Identification of metabolic pathways contributing to ER+ breast cancer disparities using a machine-learning pipeline.

African American (AA) women in the United States have a 40% higher breast cancer mortality rate than Non-Hispanic White (NHW) women. The survival disparity is particularly striking among (estrogen receptor positive) ER+ breast cancer cases. The purpose of this study is to examine whether there are racial differences in metabolic pathways typically activated in patients with ER+ breast cancer. We collected pretreatment plasma from AA and NHW ER+ breast cancer cases (AA n = 48, NHW n = 54) and cancer-free controls (AA n = 100, NHW n = 48) to conduct an untargeted metabolomics analysis using gas chromatography mass spectrometry (GC-MS) to identify metabolites that may be altered in the different racial groups. Unpaired t-test combined with multiple feature selection and prediction models were employed to identify race-specific altered metabolic signatures. This was followed by the identification of altered metabolic pathways with a focus in AA patients with breast cancer. The clinical relevance of the identified pathways was further examined in PanCancer Atlas breast cancer data set from The Cancer Genome Atlas Program (TCGA). We identified differential metabolic signatures between NHW and AA patients. In AA patients, we observed decreased circulating levels of amino acids compared to healthy controls, while fatty acids were significantly higher in NHW patients. By mapping these metabolites to potential epigenetic regulatory mechanisms, this study identified significant associations with regulators of metabolism such as methionine adenosyltransferase 1A (MAT1A), DNA Methyltransferases and Histone methyltransferases for AA individuals, and Fatty acid Synthase (FASN) and Monoacylglycerol lipase (MGL) for NHW individuals. Specific gene Negative Elongation Factor Complex E (NELFE) with histone methyltransferase activity, was associated with poor survival exclusively for AA individuals. We employed a comprehensive and novel approach that integrates multiple machine learning and statistical methods, coupled with human functional pathway analyses. The metabolic profile of plasma samples identified may help elucidate underlying molecular drivers of disproportionately aggressive ER+ tumor biology in AA women. It may ultimately lead to the identification of novel therapeutic targets. To our knowledge, this is a novel finding that describes a link between metabolic alterations and epigenetic regulation in AA breast cancer and underscores the need for detailed investigations into the biological underpinnings of breast cancer health disparities.

Using iRNA-seq analysis to predict gene expression regulatory level and activity in Zea mays tissues.

Plants regulate gene expression at the transcriptional and post-transcriptional levels to produce a variety of functionally diverse cells and tissues that ensure normal growth, development, and environmental response. Although distinct gene expression patterns have been characterized between different plant tissues, the specific role of transcriptional regulation of tissue-specific expression is not well-characterized in plants. RNA-seq, while widely used to assay for changes in transcript abundance, does not discriminate between differential expression caused by mRNA degradation and active transcription. Recently, the presence of intron sequences in RNA-seq analysis of libraries constructed with total RNA has been found to coincide with genes undergoing active transcription. We have adapted the intron RNA-sequencing analysis to determine genome-wide transcriptional activity in 2 different maize (Zea mays) tissues: husk and V2-inner stem tissue. A total of 5,341 genes were predicted to be transcriptionally differentially expressed between the 2 tissues, including many genes expected to have biological activity relevant to the functional and developmental identity of each tissue. Correlations with transcriptional enhancer and transcription factor activity support the validity of intron RNA-sequencing predictions of transcriptional regulation. A subset of transcription factors was further analyzed using gene regulatory network analysis to determine the possible impact of their activation. The predicted regulatory patterns between these genes were used to model a potential gene regulatory network of transcription factors and regulatory targets.

High-Resolution Full-3D Specimen Imaging for Lumpectomy Margin Assessment in Breast Cancer.

BACKGROUND: Two-dimensional (2D) specimen radiography (SR) and tomosynthesis (DBT) for breast cancer yield data that lack high-depth resolution. A volumetric specimen imager (VSI) was developed to provide full-3D and thin-slice cross-sectional visualization at a 360° view angle. The purpose of this prospective trial was to compare VSI, 2D SR, and DBT interpretation of lumpectomy margin status with the final pathologic margin status of breast lumpectomy specimens. METHODS: The study enrolled 200 cases from two institutions. After standard imaging and interpretation was performed, the main lumpectomy specimen was imaged with the VSI device. Image interpretation was performed by three radiologists after surgery based on VSI, 2D SR, and DBT. A receiver operating characteristic (ROC) curve was created for each method. The area under the curve (AUC) was computed to characterize the performance of the imaging method interpreted by each user. RESULTS: From 200 lesions, 1200 margins were interpreted. The AUC values of VSI for the three radiologists were respectively 0.91, 0.90, and 0.94, showing relative improvement over the AUCs of 2D SR by 54%, 13%, and 40% and DBT by 32% and 11%, respectively. The VSI has sensitivity ranging from 91 to 94%, specificity ranging from 81 to 85%, a positive predictive value ranging from 25 to 30%, and a negative predicative value of 99%. CONCLUSIONS: The ROC curves of the VSI were higher than those of the other specimen imaging methods. Full-3D specimen imaging can improve the correlation between the main lumpectomy specimen margin status and surgical pathology. The findings from this study suggest that using the VSI device for intraoperative margin assessment could further reduce the re-excision rates for women with malignant disease.

Factors Related to Injury Prevention Programming by Missouri School Nurses.

Schools often offer injury prevention (IP) programs, but little is known about the types of programs provided or how school nurses decide which to choose. Nurses in the Missouri School Health Services Staffing Survey Database were sent a survey in spring, 2011, to describe school-based IP efforts being offered. A multivariate linear regression was conducted to delineate factors associated with offering IP programs. In total, 522 school nurses participated (33% response rate). The highest priority for selecting an IP program was perceived program effectiveness (92.3% agreement, n = 482). Determinants of offering IP programs included being asked to identify a speaker, being a high school, receiving funding in the last year, prioritizing evidence-based programs, perceiving that administrators support professional development, and knowing how to address patterns of injuries. School nurses should be competent in planning, implementing, and evaluating IP programs, and additional training may be required to accomplish this.

Geographic Variation in Condom Availability and Accessibility.

Identifying predictors that contribute to geographic disparities in sexually transmitted infections (STIs) is necessary in order to reduce disparities. This study assesses the spatial relationship condom availability and accessibility in order to better identify determinants of geographic disparities in STIs. We conducted a telephone-based audit among potential-condom selling establishments. Descriptive analyses were conducted to detect differences in condom-selling characteristics by stores and by store type. Geocoding, mapping, and spatial analysis were conducted to measure the availability of condoms. A total of 850 potential condom-selling establishments participated in the condom availability and accessibility audit in St. Louis city; 29 % sold condoms. There were several significant geographic clusters of stores identified across the study area. The first consisted of fewer convenience stores and gas stations that sold condoms in the northern section of the city, whereas condoms were less likely to be sold in non-convenience store settings in the southwestern and central parts of the city. Additionally, locations that distributed free condoms clustered significantly in city center. However, there was a dearth of businesses that were neither convenience stores nor gas stations in the northern region of the city, which also had the highest concentration of condoms sold. This initial study was conducted to provide evidence that condom availability and accessibility differ by geographic region, and likely are a determinant of social norms surrounding condom use and ultimately impact STI rates.

Condom deserts: geographical disparities in condom availability and their relationship with rates of sexually transmitted infections.

BACKGROUND: Identifying predictors that contribute to geographical disparities in sexually transmitted infections (STIs) is necessary. This study assesses the spatial relationship between condom availability to locations of STIs in order to better understand these geographical disparities. OBJECTIVES: We conducted a condom availability audit among potential condom-selling establishments. New gonorrhoea and chlamydia cases in 2011 (n=6034) and HIV infection cases from 2006 to 2011 (n=565) were collected by census tract in St Louis, Missouri. 829 potential condom-selling establishments participated in the condom availability audit in St Louis City; 242 of which sold condoms. RESULTS: A negative linear relationship exists between condom vendors and cases of gonorrhoea and chlamydia, after adjusting for concentrated disadvantage and free condom locations. Higher concentrated disadvantage, higher proportions of convenience vendors and free locations were associated with higher rates of HIV. CONCLUSIONS: This study was conducted to provide evidence that lack of condom availability is associated with STI rates, and likely is an integral component to influencing the subjective norms surrounding condom use and STI rates. Condom distribution interventions may be addressing availability needs and social norms, yet are more likely to be effective when placed in locations with the highest STI rates.