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Background: Metastasis-directed therapy (MDT) is increasingly being used in oligometastatic castration-sensitive prostate cancer (omCSPC). However, it is currently unclear how to optimally integrate MDT with the standard of care of systemic hormonal therapy., Objective: To report long-term outcomes of MDT alone versus MDT and a defined course of androgen deprivation therapy (ADT) in omCSPC., Design, Setting, and Participants: Here, a multicenter, international retrospective cohort of omCSPC as defined by conventional imaging was reported., Outcome Measurements and Statistical Analysis: Biochemical progression-free survival (bPFS), distant progression-free survival (dPFS), and combined biochemical or distant progression-free survival (cPFS) were evaluated with Kaplan-Meier and multivariable Cox proportional hazard regression models., Results and Limitations: A total of 263 patients were included, 105 with MDT + ADT and 158 with MDT alone. The majority of patients had metachronous disease (90.5%). Five-year bPFS, dPFS, and cPFS were, respectively, 24%, 41%, and 19% in patients treated with MDT + ADT and 11% (hazard ratio [HR] 0.48, 95% confidence interval [CI] 0.36-0.64), 29% (HR 0.56, 95% CI 0.40-0.78), and 9% (HR 0.50, 95% CI 0.38-0.67) in patients treated with MDT alone. On a multivariable analysis adjusting for pretreatment variables, the use of ADT was associated with improved bPFS (HR 0.43, p < 0.001), dPFS (HR 0.45, p = 0.002), and cPFS (HR 0.44, p < 0.001)., Conclusions: In this large multi-institutional report, the addition of concurrent ADT to MDT appears to improve time to prostate-specific antigen progression and distant recurrence, noting that about 10% patients had durable control with MDT alone. Ongoing phase 3 studies will help further define treatment options for omCSPC., Patient Summary: Here, we report a large retrospective review evaluating the outcomes of metastasis-directed therapy with or without a limited course of androgen deprivation for patients with oligometastatic castration-sensitive prostate cancer. This international multi-institutional review demonstrates that the addition of androgen deprivation therapy to metastasis-directed therapy (MDT) improves progression-free survival. While a proportion of patients appear to have long-term disease control with MDT alone, further work in biomarker discovery is required to better identify which patients would be appropriate for de-escalated therapy., (Copyright © 2024 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Purpose: To functionally evaluate novel human sequence-derived candidate genes and variants for unsolved ocular congenital cranial dysinnervation disorders (oCCDDs)., Methods: Through exome and genome sequencing of a genetically unsolved human oCCDD cohort, we previously identified variants in 80 strong candidate genes. Here, we further prioritized a subset of these (43 human genes, 57 zebrafish genes) using a G0 CRISPR/Cas9-based knockout assay in zebrafish and generated F2 germline mutants for seventeen. We tested the functionality of variants of uncertain significance in known and novel candidate transcription factor-encoding genes through protein binding microarrays., Results: We first demonstrated the feasibility of the G0 screen by targeting known oCCDD genes phox2a and mafba . 70-90% of gene-targeted G0 zebrafish embryos recapitulated germline homozygous null-equivalent phenotypes. Using this approach, we then identified three novel candidate oCCDD genes ( SEMA3F, OLIG2 , and FRMD4B ) with putative contributions to human and zebrafish cranial motor development. In addition, protein binding microarrays demonstrated reduced or abolished DNA binding of human variants of uncertain significance in known and novel sequence-derived transcription factors PHOX2A (p.(Trp137Cys)), MAFB (p.(Glu223Lys)), and OLIG2 (p.(Arg156Leu))., Conclusions: This study nominates three strong novel candidate oCCDD genes ( SEMA3F, OLIG2 , and FRMD4B ) and supports the functionality and putative pathogenicity of transcription factor candidate variants PHOX2A p.(Trp137Cys), MAFB p.(Glu223Lys), and OLIG2 p.(Arg156Leu). Our findings support that G0 loss-of-function screening in zebrafish can be coupled with human sequence analysis and protein binding microarrays to aid in prioritizing oCCDD candidate genes/variants.

Throughout the COVID-19 pandemic, low-income, minority, and otherwise vulnerable populations have repeatedly been shown to receive unequal access to novel therapies. Addressing this inequity requires specific awareness of the barriers experienced by vulnerable patients, and systemic efforts to address these barriers to provide equitable health care. We designed and implemented an ambulatory COVID-19 treatment program expressly aimed at increasing COVID-19 treatment uptake in a safety-net healthcare system. We describe systemic and human obstacles encountered as well as strategies used to increase use of COVID-19 treatments. Thanks to these strategies, we observed an increase in monoclonal antibody acceptance rate from 29 to 69% over the course of 10 months. We found that interventions such as engaging primary care providers, creating clear-language scripts for outreach calls, assisting with logistic barriers such as transportation, and addressing medical mistrust and hesitancy among both staff and patients were critical to increasing treatment uptake among our safety-net patient population., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Importance: Visual impairment (VI) affects more than 9 million Americans age 65 yr and older, and it limits meaningful participation in daily living. Occupational therapy can have a considerable impact on the functional performance of those with VI; however, information is limited on the existing occupational therapy services available for older adults with VI across the United States., Objective: To calculate the prevalence of VI by U.S. county and quantify and locate the existing occupational therapy practitioners with certification in vision rehabilitation., Design: Synthetic estimation was used to calculate the prevalence of VI among those age 65 yr and older in the United States by county. Geographic Information Systems mapping was used to illustrate the prevalence of VI and availability of occupational therapy practitioners with specialized training in vision rehabilitation by U.S. town., Results: Communities with high concentrations of older adults with VI were more prevalent in the center of the United States, whereas occupational therapy practitioners with specialty training in vision rehabilitation were concentrated primarily on the east coast of the United States, on both Florida coasts, in selected cities in Texas and California, in western Pennsylvania, and in Alabama., Conclusions and Relevance: The availability of occupational therapy practitioners with specialty training in vision rehabilitation does not match the visual rehabilitation needs of older adults in the United States. These findings can be used to prioritize efforts for new service provision, provide outreach to underserved populations, and guide occupational therapy education to improve access to vision rehabilitation throughout the United States. What This Article Adds: The data provided in this study can inform resource allocation, workforce development, and entry-level occupational therapy education to address the ongoing needs of older adults with VI., (Copyright © 2023 by the American Occupational Therapy Association, Inc.)

The lysine acetyltransferase KAT6A (MOZ, MYST3) belongs to the MYST family of chromatin regulators, facilitating histone acetylation. Dysregulation of KAT6A has been implicated in developmental syndromes and the onset of acute myeloid leukemia (AML). Previous work suggests that KAT6A is recruited to its genomic targets by a combinatorial function of histone binding PHD fingers, transcription factors and chromatin binding interaction partners. Here, we demonstrate that a winged helix (WH) domain at the very N-terminus of KAT6A specifically interacts with unmethylated CpG motifs. This DNA binding function leads to the association of KAT6A with unmethylated CpG islands (CGIs) genome-wide. Mutation of the essential amino acids for DNA binding completely abrogates the enrichment of KAT6A at CGIs. In contrast, deletion of a second WH domain or the histone tail binding PHD fingers only subtly influences the binding of KAT6A to CGIs. Overexpression of a KAT6A WH1 mutant has a dominant negative effect on H3K9 histone acetylation, which is comparable to the effects upon overexpression of a KAT6A HAT domain mutant. Taken together, our work revealed a previously unrecognized chromatin recruitment mechanism of KAT6A, offering a new perspective on the role of KAT6A in gene regulation and human diseases., (© The Author(s) 2022. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Background: South Los Angeles (SPA6), with mostly Black (27.4%) and Latinx (68.2%) residents, has the second highest rates of new HIV diagnoses (31 per 100,000) in Los Angeles County. However, there is limited understanding of the HIV testing-to-care continuum among newly diagnosed in this setting., Methods: We conducted an exploratory study that analyzed de-identified data, including demographic characteristics and biomedical outcomes, from the electronic medical records of individuals newly diagnosed with HIV from 2016-2020 at the only public safety-net, county-run health department HIV clinic in SPA 6. We used Pearson Chi-square and Fisher's Exact test to explore associations with HIV outcomes and a Kaplan-Meier survival curve to assess the time to linkage to care., Results: A total of 281 patients were identified. The majority (74.1%) presented with a baseline CD4 <500, many of which presented with a CD4<200 (39.2%). We found twice as many newly diagnosed Black individuals in our study population (48.2%) when compared to LAC (23%), despite only accounting for 27.4% of residents in SPA 6. The majority were linked to care within 30 days of positive test and prescribed anti-retroviral therapy. Viral suppression (59.8%) and undetectable VL (52.6%) were achieved within the year following diagnosis, with 9.3% lost to follow-up. Of those who became virally suppressed, 20.7% experienced viral rebound within the year following diagnosis., Conclusion: The large proportion of patients with a baseline CD4 <500 raises concerns about late diagnoses. Despite high rates of linkage to care and ART prescription, achievement of sustained viral suppression remains low with high rates of viral rebound. Longitudinal studies are needed to understand the barriers to early testing, retention in care, and treatment adherence to develop strategies and interventions with community organizations that respond to the unique needs of people living with HIV in South Los Angeles., Competing Interests: The authors have declared that no competing interests exist.

Purpose: Adolescent dating abuse (ADA) is a public health issue. Adolescents may experience victimization, engage in perpetration, or both. This study explores the co-occurrences of ADA victimization and perpetration, specifically examining which experiences and behaviors are most likely to co-occur and whether these vary by gender., Methods: Data came from a nationally representative sample of 807 adolescents between the ages of 11 and 21 years in the United States who reported on at least one relationship in the past year through the Measure of Adolescent Relationship Harassment and Abuse (MARSHA). Using this sample, we applied network analysis to depict each ADA type as a "node" in a network where it was directly or indirectly associated with other types of victimization and perpetration. This network approach allowed for an empirical understanding of the patterns of victimization and perpetration co-occurrences., Results: Findings demonstrate multiple associations between victimization and perpetration, which were present to a greater extent among male adolescents. The results reveal clusters of co-occurring victimization and perpetration within the domains of (1) cyber and emotional ADA and (2) physical and emotional ADA. A diverse range of victimization experiences (e.g., sexual victimization) did not typically co-occur with perpetration., Discussion: The results suggest that ADA identification and specialized services require a nonbinary approach to address victims and perpetrators' trauma and abusive behaviors. Detection of certain ADA types, especially controlling behaviors within the cyber domain, can help identify and prevent a wide range of other ADA types that tend to co-occur., (Copyright © 2021 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)