Identification of targetable epigenetic vulnerabilities in uveal melanoma.

Uveal melanoma (UM) is the most prevalent primary intraocular malignancy in adults, which preferentially metastasizes to the liver in approximately half of all cases. Metastatic UM is notoriously resistant to therapy and is almost uniformly fatal. UM metastasis is most strongly associated with mutational inactivation of the tumor suppressor gene.

Developmental cascades from maternal depressive symptoms in childhood to adolescents' friendship quality: A 13-year longitudinal study.

Adolescent friendships of positive quality promote well-being for decades to come. But what impedes the development of positive friendship quality? The present study examined whether maternal depressive symptoms during early childhood predict children's friendship quality into adolescence, and whether observed negative parenting behavior and children's earlier friendship quality, social skills, and their own depressive symptoms in middle childhood mediate these associations. We used six waves of data from a prospective longitudinal community sample ( = 396).

Cognitive Control Moderates Associations Between Domains of Temperamental Reactivity and Preschoolers' Social Behaviors.

Temperamental characteristics and emerging cognitive control are meaningful predictors of children's development of adaptive and maladaptive social behaviors during the preschool period. However, knowledge of the interplay of these pathways, when examined concurrently to highlight their individual contributions, is limited. Using a cross-sectional sample of 3-year-old children, we examined parent-reported discrete traits of negative (anger, fear, sadness, and shyness) and positive (low- and high-intensity pleasure) temperamental reactivity as predictors of children's prosociality and physical aggression.

15-Gene Expression Profile and as Integrated Prognostic Test for Uveal Melanoma: First Report of Collaborative Ocular Oncology Group Study No. 2 (COOG2.1).

PURPOSEValidated and accurate prognostic testing is critical for precision medicine in uveal melanoma (UM). Our aims were to (1) prospectively validate an integrated prognostic classifier combining a 15-gene expression profile (15-GEP) and RNA expression and (2) identify clinical variables that enhance the prognostic accuracy of the 15-GEP/ classifier.MATERIALS AND METHODSThis study included 1,577 patients with UM of the choroid and/or ciliary body who were enrolled in the Collaborative Ocular Oncology Group Study Number 2 (COOG2) and prospectively monitored across 26 North American centers.

PRAME induces genomic instability in uveal melanoma.

PRAME is a CUL2 ubiquitin ligase subunit that is normally expressed in the testis but becomes aberrantly overexpressed in many cancer types in association with aneuploidy and metastasis. Here, we show that PRAME is expressed predominantly in spermatogonia around the time of meiotic crossing-over in coordination with genes mediating DNA double strand break repair. Expression of PRAME in somatic cells upregulates pathways involved in meiosis, chromosome segregation and DNA repair, and it leads to increased DNA double strand breaks, telomere dysfunction and aneuploidy in neoplastic and non-neoplastic cells.

PRAME induces genomic instability in uveal melanoma.

PRAME is a CUL2 ubiquitin ligase subunit that is normally expressed in the testis but becomes aberrantly overexpressed in many cancer types in association with aneuploidy and metastasis. Here, we show that PRAME is expressed predominantly in spermatogonia around the time of meiotic crossing-over in coordination with genes mediating DNA double strand break repair. Expression of PRAME in somatic cells upregulates pathways involved in meiosis, chromosome segregation and DNA repair, and it leads to increased DNA double strand breaks, telomere dysfunction and aneuploidy in neoplastic and non-neoplastic cells.

The Accuracy of Early Reproductive History and Physical Activity Participation Recall Across Multiple Age Ranges.

The ability to accurately recall specific reproductive health events is an integral aspect of medical decision making and evaluating a female's overall health and wellness across their lifespan. The Health and Reproductive Survey (HeRS) was developed to recall reproductive events and environmental influences on reproductive characteristics throughout the lifespan of a female. This study aimed to determine how reliably women recall certain events during menarche and early reproductive years.

Physiologic and Behavioral Correlates of Energy Intake in Emerging Adulthood: Cross-Sectional Analysis of the RIGHT Track Health Study.

Background: Consistent findings have reported that FFM is associated with EI. However, conjoint assessments of physiologic (body composition, fasting serum leptin) and behavioral [eating behaviors and physical activity (PA)] correlates of EI during emerging adulthood have not been examined.

Objectives: We assessed associations between physiologic and behavioral correlates of EI within the context of one another in emerging adults (18-28 years old).

Maternal Depressive Symptoms and Adolescents' Unhealthy Behavior: A 15-year Longitudinal Study.

Objectives: First, to leverage 15 years of longitudinal data, from child ages 2 to 17, to examine whether maternal depressive symptoms in early and middle childhood and in adolescence predict their child's unhealthy behaviors during adolescence. Second, to examine whether the timing of maternal depressive symptoms or specific unhealthy behaviors matter and whether child depressive symptoms and body mass index explain these associations.

Methods: Data came from a prospective-longitudinal community sample with multi-informant data (N = 213) from child ages 2 to17.

RB1 loss triggers dependence on ESRRG in retinoblastoma.

Retinoblastoma (Rb) is a deadly childhood eye cancer that is classically initiated by inactivation of the RB1 tumor suppressor. Clinical management continues to rely on nonspecific chemotherapeutic agents that are associated with treatment resistance and toxicity. Here, we analyzed 103 whole exomes, 20 whole transcriptomes, 5 single-cell transcriptomes, and 4 whole genomes from primary Rb tumors to identify previously unknown Rb dependencies.

BAP1 Loss Promotes Suppressive Tumor Immune Microenvironment via Upregulation of PROS1 in Class 2 Uveal Melanomas.

Uveal melanoma (UM) is the most common primary cancer of the eye and is associated with a high rate of metastatic death. UM can be stratified into two main classes based on metastatic risk, with class 1 UM having a low metastatic risk and class 2 UM having a high metastatic risk. Class 2 UM have a distinctive genomic, transcriptomic, histopathologic, and clinical phenotype characterized by biallelic inactivation of the tumor-suppressor gene, an immune-suppressive microenvironment enriched for M2-polarized macrophages, and poor response to checkpoint-inhibitor immunotherapy.

Emerging self-regulatory skills in childhood predict cardiometabolic risk in adolescence.

Cardiometabolic risk (CMR) has increased among adolescents. A growing literature shows that childhood self-regulatory skills are associated with obesity and CMR. However, the developmental nature of self-regulation has not been considered in existing studies.

Longitudinal associations between specific types of emotional reactivity and psychological, physical health, and school adjustment.

Using a multimethod, multiinformant longitudinal design, we examined associations between specific forms of positive and negative emotional reactivity at age 5, children's effortful control (EC), emotion regulation, and social skills at age 7, and adolescent functioning across psychological, academic, and physical health domains at ages 15/16 ( = 383). We examined how distinct components of childhood emotional reactivity directly and indirectly predict domain-specific forms of adolescent adjustment, thereby identifying developmental pathways between specific types of emotional reactivity and adjustment above and beyond the propensity to express other forms of emotional reactivity. Age 5 high-intensity positivity was associated with lower age 7 EC and more adolescent risk-taking; age 5 low-intensity positivity was associated with better age 7 EC and adolescent cardiovascular health, providing evidence for the heterogeneity of positive emotional reactivity.

Pathways from maternal depressive symptoms to children's academic performance in adolescence: A 13-year prospective-longitudinal study.

The pathways through which exposure to maternal depressive symptoms in early childhood are linked to academic performance during adolescence are poorly understood. This study tested pathways from maternal depressive symptoms (age 2-5) to adolescent academic performance (age 15) through cumulative parenting risk (age 7) and subsequent child functioning (age 10), using multi-informant data from a prospective longitudinal community study spanning 13 years (N = 389, 47% male, 68% White). Structural equation models testing indirect effects revealed small associations between maternal depressive symptoms and increased cumulative parenting risk and poorer child functioning, and, via these pathways, with poorer academic performance.

Measurement of Behavioral Emotion Regulation Strategies in Early Childhood: The Early Emotion Regulation Behavior Questionnaire (EERBQ).

The Early Emotion Regulation Behavior Questionnaire (EERBQ) assesses children's emotion regulation (ER) behavioral strategies in both positive and negative emotional contexts. Psychometric properties and factor structure were tested in a sample of caregivers across the United States ( = 362) with children ages 2-6 years-old (56% male; 73% White). Findings suggest that the EERBQ is psychometrically sound and correlates with other well-established measures of children's socioemotional functioning.

Multiple Genetically Distinct Uveal Melanomas Arise in the Same Eye of Two Patients with Melanosis Oculi.

Purpose: To determine whether unilateral multifocal uveal melanomas (UM) in the setting of ocular melanosis (melanosis oculi) represent genetically independent tumors.

Design: Clinical case series.

Methods: Two patients with unilateral multifocal UM in the setting of melanosis oculi were included.

Vaping and E-Cigarette Use in Children and Adolescents: Implications on Perioperative Care From the American Society of Anesthesiologists Committee on Pediatric Anesthesia, Society for Pediatric Anesthesia, and American Academy of Pediatrics Section on Anesthesiology and Pain Medicine.

Electronic cigarettes (e-cigarettes) or vaping use in adolescents has emerged as a public health crisis that impacts the perioperative care of this vulnerable population. E-cigarettes have become the most commonly used tobacco products among youth in the United States. Fruit and mint flavors and additives such as marijuana have enticed children and adolescents.

Brain tissue transcriptomic analysis of SIV-infected macaques identifies several altered metabolic pathways linked to neuropathogenesis and poly (ADP-ribose) polymerases (PARPs) as potential therapeutic targets.

Despite improvements in antiretroviral therapy, human immunodeficiency virus type 1 (HIV-1)-associated neurocognitive disorders (HAND) remain prevalent in subjects undergoing therapy. HAND significantly affects individuals' quality of life, as well as adherence to therapy, and, despite the increasing understanding of neuropathogenesis, no definitive diagnostic or prognostic marker has been identified. We investigated transcriptomic profiles in frontal cortex tissues of Simian immunodeficiency virus (SIV)-infected Rhesus macaques sacrificed at different stages of infection.

Emotional Eating in Adolescence: Effects of Emotion Regulation, Weight Status and Negative Body Image.

Emotional eating is associated with an increased risk of binge eating, eating in the absence of hunger and obesity risk. While previous studies with children and adolescents suggest that emotion regulation may be a key predictor of this dysregulated eating behavior, little is known about what other factors may be influencing the link between emotional regulation and emotional eating in adolescence. This multi-method longitudinal study ( = 138) utilized linear regression models to examine associations between childhood emotion regulation, adolescent weight status and negative body image, and emotional eating at age 17.

FAMILY-LEVEL FACTORS AFFECTING SOCIAL AND ACADEMIC COMPETENCE OF AFRICAN AMERICAN CHILDREN.

Background: Research shows children's life trajectories and outcomes are strongly influenced by factors affecting development of social and academic competence that also interact with racial disparities in academic settings. Given the importance of social and academic competencies, identifying factors that promote these competencies among African American children is critical to their success over the life course.

Objective: This study examines a socioeconomically diverse sample of African American children to determine whether family-level factors promote and protect social and academic competence.

Maternal socialization of child emotion and adolescent adjustment: Indirect effects through emotion regulation.

A fundamental question in developmental science is how parental emotion socialization processes are associated with children's subsequent adaptation. Few extant studies have examined this question across multiple developmental periods and levels of analysis. Here, we tested whether mothers' supportive and nonsupportive reactions to their 5-year-old children's negative emotions were associated with teacher and adolescent self-reported adjustment at age 15 via children's physiological and behavioral emotion regulation at age 10 (N = 404).

Developmental patterns of respiratory sinus arrhythmia from toddlerhood to adolescence.

Parasympathetic nervous system functioning as indexed by respiratory sinus arrhythmia (RSA) is widely used as a measure of physiological regulation. We examined developmental patterns of children's resting RSA and RSA reactivity from 2 to 15 years of age, a period of time that is marked by considerable advances in children's regulatory abilities. Physiological data were collected from a community sample of 270 children (116 males) during a resting period and during a frustration laboratory task when the children were 2, 4, 5, 7, 10, and 15 years old.