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Baseline Characteristics In The Synchronize™-2 Randomized Phase 3 Trial Of Survodutide, A Glucagon Receptor/Glp-1 Receptor Dual Agonist, For Obesity In People With Type 2 Diabetes, Sean Wharton, Carel W Le Roux, Biykem Bozkurt, Elke Platz, Gabriele Bleckert, Samina Ajaz Hussain, Martina Brueckmann, Elena Startseva, Isabel M Kloer, Lee M Kaplan

Faculty, Staff and Students Publications

Aims: Survodutide is an investigational glucagon receptor/glucagon-like peptide-1 receptor dual agonist that has shown promise for treating obesity and its complications in Phase 2 trials. Two double-blind, randomized, global Phase 3 trials are designed to assess the efficacy and safety of survodutide for treatment of obesity-SYNCHRONIZE™-1 in people with obesity without type 2 diabetes (T2D) and SYNCHRONIZE™-2 in people with obesity and T2D. This paper describes the baseline characteristics of participants in SYNCHRONIZE-2 (ClinicalTrials.gov identifier NCT06066528).

Materials and methods: Participants aged ≥18 years with a body mass index (BMI) ≥27 kg/m2 and T2D were randomized 1:1:1 to weekly subcutaneous …

Flare Guns And Trauma: Patterns, Severity, And Clinical Implications From Case And National Surveillance Data, Ramsay Hafer, Andrew Huff, Lara Phillips

Department of Emergency Medicine Faculty Papers

Flare guns are pyrotechnic devices capable of causing serious injury due to high-temperature combustion and projectile discharge. Though intended for signaling in maritime or wilderness settings, improper use can result in trauma patterns distinct from those seen with typical burns or fireworks. Despite their severity, flare gun injuries remain underreported and poorly characterized. We conducted a scoping review of PubMed, Scopus, and Ovid to identify 12 case reports involving 13 patients, and reviewed US National Electronic Injury Surveillance System records from 2015 to 2024, identifying 18 flare gun-specific injuries for a combined total of 31 injuries. Demographic, injury mechanism, body …

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

Children’s Nutrition Research Center Staff Publications

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

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 …

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 …

Evaluation Of The Intempo Path Set For Cyberknife Prostate And Lung Sbrt: A Single-Institution Experience, Yingcui Jia, Lei Fu, Shari Rudoler, Eric Gressen, Yevgeniy Vinogradskiy, Qianyi Xu

Department of Radiation Oncology Faculty Papers

PURPOSE: The InTempo adaptive imaging system is an important component of the Accuray CyberKnife System, designed to enhance the system's ability to track and correct tumor motion during treatment. However, a limitation of this feature is the reduction of available nodes for treatment planning. The impact of a reduced number of nodes on the quality of InTempo-based treatment plans has not previously been evaluated. This retrospective study aims to compare the dosimetry of CyberKnife plans with and without The InTempo path set for both prostate and lung stereotactic body radiotherapy (SBRT).

METHODS: This study included twelve consecutive prostate SBRT patients …

Clinical Evaluation Of Nasal Swab Specimens In Vtm/Utm And Respdirect Estm Using The Panther Fusion Sars-Cov-2/Flu A/B/Rsv Assay., Salika M. Shakir, Robert K. Mccall, Rangaraj Selvarangan, Dithi Banerjee, Yitz Goldstein, Christine Lansang, Rachel Bogh, Carmelle V. Remillard, Respdirect Clinical Study Group

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Respiratory viral infections by SARS-CoV-2, influenza A and B viruses, and RSV overlap in disease signs and symptomology, but differ in treatment modality. Nasal swab specimens have been shown to be an effective alternative specimen type for SARS-CoV-2 detection.

OBJECTIVES: This study evaluated the performance of the Panther Fusion® SARS-CoV-2/Flu A/B/RSV assay in anterior nasal swab specimens (self- or healthcare professional [HCP]-) collected in either viral/universal (VTM/UTM) transport media or the Hologic® RespDirect® collection kit (RespDirect swab in enhanced specimen transport media [eSTM]).

STUDY DESIGN: A multicenter study was conducted from October 2022 to March 2024. A total of …

Pharmacogenomics Of Thiopurine Drugs: A Bench-To-Bedside Success Story In Thailand., Mohitosh Biswas, Shobana John, Murshadul Alam Murad, Chonlaphat Sukasem

Manuscripts, Articles, Book Chapters and Other Papers

Thiopurine drugs are the cornerstone treatment for many diseases such as acute lymphoblastic leukemia (ALL), organ rejection, inflammatory bowel disease (IBD), systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and other autoimmune diseases. However, their clinical use faces limitations due to the drug-induced adverse effects, including myelosuppression. Several genetic associations have been evaluated for their association with these adverse drug reactions. TPMT and NUDT15 polymorphisms have emerged as important clinical markers for predicting and optimizing the safety and effectiveness of thiopurine drugs. The bench-to-bedside approach of exploring and assessing the genetic associations of TPMT and NUDT15 variants and the new LC-MS/MS …

Intraoperative Care And Complications Of Symptomatic Adolescent And Young Adult Patients Undergoing Laparoscopy To Diagnose And/Or To Treat Endometrioses: A Multi-Institutional Review., Jacquelyn R. Evans, Katherine Bergus, Lindsey Asti, Lesley L. Breech, Ruiqi Cen, Yuan Yuan Gong, S Paige Hertweck, Holly R. Hoefgen, Anne H. Horne, Ashli A. Lawson, Seema Menon, Kathleen E. O'Brien, Shashwati Pradhan, Brenna Rachwal, Yolanda R. Smith, Priya Suvarna, Sarah Van Son, Geri Hewitt

Manuscripts, Articles, Book Chapters and Other Papers

STUDY OBJECTIVE: This multi-institutional, retrospective study explores the risks of laparoscopy for diagnosis and treatment of endometriosis to facilitate shared medical decision-making in patients age < 22 years old with chronic pain considering surgery.

METHODS: A retrospective review of patients less than 22 years old who had surgically proven endometriosis at eight pediatric hospitals was completed. Patient demographics, operative interventions, concurrent procedures, and complications were evaluated.

RESULTS: There were 284 patients with pathologically confirmed endometriosis with a median age of 16.86 years (15.51, 18.06). During the index procedure, diagnostic biopsy alone was performed (35.92%), followed by ablation (29.93%), excision (20.07%), excision and ablation (12.68%), and cryoablation (1.41%). Most common …

Loss Of Ctlh Component Maea Impairs Dna Repair And Replication And Leads To Developmental Delay., Søren H. Hough, Satpal S. Jhujh, Samah W. Awwad, Oliver E. Lewis, Simon Lam, John C. Thomas, Thorsten Mosler, Aldo Bader, Lauren E. Bartik, Shane Mckee, Shivarajan Amudhavalli, Estelle Colin, Nadirah Damseh, Emma Clement, Pilar Cacheiro, Anirban Majumdar, Damian Smedley, Joël Fluss, Rosalinda Giannini, Isabelle Thiffault, Guido Zagnoli Vieira, Rimma Belotserkovskaya, Stephen J Smerdon, Petra Beli, Yaron Galanty, Christopher J. Carnie, Grant S. Stewart, Stephen P. Jackson

Manuscripts, Articles, Book Chapters and Other Papers

Ubiquitin E3 ligases play crucial roles in the DNA damage response (DDR) by modulating the turnover, localization, activation, and interactions of DDR and DNA replication proteins. We performed a CRISPR-Cas9 knockout screen focused on ubiquitin E3 ligases and related proteins with the DNA topoisomerase I inhibitor camptothecin. This led us to establish that MAEA, a core subunit of the CTLH E3 ligase complex, is a critical regulator of homologous recombination and the replication stress response. In tandem, we identified eight patients with variants in MAEA who present with a neurodevelopmental disorder that we term DIADEM (Developmental delay and Intellectual disability …

The Influence Of Preoperative Bowel Preparation On Surgical Site Infection In Pediatric Colorectal Surgery., Katlyn G. Mckay, Naomi-Liza Denning, Rebecca M. Rentea, Eunice Y. Huang

Manuscripts, Articles, Book Chapters and Other Papers

Surgical site infection (SSI) is one of the most common nosocomial infections that occur in pediatric patients in the United States, with colorectal procedures consistently demonstrating the highest rates of SSI. Strategies to reduce SSI in colorectal surgery include standardized perioperative colorectal care bundles, which commonly incorporate preoperative bowel preparation. Robust adult literature exists supporting the use of mechanical bowel preparation in combination with oral antibiotics to mitigate SSI; however, pediatric evidence remains less definitive. Current pediatric literature shows heterogeneity of bowel preparation use amongst surgeons, with existing literature consisting primarily of small retrospective studies. A well-designed pediatric randomized controlled …

Rare Heterozygous Missense Variants In Vsx2 Are Associated With Retinal Detachment, Daniel C Brock, Justin S Dhindsa, Yifan Chen, Vida Ravanmehr, Jonathan Mitchell, Fengyuan Hu, Xiaoyin Li, Likhita Nandigam, Quanli Wang, Kevin Wu, Jessica C Butts, Hardeep S Dhindsa, Benjamin J Frankfort, Nicholas M Tran, Slavé Petrovski, Ryan S Dhindsa

Duncan NRI Faculty and Staff Publications

Retinal detachment (RD) is a sight-threatening emergency requiring urgent intervention to prevent permanent vision loss. While both environmental and genetic risk factors contribute to RD, its complete genetic architecture remains unknown. Here, we performed the largest whole genome sequencing-based case-control study in RD to date, including data from 7,276 RD cases and 236,741 controls in the UK Biobank. Through variant- and gene-level association analyses, we identified VSX2 as a genetic determinant of RD risk while confirming established associations including FAT3, RDH5, and COL2A1. Gene-level collapsing analysis revealed that rare heterozygous missense variants in VSX2 confer a 2.8-fold …

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 …

Maternal Myo-Inositol Intake And Congenital Heart Defects In Offspring: A Population-Based Case-Control Study, Ruiqi Cen, L Joseph Su, Jun Ying, Mohammed S Orloff, Elijah H Bolin, Xiangyang Lou, Lynn M Almli, Lorenzo D Botto, Marilyn L Browne, Richard H Finnell, Mary M Jenkins, Eirini Nestoridi, Andrew F Olshan, Paul A Romitti, Gary M Shaw, Wendy N Nembhard

Faculty, Staff and Students Publications

Objective: To investigate associations between maternal periconceptional (three months prior through the third pregnancy month) myo-inositol intake and the odds of selected congenital heart defects in offspring.

Design: A population-based case-control study using the National Birth Defects Prevention Study (NBDPS) database.

Setting: United States.

Population or sample: Women with singleton live births without major birth defects (controls) and women with singleton live births, stillbirths, or terminations with selected nonsyndromic congenital heart defects (CHD; cases).

Methods: Descriptive analyses, logistic regression models, ascertainment of myo-inositol intake from supplements and food using a shortened food frequency questionnaire and survey.

Main outcome measures: Odds …

Utilization Of Intensive Care Interventions In Critically Ill Patients With Candidemia Versus Bacteremia: A Multicenter Retrospective Cohort Study, Mary North Jones, Masayuki Nigo, Stefano Casarin, James Kurian, Aarjav Sanghvi, Enshuo Hsu, Stephen L Jones, Ashton Connor, David B Corry, Cesar A Arias, Max W Adelman

Faculty, Staff and Students Publications

Objectives: Candida species are one of the most common causes of ICU-onset bloodstream infection (BSI). Yet, there is no robust guidance on when to initiate empiric antifungals for ICU patients suspected of BSI. We compared patients with ICU-onset candidemia vs. ICU-onset bacteremia to determine which patients may benefit from empiric antifungals.

Design: We compared characteristics between patients with bacteremia vs. candidemia at time of culture. We determined risk factors for death and constructed a multivariable regression to determine if candidemia is an independent risk factor for death.

Setting/patients: We included ICU patients from a hospital system in Houston, Texas (n …

Visit-Level Quality Measurement Reveals Missed Opportunities And Overuse In Preventive Oral Health Care, Bunmi Tokede, Suhasini Bangar, Swaroop Gantela, Ryan Brandon, Alfa Yansane, Donald B Rindal, Don Worley, Joel White, Joanna Mullins, Ana Neumann, Todd Johnson, Nicholas Skourtes, Gregory Olson, Janelle Urata, Heather Weidner, Katie Lamberger, Aaron Truong, Heiko Spallek, Elsbeth Kalenderian, Muhammad F Walji

Faculty, Staff and Student Publications

Background: Traditional annual dental quality measures fail to capture real-time care delivery and can mask critical gaps in patient-specific treatment. The authors developed and implemented visit-level adaptations of established caries quality measures to enable actionable, point-of-care assessment.

Methods: The authors conducted a retrospective analysis of 1.09 million dental visits across 400,000 patients (2021-2023) at 4 US institutions using axiUm (Henry Schein Corp) or Epic (Epic Systems) electronic health records. The authors transformed 2 annual measures involving caries risk assessment and risk-based preventive treatment into visit-level metrics using a 2 × 2 matrix framework: action due and performed, due and not …

Therapeutic Potential Of C1-Inhibitor In Vascular Diseases And Beyond, Linda Sundler Björkman, Harish Eswaran, Steven P Grover

Faculty, Staff and Student Publications

C1INH (C1-inhibitor) is a multifunctional SERPIN (serine protease inhibitor) that functions as a major negative regulator of the complement, coagulation, and kallikrein-kinin systems. C1INH products were originally developed for the treatment of hereditary angioedema associated with C1INH deficiency. A growing body of literature indicates that C1INH products may find utility in the management of several other disease states. In this review, we detail the key biological activities of C1INH and consider the pathophysiological role of C1INH targets in many conditions. The therapeutic potential of exogenous C1INH is highlighted in the settings of thromboembolism, ischemia-reperfusion injury, sepsis, transplantation, and coronavirus disease …

Urinary Biomarkers Of Acute Kidney Injury In Neonates < 25 Weeks’ Gestation: A Pilot Study, Jazmin D Humphreys, Aman Jain, Amir M Khan, Tina O Findley, Mar Romero-Lopez, Sepideh Saroukhani, Rita D Swinford, Matthew A Rysavy

Faculty, Staff and Student Publications

Background: Acute kidney injury (AKI) occurs in 30% of premature neonates and is associated with adverse outcomes that may be mitigated with early detection. Diagnosis of AKI relies on serum creatinine (SCr) which has several limitations, including lack of sensitivity and specificity. There are limited data on the utility of alternative urine biomarkers to predict AKI in neonates born at < 25 weeks' gestation.

Methods: Urine was collected from neonates born at < 25 weeks' gestation during the first postnatal week. Two urine AKI biomarkers, neutrophil gelatinase-associated lipocalin (NGAL) and epidermal growth factor (EGF) were measured. Study participants were prospectively followed to determine development of AKI, defined by the neonatal modified Kidney Disease-Improving Global Outcomes (KDIGO) criteria, during the first postnatal week. The association of NGAL and EGF with AKI was analyzed using mixed-effect linear regression models adjusting for gestational age at birth.

Results: A total of 26 neonates were enrolled in this study. After adjusting for gestational age at birth, the mean difference in log-transformed biomarkers at three time points for urine NGAL and …

Markvcid2 Consortium For Clinical Validation Of Biomarkers Of Cerebral Small Vessel Disease: Validation Framework And Baseline Characteristics, Steven M Greenberg, Marylin S Albert, Hongyu An, Konstantinos Arfanakis, Arnold M Evia, Arvind Caprihan, Andria L Ford, Myriam Fornage, Gregory S Day, Jason D Hinman, Gregory A Jicha, Amir H Kashani, Joel H Kramer, Christian Lachner, Jin-Moo Lee, Peiying Liu, Hanzhang Lu, Pauline Maillard, Ronald C Petersen, Bruce M Psaty, John M Ringman, Gary A Rosenberg, Claudia L Satizabal, Sean I Savitz, Julie A Schneider, Sudha Seshadri, Prashanthi Vemuri, Danny J J Wang, Donna M Wilcock, B Gwen Windham, Rong Zhang, Carissa Tuozzo, Herpreet Singh, Sue Moy, Vilma Okey-Ewurum, Courtney B Page, Hillary Mulder, Pia Kivisäkk, Deborah Blacker, Lidiya Mazina, Karl G Helmer, Kristin Schwab, Lisa M Wruck, Roderick A Corriveau

Faculty, Staff and Student Publications

Objective: To establish a framework for validating candidate biomarkers of cerebral small vessel diseases (SVD) associated with cognitive impairment and characterize individuals enrolled by the MarkVCID2 consortium under this framework.

Methods: Participants age 60 to 90 years were enrolled across 17 MarkVCID2 sites. Recruitment was targeted to enrich in cognitive symptoms (mild dementia, mild cognitive impairment, subjective cognitive decline), defined risk factors (diabetes mellitus, advanced hypertension), and Black/African American, White, and Hispanic/Latino subgroups. Enrolled participants underwent baseline visits that included cognitive testing, multimodal magnetic resonance imaging (MRI), and biofluid collection. Provisional risk for SVD-related cognitive decline was estimated primarily by …

Outcomes Of Witnessed Versus Unwitnessed Patients With Stroke After Endovascular Therapy In The Extended Time Window, Liisa Tomppo, Nicolas Martinez-Majander, Muhammad M Qureshi, Thanh N Nguyen, Raul G Nogueira, Simon Nagel, Jelle Demeestere, Volker Puetz, Hilde Henon, Marta Olive-Gadea, João Pedro Marto, Anne Dusart, Peter A Ringleb, Osama O Zaidat, Diogo C Haussen, Mahmoud H Mohammaden, Mohamad Abdalkader, Jean Raymond, Santiago Ortega-Gutierrez, Sunil A Sheth, Hiroshi Yamagami, João Nuno Ramos, Francois Caparros, Daniel P O Kaiser, Marc Ribo, Sergio Salazar-Marioni, Kanta Tanaka, Pekka Virtanen, Ajit S Puri, James E Siegler, Syed F Zaidi, Mouhammad Jumaa, Eugene Lin, Jordi Mayol, Rita Ventura, Simon Winzer, Piers Klein, Flavio Bellante, Jorge Cespedes, Anke Wouters, Hesham E Masoud, Liqi Shu, Alicia C Castonguay, Christian Herweh, Monica Cheng, Wei Hu, Daniel Roy, Shadi Yaghi, Robin Lemmens, Charlotte Cordonnier, Markus A Möhlenbruch, Daniel Strbian

Faculty, Staff and Student Publications

Background: It remains unclear whether outcomes of patients treated with endovascular thrombectomy with large-vessel occlusion and unwitnessed onset of stroke differ from those with witnessed onset in the extended time window.

Methods: We enrolled patients with anterior circulation large-vessel occlusion (internal carotid artery, M1, or M2 segment of the middle cerebral artery) undergoing endovascular thrombectomy within 6 to 24 hours from the time last seen well, from 2014 to 2022, at 66 sites in Europe, North America, and Asia. Patients with a prestroke modified Rankin Scale score of >3 or age < 18 were excluded. We categorized patients by onset mode as witnessed or unwitnessed. The primary outcome was the modified Rankin Scale shift at 90 days. Secondary outcomes were functional independence, a composite of functional independence or return of Rankin to prestroke level, symptomatic intracranial hemorrhage, mortality, and a composite of severe disability or mortality at 90 days. We applied inverse probability of treatment weighting to compare outcomes between the groups.

Results: Of 5098 patients assessed for eligibility, we included …