Digital Commons Network^™

Glucose Uptake In Pigment Glia Suppresses Tau-Induced Inflammation And Photoreceptor Degeneration, Mikiko Oka, Sho Nakajima, Emiko Suzuki, Shinya Yamamoto, Kanae Ando

Duncan NRI Faculty and Staff Publications

Brain inflammation contributes to the pathogenesis of neurodegenerative diseases, such as Alzheimer's disease (AD). Glucose hypometabolism and glial activation are pathological features seen in AD brains; however, the connection between the two is not fully understood. Using a Drosophila model of AD, we identified that glucose metabolism in glia plays a critical role in neuroinflammation under disease conditions. Expression of human MATP (hereafter referred to as Tau) in the retinal cells, including photoreceptor neurons and pigment glia, causes photoreceptor degeneration accompanied by the formation of dark-stained round inclusion-like structures and swelling of the lamina cortex. We found that inclusion-like structures …

Gastroesophageal Reflux And Gastrointestinal Symptoms After Metabolic And Bariatric Surgery In Adolescents: An 8-Year Follow-Up Analysis, John B Rode, Suhail A Zeineddin, Jane C Khoury, Todd M Jenkins, Stephanie R Sisley, Anita P Courcoulas, Justin R Ryder, Marc P Michalsky, Thomas H Inge

Children’s Nutrition Research Center Staff Publications

Importance: Vertical sleeve gastrectomy (VSG) and Roux-en-Y gastric bypass (RYGB) are the most commonly performed metabolic and bariatric surgery (MBS) procedures in adolescents and adults. Despite their safety and effectiveness, there is concern over postoperative gastrointestinal symptoms (GIS), especially gastroesophageal reflux symptoms (GERS), in those undergoing VSG.

Objective: To evaluate the long-term prevalence of GIS in adolescents who underwent RYGB or VSG.

Design, setting, and participants: This is a prospective, multicenter, observational cohort study at five academic referral centers in the United States. Patients were enrolled from February 28, 2007, through December 30, 2011. The analysis included 228 adolescents: 161 …

Most Elderly Patients With Subclinical Hypothyroidism Do Not Need To Be Treated, Risheng Xu, Nicola Abate, Nalini Ram, Kristina Little

Faculty, Staff and Students Publications

Whether subclinical hypothyroidism should be treated in elderly patients (≥ 65 years) is controversial. The authors argue for a personalized, wait-and-see approach rather than universal treatment, pointing out that randomized clinical trials have not shown that levothyroxine treatment makes any difference in terms of hard clinical end points, quality of life, or hypothyroid symptom relief in elderly patients with this condition.

Current Burden Of Steatotic Liver Disease And Fibrosis Among Adults In The United States, 2017-2023, Donghee Kim, Pojsakorn Danpanichkul, Karn Wijarnpreecha, George Cholankeril, Rohit Loomba, Aijaz Ahmed

Faculty, Staff and Students Publications

Background/aims: Multi-society experts proposed the adoption of new terminology, metabolic dysfunctionassociated steatotic liver disease (MASLD) and steatotic liver disease (SLD). We studied the current prevalence of SLD and its subcategories in the US.

Methods: Using the recent National Health and Nutrition Examination Survey from 2017 to 2023, we analyzed data from 12,199 participants (≥18 years) who completed transient elastography. SLD and its subcategories, including MASLD, metabolic and alcohol-related liver disease (MetALD), and alcohol-related liver disease (ALD), were categorized according to consensus nomenclature.

Results: The age-adjusted prevalence of SLD (cut-off: 285 dB/m) was 35.0% (95% confidence interval [CI] 33.4-36.7). Within this …

The Association Between County-Level Social Determinants Of Health And Cardio-Kidney-Metabolic Disease Attributed All-Cause Mortality In The Us: A Cross Sectional Analysis, Antoinette Cotton, Pedro Rvo Salerno, Salil V Deo, Salim S Virani, Khurram Nasir, Ian Neeland, Sanjay Rajagopalan, Naveed Sattar, Sadeer Al-Kindi, Yakov E Elgudin

Faculty, Staff and Students Publications

Background: The American Heart Association recently defined cardio-kidney-metabolic (CKM) syndrome as the intersection between metabolic, renal, and cardiovascular disease. Understanding the contemporary estimates of CKM related mortality in the US is essential for developing targeted public interventions.

Methods: We analyzed state-level and county-level CKM-associated all-cause mortality data (2010-2019) from the CDC Wide-ranging Online Data for Epidemiologic Research (WONDER). Median and interquartile (IQR) age-adjusted mortality rates (aaMR) per 100,000 were reported and linked with a multi-component metric for social deprivation: the Social Deprivation Index (SDI: range 0 - 100) grouped as: I: 0 - 25, II: 26 - 50, III: 51 …

Acute Kidney Injury In Severe Alcohol-Associated Hepatitis Treated With Anakinra Plus Zinc Or Prednisone, Kavish R Patidar, Wanzhu Tu, Thomas G Cotter, Douglas A Simonetto, Amon Asgharpour, Muhammad Y Jan, Qing Tang, Yunpeng Yu, Yang Li, Moyinoluwa Taiwo, Prashanth Thevkar Nagesh, Srinivasan Dasarathy, Patrick S Kamath, Craig J Mcclain, Naga Chalasani, Gyongyi Szabo, Ramon Bataller, Mack Mitchell, Wajahat Z Mehal, Laura E Nagy, Vijay H Shah, Samer Gawrieh, Arun J Sanyal

Faculty, Staff and Students Publications

Background and aims: In a recent trial, patients with severe alcohol-associated hepatitis treated with anakinra plus zinc (A+Z) had lower survival and higher acute kidney injury (AKI) rates versus prednisone (PRED). We characterize the clinical factors and potential mechanisms associated with AKI development in that trial.

Approach and results: Data from 147 participants in a multicenter randomized clinical trial (74 A+Z, 73 PRED) were analyzed. AKI, AKI phenotypes, and kidney injury biomarkers were compared between participants who did/did not develop AKI in the 2 treatment arms. Multivariable competing risk analyses were performed to identify baseline risk factors for incident AKI, …

Defining The Transcriptional Basis Of Organ-Specific Endothelial Cell Specialization, Joshua D. Wythe, James F. Martin

Faculty, Staff and Students Publications

Blood vessels feature extensive phenotypic and functional differences that help them meet the unique nutritive and energetic demands of the specific organ they reside in. Profiling the chromatin and transcriptional landscape of several organs identified novel gene regulatory networks that determine endothelial cell organ specialization in mammals.

Postnatal Zika And Dengue Infection And Their Effects On Neurodevelopment Among Children Living In Rural Guatemala, Edwin J Asturias, Amy K Connery, Daniel Olson, Molly M Lamb, Alejandra Paniagua-Avila, Evan J Anderson, Chris Focht, Alison M Colbert, Muktha Natrajan, Jesse J Waggoner, Erin Scherer, D Mirella Calvimontes, Guillermo A Bolaños, Desirée Bauer, Paola Arroyave, Sara Hernández, Maria A Martinez, Aida V Ralda, Neudy Rojop, Edgar E Barrios, Andrea Chacon, Walla Dempsey, Kay M Tomashek, Wendy A Keitel, Hana M El Sahly, Flor M Muñoz

Faculty, Staff and Students Publications

Background: Prenatal Zika virus (ZIKV) infection leads to microcephaly and adverse neurodevelopment. The effects of postnatal ZIKV infection on the developing brain are unknown. We assessed the neurodevelopmental outcomes of children exposed postnatally during the ZIKV epidemic.

Methods: A prospective study enrolled infants 0-3 months of age and their mothers, and children 1.5-3.5 years of age in rural Guatemala from 2017 and were followed for 12 months until 2019. Neurodevelopment was evaluated using the Mullen Scales of Early Learning (MSEL). ZIKV and dengue virus (DENV) infections were identified by polymerase chain reaction (PCR) using active surveillance. Serological analyses, stratified by …

Preferences For Survivorship Education And Delivery Among Latino And Non-Latino Childhood Cancer Survivors And Caregivers, Omar Shakeel, Shiley Aguilar, Alicia Howell, Ashley Ikwuezunma, Olga Taylor, M Fatih Okcu, Ranjan Bista, Jill Hartley, Rodrigo Eraña, Juan Carlos Bernini, Lisa Kahalley, Michael Scheurer, Maria Monica Gramatges

Faculty, Staff and Students Publications

Purpose: To assess survivor and parent perceptions of the long-term survivor visit and preferences regarding accessing health information, survivorship education, and support networks in rural and metropolitan regions of Texas.

Methods: Leveraging the multi-institutional Survivorship and Access to Care for Latinos to Understand Disparities (SALUD) cohort, we administered a 26-item bilingual survey to adult survivors of childhood cancer and parents of younger survivors. Characteristics and responses were compared between survivors vs. parents and Latinos vs. non-Latinos using a t test or Fisher exact test. Odds ratios for the outcomes of interest were calculated with 95% confidence intervals.

Results: We received …

Differential Treatment Effects On Β-Cell Function Using Model-Based Parameters In Type 2 Diabetes: Results From The Glycemia Reduction Approaches In Diabetes: A Comparative Effectiveness Study (Grade), Kristina M Utzschneider, Mark Tripputi, Nicole M Butera, Andrea Mari, Samuel P Rosin, Mary Ann Banerji, Richard M Bergenstal, Necole Brown, Anders L Carlson, Ralph A Defronzo, Michaela R Gramzinski, Tasma Harindhanavudhi, Alexandra Kozedub, William I Sivitz, Michael W Steffes, Ashok Balasubramanyam, Neda Rasouli

Faculty, Staff and Students Publications

Objective: To evaluate how model-based parameters of β-cell function change with glucose-lowering treatment and associate with glycemic deterioration in adults with type 2 diabetes (T2D).

Research design and methods: In the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE), β-cell function parameters derived from mathematical modeling of oral glucose tolerance tests were assessed at baseline (N = 4,712) and 1, 3, and 5 years following randomization to insulin glargine, glimepiride, liraglutide, or sitagliptin, added to baseline metformin. Parameters included insulin secretion rate (ISR), glucose sensitivity (insulin response to glucose), rate sensitivity (early insulin response), and potentiation. Linear mixed-effects …

Comparison Between Dynamic Models For Predicting Response To Corticosteroids In Alcohol-Associated Hepatitis: A Global Cohort Study, Francisco Idalsoaga, Luis Antonio Díaz, Leonardo Guizzetti, Winston Dunn, Heer Mehta, Jorge Arnold, Gustavo Ayares, Rokhsana Mortuza, Gurpreet Mahli, Alvi H Islam, Shiv K Sarin, Rakhi Maiwall, Wei Zhang, Steve Qian, Douglas Simonetto, Ashwani K Singal, Mohamed A Elfeki, Carolina Ramirez-Cadiz, Joaquín Cabezas, Victor Echavarría, Meritxell Ventura Cots, María Fátima Higuera-De La Tijera, Juan G Abraldes, Mustafa Al-Karaghouli, Prasun K Jalal, Mohamad Ali Ibrahim, Guadalupe García-Tsao, Daniela Goyes, Lubomir Skladaný, Daniel J Havaj, Karolina Sulejova, Svetlana Adamcova Selcanova, Diego Rincón, Vijay H Shah, Patrick S Kamath, Marco Arrese, Ramon Bataller, Juan Pablo Arab

Faculty, Staff and Students Publications

Several dynamic models predict mortality and corticosteroid response in alcohol-associated hepatitis (AH), yet no consensus exists on the most effective model. This study aimed to assess predictive models for corticosteroid response and short-term mortality in severe AH within a global cohort. We conducted a multi-national study of patients with severe AH treated with corticosteroids for at least 7 days, enrolled between 2009 and 2019. Dynamic models-Lille-4, Lille-7, trajectory of serum bilirubin (TSB), and neutrophil-to-lymphocyte ratio (NLR)-were used to estimate 30- and 90-day mortality. Lille-7 demonstrated the highest accuracy for both 30- and 90-day mortality.

Moderate Alcohol-Associated Hepatitis: A Real-World Multicenter Study, Francisco Idalsoaga, Luis Antonio Díaz, Winston Dunn, Heer Mehta, Karen Muñoz, Vicente Caldentey, Jorge Arnold, Gustavo Ayares, Rokhsana Mortuza, Shiv K Sarin, Rakhi Maiwall, Wei Zhang, Steve Qian, Douglas Simonetto, Ashwani K Singal, Mohamed A Elfeki, Carolina Ramirez-Cadiz, Gurpreet Malhi, Adan Ahmed, Hoomam Homsi, Zinia Abid, Joaquín Cabezas, Victor Echavarría, Maria Poca, German Soriano, Berta Cuyas, Meritxell Ventura Cots, María Fátima Higuera-De La Tijera, Maria Ayala-Valverde, Diego Perez, Jaime Gomez, Juan G Abraldes, Mustafa Al-Karaghouli, Prasun K Jalal, Mohamad Ali Ibrahim, Guadalupe García-Tsao, Daniela Goyes, Lubomir Skladaný, Daniel J Havaj, Karolina Sulejova, Svetlana Adamcova Selcanova, Diego Rincón, Kristina R Chacko, Juan C Restrepo, Pamela Yaquich, Luis G Toro, Vijay Shah, Marco Arrese, Patrick S Kamath, Ramon Bataller, Juan Pablo Arab

Faculty, Staff and Students Publications

Background: Severe alcohol-associated hepatitis (sAH) is a well-characterized disease with high short-term mortality. However, there is limited research on those with a "less severe condition" (moderate AH). This study aims to characterize in-depth patients with moderate AH (mAH), including the performance of mortality scoring systems, key prognostic factors, and survival over time.

Methods: A multicenter retrospective cohort study (2009-2019) included patients with mAH (MELD score ≤20 at admission). Cox regression and receiver operating characteristic curves with AUC were used for analysis.

Results: We included 1845 patients with AH (20 centers, 8 countries) between 2009 and 2019. mAH was defined as …

Postvaccination Immunogenicity Among Pediatric Solid Organ Transplant Recipients, Amy G Feldman, Brenda L Beaty, Jose A Ferrolino, Gabriela Maron, Saira A Ali, Leandra Bitterfeld, Adam Blatt, Mary Alice Boulware, Kathleen M Campbell, Emily Carr, Benhur Cetin, Shelley Chapman, Yeh-Chung Chang, Ryan Cunningham, Ronald H Dallas, Keerti L Dantuluri, Bryanna N Domenick, Noelle H Ebel, Scott Elisofon, Rima Fawaz, Marc Foca, Hayley A Gans, Vani V Gopalareddy, Nitika A Gupta, Katherine Harmann, Jessica Hollenbeck, Anna R Huppler, Catalina Jaramillo, Nagraj Kasi, Nanda Kerkar, Stacee Lerret, Steven J Lobritto, M James Lopez, Alisha Mavis, Sonia Mehra, Sindhu Mohandas, Flor M Munoz, Krupa R Mysore, Nadia Ovchinsky, Kerrigan Perkins, Stacy Postma, Lauren Pratscher, Elizabeth B Rand, Regina K Rowe, Daniel Ruderfer, Danielle Schultz, Katherine Sear, Megan L Sell, Tanvi S Sharma, Janis Stoll, Jerry Turner, Kristen G Valencia Deray, Dominique Villarin, Carly Weaver, Phoebe Wood, Olivia Woodford-Berry, George Yanni, Lara A Danziger-Isakov

Faculty, Staff and Students Publications

This cohort study assesses the protection provided by live attenuated viral vaccines among a pediatric population of solid organ transplant recipients 1 year after vaccination.

Subacute Neuropathy Post-Liver Transplantation In Zellweger Spectrum Disorder: A Case Report, Clarissa Gonzalez, Madelyn J Cohen, Juhee Hong, Daniel Calame, Kavitha Marri, Sanjiv Harpavat, Michael F Wangler, Krupa Mysore

Faculty, Staff and Students Publications

Peroxisome biogenesis disorders-Zellweger spectrum disorder (PBD-ZSD) is a rare genetic disease caused by mutations in the genes involved in peroxisome biogenesis. PBD-ZSD presentations vary in severity, and treatment of PBD-ZSD remains supportive focused on specific complications. A few reported cases of the use of liver transplantation to treat either neurological symptoms or liver dysfunction and cirrhosis in PBD-ZSD have been published. In this case report, we document the course of a 16-year-old boy diagnosed with PBD-ZSD and a delayed and unexpected neuropathy that developed after undergoing orthotopic liver transplantation (OLT) for which the indication was liver cirrhosis. Following OLT, the …

Fogarty-Funded Research Ethics Education In Latin America And The Caribbean: Progress Despite Ongoing Challenges, Timothy Daly, Ignacio Mastroleo, Luis L García Valiña, Irene Melamed, María Florencia Santi, Theresa J Ochoa, Manuela Fernández Pinto, Paul J Cummins, Bernardo García Camino, Cheryl Macpherson, Elizabeth Heitman, Florencia Luna

Faculty, Staff and Student Publications

Ten years have passed since the last regional assessment of the state of Fogarty International Center-funded research ethics education and challenges facing research ethics in Latin America and the Caribbean basin. Program directors and faculty from four international research ethics education programs met in Spring 2024 to discuss their progress, challenges, and future priorities. The themes that emerged from these discussions were the structural difficulties faced by regional ethicists, the use of pedagogical innovations to mitigate different barriers faced by fellows, and the need to anticipate future challenges for the region including climate change.

Walking Interventions And Cognitive Health In Older Adults: A Systematic Review Of Randomized Controlled Trials, Jongwon Lee, Delia West, Christine Pellegrini, Jingkai Wei, Sara Wilcox, Jean Neils-Strunjas, A Caroline Rudisill, Daniela B Friedman, David X Marquez, Jenna Dzwierzynski, Joyce Balls-Berry, Rachelle Gajadhar, Chih-Hsiang Yang

Faculty, Staff and Student Publications

ObjectiveThis systematic review summarizes the effectiveness and the dose of walking interventions on specific cognition domains in older adults, including executive function, memory, attention, processing speed, and global cognition.Data sourcePublished randomized controlled trials in PubMed, Embase, and Web of Science until 10 May 2023.Study Inclusion and Exclusion CriteriaStudies include older adults without Alzheimer's or related dementias, involving a walking intervention and performance-based neuropsychological assessments for executive function, memory, processing speed, attention, or global cognition.Data ExtractionTwo independent research assistants reviewed 8424 studies and included 17 studies.Data SynthesisParticipant demographics, intervention features (type, intensity, time, frequency, duration, format, and context), cognitive assessment tools, …

Video Discharge Instructions Increase Patient Understanding For Office-Based Procedures: A Randomized Controlled Study, Jenna Bates Maffei, Jeffrey J Song, Gal Saffati, Mohit Khera

Faculty, Staff and Students Publications

Background: Health literacy significantly influences healthcare outcomes, with poor literacy leading to worse quality of life, increased mortality, and higher readmission rates. Recent efforts to improve post-encounter education include structured teach-back methods, patient preference assessments, and standardized discharge instructions. Studies in emergency departments have shown that incorporating video discharge instructions enhances patient understanding and retention of care information. To address the gap in urology, this study aims to evaluate patient comprehension and satisfaction with video discharge instructions following clinic-based vasectomy procedures.

Methods: We performed an Institutional Review Board approved (#H-51614) unblinded randomized controlled study with written consent from each participant. …

Effects Of Prebiotic Phytocompound Administration In Gestational Diabetic Dams And Its Influence On Offspring Cognitive Outcomes, Gayathri Jagadeesan, Tushar K Das, Jennifer M Mendoza, Ghalya Alrousan, Maria P Blasco-Conesa, Parimelazhagan Thangaraj, Bhanu Priya Ganesh

Faculty, Staff and Student Publications

Gestational diabetes mellitus (GD)-induced gut dysbiosis in pregnant mothers may increase the risk of cognitive impairment and neurological disorders in both the mother and offspring as they age. Restoring gut balance could improve cognitive outcomes for both. Despite advancements in GD treatment, side effects have increased, and long-term neurocognitive impacts on offspring born to GD mothers remain underexplored. This study uses a GD mouse model, inducing pancreatic dysfunction in 3-month-old pregnant C57BL/6J mice with Streptozotocin. The efficacy and mechanism of the prebiotic phytocompound green leaf extract (

Assessing Cancer Therapeutic Efficacy In Vivo Using [2h7]Glucose Deuterium Metabolic Imaging, Mario C Chang, Vinay R Malut, Rohit Mahar, Anna Rushin, Marc A Mcleod, Geraldine L Pierre, Indu R Malut, Stephen J Staklinski, Max E Glanz, Mukundan Ragavan, Gaurav Sharma, Manoj Madheswaran, Arshee Badar, Aparna D Rao, Brian K Law, Michael S Kilberg, James H P Collins, Vikram D Kodibagkar, James A Bankson, Ralph J Deberardinis, Matthew E Merritt

Faculty, Staff and Student Publications

Metabolic imaging produces powerful visual assessments of organ function in vivo. Current techniques can be improved by safely increasing metabolic contrast. The gold standard, 2-[18F]fluorodeoxyglucose-positron emission tomography (FDG-PET) imaging, is limited by radioactive exposure and sparse assessment of metabolism beyond glucose uptake and retention. Deuterium magnetic resonance imaging (DMRI) with [6,6-2H2]glucose is nonradioactive, achieves tumor metabolic contrast, but can be improved by enriched contrast from deuterated water (HDO) based imaging. Here, we developed a DMRI protocol employing [2H7]glucose. Imaging 2H-signal and measuring HDO production in tumor-bearing mice detected differential glucose utilization across baseline tumors, tumors treated with vehicle control or …

Liver Transplantation In 3 Cholestatic Infants With History Of Covid Exposure, Shruti Sakhuja, Kalyani R Patel, Matthew Goss, Flor M Munoz, Garrett Wortham, Megan Crawford, John A Goss, Nhu Thao Galvan

Faculty, Staff and Students Publications

The COVID-19 pandemic presents several challenges during pregnancy including thromboembolic complications, direct placental infection, transplacental transmission, and systemic hyperinflammatory state. The liver is the second most commonly affected organ in SARS-CoV-2 infection after the lungs. Mechanisms of liver injury in COVID-19 patients can include: direct viral cytopathic effect, worsening of underlying liver disease, cytokine storm, hypoxic ischemic injury, and cholangiopathy leading to persistent marked cholestasis. Here we describe 3 infants at Texas Children's Hospital with perinatal SARS-CoV-2 exposure with persistent cholestasis and histologic evidence of extrahepatic biliary obstruction suggesting underlying biliary atresia (BA) with some atypical features possibly exacerbated by …

Association Of Parental Oral Health Knowledge And Self-Efficacy With Early Childhood Caries And Oral Health Quality Of Life In Texas Schoolchildren, Shreela V Sharma, Jeanette E Deason, Mengxi Wang, Alejandra Garcia-Quintana, Ru-Jye Chuang, Kila Johnson, Shalisa Garner, Steven Kelder, Jose-Miguel Yamal

Faculty, Staff and Student Publications

Improving children's oral health is a national priority. Parental knowledge and self-efficacy influence children's health behaviors; however, the relationship between parental oral health-related knowledge, self-efficacy, child oral health-related quality of life (OHQoL), and dental caries remains unclear, especially among low-income, ethnically diverse U.S. families. This study assesses the relationship between parental oral health-related knowledge, self-efficacy, child dental caries, and OHQoL. This cross-sectional seco ndary analysis uses baseline data from a school-based cluster-randomized controlled trial among children (kindergarten-second grade). Dental assessments were conducted using the International Caries Detection and Assessment System (ICDAS) on site in schools at baseline (n = 34 …

The Feasibility And Safety Of Robot-Assisted Vaginal Natural Orifice Transluminal Endoscopic Surgery (Ra-Vnotes) For Gynecologic Disease: 298-Case Series, Qiannan Yang, Daniel Y Lovell, Yingchun Ma, Chunhua Zhang, Xiaoming Guan

Faculty, Staff and Students Publications

Objectives: To explore the feasibility and surgical outcomes of robot-assisted vaginal natural orifice transluminal endoscopic surgery (RA-vNOTES) for women suffering from gynecologic disease.

Methods: We performed an observational study reporting and analyzing the perioperative outcomes of 298 patients with gynecologic disease who underwent RA-vNOTES in a single institution from June 2019 to August 2024.

Results: A total of 298 patients with a median age of 41 years and median body mass index of 29 kg/m2 underwent RA-vNOTES. The primary indications for surgery were endometriosis (43.62%), chronic pelvic pain (11.07%), abnormal uterine bleeding (20.81%), and uterine leiomyomata (14.77%). A total of …

Protocol For Unlocking Alternative Polyadenylation Insights From Bulk Rna-Seq Data With Polyaminer-Bulk, Venkata Jonnakuti, Sriya Jonnakuti, Hari Krishna Yalamanchili

Duncan NRI Faculty and Staff Publications

PolyAMiner-Bulk, a deep-learning-based algorithm to decode alternative polyadenylation (APA) dynamics from bulk RNA sequencing (RNA-seq) data, enables scientists to identify and quantify APA events from processed bulk RNA-seq data. The protocol allows researchers to explore differential APA usage between two conditions and gain a better understanding of post-transcriptional regulatory mechanisms. The major steps involve input data preparation, executing PolyAMiner-Bulk, and interpreting the results. A basic familiarity with pre-processing bulk RNA-seq data and command-line tools is suggested.

For complete details on the use and execution of this protocol, please refer to Jonnakuti et al.¹

Neighborhood Disadvantage And Inequities In Access To Preemptive And Living Kidney Transplantation, Brandon M Fairless, Oluwatunmise A Fawole, Duc T Nguyen, Ankona Banerjee, Kenneth J Nobleza, Abiodun O Oluyomi, Omar Rosales, Jayna M Dave, Elizabeth A Onugha

Children’s Nutrition Research Center Staff Publications

Key Points:

1. Pediatric patients residing in low-resource neighborhoods experienced lower rates of preemptive and living donor kidney transplantation.

2. Household-level factors (single-parent, non-English primary language, and receiving government assistance) may also affect the type of transplant received.

3. Area Deprivation Index scores offer an objective way to quantify neighborhood-level disadvantage and can enhance pretransplant screening.

Background: Living donor kidney transplant (LDKT) generally results in better outcomes than deceased donor kidney transplant (DDKT). Preemptive kidney transplant (KT) allows patients to bypass undergoing maintenance dialysis and is associated with improved patient and graft survival. Studies in the US pediatric population have shown racial-ethnic disparities …

Adipose Progenitor Cell-Derived Extracellular Vesicles Suppress Macrophage M1 Program To Alleviate Midlife Obesity, Qing Zhou, Jia Gao, Guorao Wu, Chenwei Wang, Yan Yang, Teng Huang, Yi Wang, Tiantian Yue, Zhichao Gao, Hao Xie, Fei Xiong, Ke Xiang, Tuying Yong, Wanguang Zhang, Tongtong Zhang, Wen Kong, Cai Chen, Shu Zhang, Qilin Yu, Xuemei Fan, Shiwei Liu, Yanjun Liu, Cong-Yi Wang

Children’s Nutrition Research Center Staff Publications

Among different age groups, middle-aged individuals are particularly susceptible to obesity, with a 22% higher risk of all-cause mortality. However, the underlying mechanisms remain unclear. In this study, we identify adipose progenitor cells (APCs) in the white adipose tissue (WAT) of middle-aged subjects as potential causes of midlife obesity. Specifically, the extracellular vesicles (EVs) derived from APCs display an impaired ability to mitigate the inflammaging of adipose tissue macrophages (ATMs) in middle-aged individuals. Mechanistically, these EVs, lacking miR-145-5p, fail to suppress the expression of L-selectin in ATMs, thereby facilitating their M1 program via the NF-κB signaling pathway. In contrast, EVs …

Nutritional Status, Social Determinants Of Health And Clinical Outcomes In Critically Ill Children, Yash Desai, Andrea Marroquín, Paola Hong-Zhu, Nicole Knebusch, Stephanie Vazquez, Marwa Mansour, Thomas P Fogarty, M Hossein Tcharmtchi, Fernando Stein, Jorge A Coss-Bu

Faculty, Staff and Students Publications

Introduction: Childhood malnutrition remains a risk factor for morbidity and mortality. Children admitted to the Pediatric Intensive Care Unit (PICU) are at a higher risk of worsening nutritional status with adverse clinical outcomes. The burden of malnutrition is strongly linked to various well-defined social determinants of health, including race, socioeconomic status, and geography, as these factors influence household food insecurity. This study aimed to analyze the interrelationships of nutritional status, social determinants of health, and health outcomes in critically ill children.

Methods: Retrospective cohort study of 6418 critically ill children admitted to PICU from January 2014 to December 2017. Demographic …

Improving Dietary Supplement Information Retrieval: Development Of A Retrieval-Augmented Generation System With Large Language Models, Yu Hou, Jeffrey R Bishop, Hongfang Liu, Rui Zhang

Faculty, Staff and Student Publications

Background: Dietary supplements (DSs) are widely used to improve health and nutrition, but challenges related to misinformation, safety, and efficacy persist due to less stringent regulations compared with pharmaceuticals. Accurate and reliable DS information is critical for both consumers and health care providers to make informed decisions.

Objective: This study aimed to enhance DS-related question answering by integrating an advanced retrieval-augmented generation (RAG) system with the integrated Dietary Supplement Knowledgebase 2.0 (iDISK2.0), a dietary supplement knowledge base, to improve accuracy and reliability.

Methods: We developed iDISK2.0 by integrating updated data from authoritative sources, including the Natural Medicines Comprehensive Database, the …

Molecular Assays For The Diagnosis Of Sepsis In Neonates: A Diagnostic Test Accuracy Review, Thomas H Dierikx, Douwe H Visser, Tim De Meij, James Versalovic, Mariska Mg Leeflang, Chris Cooper, Mohan Pammi

Faculty, Staff and Students Publications

Background: Microbial cultures for diagnosis of neonatal sepsis have low sensitivity and reporting delay. Advances in molecular microbiology have fostered new molecular assays that are rapid and may improve neonatal outcomes.

Objectives: To assess the diagnostic accuracy of various molecular methods for the diagnosis of culture-positive bacterial and fungal sepsis in neonates and to explore heterogeneity among studies by analyzing subgroups classified by gestational age and type of sepsis onset and compare molecular tests with one another.

Search methods: We searched CENTRAL, MEDLINE, Embase and trial registries in August 2023. We checked reference lists of included studies and systematic reviews …

Emerging Clostridioides Difficile Ribotypes Have Divergent Metabolic Phenotypes, Firas S Midani, Heather A Danhof, Nathanael Mathew, Colleen K Ardis, Kevin W Garey, Jennifer K Spinler, Robert A Britton

Faculty, Staff and Students Publications

Clostridioides difficile is a gram-positive spore-forming pathogen that commonly causes diarrheal infections in the developed world. Although C. difficile is a genetically diverse species, certain ribotypes are overrepresented in human infections, and it is unclear if metabolic adaptations are essential for the emergence of these epidemic ribotypes. To identify ribotype-specific metabolic differences, we therefore tested carbon substrate utilization by 88 C. difficile isolates and looked for differences in growth between 22 ribotypes. As expected, C. difficile was capable of growing on a variety of carbon substrates. Further, C. difficile strains clustered by phylogenetic relationship and displayed ribotype-specific and clade-specific …

Genetic Associations With C-Peptide Levels Before Type 1 Diabetes Diagnosis In At-Risk Relatives, Taylor M Triolo, Hemang M Parikh, Mustafa Tosur, Lauric A Ferrat, Lu You, Peter A Gottlieb, Richard A Oram, Suna Onengut-Gumuscu, Jeffrey P Krischer, Stephen S Rich, Andrea K Steck, Maria J Redondo

Children’s Nutrition Research Center Staff Publications

Objective: We sought to determine whether the type 1 diabetes genetic risk score-2 (T1D-GRS2) and single nucleotide polymorphisms are associated with C-peptide preservation before type 1 diabetes diagnosis.

Methods: We conducted a retrospective analysis of 713 autoantibody-positive participants who developed type 1 diabetes in the TrialNet Pathway to Prevention Study who had T1DExomeChip data. We evaluated the relationships of 16 known single nucleotide polymorphisms and T1D-GRS2 with area under the curve (AUC) C-peptide levels during oral glucose tolerance tests conducted in the 9 months before diagnosis.

Results: Higher T1D-GRS2 was associated with lower C-peptide AUC in the 9 months before …