Publications by authors named "Katie O' Brien"

Inorganic nitrate (NO) has been proposed to be of therapeutic use as a dietary supplement in obesity and related conditions including the Metabolic Syndrome (MetS), type-II diabetes and metabolic dysfunction associated steatotic liver disease (MASLD). Administration of NO to endothelial nitric oxide synthase-deficient mice reversed aspects of MetS, however the impact of NO supplementation in diet-induced obesity is not well understood. Here we investigated the whole-body metabolic phenotype and cardiac and hepatic metabolism in mice fed a high-fat high-sucrose (HFHS) diet for up to 12-months of age, supplemented with 1 mM NaNO (or NaCl) in their drinking water.

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Background: Elevated mammographic density is associated with increased breast cancer risk. However, the contribution of longitudinal changes in mammographic density to breast cancer risk beyond initial mammographic density levels, considering familial breast cancer risk and menopausal status, remains uncertain but holds important clinical implications.

Methods: In a nested case-control study within the Sister Study (323 cases, 899 controls; 12,095 mammograms), a cohort enriched for family history of breast cancer, we examined case-control status in relation to the largest annual change in percent density and dense area using mammograms available spanning 5.

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A better understanding of the factors contributing to systemic concentrations of carotenoids is necessary given the weak correlations between circulating levels and dietary intake of carotenoids. Although genetic variation may play a key role in the interindividual variability in carotenoid concentrations, few genome-wide association studies (GWAS) have focused on carotenoids. We used a random sample ( = 519) of postmenopausal participants in the Sister Study with data on genotypes and plasma carotenoid levels to conduct GWAS for each of five carotenoids (mcg/mL): alpha-carotene, beta- carotene, cryptoxanthin, lycopene, and lutein/zeaxanthin.

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Purpose: To determine the relationship between germline pathogenic variants (PVs) in cancer predisposition genes and the risk of ductal carcinoma in situ (DCIS).

Methods: Germline PV frequencies in breast cancer predisposition genes (ATM, BARD1, BRCA1, BRCA2, CDH1, CHEK2, PALB2, RAD51C, and RAD51D) were compared between DCIS cases and unaffected controls, and between DCIS and infiltrating ductal carcinoma (IDC) cases from a clinical-testing cohort (n=9,887), a population-based cohort (n=3,876) and the UK Biobank (n=2421). The risk of contralateral breast cancer for DCIS cases with PVs was estimated in the population-based cohort.

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Background: Disordered sleep and fatigue are common in the acute phase of stroke and can impede recovery.

Objective: A randomized parallel group placebo-controlled pilot study compared daily morning exposure to blue light or red light (placebo) for improving daytime sleepiness, fatigue, nocturnal sleep, and cognition in patients receiving inpatient rehabilitation for acute stroke.

Methods: 43 patients with disordered sleep secondary to first episode stroke (n = 34 ischemic, n = 9 hemorrhagic; aged 66.

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The circadian rhythm of the immune system helps to protect against pathogens; however, the role of circadian rhythms in immune homeostasis is less well understood. Innate T cells are tissue-resident lymphocytes with key roles in tissue homeostasis. Here we use single-cell RNA sequencing, a molecular-clock reporter and genetic manipulations to show that innate IL-17-producing T cells-including γδ T cells, invariant natural killer T cells and mucosal-associated invariant T cells-are enriched for molecular-clock genes compared with their IFNγ-producing counterparts.

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Article Synopsis
  • The study investigates nutrition support for critically ill children after they leave the pediatric intensive care unit (PICU), focusing on their recovery phase and identifying current nutrition practices.
  • Data was collected from children admitted to nine PICUs over two weeks, looking at their nutrition intake from the first full day in the ward and at various intervals up to 28 days post-admission.
  • Results show that a significant number of children were not meeting their estimated energy and protein needs, despite receiving nutritional support like enteral nutrition (EN) and parenteral nutrition (PN) during their recovery.
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  • Pathogenic variants (PVs) in certain genes like BRCA1 and BRCA2 increase breast cancer risk, but it's unclear how risk varies based on the type and location of these variants.
  • This study analyzed breast cancer risks associated with different PV types and locations using data from 12 US studies and clinical cohorts involving over 64,000 women.
  • Results showed that women with specific exon PTVs had higher breast cancer risks, lower rates of ER-negative breast cancer, and were diagnosed at younger ages compared to those with other variants, with these patterns observed across multiple cohorts.
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Background: During the fall of 2020, the porcine reproductive and respiratory syndrome virus (PRRSV) L1C.5 variant emerged and rapidly spread throughout southern Minnesota generating questions regarding possible transmission routes. This study aimed to investigate whether PRRSV could be detected on surfaces inside and outside pig barns housing L1C.

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Article Synopsis
  • - The study aimed to enhance breast cancer risk modeling by integrating pathogenic variants (PVs) in specific genes, a polygenic risk score (PRS), and an epidemiologic risk score (ERS) using data from over 23,000 breast cancer cases and controls.
  • - The results showed that postmenopausal women with no PVs but high ERS had a 4.4-fold increase in breast cancer risk, while some CHEK2 PV carriers had a predicted lifetime risk below 20%, indicating potential over-screening in certain groups.
  • - The findings suggest that combining these risk factors can improve risk assessment and possibly lead to more tailored screening and prevention strategies for breast cancer.
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Variable importance is a key statistical issue in exposure mixtures, as it allows a ranking of exposures as potential targets for intervention, and helps to identify bad actors within a mixture. In settings where mixtures have many constituents or high between-constituent correlations, estimators of importance can be subject to bias or high variance. Current approaches to assessing variable importance have major limitations, including reliance on overly strong or incorrect constraints or assumptions, excessive model extrapolation, or poor interpretability, especially regarding practical significance.

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The nutritional implications of spinal muscular atrophy (SMA) are profound. Disease modifying therapies (DMT) have improved clinical outcomes. This review describes the impact of DMT on nutrition outcomes.

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Uterine fibroids and endometriosis may be associated with an increased risk of ovarian cancer. Less is known about the role of hysterectomy in these associations. We estimated the independent and joint associations of hysterectomy, fibroids, and endometriosis with ovarian cancer incidence in the prospective Sister Study cohort (2003-2009).

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Background: Children who are critically ill are often reliant on enteral and oral nutrition support. However, there is limited evidence to guide "what" to prescribe, and current practice is unknown. The primary objective of this study was to describe enteral nutrition prescription in children ≤2 years of age in the pediatric intensive care unit (PICU).

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Background And Aims: There are few known risk factors for inflammatory bowel disease (IBD), an autoimmune disease characterized by chronic intestinal inflammation. Use of specific pesticides has been associated with higher incidence of IBD among pesticide applicators and their spouses, but no study has examined pesticide exposure in early life, a period where the human immune system undergoes rapid changes. We evaluated pesticide use during childhood and adolescence and incidence of IBD among US women enrolled in the Sister Study.

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  • Scientists looked at the timing of when girls start their periods (called menarche) and how it can affect their health later in life.
  • They studied about 800,000 women and found over a thousand genetic signals that influence when menstruation starts.
  • Some women have a much higher chance of starting their periods too early or too late based on their genetic makeup, suggesting that genes play a big role in this process!
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Background: Hair products may be a source of harmful chemicals and have been linked to age-related health outcomes. We investigated whether the use of hair products is related to epigenetic age in a sample of Black (both Hispanic and non-Hispanic) and non-Hispanic White women.

Methods: In a subset of 4358 participants aged 35-74 years from the Sister Study, we estimated cross-sectional associations between self-reported use of four chemical hair products (permanent dye, semipermanent dye, straighteners/relaxers, and hair permanents/body waves) in the year before enrollment (2003-2009) and three DNA methylation-based measures of epigenetic age (DunedinPACE, GrimAge age acceleration [GrimAgeAccel], and PhenoAge age acceleration [PhenoAgeAccel]) using survey-weighted multivariable linear regressions.

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Background: Healthcare workers (HCWs) are at increased risk of SARS-CoV-2 infection. This risk persists despite the implementation of mitigating factors, including vaccination. The ongoing impact of incident SARS-CoV-2 infection and symptomatic COVID-19 disease in vaccinated HCWs is poorly understood.

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Background And Aims: Tea and coffee are widely consumed beverages worldwide. We evaluated their association with biliary tract cancer (BTC) incidence.

Approach And Results: We pooled data from 15 studies in the Biliary Tract Cancers Pooling Project to evaluate associations between tea and coffee consumption and biliary tract cancer development.

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Purpose: Intimate care products may contain substances associated with increased risk of hormone-related cancers. The relationship between genital talc use and ovarian cancer, in particular, has been well studied, but concerns about recall bias and exposure misclassification have precluded conclusions. We examined the association between intimate care products and female hormone-related cancers, accounting for potential biases, using data from a US-based cohort study.

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Article Synopsis
  • - The study analyzed genetic factors linked to breast cancer in a diverse sample of 18,034 African ancestry cases and 22,104 controls, identifying 12 genetic variants tied to increased risk.
  • - Key findings included a rare variant (rs61751053) associated with overall breast cancer risk (odds ratio 1.48) and a common variant (rs76664032) connected to triple-negative breast cancer (odds ratio 1.30).
  • - A polygenic risk score (PRS) showed a predictive capability (0.60 area under the curve) for breast cancer risk, illustrating improved accuracy compared to PRS based on European data and highlighting the significance of diversity in genetic research.
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African-ancestry (AA) participants are underrepresented in genetics research. Here, we conducted a transcriptome-wide association study (TWAS) in AA female participants to identify putative breast cancer susceptibility genes. We built genetic models to predict levels of gene expression, exon junction, and 3' UTR alternative polyadenylation using genomic and transcriptomic data generated in normal breast tissues from 150 AA participants and then used these models to perform association analyses using genomic data from 18,034 cases and 22,104 controls.

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