Androgen receptor drives polyamine synthesis creating a vulnerability for prostate cancer.

Supraphysiological androgen (SPA) treatment can paradoxically restrict growth of castration-resistant prostate cancer with high androgen receptor (AR) activity, which is the basis for use of Bipolar Androgen Therapy (BAT) for patients with this disease. While androgens are widely appreciated to enhance anabolic metabolism, how SPA-mediated metabolic changes alter prostate cancer progression and therapy response is unknown. Here, we report that SPA markedly increased intracellular and secreted polyamines in prostate cancer models.

Exploring Systemic Comorbidities and Lifestyle Factors Associated With Seborrheic Dermatitis: A Scoping Review.

Seborrheic dermatitis (SD), a chronic inflammatory skin condition consisting of itchy, red patches with greasy scales, has been linked to numerous systemic conditions. This review evaluates comorbidities and lifestyle factors that are associated with seborrheic dermatitis. A literary search was conducted in August 2024 using EMBASE, PubMed, and Medline Industries, and evaluated according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.

Intimate Partner Violence Among Adolescent Mothers Living With and Without HIV: A Pre- and During-COVID-19 South African Cohort Analysis.

Purpose: Adolescent mothers face heightened economic and social vulnerabilities, which can place them at increased risk of intimate partner violence (IPV), prepandemic, and during COVID-19. However, few studies examine this population, and even less disaggregate findings by HIV status.

Methods: We analyzed data from 834 South African adolescent mothers, 35% living with HIV (LHIV), who reported on physical, psychological, and sexual IPV exposure at two interviews: 2018-2019 (prepandemic) and 2021-2022 (during COVID-19).

Vaccine coverage and timeliness among children of adolescent mothers: A community-based study in the Eastern Cape, South Africa.

Background: Children born to adolescent mothers are more vulnerable to infant mortality and morbidity than those born to adult mothers. HIV-exposed children have lower antibody protection against vaccine-preventable diseases at birth compared to unexposed children. In South Africa, 17 % of adolescent girls aged 15-19 years are mothers, yet vaccination coverage and timeliness among their children is underreported.

Mutant ARID1A: igniting cancer immunotherapy.

Maxwell et al. show that ARID1A loss enhances antitumor immunity by triggering a type I IFN response through the cGAS-STING pathway, thereby promoting T cell infiltration and cytotoxicity. These findings highlight SWI/SNF inhibitors as a strategy to augment immunotherapy efficacy by potentially transforming non-responsive tumors into responders and advancing approaches to cancer treatment.

Social scripts of violence among adolescent girls and young women in Zambia: Exploring how gender norms and social expectations are activated in the aftermath of violence.

Adolescent girls and young women ages 15-24 experience high rates of gender-based violence (GBV), underpinned by gender and social norms that shape their transitions to adulthood. For interventions that seek to leverage and build on existing infrastructure for health service provision, it is important to understand how gender norms operate in the background and how they shape service engagement or non-engagement. In formative work for our project, Screen & Support, outside of Lusaka, Zambia, we engaged in community conversations with adolescent girls and young women to understand common types and experiences of violence, perceptions of what causes violence, and pathways to post-violence service access.

Mechanisms of sensitivity and resistance to CDK4/CDK6 inhibitors in hormone receptor-positive breast cancer treatment.

Cell cycle dysregulation is a hallmark of cancer that promotes eccessive cell division. Cyclin-dependent kinase 4 (CDK4) and cyclin-dependent kinase 6 (CDK6) are key molecules in the G1-to-S phase cell cycle transition and are crucial for the onset, survival, and progression of breast cancer (BC). Small-molecule CDK4/CDK6 inhibitors (CDK4/6i) block phosphorylation of tumor suppressor Rb and thus restrain susceptible BC cells in G1 phase.

Zurletrectinib is a next-generation TRK inhibitor with strong intracranial activity against NTRK fusion-positive tumours with on-target resistance to first-generation agents.

Background: While NTRK fusion-positive cancers can be exquisitely sensitive to first-generation TRK inhibitors, resistance inevitably occurs, mediated in many cases by acquired NTRK mutations. Next-generation inhibitors (e.g.

Differences in condom access and use and associated factors between persons with and without disabilities receiving social cash transfers in Luapula province, Zambia-A cross-sectional study.

Persons with disabilities are disadvantaged in accessing sexual and reproductive health services, including condoms. In this study, we investigated whether condom access and use and their associated factors differed between persons with and without disabilities. We used data from adults in households receiving the Government of Zambia social cash transfers (SCT) in four districts of Luapula province.

Longitudinal Trajectories of Antiretroviral Treatment Adherence and Associations With Durable Viral Suppression Among Adolescents Living With HIV in South Africa.

Background: Compared with other age groups, adolescents living with HIV (ALHIV) are estimated to have lower levels of adherence to antiretroviral treatment. Despite this, we lack evidence on adolescents' adherence patterns over time to inform the customization of intervention strategies.

Setting: Eastern Cape province, South Africa.

Methylation of the chromatin modifier KMT2D by SMYD2 contributes to therapeutic response in hormone-dependent breast cancer.

Activating mutations in PIK3CA are frequently found in estrogen-receptor-positive (ER+) breast cancer, and the combination of the phosphatidylinositol 3-kinase (PI3K) inhibitor alpelisib with anti-ER inhibitors is approved for therapy. We have previously demonstrated that the PI3K pathway regulates ER activity through phosphorylation of the chromatin modifier KMT2D. Here, we discovered a methylation site on KMT2D, at K1330 directly adjacent to S1331, catalyzed by the lysine methyltransferase SMYD2.

Digital tools for youth health promotion: principles, policies and practices in sub-Saharan Africa.

Although digital health promotion (DHP) technologies for young people are increasingly available in low- and middle-income countries (LMICs), there has been insufficient research investigating whether existing ethical and policy frameworks are adequate to address the challenges and promote the technological opportunities in these settings. In an effort to fill this gap and as part of a larger research project, in November 2022, we conducted a workshop in Cape Town, South Africa, entitled 'Unlocking the Potential of Digital Health Promotion for Young People in Low- and Middle-Income Countries'. The workshop brought together 25 experts from the areas of digital health ethics, youth health and engagement, health policy and promotion and technology development, predominantly from sub-Saharan Africa (SSA), to explore their views on the ethics and governance and potential policy pathways of DHP for young people in LMICs.

Epigenetic mechanisms of cancer progression and therapy resistance in estrogen-receptor (ER+) breast cancer.

Estrogen receptor-positive (ER+) breast cancer is the most frequent breast cancer subtype. Agents targeting the ER signaling pathway have been successful in reducing mortality from breast cancer for decades. However, mechanisms of resistance to these treatments arise, especially in the metastatic setting.

Exploring the cognitive development of children born to adolescent mothers in South Africa.

Unlabelled: This study explores the cognitive development of children born to adolescent mothers within South Africa compared to existing reference data, and explores development by child age bands to examine relative levels of development. Cross-sectional analyses present data from 954 adolescents (10-19 years) and their first-born children (0-68 months). All adolescents completed questionnaires relating to themselves and their children, and standardized child cognitive assessments (Mullen Scales of Early Learning) were undertaken.

Healthcare provisions associated with multiple HIV-related outcomes among adolescent girls and young women living with HIV in South Africa: a cross-sectional study.

Introduction: Adolescent girls and young women (AGYW) living with HIV experience poor HIV outcomes and high rates of unintended pregnancy. Little is known about which healthcare provisions can optimize their HIV-related outcomes, particularly among AGYW mothers.

Methods: Eligible 12- to 24-year-old AGYW living with HIV from 61 health facilities in a South African district completed a survey in 2018-2019 (90% recruited).

Identifying potential catalysts to accelerate the achievement of Sustainable Development Goals (SDGs) among adolescents living in Nigeria.

Investing in adolescents in Africa holds great promise for the development of the continent. The steps involved in identifying factors linked to interventions that may accelerate the attainment of multiple SDGs for adolescents in Nigeria are described. Data from a survey to investigate the well-being of 1800 adolescents aged 10-19 years in Southwest Nigeria was analysed.

ERK hyperactivation serves as a unified mechanism of escape in intrinsic and acquired CDK4/6 inhibitor resistance in acral lentiginous melanoma.

Patients with metastatic acral lentiginous melanoma (ALM) suffer worse outcomes relative to patients with other forms of cutaneous melanoma (CM), and do not benefit as well to approved melanoma therapies. Identification of cyclin-dependent kinase 4 and 6 (CDK4/6) pathway gene alterations in >60% of ALMs has led to clinical trials of the CDK4/6 inhibitor (CDK4i/6i) palbociclib for ALM; however, median progression free survival with CDK4i/6i treatment was only 2.2 months, suggesting existence of resistance mechanisms.

Associations of social media and health content use with sexual risk behaviours among adolescents in South Africa.

Increasing rates of mobile phone access present potential new opportunities and risks for adolescents' sexual and reproductive health in resource-poor settings. We investigated associations between mobile phone access/use and sexual risks in a cohort of 10-24-year-olds in South Africa. 1563 adolescents (69% living with HIV) were interviewed in three waves between 2014 and 2018.

Opioid Impacts on Cardiovascular Health.

The prevalence of opioid use in the current opioid epidemic era has led to a public health emergency due to the ties to mortality and morbidity. Studies have investigated opioids' impacts on different aspects of cardiovascular health, although there seems to be a lack of a current concise review. Therefore, the aim of this literature review is to provide a summary of the most recent studies from the past decade that postulate a connection between opioids and their impact on cardiovascular health while highlighting conflicting areas among published research.

Lessons From Implementing Ask-Boost-Connect-Discuss, a Peer-Delivered Psychosocial Intervention for Young Mothers Living With HIV in Malawi, Tanzania, Uganda, and Zambia.

Adolescent girls and young women in sub-Saharan Africa are at high risk of HIV, unintended pregnancy, and early motherhood. These intersecting risks can adversely affect their developmental trajectories and lifelong well-being. Because young mothers living with HIV in these settings experience high levels of stigma, shame, and isolation, tailored psychosocial intervention approaches for this group are critical yet unavailable.