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.

Screening and treatment of anxiety symptoms within an interdisciplinary comprehensive epilepsy center.

Youth with epilepsy (YWE) are at elevated risk for anxiety, yet anxiety is often undetected and understudied in this population. Most research on anxiety in YWE is based on parent proxy-report and broad-band measures with limited sensitivity. The aim of the current study was to: 1) examine rates of anxiety symptoms in YWE using a diagnosis-specific, self-report measure of anxiety symptoms, 2) assess differences in anxiety symptoms by sociodemographic and medical variables, and 3) evaluate changes in anxiety symptoms following a brief behavioral health intervention delivered within an interdisciplinary epilepsy clinic visit.

Six elements test vs D-KEFS: what does "Ecological Validity" tell us?

Objective: Extensive research shows that tests of executive functioning (EF) predict instrumental activities of daily living (IADLs) but are nevertheless often criticized for having poor ecological validity. The Modified Six Elements Test (MSET) is a pencil-and-paper test that was developed to mimic the demands of daily life, with the assumption that this would result in a more ecologically valid test. Although the MSET has been extensively validated in its ability to capture cognitive deficits in various populations, support for its ability to predict functioning in daily life is mixed.

Pregnancy- and parenting-related barriers to receiving medication for opioid use disorder: A multi-paneled qualitative study of women in treatment, women who terminated treatment, and the professionals who serve them.

Background: Women face unique barriers when seeking treatment for substance use disorders, often related to pregnancy and parenting.

Objectives: This study adds to the extant literature by elucidating the pregnancy- and parenting-related barriers women face when initiating or continuing medication for opioid use disorder, specifically.

Design: This study is based on qualitative semi-structured interviews.

Conceptualization of the term "ecological validity" in neuropsychological research on executive function assessment: a systematic review and call to action.

Objective: "Ecological validity" (EV) is classically defined as test's ability to predict real-world functioning, either alone or together with test's similarity to real-world tasks. In neuropsychological literature on assessment of executive functions (EF), EV is conceptualized inconsistently, leading to misconceptions about the utility of tests. The goal of this systematic review was to examine how EV is conceptualized in studies of EF tests described as ecologically valid.

Test of Practical Judgment (TOP-J): Construct, Criterion, and Incremental Validity in a Community Sample of Older Adults.

Objective: The Test of Practical Judgment (TOP-J) is a stand-alone judgment measure that is considered to tap into aspects of executive functioning (EF) and inform clinical predictions of daily functioning in older adults. Past validation research is variable and has some limitations. The present study sought to examine the reliability and construct, criterion, and incremental validities of scores on TOP-J 9-item version (TOP-J/9).

Key predictors of epilepsy-specific health-related quality of life (HRQOL) in youth with epilepsy.

Purpose: Epilepsy-specific health-related quality of life (HRQOL) is an important outcome in youth with epilepsy (YWE). The PedsQL™ Epilepsy Module is the only caregiver-proxy and youth self-report epilepsy-specific HRQOL measure that can be used with youth 2-25 years. Multiple factors affect HRQOL, including epilepsy-specific characteristics, comorbid mental and behavioral health concerns, as well as sociodemographic factors.

Rethinking urban-rural designations in public health surveillance of the overdose crisis and crafting an agenda for future monitoring.

Rurality has served as a key concept in popular and scientific understandings of the US overdose crisis, with White, rural, and low-income areas thought to be most heavily affected. However, we observe that overdose trends have risen nearly uniformly across the urban-rural designations employed in most research, implying that their importance has likely been overstated or incorrectly conceptualized. Nevertheless, urbanicity/rurality does serve as a key axis to understand inequalities in overdose mortality when assessed with more nuanced modalities-employing a more granular analysis of geography at the sub-county level, and intersecting rurality sociodemographic indices such as race/ethnicity.

It's complicated: Executive functioning moderates impacts of daily busyness on everyday functioning in community-dwelling older adults.

Objective: Research shows that cognitively healthy older adults with mild executive function (EF) weaknesses are vulnerable to the negative impacts of life complexity (or daily busyness) when performing instrumental activities of daily living (IADLs). However, past research assessed life complexity only at one timepoint, not capturing daily fluctuations. Importantly, fluctuations in busyness can themselves have deleterious impacts on functioning.

Patient experiences of methadone treatment changes during the first wave of COVID-19: a national community-driven survey.

Background: During COVID-19, the Substance Abuse and Mental Health Services Administration (SAMHSA) allowed Methadone Maintenance Treatment (MMT) programs to relax in-person MMT requirements to reduce COVID-19 exposure. This study examines patient-reported changes to in-person methadone clinic attendance requirements during COVID-19.

Methods: From June 7, 2020, to July 15, 2020, a convenience sample of methadone patients (N = 392) were recruited in collaboration with National Survivors Union (NSU) in 43 states and Washington D.

Self-Disclosure Patterns Among Children and Youth with Epilepsy: Impact of Perceived-Stigma.

This review aimed to synthesize the minimal existing literature on the impact of perceived stigma on self-disclosure patterns among children and youth with epilepsy (YWE). Initial literature searches were conducted in PsycInfo, Scopus, Web of Science, and PubMed using search terms focused on epilepsy, pediatrics, disclosure, and/or stigma. Articles were included if they were original human research articles published in peer-reviewed journals that were accessible in English through Cincinnati Children's Hospital Medical Center Pratt Library and fit study aims.

STAT3 gain-of-function mutations connect leukemia with autoimmune disease by pathological NKG2D CD8 T cell dysregulation and accumulation.

The association between cancer and autoimmune disease is unexplained, exemplified by T cell large granular lymphocytic leukemia (T-LGL) where gain-of-function (GOF) somatic STAT3 mutations correlate with co-existing autoimmunity. To investigate whether these mutations are the cause or consequence of CD8 T cell clonal expansions and autoimmunity, we analyzed patients and mice with germline STAT3 GOF mutations. STAT3 GOF mutations drove the accumulation of effector CD8 T cell clones highly expressing NKG2D, the receptor for stress-induced MHC-class-I-related molecules.

Activating transcription factor 4 regulates hypoxia inducible factor 1α in chronic hypoxia in pancreatic cancer cells.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and difficult to treat cancers with tumors typically exhibiting high levels of chronic hypoxia. Hypoxia activates hypoxia-inducible factors (HIFs) that mediate cellular responses to adapt to low oxygen environments. Hypoxia also causes endoplasmic reticulum (ER) stress, increasing activating transcription factor 4 (ATF4), a master regulator of the unfolded protein response (UPR) pathway that mediates cellular response to ER stress.

Monogenic early-onset lymphoproliferation and autoimmunity: Natural history of STAT3 gain-of-function syndrome.

Background: In 2014, germline signal transducer and activator of transcription (STAT) 3 gain-of-function (GOF) mutations were first described to cause a novel multisystem disease of early-onset lymphoproliferation and autoimmunity.

Objective: This pivotal cohort study defines the scope, natural history, treatment, and overall survival of a large global cohort of patients with pathogenic STAT3 GOF variants.

Methods: We identified 191 patients from 33 countries with 72 unique mutations.

Reappraising cognitive reappraisal: The taxing impact of emotion regulation on executive functioning in older adults.

Objective: Cognitive reappraisal (CR) and expressive suppression (ES) are two common emotion regulation strategies that share similar cognitive and neural underpinnings. Prior research has consistently shown that recent engagement in ES (both self-reported and experimentally manipulated) is associated with subsequent temporary decrements in executive functioning (EF). Thus far, only one study has examined the association between CR and EF, with null results.

Functional Drug Screening of Small Molecule Inhibitors of Epigenetic Modifiers in Refractory AML Patients.

The use of inhibitors of epigenetic modifiers in the treatment of acute myeloid leukemia (AML) has become increasingly appealing due to the highly epigenetic nature of the disease. We evaluated a library of 164 epigenetic compounds in a cohort of 9 heterogeneous AML patients using an ex vivo drug screen. AML blasts were isolated from bone marrow biopsies according to established protocols and treatment response to the epigenetic library was evaluated.

Behavioral health screening in pediatric epilepsy: Which measures commonly used in the United States are 'good enough'?

Purpose: To improve evidence-based implementation of behavioral health screening measures in pediatric epilepsy care, guidance is needed in the selection and interpretation of evidence-based screening measures. Therefore, the goals of this project were to (1) evaluate the clinical utility and psychometric properties of screening instruments frequently used in the United States (US) for anxiety, depression, and behavior problems in youth with epilepsy (YWE), and (2) provide guidance around selection and interpretation of these behavioral health screening measures.

Method: The critique was conducted in three phases: (1) identification of articles based on search criteria; (2) full review of articles for eligibility assessment; (3) evaluation of screening measures and organization into Tiers.

Safety and pharmacokinetics of a highly bioavailable resveratrol preparation (JOTROL ).

Unlabelled: Resveratrol exhibits a wide range of biological properties, including anti-glycation, antioxidant, anti-inflammation, neuroprotective (including against advanced dementia and Alzheimer's disease), anti-cancer, and anti-aging activity in experimental models (Galiniak et al., Acta Biochim Pol 66:13-21, 2019). Unfortunately, this compound exhibits low bioavailability and solubility (Galiniak et al.

Perceptions Towards HCV Treatment with Direct Acting Antivirals (DAAs): A Qualitative Analysis with Persons with HIV/HCV Co-infection Who Delay or Refuse Treatment.

In the United States, approximately 25% of people with HIV (PWH) are co-infected with hepatitis C (HCV). Since 2014, highly effective and well-tolerated direct-acting antivirals (DAAs) have revolutionized HCV treatment. Uptake of DAAs by people with HIV/HCV co-infection has improved but remains suboptimal due to system, provider, and patient-level barriers.

Introducing Newborn Screening for Severe Combined Immunodeficiency-The New Zealand Experience.

Screening for severe combined immunodeficiency (SCID) was added to the New Zealand national newborn screening programme in December 2017. Documentation pertaining to the application to add SCID to the panel and screening results over the first three years were reviewed. Screening evaluation metrics were shown to differ according to site of collection (babies in a neonatal intensive care unit vs.

Reliability and validity of composite scores from the timed subtests of the D-KEFS battery.

Many neuropsychological tests of executive functioning (EF) have test-retest reliabilities below what is considered acceptable. Combining several tests into a composite can improve reliability, although due to concerns about the multifaceted nature of the EF construct, this practice is rarely applied. The present study (a) examined internal consistencies and test-retest reliabilities of two composites of four EF tests ( from timed scores and from error scores), and (b) preliminarily examined the criterion validity of the composites as a first step toward construct validation.