Daily-Level Associations between Situational Familiarity with Location and People and Use of Alcohol-related Protective Behavioral Strategy Among Adolescents and Young Adults.

OBJECTIVE: Despite protective behavioral strategies (PBS) being an important part of alcohol prevention programs, utilization of PBS is sub-optimal, and research is needed to determine factors associated with use and non-use of PBS. The present study examined daily-level associations between situational familiarity (i.e., familiarity with locations and people) and the use of alcohol-related PBS among adolescents and young adults. METHOD: Participants (analysis N = 564, 55.1% females, 45.2% White, Non-Hispanic, ages 15 to 25, mean = 21.07 years [SD = 2.79]) were part of a longitudinal ecological momentary assessment burst study on cognitions and alcohol use. Mixed effects Poisson models were used to analyze data for engagement in PBS (i.e., serious harm reduction, stopping/limiting, and manner of drinking PBS). RESULTS: Within-person results indicated when participants had elevated (i.e., higher than their own average) familiarity with their location, they were less likely to use serious harm reduction PBS (Rate ratio [RR] = 0.94, p < 0.001) and stopping/limiting PBS (RR = 0.95, p < 0.001). Results showed that on drinking days with elevated familiarity with people, individuals were more likely to use serious harm reduction PBS (RR = 1.03, p = 0.01). There were no significant daily-level associations between familiarity with people or location and manner of drinking PBS. CONCLUSION: The study suggests PBS use, particularly for serious harm reduction and stopping/limiting strategies, varies among adolescents and young adults based on familiarity with location and people. Alcohol prevention interventions, including just-in-time interventions, should consider how to promote PBS use particularly in familiar locations and with less familiar people.

A daily-level examination of willingness to pregame, blackout, and hook up across drinking days: Associations with respective behavioral outcomes among adolescents and young adults.

Research indicates general willingness to drink (i.e., "How willing are you to drink tonight?") fluctuates day-to-day and is associated with daily-level drinking. However, it is unknown whether willingness to engage in specific alcohol-related behaviors is associated with actual engagement in those behaviors above and beyond general willingness to drink at the daily level. The present study examined whether daily-level willingness to engage in specific behaviors (i.e., pre-gaming, blacking out, hooking up) predicted engaging in those respective behaviors on drinking days above and beyond one's general willingness to drink. Participants included adolescents and young adults who were part of a longitudinal ecological momentary assessment (EMA) study on cognitions and alcohol use. Participants (N = 675; 43 % male) who reported drinking on weekend days (i.e., Friday and Saturday [N = 3,727 days]), were included. The study involved a 3-week EMA burst design with bursts occurring quarterly over 12 months. Multilevel logistic regressions indicated on drinking days when participants reported being more willing than their own average to pre-game (OR = 1.77, p <.001), black out (OR = 1.46, p <.05), or drink before hooking up (OR = 1.68, p <.001), they were more likely to pregame, black out, and hook up, respectively, whereas general willingness to drink was not associated with any outcomes at the daily level.Results suggest willingness to engage in specific behaviors may be essential to target in prevention programming in comparison to general willingness to drink when aiming to reduce specific risk behaviors.

Daily level examination indicates that positive affect, but not negative affect, is associated with alcohol and marijuana use among adolescents and young adults.

OBJECTIVE: Although there is growing evidence that alcohol use at the daily level is associated with positive but not negative affect, results are mixed when examining marijuana use and simultaneous alcohol and marijuana (SAM) use (i.e., use with overlapping effects). In addition, less is known about these daily level associations among diverse samples of adolescents and young adults. The present study will address these gaps. METHOD: Participants (N = 1,006; 57.3% female, 43.1% White, Non-Hispanic, ages 15-25; Mage = 20.0) were part of a study on substance use that consisted of a 3-week ecological momentary assessment (EMA) burst design (eight surveys per week, up to 2×/day) that was repeated quarterly over a 12-month period. RESULTS: Within-person results indicated that on days with elevated positive affect, participants reported consuming more drinks, whereas positive affect was not significant for hours high from marijuana. In addition, on days with elevated negative affect, participants reported fewer hours high from marijuana. No association was found between negative affect and number of drinks. Finally, within-person results indicated that on alcohol or marijuana days with elevated positive affect, individuals were more likely to report SAM use. There was no association found between negative affect and SAM use. CONCLUSIONS: Results have implications such that in-the-moment interventions for alcohol and SAM use may be more salient when individuals have higher positive affect than average, whereas such interventions may be more relevant for marijuana use when negative affect is lower compared to average levels. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Did George Floyd's murder shape the public's felt obligation to obey the police?

OBJECTIVE: Our goal in the present study was to use longitudinal data to assess how normative (i.e., consensually motivated) and instrumental (i.e., coercively motivated) obligation to obey police changed after police murdered George Floyd and whether these changes differed by political ideology. HYPOTHESES: Using procedural justice theory, we hypothesized that after Floyd's murder, participants would feel less normatively obligated and more instrumentally obligated to obey police. We also hypothesized that these trends would be stronger for liberal-leaning than conservative-leaning participants. METHOD: Adults (N = 645) were recruited through Prolific from four politically diverse U.S. states. Participants reported their normative and instrumental obligation across three waves of data collection, each separated by 3 weeks. The first two waves were collected prior to the Floyd's murder, and the third was collected after. RESULTS: Hierarchical linear models indicated that although normative obligation remained stable before Floyd's murder, it declined after Floyd's murder (b = -0.19, 95% CI [-0.24, -0.14], p < .001). In contrast, coercive obligation to obey increased consistently across all three waves. Liberal-leaning participants drove most of the effects. CONCLUSIONS: For researchers, these findings help strengthen our understanding of procedural justice theory by differentiating normative and instrumental obligation and by distinguishing differences by political ideology within the context of a historic police-brutality event. For policymakers and law enforcement, our research suggests that police brutality may undermine the public's normative felt obligation to obey the police, which would be problematic for police reformation efforts grounded in governing by mutual consent versus by fear and coercion. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Social and structural determinants of recovery: The impact of race.

Relapse rates for substance use disorders (SUDs) after treatment are as high as 50%. Evidence suggests that social and structural determinants of recovery influence these outcomes. Important domains to consider include economic stability, educational access and quality, healthcare access and quality, neighborhood and built environment, and social and community context are the major domains of social determinants of health. All these factors influence people's ability to reach their highest health potential. However, race and racial discrimination often compound the negative effects of these factors on substance use treatment outcomes. Moreover, research is urgently needed to examine the specific mechanisms through which these issues influence SUD and SUD outcomes.

Breast Cancer Antiestrogen Resistance 3 (BCAR3) promotes tumor growth and progression in triple-negative breast cancer.

Triple-Negative Breast Cancers (TNBCs) constitute roughly 10-20% of breast cancers and are associated with poor clinical outcomes. Previous work from our laboratory and others has determined that the cytoplasmic adaptor protein Breast Cancer Antiestrogen Resistance 3 (BCAR3) is an important promoter of cell motility and invasion of breast cancer cells. In this study, we use both in vivo and in vitro approaches to extend our understanding of BCAR3 function in TNBC. We show that BCAR3 is upregulated in ductal carcinoma in situ (DCIS) and invasive carcinomas compared to normal mammary tissue, and that survival of TNBC patients whose tumors contained elevated BCAR3 mRNA is reduced relative to individuals whose tumors had less BCAR3 mRNA. Using mouse orthotopic tumor models, we further show that BCAR3 is required for efficient TNBC tumor growth. Analysis of publicly available RNA expression databases revealed that MET receptor signaling is strongly correlated with BCAR3 mRNA expression. A functional role for BCAR3-MET coupling is supported by data showing that both proteins participate in a single pathway to control proliferation and migration of TNBC cells. Interestingly, the mechanism through which this functional interaction operates appears to differ in different genetic backgrounds of TNBC, stemming in one case from potential differences in the strength of downstream signaling by the MET receptor and in another from BCAR3-dependent activation of an autocrine loop involving the production of HGF mRNA. Together, these data open the possibility for new approaches to personalized therapy for individuals with TNBCs.

HNRNPH1-dependent splicing of a fusion oncogene reveals a targetable RNA G-quadruplex interaction.

The primary oncogenic event in ∼85% of Ewing sarcomas is a chromosomal translocation that generates a fusion oncogene encoding an aberrant transcription factor. The exact genomic breakpoints within the translocated genes, EWSR1 and FLI1, vary; however, in EWSR1, breakpoints typically occur within introns 7 or 8. We previously found that in Ewing sarcoma cells harboring EWSR1 intron 8 breakpoints, the RNA-binding protein HNRNPH1 facilitates a splicing event that excludes EWSR1 exon 8 from the EWS-FLI1 pre-mRNA to generate an in-frame mRNA. Here, we show that the processing of distinct EWS-FLI1 pre-mRNAs by HNRNPH1, but not other homologous family members, resembles alternative splicing of transcript variants of EWSR1 We demonstrate that HNRNPH1 recruitment is driven by guanine-rich sequences within EWSR1 exon 8 that have the potential to fold into RNA G-quadruplex structures. Critically, we demonstrate that an RNA mimetic of one of these G-quadruplexes modulates HNRNPH1 binding and induces a decrease in the growth of an EWSR1 exon 8 fusion-positive Ewing sarcoma cell line. Finally, we show that EWSR1 exon 8 fusion-positive cell lines are more sensitive to treatment with the pan-quadruplex binding molecule, pyridostatin (PDS), than EWSR1 exon 8 fusion-negative lines. Also, the treatment of EWSR1 exon 8 fusion-positive cells with PDS decreases EWS-FLI1 transcriptional activity, reversing the transcriptional deregulation driven by EWS-FLI1. Our findings illustrate that modulation of the alternative splicing of EWS-FLI1 pre-mRNA is a novel strategy for future therapeutics against the EWSR1 exon 8 containing fusion oncogenes present in a third of Ewing sarcoma.

Is Sexting Associated with Sexual Behaviors During Adolescence? A Systematic Literature Review and Meta-Analysis.

INTRODUCTION: A growing body of research has addressed adolescent use of mobile devices to exchange sexually explicit images and messages (sexting). Although there are legal consequences in some states for sexting among adolescents, research findings have also demonstrated associations between sexting and sexual activity. The purpose of this systematic review was to synthesize research examining the association between adolescent sexting and sexual activity. METHODS: Five databases (CINAHL, Embase, Ovid MEDLINE, PsycINFO, and Scopus) were searched for studies measuring adolescent sexting and sexual behaviors. Studies were appraised for quality using a modified Downs and Black scale. Studies reporting frequencies or odds ratios were eligible for inclusion in random effects meta-analytic models. RESULTS: Of 669 articles retrieved, 9 studies met inclusion criteria for systematic review; of these, 6 were included in meta-analysis. After pooling data from 9676 adolescents, the odds of reporting sexual activity were found to be 6.3 times higher (95% CI, 4.9-8.1; Q = 14.3; I2 = 65.1) for adolescents who sent sexts compared with those who did not. DISCUSSION: These data suggest that adolescents who send sexually explicit text messages are more likely to report sexual activity than adolescents who do not. Midwives are well poised to integrate a discussion of sexting into sexual and reproductive health counseling with adolescent and young adult patients.

EWS-FLI1 reprograms the metabolism of Ewing sarcoma cells via positive regulation of glutamine import and serine-glycine biosynthesis.

Ewing sarcoma (EWS) is a soft tissue and bone tumor that occurs primarily in adolescents and young adults. In most cases of EWS, the chimeric transcription factor, EWS-FLI1 is the primary oncogenic driver. The epigenome of EWS cells reflects EWS-FLI1 binding and activation or repression of transcription. Here, we demonstrate that EWS-FLI1 positively regulates the expression of proteins required for serine-glycine biosynthesis and uptake of the alternative nutrient source glutamine. Specifically, we show that EWS-FLI1 activates expression of PHGDH, PSAT1, PSPH, and SHMT2. Using cell-based studies, we also establish that EWS cells are dependent on glutamine for cell survival and that EWS-FLI1 positively regulates expression of the glutamine transporter, SLC1A5 and two enzymes involved in the one-carbon cycle, MTHFD2 and MTHFD1L. Inhibition of serine-glycine biosynthesis in EWS cells impacts their redox state leading to an accumulation of reactive oxygen species, DNA damage, and apoptosis. Importantly, analysis of EWS primary tumor transcriptome data confirmed that the aforementioned genes we identified as regulated by EWS-FLI1 exhibit increased expression compared with normal tissues. Furthermore, retrospective analysis of an independent data set generated a significant stratification of the overall survival of EWS patients into low- and high-risk groups based on the expression of PHGDH, PSAT1, PSPH, SHMT2, SLC1A5, MTHFD2, and MTHFD1L. In summary, our study demonstrates that EWS-FLI1 reprograms the metabolism of EWS cells and that serine-glycine metabolism or glutamine uptake are potential targetable vulnerabilities in this tumor type.