Digital Commons Network^™

An Examination Of Racial Bias In Scoring The Autism Diagnostic Observation Schedule (Ados) Module 3: An Item Response Theory Analysis, Yuen Yvonne Yu, Austin Wyman, Calliana J Faulk, Lizzy J Fulop, Rebecca L Greenberg, Rachel M Benecke, Lauren K Steinbeck, Jessica Foy, Caitlyn Kim, George O Emory, Eric A Storch, Casey J Zampella, Benjamin E Yerys, Robert T Schultz, Julia Parish-Morris, John D Herrington, Caitlin C Clements

Faculty, Staff and Students Publications

Given the rising prevalence of autism among racial minority children in the United States, but persistent service use disparities, this study examines potential bias in specific items from the autism diagnostic observation schedule (ADOS), a highly regarded autism evaluation. We leveraged unidimensional item response theory graded response models and a sample of 735 children to analyze the differential item functioning (DIF) of items within ADOS Module 3. Three items showed significant signs of racial bias: A1 (overall language level), A5 (offers information), and D5 (compulsions and rituals). On these items, Black/African American and Asian children were usually more likely to …

"He Just Wants Someone To Hear Him And Listen To Him": Barriers And Facilitators To Autistic Youth With Anxiety Receiving Quality Mental Healthcare, Daylin Delgado, Shannon C Lapoint, Grace Lee Simmons, Julia M Heinly, Whitney S Shepherd De, Bridgett Kiernan, Lauren Brookman-Frazee, Eric A Storch, Brenna B Maddox

Faculty, Staff and Students Publications

About half of autistic youth present with clinically interfering anxiety. Psychotherapies with exposure-focused elements are effective in academic clinical settings and controlled trials. However, there is relatively less research examining the implementation of modified interventions for autistic youth with anxiety in community mental health settings. The current study explores community members' perceptions of barriers and facilitators that impact autistic youth with anxiety's receipt of quality mental health services in their community. Semi-structured interviews were conducted with 15 autistic youth, 15 caregivers of autistic youth, 11 community mental health clinicians, and 8 community mental health clinic leaders. Interviews were analyzed thematically. …

Validation Of The French Translation Of The Movement Disorder Society Non-Motor Symptoms Scale (Mds-Nms) In Parkinson's Disease, Clément Desjardins, Stéphan Grimaldi, Sheng Luo, Luowen Yu, Christopher G Goetz, Glenn T Stebbins, Pablo Martinez-Martin, Monica M Kurtis, Tiago A Mestre, Alvaro Sanchez-Ferro, Michelle H S Tosin, Roberta Balestrino, Chi-Ying R Lin, Carmen Gasca-Salas, Tatiana Witjas, Olivier Colin, David Maltete, Luc Defebvre, Caroline Giordana, Mahmoud Charif, Claire Thiriez, Chloé Laurencin, Mélissa Tir, Gwendoline Dupont, Philippe Remy, Christine Tranchant, Sophie Drapier, Alexandra Samier, Isabelle Benatru, Sara Sambin, Jean-Christophe Corvol, Fatma Khelifi, Margherita Fabbri, Olivier Rascol, Ns‐Part Cohort Study Group And The Mds Coa Translation Steering Committee

Faculty, Staff and Students Publications

No abstract provided.

Minifast: A Sensitive And Fast Miniaturized Microscope For In Vivo Neural Recording, Jill Juneau, Guillaume Duret, Joshua P Chu, Blake Madruga, Conor C Dorian, Alexander V Rodriguez, Savva Morozov, Daniel Aharoni, Jacob T Robinson, François St-Pierre, Peyman Golshani, Caleb Kemere

Faculty, Staff and Students Publications

Significance: Observing the activity of large populations of neurons in vivo is critical for understanding brain function and dysfunction. The use of fluorescent genetically encoded calcium indicators (GECIs) in conjunction with miniaturized microscopes is an exciting emerging toolset for recording neural activity in unrestrained animals. Despite their potential, current miniaturized microscope designs are limited using image sensors with low frame rates, sensitivity, and resolution. Beyond GECIs, there are many neuroscience applications that would benefit from the use of other emerging neural indicators, such as fluorescent genetically encoded voltage indicators (GEVIs) that have faster temporal resolution to match neuron spiking, yet …

Recognising Type 5 Diabetes – Authors’ Reply, Meredith Hawkins, Peter Schwarz, Chittaranjan S Yajnik, Mandeep Bajaj, Alvin C Powers, Michael S Boyne, Sarah Wild, Dirk L Christensen, Silver Bahendeka, Angus G Jones, Satinath Mukhopadhyay, Kaushik Ramaiya, David Phillips, Sylvia Kehlenbrink, Davis Kibirige, Charlotte Bavuma, Noel P Somasundaram, Debbie S Thompson, Jacko Abodo, Shitaye Alemu, Prasad Katulanda, Faruque Pathan, Shahjada Selim, Sarah Mathai, Mini Joseph, Mahindra Sonawane, Sandeep Mathur, Shajith Anoop, Sadishkumar Kamalanathan, Prosenjit Mondal, Dukhabandhu Naik, Ullas Kolthur-Seetharam, Riddhi Dasgupta, Felix Jebasingh, Nihal Thomas, Pradnyashree Wadivkar, Allan A Vaag

Faculty, Staff and Students Publications

No abstract provided.

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 …

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 …

The Reversibility Of Urate Tophi With Treat-To-Target In Gout: All Gone. Forever?, Jasvinder A Singh

Faculty, Staff and Students Publications

No abstract provided.

Diagnostic Evaluation And Treatment Of Utis In Children With Neurogenic Bladder, Jacqueline G Holden, Sowdhamini Wallace, Pearl W Chang, Stephanie Davis-Rodriguez, Rana F Hamdy, John M Morrison, Michael J Tchou, Victor Trevisanut, Vijaya Vemulakonda, Catherine S Forster

Faculty, Staff and Students Publications

Objective: Children with neurogenic bladder (NGB) are at increased risk for urinary tract infections (UTIs), but there is a lack of guidelines to assist clinicians in diagnosing and treating these children. Our objective was to describe the presentation and treatment of provider diagnosed UTIs in children with NGB compared to children with vesicoureteral reflux (VUR) and to assess the proportion of children with NGB who met a consortium definition of UTI.

Study design: We included children < 18 years old with either VUR or NGB who were diagnosed in the emergency department with a febrile UTI in our multicenter retrospective cohort study. We extracted and compared UTI symptoms and urinalysis results specific to children with NGB to children with VUR. We measured the proportion of UTI diagnoses concordant with the Urologic Management to Preserve Initial Renal Function (UMPIRE) consensus definition of UTI, defined as ≥ 100,000 CFU/mL of 1 or 2 organisms, pyuria, and ≥ two symptoms of UTI.

Results: The most common symptom among all children in the cohort was vomiting (38.8 %). Of the 215 children with NGB, 41.3 % met …

Artificial Intelligence In Allergy And Immunology: Recent Developments, Implementation Challenges, And The Road Toward Clinical Impact, Merlijn Van Breugel, Matt Greenhawt, Ibon Eguiluz-Gracia, Maria Jose Torres Jaén, Aikaterini Anagnostou, Gerard H Koppelman

Faculty, Staff and Students Publications

Artificial intelligence (AI) is increasingly recognized for its capacity to transform medicine. While publications applying AI in allergy and immunology have increased in number, clinical implementation substantially lags behind other specialties. By mid-2024, over 1,000 US Food and Drug Administration-approved AI-enabled medical devices existed, but none specifically addressed allergy and immunology. This gap partly reflects the field's limited reliance on imaging, which facilitated early AI breakthroughs in radiology and pathology. This narrative review examines recent AI developments, including large language models and AI agents, evaluating their applicability to allergy and immunology practice. We analyze current and potential applications, emphasizing those …

Prospective Evaluation Of The European Society Of Cardiology 0/1h-Algorithm’S Safety And Efficacy For Triage Of Patients With Suspected Myocardial Infarction (Presc1se-Mi): Rationale And Design Of A Prospective International Multicenter Stepped-Wedge Cluster Randomized Controlled Trial, Jasper Boeddinghaus, Paolo Bima, Luca Crisanti, Dagmar I Keller, Ksenija Slankamenac, Michael Christ, Philipp Schuetz, Andrea Wiencierz, Ivo Strebel, Julia Reinhardt, Iryna Vyshnevska, Tzu-Ying Tsao, Felix Mahfoud, Maria Pia Ruggieri, Stephan Steuer, Òscar Miró, Veli-Pekka Harjola, Fulvio Morello, Peiman Nazerian, Dominik Roth, José Luis Zamorano, Deborah Erica Gannon, Jason Pott, Mohammed Oa Abubakr, Hyun Suk Yang, Joe Young, Richina Bicette, Andreea Cuculici, Héctor Bueno, Juan Sanchis, Christian Mueller

Faculty, Staff and Students Publications

Background: International practice guidelines recommend the more rapid European Society of Cardiology (ESC) 0/1h-algorithm for the triage of patients with suspected myocardial infarction (MI) as the preferred option and consider the ESC 0/3h-algorithm as an alternative. However, many centers worldwide have not yet adopted the ESC 0/1h-algorithm in clinical practice due to uncertainty which approach best balances safety and efficacy.

Methods: PRESC1SE-MI (PRospective Evaluation of the European Society of Cardiology 0/1h-algorithm`s Safety and Efficacy for Triage of Patients with Suspected Myocardial Infarction) is an international, investigator-initiated multicenter, stepped-wedge, cluster randomized controlled trial. At least 52,156 consecutive adult patients with nontraumatic …

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 …

The Changing Landscape Of Pediatric Cardiology Fellowship Applications: An Update On Objective Metrics And Current Evaluation Practices, William B Kyle, Tam T Doan, James C Wilkinson

Faculty, Staff and Students Publications

The application process for medical training fellowships has evolved significantly over the last decade. Important changes in access to quantitative data, the standardized application itself, and an unprecedented shift in the interview process have forced fellowship leaders to alter their evaluation process. This study aimed to assess each of those aspects of the pediatric cardiology fellowship application process. We review the application itself, focusing on the Experiences section of the Electronic Residency Application Service (ERAS) evaluation and the Pediatric Cardiology Fellowship Evaluation Form, which accompanies each letter of recommendation (LOR). In addition to these novel analyses, we present peer-reviewed literature …

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.

Dolichocolon Is Common In Pediatric Gastroenterology Patients With Constipation And Associated Complaints, David Simon, Donovan Berens, Raul Zambrana Valenzuela, Arvind Mohan, Partha Chakraborty, Timot Kellermayer, Eric H Chiou, Craig L Jensen, Ricardo A Arbizu, Marla B K Sammer, Richard Kellermayer

Faculty, Staff and Students Publications

Objectives: Dolichocolon (DC), classified under International Classification of Diseases, Tenth Revision (ICD-10) code Q43.8 ("Other specified congenital malformations of intestine"), refers to an elongated or redundant large intestine. Recent studies in adults indicate a role for dolichocolon in constipation and disorders of gut-brain interaction. Contrast enema (CE) imaging is commonly used to identify DC, typically defined as a sigmoid colon extending above, or a transverse colon descending below, the iliac crest line. Despite its potential relevance, the prevalence and clinical significance of DC in pediatric gastroenterology remain poorly understood.

Methods: This retrospective study assessed the prevalence of DC in pediatric …

Secondary Prophylaxis Of Variceal Hemorrhage In Biliary Atresia-Analysis Of Prospective Multicenter Studies, Lee M Bass, Kieran Hawthorne, John C Magee, Benjamin L Shneider, Childhood Liver Disease Research Network (Children)

Faculty, Staff and Students Publications

No abstract provided.

Utility And Utilization Of Transabdominal Ultrasound In Pediatric Patients With Acute Recurrent Or Chronic Pancreatitis, Nicholas Norris, David Troendle, Michael Wilschanski, Fuchenchu Wang, Gretchen A Cress, Maisam A Abu-El-Haija, Ankur Chugh, Reuven Zev Cohen, Elissa M Downs, Douglas S Fishman, Cheryl E Gariepy, Matthew J Giefer, Tanja Y Gonska, Amit S Grover, Sohail Z Husain, Douglas Lindblad, Quin Y Liu, Asim Maqbool, Jacob A Mark, Brian A Mcferron, Megha S Mehta, Veronique D Morinville, Kenneth Ng, Robert A Noel, Chee Y Ooi, Emily R Perito, Zachary M Sellers, Andrew T Trout, Yuhua Zheng, Ying Yuan, Mark E Lowe, Aliye Uc, Consortium For The Study Of Chronic Pancreatitis, Diabetes And Pancreatic Cancer

Faculty, Staff and Students Publications

Objectives: Transabdominal ultrasound (TAUS) is frequently utilized in pediatric acute pancreatitis, but less is known about its use in acute recurrent (ARP) or chronic pancreatitis (CP). Our aim was to describe TAUS utilization and findings from the largest multicenter cohort of pediatric ARP and CP, the International Study Group of Pediatric Pancreatitis: In Search for a CuRE-2 (INSPPIRE-2).

Methods: Demographic and imaging data from physician questionnaires were obtained for patients with available TAUS data. Utilization and findings were compared between ARP and CP groups. Kappa statistics were used to compare agreement of TAUS to computed tomography (CT), magnetic resonance imaging/cholangiopancreatography …

Internet-Delivered Cognitive-Behavioral Intervention For Pain In Pediatric Acute Recurrent And Chronic Pancreatitis: A Multicenter Randomized Controlled Trial, Tonya M Palermo, Rui Li, Chuan Zhou, Homer Aalfs, Gretchen Cress, Mark Lowe, Maisam Abu-El-Haija, Ankur Chugh, Elissa M Downs, Douglas S Fishman, Alvin Jay Freeman, Matthew J Giefer, Tanja Y Gonska, Sohail Z Husain, Douglas Lindblad, Quin Y Liu, Asim Maqbool, Jacob A Mark, Brian A Mcferron, Megha S Mehta, Robert Adam Noel, Emily R Perito, Fuchenchu Wang, Ying Yuan, Yuhua Zheng, Aliye Uc, Consortium For The Study Of Chronic Pancreatitis, Diabetes, And Pancreatic Cancer (Cpdpc)

Faculty, Staff and Students Publications

Objectives: Abdominal pain is common and associated with high disease burden and health care costs in pediatric acute recurrent (ARP) and chronic pancreatitis (CP). Despite the effectiveness of psychological interventions in other abdominal pain populations, studies have not evaluated these interventions for pediatric pancreatitis pain. We evaluated the feasibility, acceptability, and preliminary efficacy of internet-delivered cognitive-behavioral therapy (CBT) for reducing pancreatitis-related abdominal pain and improving pain interference, anxiety, depression, activity limitations, and health-related quality of life.

Methods: We enrolled 90 adolescents (ages 10-19, 63% female) with ARP or CP and their parents into this randomized placebo-controlled multicenter trial from 15 …

Technical Considerations And Contemporary Literature Review Of The Gore Thoracic Branch Endoprosthesis®, Bruno P Schmid, Lucas R Kanamori, Hannah V Oden-Brunson, Dora Babocs, Ying Huang, Jorge Miranda, Steven Maximus, Gustavo S Oderich

Faculty, Staff and Students Publications

Thoracic endovascular aortic repair (TEVAR) has become the preferred treatment for various thoracic aortic pathologies, including blunt thoracic aortic injury, aneurysms, and dissections. Involvement of Ishimaru Zone 2 occurs in up to 60% of TEVAR cases requiring extension across the distal aortic arch and left subclavian artery (LSA). Coverage of the LSA without revascularization increases the risk of complications such as upper extremity ischemia, stroke, and spinal cord injury. Therefore, the preservation of LSA perfusion during TEVAR is essential. Cervical debranching remains an effective alternative to preserve flow to the LSA, but it poses risks of bleeding, infection, and nerve …

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 …

The Hidden Link Between Endometriosis And Obesity: A State-Of-The-Art Review, Shefali N Desai, Christina C Reed, Yamely Mendez, Qiannan Yang, Xiaoming Guan

Faculty, Staff and Students Publications

Endometriosis remains an under-researched disease with a wide range of symptoms. Endometriosis reduces a woman's quality of life and professional productivity, yet its exact causes, risk factors, and treatment have yet to be elucidated. Body mass index and endometriosis have been observed to be inversely related; however, this relationship may only be a correlation rather than a causation. Obesity may play a role in the inflammation and cell proliferation associated with endometriosis through the complex signaling pathways of adipokines. A literature review was done on endometriosis and obesity to gain insight and synthesize knowledge about opportunities to improve endometriosis care, …

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.

Age-Independent Anti-Angiogenic Therapy For Choroidal Neovascularization By Targeting Secretogranin Iii, Chengchi Huang, Hong Tian, Wei Li

Faculty, Staff and Students Publications

Recent studies reported that anti-angiogenic drugs targeting vascular endothelial growth factor (VEGF) alleviate choroidal neovascularization (CNV) in young but not aged animals. We recently developed a disease-targeted anti-angiogenic therapy against secretogranin III (Scg3), which selectively binds to diseased but not healthy vessels in young mice. Herein, using a unique in vivo ligand binding assay, we predicted and confirmed that Scg3 selectively binds CNV vessels in both young and aged mice. In contrast, VEGF with minimal increased binding to CNV vessels exhibited an age-dependent decline in binding to both CNV and healthy vessels with negligible binding in aged mice. Based on …

Multi-Institutional Modified Delphi For Genomics In Expert Consensus Survey Of Genomic Testing For Anterior Skull Base Malignancies, Anirudh Saraswathula, Shreya Sriram, Corinna Levine, Nyall R London, Shirley Y Su, Mathew Geltzeiler, Sanjeet V Rangarajan, Ian Witterick, Brian Thorp, Kathleen Kelly Gallagher, Kenneth Byrd, Ricardo Carrau, Waleed Abuzeid, Eric Wang, Carl Snyderman, Erin L Mckean

Faculty, Staff and Students Publications

Objectives: The use of genomic testing for patients with anterior skull base malignancies has grown dramatically. There are no clear guidelines on indications for testing. As the literature on the subject is still in early stages, there is a need for expert consensus. We conducted a modified Delphi expert consensus process with high-volume North American cranial base surgical programs.

Design setting participants: A modified Delphi consensus approach was used, following the method laid out by the American Academy of Otolaryngology-Head and Neck Surgery, and included 13 high-volume care centers. An otolaryngologist was appointed at each location to serve as the …

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 …

Factors Associated With Rare Pediatric Cancer Trial Enrollment: A Report From The Children's Oncology Group Rare Tumors Committee, Brian R Englum, Jin Piao, Lindsay Younis, Reto M Baertschiger, Kenneth S Chen, Emily Christison-Lagay, Hetal Dholaria, Robyn Gartrell, M John Hicks, Junne Kamihara, Sarah G Mitchell, Manuela Orjuela-Grimm, Farzana Pashankar, Samara L Potter, Jennifer H Aldrink, Jeremy Rosenblum, Michael R Sargen, Kris Ann P Schultz, Brittani K N Seynnaeve, Mary Wedekind, Theodore W Laetsch

Faculty, Staff and Students Publications

Background: Over 90% of US children with cancer are treated at Children's Oncology Group (COG) centers, which seek to maximize enrollment in therapeutic and biobanking studies. Rare cancers have demonstrated lower than expected COG enrollment. We evaluated trends in COG rare cancer enrollment compared to US incidence from Surveillance, Epidemiology, and End Results (SEER) registries, examining the impact of COG therapeutic trials and Project:EveryChild, a cancer biobank/registry.

Procedure: COG and SEER data from 2002 to 2020 were queried for US patients younger than 18 years old with adrenocortical carcinoma (ACC), nasopharyngeal carcinoma (NPC), retinoblastoma (RB), thyroid carcinoma, and melanoma. We …

Cressent: A Bioinformatics Toolkit To Explore And Improve Ssdna Virus Annotation, Ricardo R Pavan, Matthew B Sullivan, Michael J Tisza

Faculty, Staff and Students Publications

ssDNA viruses are important components of diverse ecosystems; however, it remains challenging to systematically identify and classify them. This is partly due to their broad host range and resulting genomic diversity, structure and rapid evolutionary rates. In addition, distinguishing genuine ssDNA genomes from contaminating sequences in metagenomic datasets (e.g. from commercial kits) has been an unresolved issue for years. Here, we present CRESSENT (CRESS-DNA Extended aNnotation Toolkit), a comprehensive and modular bioinformatic pipeline focused on ssDNA virus 'genome-to-analysis' and annotation. The pipeline integrates multiple functionalities organized into several modules: sequence dereplication, decontamination, phylogenetic analysis, …

Nasal Microbiome And Phageome Profiles Are Associated With Prospective Respiratory Viral Infection Risk In School-Age Children, Michael S Kelly, Ching-Ying Huang, Minsik Kim, Dastan Haghnazari, Aribah Baig, Ye Sun, Bryan R Lenneman, Michael J Tisza, Amparito Cunningham, Diane Gold, Wanda Phipatanakul, Peggy S Lai

Faculty, Staff and Students Publications

Background: Respiratory viral infections are common and can trigger asthma exacerbations in children. The roles of the nasal microbiome and phageome (viruses that infect microbes) are not well understood.

Objective: We sought to characterize the epidemiology of respiratory viral infections and the interplay between the nasal microbiome, phageome, and viral infections in school-age children with asthma.

Methods: We performed metagenomic sequencing and quantitative RT-PCR detection of respiratory viruses on 375 nasal samples from 227 school-age children with asthma collected routinely 3 times over a year. Surveys on parent-reported cold and asthma symptoms were administered routinely every 2 months. We evaluated …

Multi-Trait And Multi-Ancestry Genetic Analysis Of Comorbid Lung Diseases And Traits Improves Genetic Discovery And Polygenic Risk Prediction, Yixuan He, Wenhan Lu, Yon Ho Jee, Mu-Yi Shih, Ying Wang, Kristin Tsuo, David C Qian, James A Diao, Hailiang Huang, Chirag J Patel, Jinyoung Byun, Bogdan Pasaniuc, Elizabeth G Atkinson, Christopher I Amos, Yen-Chen Anne Feng, Matthew Moll, Michael H Cho, Alicia R Martin

Faculty, Staff and Students Publications

While respiratory diseases such as chronic obstructive pulmonary disease (COPD) and asthma share many risk factors, most studies investigate them in isolation and in predominantly European-ancestry populations. Here, we conducted the most powerful multi-trait and multi-ancestry genetic analysis of respiratory diseases and auxiliary traits to date, identifying 25 new loci associated with lung function in individuals of East Asian ancestry. Using these results, we developed PRSxtra (cross-trait and cross-ancestry), a multi-trait and multi-ancestry polygenic risk score (PRS) approach that leverages shared components of heritable risk via pleiotropic effects. PRSxtra significantly improved the prediction of asthma, COPD and lung cancer compared …

Differential Longitudinal Effects Of Glucose-Lowering Medications On Glucagon And C-Peptide Responses In The Glycemia Reduction Approaches In Diabetes: A Comparative Effectiveness Study (Grade), Steven E Kahn, Mark Tripputi, John M Lachin, Ashok Balasubramanyam, Mary Ann Banerji, Joshua Barzilay, Robert M Cohen, W Timothy Garvey, Michaela R Gramzinski, Neda Rasouli, Mary Rhee, Jesse C Seegmiller, Vatsala Singh, William I Sivitz, Michael W Steffes, Kristina Utzschneider, Ralph A Defronzo

Faculty, Staff and Students Publications

Objective: To determine the longitudinal effects on α-cell function of four classes of glucose-lowering agents added to metformin in adults with type 2 diabetes.

Research design and methods: In a multicenter, randomized study, 5,047 participants ≥30 years of age with type 2 diabetes taking 1,000-2,000 mg metformin daily, HbA1c 6.8%-8.5%, were randomized to receive insulin glargine U100, glimepiride, liraglutide, or sitagliptin. In a subset of 724 participants, baseline and longitudinal measures of α-cell function were assessed as the fasting glucagon concentration and change in glucagon from fasting to 30 min following oral glucose (glucagon index [GGI]). Whether these measures and …