Digital Commons Network^™

Accumulation Of Chronic Disease Among Survivors Of Childhood Cancer Predicts Early Mortality, Adam J Esbenshade, Lu Lu, Debra L Friedman, Kevin C Oeffinger, Gregory T Armstrong, Kevin R Krull, Joseph P Neglia, Wendy M Leisenring, Rebecca Howell, Robyn Partin, Amy Sketch, Leslie L Robison, Kirsten K Ness

Faculty, Staff and Student Publications

Purpose: Cancer survivors develop cancer and treatment-related morbidities at younger than normal ages and are at risk for early mortality, suggestive of an aging phenotype. The Cumulative Illness Rating Scale for Geriatrics (CIRS-G) is specifically designed to describe the accumulation of comorbidities over time with estimates of severity such as total score (TS) which is a sum of possible conditions weighted by severity. These severity scores can then be used to predict future mortality.

Methods: CIRS-G scores were calculated in cancer survivors and their siblings from Childhood Cancer Survivor Study cohort members from two time points 19 years apart and …

Per Oral Endoscopic Myotomy In Pregnancy, Julie Gomez, Laura Felder, Divya Chalikonda, Alexander Schlachterman, Vincenzo Berghella

Department of Obstetrics and Gynecology Faculty Papers

OBJECTIVE: To report the first successful full-term delivery following Per Oral Endoscopic Myotomy (POEM) performed during pregnancy.

METHODS/BACKGROUND: Achalasia is an esophageal motility disorder characterized by dysphagia, regurgitation, reflux, recurrent vomiting, and weight loss. Achalasia in pregnancy can affect nutritional status of the mother, and subsequently, the child, increasing morbidity and creating potential pregnancy complications. POEM is a novel endoscopic procedure which involves cutting the lower esophageal sphincter to allow food to pass, and is considered a safe and effective management option for achalasia in non-pregnant individuals.

RESULTS: We discuss the case of a patient with achalasia and a prior …

Circadian Disruption And Colorectal Cancer Incidence In Black Women, Lauren E Barber, Trang Vopham, Laura F White, Hemant K Roy, Julie R Palmer, Kimberly A Bertrand

Faculty, Staff and Students Publications

BACKGROUND: Animal and experimental studies suggest circadian disruption increases colorectal cancer risk, but evidence in humans is limited. We examined night shift work, chronotype, and residential position within a time zone, proxies for circadian disruption, in relation to colorectal cancer risk.

METHODS: Participants in the Black Women's Health Study, a prospective cohort of 59,000 Black American women established in 1995, reported history of night shift work and chronotype on follow-up questionnaires. Residential position within a time zone was estimated using participant addresses at each questionnaire cycle. Number of colorectal cancer cases and follow-up duration varied by analysis depending on timing …

Baseline Features And Reasons For Nonparticipation In The Colonoscopy Versus Fecal Immunochemical Test In Reducing Mortality From Colorectal Cancer (Confirm) Study, A Colorectal Cancer Screening Trial, Douglas J Robertson, Jason A Dominitz, Alexander Beed, Kathy D Boardman, Barbara J Del Curto, Peter D Guarino, Thomas F Imperiale, Andrew Lacasse, Meaghan F Larson, Samir Gupta, David Lieberman, Beata Planeta, Aasma Shaukat, Shanaz Sultan, Stacy B Menees, Sameer D Saini, Philip Schoenfeld, Stephan Goebel, Erik C Von Rosenvinge, Gyorgy Baffy, Ildiko Halasz, Marcos C Pedrosa, Lyn Sue Kahng, Riaz Cassim, Katarina B Greer, Margaret F Kinnard, Divya B Bhatt, Kerry B Dunbar, William V Harford, John A Mengshol, Jed E Olson, Swati G Patel, Fadi Antaki, Deborah A Fisher, Brian A Sullivan, Christopher Lenza, Devang N Prajapati, Helen Wong, Rebecca Beyth, John G Lieb, Joseph Manlolo, Fernando V Ona, Rhonda A Cole, Natalia Khalaf, Charles J Kahi, Divyanshoo Rai Kohli, Tarun Rai, Prateek Sharma, Jiannis Anastasiou, Curt Hagedorn, Ronald S Fernando, Christian S Jackson, M Mazen Jamal, Robert H Lee, Farrukh Merchant, Folasade P May, Joseph R Pisegna, Endashaw Omer, Dipendra Parajuli, Adnan Said, Toan D Nguyen, Claudio Ruben Tombazzi, Paul A Feldman, Leslie Jacob, Rachel N Koppelman, Kyle P Lehenbauer, Deepak S Desai, Mohammad F Madhoun, William M Tierney, Minh Q Ho, Heather J Hockman, Christopher Lopez, Emily Carter Paulson, Martin Tobi, Hugo L Pinillos, Michele Young, Nancy C Ho, Ranjan Mascarenhas, Kirrichai Promrat, Pritesh R Mutha, William M Pandak, Tilak Shah, Mitchell Schubert, Frank S Pancotto, Andrew J Gawron, Amelia E Underwood, Samuel B Ho, Priscilla Magno-Pagatzaurtundua, Doris H Toro, Charles H Beymer, Andrew M Kaz, Jill Elwing, Jeffrey A Gill, Susan F Goldsmith, Michael D Yao, Petr Protiva, Heiko Pohl, Tassos Kyriakides

Faculty, Staff and Student Publications

IMPORTANCE: The Colonoscopy Versus Fecal Immunochemical Test in Reducing Mortality From Colorectal Cancer (CONFIRM) randomized clinical trial sought to recruit 50 000 adults into a study comparing colorectal cancer (CRC) mortality outcomes after randomization to either an annual fecal immunochemical test (FIT) or colonoscopy.

OBJECTIVE: To (1) describe study participant characteristics and (2) examine who declined participation because of a preference for colonoscopy or stool testing (ie, fecal occult blood test [FOBT]/FIT) and assess that preference's association with geographic and temporal factors.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study within CONFIRM, which completed enrollment through 46 Department of Veterans Affairs …

Baseline Features And Reasons For Nonparticipation In The Colonoscopy Versus Fecal Immunochemical Test In Reducing Mortality From Colorectal Cancer (Confirm) Study, A Colorectal Cancer Screening Trial, Douglas J Robertson, Jill Elwing, Et Al.

2020-Current year OA Pubs

IMPORTANCE: The Colonoscopy Versus Fecal Immunochemical Test in Reducing Mortality From Colorectal Cancer (CONFIRM) randomized clinical trial sought to recruit 50 000 adults into a study comparing colorectal cancer (CRC) mortality outcomes after randomization to either an annual fecal immunochemical test (FIT) or colonoscopy.

OBJECTIVE: To (1) describe study participant characteristics and (2) examine who declined participation because of a preference for colonoscopy or stool testing (ie, fecal occult blood test [FOBT]/FIT) and assess that preference's association with geographic and temporal factors.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study within CONFIRM, which completed enrollment through 46 Department of Veterans Affairs …

Invited Review: Adrenocortical Function In Avian And Non-Avian Reptiles: Insights From Dispersed Adrenocortical Cells., Rocco V. Carsia, Patrick J. Mcilroy, Henry B John-Alder

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Herein we review our work involving dispersed adrenocortical cells from several lizard species: the Eastern Fence Lizard (Sceloporus undulatus), Yarrow's Spiny Lizard (Sceloporus jarrovii), Striped Plateau Lizard (Sceloporus virgatus) and the Yucatán Banded Gecko (Coleonyx elegans). Early work demonstrated changes in steroidogenic function of adrenocortical cells derived from adult S. undulatus associated with seasonal interactions with sex. However, new information suggests that both sexes operate within the same steroidogenic budget over season. The observed sex effect was further explored in orchiectomized and ovariectomized lizards, some supported with exogenous testosterone. Overall, a suppressive effect of testosterone was evident, especially in cells …

Genome-Wide Association Study Of Bladder Cancer Reveals New Biological And Translational Insights, Stella Koutros, Lambertus A Kiemeney, Parichoy Pal Choudhury, Roger L Milne, Evangelina Lopez De Maturana, Yuanqing Ye, Vijai Joseph, Oscar Florez-Vargas, Lars Dyrskjøt, Jonine Figueroa, Diptavo Dutta, Graham G Giles, Michelle A T Hildebrandt, Kenneth Offit, Manolis Kogevinas, Elisabete Weiderpass, Marjorie L Mccullough, Neal D Freedman, Demetrius Albanes, Charles Kooperberg, Victoria K Cortessis, Margaret R Karagas, Alison Johnson, Molly R Schwenn, Dalsu Baris, Helena Furberg, Dean F Bajorin, Olivier Cussenot, Geraldine Cancel-Tassin, Simone Benhamou, Peter Kraft, Stefano Porru, Angela Carta, Timothy Bishop, Melissa C Southey, Giuseppe Matullo, Tony Fletcher, Rajiv Kumar, Jack A Taylor, Philippe Lamy, Frederik Prip, Mark Kalisz, Stephanie J Weinstein, Jan G Hengstler, Silvia Selinski, Mark Harland, Mark Teo, Anne E Kiltie, Adonina Tardón, Consol Serra, Alfredo Carrato, Reina García-Closas, Josep Lloreta, Alan Schned, Petra Lenz, Elio Riboli, Paul Brennan, Anne Tjønneland, Thomas Otto, Daniel Ovsiannikov, Frank Volkert, Sita H Vermeulen, Katja K Aben, Tessel E Galesloot, Constance Turman, Immaculata De Vivo, Edward Giovannucci, David J Hunter, Chancellor Hohensee, Rebecca Hunt, Alpa V Patel, Wen-Yi Huang, Gudmar Thorleifsson, Manuela Gago-Dominguez, Pilar Amiano, Klaus Golka, Mariana C Stern, Wusheng Yan, Jia Liu, Shengchao Alfred Li, Shilpa Katta, Amy Hutchinson, Belynda Hicks, William A Wheeler, Mark P Purdue, Katherine A Mcglynn, Cari M Kitahara, Christopher A Haiman, Mark H Greene, Thorunn Rafnar, Nilanjan Chatterjee, Stephen J Chanock, Xifeng Wu, Francisco X Real, Debra T Silverman, Montserrat Garcia-Closas, Kari Stefansson, Ludmila Prokunina-Olsson, Núria Malats, Nathaniel Rothman

Faculty, Staff and Student Publications

BACKGROUND: Genomic regions identified by genome-wide association studies (GWAS) for bladder cancer risk provide new insights into etiology.

OBJECTIVE: To identify new susceptibility variants for bladder cancer in a meta-analysis of new and existing genome-wide genotype data.

DESIGN, SETTING, AND PARTICIPANTS: Data from 32 studies that includes 13,790 bladder cancer cases and 343,502 controls of European ancestry were used for meta-analysis.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSES: Log-additive associations of genetic variants were assessed using logistic regression models. A fixed-effects model was used for meta-analysis of the results. Stratified analyses were conducted to evaluate effect modification by sex and smoking status. …

Association Of Timing Of Moderate-To-Vigorous Physical Activity With Changes In Glycemic Control Over 4 Years In Adults With Type 2 Diabetes From The Look Ahead Trial, Jingyi Qian, Qian Xiao, Michael P Walkup, Mace Coday, Melissa L Erickson, Jessica Unick, John M Jakicic, Kun Hu, Frank A J L Scheer, Roeland J W Middelbeek, Look Ahead Research Group

Faculty, Staff and Student Publications

OBJECTIVE: We aimed to determine the association of the time-of-day of bout-related moderate-to-vigorous physical activity (bMVPA) with changes in glycemic control across 4 years in adults with overweight/obesity and type 2 diabetes.

RESEARCH DESIGN AND METHODS: Among 2,416 participants (57% women; mean age, 59 years) with 7-day waist-worn accelerometry recording at year 1 or 4, we assigned bMVPA timing groups based on the participants' temporal distribution of bMVPA at year 1 and recategorized them at year 4. The time-varying exposure of bMVPA (≥10-min bout) timing was defined as ≥50% of bMVPA occurring during the same time period (morning, midday, afternoon, …

Exploring The Role Of Vitamin D And The Gut Microbiome: A Cross-Sectional Study Of Individuals With Irritable Bowel Syndrome And Healthy Controls, Sarah W Matthews, Anna Plantinga, Robert Burr, Kevin C Cain, Tor Savidge, Kendra Kamp, Margaret M Heitkemper

Faculty, Staff and Students Publications

Irritable bowel syndrome (IBS) is a common disorder of gut-brain interaction with multifaceted pathophysiology. Prior studies have demonstrated higher rates of vitamin D deficiency in individuals with IBS compared to healthy controls (HC), as well as associations of vitamin D concentration with IBS symptoms. A systematic review of 10 mouse and 14 human studies reported a positive association between vitamin D (serum levels and supplementation) and beta diversity of gut microbiome in a variety of conditions. The present retrospective case-control study aimed to compare vitamin D (25(OH)D) plasma concentrations and gut microbiome composition in adult women with IBS (n=99) and …

Prematurity Blunts Protein Synthesis In Skeletal Muscle Independently Of Body Weight In Neonatal Pigs, Marko Rudar, Jane K Naberhuis, Agus Suryawan, Hanh V Nguyen, Marta L Fiorotto, Teresa A Davis

Faculty, Staff and Students Publications

Background

Postnatal growth failure in premature infants is associated with reduced lean mass accretion. Prematurity impairs the feeding-induced stimulation of translation initiation and protein synthesis in the skeletal muscle of neonatal pigs. The objective was to determine whether body weight independently contributes to the blunted postprandial protein synthesis.

Methods

Preterm and term pigs that were either fasted or fed were stratified into quartiles according to birth weight to yield preterm and term groups of similar body weight; first and second quartiles of preterm pigs and third and fourth quartiles of term pigs were compared (preterm-fasted, n = 23; preterm-fed, n …

Predictors, Disparities, And Facility-Level Variation: Sglt2 Inhibitor Prescription Among Us Veterans With Ckd, L Parker Gregg, David J Ramsey, Julia M Akeroyd, Shehrezade A Jafry, Michael E Matheny, Salim S Virani, Sankar D Navaneethan

Faculty, Staff and Students Publications

RATIONALE & OBJECTIVE: Sodium/glucose cotransporter 2 (SGLT2) inhibitors are recommended for type 2 diabetes mellitus (T2DM) in patients with chronic kidney disease (CKD) or atherosclerotic cardiovascular disease (ASCVD). We evaluated factors associated with SGLT2 inhibitor prescription, disparities by race and sex, and facility-level variation in prescription patterns.

STUDY DESIGN: Retrospective cohort.

SETTING & PARTICIPANTS: A national sample of US veterans with comorbid T2DM, CKD, and ASCVD with a primary care visit between January 1 and December 31, 2020.

EXPOSURE: Race, sex, and individual Veterans Affairs (VA) location.

OUTCOME: SGLT2 inhibitor prescription.

ANALYTICAL APPROACH: Multivariable logistic regression assessed associations of race …

Advancing Asms With Lc-Ms/Ms For The Discovery Of Novel Pdcl2 Ligands From Dna-Encoded Chemical Library Selections, Qiuji Ye, Hassane Belabed, Yong Wang, Zhifeng Yu, Murugesan Palaniappan, Jian-Yuan Li, Stacey A Kalovidouris, Kevin R Mackenzie, Mingxing Teng, Damian W Young, Yoshitaka Fujihara, Martin M Matzuk

Faculty, Staff and Students Publications

BACKGROUND: A safe, effective, and reversible nonhormonal male contraceptive drug is greatly needed for male contraception as well as for circumventing the side effects of female hormonal contraceptives. Phosducin-like 2 (PDCL2) is a testis-specific phosphoprotein in mice and humans. We recently found that male PDCL2 knockout mice are sterile due to globozoospermia caused by impaired sperm head formation, indicating that PDCL2 is a potential target for male contraception. Herein, our study for the first time developed a biophysical assay for PDCL2 allowing us to screen a series of small molecules, to study structure-activity relationships, and to discover two PDCL2 binders …

Nutrient Supplementation During The Prenatal Period In Substance-Using Mothers: A Narrative Review Of The Effects On Offspring Development., Catherine Serwatka, Adrianne K. Griebel-Thompson, Rina D. Eiden, Kai Ling Kong

Manuscripts, Articles, Book Chapters and Other Papers

Substance use during pregnancy increases the risk for poor developmental outcomes of the offspring, and for substance-dependent mothers, abstaining from substance use during pregnancy is often difficult. Given the addictive nature of many substances, strategies that may mitigate the harmful effects of prenatal substance exposure are important. Prenatal nutrient supplementation is an emerging intervention that may improve developmental outcomes among substance-exposed offspring. We provide a narrative review of the literature on micronutrient and fatty acid supplementation during pregnancies exposed to substance use in relation to offspring developmental outcomes. We first discuss animal models exposed to ethanol during pregnancy with supplementation …

Heterogeneity In The Effect Of Marked Weight Loss On Metabolic Function In Women With Obesity, Bettina Mittendorfer, Brandon D. Kayser, Mihoko Yoshino, Jun Yoshino, Jeramie D. Watrous, Mohit Jain, J. Christopher Eagon, Bruce W. Patterson, Samuel Klein

2020-Current year OA Pubs

BACKGROUNDThere is considerable heterogeneity in the effect of weight loss on metabolic function in people with obesity.METHODSWe evaluated muscle and liver insulin sensitivity, body composition, and circulating factors associated with insulin action before and after approximately 20% weight loss in women identified as "Responders" (n = 11) or "Non-responders" (n = 11), defined as the top (>75% increase) and bottom (<5% increase) quartiles of the weight loss-induced increase in glucose disposal rate (GDR) during a hyperinsulinemic-euglycemic clamp procedure, among 43 women with obesity (BMI: 44.1 ± 7.9 kg/m2).RESULTSAt baseline, GDR, which provides an index of muscle insulin sensitivity, and the hepatic insulin sensitivity index were more than 50% lower in Responders than Non-responders, but both increased much more after weight loss in Responders than Non-responders, which eliminated the differences between groups. Weight loss also caused greater decreases in intrahepatic triglyceride content and plasma adiponectin and PAI-1 concentrations in Responders than Non-responders and greater insulin-mediated suppression of plasma free fatty acids, branched-chain amino acids, and C3/C5 acylcarnitines in Non-responders than Responders, so that differences between groups at baseline were no longer present after weight loss. The effect of weight loss on total body fat mass, intra-abdominal adipose tissue volume, adipocyte size, and circulating inflammatory markers were not different between groups.CONCLUSIONThe results from our study demonstrate that the heterogeneity in the effects of marked weight loss on muscle and hepatic insulin sensitivity in people with obesity is determined by baseline insulin action, and reaches a ceiling when "normal" insulin action is achieved.TRIAL REGISTRATIONNCT00981500, NCT01299519, NCT02207777.FUNDINGNIH grants P30 DK056341, P30 DK020579, P30 DK052574, UL1 TR002345, and T32 HL13035, the American Diabetes Association (1-18-ICTS-119), the Longer Life Foundation (2019-011), and the Atkins Philanthropic Trust.

Microbiome Alteration Via Fecal Microbiota Transplantation Is Effective For Refractory Immune Checkpoint Inhibitor-Induced Colitis, Taylor M Halsey, Anusha S Thomas, Tomo Hayase, Weijie Ma, Hamzah Abu-Sbeih, Baohua Sun, Edwin Roger Parra, Zhi-Dong Jiang, Herbert L Dupont, Christopher Sanchez, Rawan El-Himri, Alexandria Brown, Ivonne Flores, Lauren Mcdaniel, Miriam Ortega Turrubiates, Matthew Hensel, Dung Pham, Stephanie S Watowich, Eiko Hayase, Chia-Chi Chang, Robert R Jenq, Yinghong Wang

Faculty, Staff and Student Publications

Immune checkpoint inhibitors (ICIs) target advanced malignancies with high efficacy but also predispose patients to immune-related adverse events like immune-mediated colitis (IMC). Given the association between gut bacteria with response to ICI therapy and subsequent IMC, fecal microbiota transplantation (FMT) represents a feasible way to manipulate microbial composition in patients, with a potential benefit for IMC. Here, we present a large case series of 12 patients with refractory IMC who underwent FMT from healthy donors as salvage therapy. All 12 patients had grade 3 or 4 ICI-related diarrhea or colitis that failed to respond to standard first-line (corticosteroids) and second-line …

Assessment Of The First Presentations Of Common Variable Immunodeficiency In A Large Cohort Of Patients, Hossein Esmaeilzadeh, Armita Jokar-Derisi, Amir Hossein Hassani, Reza Yazdani, Samaneh Delavari, Hassan Abolhassani, Negar Mortazavi, Aida Askarisarvestani

Department of Neurology Faculty Papers

BACKGROUND: Common Variable Immunodeficiency (CVID) is a primary immunodeficiency syndrome resulting in recurrent infections, autoimmunity, and granulomatous manifestations.

METHODS AND MATERIALS: This retrospective study was conducted on an Iranian national registry of immunodeficient patients from 2010 to 2021. The frequency of first presentations of CVID and its association with sex, age of onset, and family history of CVID was evaluated.

RESULTS: A total of 383 patients entered the study, 164 of whom were female, and the rest were male. The mean age of the patients was 25.3 ± 14.5 years. The most frequent first presentations of CVID were pneumonia (36.8%) …

Diet Quality Among Pre-Adolescent African American Girls In A Randomized Controlled Obesity Prevention Intervention Trial, Debbe Thompson, Yiming Mirabile, Noemi Islam, Chishinga Callender, Salma M A Musaad, Julie Miranda, Jennette P Moreno, Jayna M Dave, Tom Baranowski

Faculty, Staff and Students Publications

Consuming an unhealthy diet increases health risks. This study assessed the impact of a culturally adapted behaviorally innovative obesity prevention intervention (The Butterfly Girls and the Quest for Founder’s Rock) on diet quality in pre-adolescent non-Hispanic Black/African American girls. The RCT consisted of three groups (experimental, comparison, and waitlist control); block randomization allocated participants to each group. The two treatment groups varied in terms of whether or not they set goals. Data were collected at baseline (prior to receiving the intervention), post 1 (3 months post-baseline), and post 2 (6 months post-baseline). Two dietitian-assisted 24 h dietary recalls …

Early Postpartum Hba1c After Hyperglycemia First Detected In Pregnancy-Imperfect But Not Without Value, Ankia Coetzee, David R Hall, Mari Van De Vyver, Magda Conradie

Faculty, Staff and Student Publications

BACKGROUND: South African women of childbearing age are disproportionally affected by obesity and at significant risk of Type 2 Diabetes Mellitus (T2DM). Unless pregnant, they do not readily undergo screening for T2DM. With a local focus on improved antenatal care, hyperglycemia is often first detected in pregnancy (HFDP). This may erroneously be attributed to Gestational Diabetes Mellitus (GDM) in all without considering T2DM. Glucose evaluation following pregnancy is essential for early detection and management of women with T2DM in whom persistent hyperglycemia is to be expected. Conventional testing with an oral glucose tolerance test (OGTT) is cumbersome, prompting investigation for …

Evaluating The Use Of Blood Pressure Polygenic Risk Scores Across Race/Ethnic Background Groups, Nuzulul Kurniansyah, Matthew O Goodman, Alyna T Khan, Jiongming Wang, Elena Feofanova, Joshua C Bis, Kerri L Wiggins, Jennifer E Huffman, Tanika Kelly, Tali Elfassy, Xiuqing Guo, Walter Palmas, Henry J Lin, Shih-Jen Hwang, Yan Gao, Kendra Young, Gregory L Kinney, Jennifer A Smith, Bing Yu, Simin Liu, Sylvia Wassertheil-Smoller, Joann E Manson, Xiaofeng Zhu, Yii-Der Ida Chen, I-Te Lee, C Charles Gu, Donald M Lloyd-Jones, Sebastian Zöllner, Myriam Fornage, Charles Kooperberg, Adolfo Correa, Bruce M Psaty, Donna K Arnett, Carmen R Isasi, Stephen S Rich, Robert C Kaplan, Susan Redline, Braxton D Mitchell, Nora Franceschini, Daniel Levy, Jerome I Rotter, Alanna C Morrison, Tamar Sofer

Faculty, Staff and Student Publications

We assess performance and limitations of polygenic risk scores (PRSs) for multiple blood pressure (BP) phenotypes in diverse population groups. We compare "clumping-and-thresholding" (PRSice2) and LD-based (LDPred2) methods to construct PRSs from each of multiple GWAS, as well as multi-PRS approaches that sum PRSs with and without weights, including PRS-CSx. We use datasets from the MGB Biobank, TOPMed study, UK biobank, and from All of Us to train, assess, and validate PRSs in groups defined by self-reported race/ethnic background (Asian, Black, Hispanic/Latino, and White). For both SBP and DBP, the PRS-CSx based PRS, constructed as a weighted sum of PRSs …

Evaluating The Use Of Blood Pressure Polygenic Risk Scores Across Race/Ethnic Background Groups, Nuzulul Kurniansyah, C Charles Gu, Et Al.

2020-Current year OA Pubs

We assess performance and limitations of polygenic risk scores (PRSs) for multiple blood pressure (BP) phenotypes in diverse population groups. We compare "clumping-and-thresholding" (PRSice2) and LD-based (LDPred2) methods to construct PRSs from each of multiple GWAS, as well as multi-PRS approaches that sum PRSs with and without weights, including PRS-CSx. We use datasets from the MGB Biobank, TOPMed study, UK biobank, and from All of Us to train, assess, and validate PRSs in groups defined by self-reported race/ethnic background (Asian, Black, Hispanic/Latino, and White). For both SBP and DBP, the PRS-CSx based PRS, constructed as a weighted sum of PRSs …

Machine Learning Reveals Lipidome Remodeling Dynamics In A Mouse Model Of Ovarian Cancer, Olatomiwa O Bifarin, Samyukta Sah, David A Gaul, Samuel G Moore, Ruihong Chen, Murugesan Palaniappan, Jaeyeon Kim, Martin M Matzuk, Facundo M Fernández

Faculty, Staff and Students Publications

Ovarian cancer (OC) is one of the deadliest cancers affecting the female reproductive system. It may present little or no symptoms at the early stages and typically unspecific symptoms at later stages. High-grade serous ovarian cancer (HGSC) is the subtype responsible for most ovarian cancer deaths. However, very little is known about the metabolic course of this disease, particularly in its early stages. In this longitudinal study, we examined the temporal course of serum lipidome changes using a robust HGSC mouse model and machine learning data analysis. Early progression of HGSC was marked by increased levels of phosphatidylcholines and phosphatidylethanolamines. …

The Microbial Community Dynamics Of Cocaine Sensitization In Two Behaviorally Divergent Strains Of Collaborative Cross Mice., Thi Dong Binh Tran, Christian Monroy Hernandez, Hoan Nguyen, Susan Wright, Center For Systems Neurogenetics Of Addiction, Lisa M Tarantino, Elissa J Chesler, George M. Weinstock, Yanjiao Zhou, Jason A. Bubier

Faculty Research 2023

The gut-brain axis is increasingly recognized as an important pathway involved in cocaine use disorder. Microbial products of the murine gut have been shown to affect striatal gene expression, and depletion of the microbiome by antibiotic treatment alters cocaine-induced behavioral sensitization in C57BL/6J male mice. Some reports suggest that cocaine-induced behavioral sensitization is correlated with drug self-administration behavior in mice. Here, we profile the composition of the naïve microbiome and its response to cocaine sensitization in two collaborative cross (CC) strains. These strains display extremely divergent behavioral responses to cocaine sensitization. A high-responding strain, CC004/TauUncJ (CC04), has a gut microbiome …

Diabetes-Related Quality Of Life Assessment In Children Following Total Pancreatectomy With Islet Autotransplantation., Jacob M. Redel, Lindsey Hornung, Deborah Elder, Jaimie D. Nathan, Sarah Corathers, Kristin L. Rich, Maisam Abu-El-Haija

Manuscripts, Articles, Book Chapters and Other Papers

Total pancreatectomy with islet autotransplantation (TPIAT) can improve pain and reduce functional impairment associated with acute recurrent or chronic pancreatitis. However, long-term glucose monitoring and insulin therapy are often required, which can adversely affect the quality of life. We sought to evaluate diabetes-related quality of life (DR-QOL) in youth who underwent TPIAT and compare it to the youth with new-onset type 1 diabetes (T1D). The Pediatric Quality of Life Inventory™ 3.2 Diabetes Module (PedsQL™ DM) was used to assess DR-QOL in 46 youth (< 20 years old) who underwent TPIAT. The PedsQL™ DM scores were analyzed for statistically significant changes and minimally important clinical differences (MCID) over time post-TPIAT. Scores at 12 months (n = 52) and 24 months (n = 58) after diagnosis of T1D. The diabetes …

Recruitment And Reach In A School-Based Pediatric Obesity Intervention Trial In Rural Areas., Bethany Forseth, Brittany Lancaster, Megan Olalde, Christie A. Befort, Rebecca E. Swinburne Romine, Meredith Dreyer, Kelsey Dean, Eve-Lynn Nelson, Ann M. Davis

Manuscripts, Articles, Book Chapters and Other Papers

INTRODUCTION: The purpose of this study is to evaluate two recruitment strategies on schools and participant participation rates and representativeness (reach) within a pediatric obesity treatment trial tailored for families who live in rural areas.

METHODS: Recruitment of schools was evaluated based on their progress toward enrolling participants. Recruitment and reach of participants were evaluated using (1) participation rates and (2) representativeness of demographics and weight status of participants compared to eligible participants (who did not consent and enroll) and all students (regardless of eligibility). School recruitment, as well as participant recruitment and reach, were evaluated across recruitment methods comparing …

Efficacy Of Systemic Chemotherapy In Patients With Low-Grade Mucinous Appendiceal Adenocarcinoma: A Randomized Crossover Trial, John Paul Shen, Abdelrahman M Yousef, Fadl A Zeineddine, Mohammad A Zeineddine, Rebecca S Tidwell, Karen A Beaty, Lisa C Scofield, Safia Rafeeq, Nicholas Hornstein, Elizabeth Lano, Cathy Eng, Aurelio Matamoros, Wai Chin Foo, Abhineet Uppal, Christopher Scally, Paul Mansfield, Melissa Taggart, Kanwal P Raghav, Michael J Overman, Keith Fournier

Faculty, Staff and Student Publications

IMPORTANCE: Appendiceal adenocarcinoma is a rare tumor, and given the inherent difficulties in performing prospective trials in such a rare disease, there are currently minimal high-quality data to guide treatment decisions, highlighting the need for more preclinical and clinical investigation for this disease.

OBJECTIVE: To prospectively evaluate the effectiveness of fluoropyrimidine-based systemic chemotherapy in patients with inoperable low-grade mucinous appendiceal adenocarcinoma.

DESIGN, SETTING, AND PARTICIPANTS: This open-label randomized crossover trial recruited patients at a single tertiary care comprehensive cancer center from September 2013 to January 2021. The data collection cutoff was May 2022. Enrollment of up to 30 patients was …

Birth Weight Moderates The Association Between Obesity And Mortality Rate, Gregory Pavela, Nengjun Yi, Luis Mestre, Pengcheng Xun, David B Allison

Children’s Nutrition Research Center Staff Publications

Purpose: The strength of the association between obesity and mortality rate (MR) varies by body mass index (BMI) and sociodemographic groups. We test the hypothesis that the association between obesity and MR varies, in part, due to the moderating effect of parental BMI and birth weight.

Methods: Data come from the 1958 National Child Development Study, an ongoing longitudinal dataset initiated in 1958 with baseline measures of birth weight from 18,059 infants born in Great Britain over 1 week. We tested whether the association between BMI and MR was moderated by parental BMI and birth weight using generalized additive proportional …

Comparison Of Female Ovarian Reserve Before Vs After Covid-19 Vaccination, Liubin Yang, Samantha Neal, Tiffany Lee, Andrew Chou, Amy K Schutt, William Gibbons

Children’s Nutrition Research Center Staff Publications

This cohort study examines the association of COVID-19 vaccination with levels of anti-Mullerian hormone and antral follicle count in women seeking fertility treatment.

Sex- And Ethnic-Specific Patterns In The Incidence Of Hip Fracture Among Older Us Asian And Non-Hispanic White Adults, Joan C Lo, Malini Chandra, David R Lee, Jeanne A Darbinian, Nancy P Gordon, David W Zeltser, Christopher D Grimsrud, Catherine Lee

Faculty, Staff and Student Publications

BACKGROUND: Asian and Pacific Islander (Asian/PI) adults have lower hip fracture incidence than non-Hispanic White (NHW) adults, but data regarding Asian/PI subgroups are limited. We compared hip fracture incidence among older US Asian/PI and NHW populations, including ethnic subgroup differences.

METHODS: Using observational data from a California healthcare system, we identified Asian/PI and NHW adults aged ≥50 years (2000-2019) and followed subjects to 2021 for hip fracture determined by principal/primary hospital diagnosis or by secondary hospital diagnosis with hip/femur procedure codes. Age-adjusted hip fracture incidence was calculated with 95% confidence intervals (CIs). Log-Poisson regression was used to determine fracture incidence …

The Detrimental Role Of Angiotensin Receptor Agonistic Autoantibodies In Intrauterine Growth Restriction Seen In Preeclampsia, Monika M Safford, Doyle M Cummings, Jacqueline Halladay, James M Shikany, Joshua Richman, Suzanne Oparil, James Hollenberg, Alyssa Adams, Muna Anabtawi, Lynn Andreae, Elizabeth Baquero, Joanna Bryan, Debra Clark, Ethel Johnson, Erica Richman, Orysya Soroka, James Tillman, Andrea L Cherrington

Faculty, Staff and Student Publications

BACKGROUND: Impoverished African Americans (AA) with hypertension face poor health outcomes.

PURPOSE: To conduct a cluster-randomized trial testing two interventions, alone and in combination, to improve blood pressure (BP) control in AA with persistently uncontrolled hypertension.

METHODS: We engaged primary care practices serving rural Alabama and North Carolina residents, and in each practice we recruited approximately 25 AA adults with persistently uncontrolled hypertension (mean systolic BP >140 mmHg over the year prior to enrollment plus enrollment day BP assessed by research assistants ≥140/90 mmHg). Practices were randomized to peer coaching (PC), practice facilitation (PF), both PC and PF (PC + …

Association Of Diet Quality With Metabolic (Dysfunction) Associated Fatty Liver Disease In Veterans In Primary Care, Natalia I Heredia, Aaron P Thrift, David J Ramsey, Rohit Loomba, Hashem B El-Serag

Faculty, Staff and Student Publications

BACKGROUND: Diet is associated with metabolic (dysfunction)-associated fatty liver disease (MAFLD), but the dietary composition associated with MAFLD risk has not been well-examined.

AIM: The purpose of this study was to assess the association of two healthy eating indices with the presence and severity of MAFLD in a sample of Veterans in a primary care setting.

METHODS: This was a single center cross-sectional study using a random stratified sample of Veterans enrolled in primary care. Participants underwent a Fibroscan and completed an interviewer-administered Diet History Questionnaire II from which we calculated the Healthy Eating Index-2015 and Alternate Mediterranean Diet Score. …