Brief Report: Antiretroviral Treatment Use Over Time Among Adolescents and Young Adults in the Rakai Community Cohort Study, 2011-2020.

Background: In sub-Saharan Africa, pediatric and adult treatment programs have not met the needs of youth living with HIV (15-24 years), whose enrollment in antiretroviral treatment (ART) programs is much lower than that of adults. To inform targeted interventions, we analyzed factors associated with ART use among youth in Uganda.

Methods: Data were from 42 communities between 2011 and 2020 (5 survey rounds) from the Rakai Community Cohort Study, an open, population-based cohort.

Engagement in moderate-intensity physical activity supports overnight memory retention in older adults.

Preserving the ability to vividly recall emotionally rich experiences contributes to quality of life in older adulthood. While prior works suggest that moderate-intensity physical activity (MPA) may bolster memory, it is unclear whether this extends to emotionally salient memories consolidated during sleep. In the current study, older adults (mean age = 72.

What's driving girls' adolescent marriage decline in Rakai, Uganda? The interplay between adolescent pregnancies and social determinants, 1999 - 2018.

Few studies have sought to untangle the influence of social determinants and pregnancy on adolescent marriage declines. Using longitudinal data from 15- to 17-year-old girls in the Rakai Community Cohort Survey, we assessed how education, socio-economic status, orphanhood and pregnancy contributed to trends in adolescent marriage. We examined descriptive trends and logistic regressions of the associations between social determinants and adolescent marriage, and conducted causal mediation analysis to assess the extent that pregnancy mediated the effect of education on marriage.

Mutant p53 Exploits Enhancers to Elevate Immunosuppressive Chemokine Expression and Impair Immune Checkpoint Inhibitors in Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer without effective treatments. It is characterized by activating KRAS mutations and p53 alterations. However, how these mutations dysregulate cancer-cell-intrinsic gene programs to influence the immune landscape of the tumor microenvironment (TME) remains poorly understood.

Cerebrovascular pathology mediates associations between hypoxemia during rapid eye movement sleep and medial temporal lobe structure and function in older adults.

Obstructive sleep apnea (OSA) is common in older adults and is associated with medial temporal lobe (MTL) degeneration and memory decline in aging and Alzheimer's disease (AD). However, the underlying mechanisms linking OSA to MTL degeneration and impaired memory remains unclear. By combining magnetic resonance imaging (MRI) assessments of cerebrovascular pathology and MTL structure with clinical polysomnography and assessment of overnight emotional memory retention in older adults at risk for AD, cerebrovascular pathology in fronto-parietal brain regions was shown to statistically mediate the relationship between OSA-related hypoxemia, particularly during rapid eye movement (REM) sleep, and entorhinal cortical thickness.

Cardiorespiratory fitness and circadian rhythms in adolescents: a pilot study.

Although cardiorespiratory fitness (CRF), an important marker of youth health, is associated with earlier sleep/wake schedule, its relationship with circadian rhythms is unclear. This study examined the associations between CRF and rhythm variables in adolescents. Eighteen healthy adolescents (10 females and 8 males;  = 14.

Medial temporal lobe functional network architecture supports sleep-related emotional memory processing in older adults.

Memory consolidation occurs via reactivation of a hippocampal index during non-rapid eye movement slow-wave sleep (NREM SWS) which binds attributes of an experience existing within cortical modules. For memories containing emotional content, hippocampal-amygdala dynamics facilitate consolidation over a sleep bout. This study tested if modularity and centrality-graph theoretical measures that index the level of segregation/integration in a system and the relative import of its nodes-map onto central tenets of memory consolidation theory and sleep-related processing.

Capacity to Consent to Research Among Adolescent-Parent Dyads in Rakai, Uganda.

Objectives: To assess the cognitive capacity of early, middle, and late adolescents and their parents or guardians to provide informed consent to a population-based cohort study.

Study Design: Adolescent-parent/guardian dyads including 40 early (n = 80; 10-14 years), 20 middle (15-17 years), and 20 late (18-19 years) adolescents were recruited from the Rakai Community Cohort Study, an open demographic cohort in Uganda. Participants were administered the MacArthur Competence Assessment Tool for Clinical Research, a structured open-ended assessment; interviews were recorded and transcribed.

Inflammation, tau pathology, and synaptic integrity associated with sleep spindles and memory prior to β-amyloid positivity.

Study Objectives: Fast frequency sleep spindles are reduced in aging and Alzheimer's disease (AD), but the mechanisms and functional relevance of these deficits remain unclear. The study objective was to identify AD biomarkers associated with fast sleep spindle deficits in cognitively unimpaired older adults at risk for AD.

Methods: Fifty-eight cognitively unimpaired, β-amyloid-negative, older adults (mean ± SD; 61.

Appropriateness, Acceptability, and Feasibility of a Neurodiversity-Based Self-determination Program for Autistic Adults.

Published self-determination programs do not adequately address the needs of autistic adults. We designed a multi-component self-determination program, grounded in the neurodiversity paradigm, to help autistic adults achieve goals to improve their quality of life. The first phase involved 5 days of psychoeducation, practice, and social events; the second phase included 3 months of telecoaching; and the third phase included follow-up.

Hypertension and Socioeconomic Status in South Central Uganda: A Population-Based Cohort Study.

Background: Limited studies exploring the impact of socioeconomic status (SES) on hypertension in Africa suggest a positive association between higher SES and hypertension. The economic development in sub-Saharan African countries has led to changes in SES and associated changes in lifestyle, diet, and physical activity, which may affect the relationship between hypertension and SES differently compared with higher income countries. This cross-sectional study from a large population-based cohort, the Rakai Community Cohort Study (RCCS), examines SES, hypertension prevalence, and associated risk factors in the rural Rakai Region in south-central Uganda.

Incident HIV Infection Among Young Men Associated With Female Sexual Partner Types Identified Through Latent Class Analysis, Rakai, Uganda.

Background: Sexual partner characteristics are important determinants of HIV acquisition, but little is known about partner types of young men in sub-Saharan Africa.

Methods: Sexually active men aged 15-24 years from 5 rounds (2005-2013) of the Rakai Community Cohort Study in Uganda reported characteristics of up to 4 past-year female partners. Partner types were identified using latent class analysis.

Latent anxiety in clinical depression is associated with worse recognition of emotional stimuli.

Background: Major Depressive Disorder, characterized by cognitive affective biases, is a considerable public health challenge. Past work has shown that higher depressive symptoms are associated with augmented memory of negative stimuli. In contrast, anxiety symptoms have been associated with overgeneralization of emotional memories.

Brief Report: Mobile Phones, Sexual Behaviors, and HIV Incidence in Rakai, Uganda, From 2010 to 2018.

Background: Sub-Saharan Africa has the highest HIV incidence and prevalence in the world. In the past decade, mobile phone ownership has doubled, affecting social and sexual practices. Using longitudinal follow-up data, this study examined whether mobile phone ownership was associated with sexual behaviors and HIV incidence for youth and adults.

Dendritic cell paucity in mismatch repair-proficient colorectal cancer liver metastases limits immune checkpoint blockade efficacy.

Liver metastasis is a major cause of mortality for patients with colorectal cancer (CRC). Mismatch repair-proficient (pMMR) CRCs make up about 95% of metastatic CRCs, and are unresponsive to immune checkpoint blockade (ICB) therapy. Here we show that mouse models of orthotopic pMMR CRC liver metastasis accurately recapitulate the inefficacy of ICB therapy in patients, whereas the same pMMR CRC tumors are sensitive to ICB therapy when grown subcutaneously.

Solid stress impairs lymphocyte infiltration into lymph-node metastases.

Strong and durable anticancer immune responses are associated with the generation of activated cancer-specific T cells in the draining lymph nodes. However, cancer cells can colonize lymph nodes and drive tumour progression. Here, we show that lymphocytes fail to penetrate metastatic lesions in lymph nodes.

FATTY ACID SYNTHESIS IS REQUIRED FOR BREAST CANCER BRAIN METASTASIS.

Brain metastases are refractory to therapies that control systemic disease in patients with human epidermal growth factor receptor 2 (HER2+) breast cancer, and the brain microenvironment contributes to this therapy resistance. Nutrient availability can vary across tissues, therefore metabolic adaptations required for brain metastatic breast cancer growth may introduce liabilities that can be exploited for therapy. Here, we assessed how metabolism differs between breast tumors in brain versus extracranial sites and found that fatty acid synthesis is elevated in breast tumors growing in brain.

Household wealth and HIV incidence over time, rural Uganda, 1994-2018.

Objective: To examine the relationship between household wealth and HIV incidence in rural Uganda over time from 1994 to 2018. In research conducted early in the epidemic, greater wealth (i.e.

Aerobic fitness and the sleeping brain of adolescents-a pilot study.

Study Objectives: Aerobic fitness (AF) and sleep are major determinants of health in adolescents and impact neurocognitive and psychological development. However, little is known about the interactions between AF and sleep during the developmental transition experienced across adolescence. This study aimed to consider the relationships between AF and habitual sleep patterns and sleep neurophysiology in healthy adolescents.