insults, harassment, coercion, or threats carried out using digital tools such as smartphones and computers-among a US nationally representative sample of young men. METHODS: Analyses were based on 1,079 men aged 18 to 35 years who completed questionnaires during August and September of 2014 and reported ever having been in a romantic relationship. We used validated measures to assess demographics, health service use, mental health and substance use, and TFA delivered to and received from partners in the past year. We calculated survey-weighted descriptive statistics and conducted multinomial logistic regression analysis. RESULTS: Overall, 4.1% of men reported delivering TFA only, 8.0% receiving TFA only, and 25.6% both delivering and receiving TFA. Men were more likely to report only delivering TFA if they identified as Hispanic (adjusted odds ratio [AOR] = 2.72; 95% CI, 1.13 to 6.57), used marijuana (AOR = 1.31; 95% CI, 1.02 to 1.68), and used prescription opioids for nonmedical reasons (AOR 2.86; 95% CI, 1.48 to 5.54). Men were more likely to report only receiving TFA if they identified as Hispanic (AOR = 2.55; 95% CI, 1.01 to 6.43) and used prescription opioids for nonmedical reasons (AOR = 2.43; 95% CI, 1.34 to 4.39), whereas a primary care connection appeared protective (AOR = 0.43; 95% CI, 0.22 to 0.86). Men were more likely to report both delivering and receiving TFA if they identified as non-Hispanic Black (AOR = 2.83; 95% CI, 1.44 to 5.58), owned a smartphone (AOR = 1.80; 95% CI, 1.05 to 3.09), had ever had mental health care visits (AOR = 1.86; 95% CI, 1.16 to 2.98), misused alcohol (AOR = 1.10; 95% CI, 1.04 to 1.17), and used prescription opioids for nonmedical reasons (AOR = 1.79; 95% CI, 1.04 to 3.08). CONCLUSIONS: We found that TFA was prevalent among young men, with 1 in 25 reporting delivery only, 1 in 12 reporting receipt only, and 1 in 4 reporting both. Primary care physicians can consider assessing TFA among male patients and developing interventions to mitigate this behavior.VISUAL ABSTRACT.

Living Life as the Bachelor/ette: Contributions of Diverse Television Genres to Adolescents' Acceptance of Gendered Sexual Scripts.

Gendered sexual scripts (GSS) reflect stereotypes about the gender-specific behaviors expected in romantic and sexual relationships. Television may be a powerful contributor to these scripts for adolescents because of its stereotypical portrayals and prominence in their lives. However, although television use is a consistent predictor of adults' GSS, few studies have tested these relations among adolescents, especially U.S. adolescents, and most report null results. Across two studies, we sought to decipher these patterns, investigating whether U.S. adolescents' regular exposure to diverse TV genres predicted their acceptance of GSS. In Study 1, we surveyed 574 adolescents aged 13-18, testing whether their viewing of three TV genres (scripted programming, reality TV, music videos) was associated with their support of GSS, as measured by four scales. In study 2, we surveyed a national sample of 398 adolescents, testing whether their viewing of four TV genres was associated with their support of GSS. For both studies, viewing of reality TV was associated with stronger support of each measure of GSS; there were few contributions of other genres. Gender moderated one interaction in each study, demonstrating stronger contributions for girls. Implications are discussed for media literacy programs and for teen dating abuse.

The Association Between Stereotypical Gender and Dating Beliefs and Digital Dating Abuse Perpetration in Adolescent Dating Relationships.

Digital media have become a significant context for adolescent dating relationships. As the use of social media and mobile phones increases, so do concerns that these media might be a context for "digital dating abuse" (DDA), or the use of digital media to harass, pressure, threaten, coerce, or monitor a dating partner. Although DDA has been shown to be common in adolescent dating relationships, little is known about the predictors of DDA perpetration or the role of stereotypical gender and dating beliefs in shaping these behaviors. This survey study of 703 high school students with dating experience investigated the role of gender beliefs in DDA perpetration using structural equation modeling. The survey included items pertaining to participants' digital media use, stereotypical gender and dating beliefs, and three types of DDA perpetration. Girls reported more frequent perpetration of some types of DDA, and boys expressed greater endorsement of stereotypical gender and dating beliefs. The data supported our hypothesized models, such that endorsement of stereotypical beliefs was associated with different types of DDA perpetration for girls and boys. Higher endorsement of stereotypical beliefs was related to perpetration of digital monitoring and control behaviors for girls, and to directly aggressive and hostile digital behaviors for boys. These patterns align with stereotypical gender roles. Associations with sexually coercive digital behaviors for both girls and boys are discussed. This study suggests that beyond the gender of the perpetrator, societal beliefs about gender and dating may shape the problematic use of digital media in dating relationships.

Elevating the Voices of Girls in Custody for Improved Treatment and Systemic Change in the Juvenile Justice System.

The U.S. juvenile justice system does not meet the needs of girls in custody, and often fails to address girls' symptoms of trauma and high rates of sexual exploitation histories. As the system shifts away from punitive detention to a trauma-informed approach with community-based services, community psychologists and other helping professionals can help center the needs and experiences of girls in custody. As part of a multi-year collaboration, our research team created a confidential youth advisory process in one juvenile detention center (JDC). We acted as liaisons between the girls in custody and JDC administrators, reporting girls' feedback to agencies at monthly meetings. Participant confidentiality, safety, and consent were priorities. The girls' feedback, which was conceptualized within a System Responsiveness and hierarchy of needs framework, led JDC probation and mental health staff to improve services (e.g., better laundry system, longer showers, warmer food), climate (e.g., consistent reward system, confidentiality of grievances), and treatment (e.g., increase focus on gender and culture) to reduce the trauma of incarceration among girls in custody. Girls' feedback also catalyzed systemic change that led to a reduction in the JDC population in favor of wraparound community-based services better suited to meet girls' needs. Implications for community psychology values and the juvenile justice system, including the benefits and challenges of this type of collaboration, are discussed.

Cyberbullying victimization and student engagement among adolescents: Does school climate matter?

Although the psychological impacts of cyberbullying victimization (CBV) have been documented, research is inconclusive about the role of contextual factors in the association between CBV and student engagement. Sampling 16,237 adolescents from 43 schools in Delaware, we used multilevel modeling to test how CBV was associated with emotional and cognitive-behavioral engagement at both the student and school levels, with the control for demographic factors and traditional bullying victimization (TBV). We also examined the moderating effects of school climate and grade level on the association between CBV and student engagement. CBV had a small but significant positive association with emotional engagement and a small but significant negative association with cognitive-behavioral engagement. School-level climate intensified the negative association between student-level CBV and cognitive-behavioral engagement and mitigated the positive association between student-level school climate and emotional engagement. The positive association between CBV and emotional engagement was stronger for high school than middle school students, whereas the negative association between CBV and cognitive-behavioral engagement was stronger for middle than high school students. The findings support the promotive role of positive school climate in student engagement promotion. The findings also support the healthy context paradox, which suggests that bullying victims' engagement in schools may be exacerbated in a social context with positive school climate perceived by the group members. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Vaccine administration error rates at a large academic medical center and its affiliated clinics - Familiarity matters.

OBJECTIVE: The purpose of this study was to track and describe the absolute number of vaccine administration errors and corresponding error rates over time and by patient age and vaccine type. METHODS: Total vaccines administered to patients aged 0 through 19 years 364 days from 1/1/2006 through 12/31/2017 at a large academic health system in the Midwest United States with primary, specialty and school-based clinics, and a pediatric hospital were obtained from an electronic medical record. Vaccine administration errors over the same time period for the same patient criteria were analyzed from the health system's incident reporting system and further compared to the frequency of all incidents reported. Vaccine administration error rates were calculated. Data were analyzed by patient age, vaccine type and year administered. RESULTS: Of the 1,431,206 vaccine doses given, 552 vaccine administration errors were identified (0.04%). The highest error rates occurred in children aged 2, 3, and 19 years. Vaccine types with the highest error rate were Td, rabies and pneumococcal polysaccharide vaccines. Overall vaccine doses given and errors reported increased over the study period. However, the increase was disproportionate, resulting in an increase in the error rate initially followed by a stabilization at the end of the study period. CONCLUSIONS: Vaccine administration errors are uncommon. The error rate appears to be stabilizing. Errors are more likely at ages when vaccines are not commonly given, with vaccines that have age-specific dosing and with vaccines that are given less often. This suggests more safety checks are needed for vaccines that are rarely used or given off-schedule, and manufacturers should avoid vaccines with age-specific dosing.

Bullying victimization and student engagement in elementary, middle, and high schools: Moderating role of school climate.

Bullying is the most common form of school violence and is associated with a range of negative outcomes, including traumatic responses. This study used hierarchical linear modeling to examine the multilevel moderating effects of school climate and school level (i.e., elementary, middle, and high schools) on the association between bullying victimization and student engagement. Participants included 25,896 students in 4th to 12th grades from 114 schools. Results indicated that, after controlling for student and school demographic factors, positive school climate was associated with higher behavioral/cognitive and emotional engagement of students across all grades. This highlights the critical and fundamental role of positive school climate in bullying prevention and intervention, among students across all grade levels, including those with frequent bullying victimization experience. Results also showed that negative associations between student-level bullying victimization and engagement were intensified in more positive school climates. This finding suggests that, in comparison with students in schools with less positive school climates, the engagement of bullying victims in schools with a more positive school climate might be more negatively influenced by their victimization experience. Additionally, the relation between student-level bullying victimization and emotional engagement was significantly different across middle and high schools. (PsycINFO Database Record

Diagnostic Value of Early Magnetic Resonance Imaging After Acute Lateral Ankle Injury.

We report a retrospective study of 171 consecutive patients with a lateral ankle sprain. All the patients with direct or blunt force trauma were excluded. Within 21 days of injury, 115 (67.25%) patients had undergone magnetic resonance imaging to evaluate for more serious or significant injuries. The average patient age was 44.09 years. Of the 115 patients, 75 (65.23%) had findings noted to be "significant." MRI can serve as a valuable and underused tool in the evaluation of acute lateral ankle injuries. The underuse of MRI might explain the high degree of variability in patients recovering from a lateral ankle sprain.

Dating and Sexual Violence Research in the Schools: Balancing Protection of Confidentiality with Supporting the Welfare of Survivors.

Rigorous research and program evaluation are needed to understand the experience of dating and sexual violence among youth and the impact of prevention and intervention efforts. Our dilemma in doing this work occurred when youth disclosed dating and sexual violence on a research survey. What responsibility do researchers have to protect survivors' confidentiality as a research participant versus taking steps to ensure the student has the opportunity to access help? In our evaluation of a pilot dating violence prevention program, our protocols employed widely used procedures for providing resources to participants upon their completion of the survey and de-identifying survey data. Upon reviewing preliminary survey results, we became concerned that these established procedures were not sufficient to support research participants who were adolescent survivors of dating and sexual violence. We followed a structured ethical decision-making process to examine legal and ethical considerations, consult with colleagues, consider impacts and alternative solutions, and ultimately find a solution. Through this process, we developed procedures that balance participant confidentiality and the desire to support the welfare of survivors, which other researchers may want to employ when conducting youth sexual and dating violence research in school and community settings.

Gender matters: Experiences and consequences of digital dating abuse victimization in adolescent dating relationships.

Digital dating abuse (DDA) behaviors include the use of digital media to monitor, control, threaten, harass, pressure, or coerce a dating partner. In this study, 703 high school students reported on the frequency of DDA victimization, whether they were upset by these incidents, and how they responded. Results suggest that although both girls and boys experienced DDA at similar rates of frequency (with the exception of sexual coercion), girls reported that they were more upset by these behaviors. Girls also expressed more negative emotional responses to DDA victimization than boys. Although DDA is potentially harmful for all youth, gender matters. These findings suggest that the experience and consequences of DDA may be particularly detrimental for girls.

Contributions of Social Comparison and Self-Objectification in Mediating Associations Between Facebook Use and Emergent Adults' Psychological Well-Being.

Although Facebook was created to help people feel connected with each other, data indicate that regular usage has both negative and positive connections to well-being. To explore these mixed results, we tested the role of social comparison and self-objectification as possible mediators of the link between Facebook use and three facets of psychological well-being: self-esteem, mental health, and body shame. Participants were 1,104 undergraduate women and men who completed surveys assessing their Facebook usage (minutes, passive use, and active use), social comparison, self-objectification, and well-being. Data were analyzed using structural equation modeling, testing separate models for women and men. Models for each gender fit the data well. For women and men, Facebook use was associated with greater social comparison and greater self-objectification, which, in turn, was each related to lower self-esteem, poorer mental health, and greater body shame. Mediated models provided better fits to the data than models testing direct pathways to the mediators and well-being variables. Implications are discussed for young people's social media use, and future directions are provided.

PEG-mimetic peptoid reduces protein fouling of polysulfone hollow fibers.

Biofouling is a persistent problem for membranes exposed to blood or other complex biological fluids, affecting surface structure and hindering performance. In this study, a peptoid with 2-methoxyethyl (NMEG5) side chains was immobilized on polysulfone hollow fiber membranes to prevent protein fouling. The successful attachment of NMEG5 to the polysulfone surface was confirmed by X-ray photoelectron spectroscopy and an increase in hydrophilicity was confirmed by contact angle analysis. The NMEG5-modified surface was found to resist fouling with bovine serum albumin, lysozyme, and adsorbed significantly less fibrinogen as compared with other published low-fouling surfaces. Due to the low fouling nature and increased biocompatibility of the NMEG5 coated membranes, they have potential applicability in numerous biomedical applications including artificial lungs and hemodialysis.

Snooping and Sexting: Digital Media as a Context for Dating Aggression and Abuse Among College Students.

Digital dating abuse (DDA) is a pattern of behaviors that control, pressure, or threaten a dating partner using a cell phone or the Internet. A survey of 365 college students was conducted, finding that digital monitoring behaviors were especially common. There were no gender differences in number of DDA behaviors experienced, but women reported more negative hypothetical reactions to sexual messaging than men. DDA was associated with measures of physical, sexual, and psychological dating violence. Results suggest that digital media are a context for potentially harmful dating behaviors, and the experience of DDA may differ by gender for sexual behaviors.

Differences in Symptom Reporting Between Males and Females at Baseline and After a Sports-Related Concussion: A Systematic Review and Meta-Analysis.

BACKGROUND: Concussion literature and treatment guidelines are inconclusive regarding the role of sex in symptom reporting at baseline and post-concussion. Although empirical evidence is lacking, it is generally regarded that females have a more severe symptomatic presentation than males at all time-points on the concussion spectrum. OBJECTIVES: Our objective was to determine whether differences exist between males and females at baseline (pre-season/before concussion) or post-concussion for self-reported (1) prevalence of individual symptoms and (2) total symptom scores in high school and college athletes. DESIGN: Systematic review and meta-analysis of observational cohort studies; level of evidence, 1. METHODS: A computerized search of the PubMed, SPORTDiscus, CINAHL, and Scopus databases was performed. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) guidelines were followed. Criteria for inclusion were (1) self-report of symptoms at any time within the concussion spectrum, including baseline and after concussion, (2) study sample included high school and/or collegiate athletes aged 12-26 years, (3) concussions occurred during participation in sport, and (4) symptom reporting was separated by sex. The Quality Assessment Tool for Cohort Studies, Q-Coh, was utilized for quality assessment. RESULTS: Twenty-one studies met the criteria for inclusion: seventeen had good quality and four, acceptable quality. At baseline, females had significantly higher odds than males of reporting the individual symptoms of vision/hearing problems, headache/migraine, difficulty concentrating, energy/sleep disturbances, and emotional disturbances. Post-concussion, only one symptom demonstrated significant differences between males and females, with females demonstrating lower odds of reporting confusion than males. Statistically, at baseline and post-concussion, females had significantly higher total symptom scores on the Post-Concussion Scale (PCS) and the Sport Concussion Assessment Tool 2 (SCAT2), but when the standard mean difference was interpreted after back-transformation, these results were clinically insignificant. CONCLUSIONS: The symptomatic presentation of males and females, most notably the prevalence of specific symptoms, is very divergent. Females had higher total symptom scores at baseline and post-concussion, however, clinically this cannot be interpreted as a meaningful difference. It is possible that these differences can be explained by normal hormonal changes associated with the menstrual cycle. The implications of these findings are that symptomatic presentation during an individual female's menstrual cycle needs to be taken into consideration post-concussion when making return-to-play decisions, as returning to a completely asymptomatic level may not be a reasonable expectation.