Browsing by Author "Vielot, Nadja A"
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Item Open Access Epigenome-wide methylation and progression to high-grade cervical intraepithelial neoplasia (CIN2+): a prospective cohort study in the United States.(BMC cancer, 2023-11) Bukowski, Alexandra; Hoyo, Cathrine; Vielot, Nadja A; Graff, Misa; Kosorok, Michael R; Brewster, Wendy R; Maguire, Rachel L; Murphy, Susan K; Nedjai, Belinda; Ladoukakis, Efthymios; North, Kari E; Smith, Jennifer SBackground
Methylation levels may be associated with and serve as markers to predict risk of progression of precancerous cervical lesions. We conducted an epigenome-wide association study (EWAS) of CpG methylation and progression to high-grade cervical intraepithelial neoplasia (CIN2 +) following an abnormal screening test.Methods
A prospective US cohort of 289 colposcopy patients with normal or CIN1 enrollment histology was assessed. Baseline cervical sample DNA was analyzed using Illumina HumanMethylation 450K (n = 76) or EPIC 850K (n = 213) arrays. Participants returned at provider-recommended intervals and were followed up to 5 years via medical records. We assessed continuous CpG M values for 9 cervical cancer-associated genes and time-to-progression to CIN2+. We estimated CpG-specific time-to-event ratios (TTER) and hazard ratios using adjusted, interval-censored Weibull accelerated failure time models. We also conducted an exploratory EWAS to identify novel CpGs with false discovery rate (FDR) < 0.05.Results
At enrollment, median age was 29.2 years; 64.0% were high-risk HPV-positive, and 54.3% were non-white. During follow-up (median 24.4 months), 15 participants progressed to CIN2+. Greater methylation levels were associated with a shorter time-to-CIN2+ for CADM1 cg03505501 (TTER = 0.28; 95%CI 0.12, 0.63; FDR = 0.03) and RARB Cluster 1 (TTER = 0.46; 95% CI 0.29, 0.71; FDR = 0.01). There was evidence of similar trends for DAPK1 cg14286732, PAX1 cg07213060, and PAX1 Cluster 1. The EWAS detected 336 novel progression-associated CpGs, including those located in CpG islands associated with genes FGF22, TOX, COL18A1, GPM6A, XAB2, TIMP2, GSPT1, NR4A2, and APBB1IP.Conclusions
Using prospective time-to-event data, we detected associations between CADM1-, DAPK1-, PAX1-, and RARB-related CpGs and cervical disease progression, and we identified novel progression-associated CpGs.Impact
Methylation levels at novel CpG sites may help identify individuals with ≤CIN1 histology at higher risk of progression to CIN2+ and inform risk-based cervical cancer screening guidelines.Item Open Access Students with global experiences during medical school are more likely to work in settings that focus on the underserved: an observational study from a public U.S. institution.(BMC medical education, 2021-10) Slifko, Shay E; Vielot, Nadja A; Becker-Dreps, Sylvia; Pathman, Donald E; Myers, Justin G; Carlough, MarthaBackground
Global health interest has grown among medical students over the past 20 years, and most medical schools offer global health opportunities. Studies suggest that completing global health electives during medical school may increase the likelihood of working with underserved populations in a clinical or research capacity. This study aimed to assess the association of global electives in medical school on subsequently working in global health and with underserved populations in the United States (U.S.), additionally considering students' interests and experiences prior to medical school. We also examined whether respondents perceived benefits gained from global electives.Methods
We surveyed medical school graduates (classes of 2011-2015) from a large public medical school in the U.S. to describe current practice settings and previous global health experience. We evaluated work, volunteer, and educational experiences preceding medical school, socioeconomic status, race and ethnicity using American Medical College Application Service (AMCAS) data. We assessed the association between students' backgrounds, completing global health electives in medical school and current work in global health or with underserved populations in the U.S.Results
In the 5 to 8 years post-graduation, 78% of 161 respondents reported work, research, or teaching with a focus on global or underserved U.S.Populations
Completing a global health elective during medical school (p = 0.0002) or during residency (p = 0.06) were positively associated with currently working with underserved populations in the U.S. and pre-medical school experiences were marginally associated (p = 0.1). Adjusting for pre-medical school experiences, completing a global health elective during medical school was associated with a 22% greater prevalence of working with an underserved population. Perceived benefits from global electives included improved cultural awareness, language skills, public health and research skills, and ability to practice in technology-limited settings.Conclusion
Medical school graduates who participated in global electives as students were more likely than their peers to pursue careers with underserved populations, independent of experiences prior to medical school. We hypothesize that by offering global health experiences, medical schools can enhance the interests and skills of graduates that will make them more likely and better prepared to work with underserved populations in the U.S. and abroad.