Digital Commons Network^™

Use Of The Selective Cytopheretic Device With Continuous Renal Replacement Therapy In Children: A Comparison Of Contemporary Cohorts, Natalja L Stanski, Jangdong Seo, Todd Jenkins, Kelli A Krallman, Shina Menon, H David Humes, David J Askenazi, Rajit K Basu, Ayse Akcan-Arikan, Stuart L Goldstein, Katja M Gist

Faculty, Staff and Students Publications

Introduction: The selective cytopheretic device (SCD) is a cell-directed extracorporeal therapy approved for use in children with acute kidney injury (AKI) receiving continuous renal replacement therapy (CRRT) with sepsis/sepsis-like conditions. We compared outcomes for children treated with SCD to a contemporary cohort of children treated with CRRT alone.

Methods: Secondary analysis and comparison of patients ≤22 years old and ≥10 kg from a multicenter registry of patients receiving CRRT for AKI and/or fluid overload (WE-ROCK; 2015-2021) to patients from two multicenter, prospective, interventional studies of children with AKI and multiple organ dysfunction (MODS) receiving SCD (SCD-PED-01/SCD-PED-02; 2016-2022).

Results: Eighteen patients …

A Quantitative, Bayesian-Informed Approach To Gene-Specific Variant Classification: Updated Expert Panel Recommendations Improve Classification Of Tp53 Germline Variants For Li-Fraumeni Syndrome, Cristina Fortuno, Megan N Frone, Jessica Mester, Miguel De La Hoya, Phuong L Mai, Tina Pesaran, Maria Isabel Achatz, Rebecca Bassett, Carolina Bustamante, Stephanie Crowley, Kelvin Cesar De Andrade, D Gareth Evans, Bingjian Feng, Laura Fuqua, Maria Isabel Harrell, Jessica N Hatton, Robert Huether, Chimene Kesserwan, Kristy Lee, Suzanne P Macfarland, Jamie L Maciaszek, Kara Maxwell, Kelly Mcgoldrick, Maureen Murphy, Bita Nehoray, Judith Penkert, Emilia Modolo Pinto, Sharon E Plon, Alison Schwartz-Levine, Ashley S Thompson, Wenyi Wang, Gerard P Zambetti, Kristin Zelley, Paul A James, Sharon A Savage, Christian P Kratz, Amanda B Spurdle

Faculty, Staff and Students Publications

Background: Germline pathogenic variants in TP53 cause Li-Fraumeni syndrome, with significantly elevated cancer risk from infancy. Accurate classification of TP53 variants is essential to guide clinical management and surveillance, yet many variants remain classified as variants of uncertain significance (VUS). To improve classification accuracy and reduce the proportion of VUS, the ClinGen TP53 Variant Curation Expert Panel (VCEP) has updated its specifications.

Methods: The updated specifications incorporate the latest ClinGen recommendations and methodological advances, providing greater granularity for multiple evidence types, and also introduce the novel use of variant allele fraction as evidence of pathogenicity, particularly in the context of …

Genome-Wide Association Study Of Childhood B-Cell Acute Lymphoblastic Leukemia Reveals Novel African Ancestry-Specific Susceptibility Loci, Cindy Im, Andrew R Raduski, Lauren J Mills, Kashi Raj Bhattarai, Robert J Mobley, Kelly R Barnett, Zhanni Lu, Kenneth Liao, Nathan Anderson, Rebecca A Johnson, Erica Langer, Anthony J Hooten, Alix E Seif, Kathrin M Bernt, Matthew Tsang, Brandon A Mamou, Luis Gil-De-Gómez, Julie A Wolfson, Danielle N Friedman, Neerav Shukla, Laura J Klesse, Erin L Marcotte, Lingyun Ji, Alice Dang, Minjie Luo, Yiming Zhong, Jalen Langie, Charleston W K Chiang, Adam De Smith, Joseph L Wiemels, Andrew Dewan, Xiaomei Ma, Catherine Metayer, Zhaoming Wang, Heather H Nelson, Nathan Pankratz, Tianzhong Yang, Saonli Basu, Lucie M Turcotte, Jun J Yang, Daniel Savic, Michael E Scheurer, Logan G Spector

Faculty, Staff and Students Publications

B-cell acute lymphoblastic leukemia (B-ALL) is the most common pediatric malignancy. Given racial/ethnic differences in incidence and outcomes, B-ALL genome-wide association studies among children of African ancestry are needed. Leveraging multi-institutional datasets with 840 African American children with B-ALL and 3360 controls, nine loci achieved genome-wide significance (P <  5 × 10−8) after meta-analysis. Two loci were established trans-ancestral susceptibility regions (IKZF1, ARID5B), while the remaining novel loci were specific to African populations. Five-year overall survival among children carrying novel risk alleles was significantly worse (83% versus 96% in non-carriers, P = 4.8 × 10−3). Novel risk variants were also associated with subtype-specific disease (P <  0.05), including higher susceptibility for a subtype overrepresented in African American children (TCF3-PBX1) and lower …

Emergency Department-Initiated Palliative Care Screening Among Older Adults: A Systematic Review And Meta-Analysis Protocol, Dimitri E Lin, Satheesh Gunaga, Fabrice I Mowbray, Eric D Isaacs, Daniel Markwalter, Naomi George, Alison E Hay, Rita Manfredi, Erica Westlake, Murtaza Akhter, Jason K Bowman, Naomi Rebollo-Lee, Brian Gacioch, Alexander D Ginsburg, Justin Kenneth Brooten, Sarah Pajka, Katie Selman, Paul Bain, Joshua J Davis, Shan Liu, Kei Ouchi

Faculty, Staff and Students Publications

Introduction: The rapidly growing population of older adults (individuals aged 65 years and older) presents a new set of challenges for healthcare providers in the emergency department (ED), given the prevalence of severe and life-threatening conditions among this group, such as chronic cancer, Alzheimer's disease/dementia and congestive heart failure. ED encounters often represent a critical point in an older patient's trajectory of care and can thus be an important opportunity for various interventions such as palliative care consultation. Therefore, identifying those who will benefit most from palliative care is of high importance, especially in determining the course of future treatment. …

Everolimus And Low-Dose Tacrolimus After Heart Transplant In Children: A Randomized Clinical Trial, Christopher S Almond, Kevin P Daly, Erin L Albers, Juan C Alejos, Rebecca Ameduri, Scott R Auerbach, Lynsey Barkoff, Aliessa P Barnes, Matthew J Bock, Arene Butto, Waldemar F Carlo, Chesney D Castleberry, Maryanne R Chrisant, Shriprasad R Deshpande, William J Dreyer, Melanie D Everitt, Brian Feingold, Selena Gonzales, Seth A Hollander, Steven J Kindel, Gloria L Klein, Ashwin K Lal, Jacqueline M Lamour, Joanne Lee, Minmin Lu, Irene D Lytrivi, Shelley D Miyamoto, Elfriede Pahl, David M Peng, Thomas D Ryan, Tajinder P Singh, Jennifer A Su, David L Sutcliffe, A Marian Ybarra, Steven Zangwill, Joseph W Rossano, Lynn A Sleeper

Faculty, Staff and Students Publications

Importance: Studies suggest that everolimus may reduce the risk of rejection, cardiac allograft vasculopathy (CAV), chronic kidney disease (CKD), and cytomegalovirus (CMV) after heart transplant. Everolimus use is controversial because of data demonstrating higher infection deaths when everolimus is introduced de novo after transplant. It is unclear whether everolimus is safe and effective when initiated at 6 months posttransplant in children, a population in which median graft survival is limited to 15 years and randomized clinical trials are lacking.

Objective: To evaluate the safety and efficacy of everolimus combined with low-dose tacrolimus to prevent major adverse transplant events (MATEs) in …

Apoa1 Binding Protein Promotes Lymphatic Cell Fate And Lymphangiogenesis By Relieving Caveolae-Mediated Inhibition Of Vegfr3 Signaling, Jun-Dae Kim, Surbhi Chaudhary, Weiqing Chen, Jonathan Astin, Philip S Crosier, Pengchun Yu, John P Cooke, Henry J Pownall, Hugo J Bellen, Nhat-Tu Le, Daniel L Kiss, Guangyu Wang, Stanley G Rockson, Hong Chen, Longhou Fang

Faculty, Staff and Students Publications

The lymphatic system maintains tissue fluid balance, and its dysfunction can result in lymphedema. Although cholesterol is essential for cellular function, its role in lymphatic development has remained unknown. Here, we identify APOA1 binding protein (AIBP) as a key regulator that promotes lymphatic endothelial cell fate specification and lymphangiogenesis. Mechanistically, AIBP reduces plasma membrane cholesterol content, thereby enhancing VEGFR3 signaling by disrupting caveolae—small plasma membrane invaginations formed by the scaffolding protein caveolin-1 (CAV-1)—and relieving CAV-1–mediated inhibition. In zebrafish and mice, AIBP loss impairs VEGFR3 signaling and lymphatic development, defects that can be rescued by CAV-1 deletion or by a VEGFR3 …

Sperm And Offspring Production In A Nonobstructive Azoospermia Mouse Model Via Testicular Mrna Delivery Using Lipid Nanoparticles, Daisuke Mashiko, Chihiro Emori, Yuki Hatanaka, Daisuke Motooka, Chen Pan, Yuki Kaneda, Martin M Matzuk, Masahito Ikawa

Faculty, Staff and Students Publications

Microsurgical testicular sperm extraction (microTESE) with intracytoplasmic sperm injection (ICSI) represents the current standard treatment for nonobstructive azoospermia (NOA). However, cures remain unavailable for NOA patients lacking retrievable haploid cells. mRNA supplementation could be a potential treatment for genetic defects leading to impaired spermatogenesis. Lipid nanoparticles (LNPs) have emerged as mRNA delivery vehicles with minimal risk of genome integration; however, their ability to selectively deliver mRNA to specific cell types remains limited. To overcome this, microRNA (miRNA) target sequences were incorporated into mRNA constructs to restrict expression specifically to germ cells. Using pyruvate dehydrogenase E1 subunit alpha 2 (PDHA2) knockout …

Clinical Course And Treatment Outcomes In Solid-Basaloid Adenoid Cystic Carcinoma Of The Breast: A Systematic Review And Case Report, Stephanie Kim, Kyle Sheth, Xiaoying Yu, Laura Porterfield, Elizabeth M Vaughan

Faculty, Staff and Students Publications

Background: Adenoid Cystic Carcinoma (ACC) is a rare, indolent subtype of triple-negative breast cancer, accounting for < 0.1 % of cases. The solid-basaloid subtype (SBACC), comprising approximately one-quarter of breast ACCs, has a poorer prognosis. While ACC is typically managed with surgery and is chemo-resistant, SBACC is more aggressive and often treated with chemotherapy and, more recently, immunotherapy-though supporting evidence remains limited.

Aim: To assess clinical characteristics and treatment outcomes of SBACC of the breast.

Methods: This study presents a case of breast SBACC and a systematic review of five databases (inception-September 10, 2024). Eligible studies reported clinical course, treatment, and outcomes. Exclusions included duplicates, non-SBACC focus, animal studies, and those lacking clinical or with only pathological data. Descriptive statistics were used for binary and categorical variables. Risk of bias was assessed using JBI tools, following PRISMA 2020 guidelines. The review is registered in PROSPERO.

Results: …

Biallelic Loss-Of-Function Variants In C19orf44 Lead To Retinal Degeneration, Hafiz Muhammad Jafar Hussain, Wang Meng, Yumei Li, Sabika Firasat, Mark E Pennesi, Michael B Gorin, Bin Guan, Rebecca Lynn Clark, Emma Fale-Olsen, Ranya Al Rawi, Aime Agather, Laryssa A Huryn, Paul Yang, Anna Matynia, Rui Chen

Faculty, Staff and Students Publications

Background: Inherited retinal diseases (IRDs) are a group of disorders often resulting in progressive vision loss, ultimately leading to blindness. A significant portion of their genetic causes remain unresolved, partly due to undiscovered disease-associated genes or variants. This study aimed to identify novel genetic links to IRDs.

Methods: All patients underwent comprehensive ophthalmological evaluation, including retinal imaging (fundus autofluorescence and macular optical coherence tomography) and electroretinogram testing. Whole exome sequencing and whole genome sequencing were performed on patients with clinically unsolved IRD, and data were analysed using an in-house pipeline to identify causal variants. Subsequently, Sanger sequencing was performed to …

Global Age-Sex-Specific All-Cause Mortality And Life Expectancy Estimates For 204 Countries And Territories And 660 Subnational Locations, 1950–2023: A Demographic Analysis For The Global Burden Of Disease Study 2023, Gbd 2023 Demographics Collaborators

Faculty, Staff and Students Publications

BACKGROUND: Comprehensive, comparable, and timely estimates of demographic metrics-including life expectancy and age-specific mortality-are essential for evaluating, understanding, and addressing trends in population health. The COVID-19 pandemic highlighted the importance of timely and all-cause mortality estimates for being able to respond to changing trends in health outcomes, showing a strong need for demographic analysis tools that can produce all-cause mortality estimates more rapidly with more readily available all-age vital registration (VR) data. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) is an ongoing research effort that quantifies human health by estimating a range of epidemiological quantities of …

Global Burden Of 292 Causes Of Death In 204 Countries And Territories And 660 Subnational Locations, 1990–2023: A Systematic Analysis For The Global Burden Of Disease Study 2023, Gbd 2023 Causes Of Death Collaborators

Faculty, Staff and Students Publications

Background: Timely and comprehensive analyses of causes of death stratified by age, sex, and location are essential for shaping effective health policies aimed at reducing global mortality. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023 provides cause-specific mortality estimates measured in counts, rates, and years of life lost (YLLs). GBD 2023 aimed to enhance our understanding of the relationship between age and cause of death by quantifying the probability of dying before age 70 years (70q0) and the mean age at death by cause and sex. This study enables comparisons of the impact of causes of …

The Fast And The Very Fast: High-Frequency Oscillations In Alzheimer's Disease, Manuel Silva-Pérez, Jeannie Chin

Faculty, Staff and Students Publications

Alzheimer's disease increases the risk of developing epilepsy together with cognitive decline. Early diagnosis or prediction of parameters associated with epileptic activity can greatly help in managing disease outcomes. Network hyperexcitability is a candidate of interest as a neurophysiological biomarker of Alzheimer's disease. High-frequency oscillations are increasingly recognized as potential biomarkers of hyperexcitability and epileptic activity. However, they have not yet been identified in Alzheimer's disease. In this study, we measured high-frequency oscillations via magnetoencephalography recordings in Alzheimer's disease patients with and without epileptic activity, as part of a Phase 2a randomized, double blind clinical trial of the efficacy of …

Cep76 Impairment At The Centrosome-Cilium Interface Contributes To A Spectrum Of Ciliopathies, Kamal Khan, Erika Tavares, Katherine Bishara, Aysegul Ozanturk, Leila Qebibo, Stephan Frangakis, Daniel G Calame, Isabelle Meunier, Béatrice Bocquet, Rafal Ploski, Mohammad Ayman Al Khateeb, Dana Marafi, Luke Mansard, Lena Damaj, Richard A Lewis, Farid Ullah, Thomas Arbogast, Jackson P Ogden, Madeleine Harion, Marjolaine Willems, Maha S Zaki, Tobias Bartolomaeus, Anne-Françoise Roux, James R Lupski, Malgorzata Rydzanicz, Rami Abou Jamra, Francis Ramond, Elise Heon, Lydie Burglen, Erica E Davis

Faculty, Staff and Students Publications

Dysfunction at the centrosome-cilium interface underlies a broad range of ciliopathies. Here, we identify biallelic variants in CEP76, encoding a centrosomal protein, in eight unrelated individuals presenting with neurodevelopmental, ocular, and variable additional multisystem features. Proband-derived fibroblasts and CEP76-depleted RPE1 cells display ciliary deficits, including impaired cilium formation and length, disrupted transition zone architecture, and impaired IFT88-mediated anterograde intraflagellar transport. Zebrafish cep76 mutants recapitulate key clinical phenotypes, and in vitro complementation assays confirm pathogenicity for all tested human disease-associated variants. Proteomics analysis identifies CEP76 interactors, including known partners CCP110 and CEP97, and highlights clinically and functionally relevant candidates, including …

Metabolic Impact Of Dietary Glycine Supplementation In Individuals With Severe Obesity, Hong Chang Tan, Jean W Hsu, E Shyong Tai, Shaji Chacko, Vieon Wu, Paul M Yen, Jean-Paul Kovalik, Farook Jahoor

Faculty, Staff and Students Publications

Glycine plays a central role in human metabolism, and an adequate supply is required for synthesizing glutathione (GSH), eliminating excess metabolites as acylglycine via the glycine conjugation detoxification pathway, and maintaining 1-carbon cycle activity. However, glycine is deficient in individuals with severe obesity, which may compromise these pathways and metabolic health. This exploratory study examines whether dietary glycine supplementation could correct glycine deficiency and impairments in glycine-dependent metabolic pathways. 19 participants with severe obesity (BMI 38.3 ± 5.3 kg/m2) were treated with dietary glycine (100 mg/kg/day) for two weeks. We found that treatment significantly increased the plasma concentration of glycine …

Genetic Determinants And Genomic Consequences Of Non-Leukemogenic Somatic Point Mutations, Joshua S Weinstock, Sharjeel A Chaudhry, Maria Ioannou, Maria Viskadourou, Paula Reventun, Yasminka A Jakubek, L Alexander Liggett, Cecelia Laurie, Jai G Broome, Alyna Khan, Kent D Taylor, Xiuqing Guo, Patricia A Peyser, Eric Boerwinkle, Nathalie Chami, Eimear E Kenny, Ruth J Loos, Bruce M Psaty, Russell P Tracy, Jennifer A Brody, Jeong H Yun, Michael H Cho, Ramachandran S Vasan, Sharon L Kardia, Jennifer A Smith, Laura M Raffield, Aurelian Bidulescu, Emily C O'Brien, Mariza De Andrade, Jerome I Rotter, Stephen S Rich, Russell P Tracy, Yii Der Ida Chen, C Charles Gu, Chao A Hsiung, Charles Kooperberg, Bernhard Haring, Rami Nassir, Rasika Mathias, Alex Reiner, Vijay G Sankaran, Charles J Lowenstein, Thomas W Blackwell, Goncalo R Abecasis, Albert V Smith, Hyun M Kang, Pradeep Natarajan, Siddhartha Jaiswal, Alexander Bick, Wendy S Post, Paul Scheet, Paul Auer, Theodoros Karantanos, Alexis Battle, Marios Arvanitis

Faculty, Staff and Students Publications

Clonal hematopoiesis (CH) is defined by the expansion of a lineage of genetically identical cells in blood. Genetic lesions that confer a fitness advantage, such as leukemogenic point mutations or mosaic chromosomal alterations (mCAs), are frequent mediators of CH. However, recent analyses of both single cell-derived colonies of hematopoietic cells and population sequencing cohorts have revealed CH frequently occurs in the absence of known driver genetic lesions. To characterize CH without known driver genetic lesions, we use 51,399 deeply sequenced whole genomes from the NHLBI TOPMed sequencing initiative to perform simultaneous germline and somatic mutation analyses among individuals without leukemogenic …

Two Commonly Reported Incidental Variants In Otc Are Associated With Late-Onset Disease, Steven H Lang, Russell S Lo, Gareth A Cromie, Aimée M Dudley, Nicholas Ah Mew, Kara Simpson, Vernon Reid Sutton, Sandra Darilek, Saima Ali, Matthew T Snyder, Brendan Lee, Ronit Marom, Sandesh C S Nagamani, Lindsay C Burrage

Faculty, Staff and Students Publications

Asymptomatic individuals with pathogenic variants in OTC, the gene encoding ornithine transcarbamylase are increasingly being identified through cascade testing, carrier screening, or as secondary findings from genome-wide sequencing tests. However, guidance for counseling and management of such individuals is currently lacking. We selected two common OTC variants for phenotypic and functional characterization: NM_000531.6:c.118C>T p.(Arg40Cys) and NM_000531.6:c.1061T>G p.(Phe354Cys). The former is the most frequently reported pathogenic/likely pathogenic missense variant present in gnomAD, and the latter has been frequently encountered in our clinical practice. We performed a retrospective chart review at our center, queried the database of the Urea Cycle …

Predictors Of Long-Term Follow-Up Clinic Attendance And Continued Engagement Among Survivors Of Cancer In Childhood And Adolescence, Ji Yun Tark, Kayla L Foster, Shawki L Qasim, Omar Shakeel, Alicia Howell, Mary C Shapiro, Abiodun Oluyomi, Zoann E Dreyer, Ashley M Butler, Austin L Brown, Maria M Gramatges

Faculty, Staff and Students Publications

Purpose: Survivorship care is vital to screen for and manage late effects, yet follow-up remains suboptimal. We examined factors associated with long-term survivor clinic (LTSC) nonattendance, delayed initiation, and disengagement at a large, diverse pediatric cancer center.

Methods: We analyzed outcomes in 1138 survivorship-eligible childhood cancer survivors diagnosed between 2011 and 2019. Outcomes included (1) LTSC nonattendance (no visit ≥ 2 years post-treatment), (2) delayed LTSC visit initiation (first visit > 5 years from end of treatment), and (3) LTSC visit disengagement (no follow-up after initial LTSC visit). Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for factors associated with …

Sub-Ciliary Localization Of Cep290 And Effects Of Its Loss In Mouse Photoreceptors During Development, Abigail R. Moye, Michael A. Robichaux, Melina A. Agosto, Alexandre P. Moulin, Alexandra Graff-Meyer, Carlo Rivolta, Theodore G. Wensel

Faculty, Staff and Students Publications

No abstract provided.

Differential Bk Channel Potentiation By Vanzacaftor Enantiomers Enables Therapy For Modulator-Ineligible People With Cystic Fibrosis, Nathalie Baumlin, Sumedha Gunewardena, Scott H Randell, Frank T Horrigan, Matthias Salathe

Faculty, Staff and Students Publications

No abstract provided.

Resilience And Vulnerabilities Of Tumor Cells Under Purine Shortage Stress, Jianpeng Yu, Chen Jin, Cheng Su, David Moon, Michael A Sun, Hong Zhang, Xue Jiang, Fan Zhang, Nomi Tserentsoodol, Michelle L Bowie, Christopher J Pirozzi, Daniel J George, Robert Wild, Xia Gao, David M Ashley, Yiping He, Jiaoti Huang

Faculty, Staff and Students Publications

Purpose: Purine metabolism is a promising therapeutic target in cancer; however, how cancer cells respond to purine shortage, particularly their adaptation and vulnerabilities, remains unclear.

Experimental design: Using the recently developed purine shortage-inducing prodrug DRP-104 and genetic approaches, we investigated the responses in prostate, lung, and glioma cancer models.

Results: We demonstrate that when de novo purine biosynthesis is compromised, cancer cells employ microtubules to assemble purinosomes, multiprotein complexes of de novo purine biosynthesis enzymes that enhance purine biosynthesis efficiency. Although this process enables tumor cells to adapt to purine shortage stress, it also renders them more susceptible to the …

Alterations Of The Upper Respiratory Microbiome Among Children Living With Hiv Infection In Botswana, Sweta M Patel, John Farirai, Mohamed Z Patel, Sifelane Boiditswe, Leabaneng Tawe, Shimane Lekalake, Mogomotsi Matshaba, Andrew P Steenhoff, Tonya Arscott-Mills, Kristen A Feemster, Samir S Shah, Nathan Thielman, Coleen K Cunningham, Lawrence A David, David M Murdoch, Matthew S Kelly

Faculty, Staff and Students Publications

Children living with HIV (CLWH) are at high risk of colonization and infection by respiratory pathogens, though this risk can be reduced by other microbes in the upper respiratory microbiome. The impact of HIV infection on the pediatric upper respiratory microbiome is poorly understood, and we sought to address this knowledge gap by identifying associations between HIV infection and the nasopharyngeal microbiomes of Batswana children. We enrolled Batswana CLWH (< 5 years) and age- and sex-matched HIV-exposed, uninfected and HIV-unexposed, uninfected children in a cross-sectional study. We used shotgun metagenomic sequencing to compare nasopharyngeal microbiomes by HIV status. Among the 143 children in this study, HIV and HIV-associated immunosuppression were associated with alterations in nasopharyngeal microbiome composition, including lower abundances of Corynebacterium species associated with resistance to bacterial pathogen colonization. These findings suggest that the upper respiratory microbiome may contribute to the high risk of respiratory infections among CLWH.

Stereoelectroencephalography Reveals Neural Signatures Of Multisensory Integration In The Human Superior Temporal Sulcus During Audiovisual Speech Perception, Yue Zhang, John F Magnotti, Xiang Zhang, Zhengjia Wang, Yingjia Yu, Kathryn A Davis, Sameer A Sheth, H Isaac Chen, Daniel Yoshor, Michael S Beauchamp

Faculty, Staff and Students Publications

Human speech perception is multisensory, integrating auditory information from the talker's voice with visual information from the talker's face. BOLD fMRI studies have implicated the superior temporal gyrus (STG) in processing auditory speech and the superior temporal sulcus (STS) in integrating auditory and visual speech, but as an indirect hemodynamic measure, fMRI is limited in its ability to track the rapid neural computations underlying speech perception. Using stereoelectroencephalography (sEEG) electrodes, we directly recorded from the STG and STS in 42 epilepsy patients (25F, 17M). Participants identified single words presented in auditory, visual, and audiovisual formats with and without added auditory …

Probabilistic Data Linkage To Study The Epidemiology Of Unintentional Fatal Drowning In A Large Metropolitan Region, Rohit P Shenoi, Ned Levine, Elizabeth A Camp, Linh Nguyen, Sandra Mckay, Shaila Zaman

Faculty, Staff and Students Publications

Background: It is difficult to study the epidemiology of drowning at the regional level because of multiple data sources, many of which have a high degree of unstandardized and missing data. We aimed to link multiple datasets to identify demographics and geographic locations of unintentional fatal drowning in a metropolitan region and compare linked data with vital statistic data.

Methods: This cross-sectional study included unintentional drowning fatalities among persons of all ages in metropolitan Houston between 2016 and 2022. Probabilistic linking was used to link multiple datasets and geographical mapping to identify drowning locations. The effectiveness of data linkage was …

The Clingen Severe Combined Immunodeficiency Disease Variant Curation Expert Panel: Specifications For Classification Of Variants In Ada, Dclre1c, Il2rg, Il7r, Jak3, Rag1, And Rag2, Vanessa C Jacovas, Michelle Zelnick, Shannon Mcnulty, Justyne E Ross, Namrata Khurana, Xueyang Pan, Alejandro Nieto, Shiloh Martin, Benjamin Mclean, Marwa A Elnagheeb, Morton J Cowan, Jennifer M Puck, Mike S Hershfield, James Verbsky, Jolan Walter, Eric J Allenspach, Alice Y Chan, Nicolai S C Van Oers, Rajarshi Ghosh, Megan Piazza, Bo Yuan, Luigi D Notarangelo, Britt A Johnson, Ivan K Chinn, Severe Combined Immunodeficiency Variant Curation Expert Panel

Faculty, Staff and Students Publications

Purpose: This collaborative study, led by the Clinical Genome Resource Severe Combined Immunodeficiency Disease Variant Curation Expert Panel (ClinGen SCID-VCEP), implemented and adapted the American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) guidelines for interpreting germline variants in genes with established relationships to SCID. The effort focused on the 7 most common SCID-related genes identified by SCID newborn screening in North America: ADA, DCLRE1C, IL2RG, IL7R, JAK3, RAG1, and RAG2.

Methods: The SCID-VCEP conducted a rigorous review of variants that involved database analyses, literature review, and expert feedback to derive gene-specific modifications to the ACMG/AMP guidelines. These …

Generative Modeling For Interpretable Anomaly Detection In Medical Imaging: Applications In Failure Detection And Data Curation, Mckell E Woodland, Mais Altaie, Caleb S O'Connor, Austin H Castelo, Olubunmi C Lebimoyo, Aashish C Gupta, Joshua P Yung, Paul E Kinahan, Clifton D Fuller, Eugene J Koay, Bruno C Odisio, Ankit B Patel, Kristy K Brock

Faculty, Staff and Students Publications

This work aims to leverage generative modeling-based anomaly detection to enhance interpretability in AI failure detection systems and to aid data curation for large repositories. For failure detection interpretability, this retrospective study utilized 3339 CT scans (525 patients), divided patient-wise into training, baseline test, and anomaly (having failure-causing attributes—e.g., needles, ascites) test datasets. For data curation, 112,120 ChestX-ray14 radiographs were used for training and 2036 radiographs from the Medical Imaging and Data Resource Center for testing, categorized as baseline or anomalous based on attribute alignment with ChestX-ray14. StyleGAN2 networks modeled the training distributions. Test images were reconstructed with backpropagation and …

Risk Factors And Clinical Significance Of Urologic Injury In Cesarean Hysterectomy For Placenta Accreta Spectrum, J Connor Mulhall, Kayla E Ireland, John J Byrne, Patrick S Ramsey, Georgia A Mccann, Jessian L Munoz

Faculty, Staff and Students Publications

Background/Objectives: Placenta accreta spectrum (PAS) is an obstetric condition with placental adherence to the underling myometrium characterized by significant surgical morbidity at time of delivery. PAS delivery is most commonly performed by cesarean hysterectomy. The most common morbidities associated with PAS cesarean hysterectomy are blood transfusion, intensive care unit admission and urinary tract injuries. This requires interdisciplinary team management including obstetricians and urologists. Our objective was to identify pre- and intra-operative risk factors for urologic injury in this high-risk condition.

Methods: A retrospective cohort study was performed at a single tertiary center with the Center for the Management …

Intracranial Neural Biomarkers Of Psychiatric Symptoms And Their Utility For Guiding Neuromodulation Therapy: A Systematic Review, Katherine E Kabotyanski, Nicole R Provenza, Sameer A Sheth

Faculty, Staff and Students Publications

The quest to develop and improve neuromodulatory therapies for treatment-resistant psychiatric disorders has been fueled by the discovery of intracranial neural biomarkers of symptom dimensions. These neural correlates shed light on the underlying neurophysiology of the disorder and may even be useful in guiding therapy delivery. This systematic review summarizes recent efforts in this field relating neural activity to behavior and symptomatology. For years, the majority of these neurobehavioral relationships had been studied in the hospital or clinic environment. Recent technological advances in implanted neuromodulation devices that permit not only stimulation, but also intracranial neural recording have enabled this research …

A Safety-Ii Approach To Learn From Practice Variation In The Diagnostic Process In The Emergency Department: An Action Research Study, Rick Roos, Laura Zwaan, Myrthe Maranus, Iwan A Meynaar, Vanessa J Valk, Cees Van Nieuwkoop, Gert-Jan Kamps, Hardeep Singh, Maarten O Van Aken

Faculty, Staff and Students Publications

Objectives: The focus on improving patient safety has mainly been by learning from errors and near misses (Safety-I). We applied a novel Safety-II approach to identify and learn from practice variations in the diagnostic process in the emergency department (ED), and subsequently design and implement practice changes.

Methods: In this single-center study, we used action research (cycles of micro-experiments to study and improve processes with active stakeholder involvement) in the diagnostic process. We used three subsequent observation cycles of the following six steps: observations, gathering of follow-up data, analyses, a co-creation session with involved stakeholders, sharing of best practices, and …

Establishing Priority Pediatric Antimicrobial Stewardship Interventions In The Us: Findings From A Delphi Consensus Study, Harry Obeng, Emmanuel Tetteh, Sara Malone, Lauren Walsh, Tyler Walsh, Fernando J Bula-Rudas, Ritu Banerjee, Adam W Brothers, Joshua C Herigon, Katie Namtu, Scott Weissman, Daniel Riggsbee, Jared Olson, Debra Lynn Palazzi, Ann Wirtz, Matthew Sattler, Jessica Tansmore, Brittany A Rodriguez, Monica Abdelnour, Joshua R Watson, Alison C Tribble, Jessica Gillon, Mari Nakamura, Sarah Jones, Jason G Newland, Virginia R Mckay

Faculty, Staff and Students Publications

Background/objectives: Antimicrobial resistance (AMR) is a major global health threat, with children at higher risk due to developmental differences in drug metabolism, limited treatment options and inappropriate antibiotic use. Pediatric antimicrobial stewardship programs (ASPs) face implementation challenges, often relying on adult-based guidelines and limited pediatric-specific evidence. This study aimed to identify and prioritize the most critical areas for pediatric ASP intervention development through a structured, multi-round Delphi consensus process with experts in antimicrobial stewardship and infectious diseases.

Method: A four-round modified Delphi process was conducted to identify and prioritize key pediatric ASP interventions. Experts in antimicrobial stewardship and infectious diseases …

The Effect Of Type 2 Diabetes Genetic Predisposition On Non-Cardiovascular Comorbidities, Ana Luiza Arruda, Ozvan Bocher, Henry J Taylor, Davis Cammann, Satoshi Yoshiji, Xianyong Yin, Chi Zhao, Jingchun Chen, Alexis C Wood, Ken Suzuki, Josep M Mercader, Cassandra N Spracklen, James B Meigs, Marijana Vujkovic, George Davey Smith, Jerome I Rotter, Benjamin F Voight, Andrew P Morris, Eleftheria Zeggini

Faculty, Staff and Students Publications

Type 2 diabetes is associated with a range of non-cardiovascular non-oncologic comorbidities. To move beyond associations and evaluate causal effects between type 2 diabetes genetic predisposition and 21 comorbidities, we apply Mendelian randomization analysis using genome-wide association studies across multiple genetic ancestries. Additionally, leveraging eight mechanistic clusters of type 2 diabetes genetic profiles, each representing distinct biological pathways, we investigate causal links between cluster-stratified type 2 diabetes genetic predisposition and comorbidity risk. We identify causal effects of type 2 diabetes genetic predisposition driven by distinct genetic clusters. For example, the risk-increasing effects of type 2 diabetes genetic predisposition on cataracts …