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Background In Saudi Arabia, the rapid growth of digital media and smartphone use has raised concerns about problematic usage and its impacts on well-being, especially among young people. Research on stakeholder perspectives regarding intervention strategies remains limited. Objective This study aimed to gather insights from societal stakeholders, including youth, parents, policymakers, industry leaders, clinicians, educators, and digital media users, to inform culturally tailored interventions for digital well-being in Saudi Arabia. Methods A purposeful non-random sample of 92 participants representing different stakeholder groups was recruited to complete an online survey, answering questions about their experiences and perspectives on digital media use. Primary stakeholder group was assigned based on participant self-selection. We analyzed distributions of categorical variables related to media use time, reasons for use, impacts, self-regulation strategies, and perceived effectiveness of interventions (e.g., education programs, media campaigns, Internet use restrictions). Results Of the participants, 63.0% were male, and 46.7% were under 25 years old. Regular digital media users, individuals with problematic Internet use, and clinicians/health professionals comprised 26.1%, 18.5%, and 18.5% of respondents, respectively. Extensive screen time was common, with 47.8% reporting four or more hours of recreational digital use on weekdays and 56.6% on weekends. Participants reported both positive impacts (e.g., social connections, school/work performance) and negative impacts (e.g., sleep disruption, reduced physical activity) of digital media use. Efforts to regulate media use were reported by 72.8%, with strategies like deleting apps or digital detoxes. At least 50.0% of participants endorsed all proposed intervention approaches as likely effective for improving digital well-being, with educational programs for parents, school programs, and regulatory apps receiving over 75.0% support. Children and adolescents were seen as key target groups for these interventions. Conclusions Findings from this diverse stakeholder sample suggest that digital well-being interventions in Saudi Arabia should prioritize youth, focusing on education-based approaches and apps for media regulation. Incorporating these perspectives can lead to culturally relevant interventions addressing the unique challenges of digital media use in Saudi Arabia. The generalizability of the findings may be limited due to sample size and potential overrepresentation of certain stakeholder groups.

IntroductionSystemic racism exposes Black and Latinx adolescents to a range of traumatic stressors that increase the risk for long-term emotional and behavioural health (EBH) problems. Researchers have theorised that critical consciousness (CC)—awareness of societal inequities and engagement in action to promote social justice—may serve as a protective factor that promotes youth well-being. There are few rigorous longitudinal research studies, however, that examine the development of CC among adolescents, the association over time of CC with EBH and the potential of CC to protect against harmful effects of race-related stress. This longitudinal study, Resilience in a Stressful Era (RISE), addresses these gaps using a mixed methods approach with Black, Latinx and White adolescents in Baltimore.Methods and analysisWe plan to enrol up to 650 Black, Latinx and White adolescents ages 14–19 who reside in Baltimore, Maryland. The recruitment will include outreach through youth-serving organisations, community events, youth networks, social media, snowball sampling and re-contacting adolescents who participated in a prior study (R01HD090022; PI: Mendelson). Participants will complete online questionnaires assessing exposure to pandemic- and race-related stress, CC and EBH twice per year over 4 years as they transition into early adulthood. Using an explanatory sequential mixed methods approach, in-depth interviews exploring the development and impact of CC will be conducted with a subset of participants selected based on their CC scores and, separately, their caregivers. A Youth Advisory Board comprised of adolescents who are representative of our target study population will be developed to provide input on the study and its implementation. Growth mixture modelling and latent variable modelling will be used to analyse quantitative data. Themes identified through qualitative analyses will expand the understanding of quantitative findings.Ethics and disseminationAll study procedures were approved by the Johns Hopkins Bloomberg School of Public Health Institutional Review Board. Findings will be disseminated through publications in peer-reviewed journals and presentations at academic conferences. We will also communicate research findings with study participants and disseminate findings to the Baltimore community, such as developing briefs for the Baltimore City Health Department and/or hosting a town hall meeting for Baltimore families.

Prior work has identified the need for replication of psychological research; however, validation efforts are rare. The purpose of the current study was to confirm latent profiles of comorbid psychological symptoms in an urban adolescent sample and examine differences in gender and trait mindfulness across these profiles. Cross-sectional data from 201 eighth grade students (63% female; Mage = 13.24; 86% Black) across nine Baltimore City public middle schools were analyzed. Confirmatory latent profile analyses showed that the previously-identified 3-profile solution with boundary constraints was the best fit for the data, and significant sex and trait mindfulness differences were identified. The current study supports the need for future replication studies using this methodology to improve theory and targeted interventions.

Background: Polysubstance use is a highly prevalent public health issue, particularly among adolescents, and decisions on prevention programming and policies are often made at the local level. While there is a growing literature examining patterns of polysubstance use among adolescents, little is known about differences in those patterns across geographic regions. Methods: Using a large, representative sample of high school students from the state of Maryland (n = 41,091) from the 2018 Maryland Youth Risk Behavior Survey, we conducted a latent class analysis (LCA) of adolescent substance use along nine binary indicators, including past 30-day combustible tobacco, e-cigarette, alcohol, and cannabis use, as well as lifetime use of prescription opioids, cocaine, heroin, methamphetamine, and injection drug use. Measurement invariance across counties was examined using the Multiple Indicators and Multiple Causes (MIMIC) procedure. Results: The results of the LCA show three classes of adolescent substance use for the total sample: (1) low substance use, (2) commonly used substances (i.e., e-cigarette, alcohol, and cannabis use), and (3) polysubstance use. The results from the MIMIC procedure demonstrated geographic differences in students’ endorsement of specific indicators and their class membership. Conclusions: These differences demonstrate the need for an examination of local trends in adolescent polysubstance use to inform multi-tiered prevention programming and policy.

For some children, peer victimization stops rather quickly, whereas for others it marks the beginning of a long trajectory of peer abuse (Kochenderfer-Ladd & Wardrop, 2001). Unfortunately, we know little about these trajectories and what factors may influence membership in increasing or decreasing victimization over time. To address this question, I identified children's developmental patterns of victimization in early elementary school and examined which child-level factors influenced children's membership in victimization trajectories using latent growth mixture modeling. Results showed that boys and girls demonstrated differential victimization patterns over time that also varied by victimization type. For example, boys experienced more physical victimization than girls and increased victimization over time was predicted by boys who display high levels of negative emotion (e.g., anger) towards peers and low levels of effortful control (e.g., gets frustrated easily). Conversely, girls exhibited multiple trajectories of increasing relational victimization (i.e., talking about others behind their back) over time, whereas most boys experienced low levels or only slightly increasing relational victimization over time. For girls, withdrawn behavior lack of positive emotion, and displaying of negative emotions was predictive of experiencing high levels of victimization over time.

Malignancy is accompanied by changes in the metabolism of both cells and the organism 1 , 2 . Pancreatic ductal adenocarcinoma (PDAC) is associated with wasting of peripheral tissues, a metabolic syndrome that lowers quality of life and has been proposed to decrease survival of patients with cancer 3 , 4 . Tissue wasting is a multifactorial disease and targeting specific circulating factors to reverse this syndrome has been mostly ineffective in the clinic 5 , 6 . Here we show that loss of both adipose and muscle tissue occurs early in the development of pancreatic cancer. Using mouse models of PDAC, we show that tumour growth in the pancreas but not in other sites leads to adipose tissue wasting, suggesting that tumour growth within the pancreatic environment contributes to this wasting phenotype. We find that decreased exocrine pancreatic function is a driver of adipose tissue loss and that replacement of pancreatic enzymes attenuates PDAC-associated wasting of peripheral tissues. Paradoxically, reversal of adipose tissue loss impairs survival in mice with PDAC. When analysing patients with PDAC, we find that depletion of adipose and skeletal muscle tissues at the time of diagnosis is common, but is not associated with worse survival. Taken together, these results provide an explanation for wasting of adipose tissue in early PDAC and suggest that early loss of peripheral tissue associated with pancreatic cancer may not impair survival. Pancreatic ductal adenocarcinoma in mice induces loss of adipose tissue through altered function of the exocrine pancreas, and supplementing pancreatic enzymes attenuates the wasting of peripheral tissues induced by pancreatic cancer.

McArdle disease and mitochondrial myopathy impair muscle oxidative phosphorylation (OXPHOS) by distinct mechanisms: the former by restricting oxidative substrate availability caused by blocked glycogen breakdown, the latter because of intrinsic respiratory chain defects. We applied metabolic profiling to systematically interrogate these disorders at rest, when muscle symptoms are typically minimal, and with exercise, when symptoms of premature fatigue and potential muscle injury are unmasked. At rest, patients with mitochondrial disease exhibit elevated lactate and reduced uridine; in McArdle disease purine nucleotide metabolites, including xanthine, hypoxanthine, and inosine are elevated. During exercise, glycolytic intermediates, TCA cycle intermediates, and pantothenate expand dramatically in both mitochondrial disease and control subjects. In contrast, in McArdle disease, these metabolites remain unchanged from rest; but urea cycle intermediates are increased, likely attributable to increased ammonia production as a result of exaggerated purine degradation. Our results establish skeletal muscle glycogen as the source of TCA cycle expansion that normally accompanies exercise and imply that impaired TCA cycle flux is a central mechanism of restricted oxidative capacity in this disorder. Finally, we report that resting levels of long-chain triacylglycerols in mitochondrial myopathy correlate with the severity of OXPHOS dysfunction, as indicated by the level of impaired O₂ extraction from arterial blood during peak exercise. Our integrated analysis of exercise and metabolism provides unique insights into the biochemical basis of these muscle oxidative defects, with potential implications for their clinical management.

A strategy for HIV-1 vaccine development is to define envelope (Env) evolution of broadly neutralizing antibodies (bnAbs) in infection and to recreate those events by vaccination. Here, we report host tolerance mechanisms that limit the development of CD4-binding site (CD4bs), HCDR3-binder bnAbs via sequential HIV-1 Env vaccination. Vaccine-induced macaque CD4bs antibodies neutralize 7% of HIV-1 strains, recognize open Env trimers, and accumulate relatively modest somatic mutations. In naive CD4bs, unmutated common ancestor knock-in mice Env + B cell clones develop anergy and partial deletion at the transitional to mature B cell stage, but become Env − upon receptor editing. In comparison with repetitive Env immunizations, sequential Env administration rescue anergic Env + (non-edited) precursor B cells. Thus, stepwise immunization initiates CD4bs-bnAb responses, but immune tolerance mechanisms restrict their development, suggesting that sequential immunogen-based vaccine regimens will likely need to incorporate strategies to expand bnAb precursor pools. An efficient HIV-1 vaccine will likely depend on eliciting broadly neutralizing antibodies (bnAb). Here the authors analyze the B cell repertoire in macaques and knock-in mice in response to sequential immunization with Env variants that induce a bnAb targeting the CD4-binding site of Env in a HIV-1 infected individual.

Now in its 25th year, the Mutant Mouse Resource and Research Center (MMRRC) consortium continues to serve the United States and international biomedical scientific community as a public repository and distribution archive of laboratory mouse models of human disease for research. Supported by the National Institutes of Health (NIH), the MMRRC consists of 4 regionally distributed and dedicated vivaria, offices, and specialized laboratory facilities and an Informatics Coordination and Service Center (ICSC). The overarching purpose of the MMRRC is to facilitate groundbreaking biomedical research by offering an extensive repertoire of mutant mice that are essential for advancing the understanding of human physiology and disease. The function of the MMRRC is to identify, acquire, evaluate, characterize, cryopreserve, and distribute mutant mouse strains to qualified biomedical investigators around the nation and the globe. Mouse strains accepted from the research community are held to the highest scientific standards to optimize reproducibility and enhance scientific rigor and transparency. All submitted strains are thoroughly reviewed, documented, and validated using extensive scientific quality control measures. In addition, the MMRRC conducts resource-related research on cryopreservation, mouse genetics, environmental conditions, and other topics that enhance operations of the MMRRC. Today, the MMRRC maintains an archive of mice, cryopreserved embryos and sperm, embryonic stem (ES) cell lines, and murine hybridomas for nearly 65,000 alleles. Since its inception, the MMRRC has fulfilled more than 20,000 orders from 13,651 scientists at 8441 institutions worldwide. The MMRRC also provides numerous services to assist researchers, including scientific consultation, technical assistance, genetic assays, microbiome analysis, analytical phenotyping, pathology, cryorecovery, husbandry, breeding and colony management, infectious disease surveillance, and disease modeling. The ICSC coordinates MMRRC operations, interacts with researchers, and manages the website (mmrrc.org) and online catalogue. Researchers benefit from an expansive list of well-defined mouse models of disease that meet the highest scientific standards while submitting investigators benefit by having their mouse strains cryopreserved, protected, and distributed in compliance with NIH policies.

Measures from affinity-proteomics platforms often correlate poorly, challenging interpretation of protein associations with genetic variants and phenotypes. Here, we examine 2157 proteins measured on both SomaScan 7k and Olink Explore 3072 across 1930 participants with genetic similarity to European, African, East Asian, and Admixed American ancestry references. Inter-platform correlation coefficients for these 2157 proteins follow a bimodal distribution (median r = 0.30). We evaluate protein measure associations with genetic variants, and find approximately 25-30% of the signals on each platform are likely driven by protein-altering variants. We highlight 80 proteins that correlate differently across ancestry groups likely in part due to differing protein-altering variant frequencies by ancestry. Furthermore, adjustment for protein-altering variants with opposite directions of effect by platform improves inter-platform protein measure correlation and results in more concordant genetic and phenotypic associations. Hence, protein-altering variants need to be accounted for across ancestries to facilitate platform-concordant and accurate protein measurement. Affinity-proteomics platforms often yield poorly correlated measurements. Here, the authors show that protein-altering variants drive a portion of inter-platform inconsistency and that accounting for genetic variants can improve concordance of protein measures and phenotypic associations across ancestries.