Endocrinology, Diabetes, and Metabolism Commons^™

Pair-Feeding Study Designs Can Create Biases And Inflate Type I Error Rates: A Simulation Study, Wasiuddin Najam, Daniel E Kpormegbey, Deependra K Thapa, Bret Rust, Lilian Golzarri-Arroyo, Lance H Baumgard, Louis Wai-Tong Fan, Joseph G Ibrahim, Edith J Mayorga, David B Allison

Children’s Nutrition Research Center Staff Publications

Objective: Pair-feeding is a study design element where one group's food intake is provided to another group to assess whether a treatment effect is independent of food intake. Investigators often assume equivalent food intake across experimental conditions and exclude it from the statistical analysis. However, the impact of this practice on type I error (T1Er) rates has not been quantified.

Methods: We conducted a Monte Carlo simulation in which animals were assigned baseline weights and food intakes, then randomized to non-pair-fed or pair-fed groups. Daily food intake for both groups was initially drawn from the baseline food intake distribution. For …

Enteral And Intravenous Supplementation Of Arginine And Citrulline Fail To Prevent Necrotizing Enterocolitis In Preterm Neonatal Pigs, Caitlin Vonderohe, Julia Garcia Mancebo, Valeria Melendez Hebib, Barbara Stoll, Inka Didelija, Sarah Elefson, Mahmoud Mohammad, Brooklynn Earls, Greg Guthrie, Doug Burrin

Children’s Nutrition Research Center Staff Publications

Background: Necrotizing enterocolitis (NEC) is the most common gastrointestinal emergency in preterm infants with a morality rate that approaches 50%. Arginine has been widely studied in the field of clinical nutrition as a supplement for patients experiencing critical illness because it can be metabolized into nitric oxide, an important agent for supporting immunity and microcirculation. Citrulline has received less attention but can be metabolized into arginine and has a much longer plasma half-life than arginine. We used the highly translational preterm pig model to determine the effect of intravenous and enteral supplementation of arginine and citrulline on NEC incidence in …

Unravelling The Molecular Mechanisms Causal To Type 2 Diabetes Across Global Populations And Disease-Relevant Tissues, Ozvan Bocher, Ana Luiza Arruda, Satoshi Yoshiji, Chi Zhao, Alicia Huerta-Chagoya, Chen-Yang Su, Xianyong Yin, Davis Cammann, Henry J Taylor, Jingchun Chen, Ken Suzuki, Ravi Mandla, Ta-Yu Yang, Fumihiko Matsuda, Josep M Mercader, Jason Flannick, James B Meigs, Alexis C Wood, Marijana Vujkovic, Benjamin F Voight, Cassandra N Spracklen, Jerome I Rotter, Andrew P Morris, Eleftheria Zeggini

Children’s Nutrition Research Center Staff Publications

Type 2 diabetes (T2D) is a prevalent disease arising from complex molecular mechanisms. Here we leverage T2D genetic associations to identify causal molecular mechanisms in an ancestry-aware and tissue-aware manner. Using two-sample Mendelian randomization corroborated by colocalization across four global ancestries, we analyse 20,307 gene and 1,630 protein expression levels using blood-derived cis-quantitative trait loci (QTLs). We detect causal effects of genetically predicted levels of 335 genes and 46 proteins on T2D risk, with 16.4% and 50% replication in independent cohorts, respectively. Using gene expression cis-QTLs derived from seven T2D-relevant tissues, we identify causal links between the expression of 676 …

Uncovering Predictors Of Bipolar Ii Conversion To Bipolar I: A Machine Learning Analysis Of National Health Records In Taiwan, Chih-Wei Hsu, Yang-Chieh Brian Chen, Liang-Jen Wang, Kuo-Chuan Hung, Mu-Hong Chen, Eduard Vieta, Chien-Yuan Chen, Chih-Sung Liang, Andre F Carvalho

Children’s Nutrition Research Center Staff Publications

Background: Bipolar II disorder (BD-II) can progress to bipolar I disorder (BD-I), carrying profound psychosocial consequences. However, limited research has investigated the transition from BD-II to BD-I. Our study uses machine learning to predict the conversion using real-world data.

Methods: We conducted a retrospective cohort study using the Taiwan National Health Insurance Research Database (2000-2013) to identify adults diagnosed with BD-II. A predictive model for BD-I conversion was developed using extreme gradient boosting (XGBoost), incorporating demographic factors, healthcare utilization, comorbidities, and psychotropic medication use. The dataset was randomly divided into development (80 %) and test (20 %) sets. Model performance …

Catatonia And Elevated Mortality: A Population-Wide Cohort Study With Healthy, Sibling, And Schizophrenia Spectrum Controls, Chih-Wei Hsu, Yang-Chieh Brian Chen, Marco Solmi, Chih-Sung Liang, Mu-Hong Chen, Yao-Hsu Yang, Liang-Jen Wang, Edward Chia-Cheng Lai

Children’s Nutrition Research Center Staff Publications

Aim: To determine whether catatonia is associated with increased long-term all-cause and cause-specific mortality.

Methods: Using Taiwan's National Health Insurance Database (2000-2022), we assembled a population-based cohort of all adults (≥18 years) with catatonia and matched each to four controls without catatonia on sex and birthdate. Mortality was compared between (1) individuals with catatonia and their unaffected siblings and (2) individuals with schizophrenia spectrum disorders with catatonia and those with schizophrenia spectrum disorders without catatonia. The primary outcome was all-cause mortality; secondary outcomes were natural- and unnatural-cause deaths. Adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated with …

Life-Extending Interventions Do Not Necessarily Result In Compression Of Morbidity: A Case Example Offering A Robust Statistical Approach, Deependra K Thapa, Wasiuddin Najam, Erik S Parker, Xi Rita Wang, Daniel L Smith, Ufuk Beyaztas, James F Nelson, Steven N Austad, Gary A Churchill, David B Allison

Children’s Nutrition Research Center Staff Publications

Despite extensive research on life-extending interventions, rigorous statistical techniques to determine their impact on compression of morbidity (CoM) are rarely used. We present a case example of an analytical method for examining the effect of life-extending dietary interventions on CoM by comparing the rates of decline in vitality and survival toward the end of life. Using data from previous experimental studies in mice, we calculated the average rate of vitality decline by fitting exponential decay models to individual vitality trajectories and compared this rate with the rate of survival decline estimated from Cox proportional hazards model. The results showed that, …

Rab5c Increases Endothelial Release Of Vwf By Regulating Vesicle Trafficking, Paula Reventun, Pablo Toledano-Sanz, Maria Delgado-Marin, Maria Viskadourou, D Brian Foster, Paul S De Vries, Maria Sabater-Lleal, Nunzio Alcharani, Claudia Gonzalez-Cucharero, William O Osburn, Alanna C Morrison, Alisa S Wolberg, Nicholas L Smith, Marios Arvanitis, Charles J Lowenstein

Faculty, Staff and Student Publications

Background: Abnormal levels of VWF (von Willebrand Factor) are a risk factor for venous thromboembolism (VTE) and bleeding. Genome-wide association studies for VWF have identified novel candidate genes that may regulate VWF levels in humans, including RAB5C (RAS-associated protein RAB5C). We hypothesized that RAB5C regulates VWF release from endothelial cells.

Methods: We studied the effect of RAB5C on vesicle trafficking in human endothelial cells. We performed CRISPR (clustered regularly interspaced short palindromic repeats) interference targeting 2 genetic variants linked to altered VWF levels and evaluated RAB5C expression by reverse transcription-quantitative polymerase chain reaction. We silenced RAB5C or overexpressed RAB5C wild-type, …

Association Between Ultraprocessed Food Consumption And Cardiovascular Disease Risk: Mesa (Multiethnic Study Of Atherosclerosis), Amier Haidar, Rishi Rikhi, Karol E Watson, Alexis C Wood, Michael D Shapiro

Children’s Nutrition Research Center Staff Publications

Background: Ultraprocessed foods (UPFs) have been linked to adverse cardiometabolic outcomes and increased atherosclerotic cardiovascular disease (CVD) (ASCVD) risk. However, prior research has largely focused on homogenous populations, lacking racial and ethnic diversity.

Objectives: The objectives are to examine the longitudinal relationship between UPF consumption and ASCVD risk and to investigate whether these associations differ by race/ethnicity, sex, or socioeconomic status.

Methods: The MESA (Multiethnic Study of Atherosclerosis) is a prospective cohort study of 6,814 U.S. adults aged 45 to 84 years, without clinically apparent CVD. UPF consumption was classified according to the Nova classification system. Multivariable cox proportional hazards …

N-Palmitoyl Glutamine Is A Candidate Mediator Of Cardiorespiratory Fitness, Jeremy M Robbins, Mark Benson, Anthony R P Verkerke, Gaurav Tiwari, Shuliang Deng, Prashant Rao, Usman A Tahir, Julian Avila-Pacheco, Xu Shi, Yuntian Guan, Foje-Geh Tendoh, Jacob L Barber, Patricia E Miller, Andrew S Perry, Michael E Hall, Alexis C Wood, Kent D Taylor, Wendy S Post, Stephen S Rich, Matthew Nayor, James G Wilson, Gregory D Lewis, Ravi V Shah, Jerome I Rotter, Scott A Summers, Laura M Raffield, Shingo Kajimura, Claude Bouchard, Clary B Clish, Mark A Sarzynski, Robert E Gerszten

Children’s Nutrition Research Center Staff Publications

Background: Cardiorespiratory fitness is an integrative measure of cardiometabolic health and predictor of survival, yet little is known about its molecular underpinnings. Small molecule metabolites and lipids are increasingly recognized as exercise-stimulated signaling molecules and candidate molecular transducers of cardiorespiratory fitness.

Methods: We performed nontargeted liquid chromatography mass spectrometry-based plasma metabolomics in 654 participants (mean age, 35 years; 55% women) from the HERITAGE Family Study (Health, Risk Factors, Exercise Training, and Genetics) who had cardiorespiratory fitness (maximal oxygen uptake [VO2max]) measured by cardiopulmonary exercise testing and underwent 20 weeks of supervised endurance training. Metabolite-VO2max relationships were assessed using linear regression …

Conclusions Are Not Supported By The Published Statistical Analysis Comment On López-Toledo Et Al Flaxseed Improves Glucose And Lipid Metabolism In Mexican Subjects With Type 2 Diabetes: A Parallel Randomized Clinical Trial, Robert W Spitz, Deependra K Thapa, Thirupathi Reddy Mokalla, Wasiuddin Najam, Andrew W Brown, David B Allison

Children’s Nutrition Research Center Staff Publications

López-Toledo et al [...].

The Impact Of Gastric Sleeve And Roux-En-Y Gastric Bypass On Chief Cell Function And Protein Digestion In Obese Patients, Garikoitz Mikel Gainza

Honors Undergraduate Theses

Obesity has become one of the largest global health concerns of the 21^st century, correlating with numerous associated diseases. To help address the growing prevalence and burden of obesity, sleeve gastrectomy and Roux-en-Y gastric bypass have become two commonly performed surgical procedures done to promote weight loss by altering the anatomical structure of the stomach and surrounding organs of the gastrointestinal system. Although the benefits of improved metabolism linked to these surgical procedures are well studied, their impact on the physiology of gastric cells, and more specifically chief cells as they relate to protein digestion post-surgery, is yet to …

“Shaking The Ladder” Reveals How Analytic Choices Can Influence Associations In Nutrition Epidemiology: Beef Intake And Coronary Heart Disease As A Case Study, Colby J Vorland, Lauren E O'Connor, Beate Henschel, Cuiqiong Huo, James M Shikany, Carlos A Serrano, Robert Henschel, Stephanie L Dickinson, Keisuke Ejima, Aurelian Bidulescu, David B Allison, Andrew W Brown

Children’s Nutrition Research Center Staff Publications

Nutrition epidemiological models involve many analytic decisions, such as defining exposures, selecting which covariates to include, or configuring variables in different ways. We explored the impact of analytical decisions on conclusions in nutrition epidemiology using self-reported beef intake and incident coronary heart disease as a case study. We used REasons for Geographic and Racial Differences in Stroke (REGARDS) data, and selected covariates and their configurations from published literature to recapitulate common models used to assess associations between meat intake and health outcomes. Three model sets were designed: sets one and two used continuous and quintile-defined beef intakes, respectively, each with …

Polyfluoroalkyl Substances And Altered Glucose Homeostasis In Adolescents Following Bariatric Surgery, Elizabeth Costello, Brittney O Baumert, Zhenjiang Li, Vishal Midya, Shudi Pan, Justin R Ryder, Thomas H Inge, Todd M Jenkins, Stephanie Sisley, Stavra A Xanthakos, Anita Courcoulas, Douglas I Walker, Nikos Stratakis, Damaskini Valvi, Scott M Bartell, Angela L Slitt, Rohit Kohli, Sarah Rock, Michele A La Merrill, Sandrah P Eckel, Max T Aung, Rob Mcconnell, David V Conti, Lida Chatzi

Children’s Nutrition Research Center Staff Publications

Objectives: Bariatric surgery is an effective treatment for severe obesity and associated metabolic comorbidities. Exposure to polyfluoroalkyl substance (PFAS) before bariatric surgery may attenuate improvements in glucose metabolism and explain some of the heterogeneity in post-surgery outcomes.

Design: This is an observational cohort study.

Methods: Adolescents (n = 186) enrolled in the Teen-Longitudinal Assessment of Bariatric Surgery study were included. Eight-PFAS congeners were measured in plasma before surgery. Linear and logistic regressions were used to examine cross-sectional associations between log2-transformed PFAS (ng/mL) and fasting glucose, insulin, hemoglobin A1c (HbA1c), and homeostatic model assessment for insulin resistance (HOMA-IR). Linear mixed …

Examining Widely Held Propositions On Human Dietary Protein Needs And Benefits: A Critical Review Of The Science That Shapes Both The Data And Our Understanding Of An Essential Macronutrient, Mitchell M Kanter, Sally Aaron, Steven N Austad, Andrew W Brown, Nicholas A Burd, Wayne W Campbell, Mark Cope, Teresa A Davis, John W Erdman, Miguel Freitas, Kristen Hicks-Roof, Samuel Klein, Wantanee Kriengsinyos, Dudley W Lamming, Donald K Layman, Heather J Leidy, Kevin C Maki, Richard D Mattes, Shalene Mcneill, Daniel R Moore, Stefan M Pasiakos, Stuart M Phillips, David Raubenheimer, Wendy Reinhardt, Nancy R Rodriguez, Stephen Simpson, Hans H Stein, Luc J C Van Loon, Connie M Weaver, David B Allison

Children’s Nutrition Research Center Staff Publications

The essentiality of protein in the human diet is unequivocal. Yet researchers, clinicians, and lay people often believe numerous propositions about dietary protein despite insufficient supporting or refuting data in some instances. To address this disconnect, and to "pressure-test" current beliefs about dietary protein, the Indiana University School of Public Health-Bloomington convened a workshop in February 2025 titled "Human Dietary Protein Needs and Benefits: A Critical Assessment of Postulated Propositions." More than 20 international experts discussed (1) methodologic issues affecting data acquisition and interpretation; (2) "optimal" dietary protein intakes and effects on muscle protein synthesis rates, muscle protein accretion, …

Limosilactobacillus Reuteri Alleviates Proinflammatory T-Cell-Mediated Liver Injury And Transcriptomic Changes In Immunocompromised Mice, Ana Fadhel Alvarez, Zheng Yin, Beanna Okeugo, Alexander Banerjee, Meng Luo, Christopher M Taylor, Salomea Giorgberidze, Vaishali Harne, Rambabu Majji, Melissa N Munroe, Ji Ho Suh, Stephen T C Wong, Kang Ho Kim, Hari Krishna Yalamanchili, Suhair Al Salihi, Jon Marc Rhoads, Yuying Liu

Children’s Nutrition Research Center Staff Publications

Background: A deficiency of immunosuppressive regulatory T cells, as seen in scurfy (SF) mice or in IPEX syndrome in humans, can lead to multiorgan inflammation. Oral administration of the probiotic Limosilactobacillus reuteri Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH (DSM) 17938 prolongs survival and reduces Th1- and Th2-associated inflammation in SF mice. It remains unclear how DSM 17938-educated SF-CD4+ T cells modulate T-cell-liver communication.

Methods: To characterize CD4+ T cells from SF mice orally administered DSM 17938 (Prob-SF-CD4+ T cells) and to compare them with CD4+ T cells from SF mice (SF-CD4+ T cells), cells isolated from SF spleens were …

Insulinemic And Inflammatory Dietary Patterns And Colorectal Cancer Risk: A Dietary Data Harmonization Study Of One Million Participants In The Consortium Of Metabolomics Studies (Comets), Ni Shi, Rachel Hoobler, Rhea Harewood, Amanda E Toland, Demetrius Albanes, Emmanouil Bouras, Marc J Gunter, Linda M Liao, Steven C Moore, Fulvio Ricceri, Jerome I Rotter, Rashmi Sinha, Rachael Stolzenberg-Solomon, Anne Tjønneland, Alexis C Wood, Danxia Yu, Mary C Playdon, Fred K Tabung

Children’s Nutrition Research Center Staff Publications

Background: Inflammatory and insulinemic dietary patterns have been associated with colorectal cancer (CRC) risk, but generalizability across diverse populations with heterogeneous food supplies and dietary behaviors has not been established.

Objectives: We harmonized disparate dietary and covariate data on a large scale to compute the reverse Empirical Dietary Index for Hyperinsulinemia (rEDIH), reverse Empirical Dietary Inflammatory Pattern (rEDIP), and Healthy Eating Index (HEI)-2015 scores, and tested their associations with CRC risk.

Methods: We leveraged data among 501,892 women and 407,390 men from 6 cohorts across the United States (NIH-AARP, Multi-Ethnic Study of Atherosclerosis, Prostate, Lung, Colorectal, and Ovarian, SCCS) and …

Cross-Sectional And Longitudinal Relationships Between Abdominal Fat Depots And Cardiometabolic Risk In A Sample Of Mexican Adolescents, Luis Ortíz-Hernández, Erica G Soltero, Miguel Camejo, Jesús Valdes

Children’s Nutrition Research Center Staff Publications

Background: The relationship between abdominal fat depots and cardiometabolic risk among youth is inconclusive due to the cross-sectional nature of existing studies and limitations in assessment methods. In this study, we examined cross-sectional and longitudinal associations of subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) with cardiometabolic risk indicators among Mexican adolescents.

Methods: Participants (n = 169 at baseline and 134 at follow-up) were assessed for diastolic or systolic blood pressure (DBP or SBP), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides, glucose, and insulin. VAT and SAT were measured using magnetic resonance imaging. Measures …

A Pragmatic Guide To Data Integration For Pediatric Researchers: The Nuts And Bolts Of Mixed Methods Analysis, Kathleen A Knafl, Janet A Deatrick, Veronica M Swallow, Yelena P Wu, Debbe Thompson

Children’s Nutrition Research Center Staff Publications

Objective: To provide pragmatic guidance on data analysis, integration, and reporting guidance for investigators new to mixed methods research.

Methods: Three core mixed methods designs (convergent, explanatory sequential, and exploratory sequential) are described. Key decision points related to data integration-specifying intent, data selection, data preparation, integration strategies, use of analysis software, reporting-are explained, including comparison of decision points across the different mixed methods designs.

Results: Recommendations for addressing key decisions during analysis are provided and supported with published examples from mixed methods studies focused on pediatric populations.

Conclusions: Integration of qualitative and quantitative data is the defining characteristic of mixed …

Sustainable Community-Wide Model To Enhance Cancer Data Usage And Utility, Emily S Boja, Mousumi Ghosh, Ying Huang, Tung-Shing Mamie Lih, Rawan Shraim, Gregory Wheeler, Diana Thomas, Rakesh Khanna, Stephanie Sandor, Jinghui Zhang, Sapna Oberoi, Nicolas J Llosa, Aditya Suru, Fernanda Silva Michels, Eric Durbin, Anna Fernandez, Lucy Han, James Galbraith, Yin Lu, Brian Furner, James H Tanis, Michael Watkins, David Higgins, Gavriel Matt, Xin Zhou, Yang Li, Marcin Cieslik, Jamie Estill, Michael Sierk, Yanling Sun, Weiping Ma, Joseph Flores-Toro, Freddie Pruitt, Subhashini Jagu, Elmer A Fernández, Daniela Orschanski, Stephanie J Spielman, Jaclyn Taroni, Trinh Nguyen, Brian Capaldo, Erin Beck, Tanja Davidsen, Johanna Goderre Jones, Minghong Ward, Anne Sturcke, Jennifer M Torres Del Valle, Sean Hanlon, Danielle Daee, Brandon Wright, Nathaniel Boyd, Heather Basehore, Liang Liu, Ying Hu, Daoud Meerzaman, Huiqing Li, Ying Wu, Gregory H Reaman, Erin Rudzinski, Jack F Shern, Brigitte Widemann, Warren Kibbe, Jaime Guidry Auvil

Children’s Nutrition Research Center Staff Publications

Despite vast investments in data collection, generation, and sharing from childhood cancer studies, for example, Gabriella Miller Kids First Research Program, Childhood Cancer Data Initiative, and other efforts, secondary use of data remains a challenge especially for rare diseases. The National Cancer Institute (NCI) Office of Data Sharing (ODS) aimed to promote FAIR (Findable, Accessible, Interoperable, Reusable) data sharing practices to enhance data utility, accelerate discovery, and foster interdisciplinary collaboration. NCI ODS launched its inaugural Data Jamboree focusing on childhood cancer alongside its third Annual Symposium in September 2025. Over 120 participants with diverse backgrounds coalesced into 23 multidisciplinary teams …

Evaluating The Impact Of Telemedicine-Based Medication Education On Glycemic Control In Adult Male Veterans With Type 2 Diabetes Mellitus, Megan N. Calter

West Chester University Graduate Theses, Dissertations, and Final Projects

Veterans experience disproportionately high rates of type 2 diabetes mellitus (20.5% vs 11.6% nationally), driven by military-related factors such as PTSD, deployment-related obesity, and service-connected disabilities. At a large urban primary care clinic, 28% (40/141) of veterans with type 2 diabetes mellitus had persistently elevated HbA1c levels of ≥8%, indicating a high risk for diabetes-related complications. This quality improvement project aimed to reduce the proportion of veterans with HbA1c of ≥8% by implementing tailored telemedicine-based medication education, leveraging underutilized virtual care infrastructure to address access barriers and improve diabetes self-management. Participants received two 30-minute telemedicine medication and disease management education …

Stones, Bones, And Hormones: A Multisystem Presentation Of Primary Hyperparathyroidism Due To Parathyroid Adenoma, Gadgesh B, Varsha Tandure, Nandini K, Chandana Srinath

Digital Journal of Clinical Medicine

Primary hyperparathyroidism is an endocrine disorder characterized by excessive secretion of parathyroid hormone, most commonly due to a solitary parathyroid adenoma, resulting in hypercalcemia and multisystem involvement [1]. Although many patients are diagnosed incidentally, delayed recognition may lead to severe renal, skeletal, gastrointestinal, and cardiovascular complications.

We report the case of a 44-year-old male who presented with sepsis and acute kidney injury, later found to have hypercalcemia with nephrocalcinosis, chronic calcific pancreatitis, skeletal deformities, and markedly elevated parathyroid hormone levels. Imaging localized a parathyroid adenoma, and the patient underwent successful parathyroidectomy with significant biochemical and clinical improvement.

This case emphasizes …

Assessing Access To Orthopaedic Care For Patients With Osteogenesis Imperfecta, Annemarie K. Leonard, Kara Ayers, Lauren Faokunla, Kaeli Samson, Erika Carter, Tracy Hart, Maegen Wallace

Graduate Medical Education Research Journal

Background. Osteogenesis Imperfecta (OI) is a rare disorder caused by variations in collagen. Clinical manifestations include multiple fractures, short stature, scoliosis, blue sclera, hearing loss, and opalescent teeth. Patients often need many different medical providers frequently, which may place financial burdens on families. This study sought to identify and understand barriers to care for children with OI.

Methods. We utilized an Institutional Review Board (IRB)-approved survey for primary caregivers of children with OI. Questions included demographic data, type of health insurance, history of and reasons for insurance denials, access to multidisciplinary OI care, and travel to receive OI care. The …

Spinach (Spinacia Oleracea L) Flavonoids Are Hydrolyzed During Digestion And Their Bioaccessibility Is Under Stronger Genetic Control Than Raw Material Content, Michael P Dzakovich, Alvin L Tak, Elaine A Le, Rachel P Dang, Benjamin W Redan, Geoffrey A Dubrow

Children’s Nutrition Research Center Staff Publications

Spinach (

Sleep-Disordered Breathing Subtypes And Future Diet Quality In The Multi-Ethnic Study Of Atherosclerosis, Kaitlin S Potts, Cecilia Castro-Diehl, Tianyi Huang, Alexis C Wood, Jerome I Rotter, Stephen S Rich, Tamar Sofer, Susan Redline, Heming Wang

Children’s Nutrition Research Center Staff Publications

Objectives: Sleep-disordered breathing (SDB) and diet quality impact cardiometabolic disease, but few studies have examined if SDB influences diet quality. This study estimated the association between SDB subtypes (with and without sleepiness) and future diet quality in the Multi-Ethnic Study of Atherosclerosis.

Methods: Probable SDB was characterized by self-reported physician-diagnosed sleep apnea (PDSA) or habitual snoring and subtyped by presence or absence of sleepiness. A food frequency questionnaire measured diet 1.6 years before, and 7.8 years after SDB assessment. Diet quality was measured with the Alternate Healthy Eating Index-2010 (AHEI). Mean differences in AHEI at follow-up by SDB subtypes were …

Predicting Five-Year Comorbid Bipolar Disorder After Attention-Deficit/Hyperactivity Disorder Diagnosis: A Population-Based Machine Learning Approach, Yen-Shan Yang, Chih-Wei Hsu, Liang-Jen Wang, Kuo-Chuan Hung, Yang-Chieh Brian Chen, Chih-Sung Liang, Mu-Hong Chen

Children’s Nutrition Research Center Staff Publications

Background

Early detection and accurate prediction of bipolar disorders (BDs) comorbidity in individuals with attention-deficit/hyperactivity disorder (ADHD) are clinically critical. This study used machine-learning methods to identify features predictive of subsequent BD among patients initially diagnosed with ADHD.

Methods

We analyzed claims from the Taiwan National Health Insurance Research Database (2000–2013) and included patients aged ≥ 12 years with at least two diagnoses of ADHD. Predictor features included demographics (sex, age at ADHD onset), healthcare utilization (psychiatric outpatient visit counts), comorbidities (International Classification of Diseases–coded diagnoses), psychiatric medications (Anatomical Therapeutic Chemical–coded prescriptions), and family psychiatric history. All features were extracted …

A Class Of Benzofuranoindoline-Bearing Heptacyclic Fungal Ripps With Anticancer Activities, Qiuyue Nie, Fanglong Zhao, Xuerong Yu, Mithun C Madhusudhanan, Caleb Chang, Siting Li, Sandipan Roy Chowdhury, Bryce Kille, Andy Xu, Rory Sharkey, Chunxiao Sun, Hongzhi Zeng, Shuai Liu, Dishu Zhou, Xin Yu, Kevin Yang, Sandra A C Figueiredo, Maria Zotova, Zichen Hu, Alan Y Du, Dongyin Guan, Rui Tang, Todd Treangen, Jin Wang, Pedro N Leão, Yang Gao, Junjie Chen, Peng Liu, Hans Renata, Xue Gao

Children’s Nutrition Research Center Staff Publications

Ribosomally synthesized and post-translationally modified peptides (RiPPs) are a promising source of new pharmaceuticals, yet the therapeutic potential of fungal RiPPs remains largely underexplored. Here, we report asperigimycins as a distinct class of fungal RiPPs, featuring a unique heptacyclic scaffold consisting of a benzofuranoindoline core and three additional macrocycles, primarily assembled by six distinct fungi-specific DUF3328 oxidases. Inspired by the enhancement of anticancer activity through the N-terminal pyroglutamate in naturally occurring asperigimycins C and D, we chemically modify the inactive asperigimycin B with a series of lipid substitutions at its N-terminus. A derivative with a C-11 linear fatty …

Transcriptional Coregulator Zmiz1 Modulates Estrogen Responses That Are Essential For Healthy Endometrial Function, Sylvia C Hewitt, Frank Orellana, Ryan M Marquardt, Myeongjin Yi, Cynthia J Willson, Mark Y Chiang, Yong Song, Goutham Venkata Naga Davuluri, Christopher Day, Ramakrishna Kommagani, Joseph Rodriguez, Asgerally T Fazleabas, John P Lydon, Francesco J Demayo

Faculty, Staff and Students Publications

Estrogen is a critical regulator of endometrial health. Aberrant estrogen stimulation can result in infertility, endometrial cancer, and endometriosis. Here, we identified Zinc Finger MIZ-Type Containing 1 (Zmiz1) as a coregulator of uterine estrogen signaling. ZMIZ1 is colocalized with an estrogen receptor α–binding (ESR1-binding) super enhancer. ZMIZ1 mutations are found in endometrial cancer and its RNA levels trend toward reduction in endometrium of patients with endometriosis. ZMIZ1 is dynamically expressed in human endometrial tissues during the menstrual cycle. Disrupting ZMIZ1 in cultured human endometrial stromal cells resulted in impaired cell proliferation and decidual differentiation. Ablation of Zmiz1 using …

Mortality Among Transgender Persons: A Taiwan Matched-Population And Sibling-Comparison Cohort Study, Chih-Wei Hsu, Yang-Chieh Brian Chen, Liang-Jen Wang, Mu-Hong Chen, Yao-Hsu Yang, Chih-Sung Liang, Po-Yen Chen, Edward Chia-Cheng Lai

Children’s Nutrition Research Center Staff Publications

Background: Transgender persons have been reported to experience excess mortality, but evidence is dominated by Western cohorts and seldom addresses familial confounding.

Methods: We conducted a nationwide, retrospective cohort study using two prespecified comparison designs: matched population controls (1:4, matched on legal sex and birth date) and within-family cisgender sibling comparisons. Transgender persons were identified by ≥2 psychiatrist-recorded gender identity disorder diagnoses during 2001-2021; cohort entry required age ≥6 years. Participants were followed until death or December 31, 2022. We compared all-cause, external-cause (suicide and accidents), and internal-cause mortality using Cox regression adjusted for sociodemographics and medical comorbidity.

Findings: Among …

Concerns Regarding The Standard Deviation Of Individual Responses For Assessing Treatment Response Heterogeneity, Aaron R Caldwell, David B Allison, Andrew W Brown, Gary L Gadbury, Thirupathi Reddy Mokalla, R Drew Sayer, Andrew D Vigotsky

Children’s Nutrition Research Center Staff Publications

The estimation of treatment response heterogeneity (TRH) is increasingly important as medicine moves toward personalized approaches. While various statistical methods have been proposed to quantify TRH in parallel-group trials, the standard deviation of individual responses (SDIR) has gained prominence within physiological research. This method is intended to quantify individual response variation by comparing standard deviations of change scores between intervention and control groups. We acknowledge that SDIR represents an improvement over many other flawed approaches that often involve responder counting. However, SDIR has critical limitations: 1) it cannot overcome the fundamental problem of causal inference because the correlation between potential …

Glycerol-3-Phosphate Activates Chrebp, Fgf21 Transcription And Lipogenesis In Citrin Deficiency, Vinod Tiwari, Byungchang Jin, Olivia Sun, Edwin D J Lopez Gonzalez, Min-Hsuan Chen, Xiwei Wu, Hardik Shah, Andrew Zhang, Mark A Herman, Cassandra N Spracklen, Russell P Goodman, Charles Brenner

Faculty, Staff and Students Publications

Citrin deficiency (CD) is caused by the inactivation of SLC25A13, a mitochondrial membrane protein required to move electrons from cytosolic NADH to the mitochondrial matrix in hepatocytes. People with CD do not like sweets. Here we show that SLC25A13 loss causes the accumulation of glycerol-3-phosphate (G3P), which activates the carbohydrate response element-binding protein (ChREBP) to transcribe FGF21, which acts in the brain to restrain intake of sweets and alcohol and to transcribe key genes driving lipogenesis. Mouse and human data suggest that G3P-ChREBP is a mechanistic component of the Randle Cycle that contributes to metabolic-dysfunction-associated steatotic liver disease and forms …