Western Blot Characterization of Human Serum Prestin, an Outer Hair Cell Biomarker.

Hypothesis: Western blot analysis of human prestin in the blood reveals multiple bands, rather than a single band.

Background: Previously, using the ELISA method, prestin was shown to be a good biomarker of outer hair cell (OHC) health and sensorineural hearing loss that could be measured in the blood. Recently, we found that a Western blot approach in an experimental model demonstrated three prestin bands providing greater insights into prestin in the blood and its origins.

A panel-based mutational signature of homologous recombination deficiency associates with response to PARP inhibition in metastatic castration-resistant prostate cancer.

Background: The PARP inhibitor (PARPi) olaparib is approved for homologous recombination repair (HRR) gene-altered metastatic castration-resistant prostate cancer (mCRPC). However, there is significant heterogeneity in response to PARPi in patients with mCRPC. Better clinical biomarkers are needed to identify patients likely to benefit from PARPi.

Detecting Small Cell Transformation in Patients with Advanced EGFR Mutant Lung Adenocarcinoma through Epigenomic cfDNA Profiling.

Purpose: Histologic transformation to small cell lung cancer (SCLC) is a mechanism of treatment resistance in patients with advanced oncogene-driven lung adenocarcinoma (LUAD) that currently requires histologic review for diagnosis. Herein, we sought to develop an epigenomic cell-free DNA (cfDNA)-based approach to noninvasively detect small cell transformation in patients with EGFR mutant (EGFRm) LUAD.

Experimental Design: To characterize the epigenomic landscape of transformed (t)SCLC relative to LUAD and de novo SCLC, we performed chromatin immunoprecipitation sequencing (ChIP-seq) to profile the histone modifications H3K27ac, H3K4me3, and H3K27me3; methylated DNA immunoprecipitation sequencing (MeDIP-seq); assay for transposase-accessible chromatin sequencing; and RNA sequencing on 26 lung cancer patient-derived xenograft (PDX) tumors.

A Panel-Based Mutational Signature of Mismatch Repair Deficiency is Associated With Durable Response to Pembrolizumab in Metastatic Castration-Resistant Prostate Cancer.

Introduction/background: Immune checkpoint inhibitors (ICIs) have limited efficacy in prostate cancer (PCa). Better biomarkers are needed to predict responses to ICIs. We sought to demonstrate that a panel-based mutational signature identifies mismatch repair (MMR) deficient (MMRd) PCa and is a biomarker of response to pembrolizumab.

Co-occurring BRCA2/SPOP Mutations Predict Exceptional Poly (ADP-ribose) Polymerase Inhibitor Sensitivity in Metastatic Castration-Resistant Prostate Cancer.

Background And Objective: BRCA2 mutations in metastatic castration-resistant prostate cancer (mCRPC) confer sensitivity to poly (ADP-ribose) polymerase (PARP) inhibitors. However, additional factors predicting PARP inhibitor efficacy in mCRPC are needed. Preclinical studies support a relationship between speckle-type POZ protein (SPOP) inactivation and PARP inhibitor sensitivity.

Nucleosome Patterns in Circulating Tumor DNA Reveal Transcriptional Regulation of Advanced Prostate Cancer Phenotypes.

Unlabelled: Advanced prostate cancers comprise distinct phenotypes, but tumor classification remains clinically challenging. Here, we harnessed circulating tumor DNA (ctDNA) to study tumor phenotypes by ascertaining nucleosome positioning patterns associated with transcription regulation. We sequenced plasma ctDNA whole genomes from patient-derived xenografts representing a spectrum of androgen receptor active (ARPC) and neuroendocrine (NEPC) prostate cancers.

Differential responses to taxanes and PARP inhibitors in ATM- versus BRCA2-mutated metastatic castrate-resistant prostate cancer.

Background: PARP (poly(ADP-ribose) polymerase) inhibitors (PARPi) are now standard of care in metastatic castrate-resistant prostate cancer (mCRPC) patients with select mutations in DNA damage repair (DDR) pathways, but patients with ATM- and BRCA2 mutations may respond differently to PARPi. We hypothesized that differences may also exist in response to taxanes, which may inform treatment sequencing decisions.

Methods: mCRPC patients (N = 158) with deleterious ATM or BRCA2 mutations who received taxanes, PARPi, or both were retrospectively identified from 11 US academic centers.

Addition of Germline Testing to Tumor-Only Sequencing Improves Detection of Pathogenic Germline Variants in Men With Advanced Prostate Cancer.

Purpose: Guidelines recommend somatic and germline testing for men with advanced prostate cancer (PCa). Barriers to widespread implementation result in underutilization of germline testing. Somatic testing alone risks missing pathogenic germline variants (PGVs).

The Prostate Cancer Androgen Receptor Cistrome in African American Men Associates with Upregulation of Lipid Metabolism and Immune Response.

Unlabelled: African-American (AA) men are more likely to be diagnosed with and die from prostate cancer than European American (EA) men. Despite the central role of the androgen receptor (AR) transcription factor in prostate cancer, little is known about the contribution of epigenetics to observed racial disparities. We performed AR chromatin immunoprecipitation sequencing on primary prostate tumors from AA and EA men, finding that sites with greater AR binding intensity in AA relative to EA prostate cancer are enriched for lipid metabolism and immune response genes.

Detecting Neuroendocrine Prostate Cancer Through Tissue-Informed Cell-Free DNA Methylation Analysis.

Purpose: Neuroendocrine prostate cancer (NEPC) is a resistance phenotype that emerges in men with metastatic castration-resistant prostate adenocarcinoma (CR-PRAD) and has important clinical implications, but is challenging to detect in practice. Herein, we report a novel tissue-informed epigenetic approach to noninvasively detect NEPC.

Experimental Design: We first performed methylated immunoprecipitation and high-throughput sequencing (MeDIP-seq) on a training set of tumors, identified differentially methylated regions between NEPC and CR-PRAD, and built a model to predict the presence of NEPC (termed NEPC Risk Score).

Suppression of Kv3.3 channels by antisense oligonucleotides reverses biochemical effects and motor impairment in spinocerebellar ataxia type 13 mice.

Mutations in KCNC3, the gene that encodes the Kv3.3 voltage dependent potassium channel, cause Spinocerebellar Ataxia type 13 (SCA13), a disease associated with disrupted motor behaviors, progressive cerebellar degeneration, and abnormal auditory processing. The Kv3.

Promoting Strong Latino Families Within an Emerging Immigration Context: Results of a Replication and Extension Trial of a Culturally Adapted Preventive Intervention.

We conducted a randomized controlled trial (RCT) of Nuestras Familias: Andando Entre Culturas, a culturally adapted evidence-based parent management training (PMT) preventive intervention, with a sample of 241 Spanish-speaking Latino parents and their middle-school-aged children residing in an emerging immigration context. Scientifically rigorous studies of programs designed for this setting are rare. The intervention was designed to promote prosocial parenting practices and to prevent youth substance use and related problem behaviors.

Alcohol use severity, depressive symptoms, and optimism among Hispanics: Examining the immigrant paradox in a serial mediation model.

Objective: Hispanic immigrants exhibit more positive outcomes than U.S.-born Hispanics across educational, psychological, and physical health indices, a phenomenon called the immigrant paradox.

Impaired motor skill learning and altered seizure susceptibility in mice with loss or gain of function of the Kcnt1 gene encoding Slack (K1.1) Na-activated K channels.

Gain-of-function mutations in KCNT1, the gene encoding Slack (K1.1) channels, result in epilepsy of infancy with migrating focal seizures (EIMFS) and several other forms of epilepsy associated with severe intellectual disability. We have generated a mouse model of this condition by replacing the wild type gene with one encoding Kcnt1, a cytoplasmic C-terminal mutation homologous to a human R474H variant that results in EIMFS.

The Effects of Cooperative Learning on Peer Relations, Academic Support, and Engagement in Learning Among Students of Color.

Despite , prejudice still exists in the American school system. These attitudes can give rise to negative social experiences for students of color (i.e.

Latinx Immigrant Farmworker Community Health Promotion: A Needs Assessment.

The present study examined the health promotion intervention needs of Latinx immigrant farmworker families residing in Oregon. Grounded theory qualitative procedures were used to analyze the needs assessment data from 31 Latinx immigrant farmworker residents and key informant interviews as well as four focus groups with resident youth and parents. A theoretical model of how key family-based health behaviors can both confer risk for and protection against negative physical, mental, and social health outcomes among Latinx farmworking communities emerged.

Climbing the ladder of decline: Income and acculturation associated with chronic inflammation among Mexican immigrants.

Objectives: Financial hardship and immigrant status are often associated with poorer health as immigrant groups acculturate to life in the US. Known as the Latino health paradox, studies have shown that Latino/a immigrants in particular often experience declines in health the more they embrace ways of life considered "dominant" by US society. At present, critical biological pathways linking socioeconomic and acculturative processes remain to be better explained.

Mind the Gap: Bridging the Divide Between Current Binge Drinking Prevention and the Needs of Hispanic Underage Emerging Adults.

In this article, we highlight the urgent public health need for prevention of heavy episodic drinking among underage Hispanic emerging adults in the USA. We outline the current state of binge drinking prevention programming and contrast it with the unique cultural, social, and developmental realities of this population using an ecodevelopmental framework (Szapocznik and Coatsworth 1999). Finally, we advance specific recommendations for the development and delivery of culturally tailored, multisystemic binge drinking prevention programs for underage Hispanic emerging adults.

Longitudinal effects of acculturation and enculturation on mental health: Does the measure matter?

A great deal of research has focused on acculturation and enculturation, which represent the processes of adapting to a new culture. Despite this growing literature, results have produced inconsistent findings that may be attributable to differences in terms of the instruments used to assess acculturation and enculturation. Utilizing a 3-year longitudinal data set (with 1-year lags between assessments), the present study explored the psychometric properties of the Bicultural Involvement Questionnaire-Short Version (BIQ-S) and the Acculturation Rating Scale for Mexican Americans II (ARSMA-II) and examined the overlap between changes in these measures as they relate to internalizing and externalizing problem behavior.

Food insecurity partially mediates associations between social disadvantage and body composition among older adults in india: Results from the study on global AGEing and adult health (SAGE).

Objective: Our objective was to test whether food insecurity mediates cross-sectional associations between social disadvantage and body composition among older adults (aged 50+) in India (n = 6556).

Methods: Adjusting for key sociodemographic and dietary variables, we examined whether markers of social disadvantage (lower educational attainment, lower household wealth, belonging to a disadvantaged caste/tribe, and belonging to a minority religion) were associated with food insecurity. We then examined whether food insecurity, in turn, was associated with anthropometric measures of body composition, body mass index (BMI), and waist circumference (WC).

A tale of two measures: Concordance between the ARSMA-II and the BIQ acculturation scales among Latino immigrant families.

Acculturation refers to the extent to which an individual immigrant (or immigrant group) acquires the customs and characteristics of a new receiving society and/or retains the customs and characteristics of the person's or group's cultural heritage. Different acculturation measures are often assumed to be interchangeable, although this assumption is rarely tested empirically. The purpose of the present study was to examine the overlap between 2 commonly used measures of acculturation among individuals of Latino/Hispanic ancestry in the United States, the Acculturation Rating Scale for Mexican Americans II (ARSMA-II) and the Bicultural Involvement Questionnaire-Short Version (BIQ-S).