Life Sciences Commons^™

Investigating The Role Of Abro1 In Dna Damage-Induced Immune Response, Ahmed Emam

Dissertations and Theses (Open Access)

Genomic instability can be induced by various forms of genotoxic stress and it is a hallmark of human cancer that is associated with metastasis, therapeutic resistance, and poor prognosis. During replication stress, the replication fork stalls and forms a reversed fork which may be degraded by several DNA nucleases. At the stalled fork, genome stability is maintained by fork end protection and subsequent restart of the replication. Abro1 has been shown to play an important role in protecting the integrity of the stalled replication forks by inhibiting DNA2 nuclease. Deficiency of Abro1 leads to stalled replication fork degradation and genomic …

Pedsql™ Gastroparesis Symptoms Module Domain And Item Development: Qualitative Methods, James W Varni, Robert J Shulman, Mariella M Self, Liz Febo-Rodriguez, Heather Charron, Kent Williams, Sam Nurko, Rachel L Rosen, Bruno P Chumpitazi

Children’s Nutrition Research Center Staff Publications

Objectives: Like adults, children suffer from gastroparesis; however, there are currently no validated instruments to determine the impact of gastroparesis in pediatric patients. The objective of this study was to develop the items and domains to support the content validity of the new Pediatric Quality of Life Inventory (PedsQL™) Gastroparesis Symptoms Module.

Methods: Patients were recruited from the National Institute of Diabetes and Digestive and Kidney Diseases Pediatric Gastroparesis Registry. The qualitative methods involved an iterative process comprising a literature review of existing questionnaires and gastroparesis clinical research, an expert review panel of pediatric gastroenterologists who provided feedback on the …

Genome-Wide Association Study Of Serum Metabolites In The African American Study Of Kidney Disease And Hypertension, Eugene P Rhee, Aditya Surapaneni, Pascal Schlosser, Yong Li, Anna Köttgen, Bing Yu, Morgan E Grams

Faculty, Staff and Student Publications

The genome-wide association study (GWAS) is a powerful means to study genetic determinants of disease traits and generate insights into disease pathophysiology. to date, few GWAS of circulating metabolite levels have been performed in African Americans with chronic kidney disease. Hypothesizing that novel genetic-metabolite associations may be identified in a unique population of African Americans with a lower glomerular filtration rate (GFR), we conducted a GWAS of 652 serum metabolites in 619 participants (mean measured glomerular filtration rate 45 mL/min/1.73m

Associations Between Physiological Biomarkers And Psychosocial Measures Of Pregnancy-Specific Anxiety And Depression With Support Intervention, Wenyaw Chan

Faculty, Staff and Student Publications

Stress and anxiety significantly impact the hypothalamic-pituitary axis, and in pregnancy, the subsequent maternal-fetal response can lead to poor outcomes. The objective of this study was to assess the association between psychosocial measures of pregnancy-specific anxiety and physiologic inflammatory responses. Specifically, to determine the effectiveness of the Mentors Offering Maternal Support (M-O-M-S

Impact Of Amerind Ancestry And Fads Genetic Variation On Omega-3 Deficiency And Cardiometabolic Traits In Hispanic Populations, Chaojie Yang, Brian Hallmark, Jin Choul Chai, Timothy D O'Connor, Lindsay M Reynolds, Alexis C Wood, Michael Seeds, Yii-Der Ida Chen, Lyn M Steffen, Michael Y Tsai, Robert C Kaplan, Martha L Daviglus, Lawrence J Mandarino, Amanda M Fretts, Rozenn N Lemaitre, Dawn K Coletta, Sarah A Blomquist, Laurel M Johnstone, Chandra Tontsch, Qibin Qi, Ingo Ruczinski, Stephen S Rich, Rasika A Mathias, Floyd H Chilton, Ani Manichaikul

Children’s Nutrition Research Center Staff Publications

Long chain polyunsaturated fatty acids (LC-PUFAs) have critical signaling roles that regulate dyslipidemia and inflammation. Genetic variation in the FADS gene cluster accounts for a large portion of interindividual differences in circulating and tissue levels of LC-PUFAs, with the genotypes most strongly predictive of low LC-PUFA levels at strikingly higher frequencies in Amerind ancestry populations. In this study, we examined relationships between genetic ancestry and FADS variation in 1102 Hispanic American participants from the Multi-Ethnic Study of Atherosclerosis. We demonstrate strong negative associations between Amerind genetic ancestry and LC-PUFA levels. The FADS rs174537 single nucleotide polymorphism (SNP) accounted for much …

Potential Benefits Of Bovine Colostrum In Pediatric Nutrition And Health, Per Torp Sangild, Caitlin Vonderohe, Valeria Melendez Hebib, Douglas G Burrin

Children’s Nutrition Research Center Staff Publications

Bovine colostrum (BC), the first milk produced from cows after parturition, is increasingly used as a nutritional supplement to promote gut function and health in other species, including humans. The high levels of whey and casein proteins, immunoglobulins (Igs), and other milk bioactives in BC are adapted to meet the needs of newborn calves. However, BC supplementation may improve health outcomes across other species, especially when immune and gut functions are immature in early life. We provide a review of BC composition and its effects in infants and children in health and selected diseases (diarrhea, infection, growth-failure, preterm birth, necrotizing …

Feasibility And Efficacy Of The "Funpals Playgroup" Intervention To Improve Toddler Dietary And Activity Behaviors: A Pilot Randomized Controlled Trial, Aliye B Cepni, Ashley Taylor, Christine Crumbley, Debbe Thompson, Nancy E Moran, Norma Olvera, Daniel P O'Connor, Katherine R Arlinghaus, Craig A Johnston, Tracey A Ledoux

Children’s Nutrition Research Center Staff Publications

This study evaluated the feasibility and effects of the Families Understanding Nutrition and Physically Active Lifestyles (FUNPALs) Playgroup on toddler (12–36-month-old) diet and activity behaviors. Parent–toddler dyads were recruited from disadvantaged communities and randomly assigned to receive 10-weekly sessions of the FUNPALs Playgroup (n = 24) or dose-matched health education control group (n = 26). FUNPALs Playgroups involved physical and snack activities, delivery of health information, and positive parenting coaching. The control group involved group health education for parents only. Process outcomes (e.g., retention rate, fidelity) and focus groups determined feasibility and perceived effects. To evaluate preliminary effects, …

Later Sleep Timing Predicts Accelerated Summer Weight Gain Among Elementary School Children: A Prospective Observational Study, Jennette P Moreno, Javad Razjouyan, Houston Lester, Hafza Dadabhoy, Mona Amirmazaheri, Layton Reesor-Oyer, Teresia M O'Connor, Daphne C Hernandez, Bijan Najafi, Candice A Alfano, Stephanie J Crowley, Debbe Thompson, Tom Baranowski

Children’s Nutrition Research Center Staff Publications

Objectives and background: Social demands of the school-year and summer environment may affect children's sleep patterns and circadian rhythms during these periods. The current study examined differences in children's sleep and circadian-related behaviors during the school-year and summer and explored the association between sleep and circadian parameters and change in body mass index (BMI) during these time periods.

Methods: This was a prospective observational study with 119 children ages 5 to 8 years with three sequential BMI assessments: early school-year (fall), late school-year (spring), and beginning of the following school-year in Houston, Texas, USA. Sleep midpoint, sleep duration, variability of …

Reciprocal Control Of Obesity And Anxiety-Depressive Disorder Via A Gaba And Serotonin Neural Circuit, Guobin Xia, Yong Han, Fantao Meng, Yanlin He, Dollada Srisai, Monica Farias, Minghao Dang, Richard D Palmiter, Yong Xu, Qi Wu

Children’s Nutrition Research Center Staff Publications

The high comorbidity between obesity and mental disorders, such as depression and anxiety, often exacerbates metabolic and neurological symptoms significantly. However, neural mechanisms that underlie reciprocal control of feeding and mental states are largely elusive. Here we report that melanocortin 4 receptor (MC4R) neurons located in the dorsal bed nucleus of the stria terminus (dBNST) engage in the regulation of mentally associated weight gain by receiving GABAergic projections from hypothalamic AgRP neurons onto α5-containing GABA

Quality Improvement In Diabetes Care: A Review Of Initiatives And Outcomes In The T1d Exchange Quality Improvement Collaborative, Olivia Z B Ginnard, G Todd Alonso, Sarah D Corathers, Carla Demeterco-Berggren, Lauren H Golden, Brian T Miyazaki, Grace Nelson, Emma Ospelt, Osagie Ebekozien, Joyce M Lee, Kathryn S Obrynba, Daniel J Desalvo, T1d Exchange Quality Improvement Collaborative Study Group

Children’s Nutrition Research Center Staff Publications

Despite immense strides in therapeutic advances, clinical outcomes continue to be less than ideal for people with type 1 diabetes. This discrepancy has prompted an outpouring of quality improvement (QI) initiatives to address the medical, psychosocial, and health equity challenges that complicate ideal type 1 diabetes care and outcomes. This article reviews a framework for QI in diabetes care that guided the development of the T1D Exchange Quality Improvement Collaborative to improve care delivery and health outcomes in type 1 diabetes. Evaluation of the methodology, outcomes, and knowledge gained from these initiatives will highlight the importance of continued QI initiatives …

Body Composition Changes In Children During Treatment For Moderate Acute Malnutrition: Findings From A 4-Arm Cluster-Randomized Trial In Sierra Leone, Devika J Suri, Isabel Potani, Akriti Singh, Stacy Griswold, William W Wong, Breanne Langlois, Ye Shen, Kwan Ho Kenneth Chui, Irwin H Rosenberg, Patrick Webb, Beatrice L Rogers

Children’s Nutrition Research Center Staff Publications

Background: Measures that better describe "healthy" and sustainable recovery during nutritional treatment of children with moderate acute malnutrition (MAM) are needed.

Objectives: We compared changes to body composition among children receiving 1 of 4 specialized nutritious food (SNFs) during treatment of MAM and by recovery and relapse outcomes.

Methods: The study was nested within a prospective, cluster-randomized, community-based, cost-effectiveness trial assessing 4 SNFs to treat children aged 6-59 mo with MAM [midupper arm circumference (MUAC) ≥11.5 cm and <12.5 cm without bipedal edema] in Sierra Leone. Biweekly SNF rations (1 of 3 fortified-blended foods or a lipid-based nutrient supplement) were given until children recovered (MUAC ≥12.5 cm), or up to 7 rations (∼12 wk). Deuterium dilution was used to estimate fat-free mass (FFM) and fat mass (FM) at enrollment and after 4 wk of treatment to ensure similar treatment exposure among the participants. Another MUAC measurement was performed among recovered children 4 wk after program exit to determine whether recovery was sustained. ANOVA, paired t tests, and linear regression models were used to determine significant differences in changes from baseline to 4 wk.

Results: Among 312 analyzed participants, mean baseline weight comprised ∼80% FFM; mean weight gained after 4 wk comprised ∼82% FFM. Changes in …

Barbadin Potentiates Long-Term Effects Of Lorcaserin On Pomc Neurons And Weight Loss, Yang He, Hailan Liu, Na Yin, Yongjie Yang, Chunmei Wang, Meng Yu, Hesong Liu, Chen Liang, Julia Wang, Longlong Tu, Nan Zhang, Lina Wang, Yanlin He, Makoto Fukuda, Qi Wu, Zheng Sun, Qingchun Tong, Yong Xu

Children’s Nutrition Research Center Staff Publications

Obesity is a serious global health problem because of its increasing prevalence and comorbidities, but its treatments are limited. The serotonin 2C receptor (5-HT_2CR), a G-protein-coupled receptor, activates proopiomelanocortin (POMC) neurons in the arcuate nucleus of hypothalamus (ARH) to reduce appetite and weight gain. However, several 5-HT analogs targeting this receptor, e.g., lorcaserin (Lor), suffer from diminished efficacy to reduce weight after prolonged administration. Here, we show that barbadin (Bar), a novel β-arrestin/β2-adaptin inhibitor, can prevent 5-HT_2CR internalization in cells and potentiate long-term effects of Lor to reduce appetite and body weight in male mice. Mechanistically, …

The Shape Of The Oral Glucose Tolerance Test-Glucose Response Curve In Islet Cell Antibody-Positive Vs -Negative Obese Youth Clinically Diagnosed With Type 2 Diabetes, Joon Young Kim, Hala Tfayli, Fida Bacha, Silva Arslanian

Children’s Nutrition Research Center Staff Publications

BACKGROUND: The oral glucose tolerance test (OGTT)-glucose response curves (GRCs; incessant increase, monophasic, and biphasic) reflect insulin sensitivity and β-cell function, being worse in the former and superior in the latter. Here, we examined if the OGTT-GRC pattern is worse in obese antibody (glutamic acid decarboxylase 65-kDa [GAD65] and insulinoma-associated protein-2 [IA-2])-positive (Ab

METHODS: Forty-seven obese youth, 15 Ab

RESULTS: Incessant increase OGTT-GRC is the most frequent curve type and is three-fold higher in Ab

CONCLUSION: Severe insulin deficiency, a characteristic of type 1 diabetes, seems to be related to higher prevalence of incessant increase in Ab

Restoration Of The Molecular Clock Is Tumor Suppressive In Neuroblastoma, Myrthala Moreno-Smith, Giorgio Milazzo, Ling Tao, Baharan Fekry, Bokai Zhu, Mahmoud A Mohammad, Simone Di Giacomo, Roshan Borkar, Karthik Reddy Kami Reddy, Mario Capasso, Sanjeev A Vasudevan, Pavel Sumazin, John Hicks, Nagireddy Putluri, Giovanni Perini, Kristin Eckel-Mahan, Thomas P Burris, Eveline Barbieri

Children’s Nutrition Research Center Staff Publications

MYCN activation is a hallmark of advanced neuroblastoma (NB) and a known master regulator of metabolic reprogramming, favoring NB adaptation to its microenvironment. We found that the expression of the main regulators of the molecular clock loops is profoundly disrupted in MYCN-amplified NB patients, and this disruption independently predicts poor clinical outcome. MYCN induces the expression of clock repressors and downregulates the one of clock activators by directly binding to their promoters. Ultimately, MYCN attenuates the molecular clock by suppressing BMAL1 expression and oscillation, thereby promoting cell survival. Reestablishment of the activity of the clock activator RORα via its genetic …

Defining The Relative Role Of Insulin Clearance In Early Dysglycemia In Relation To Insulin Sensitivity And Insulin Secretion: The Microbiome And Insulin Longitudinal Evaluation Study (Miles), Alexis C Wood, Elizabeth T Jensen, Alain G Bertoni, Gautam Ramesh, Stephen S Rich, Jerome I Rotter, Yii-Der I Chen, Mark O Goodarzi

Children’s Nutrition Research Center Staff Publications

Insulin resistance and insufficient insulin secretion are well-recognized contributors to type 2 diabetes. A potential role of reduced insulin clearance has been suggested, but few studies have investigated the contribution of insulin clearance while simultaneously examining decreased insulin sensitivity and secretion. The goal of this study was to conduct such an investigation in a cohort of 353 non-Hispanic White and African American individuals recruited in the Microbiome and Insulin Longitudinal Evaluation Study (MILES). Participants underwent oral glucose tolerance tests from which insulin sensitivity, insulin secretion, insulin clearance, and disposition index were calculated. Regression models examined the individual and joint contributions …

Associations Between Screen-Based Activities, Physical Activity, And Dietary Habits In Mexican Schoolchildren, Erica G Soltero, Alejandra Jáuregui, Edith Hernandez, Simón Barquera, Edtna Jáuregui, Juan Ricardo López-Taylor, Luis Ortiz-Hernández, Lucie Lévesque, Rebecca E Lee

Children’s Nutrition Research Center Staff Publications

Screen-based activities are associated with increased risk of obesity and contribute to physical inactivity and poor dietary habits. The primary aim of this study was to examine the associations among screen-based activities, physical activity, and dietary habits in school-aged children in Guadalajara, Puerto Vallarta, and Mexico City, Mexico. The secondary aim was to examine these associations across sex. The School Physical Activity and Nutrition survey was used to assess screen-based activities (TV watching, video game use, computer use), physical activity, and dietary habits. Organized activity/sports participation, unhealthy dietary habits, and household income were correlated with screen-based activities. While TV watching …

Deciphering An Agrp-Serotoninergic Neural Circuit In Distinct Control Of Energy Metabolism From Feeding, Yong Han, Guobin Xia, Dollada Srisai, Fantao Meng, Yanlin He, Yali Ran, Yang He, Monica Farias, Giang Hoang, István Tóth, Marcelo O Dietrich, Miao-Hsueh Chen, Yong Xu, Qi Wu

Children’s Nutrition Research Center Staff Publications

Contrasting to the established role of the hypothalamic agouti-related protein (AgRP) neurons in feeding regulation, the neural circuit and signaling mechanisms by which they control energy expenditure remains unclear. Here, we report that energy expenditure is regulated by a subgroup of AgRP neurons that send non-collateral projections to neurons within the dorsal lateral part of dorsal raphe nucleus (dlDRN) expressing the melanocortin 4 receptor (MC4R), which in turn innervate nearby serotonergic (5-HT) neurons. Genetic manipulations reveal a bi-directional control of energy expenditure by this circuit without affecting food intake. Fiber photometry and electrophysiological results indicate that the thermo-sensing MC4RdlDRN neurons …

Subchronic Tolerance Trials Of Graded Oral Supplementation With Phenylalanine Or Serine In Healthy Adults, Naoki Miura, Hideki Matsumoto, Luc Cynober, Patrick J Stover, Rajavel Elango, Motoni Kadowaki, Dennis M Bier, Miro Smriga

Children’s Nutrition Research Center Staff Publications

Phenylalanine and serine are amino acids used in dietary supplements and nutritional products consumed by healthy consumers; however, the safe level of phenylalanine or serine supplementation is unknown. The objective of this study was to conduct two 4-week clinical trials to evaluate the safety and tolerability of graded dosages of oral phenylalanine and oral serine. Healthy male adults (n = 60, 38.2 ± 1.8y) completed graded dosages of either phenylalanine or serine supplement (3, 6, 9 and 12 g/d) for 4 weeks with 2-week wash-out periods in between. Primary outcomes included vitals, a broad spectrum of circulating biochemical analytes, …

Gene Expression Analysis Of Environmental Temperature And High-Fat Diet-Induced Changes In Mouse Supraclavicular Brown Adipose Tissue, Yufeng Shi, Honglei Zhai, Sharon John, Yi-Ting Shen, Yali Ran, Giang Hoang, Miao-Hsueh Chen

Children’s Nutrition Research Center Staff Publications

Obesity, a dysregulation of adipose tissue, is a major health risk factor associated with many diseases. Brown adipose tissue (BAT)-mediated thermogenesis can potentially regulate energy expenditure, making it an attractive therapeutic target to combat obesity. Here, we characterize the effects of cold exposure, thermoneutrality, and high-fat diet (HFD) feeding on mouse supraclavicular BAT (scBAT) morphology and BAT-associated gene expression compared to other adipose depots, including the interscapular BAT (iBAT). scBAT was as sensitive to cold induced thermogenesis as iBAT and showed reduced thermogenic effect under thermoneutrality. While both scBAT and iBAT are sensitive to cold, the expression of genes involved …

Defining Vdr Expression In The Brain Using A Novel Vdrcre Mouse, Hailan Liu, Yang He, Jessie Beck, Silvania Da Silva Teixeira, Keisha Harrison, Yong Xu, Stephanie Sisley

Children’s Nutrition Research Center Staff Publications

Vitamin D action has been linked to several diseases regulated by the brain including obesity, diabetes, autism, and Parkinson’s. However, the location of the vitamin D receptor (VDR) in the brain is not clear due to conflicting reports. We found that two antibodies previously published as specific in peripheral tissues are not specific in the brain. We thus created a new knockin mouse with cre recombinase expression under the control of the endogenous VDR promoter (VDRCre). We demonstrated that the cre activity in the VDRCre mouse brain (as reported by a cre-dependent tdTomato expression) is highly overlapping with endogenous VDR …

Health-Related Quality Of Life In Parents And Partners Of People With Type 1 Diabetes: Development And Validation Of Type 1 Diabetes And Life (T1dal) Measures, Marisa E Hilliard, Charles G Minard, David G Marrero, Maartje De Wit, Stephanie N Dubose, Alandra Verdejo, Sarah S Jaser, Davida Kruger, Roshanak Monzavi, Viral N Shah, R Paul Wadwa, Ruth S Weinstock, Debbe Thompson, Viena T Cao, Barbara J Anderson

Children’s Nutrition Research Center Staff Publications

Introduction: Despite the significant impact of type 1 diabetes (T1D) on family, few instruments are available to assess health-related quality of life (HRQOL) among family members of people with T1D. This study aimed to develop and evaluate the psychometric properties of new measures of diabetes-specific HRQOL for parents and partners of people with T1D. We report on the multistep development and validation process for the self-report Type 1 Diabetes and Life (T1DAL) measures, with versions for parents of youth age <8, 8-11, 12-17, and 18-25 years, and for partners of people age ≥18 years with T1D.

Method: First, we conducted qualitative interviews (total parents/partners n = 38) to develop draft measures and piloted them (total n …

Impact Of Intratumor Heterogeneity And The Tumor Microenvironment In Shaping Tumor Evolution And Response To Therapy, Akash Mitra

Dissertations and Theses (Open Access)

Intratumor heterogeneity (ITH) is a crucial challenge in cancer treatment. The genotypic and phenotypic heterogeneity underlying diverse cancer types leads to subclonal variation, which may result in mixed or failed response to therapy. The heterogeneity at the tumor level, along with the tumor microenvironment (TME), often shapes tumor evolution and ultimately clinical outcome. Given that modern treatment paradigms increasingly expose patients with metastatic disease to multiple treatment modalities through the course of their disease, there exists a need to characterize robust and predictive biomarkers of response to therapy. In order to accurately characterize tumor evolution, we need to account for …

Hypoxia Acts As An Environmental Cue For The Human Tissue-Resident Memory T-Cell Differentiation Program, Farah Hasan

Dissertations and Theses (Open Access)

Tissue-resident memory T-cells (T_RM) provide frontline defense against viral diseases and can contribute to anti-tumor immunity; however, aside from the necessity of TGF-β, little is known regarding cues for T_RM differentiation. Oxygen tension is an environmental cue that distinguishes peripheral tissues from the circulation and here, we demonstrate that differentiation of human CD8+ T-cells under hypoxic conditions in the presence of TGF-β1 led to the development of a T_RM phenotype, characterized by a greater than five-fold increase in CD69+CD103+ cells expressing human T_RM hallmarks and enrichment for endogenous human T_RM gene signatures, including increased …

Clinical Characterization Of Pediatric Gastroparesis Using A Four-Hour Gastric Emptying Scintigraphy Standard, Sharon Wolfson, Zoe Wilhelm, Antone R Opekun, Robert Orth, Robert J Shulman, Bruno P Chumpitazi

Children’s Nutrition Research Center Staff Publications

Objectives: Four-hour gastric emptying scintigraphy (GES) is the recommended method to identify both adult and childhood gastroparesis (GP). Previous pediatric studies have, however, not used this standard. We sought to determine the characteristics and outcomes of children versus adolescents with GP using the 4-hour GES evaluation.

Methods: We performed a retrospective chart review of pediatric patients diagnosed with GP by 4-hour GES (>10% retention at 4 hours). Demographics, body mass index, GP-related symptoms, comorbidities, etiologies, therapies (eg, medications), healthcare utilization, and response to therapy were captured systematically. Symptoms were compared from the initial versus last gastroenterology visit. Outcomes were …

Digital Technology Needs In Maternal Mental Health: A Qualitative Inquiry, Alexandra Zingg, Laura Carter, Deevakar Rogith, Amy Franklin, Sudhakar Selvaraj, Jerrie Refuerzo, Sahiti Myneni

Faculty, Staff and Student Publications

Digital technologies offer many opportunities to improve mental healthcare management for women seeking pre- and-postnatal care. They provide a discrete, practical medium that is well-suited for the sensitive nature of mental health. Women who are more prone to experiencing peripartum depression (PPD), such as those of low-socioeconomic background or in high-risk pregnancies, can benefit the most from such technologies. However, current digital interventions directed towards this population provide suboptimal support, and their responsiveness to end user needs is quite limited. Our objective is to understand the digital terrain of information needs for low-socioeconomic status women with high-risk pregnancies, specifically within …

Cell Lineage Tracing Links Erα Loss In Erbb2-Positive Breast Cancers To The Arising Of A Highly Aggressive Breast Cancer Subtype, Yunfeng Ding, Yonghong Liu, Dong-Kee Lee, Zhangwei Tong, Xiaobin Yu, Yi Li, Yong Xu, Rainer B Lanz, Bert W O'Malley, Jianming Xu

Children’s Nutrition Research Center Staff Publications

HER2-positive (HER2+) breast cancers (BrCs) contain approximately equal numbers of ERα+HER2+ and ERα−HER2+ cases. An enduring obstacle is the unclear cell lineage-related characteristics of these BrCs. Although ERα+HER2+ BrCs could lose ERα to become ERα−HER2+ BrCs, direct evidence is missing. To investigate ERα dependencies and their implications during BrC growth and metastasis, we generated ERαCreRFP-T mice that produce an RFP-marked ERα+ mammary gland epithelial cell (MGEC) lineage. RCAS virus-mediated expression of Erbb2, a rodent Her2 homolog, first produced comparable numbers of ERα+RFP+Erbb2+ and ERα−RFP−Erbb2+ MGECs. Early hyperplasia developed mostly from ERα+RFP+Erbb2+ cells and ERα−RFP−Erbb2+ cells in these lesions were rare. …

Med-Bert: Pretrained Contextualized Embeddings On Large-Scale Structured Electronic Health Records For Disease Prediction, Laila Rasmy, Yang Xiang, Ziqian Xie, Cui Tao, Degui Zhi

Faculty, Staff and Student Publications

Deep learning (DL)-based predictive models from electronic health records (EHRs) deliver impressive performance in many clinical tasks. Large training cohorts, however, are often required by these models to achieve high accuracy, hindering the adoption of DL-based models in scenarios with limited training data. Recently, bidirectional encoder representations from transformers (BERT) and related models have achieved tremendous successes in the natural language processing domain. The pretraining of BERT on a very large training corpus generates contextualized embeddings that can boost the performance of models trained on smaller datasets. Inspired by BERT, we propose Med-BERT, which adapts the BERT framework originally developed …

Perceptions Of Family-Level Social Factors That Influence Health Behaviors In Latinx Adolescents And Young Adults At High Risk For Type 2 Diabetes, Erica G Soltero, Neeku Navabi, Felipe G Castro, Stephanie L Ayers, Jenny Mendez, Deborah I Thompson, Gabriel Q Shaibi

Children’s Nutrition Research Center Staff Publications

Given that health behaviors occur within the context of familial social relationships, a deeper understanding of social factors that influence health behaviors in Latinx families is needed to develop more effective diabetes prevention programming. This qualitative study identified perceived family-level social factors that influence health behaviors in Latinx adolescents (12–16 years; N = 16) and young adults (18–24 years; N = 15) with obesity and explored differences in perceptions across sex and age. Participants completed an in-depth interview that was recorded, transcribed, and coded using thematic content analysis. Emergent themes central to health behaviors included: perceived parental roles and responsibilities, …

A Neural Basis For Brain Leptin Action On Reducing Type 1 Diabetic Hyperglycemia, Shengjie Fan, Yuanzhong Xu, Yungang Lu, Zhiying Jiang, Hongli Li, Jessie C Morrill, Jing Cai, Qi Wu, Yong Xu, Mingshan Xue, Benjamin R Arenkiel, Cheng Huang, Qingchun Tong

Children’s Nutrition Research Center Staff Publications

Central leptin action rescues type 1 diabetic (T1D) hyperglycemia; however, the underlying mechanism and the identity of mediating neurons remain elusive. Here, we show that leptin receptor (LepR)-expressing neurons in arcuate (LepRArc) are selectively activated in T1D. Activation of LepRArc neurons, Arc GABAergic (GABAArc) neurons, or arcuate AgRP neurons, is able to reverse the leptin’s rescuing effect. Conversely, inhibition of GABAArc neurons, but not AgRP neurons, produces leptin-mimicking rescuing effects. Further, AgRP neuron function is not required for T1D hyperglycemia or leptin’s rescuing effects. Finally, T1D LepRArc neurons show defective nutrient sensing and signs of cellular energy deprivation, which are …

Consumption Of High-Fructose Corn Syrup Compared With Sucrose Promotes Adiposity And Increased Triglyceridemia But Comparable Nafld Severity In Juvenile Iberian Pigs, Magdalena Maj, Brooke Harbottle, Payton A Thomas, Gabriella V Hernandez, Victoria A Smith, Mark S Edwards, Rob K Fanter, Hunter S Glanz, Chad Immoos, Douglas G Burrin, Tasha M Santiago-Rodriguez, Michael R La Frano, Rodrigo Manjarín

Children’s Nutrition Research Center Staff Publications

Background: Fructose consumption has been linked to nonalcoholic fatty liver disease (NAFLD) in children. However, the effect of high-fructose corn syrup (HFCS) compared with sucrose in pediatric NAFLD has not been investigated.

Objectives: We tested whether the isocaloric substitution of dietary sucrose by HFCS would increase the severity of NAFLD in juvenile pigs, and whether this effect would be associated with changes in gut histology, SCFA production, and microbial diversity.

Methods: Iberian pigs, 53-d-old and pair-housed in pens balanced for weight and sex, were randomly assigned to receive a mash diet top-dressed with increasing amounts of sucrose (SUC; n = …