Faculty Bibliography

BACKGROUND:At the start of the COVID-19 pandemic, HIV experts suggested that an increase in mental health diagnoses and substance use among people living with HIV (PLHIV) may be an unintended consequence of COVID-19 mitigation efforts (e.g., limiting social contact). We evaluated short-term trajectories in binge drinking, marijuana, and recreational drug use in a prospective cohort of PLHIV. METHODS:Data (N = 2121 PLHIV) consist of survey responses on substance use behaviors from two pre-COVID-19 (October 2018-September 2019) and one COVID-19-era (April 2020-September 2020) timepoints within the MACS/WIHS Combined Cohort Study (MWCCS). We conducted group-based trajectory models, triangulated with generalized linear mixed models, to assess changes in binge drinking, daily marijuana use, and recreational drug use at the start of the pandemic. Controlling for age and race/ethnicity, we tested whether trajectories differed by sex and early-pandemic depressive symptoms, loneliness, and social support. RESULTS:Group-based trajectory models yielded two trajectory groups for binge drinking (none vs. any), marijuana (none/infrequent vs. daily), and recreational drug use (none vs. any). Binge drinking and recreational drug use decreased at the beginning of the pandemic. Generalized linear mixed model supported these trends. Consistent with prior research, male sex and having depressive symptoms early pandemic were positively associated with each substance use outcomes. Social support was inversely associated with recreational drug use. CONCLUSIONS:Contrary to hypotheses, problematic substance use behaviors decreased from pre-pandemic to the post-pandemic follow-up in our sample of PLHIV. Ongoing surveillance is needed to assess whether this pattern persists as the pandemic continues.

BACKGROUND:Oral squamous cell carcinoma (OSCC) has poor survival rates. There is a pressing need to develop more precise risk assessment methods to tailor clinical treatment. Epigenome-wide association studies in OSCC have not produced a viable biomarker. These studies have relied on methylation array platforms, which are limited in their ability to profile the methylome. In this study, we use MethylCap-Seq (MC-Seq), a comprehensive methylation quantification technique, and brush swab samples, to develop a noninvasive, readily translatable approach to profile the methylome in OSCC patients. METHODS:Three OSCC patients underwent collection of cancer and contralateral normal tissue and brush swab biopsies, totaling 4 samples for each patient. Epigenome-wide DNA methylation quantification was performed using the SureSelectXT Methyl-Seq platform. DNA quality and methylation site resolution were compared between brush swab and tissue samples. Correlation and methylation value difference were determined for brush swabs vs. tissues for each respective patient and site (i.e., cancer or normal). Correlations were calculated between cancer and normal tissues and brush swab samples for each patient to determine the robustness of DNA methylation marks using brush swabs in clinical biomarker studies. RESULTS:There were no significant differences in DNA yield between tissue and brush swab samples. Mapping efficiency exceeded 90% across all samples, with no differences between tissue and brush swabs. The average number of CpG sites with at least 10x depth of coverage was 2,716,674 for brush swabs and 2,903,261 for tissues. Matched tissue and brush swabs had excellent correlation (r = 0.913 for cancer samples and r = 0.951 for normal samples). The methylation profile of the top 1000 CpGs was significantly different between cancer and normal samples (mean p-value = 0.00021) but not different between tissues and brush swabs (mean p-value = 0.11). CONCLUSIONS:Our results demonstrate that MC-Seq is an efficient platform for epigenome profiling in cancer biomarker studies, with broader methylome coverage than array-based platforms. Brush swab biopsy provides adequate DNA yield for MC-Seq, and taken together, our findings set the stage for development of a non-invasive methylome quantification technique for oral cancer with high translational potential.

OBJECTIVES:This study describes prevention behavior and psychosocial health among people living with HIV (PLHIV) and HIV-negative people during the early wave of the coronavirus disease 2019 (COVID-19) pandemic in the United States. We assessed differences by HIV status and associations between social disruption and psychosocial health. DESIGN:A cross-sectional telephone/videoconference administered survey of 3411 PLHIV and HIV-negative participants in the Multicenter AIDS Cohort Study/WIHS Combined Cohort Study (MWCCS). METHODS:An instrument combining new and validated measures was developed to assess COVID-19 prevention efforts, social disruptions (loss of employment, childcare, health insurance, and financial supports), experiences of abuse, and psychosocial health. Interviews were performed between April and June 2020. Associations between social disruptions and psychosocial health were explored using multivariable logistic regression, adjusting for sociodemographics and HIV status. RESULTS:Almost all (97.4%) participants reported COVID-19 prevention behavior; 40.1% participants reported social disruptions, and 34.3% reported health care appointment disruption. Men living with HIV were more likely than HIV-negative men to experience social disruptions (40.6% vs. 32.9%; P < 0.01), whereas HIV-negative women were more likely than women with HIV to experience social disruptions (51.1% vs. 39.8%, P < 0.001). Participants who experienced ≥2 social disruptions had significantly higher odds of depression symptoms [aOR = 1.32; 95% confidence interval (CI): 1.12 to 1.56], anxiety (aOR = 1.63; 95% CI: 1.17 to 2.27), and social support dissatisfaction (aOR = 1.81; 95% CI: 1.26 to 2.60). CONCLUSIONS:This study builds on emerging literature demonstrating the psychosocial health impact related to the COVID-19 pandemic by providing context specific to PLHIV. The ongoing pandemic requires structural and social interventions to decrease social disruption and address psychosocial health needs among the most vulnerable populations.

OBJECTIVES/OBJECTIVE:Research has shown inconsistent patterns of patients' HIV serostatus disclosure to their dentists. Common barriers to disclosure have included confidentiality concerns, fear of treatment refusal, and discrimination. This study evaluated the prevalence of HIV serostatus disclosure to the dentist, whether the frequency of dental care utilization is associated with disclosure, and reasons for nondisclosure among women living with HIV. METHODS:We administered a cross-sectional oral health survey to 1,526 women living with HIV in the Women's Interagency HIV Study including questions regarding HIV serostatus disclosure to dentists. Logistic regression models were used to analyze the association between dental care utilization (at least annually versus less than annually) and HIV serostatus disclosure to dentists. RESULTS:Overall, 83 percent of women reported that they disclosed their HIV serostatus to their dentist. The most common reasons for nondisclosure were: a) the dentist did not ask, b) believing that the dentist did not need to know, and c) not having a consistent dentist. In the multivariable logistic regression model, at least annual dental care utilization, compared to less than annual, led to a 59 percent reduction in the odds of HIV nondisclosure to the dentist. DISCUSSION/CONCLUSIONS:Study findings highlight that dentists who see their patients infrequently should consider methods for overcoming barriers to HIV nondisclosure and the possibility that their patient's HIV serostatus is undisclosed. Educating women living with HIV about how disclosure to dentists is a critical component of their dental assessment and treatment, and how preventive dental treatment can improve overall health outcomes, is important.

INTRODUCTION/BACKGROUND:MicroRNAs (miRs) may be important regulators of risk for type 2 diabetes (T2D). Circulating miRs may provide information about which individuals are at risk for T2D. The purpose of this study was to assess longitudinal associations between circulating miR expression and variability in fasting blood glucose (FBG) and to identify miR-targeted genes and biological pathways. METHODS:= 20) in a previously completed yoga trial. Expression of 402 miRs was measured using hydrogel particle lithography. MirTarBase was used to identify mRNAs, and miRPathDB was used to identify pathways targeted by differentially expressed miRs. RESULTS:) were targeted by at least two miRs and four of those were located in miR-targeted KEGG pathways. CONCLUSIONS:Circulating miRs are associated with variability in FBG in individuals at risk for T2D. Further studies are needed to determine whether miRs may be prodromal biomarkers that can identify which individuals are at greatest risk to progress to T2D and which biological pathways underlie this risk.

BACKGROUND:Globally, type 2 diabetes is highly prevalent in individuals of Latino ancestry. The reasons underlying this high prevalence are not well understood, but both genetic and lifestyle factors are contributors. Circulating microRNAs are readily detectable in blood and are promising biomarkers to characterize biological responses (i.e., changes in gene expression) to lifestyle factors. Prior studies identified relationships between circulating microRNAs and risk for type 2 diabetes, but Latinos have largely been under-represented in these study samples. AIMS/HYPOTHESIS/OBJECTIVE:The aim of this study was to assess for differences in expression levels of three candidate microRNAs (miR-126, miR-146, miR-15) between individuals who had prediabetes compared to normal glycemic status and between individuals who self-identified with Latino ancestry in the United States (US) and native Mexicans living in or near Leon, Mexico. METHODS:This was a cross-sectional study that included 45 Mexicans and 21 Latino participants from the US. Prediabetes was defined as fasting glucose 100-125 mg/dL or 2-h post-glucose challenge between 140 and 199 mg/dL. Expression levels of microRNAs from plasma were measured by qPCR. Linear and logistic regression models were used to assess relationships between individual microRNAs and glycemic status or geographic site. RESULTS:None of the three microRNAs was associated with risk for type 2 diabetes. MiR-146a and miR-15 were significantly lower in the study sample from Mexico compared to the US. There was a significant interaction between miR-146a and BMI associated with fasting blood glucose. CONCLUSIONS/INTERPRETATION/CONCLUSIONS:This study did not replicate in Latinos prior observations from other racial groups of associations between miR-126, miR-146a, and miR-15 and risk for type 2 diabetes. Future studies should consider other microRNAs related to different biological pathways as possible biomarkers for type 2 diabetes in Latinos.

BACKGROUND:MicroRNAs may be important regulators of risk for type 2 diabetes. The purpose of this longitudinal observational study was to assess whether circulating microRNAs predicted improvements in fasting blood glucose, a major risk factor for type 2 diabetes, over 12 months. METHODS:The study included participants (n = 82) from a previously completed trial that tested the effect of restorative yoga on individuals with prediabetes. Circulating microRNAs were measured using a flow cytometry miRNA assay. Linear models were used to determine the optimal sets of microRNA predictors overall and by intervention group. RESULTS: = 0.731, p < 0.001). Three microRNAs (let-7c, miR-363, miR-374b) were significant for the control group only, however there was no significant interaction by intervention group. CONCLUSIONS:Circulating microRNAs are significant predictors of fasting blood glucose in individuals with prediabetes. Among the identified microRNAs, several have previously been associated with risk for type 2 diabetes. This is one of the first studies to use a longitudinal design to assess whether microRNAs predict changes in fasting blood glucose over time. Further exploration of the function of the microRNAs included in these models may provide new insights about the complex etiology of type 2 diabetes and responses to behavioral risk reduction interventions. TRIAL REGISTRATION/BACKGROUND:This study was a secondary analysis of a previously completed clinical trial that is registered at clinicaltrials.gov (NCT01024816) on December 3, 2009.

OBJECTIVE:Fear of cancer recurrence (FCR) is the greatest unmet psychosocial need among breast cancer survivors (BCS). The Oncotype Dx® test predicts the 10-year risk of distant recurrence and benefit of adjuvant chemotherapy among women with early stage hormone receptor-positive breast cancer. Despite the test's clinical utility, psychosocial responses are poorly understood. METHODS:A descriptive cross-sectional study was conducted to explore associations between Oncotype Dx® test results (Recurrence Score) and FCR, health-related quality of life (HRQOL), distress, anxiety, depression, illness representation and perceived risk. Bivariate analyses were used to examine the associations between variables followed by multiple linear regression to examine predictors of FCR. RESULTS: CONCLUSION/CONCLUSIONS:BCS's with higher risk of recurrence may experience higher FCR. However, for FCR, modifiable factors such as anxiety and illness representation (greater emotional response and perceived consequences of illness) may be more important than non-modifiable factors such as Oncotype Dx® test results and age. Further research is needed to develop personalized interventions to improve BCS's outcomes. This article is protected by copyright. All rights reserved.

BACKGROUND:Oral squamous cell carcinoma (OSCC) is a capricious cancer with poor survival rates, even for early-stage patients. There is a pressing need to develop more precise risk assessment methods to appropriately tailor clinical treatment. Genome-wide association studies have not produced a viable biomarker. However, these studies are limited by using heterogeneous cohorts, not focusing on methylation although OSCC is a heavily epigenetically-regulated cancer, and not combining molecular data with clinicopathologic data for risk prediction. In this study we focused on early-stage (I/II) OSCC and created a risk score called the REASON score, which combines clinicopathologic characteristics with a 12-gene methylation signature, to predict the risk of 5-year mortality. METHODS:We combined data from an internal cohort (n = 515) and The Cancer Genome Atlas (TCGA) cohort (n = 58). We collected clinicopathologic data from both cohorts to derive the non-molecular portion of the REASON score. We then analyzed the TCGA cohort DNA methylation data to derive the molecular portion of the risk score. RESULTS:5-year disease specific survival was 63% for the internal cohort and 86% for the TCGA cohort. The clinicopathologic features with the highest predictive ability among the two the cohorts were age, race, sex, tobacco use, alcohol use, histologic grade, stage, perineural invasion (PNI), lymphovascular invasion (LVI), and margin status. This panel of 10 non-molecular features predicted 5-year mortality risk with a concordance (c)-index = 0.67. Our molecular panel consisted of a 12-gene methylation signature (i.e., HORMAD2, MYLK, GPR133, SOX8, TRPA1, ABCA2, HGFAC, MCPH1, WDR86, CACNA1H, RNF216, CCNJL), which had the most significant differential methylation between patients who survived vs. died by 5 years. All 12 genes have already been linked to survival in other cancers. Of the genes, only SOX8 was previously associated with OSCC; our study was the first to link the remaining 11 genes to OSCC survival. The combined molecular and non-molecular panel formed the REASON score, which predicted risk of death with a c-index = 0.915. CONCLUSIONS:The REASON score is a promising biomarker to predict risk of mortality in early-stage OSCC patients. Validation of the REASON score in a larger independent cohort is warranted.

Purpose of the Study/UNASSIGNED:More than 50% of breast cancer survivors without a diagnosis of lymphedema suffer daily from numerous and co-occurring lymphedema symptoms. This study aimed to identify lymphedema symptom patterns and the association of such patterns with phenotypic characteristics and biomarkers using latent class analysis (LCA). A prospective, descriptive, and repeated-measure design was used to enroll 140 women and collect data. Recent Findings/UNASSIGNED:LCA identified three distinct lymphedema symptom classes at 8 weeks and 12 months post-surgery: low, moderate, and severe symptom classes and associated phenotypic characteristics. Participants were more likely to be in the severe symptom classes at 12 months post-surgery if they had lower education level, cording, an axillary syndrome at 8 weeks post-surgery, neoadjuvant chemotherapy, and radiation. Summary/UNASSIGNED:Pre-surgery level of IL1-a, IL-6, IL-8, and VEGF was associated with the severe symptom class at 8 weeks post-surgery, suggesting that such biomarkers may be used to predict risk for lymphedema symptoms.