Differences in Serum miRNA Profiles by Race, Ethnicity, and Socioeconomic Status: Implications for Developing an Equitable Ovarian Cancer Screening Test.

Serum miRNAs are promising biomarkers for several clinical conditions, including ovarian cancer. To inform equitable implementation of these tests, we investigated the effects of race, ethnicity, and socioeconomic status on serum miRNA profiles. Serum samples from a large institutional biobank were analyzed using a custom panel of 179 miRNA species highly expressed in human serum, measured using the Abcam Fireplex assay via flow cytometry. Data were log-transformed prior to analysis. Differences in miRNA by race and ethnicity were assessed using logistic regression. Pairwise t tests analyzed racial and ethnic differences among eight miRNAs previously associated with ovarian cancer risk. Pearson correlations determined the relationship between mean miRNA expression and the social deprivation index (SDI) for Massachusetts residents. Of 1,586 patients (76.9% white, non-Hispanic), compared with white, non-Hispanic patients, those from other racial and ethnic groups were younger (41.9 years ± 13.2 vs. 51.3 ± 15.1, P < 0.01) and had fewer comorbidities (3.5 comorbidities ± 2.7 vs. 4.6 ± 2.8, P < 0.01). On logistic regression, miRNAs predicted race and ethnicity at an AUC of 0.69 (95% confidence interval, 0.66-0.72), which remained consistent when stratified by most comorbidities. Among eight miRNAs previously associated with ovarian cancer risk, seven significantly varied by race and ethnicity (all P < 0.01). There were no significant differences in SDI for any of these eight miRNAs. miRNA expression is significantly influenced by race and ethnicity, which remained consistent after controlling for confounders. Understanding baseline differences in biomarker test characteristics prior to clinical implementation is essential to ensure instruments perform comparably across diverse populations. PREVENTION RELEVANCE: This study aimed to understand factors affecting miRNA expression, to ensure we create equitable screening tests for ovarian cancer that perform well in diverse populations. The goal is to ensure that we are detecting ovarian cancer cases earlier (secondary prevention) in women of all races, ethnic backgrounds, and socioeconomic means.

Endo-lysosomal dysfunction in neurodegenerative diseases: opinion on current progress and future direction in the use of exosomes as biomarkers.

Over the past two decades, increased research has highlighted the connection between endosomal trafficking defects and neurodegeneration. The endo-lysosomal network is an important, complex cellular system specialized in the transport of proteins, lipids, and other metabolites, essential for cell homeostasis. Disruption of this pathway is linked to a wide range of neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease and frontotemporal dementia. Furthermore, there is strong evidence that defects in this pathway create opportunities for diagnostic and therapeutic intervention. In this Opinion piece, we concisely address the role of endo-lysosomal dysfunction in five neurodegenerative diseases and discuss how future research can investigate this intracellular pathway, including extracellular vesicles with a specific focus on exosomes for the identification of novel disease biomarkers. This article is part of a discussion meeting issue 'Understanding the endo-lysosomal network in neurodegeneration'.

The effects of social pressure and emotional expression on the cone of gaze in patients with social anxiety disorder.

BACKGROUND AND OBJECTIVES: Patients with social anxiety disorder suffer from pronounced fears in social situations. As gaze perception is crucial in these situations, we examined which factors influence the range of gaze directions where mutual gaze is experienced (the cone of gaze). METHODS: The social stimulus was modified by changing the number of people (heads) present and the emotional expression of their faces. Participants completed a psychophysical task, in which they had to adjust the eyes of a virtual head to gaze at the edge of the range where mutual eye-contact was experienced. RESULTS: The number of heads affected the width of the gaze cone: the more heads, the wider the gaze cone. The emotional expression of the virtual head had no consistent effect on the width of the gaze cone, it did however affect the emotional state of the participants. Angry expressions produced the highest arousal values. Highest valence emerged from happy faces, lowest valence from angry faces. CONCLUSION: These results suggest that the widening of the gaze cone in social anxiety disorder is not primarily mediated by their altered emotional reactivity. Implications for gaze assessment and gaze training in therapeutic contexts are discussed. LIMITATIONS: Due to interindividual variability, enlarged gaze cones are not necessarily indicative of social anxiety disorder, they merely constitute a correlate at the group level.

The widening of the gaze cone in patients with social anxiety disorder and its normalization after CBT.

Gaze plays a crucial role in social interactions. Social Anxiety Disorder (SAD), which is associated with severe impairment of social interactions, is thus likely to exhibit disturbances of gaze perception. We conducted two experiments with SAD-patients and healthy control participants using a virtual head whose gaze could be interactively manipulated. We determined the subjective area of mutual gaze, the so-called gaze cone, and measured it prior to and after a psychotherapeutic intervention (Exp. 1). Patients exhibited larger gaze cones than control subjects. Exp. 2 varied the emotional expression of the virtual head. These data were validated using a real person (professional actor) as stimulus. Excellent reliability indices were found for our gaze cone measure. After Cognitive Behavioral Therapy, group differences in gaze cone width had disappeared. Emotional expressions were observed to modulate the gaze cone's width. Especially an angry expression caused the gaze cone to widen, possibly mediated by increased arousal. Finally, wider gaze cones in SAD-patients could be demonstrated for virtual and for real human heads confirming the ecological validity of virtual heads. The findings are of relevance for a more fine-grained understanding of perceptual processes in patients with SAD.