Digital Commons Network^™

Lysine Demethylase 4a (Kdm4a) Maintains Basal Body Architecture And Protects Against Ciliary Destabilization, Manga Motrapu, Lindsey Hudson, Pratim Chowdhury, Xiaoli Wang, Yuya Nakatani, Sofia Vargas-Hernandez, Sung Y Jung, Menuka Karki, Cheryl Walker, Anna-Karin Gustavsson, Ruhee Dere

Faculty, Staff and Students Publications

Primary cilia are sensory organelles essential for signaling and defects in formation, maintenance or structure underlie diverse ciliopathies. Here, we identify lysine demethylase 4A (KDM4A) as a previously unrecognized mediator of ciliogenesis. Using genetic depletion and pharmacologic inhibition, we show that KDM4A is required for cilia assembly and maintenance. Super-resolution imaging reveals KDM4A localization at the basal body, where it distinctively wraps around the centrioles. We uncover a direct interaction between KDM4A and Rootletin (CROCC), a structural protein mediating centriole cohesion, and demonstrate that KDM4A loss increases inter-centriolar distances, implicating basal body architecture in ciliary failure. Together, these findings define …

Mapping The Causal Chain From Genetic Risk Variants To Lipid Dysmetabolism In Parkinson’S Disease, Ruth B De-Paula, Jonggeol Kim, Herve Rhinn, Hiba Saade, Fatima Chavez, Téah Segura, Maria Valeria Lozano, Michelle Etoundi, Karla Silos, Naomi Kass, Viktoriya Korchina, Harshavardhan Doddapaneni, Eric Venner, Joseph C Masdeu, Valory Pavlik, Melissa M Yu, Chi-Ying R Lin, Joseph Jankovic, Aron S Buchman, Donna Muzny, Richard A Gibbs, Sarah H Elsea, Asa Abeliovich, Peter Lansbury, Nora Vanegas-Arroyave, Chad A Shaw, Joshua M Shulman

Faculty, Staff and Students Publications

The molecular pathways linking genetic variants to Parkinson's disease (PD) onset and progression remain incompletely defined; however, risk alleles in multiple genes, including GBA1, strongly implicate lipid metabolism. To systematically identify causal biomarker signatures, we analyzed comprehensive metabolome profiles from blood plasma in 149 PD patients and 150 controls, along with complementary genetic, RNA-sequencing, and metabolic data from other available clinical and pathologic cohorts. Using colocalization and summary-data-based Mendelian randomization, we tested whether expression and metabolic quantitative trait loci mediate the association between implicated genetic variants and PD risk. We further integrated differential metabolomics and proteomics from blood and brain …

Insomnia In Stimulant Use Disorders: Prevalence And Associations With Negative Affect, Isabella G Bourtin, Constanza De Dios, Jessica Vincent, Joy M Schmitz, Scott D Lane, Heather E Webber

Faculty, Staff and Student Publications

Research suggests that sleep disturbances are common among people who use psychostimulants, including cocaine use and methamphetamine use. These sleep disturbances hinder recovery, heighten relapse risk, and worsen physical and mental health outcomes. This study aimed to estimate the prevalence and severity of insomnia among individuals who use cocaine and methamphetamine and to explore potential psychological factors that are associated with more severe insomnia. The sample included participants who completed in-person screening assessments for ongoing studies at an outpatient research clinic. As a part of this screening, participants completed the Insomnia Severity Index (ISI) and validated assessments of psychological domains …

The Long-Term Effectiveness Of The Anti-Obesity Medication Phentermine (Leap) Trial: Rationale, Design, And Baseline Characteristics, Caroline Blackwell Young, Emily Rives, Kimberly A Gudzune, Byron C Jaeger, Courtney G Simmons, Brian N White, Stephanie A Hooker, Deborah B Horn, Deborah R Young, Jennifer Vesely, Amanda Velazquez, Catherine Price, Shelly D Cook, Katy Martin-Fernandez, Galina Inzhakova, Nicholas M Pajewski, Jamy D Ard, Kristina H Lewis

Faculty, Staff and Student Publications

Background: Current clinical practice guidelines support the long-term use of pharmacotherapy for obesity treatment. Historically, phentermine has been one of the most prescribed obesity medications (OMs), however, its long-term efficacy and safety have never been evaluated in a randomized trial as its market approval predates such requirements. Here we describe the design, rationale, and baseline characteristics for a 24-month, double-blind, randomized controlled trial evaluating the efficacy, cardiovascular risk, and safety of phentermine in adults with overweight or obesity.

Methods: This multicenter trial will compare outcomes among participants randomized to phentermine 24 mg daily versus placebo for 24 months. All participants …

Transcriptomics And Metabolomics Analysis Reveal Cell Subpopulations Of Trophoblast Cells Associated With Preeclampsia, Xiaojun Zhu, Ying Jiang, Lilin Wang, Peiyue Jiang, Zixing Zhong, Hetong Li, Caihong Zheng, Lujiao Chen, Juan Wei, Xishi Lin, Peng Ding, Zehua Dong, Xiaosheng Wang, Qiong Luo

Faculty, Staff and Student Publications

Placental abnormalities are central to preeclampsia (PE), yet the cellular and molecular mechanisms underlying this dysfunction remain unclear. We applied a multi-layered, integrative approach to investigate placental tissue from patients with PE and matched controls. Single-cell RNA sequencing (scRNA-seq; GSE173193) and bulk RNA sequencing (bulk RNA-seq; GSE203507) datasets were obtained from the Gene Expression Omnibus. The scRNA-seq dataset included two PE and two control samples, whereas the bulk RNA-seq dataset focused on eight early-onset PE and five uncomplicated term births. Trophoblast subpopulations were identified via scRNA-seq, and pseudotime analysis was used to trace differentiation trajectories. Differential expression and pathway enrichment …

Population-Scale Sequencing Resolves Determinants Of Persistent Ebv Dna, Sherry S Nyeo, Erin M Cumming, Oliver S Burren, Meghana S Pagadala, Jacob C Gutierrez, Thahmina A Ali, Laura C Kida, Yifan Chen, Hoyin Chu, Fengyuan Hu, Xueqing Zoe Zou, Benjamin Hollis, Margarete A Fabre, Stewart Macarthur, Quanli Wang, Leif S Ludwig, Kushal K Dey, Slavé Petrovski, Ryan S Dhindsa, Caleb A Lareau

Duncan NRI Faculty and Staff Publications

Epstein–Barr virus (EBV) is an endemic herpesvirus implicated in autoimmunity, cancer and neurological disorders. Although primary infection is often subclinical, persistent EBV infection can drive immune dysregulation and long-term complications. Despite the ubiquity of infection, the determinants of EBV persistence following primary exposure remain poorly understood, although human genetic variation partially contributes to this phenotypic spectrum1–3. Here we demonstrate that existing whole genome sequencing (WGS) data of human populations can be used to quantify persistent EBV DNA. Using WGS and health record data from the UK Biobank (n = 490,560) and All of Us ( …

Integrated Transcriptomic Landscape Of Medulloblastoma And Ependymoma Reveals Novel Tumor Subtype-Specific Biology, Sonali Arora, Nicholas Nuechterlein, Matt Jensen, Gregory Glatzer, Philipp Sievers, Srinidhi Varadharajan, Andrey Korshunov, Felix Sahm, Stephen C Mack, Michael D Taylor, Taranjit S Gujral, Eric C Holland

Faculty, Staff and Students Publications

Background: Medulloblastoma and ependymoma are common pediatric central nervous system tumors with significant molecular and clinical heterogeneity. While molecular subgrouping has enabled classification into molecular subtypes, the extent of heterogeneity within these subgroups remains poorly defined.

Methods: We collected bulk RNA sequencing data from 888 medulloblastoma and 370 ependymoma tumors to establish a comprehensive reference landscape. After rigorous batch effect correction, normalization, and dimensionality reduction, we generated a unified landscape to explore gene expression, signaling pathways, RNA fusions, and copy number variations.

Results: Our transcriptional analysis revealed distinct clustering patterns, including two primary ependymoma compartments, EPN-E1 and EPN-E2, each with …

Bradycardia, Asystole, And Sudden Cardiac Death In Zc4h2 R198q-Associated Wieacker-Wolff Syndrome, Emily M Masterson, Alexandra M Menillo, Tam Dan Pham, Taylor A Beecroft-Dawson, Steven B Wolfe, Taylor S Howard, Christina Y Miyake

Faculty, Staff and Students Publications

No abstract provided.

Icosapent Ethyl Reduces Cvd Risk In Cardiovascular-Kidney-Metabolic Syndrome: Reduce-It Ckm, Michael Miller, Deepak L Bhatt, Eliot A Brinton, Terry A Jacobson, Ph Gabriel Steg, Steven B Ketchum, Armando Lira Pineda, Jean-Claude Tardif, Christie M Ballantyne

Faculty, Staff and Students Publications

Background/introduction: Cardiovascular-kidney-metabolic (CKM) syndrome was recently identified as a cardiometabolic disorder that incorporates chronic kidney disease with the metabolic syndrome (MetS). REDUCE-IT (Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial) was an international, double-blind, placebo-controlled trial that randomized hypertriglyceridemic (TG, 150-499 mg/dL) statin-treated patients with established cardiovascular disease (CVD) or diabetes and multiple CVD risk factors to icosapent ethyl (IPE) or placebo (4 grams/day). It is unknown if renal insufficiency added to MetS confers incremental CVD risk in secondary prevention patients without diabetes and if IPE lowers that risk.

Methods: The current study evaluated the secondary prevention patient subgroup with …

Analysis Of Failure To Rescue In Adult Patients Who Undergo Open, Proximal Aortic Repair, Kyle W Blackburn, Joseph S Coselli, Armin Farazdaghi, Lynna Nguyen, Susan Y Green, Anna Xue, Vicente Orozco-Sevilla, Scott M Leikin, Marc R Moon, Subhasis Chatterjee

Faculty, Staff and Students Publications

Objective: Failure to rescue (FTR) is a metric of postoperative care, measuring a center's ability to prevent operative death after a surgical complication. We evaluated trends in and contributors to FTR after proximal aortic surgery at a high-volume institution.

Methods: Of 4180 patients in our single practice who underwent open proximal aortic repair from 1990 to 2024, 1304 (31.2%) had at least 1 of 4 FTR-related complications identified by the Society of Thoracic Surgeons (STS). Operative death was defined as death within 30 days of surgery or before hospital discharge or transfer. We analyzed FTR rate by specific complication, including …

Cyclic Amp-Dependent Regulation Of Ryanodine Receptors In Healthy And Diseased Hearts, Mohit M Hulsurkar, Isabelle Ong, Joshua A Keefe, Issam H Abu-Taha, Dobromir Dobrev, Xander H T Wehrens

Faculty, Staff and Students Publications

Cyclic adenosine monophosphate (cAMP) is a critical second messenger in cardiomyocytes, regulating essential cellular functions. Upon G-protein-coupled receptor stimulation, adenylyl cyclase (AC) synthesizes cAMP, which phosphodiesterase (PDE) enzymes subsequently degrade. Recent studies challenge the traditional view of uniform cAMP signaling, revealing nanodomain-specific regulation within cardiomyocytes. This localized cAMP signaling modulates key Ca2+-handling proteins, including ryanodine receptor type-2 (RyR2), through channel-bound protein kinases and PDEs. Additionally, nucleoside-diphosphate kinases (NDPKs), particularly NDPK-C, contribute to cAMP synthesis and RyR2 regulation. Elevated NDPK-C levels in failing hearts correlate with increased cAMP levels, enhanced sarcoplasmic reticulum Ca2+ release, and cardiac arrhythmias. Furthermore, cAMP influences the …

Trans-Broad-Ligament Abdominal Cerclage Versus Blind Needle-Piercing Abdominal Cerclage During Pregnancy: A Comparison Of Surgical Outcomes, Qiannan Yang, Daniel Y Lovell, Joseph Nassif, Lubna Chohan, Jugnu Biba Nijjar, Nurul Farhanah Binte Abdul Latif, Zhenkun Guan, Xiaoming Guan

Faculty, Staff and Students Publications

No abstract provided.

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 …

Does Hla-B27 Status Influence Ixekizumab Efficacy In Axial Spondyloarthritis? Results From The Coast-V, Coast-W, And Coast-X Trials, John D Reveille, Martin Rudwaleit, Proton Rahman, Jose A Maldonado-Cocco, Marina Magrey, Rebecca Bolce, Khai Jing Ng, Theresa Hunter Gibble, Jeffrey Lisse, So Young Park, Andris Kronbergs, Victoria Navarro-Compán

The Brown Foundation: Institute of Molecular Medicine

Introduction: The human leukocyte antigen (HLA)-B27 is associated with axial spondyloarthritis (axSpA) and is a predictor of response to tumor necrosis factor inhibitors. However, limited data are available on HLA-B27 and interleukin-17 inhibitors. We evaluated the influence of HLA-B27 status on ixekizumab response through 52 weeks in patients with axSpA.

Methods: Data were analyzed from three randomized placebo-controlled trials: COAST-V (NCT02696785), COAST-W (NCT02696798), and COAST-X (NCT02757352). Patients fulfilled the Assessment of SpondyloArthritis international Society (ASAS) criteria for radiographic (r)-axSpA or non-radiographic (nr)-axSpA. Patients were randomized to receive 80 mg ixekizumab every 2 weeks, 80 …

Proceedings Of The Second Artificial Intelligence In Primary Immunodeficiency (Aipi) Meeting, Jacques G Rivière, Lisa Bastarache, Luiza C Campos, Gerard Carot-Sans, Aaron Chin, Rumi Chunara, Charlotte Cunningham-Rundles, Lorenzo Erra, Jocelyn Farmer, Nicolas Garcelon, Elena Hsieh, Helen Leavis, Seungwon Lee, Liangying Liu, Maaike Kusters, Brian C Lloyd, Alexandra K Martinson, Rachel Mester, Justin B Moore, Despina Moshous, Jordan S Orange, Nefatia Parrish, Sarah Henrickson Parker, Bogdan Pasaniuc, Xiao P Peng, Martine Pergent, Jordi Piera-Jiménez, Jessica Quinn, Sidharth Ramesh, Kirk Roberts, Peter N Robinson, Guergana Savova, Christopher Scalchunes, Markus G Seidel, Rachel Simoneau, Pere Soler-Palacin, Kathleen E Sullivan, Marielle Van Gijn, Chung-Il Wi, Dawei Zhou, Vanessa Tenembaum, Manish J Butte, Nicholas L Rider

Faculty, Staff and Student Publications

The use of artificial intelligence (AI) in inborn errors of immunity offers transformative potential in diagnostics and disease management but faces multiple challenges that were discussed at the second Artificial Intelligence in Primary Immunodeficiency conference, held in New York City (March 19-22, 2025). The conference addressed 7 themes: predictive diagnostic algorithms, health equity, industry collaboration, advanced computational tools like large language models, patient-led AI initiatives, multiomics integration, and implementation science. Discussions highlighted the growing impact of AI on diagnostics, genomics, and health systems, emphasizing the need for high-quality, diverse datasets and ethical safeguards to ensure equitable application. Participants stressed that …

Scper: A Rigorous Computational Approach To Determine Cellular Subtypes In Tumors Aligned With Cancer Phenotypes From Total Rna Sequencing, Bingrui Li, Xiaobo Zhou, Raghu Kalluri

Faculty, Staff and Student Publications

Single-cell RNA sequencing (scRNA-seq) is a powerful technique for understanding cellular diversity, but processing large patient cohorts to identify phenotype-associated cell populations remains challenging. Here, scPER (Estimating cell Proportions using single-cell RNA-seq Reference), a rigorous approach combining adversarial autoencoder and extreme gradient boosting to estimate tumor microenvironment cell compositions and identify phenotype-associated subclusters for bulk RNA-seq samples. Integrating scRNA-seq datasets from diverse studies, scPER constructed comprehensive reference panels and disentangled confounders from true signals. scPER achieved superior accuracy in cellular proportion estimation compared to CIBERSORTx, BayesPrism, Scaden, MuSiC, SCDC, DeSide and ReCIDE. It showed high accuracy in predicting metastatic melanoma …

Genetic Architecture Of N-Terminal Pro-B-Type Natriuretic Peptide In A Multiancestry Study Population, Naman S Shetty, Akhil Pampana, Mokshad Gaonkar, Amrita Nayak, Harshvir S Bal, Nirav Patel, Nehal Vekariya, J Gustav Smith, Alanna C Morrison, Bing Yu, Bruce M Psaty, Eric Boerwinkle, James S Floyd, Jerome I Rotter, Kent D Taylor, Leslie A Lange, Marguerite R Irvin, Mary Cushman, Stephen S Rich, Ramachandran S Vasan, Thomas J Wang, Xiuqing Guo, Peng Li, Garima Arora, Pankaj Arora

Faculty, Staff and Student Publications

Background: NPs (natriuretic peptides) are bioactive hormones crucial for regulating blood pressure, glucose homeostasis, and lipid metabolism. Despite the high heritability of circulating NP levels, the genetic determinants of NP regulation, particularly across ancestries and sexes, remain poorly understood. The objective of the current study was to identify genetic variants associated with NT-proBNP (N-terminal pro-B-type NP) levels in a multiancestry study population.

Methods: Whole genome sequencing and array-based data from 81 213 individuals without heart failure were analyzed from the Trans-Omics for Precision Medicine cohorts, UK Biobank, All of Us Research Program, and REGARDS (Reasons for Geographic and Racial Differences …

Bispectral Index-Guided Anesthesia For Older Patients Having Noncardiac Surgery: A Randomized Multicenter Trial, Li Zhou, Lin Ding, Hui Yang, Chengyu Li, Zhangsheng Yu, Wei Ma, Qiuyu Chen, Yanzhuo Zhang, Yong Li, Qingxiang Mao, Minghua Cheng, Gu Gong, Enqin Wang, Cunming Liu, Wei Hao, Hong Li, Changlin Chen, Yaling Fan, Zhenbo Su, Xiaoli Cai, Xiaole Zhang, Zhi Li, Bing Zhang, Yi Li, Chunxiu Jiang, Qinqin Yin, Jiali Jiao, Daniel I Sessler, Qian Li, Jin Liu

Faculty, Staff and Student Publications

Background: Older surgical patients are at risk because of age-related physiologic decline and comorbidities. Some guidelines recommend Bispectral Index (BIS; Medtronic, USA) monitoring to optimize anesthetic depth, but robust evidence supporting improved outcomes is lacking.

Methods: A randomized, multicenter, double-blind trial was conducted across 21 tertiary-care hospitals in China (March 17, 2015, to February 5, 2022). Patients aged 65 yr or older scheduled for elective noncardiac surgery (American Society of Anesthesiologists [ASA] Physical Status I to IV) were randomized 1:1 to BIS-guided or routine anesthetic management. In patients assigned to BIS guidance, hypnotic depth was adjusted to maintain BIS between …

Examination Of Traffic Safety In Neighborhoods Associated With Active Commuting To School In Austin, Texas, Kathryn G Burford, Deborah Salvo, Harold W Kohl, Leigh Ann Ganzar, Cici X Bauer, Eugen Resendiz, Yuzi Zhang, Deanna M Hoelscher

Faculty, Staff and Student Publications

Background: Only 10% of US children participate in active commuting (walking and bicycling) to school (ACS). Parental concerns related to traffic are a primary barrier to ACS, yet no studies have assessed these concerns together with neighborhood traffic safety-related features. This study examined the associations between traffic safety-related features in neighborhoods and ACS among school-age children in Austin, Texas.

Methods: This cross-sectional analysis utilized pre-COVID-19 baseline data (2019-2020) of parent-child dyads enrolled in the Safe TRavel Environment Evaluation in Texas Schools study. ACS, traffic safety-related features in the neighborhood (sidewalk availability, safe road crossings, traffic safety, traffic speed, and safety …

Cellstaar: Incorporating Single-Cell-Sequencing-Based Functional Data To Boost Power In Rare Variant Association Testing Of Noncoding Regions, Eric Van Buren, Yi Zhang, Xihao Li, Margaret Sunitha Selvaraj, Zilin Li, Hufeng Zhou, Nicholette D Palmer, Donna K Arnett, John Blangero, Eric Boerwinkle, Brian E Cade, Jenna C Carlson, April P Carson, Yii-Der Ida Chen, Joanne Curran, Ravindranath Duggirala, Myriam Fornage, Nora Franceschini, Misa Graff, Charles Gu, Xiuqing Guo, Jiang He, Nancy Heard-Cosa, Lifang Hou, Yi-Jen Hung, Rita R Kalyani, Sharon L R Kardia, Eimear Kenny, Charles Kooperberg, Brian G Kral, Leslie Lange, Dan Levy, Changwei Li, Simin Liu, Donald Lloyd-Jones, Ruth J F Loos, Ani W Manichaikul, Lisa Warsinger Martin, Rasika Mathias, Ryan L Minster, Braxton D Mitchell, Josyf C Mychaleckyj, Take Naseri, Kari North, Jeff O'Connell, James A Perry, Patricia A Peyser, Bruce M Psaty, Laura M Raffield, Ramachandran S Vasan, Susan Redline, Alex P Reiner, Stephen S Rich, Jennifer A Smith, Brian Spitzer, Hua Tang, Kent D Taylor, Russell Tracy, Satupa'itea Viali, Lisa Yanek, Wei Zhao, Nhlbi Trans-Omics For Precision Medicine (Topmed) Consortium, Jerome I Rotter, Gina M Peloso, Pradeep Natarajan, Xihong Lin

Faculty, Staff and Student Publications

Understanding how rare genetic variants influence complex traits remains a major challenge, particularly when these variants lie in noncoding regions of the genome. The effects of variants within candidate cis-regulatory elements (cCREs) often depend on the cell type, making interpretation difficult. Here we introduce cellSTAAR, which integrates whole-genome sequencing data with single-cell assay for transposase-accessible chromatin using sequencing data to capture variability in chromatin accessibility across cell types via the construction of cell-type-specific functional annotations and regulatory elements. To reflect the uncertainty in cCRE-gene linking, cellSTAAR uses a comprehensive strategy to link cCREs to their target genes. We applied cellSTAAR …

Volumetric Buccal Bone Alterations At Immediate Implant Sites With Or Without Soft Tissue Augmentation: A 6-Month Assessment, Mary Jung, Duong Tran, Chi-Ching Chang, Sung K Kim, Yosuke Tsukiboshi, Seiko Min, Srinivas Ayilavarapu, Chun-Teh Lee

Faculty, Staff and Student Publications

Background: This study is part of a randomized controlled trial investigating the impact of soft tissue augmentation (STA) using subepithelial connective tissue graft (SCTG) (immediate implant with subepithelial connective tissue graft [ICT] group) or acellular dermal matrix (ADM) (immediate implant with acellular dermal matrix [IAD] group) versus no STA (control) on the clinical outcomes following immediate implant placement (IIP). This study aimed to investigate volumetric buccal bone dimensional changes at immediate implant sites 6 months after the surgery.

Methods: Forty-five patients requiring extraction of a maxillary anterior tooth or premolar and randomly assigned to one of the three groups were …

Ex Vivo Comparative Analysis Of Retrievability Among Four Calcium Silicate-Based Sealers For Regaining Apical Patency, Darian Shomali, Timothy Kirkpatrick, Sang Won Kwak, Hyeon-Cheol Kim, Ji Wook Jeong

Faculty, Staff and Student Publications

Objectives: : Efficient retrievability is a key requirement for endodontic sealers. This study evaluated the retrievability of four different calcium silicate-based sealers (CSS).

Methods: A total of 153 single-rooted human teeth with straight canals were decoronated to a standardized working length of 12 mm. The canals were negotiated to working length using K files up to size 15/.02, followed by rotary instrumentation up to 35/.04, 2 mm short of working length. The teeth were randomly assigned to five groups: NeoSEALER Flo (NEO; Avalon Biomed), Ceraseal (CS; Meta Biomed), Endosequence BC Sealer (BC; Brasseler USA), AH Plus Bioceramic Sealer (AHB; Dentsply …

Investigation Of Teratogenic Concerns In The Coronavirus Disease Of 2019 Era, Kate Richardson, Emily C Daykin, Kathleen Shields, S Shahrukh Hashmi, Lorrie Harris-Sagaribay, Molly Daniels, Myla Ashfaq

Faculty, Staff and Student Publications

Background: MotherToBaby (MTB) is a teratogen information service that provides information about exposures during pregnancy and breastfeeding to the public and healthcare providers. During the Coronavirus Disease of 2019 (COVID-19) pandemic, MTB received an influx of queries regarding the teratogenicity of the virus and the vaccine. The purpose of this study was to assess the frequency and type of exposures asked about prior to the onset of the COVID-19 pandemic through March 2022 and to evaluate the demographics of individuals who made inquiries.

Methods: Data from MTB contacts (2018-2022) were accessed through a data-sharing agreement. The data were cleaned and …

Development And Implementation Of An Mri-Only Simulation, Planning, And Treatment Workflow For Prostate Radiotherapy Using Synthetic Ct On Mr-Linac, Reza Reiazi, Yao Ding, Sarath Vijayan, Jinzhong Yang, Ergys Subashi, Yao Zhao, Belinda M Lee, Hunter L Emory, Vi T Dinh, Greg L Swiedom, Jie Deng, Mu-Han Lin, Peter Balter, Rajat J Kudchadker, Elaine E Cha, Seungtaek Choi, Yusung Kim, Eun Young Han, Surendra Prajapati

Faculty, Staff and Student Publications

Purpose: We evaluated the feasibility of a magnetic resonance (MR)-only simulation, planning, and treatment (MROSPT) workflow for prostate cancer patients using synthetic computed tomography (sCT) generated from magnetic resonance imaging (MRI) data. By validating sCT-based dose calculations, we aimed to streamline radiotherapy workflows, eliminate the need for CT simulation, and enable reliable clinical implementation of MR-based radiotherapy for MR-linac (MRL).

Methods: We developed a comprehensive workflow encompassing the entire process from initial consultation to treatment delivery. After developing the workflow, a retrospective dosimetric validation study was performed on nine men with prostate cancer. They underwent CT and MRI simulations, and …

Inferring High-Fat Dietary Patterns From Electronic Health Record Data Using Machine Learning, Ya-Yun Yeh, Hsin-Yueh Lin, Jingchuan Guo, Ramon C Sun, Sizun Jiang, Jiang Bian, Hao Dai

Faculty, Staff and Student Publications

Objectives: Electronic health records (EHRs) rarely capture dietary detail, limiting diet-disease research. We aimed to develop machine learning (ML) computable phenotypes to identify high-fat diet (HFD) using variables typically available in EHRs.

Materials and methods: We used National Health and Nutrition Examination Survey (NHANES) 1999-2020 data, where 24-h dietary recall served as ground truth. Dietary fat intake was summarized into a score (0-30) based on percent energy from fat, carbohydrate, and protein; lower scores indicated HFD. We defined HFD at cutoffs of 10, 15, and 20, and trained ML models (Extreme Gradient Boosting, logistic regression, random forest) using EHR-compatible variables …

Implanting Microelectrode Arrays In The Bottom Of The Central Sulcus Targeting Somatosensory Area 3a For Restoration Of Proprioception, Tyler R Johnson, Sarah Moralle, Ziling Luo, Dawn M Taylor

Faculty, Staff and Student Publications

Objective: The long-term goal of this work is to develop a sensorimotor brain-machine interface (BMI) in which intended movements are decoded from the motor cortex and proprioceptive feedback is delivered via intracortical microstimulation of Brodmann's area 3a. A vital step toward this goal is to demonstrate in rhesus macaques a novel surgical approach for the precise and safe implantation of custom-length microelectrode arrays into area 3a at the bottom of the central sulcus.

Methods: Preoperative planning combined high-resolution 7-T MR and CT imaging to generate 3D models of the cortices of 2 subjects. These models were used to fabricate 3D-printed …

Hootation: A Gui And Api Library For Ontology Validation And Verbalization., Muhammad Amith, Xubing Hao, Warren Manuel, Manqi Li, Shun Rao, Kirk Roberts, Hua Xu, Yang Gong, Frank Manion, Cui Tao, Licong Cui

Faculty, Staff and Student Publications

Ontology verbalization refers to the process of translating formal axioms into natural language expressions. The primary objective is to facilitate the review and validation of ontology content by subject matter experts without requiring extensive technical expertise. While previous approaches based on templates or controlled grammar have been effective, they often face limitations in scalability, fluency, and adaptability. To address these issues, we developed Hootation, an open-source software system that supports ontology verbalization through both a graphical user interface and an API library. The tool implements rule-based translation of OWL2 axioms and further incorporates optional Large Language Model (LLM) components for …