Digital Commons Network^™

Placental Clues To Congenital Heart Disease: A Modeling Approach, Ashley S. Howard, Selina M. Tucker, Kaela Varberg

Manuscripts, Articles, Book Chapters and Other Papers

Congenital heart disease (CHD) remains the most common birth defect and a leading contributor to global infant morbidity and mortality. Early diagnosis improves outcomes, yet current screening methods frequently miss CHD during routine prenatal screening. The placenta, which develops in parallel with the fetal heart and shares critical molecular pathways, represents an underexplored diagnostic tissue. We highlight clinical, epidemiological, and mechanistic insights that link placental abnormalities to CHD and explore how imaging, in vitro models, and multiomics can improve our understanding of the placenta–heart axis. Leveraging these tools will offer opportunities for earlier CHD detection and illuminate avenues for intervention …

Defining The Society Of Pediatric Liver Transplantation (Split) Research Agenda: A Delphi Consensus Project., Sharad I. Wadhwani, Pooja Reddy Spector, Amy G. Feldman, Katryn N. Furuya, Kayla Hartjes, Chaowapong Jarasvaraparn, Beau Kelly, Stacee M. Lerret, Krupa Mysore, Arti Pawaria, Philip Rosenthal, Amy Shui, Voytek Slowik, Sarah Taylor, Jennifer Vittorio, Pamela L. Valentino, Society Of Pediatric Liver Transplantation (Split)

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Despite major advances in surgical and medical management, only one-third of pediatric liver transplant (LT) recipients remain morbidity-free at 10 years. The Society of Pediatric Liver Transplantation (SPLIT) published a research agenda over 10 years ago, and much progress has been made since then. An updated consensus-driven SPLIT research agenda could guide future research and funding priorities. We aimed to identify and prioritize key research needs across the continuum of pediatric LT care using a modified Delphi consensus approach.

METHODS: We conducted a three-round modified Delphi process among SPLIT members. In round 1, participants submitted open-ended research priorities. In …

Impact Of Cyp2d6 Genotype And Inhibitor Use On Risperidone Metabolism In Children: Functional Insights Into The *17 And *29 Alleles., Matthew H. Bennett, Ethan A. Poweleit, Samuel E. Vaughn, Brandon Retke, Paul C. Toren, Jeffrey R. Strawn, Laura Ramsey

Manuscripts, Articles, Book Chapters and Other Papers

Risperidone, an atypical antipsychotic, is increasingly prescribed in pediatric patients with psychiatric disorders. It is primarily metabolized by CYP2D6 to 9-hydroxyrisperidone, an active metabolite associated with a higher risk of adverse effects. The CYP2D6*17 and *29 alleles are prevalent in individuals of African ancestry and less studied than variants found in European ancestry individuals. This knowledge gap contributes to differences in health outcomes in individuals of non-European origin. The primary objective of this study is to replicate recently identified risperidone-specific activity for the CYP2D6*17 and *29 alleles. During psychiatric hospitalization, CYP2D6 was genotyped as part of routine care. Remnant plasma …

Effect Of Dental Treatments On Reduction Of Preterm Birth: A Systematic Review And Meta-Analysis, Camille Thomas, Shakil Ahmed, Vincenzo Berghella, Romina Brignardello-Petersen, Mohamed El-Rabbany, Catherine Devion, Stefania Ronzoni

Department of Obstetrics and Gynecology Faculty Papers

OBJECTIVE: Periodontal disease is associated with increased risk of preterm birth. Effective management during pregnancy may reduce preterm birth, though clinical trial evidence has been inconsistent. This study aimed to assess whether treating dental disease during pregnancy reduces preterm birth.

DATA SOURCES: A systematic search was performed of EMBASE, MEDLINE, PubMed, Cochrane Library, and trial registries up to December 2023 and re-run in January 2025.

STUDY ELIGIBILITY CRITERIA: Randomized controlled trials (RCTs) enrolling pregnant persons with any dental disease randomized to receive dental treatment vs no treatment were included. No language restriction was applied.

STUDY APPRAISAL AND SYNTHESIS METHODS: Data …

Empirical Comparisons Of Partial Dimension Reduction Algorithms In High-Dimensional Regression, Nathan Greenfield

Master's Theses

In high-dimensional regression problems, dimension reduction methods are often used to address the challenges of multicollinearity and estimation instability. Partial dimension reduction extends these ideas by applying dimension reduction to a subset of the predictors, while the remaining predictors are modeled without compression. This approach is particularly useful when it is important to retain variability and interpretability in certain predictors.

This thesis investigates the empirical performance of partial dimension reduction algorithms and introduces a novel algorithm, Iterative Partial Residual (IPR). Two algorithms are considered: a baseline algorithm, Marginal Residual (MR), and the proposed IPR method. Their predictive performance is evaluated …

Impact Of Femalized Kinesthetic Learning Model On African American Middle School Girls’ Career Interest, Mercy F. Fash, Andrea Ofori-Boadu

Journal of Global Education and Research

Engaging African American middle school girls in out-of-school-time (OST) Architecture, Engineering, and Construction (AEC) programs can boost interest in male-dominated AEC careers. This study adopts Lent’s Social Cognitive Career Theory to evaluate the impact of an OST feminized AEC kinesthetic learning model (fAEC-KLM) on the career interests of this demographic. Through a qualitative research approach, fourteen (14) African American middle school girls from Guilford County, NC, completed pre- and post-interviews on how fAEC-KLM interactions influenced their AEC career interests. Inductive thematic analysis was carried out on transcribed interviews. Results show that effective components, such as lectures on AEC, bridge construction …

Development Of An Automated Platform For Cell Biology Experiments, Dipendra Nepal

Shelby Hall Graduate Research Forum Posters

Cell biology experiments involve repetitive tasks such as pipetting, sample preparation, and imaging, which are typically performed manually. These manual processes can introduce variability, reduce efficiency, and increase the cost of biomedical research. To address these challenges, our lab is developing a modular robotic platform, iEye™, to automate key steps in cell biology workflows [1]. The system is designed as self-contained modules, allowing flexible development and integration of different functionalities. In this work, we focus on a sample preparation module that integrates a 6-degree-of-freedom robotic arm, a motorized stage, and a pneumatic pipetter. This module is being developed to automate …

Trophic Structure And Mercury Bioaccumulation In Walleye And Yellow Perch In The Upper And Lower Red Lake Basins, Marissa Pribyl

Biology Graduate Theses

Mercury is a persistent global contaminant that biomagnifies through aquatic food webs, with dietary and environmental factors serving as the primary drivers of accumulation in fishes. Trophic structure and methylmercury dynamics in Walleye (ogaa; Sander vitreus) and Yellow Perch (asaawens; Perca flavescens) were investigated in the Upper and Lower Red Lake basins in Red Lake, Minnesota, during 2024-2025. Diets of Walleye and Yellow Perch were assessed through stomach dissections, and tissue samples from both species were analyzed for total mercury concentrations. Additional analyses included shiners (gigoozens; Notropis spp., Hudsonius spp.) along with a variety of freshwater fish and …

The Filamentous Ultrastructure Of The Popz Condensate Is Required For Its Cellular Function, Daniel Scholl, Tumara Boyd, Andrew P Latham, Alexandra Salazar, Asma M A M Khan, Steven Boeynaems, Alex S Holehouse, Gabriel C Lander, Andrej Sali, Donghyun Park, Ashok A Deniz, Keren Lasker

Duncan NRI Faculty and Staff Publications

Biomolecular condensates have key roles in regulating cellular processes. Yet, the relationship between atomic features and condensate function remains poorly understood. We studied this relationship using the polar organizing protein Z (PopZ). Here, we revealed hierarchical assembly of PopZ into a filamentous condensate by integrating cryo-electron tomography, biochemistry, single-molecule techniques and molecular dynamics simulations. The PopZ helical domain drives filamentation and condensation, while the disordered region inhibits them. Phase-dependent conformational changes prevent interfilament contacts in the dilute phase and expose client-binding sites in the dense phase. Perturbing filament formation in vitro alters the dynamics of scaffold and client proteins and …

Non-Synaptic Function And Localization Of Syntaxin-Binding Protein 1 In A Mouse Model Of Stxbp1-Related Epileptic Encephalopathy, Tao Yang, Rajat Banerjee, Yamei Deng, Sheetal Jahagirdar, Joo Hyun Kim, Wu Chen, Mingshan Xue, Alexey I Nesvizhskii, Michael D Uhler, Jack M Parent, Yu Wang

Duncan NRI Faculty and Staff Publications

Objective: De novo mutations in the syntaxin-binding protein 1 (STXBP1), encoded by STXBP1, are among the most prevalent causes of variable neurodevelopmental disorders, including epileptic encephalopathy, developmental delay, and movement disorders. Although STXBP1 has been proposed as a critical presynaptic protein controlling synaptic vesicle exocytosis, clinical phenotypes also suggest that its biological function could be more diverse.

Methods: The expression pattern of STXBP1 was studied using immunostaining in vitro and in vivo. Synaptosome isolation was performed to investigate the synaptic and non-synaptic localization of STXBP1 in the brain. STXBP1 immunoprecipitation followed by mass spectrometry (MS) was conducted to identify protein …

Age-Specific Concentrations And Seroprevalence Of Antibodies Against Salmonella Enteritidis (O:9) And Salmonella Typhimurium (O:4,5) Across Three Sites In Kenya., Esther Muthumbi, Sean Elias, Alfred Mwanzu, Agnes Mutiso, Perpetual Wanjiku, Cecilia Mbae, Godfrey Bigogo, Jennifer Verani, Stefan Flasche, Samuel Kariuki

Population Health, East Africa

Background Seroprevalence studies can indicate the age distribution of first infection with nontyphoidal Salmonella and estimate the rate of infection by age.

Method We collected 1254 paired samples of serum and stool from healthy children and adults in Kilifi, Nairobi, and Siaya counties in Kenya, areas of low, medium, and high incidence of invasive nontyphoidal Salmonella disease, respectively. We quantified the age- and site-specific geometric mean concentrations (GMCs) of IgG and IgA antibodies against S Enteritidis O-antigen (O:9, serogroup D) and S Typhimurium O-antigen (O:4,5, serogroup B) using an in-house standardized enzyme-linked immunosorbent assay. Serum concentrations were estimated against a …

Awarded Research Grants As A Pathway To Sustainable Development Goals, Maha Inam, Salim S. Virani, Melaine D'Cruze, Veronica Robi, Peter Gatiti, Anil Khamis

Population Health, East Africa

The United Nations Sustainable Development Goals (SDGs) are a set of global goals that provide an agenda for sustainable growth and development across all sectors and disciplines. However, the contribution of academic institutions from the developing world towards the SDGs has not received adequate attention from the scientific community. A review of all the awarded grants in 2022 and 2023 at an international academic institution was conducted. The objectives outlined in the grant proposals were used to map the SDGs accordingly. A quantitative frequency analysis was conducted to tabulate the results. A total of 293 grants obtained in 2022 and …

Stepreg: A Comprehensive And Intuitive R Package For Stepwise Regression Analysis, Junhui Li, Kai Hu, Xiaohuan Lu, Cesar B. Sotelo, Sushmita Nayak, Michael A. Lodato, Wenxin Liu, Lihua Julie Zhu

Student Publications [Scholarly]

Stepwise regression remains widely used for model selection, yet the field lacks a comprehensive, well-documented tool that supports diverse model families and selection strategies, implements multiple information criteria, and addresses overfitting and post-selection inference. We present StepReg, an R package that unifies stepwise selection across linear, generalized linear (e.g., logistic, Poisson, Gamma, negative binomial), and Cox models, supporting forward, backward, bidirectional, and best-subset search under various information criteria. StepReg also supports multivariate multiple linear stepwise regression, enabling simultaneous modeling of multiple dependent variables. Users can explore multiple strategies and information criteria within a single function call, and optionally combine them …

Pharmacokinetic Modeling Strategies For Dynamic Hyperpolarized Urea Imaging, Keith A Michel, Collin J Harlan, Christopher M Walker, Matthew E Merritt, Yunyun Chen, Stephen Y Lai, James A Bankson

Faculty, Staff and Student Publications

Purpose: To evaluate pharmacokinetic modeling methods for quantification of tissue perfusion/permeability with hyperpolarized 13C urea.

Methods: Three models for quantitative analysis of dynamic HP urea imaging data were proposed and evaluated in numerical simulations and a thyroid cancer mouse model. A multicompartment model resembling the extended Tofts model for DCE-MRI (Model I) and two simplified models were used. The simplified models each eliminate a volume parameter representing vascular (Model II) or impermeable cellular space (Model III). Signal curves were generated from Model I, and models were fit to these synthetic data to quantify the effects of acquisition settings, bias in …

Impact Of Cyp2d6 Genotype And Inhibitor Use On Risperidone Metabolism In Children: Functional Insights Into The *17 And *29 Alleles, Matthew H. Bennett, Ethan A. Poweleit, Samuel E. Vaughn, Brandon Retke, Paul Toren, Jeffrey R. Strawn, Laura B. Ramsey

Student Publications

Risperidone, an atypical antipsychotic, is increasingly prescribed in pediatric patients with psychiatric disorders. It is primarily metabolized by CYP2D6 to 9-hydroxyrisperidone, an active metabolite associated with a higher risk of adverse effects. The CYP2D6*17 and *29 alleles are prevalent in individuals of African ancestry and less studied than variants found in European ancestry individuals. This knowledge gap contributes to differences in health outcomes in individuals of non-European origin. The primary objective of this study is to replicate recently identified risperidone-specific activity for the CYP2D6*17 and *29 alleles. During psychiatric hospitalization, CYP2D6 was genotyped as part of routine care. Remnant plasma …

Validation And Longitudinal Trajectory Analysis Of An Ai-Based Ecg Model For Aortic Stenosis: From Community Screening To Pre-Ta\Vr Risk Stratification, Matthew W Segar, Kaleb D Lambeth, Alexander Postalian, Stephanie Coulter, Jasen Gilge, Naveed Razvi, Mohammad Saeed, Robert D Paisley, Ambarish Pandey, Mehdi Razavi

Faculty, Staff and Students Publications

Aims: Early aortic stenosis (AS) detection remains challenging, with many patients presenting late when left ventricular dysfunction may be irreversible. We evaluated whether longitudinal AI-enhanced ECG patterns can predict outcomes years before intervention and assessed the community screening potential of the AK-AVS model.

Methods and results: We conducted two complementary analyses: (1) community validation of the AK-AVS model in 3632 cardiovascular disease-free ARIC participants, and (2) longitudinal trajectory analysis of 7860 ECGs from 2040 TAVR recipients collected up to 10 years pre-procedure. Unsupervised clustering identified distinct AK-AVS trajectories, with mortality associations assessed using Cox regression and net reclassification improvement. In …

Rab4 Spatially And Functionally Converges With Rab7 In The Degradative Endolysosomal Network, Stephen M Farmer, Shiyu Xu, Yue Yu, Xin Ye, Haoyi Yang, Jing Cai, Beatriz Rios, Wen-Wen Lin, Daniela Covarrubias, Vicky Chuong, Lili Ye, German Zylberberg, Charissa Wang, Erin Furr-Stimming, Qingchun Tong, Oguz Kanca, Hugo J Bellen, Travis I Moore, Sheng Zhang

Faculty, Staff and Students Publications

Rab GTPases are key regulators of endosomal trafficking in eukaryotes. In mammalian cells, Rab4 and Rab7 were shown to localize to distinct compartments, with Rab4 on early endosomes for fast recycling and Rab7 on late endosomes for degradation. Here, we show that in Drosophila, endogenous Rab4 and Rab7 extensively colocalize across tissues and developmental stages. Recruited to the same compartments through mechanisms that do not require the activity of the other, they have opposing effects on endolysosomal size: Rab4 overexpression or Rab7 impairment leads to enlarged endolysosomes, whereas Rab4 loss or constitutively active Rab7 reduces their sizes. Rab4 deficiency suppresses …

Lonp1 Variants Are Associated With Clinically Diverse Phenotypes, Randee E Young, Lu Qiao, Rebecca Hernan, David A Sweetser, Jessica L Waxler, Daryl A Scott, Tiana M Scott, Seema R Lalani, Mahshid S Azamian, Jill A Rosenfeld, Bret Bostwick, Lindsay C Burrage, Lance H Rodan, Bianca E Russell, Marina Dutra-Clarke, Michael Kruer, Somayeh Bakhtiarim, Hossein Darvish, David J Amor, Shamima Rahman, Karen Stals, Lisa Bradley, Susan Byrne, Leandra K Tolusso, Beatrix Wong, Laura Benedict, Kimberly Wallis, Kestutis Micke, Cindy Colson, Thomas Smol, Sabrina V Southwick, Kristen A Miller, Michelle L Kush, Odelia Chorin, Annick Rothschild, Wei Wang, Yufeng Shen, Wendy K Chung

Faculty, Staff and Students Publications

LONP1 encodes a mitochondrial protease essential for protein quality control and metabolism. Variants in LONP1 are associated with a diverse and expanding spectrum of disorders, including Cerebral, Ocular, Dental, Auricular, and Skeletal anomalies syndrome (CODAS), congenital diaphragmatic hernia (CDH), and neurodevelopmental disorders (NDD), with some individuals exhibiting features of mitochondrial encephalopathy. We report 16 novel LONP1 variants identified in 16 individuals (11 with NDD, 5 with CDH), further expanding the clinical spectrum. Structural mapping of disease-associated missense variants revealed phenotype-specific clustering, with CODAS variants enriched in the proteolytic chamber and NDD variants more broadly distributed. CODAS is caused by biallelic …

Comparison Of Variant Callers Using 60 532 Multi-Ancestry Whole Genome Sequences, Hufeng Zhou, Zilin Li, Derek Shyr, Xihao Li, Haoyu Yang, Rounak Dey, Yushi Tang, Robert Maier, Eric Boerwinkle, Steve Buyske, Mark Daly, Adam Felsenfeld, Richard A Gibbs, Namrata Gupta, Ira M Hall, Tara Matise, Ginger A Metcalf, Albert Smith, Catherine Reeves, Heidi J Sofia, Nathan O Stitziel, Michael C Zody, Nhgri Genome Sequencing Program (Gsp) Consortium, Benjamin Neale, Xihong Lin

Faculty, Staff and Students Publications

Whole genome sequencing (WGS) studies play a pivotal role in studying the genetic underpinnings of human diseases and traits. High quality and reproducible variant calling is the cornerstone for the success of downstream analyses, including WGS association studies and polygenic risk prediction. This paper compares the data quality, performance, and concordance of two widely used WGS variant callers, the Genome Analysis Toolkit (GATK) and Variant Tool set that discovers short variants (VT), using 60 532 multi-ancestry whole genomes sequenced by the Centers for Common Disease Genomics (CCDGs) of the NHGRI Genome Sequencing Program. Our findings show that both QCed GATK …

Lower Gyrification Of The Ventromedial Prefrontal Cortex In Posttraumatic Stress Disorder: An Enigma-Ptsd Study., Ahmed Hussain, C Lexi Baird, Ashley A Huggins, Courtney C Russell, Delin Sun, Leonel Rangel-Jimenez, Chadi G Abdallah, Michael Angstadt, Geoffrey May, Hannah Berg, Jennifer U Blackford, Josh Cisler, Judith K Daniels, Nicholas D Davenport, Richard J Davidson, Maria Densmore, Seth G Disner, Wissam El-Hage, Amit Etkin, Negar Fani, Jessie L Frijling, Evan M Gordon, Daniel W Grupe, Ryan A Herringa, Julia I Herzog, David Hofmann, Anna R Hudson, Tanja Jovanovic, Anthony King, Saskia B J Koch, Ruth A Lanius, Amit Lazarov, Gen Li, Israel Liberzon, Shmuel Lissek, Guangming Lu, Antje Manthey, Adi Maron-Katz, Katie A Mclaughlin, Sven C Mueller, Laura Nawijn, Steven M Nelson, Yuval Neria, Richard W J Neufeld, Jack B Nitschke, Bunmi O Olatunji, Miranda Olff, Matthew Peverill, Rongfeng Qi, Yann Quidé, Orren Ravid, Ivan Rektor, Kerry J Ressler, Pavel Říha, Marisa Ross, Kelly Sambrook, Christian Schmahl, Anika Sierk, Scott R Sponheim, Jennifer S Stevens, Thomas Straube, Benjamin Suarez-Jimenez, Jean Théberge, Nic J A Van Der Wee, Steven J A Van Der Werff, Sanne J H Van Rooij, Mirjam Van Zuiden, Dick J Veltman, Robert R J M Vermeiren, Henrik Walter, Li Wang, Xi Zhu, Ye Zhu, Sigal Zilcha-Mano, Neda Jahanshad, Paul M Thompson, Rajendra A Morey

Faculty, Staff and Students Publications

Background: Cortical gyrification involves the formation of folds in the cerebral cortex, coinciding with key neurodevelopmental processes. Its strong correlation with increased cortical surface area and decreased cortical thickness may improve cortical signaling efficiency by decreasing cortico-cortical distance. Differences in brain structure have been found in posttraumatic stress disorder (PTSD), yet few small studies have examined cortical gyrification.

Methods: Gyrification was quantified using FreeSurfer's Local Gyrification Index (lGI), derived from 3-dimensional T1-weighted volumetric brain magnetic resonance imaging in 1876 participants (PTSD n = 789, control n = 1087) across 24 sites from the ENIGMA-PGC (Enhancing Neuro Imaging Genetics through Meta-Analysis …

Relationship Between Heart Rate Variability And Sleep Among Girls And Boys With Abdominal Pain-Related Disorders Of Gut-Brain Interaction, Kendra J Kamp, Robert L Burr, Camden E Matherne, Emily Simonds, Tasha Murphy, Margaret M Heitkemper, Rona L Levy, Robert J Shulman, Miranda A L Van Tilburg

Faculty, Staff and Students Publications

Background: Children with abdominal pain-related disorders of gut-brain interaction (AP-DGBI) often experience sleep disturbances which may be linked to the autonomic nervous system. Heart rate variability (HRV) is a non-invasive measure of autonomic nervous system activity. Our aim was to examine if HRV was associated with characteristics of disturbed sleep in children with AP-DGBI in order to elucidate the underlying physiological mechanisms of disturbed sleep.

Methods: This analysis used baseline data from a randomized control trial of 156 children ages 7-12 years with AP-DGBI. HRV was measured after dinner using a Polar monitor. Sleep disturbances were evaluated using the Children's …

Statistical Methods In Aging Research: Improving Current Practices And Embracing Emerging Approaches, Deependra K Thapa, Erik S Parker, Mounika Kandukuri, Xi Rita Wang, Thirupathi R Mokalla, Olivia C Robertson, Wasiuddin Najam, Andrew E Teschendorff, Andrew W Brown, John R Speakman, Yisheng Peng, Bernard S Gorman, Heping Zhang, Luis-Enrique Becerra-Garcia, Colby J Vorland, David B Allison

Faculty, Staff and Students Publications

Aging research relies on varied statistical methods, and applying these methods appropriately is important for scientific rigor. However, proper use of these statistical techniques is a challenge. We discuss two categories of statistical methods in aging research: (a) emerging methods requiring further validation, including techniques to examine compression of morbidity, maximum lifespan, immortal time bias, molecular aging clocks, and treatment response heterogeneity, and (b) classic and existing methods needing reconsideration and improvement, such as stepwise regression, generalized linear models, methods for accounting for clustering and nesting effects, methods for testing for group differences, methods for mediation …

Information Extraction From Clinical Notes: Are We Ready To Switch To Large Language Models?, Yan Hu, Xu Zuo, Yujia Zhou, Xueqing Peng, Jimin Huang, Vipina K Keloth, Vincent J Zhang, Ruey-Ling Weng, Cathy Shyr, Qingyu Chen, Xiaoqian Jiang, Kirk E Roberts, Hua Xu

Faculty, Staff and Student Publications

Objectives: To assess the performance, generalizability, and computational efficiency of instruction-tuned Large Language Model Meta AI (LLaMA)-2 and LLaMA-3 models compared to bidirectional encoder representations from transformers (BERT) for clinical information extraction (IE) tasks, specifically named entity recognition (NER) and relation extraction (RE).

Materials and methods: We developed a comprehensive annotated corpus of 1588 clinical notes from 4 data sources-UT Physicians (UTP) (1342 notes), Transcribed Medical Transcription Sample Reports and Examples (MTSamples) (146), Medical Information Mart for Intensive Care (MIMIC)-III (50), and Informatics for Integrating Biology and the Bedside (i2b2) (50), capturing 4 clinical entities (problems, tests, medications, other treatments) …

A Patient-Derived Organ-On-Chip Platform For Modeling The Tumor Microenvironment And Drug Responses In Pancreatic Cancer, Darbaz Adnan, Natan Roberto De Barros, Luca S Santovito, Xuhong Cheng, Kristi M Lawrence, Mariah K Barnett, Martine D Boetto, Neal Mehta, Ajaypal Singh, Lin Cheng, Xiangsheng Huang, Faraz Bishehsari

Faculty, Staff and Student Publications

Pancreatic ductal adenocarcinoma (PDAC) is a fatal malignancy. Current conventional chemotherapeutics are inadequate in controlling the disease; hence, there is an urgent need for precision medicine. Ex vivo models that replicate the tumor and its microenvironment can advance precision medicine in PDAC. Patient‐derived organoids (PDOs) offer a promising solution by retaining the functional features of the tumor, allowing for individualized study of cancer biology and drug response. However, PDOs fall short in replicating the tumor microenvironment (TME), which includes various stromal and immune cells influencing tumor growth and chemoresistance. We hypothesize that combining PDO technology with organ‐on‐a‐chip (OoC) systems can …

[Factors Associated With Adhd Medication Adherence And Treatment Outcomes, Hali Temkin, Kerri L Daniel, Diana Martinez, Julia C Bennett, Paris A Nix, Linh Nguyen, Yen-Chi Le, Bruno Kluwe-Schiavon, Cesar A Soutullo

Faculty, Staff and Student Publications

Introduction: Attention-Deficit/Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder that affects 5 to 8% of youth and 2.5 to 4% of adults. Pharmacological treatments are among the most effective when treating ADHD, yet adherence to medication is still sub-optimal. We reviewed the literature on clinical and socio demographic factors that may influence adherence and compared it to our clinical data.

Methods: We conducted a targeted literature review on factors associated with ADHD medication adherence. These factors were compared within our sample of patients aged 3-18 with ADHD at the Child and Adolescent Mood Disorders Program (ChAMP) at (UT Health) - Houston. …

Childhood Pulmonary Outcomes After Late Preterm Antenatal Corticosteroids, Cynthia Gyamfi-Bannerman, Rebecca G Clifton, Robert A Wise, Alan T N Tita, Jessica A De Voest, Sharon A Mcgrath-Morrow, Elizabeth C Matsui, Sean C Blackwell, Monica Longo, Sabine Z Bousleiman, Felecia Ortiz, Sankaran Krishnan, Dwight J Rouse, Torri D Metz, George R Saade, Maged M Costantine, Kent D Heyborne, John M Thorp, Kelly S Gibson, Geeta K Swamy, William A Grobman, Yasser Y El-Sayed, George A Macones, Eunice Kennedy Shriver National Institute Of Child Health And Human Development Maternal-Fetal Medicine Units Network And The National Heart, Lung, And Blood Institute

Faculty, Staff and Student Publications

Objective: To evaluate whether antenatal betamethasone affects childhood respiratory impairment.

Methods: This was a prospective follow-up study of children aged 6 years and older from parents in the ALPS (Antenatal Late Preterm Steroids) trial randomized to betamethasone or placebo from 34 0/7 to 36 6/7 weeks of gestation. Primary outcome composite included the following: 1) abnormal spirometry, forced expiratory volume in 1 second (FEV 1 ) below the lower limit of normal, FEV 1 /forced vital capacity (FVC) below the lower limit of normal, or FVC below the lower limit of normal, defined as below the 5th percentile by the …

Impact Of Mutational Landscape And Burden On Rbc Transfusion Response In Patients With Lower-Risk Myelodysplastic Syndromes (Lr-Mds) In The Commands Study, Rami S Komrokji, Sheida Hayati, Manuel Ugidos, Guillermo Garcia-Manero, Matteo Giovanni Della Porta, Amer M Zeidan, Valeria Santini, Uwe Platzbecker, Anita K Gandhi, Rajasekhar N V S Suragani

Faculty, Staff and Student Publications

The COMMANDS trial established luspatercept as a first‐line treatment for anemia in transfusion‐dependent lower‐risk (LR) myelodysplastic syndromes (MDS). Here we report red blood cell (RBC) transfusion response analysis based on somatic mutations profile and disease risk for patients treated with luspatercept or epoetin alfa in the COMMANDS trial. Of 350 evaluable patients, 238 (68.0%) had MDS with multiple lineage dysplasia and ring sideroblasts (RS) according to World Health Organization 2016 criteria, and 320 (91.4%) had somatic mutations in ≥ 1 gene (median, 2) with median variant allele frequencies (VAF) of 2%–59%. Mutation profiles were similar in the treatment groups. Luspatercept …

Reconstruction Of A Composite Heel Defect Using Achilles Tendon Allograft And Latissimus Dorsi Free Flap: Case Report And Literature Review, Georgios Karamitros, Carolyn Drogt, Stephen J Warner, Michael P Grant, Gregory A Lamaris

Faculty, Staff and Student Publications

Background: Composite heel defects involving the Achilles tendon and overlying soft tissue are rare and technically demanding. Successful management requires restoration of tendon continuity and durable coverage. We reviewed the literature and presented a representative case to illustrate current strategies.

Methods: A literature review of 28 studies that reported outcomes of Achilles tendon reconstruction with concomitant soft tissue coverage was performed. Tendon restoration techniques(allografts, autografts, vascularized grafts) and flap types (muscle and fasciocutaneous) were analyzed for functional recovery, complication rates, and donor-site morbidity. Additionally, we report the case of a 14-year-old woman with a 7-cm Achilles tendon defect and full-thickness …

Beyond Short Microhomologies: Mismatch-Compatible Pol Θ-Mediated Dna Damage Repair, Yuzhen Li, Richard D Wood

Faculty, Staff and Student Publications

DNA polymerase θ (Pol θ)-mediated end-joining (TMEJ), one of several pathways for repairing DNA double-strand breaks, is traditionally thought to initiate via anchoring at short, consecutive, and perfectly matched microhomologies (MHs). Emerging evidence indicates that Pol θ can utilize MHs containing mismatches both in vitro and in vivo. This revised definition of MH provides a mechanistic explanation for a broader spectrum of Pol θ-dependent repair outcomes. Here, we summarize recent findings on the revised definition of MHs utilized by Pol θ, assess the applicability of this concept across species, and compare TMEJ with other (micro)hom(e)ology-mediated repair pathways. We explore how …

Spatial Profiling Reveals Distinct Molecular And Immune Evolution Of Mouse Lung Adenocarcinoma Precancers With Or Without Carcinogen Exposure, Bo Zhu, Muhammad Aminu, Pingjun Chen, Jian-Rong Li, Chuanpeng Dong, Chenyang Li, Yanhua Tian, Shao-Wei Lu, Hong Chen, Chenxi Ma, Xin Hu, Jie Ye, Andrew Y Liu, Beibei Huang, Frank R Rojas, Parra Cuentas Edwin Roger, Ou Shi, Monique B Nilsson, Alissa Poteete, Khaja B Khan, Wei Lu, Luisa M Solis Soto, Junya Fujimoto, Cara Haymaker, Ignacio I Wistuba, Zhubo Wei, Linghua Wang, Don L Gibbons, Ken Chen, Alexandre Reuben, Jason M Schenkel, John V Heymach, Chao Cheng, Jia Wu, Jianjun Zhang

Faculty, Staff and Student Publications

Tumor evolution involves genetic, transcriptional, and phenotypic alterations that shape cancer cell behavior and interactions with the microenvironment. While single‐cell technologies have advanced our understanding of this process, spatial dynamics remain incompletely characterized. Here, whole‐exome sequencing (WES), imaging mass cytometry (IMC), and spatial transcriptomics (ST) were integrated to study molecular evolution and immune responses in two lung adenocarcinoma (LUAD) mouse models: a genetically engineered model (129S4/Sv‐KrasLSL‐G12D, termed 129S4 K) and a carcinogen‐induced precancer model (129S4 U). Compared to 129S4 K, 129S4 U tumors exhibited higher mutational, neoantigen but lower copy number variation (CNV) burdens at matched developmental timepoints, consistent with …