Meeting Report From the 2023 Cure Ocular Melanoma (CURE OM) Global Science Meeting, Philadelphia, PA, November 2023.

The 2023 Cure Ocular Melanoma (CURE OM) Global Science Meeting was held in Philadelphia on November 6, 2023. There is increased awareness and dedicated research in uveal melanoma (UM), but unmet needs remain in the prevention, detection, and treatment of UM. The purpose of this meeting was to provide an international forum for the exchange of research ideas, to allow for discussion of basic science as well as clinical research on UM, and to gather input about advocacy and patient needs.

Pima County COVID-19 vaccine solutions dashboard project: lessons learned.

Recent improvements in the accessibility of mapping tools and an increased recognition of the importance of leveraging data to inform public health operations has led to enthusiasm among public health departments to rapidly evolve their ability to analyze and apply data to programs. As the COVID-19 pandemic made evident, many health department data systems have been neglected for decades and data literacy among staff low. Significant federal dollars have been allocated to local health departments to modernize health systems.

ICF1-Syndrome-Associated Mutations Prevent De Novo Methylation at a Subset of Imprinted Loci during iPSC Reprogramming.

Parent-of-origin-dependent gene expression of a few hundred human genes is achieved by differential DNA methylation of both parental alleles. This imprinting is required for normal development, and defects in this process lead to human disease. Induced pluripotent stem cells (iPSCs) serve as a valuable tool for in vitro disease modeling.

Proceedings from the Melanoma Research Foundation Mucosal Melanoma Meeting (December 16, 2022, New York, USA).

Mucosal melanoma remains a rare cancer with high mortality and a paucity of therapeutic options. This is due in significant part to its low incidence leading to limited patient access to expert care and downstream clinical/basic science data for research interrogation. Clinical challenges such as delayed and at times inaccurate diagnoses, and lack of consensus tumor staging have added to the suboptimal outcomes for these patients.

The aberrant epigenome of -mutated ICF1 patient iPSCs is amenable to correction, with the exception of a subset of regions with H3K4me3- and/or CTCF-based epigenetic memory.

Bi-allelic hypomorphic mutations in disrupt DNA methyltransferase activity and lead to immunodeficiency, centromeric instability, facial anomalies syndrome, type 1 (ICF1). Although several ICF1 phenotypes have been linked to abnormally hypomethylated repetitive regions, the unique genomic regions responsible for the remaining disease phenotypes remain largely uncharacterized. Here we explored two ICF1 patient-derived induced pluripotent stem cells (iPSCs) and their CRISPR-Cas9-corrected clones to determine whether correction can globally overcome DNA methylation defects and related changes in the epigenome.

Mental health and quality of life during weight loss in females with clinically severe obesity: a randomized clinical trial.

The purpose of this investigation was to explore the effects of dietary weight loss intervention, with and without the addition of exercise on health-related quality of life, depressive symptoms, and anxiety. As part of the EMPOWER study for women, sixty premenopausal women (BMI of 40.4 ± 6.

MBTPS1 regulates proliferation of colorectal cancer primarily through its action on sterol regulatory element-binding proteins.

Among the main metabolic pathways implicated in cancer cell proliferation are those of cholesterol and fatty acid synthesis, both of which are tightly regulated by sterol regulatory element-binding proteins (SREBPs). SREBPs are activated through specific cleavage by membrane-bound transcription factor protease 1 (MBTPS1), a serine protease that cleaves additional substrates (ATF6, BDNF, CREBs and somatostatin), some of which are also implicated in cell proliferation. The goal of this study was to determine whether MBTPS1 may serve as a master regulator in proliferation of colorectal cancer (CRC).

The drinking water crises of Flint and Havelock North: a failure of public health risk management.

Between 2014 and 2016, there were two severe community water system (CWS) failures in Flint, Michigan (MI), USA and Havelock North, Hawkes Bay, New Zealand. These events had profound implications for public health in their respective countries. While the nature of both crises was different, certain aspects of the failings were strikingly similar.

Uveal melanoma patient attitudes towards prognostic testing using gene expression profiling.

Aim: This study explored uveal melanoma patient experiences and regret following molecular prognostic testing using a 15-gene expression profile (GEP) test.

Materials & Methods: A retrospective, cross-sectional survey study was conducted through an online questionnaire capturing patient-reported experiences with prognostic biopsy/molecular testing.

Results: Of 177 respondents, 159 (90%) wanted prognostic information at diagnosis.

Prescribing Exercise in Early-Stage Breast Cancer During Chemotherapy: A Simple Periodized Approach to Align With the Cyclic Phases of Chemotherapy.

Bigaran, A, Howden, EJ, Foulkes, S, Janssens, K, Beaudry, R, Haykowsky, MJ, La Gerche, A, Fraser, SF, and Selig, SE. Prescribing exercise in early-stage breast cancer during chemotherapy: a simple periodized approach to align with the cyclic phases of chemotherapy. J Strength Cond Res 36(10): 2934-2941, 2022-To evaluate whether a periodized aerobic and resistance training plan aligned to the anthracycline chemotherapy (AC) cycles would be well tolerated, feasible, and attenuate the decline in peak oxygen uptake (V̇o2peak) in breast cancer (BC) patients.

Comparative Analysis of the APOL1 Variants in the Genetic Landscape of Renal Carcinoma Cells.

Although the relative risk of renal cell carcinoma associated with chronic kidney injury is particularly high among sub-Saharan African ancestry populations, it is unclear yet whether the gene risk variants (RV) for kidney disease additionally elevate this risk. APOL1 G1 and G2 RV contribute to increased risk for kidney disease in black populations, although the disease mechanism has still not been fully deciphered. While high expression levels of all three APOL1 allelic variants, G0 (the wild type allele), G1, and G2 are injurious to normal human cells, renal carcinoma cells (RCC) naturally tolerate inherent high expression levels of APOL1.

White Paper on Ophthalmic Imaging for Choroidal Nevus Identification and Transformation into Melanoma.

Purpose: To discuss the evolution of noninvasive diagnostic methods in the identification of choroidal nevus and determination of risk factors for malignant transformation as well as introduce the novel role that artificial intelligence (AI) can play in the diagnostic process.

Methods: White paper.

Results: Longstanding diagnostic methods to stratify benign choroidal nevus from choroidal melanoma and to further determine the risk for nevus transformation into melanoma have been dependent on recognition of key clinical features by ophthalmic examination.

RBL2 bi-allelic truncating variants cause severe motor and cognitive impairment without evidence for abnormalities in DNA methylation or telomeric function.

RBL2/p130, a member of the retinoblastoma family of proteins, is a key regulator of cell division and propagates irreversible senescence. RBL2/p130 is also involved in neuronal differentiation and survival, and eliminating Rbl2 in certain mouse strains leads to embryonic lethality accompanied by an abnormal central nervous system (CNS) phenotype. Conflicting reports exist regarding a role of RBL2/p130 in transcriptional regulation of DNA methyltransferases (DNMTs), as well as the control of telomere length.

Epigenetic Characteristics of Human Subtelomeres Vary in Cells Utilizing the Alternative Lengthening of Telomeres (ALT) Pathway.

Most human cancers circumvent senescence by activating a telomere length maintenance mechanism, most commonly involving telomerase activation. A minority of cancers utilize the recombination-based alternative lengthening of telomeres (ALT) pathway. The exact requirements for unleashing normally repressed recombination at telomeres are yet unclear.

The Latest on Uveal Melanoma Research and Clinical Trials: Updates from the Cure Ocular Melanoma (CURE OM) Science Meeting (2019).

Uveal melanoma is a rare cancer in adults, but its treatment is one of the clinical unmet needs in the melanoma field. Metastatic disease develops in approximately 50% of patients and is associated with poor survival due to the lack of effective treatment options. It provides a paradigm for cancers that show evidence of aberrant G protein-coupled receptor signaling, tumor dormancy, and liver-selective metastatic tropism and are associated with the loss of the BAP1 tumor suppressor.

Regulation of telomeric function by DNA methylation differs between humans and mice.

The most distal 2 kb region in the majority of human subtelomeres contains CpG-rich promoters for TERRA, a long non-coding RNA. When the function of the de novo DNA methyltransferase DNMT3B is disrupted, as in ICF1 syndrome, subtelomeres are abnormally hypomethylated, subtelomeric heterochromatin acquires open chromatin characteristics, TERRA is highly expressed, and telomeres shorten rapidly. In this study, we explored whether the regulation of subtelomeric epigenetic characteristics by DNMT3B is conserved between humans and mice.

Impact of a Fruit and Vegetable Prescription Program on Health Outcomes and Behaviors in Young Navajo Children.

Background: Rates of childhood obesity are higher in American Indian and Alaska Native populations, and food insecurity plays a major role in diet-related disparities. To address this need, local healthcare providers and a local nonprofit launched the Navajo Fruit and Vegetable Prescription (FVRx) Program in 2015. Children up to 6 y of age and their caregivers are enrolled in the 6-mo program by healthcare providers.

Fitness, Strength and Body Composition during Weight Loss in Women with Clinically Severe Obesity: A Randomised Clinical Trial.

Introduction: To determine whether combined exercise training with an energy-restricted diet leads to improved physical fitness and body composition when compared to energy restriction alone in free-living premenopausal women with clinically severe obesity.

Methods: Sixty premenopausal women (BMI of 40.4 ± 6.

Implementation of the Navajo fruit and vegetable prescription programme to improve access to healthy foods in a rural food desert.

Objective: To utilise a community-based participatory approach in the design and implementation of an intervention targeting diet-related health problems on Navajo Nation.

Design: A dual strategy approach of community needs/assets assessment and engagement of cross-sectorial partners in programme design with systematic cyclical feedback for programme modifications.

Setting: Navajo Nation, USA.

Human subtelomeric DNA methylation: regulation and roles in telomere function.

Subtelomeres are the regions at chromosome ends, immediately adjacent to the terminal telomeric repeats. The majority of human subtelomeres are CpG-rich in their distal two kilobases, and are methylated during early embryonic development by the de novo DNA methyltransferase DNMT3B. The biological relevance of subtelomeric DNA methylation is highlighted by the presence of promoters for the long non-coding TERRA transcripts in these CpG-rich regions.

The Continuum of Community Engagement in Research: A Roadmap for Understanding and Assessing Progress.

Background: The past two decades have been marked by increased community involvement in the research process. Community-engaged research (CEnR) is increasingly promoted in the literature, and academic programs with a community-academic partnership focus. Community-based participatory research (CBPR) is an approach to frame equitable community involvement in research and is a critical component of the CEnR continuum.

Persistent epigenetic memory impedes rescue of the telomeric phenotype in human ICF iPSCs following DNMT3B correction.

DNA methyltransferase 3B (DNMT3B) is the major DNMT that methylates mammalian genomes during early development. Mutations in human disrupt genome-wide DNA methylation patterns and result in ICF syndrome type 1 (ICF1). To study whether normal DNA methylation patterns may be restored in ICF1 cells, we corrected mutations in induced pluripotent stem cells from ICF1 patients.

Study protocol for a multicentre, controlled non-randomised trial: benefits of exercise physiology services for type 2 diabetes (BEST).

Introduction: Controlled trials support the efficacy of exercise as a treatment modality for chronic conditions, yet effectiveness of real-world Exercise Physiology services is yet to be determined. This study will investigate the efficacy and cost-effectiveness of services provided by Accredited Exercise Physiologists (AEPs) for clients with type 2 diabetes (T2D) in clinical practice.

Methods And Analysis: A non-randomised, opportunistic control, longitudinal design trial will be conducted at ten Exercise Physiology Clinics.

Exercise as a diagnostic and therapeutic tool for the prevention of cardiovascular dysfunction in breast cancer patients.

Background: Anthracycline chemotherapy may be associated with decreased cardiac function and functional capacity measured as the peak oxygen uptake during exercise ( peak). We sought to determine (a) whether a structured exercise training program would attenuate reductions in peak and (b) whether exercise cardiac imaging is a more sensitive marker of cardiac injury than the current standard of care resting left ventricular ejection fraction (LVEF).

Methods: Twenty-eight patients with early stage breast cancer undergoing anthracycline chemotherapy were able to choose between exercise training (mean ± SD age 47 ± 9 years, n = 14) or usual care (mean ± SD age 53 ± 9 years, n = 14).

Subtelomeric methylation distinguishes between subtypes of Immunodeficiency, Centromeric instability and Facial anomalies syndrome.

Human telomeres and adjacent subtelomeres are packaged as heterochromatin. Subtelomeric DNA undergoes methylation during development by DNA methyltransferase 3B (DNMT3B), including the CpG-rich promoters of the long non-coding RNA (TERRA) embedded in these regions. The factors that direct DNMT3B methylation to human subtelomeres and maintain this methylation throughout lifetime are yet unknown.