Medical Specialties Commons^™

Diagnostic And Prognostic Value Of Cystatin C In Acute Coronary Syndrome: An Up-To-Date Meta-Analysis, Michal Pruc, Damian Swieczkowski, Basar Cander, Milosz J Jaguszewski, Sagar Galwankar, Salvatore Di Somma, Fatimah Lateef, Indrani Sardesai, Ayman El-Menyar, Michal Zembala, Jacek Kubica, Togay Evrin, Burak Katipoglu, Zubaid Rafique, Frank William Peacock, Lukasz Szarpak

Faculty, Staff and Students Publications

Background: The role of Cystatin C (CysC) in the diagnosis and prognosis of cardiovascular disease, particularly acute coronary syndrome (ACS), is increasingly significant. The goal of this meta-analysis was to assess the diagnostic and prognostic value of CysC in patients with ACS, as well as its association with major adverse cardiovascular events (MACE), defined as mortality, myocardial infarction, heart failure, and stroke.

Methods: The present study is a systematic review and meta-analysis. Using PubMed, Web of Science, Cochrane Library, and Embase, a literature review of cohort and case control studies reporting MACE and using the terms ACS and Cystatin C …

Zero-Inflated Models For The Evaluation Of Colorectal Polyps In Colon Cancer Screening Studies-A Value-Based Biostatistics Practice, Alok K Dwivedi, Sherif E Elhanafi, Mohamed O Othman, Marc J Zuckerman

Faculty, Staff and Students Publications

Background: Colon cancer screening studies are needed for the early detection of colorectal polyps to reduce the risk of colorectal cancer. Unfortunately, the data generated on colon polyps are typically analyzed in their dichotomized form and sometimes with standard count models, which leads to potentially inaccurate findings in research studies. A more appropriate approach for evaluating colon polyps is zero-inflated models, considering undetected existing polyps at colonoscopy screening.

Method: We demonstrated the application of the zero-inflated and hurdle models including zero-inflated Poisson (ZIP), zero-inflated robust Poisson (ZIRP), zero-inflated negative binomial (ZINB), zero-inflated generalized Poisson (ZIGP), zero hurdle Poisson (ZHP), and …

Effects Of Dialysate Potassium Concentration Of 30 Mmol/Leffects Of Dialysate Potassium Concentration Of 30 Mmol/L With Sodium Zirconium Cyclosilicate On Dialysis-Free Days Versus Dialysate Potassium Concentration Of 20 Mmol/L Alone On Rates Of Cardiac With Sodium Zirconium Cyclosilicate On Dialysis-Free Days Versus Dialysate Potassium Concentration Of 20 Mmol/L Alone On Rates Of Cardiac Arrhythmias In Hemodialysis Patients With Hyperkalemia Arrhythmias In Hemodialysis Patients With Hyperkalemia, David M Charytan, Wolfgang C Winkelmayer, Christopher B Granger, John P Middleton, Charles A Herzog, Glenn M Chertow, James M Eudicone, Jeremy D Whitson, James A Tumlin

Faculty, Staff and Students Publications

The optimal approach towards managing serum potassium (sK+) and hemodialysate potassium concentrations is uncertain. To study this, adults receiving hemodialysis for three months or more with hyperkalemia (pre-dialysis sK+ 5.1-6.5 mmol/l) had cardiac monitors implanted and were randomized to either eight weeks of 2.0 mmol/l potassium/1.25 mmol/l calcium dialysate without sodium zirconium cyclosilicate (SZC) (2.0 potassium/noSZC) or 3.0 mmol/l potassium/1.25 mmol/l calcium dialysate combined with SZC (3.0 potassium/SZC) on non-dialysis days to maintain pre-dialysis sK+ 4.0-5.5 mmol/l, followed by treatment crossover for another eight weeks. The primary outcome was the rate of adjudicated atrial fibrillation (AF) episodes of at least …

Previously Undescribed Transient Trifascicular Block: Left Septal Fascicular Block Associated With Left Anterior Fascicular Block And Complete Right Bundle Branch Block, Kjell Nikus, Jani Rankinen, Raine Virtanen, Yochai Birnbaum, Andrés Ricardo Pérez-Riera

Faculty, Staff and Students Publications

Exercise-induced complete right bundle branch block (CRBBB) remains a rare finding during a treadmill test. Both exercise-induced CRBBB and left anterior fascicular block (LAFB) have been associated with coronary artery disease, more specifically with stenosis of the left anterior descending coronary artery. Left septal fascicular block (LSFB) has been associated with acute and chronic coronary syndromes. We describe a patient case with severe left main coronary artery disease. In an exercise test, a rare combination of these three ventricular conduction disorders developed. In a second exercise test after coronary bypass surgery, LAFB and typical CRBBB developed without LSFB.

The Uses Of Right Heart Catheterization In Cardio-Pulmonary Disease: State-Of-The-Art, Bhavesh Katbamna, Lingling Wu, Mario Rodriguez, Phillip King, Joel Schilling, Jamal Mahar, Ajith P Nair, Hani Jneid, Elizabeth S Klings, Gerald L Weinhouse, Sula Mazimba, Marc A Simon, Markus Strauss, Chayakrit Krittanawong

Faculty, Staff and Students Publications

The right heart catheterization (RHC) remains an important diagnostic tool for a spectrum of cardiovascular disease processes including pulmonary hypertension (PH), shock, valvular heart disease, and unexplained dyspnea. While it gained widespread utilization after its introduction, the role of the RHC has evolved to provide valuable information for the management of advanced therapies in heart failure (HF) and cardiogenic shock (CS) to name a few. In this review, we provide a comprehensive overview on the indications, utilization, complications, interpretation, and calculations associated with RHC.

From Trials To Practice: Implementing A Clinical Intervention In Community Settings, Elizabeth M Vaughan, Xiaoying Yu, Victor J Cardenas, Craig A Johnston, Salim S Virani, Ashok Balasubramanyam, Christie M Ballantyne, Aanand D Naik

Faculty, Staff and Students Publications

Introduction/objectives: Diabetes increases the risk of complications, especially for vulnerable populations. Our previous randomized clinical trial (RCT), TIME (Telehealth-supported, Integrated Community Health Workers (CHWs), Medication access, group visit Education), showed the efficacy of CHW-led diabetes care. This study aimed to gather data on transitioning TIME from clinical trials to practical implementation.

Methods: We conducted a 12-month RCT at a nonprofit community clinic using the Consolidated Framework for Implementation Research (CFIR). Participants, Hispanic adults without insurance and with type 2 diabetes (N = 58; 29/arm), were randomized to TIME (intervention) or usual care (control). The intervention included monthly group visits and …

Syndromic Forms Of Inherited Retinal Dystrophies: A Comprehensive Molecular Diagnosis Of Consanguineous Pakistani Families Using Capture Panel Sequencing, Aleesha Asghar, Sumbal Wazir, Shehzeen Fatima, Hussan Bilal, Muhammad Shoaib, Saqib Ur Rehman, Sumaira Altaf, Yumei Li, Kiran Afshan, Rui Chen, Sabika Firasat

Faculty, Staff and Students Publications

Background: Inherited retinal dystrophies (IRDs) represent a clinically and genetically heterogeneous group of genetic disorders that involve photoreceptors and/or retinal pigment epithelium degeneration. IRDs may occur as an isolated condition or may represent an ocular manifestation of a multisystemic disorder referred as syndromic IRD. To increase the understanding of the molecular determinants of syndromic IRD-related genes in the Pakistani population, we revealed the genetic profile of 13 consanguineous Pakistani families using capture panel sequencing.

Methods: We performed comprehensive molecular testing on 72 IRD segregating Pakistani families using targeted capture panel sequencing of 344 known genes. The pathogenicity of candidate variants …

What Is The Robustness Of Randomized Controlled Trials Supporting Rhinosinusitis Guidelines?, Najm S Khan, Aatin K Dhanda, Masayoshi Takashima, Richard Liu, Yuki Yoshiyasu, Wenbo Wu, Whitney Jin, Edward D Mccoul, Murugappan Ramanathan, Omar G Ahmed

Faculty, Staff and Students Publications

Purpose: To determine the robustness of randomized controlled trials (RCTs) supporting the current rhinosinusitis guideline; International Consensus Statement on Allergy and Rhinology: rhinosinusitis (ICAR-RS).

Materials & methods: RCTs referenced by ICAR-RS with primary dichotomous outcomes were analyzed. The Fragility Index (FI) was calculated for trials with statistically significant findings. Trial characteristics, the FI, and FI minus number lost to follow-up (LTF) were assessed for associations.

Results: A total of 317 RCTs were identified, with 38 trials possessing a primary dichotomous outcome. Thirty-one percent evaluated surgical interventions and 24 % were industry-sponsored. The mean sample size was 116 with 9 patients, …

Developing An Annual Review Of The Literature, Weinstein R Amy, Szauter Karen, Duca Nicholas, Jacob Jackcy, Ismail Nadia, Pincavage Amber, Walsh Katherine, Alexandraki Irene

Faculty, Staff and Students Publications

Many national meetings and speaker series feature an "Annual Review of the Literature" (ARL) session in which an individual or team presents a sampling of articles, selected and prepared because they represent important current topics or new ideas in the discipline of interest. Despite this, there is little in the medical literature describing how to thoughtfully and systematically develop these sessions. We identify best practices that we have developed and used in the United States Clerkship Directors of Internal Medicine (CDIM) over many years. These include identification of a theme, team assembly, timeline development, search strategy and rubric development and …

Comparative Analysis Of Imaging Modalities For Surveillance On Outcomes In Patients With Hepatocellular Carcinoma, Ahmed El Sabagh, Islam Mohamed, Mazen Elsheikh, Megha Bhongade, Eunji Jo, Susan G Hilsenbeck, Fasiha Kanwal, Prasun K Jalal

Faculty, Staff and Students Publications

Background and aims: The American Association for the Study of Liver Diseases recommends regular surveillance with ultrasonography (US) and alpha-feto protein every 6 months for patients at high risk of hepatocellular carcinoma (HCC). However, US is considered to be less effective than cross-sectional imaging modalities like computed tomography and magnetic resonance imaging for detecting early HCC. Limited data exist on the overall survival and receipt of curative treatment for patients undergoing surveillance with different imaging modalities.

Methods: We retrospectively reviewed patients (n = 1954) diagnosed with HCC between January 2011 and June 2021. Patients who developed HCC while on strict …

Cervical Cancer Prevention Behaviors In Young Black Women, Angela J Johnson, Monica J Johnson, Juinell B Williams, Emma Muscari, Laura Palmo, Michelle Ruiz, Brianna Bush, Lisa C Campbell

Faculty, Staff and Students Publications

Background: In the United States, Black women have the second highest incidence of cervical cancer (CC) due to high incidence of human papillomavirus (HPV), slow HPV clearance rates, and low receipt of preventive pap smears and vaccines.

Objective: A Black Feminist Thought framework was used to examine how the media portrayal of Black women, racial identity, and familial factors impact CC prevention behaviors among young Black women.

Design: Black women enrolled at a large southeastern university consented and participated in an online mixed-methods survey examining facilitators and barriers to CC prevention behaviors. Quantitative items were analyzed via descriptive statistics, and …

Association Between Hemoglobin A1c And Pediatric Asthma Control, Hewlett Pham, Rachelle Koehl, Han Woo, Tianshi David Wu, Anna Yue Qiu, Emily P Brigham, Nadia N Hansel, Meredith C Mccormack

Faculty, Staff and Students Publications

Purpose: To examine the relationship between Hemoglobin A1c (HbA1c) and asthma outcomes in an urban cohort of children with asthma.

Methods: The AIRWEIGHS Study was a randomized controlled clinical trial of an air cleaner intervention testing the hypothesis that overweight/obese children would experience greater improvement in asthma control compared to normal weight children. The study enrolled 164 children with asthma from Baltimore, MD and assessed HbA1c levels and asthma outcomes during clinic visits at baseline and three months. HbA1c levels were analyzed as a continuous measure and categorized as either normal (< 5.7%) or consistent with pre-diabetes (≥5.7%). Asthma outcomes included standardized questionnaires, spirometry, and fractional exhaled nitric oxide (FeNO). Generalized Estimating Equation (GEE) regression models were used to analyze the association between the HbA1c and asthma outcomes.

Results: Participants included 164 children with an average …

Candidiasis Epidemiology And Outcomes Including Emergence Of Candida Auris From A Large, Southern Us Metro Area: A Six-Year Evaluation, Ricky Huynh-Phan, Ardath Plauche, William L Musick, Kady Phe, Wesley J Hoffman, Mayar Al Mohajer, Todd Lasco, Nicholas D Beyda, Taryn A Eubank, Kevin W Garey

Faculty, Staff and Students Publications

Background: Invasive candidiasis including candidemia is a common healthcare-associated infections with significant morbidity and mortality. The USA does not have mandatory national surveillance for mucocutaneous or invasive candidiasis which complicates estimation of epidemiology and outcomes. The aim of this project was to describe the epidemiology, mortality, and Candida-associated hospital readmissions in hospitalized patients with Candida species infections.

Methods: This secondary database analysis used clinical microbiology data from adults hospitalized at three large health systems (25-hospitals) in the Greater Houston area totaling over 1.6 million hospitalization days per year from 2018 to 2023. Proportion and rates of Candida cultures per …

Investigating Socioeconomic Deprivation And Antibiotic Prescribing Among Older Medicare Patients Using An Instrumental Variable Approach, Mayar Al Mohajer, David Slusky, David Nix, Catia Nicodemo

Faculty, Staff and Students Publications

Background: Socioeconomic deprivation has been associated with antibiotic overprescription in the US; however, prior studies could not quantify a causal relationship due to endogeneity. This study examines how socioeconomic deprivation is related to the rate of antibiotic days supplied to older Medicare Part D beneficiaries, utilizing an Instrumental Variable (IV) approach.

Methods: Data from the Medicare Part D and the Social Deprivation Index (SDI) repositories were analyzed. To address potential endogeneity and omitted variable bias in the relationship between SDI and antibiotic prescribing, we used the maximum Earned Income Tax Credit as an IV. Bivariate Moran's I assessed the spatial …

Inclusion Of Patient-Centered, Non-Microbiological Endpoints And Biomarkers In Tuberculosis Drug Trials, Andrew R Dinardo, Wilbert Sabiiti, Stephen H Gillespie, Sophia B Georghiou, Norbert Heinrich, Norbert Hittel, Sami Taghlabi, Danna Carrero Longlax, Mikashmi Kohli, Ursula Panzner, Collins Musia, Christoph Lange, Anca Vasiliu, Rob J W Arts, Anna M Mandalakas, Morten Ruhwald, Lieven J Stuyver, Reinout Van Crevel

Faculty, Staff and Students Publications

Tuberculosis drug trials are primarily designed to identify antibiotic regimens with the strongest potency to kill Mycobacterium tuberculosis. However, microbiologic cure is not synonymous with improved health and recovery. Beyond antimicrobial efficacy, parameters such as morbidity and mortality related to lung function, cardiovascular health, and cancer should be prioritized. This narrative review emphasizes the critical need to emphasize clinical outcomes as much, if not more, than microbiological endpoints. We examine the underlying pathophysiological mechanisms and determinants of non-microbiological outcomes in tuberculosis, providing a synthesis of current knowledge. While there is growing evidence for some biomarkers to risk stratify TB …

Biallelic Variation In The Choline And Ethanolamine Transporter Flvcr1 Underlies A Severe Developmental Disorder Spectrum, Daniel G Calame, Jovi Huixin Wong, Puravi Panda, Dat Tuan Nguyen, Nancy C P Leong, Riccardo Sangermano, Sohil G Patankar, Mohamed S Abdel-Hamid, Lama Alabdi, Sylvia Safwat, Kyle P Flannery, Zain Dardas, Jawid M Fatih, Chaya Murali, Varun Kannan, Timothy E Lotze, Isabella Herman, Farah Ammouri, Brianna Rezich, Stephanie Efthymiou, Shahryar Alavi, David Murphy, Zahra Firoozfar, Mahya Ebrahimi Nasab, Amir Bahreini, Majid Ghasemi, Nourelhoda A Haridy, Hamid Reza Goldouzi, Fatemeh Eghbal, Ehsan Ghayoor Karimiani, Amber Begtrup, Houda Elloumi, Varunvenkat M Srinivasan, Vykuntaraju K Gowda, Haowei Du, Shalini N Jhangiani, Zeynep Coban-Akdemir, Dana Marafi, Lance Rodan, Sedat Isikay, Jill A Rosenfeld, Subhadra Ramanathan, Michael Staton, Kerby C Oberg, Robin D Clark, Catharina Wenman, Sam Loughlin, Ramy Saad, Tazeen Ashraf, Alison Male, Shereen Tadros, Reza Boostani, Ghada M H Abdel-Salam, Maha Zaki, Ali Mardi, Farzad Hashemi-Gorji, Ebtesam Abdalla, M Chiara Manzini, Davut Pehlivan, Jennifer E Posey, Richard A Gibbs, Henry Houlden, Fowzan S Alkuraya, Kinga Bujakowska, Reza Maroofian, James R Lupski, Long N Nguyen

Faculty, Staff and Students Publications

Purpose: FLVCR1 encodes a solute carrier protein implicated in heme, choline, and ethanolamine transport. Although Flvcr1-/- mice exhibit skeletal malformations and defective erythropoiesis reminiscent of Diamond-Blackfan anemia (DBA), biallelic FLVCR1 variants in humans have previously only been linked to childhood or adult-onset ataxia, sensory neuropathy, and retinitis pigmentosa.

Methods: We identified individuals with undiagnosed neurodevelopmental disorders and biallelic FLVCR1 variants through international data sharing and characterized the functional consequences of their FLVCR1 variants.

Results: We ascertained 30 patients from 23 unrelated families with biallelic FLVCR1 variants and characterized a novel FLVCR1-related phenotype: severe developmental disorders with profound developmental delay, microcephaly …

Targeted Analysis Of Dyslexia-Associated Regions On Chromosomes 6, 12 And 15 In Large Multigenerational Cohorts, Nicola H Chapman, Patrick A Navas, Michael O Dorschner, Michele Mehaffey, Karen G Wigg, Kaitlyn M Price, Oxana Y Naumova, Elizabeth N Kerr, Sharon L Guger, Maureen W Lovett, Elena L Grigorenko, Virginia Berninger, Cathy L Barr, Ellen M Wijsman, Wendy H Raskind

Faculty, Staff and Students Publications

Dyslexia is a common learning impairment with a genetic basis that affects word reading and spelling. An increasing list of loci and genes have been implicated, but analyses to-date have investigated only limited genomic variation within each locus with no confirmed pathogenic variants identified. Our study is the first to comprehensively sequence both coding and cis-acting regulatory regions of such genes in a large study sample. In a collection of >2000 participants in families from three independent sites, we performed targeted capture and comprehensive sequencing of all exons and some regulatory elements of five candidate risk genes (DNAAF4, CYP19A1, DCDC2, …

Toward Precision Longevity: Aging Interventions In The Single-Cell Atlas Era, Jason B Chen, Miranda C Wang, Shangyu Gong, Hongjie Li

Faculty, Staff and Students Publications

With growing global interest in extending not only lifespan but also healthspan, healthy aging has emerged as a central goal in biomedical research. This review provides an overview of current longevity interventions, including genetic manipulations, dietary restriction, exercise, pharmacological treatments, targeting senescence and cellular reprogramming strategies, as studied in key model organisms such as Caenorhabditis elegans, Drosophila melanogaster, and Mus musculus. We examine the limitations and challenges associated with these approaches, particularly their variability across tissues and cell types. Furthermore, we emphasize the critical role of single-cell aging atlas technologies in uncovering cell-type–specific aging patterns and molecular …

Efficacy Of Nampt Inhibition In T-Cell Acute Lymphoblastic Leukemia, Chelsea Vrana, Matthew Zhang, Max Rochette, Michelle Alozie, Hailey Oviedo, Alan Gonzalez, Jaden Sherman, Barry Zorman, Pavel Sumazin, Karen R Rabin, Jacob J Junco

Faculty, Staff and Students Publications

Novel agents targeting upregulated signaling pathways are needed to improve outcomes in T-cell acute lymphoblastic leukemia (T-ALL), since conventional cytotoxic chemotherapy regimens have reached the limits of tolerability. We identified upregulated, targetable signaling pathways common to both human T-ALL samples and a KrasLSL-G12D/+.Mb1Cre/+ murine model of T-ALL. We found the NAMPT inhibitor FK866 had the greatest cytotoxicity of a panel of small molecule inhibitors tested in human and mouse T-ALL cell lines, and in patient derived xenograft (PDX)-expanded T-ALL patient samples. We subsequently tested FK866 in vivo in PDX mouse models of T-ALL, and found that it significantly reduced the …

Mapping The Functional Network Of Human Cancer Through Machine Learning And Pan-Cancer Proteogenomics, Zhiao Shi, Jonathan T Lei, John M Elizarraras, Bing Zhang

Faculty, Staff and Students Publications

Large-scale omics profiling has uncovered a vast array of somatic mutations and cancer-associated proteins, posing substantial challenges for their functional interpretation. Here we present a network-based approach centered on FunMap, a pan-cancer functional network constructed using supervised machine learning on extensive proteomics and RNA sequencing data from 1,194 individuals spanning 11 cancer types. Comprising 10,525 protein-coding genes, FunMap connects functionally associated genes with unprecedented precision, surpassing traditional protein-protein interaction maps. Network analysis identifies functional protein modules, reveals a hierarchical structure linked to cancer hallmarks and clinical phenotypes, provides deeper insights into established cancer drivers and predicts functions for understudied cancer-associated …

Placentas From Sars-Cov-2 Infection During Pregnancy Exhibit Foci Of Oxidative Stress And Dna Damage, Guilherme M Nobrega, Eliza R Mccoll, Arthur Antolini-Tavares, Renato T Souza, José Guilherme Cecatti, Maria Laura Costa, Indira U Mysorekar

Faculty, Staff and Students Publications

Problem: COVID-19 during pregnancy is linked to increased maternal morbidity and a higher incidence of preterm births (PTBs), yet the underlying mechanisms remain unclear. Cellular senescence, characterized by the irreversible cessation of cell division, is a critical process in placental function, and its dysregulation has been implicated in pregnancy complications like PTB. Senescence can be induced by various stressors, including oxidative stress, DNA damage, and viral infections.

Method of study: In this study, we determined whether COVID-19 had an impact on placental senescence. We examined placentas from women infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (n = 10 …

Evaluation Of Methotrexate Pharmacogenomic Variation To Predict Acute Neurotoxicity In Children With Acute Lymphoblastic Leukemia, Rachel D Harris, Olga A Taylor, M Monica Gramatges, Amy E Hughes, Mark Zobeck, Sandi Pruitt, M Brooke Bernhardt, Ashley Chavana, Van Huynh, Kathleen Ludwig, Laura Klesse, Kenneth Heym, Timothy Griffin, Rodrigo Erana, Juan Carlos Bernini, Ashley Choi, Yuu Ohno, Melissa A Richard, Alanna C Morrison, Han Chen, Bing Yu, Philip J Lupo, Karen Rabin, Michael E Scheurer, Austin L Brown

Faculty, Staff and Students Publications

BACKGROUND: Methotrexate is an important component of curative therapy in childhood acute lymphoblastic leukemia (ALL), but the role of genetic variation influencing methotrexate clearance and transport in toxicity susceptibility in children with ALL is not well established. Therefore, we evaluated the association between suspected methotrexate pharmacogenomic variants and methotrexate-related neurotoxicity.

METHODS: This study included children (aged 2-20 years) diagnosed with ALL (2005-2019) at six treatment centers in the southwest United States. Clinical information was abstracted from medical records. Suspected neurotoxic events occurring within 21 days of intravenous and/or intrathecal methotrexate delivered between the end of induction and start of maintenance …

An Evaluation Of Genetic Predisposition To Congenital Anomalies And Pediatric Cancer Supports, Hyunjung Gu, Yao Yu, Saumya Dushyant Sisoudiya, Pamela Mishra, He Li, Jeremy M Schraw, Michael E Scheurer, Donna M Muzny, Danielle Mitchell, Olga Taylor, Shalini N Jhangiani, Shannon Dugan-Perez, Yifan Wu, Harsha Doddapaneni, Sravya Venkata Bhamidipati, Marie-Claude Gingras, Jennifer E Posey, Richard A Gibbs, Chad D Huff, Sharon E Plon, Philip J Lupo, Aniko Sabo

Faculty, Staff and Students Publications

Purpose: Although congenital anomalies are among the strongest risk factors for developing pediatric cancer, the genetic underpinnings remain unclear. Therefore, we evaluated germline susceptibility in children with congenital anomalies and cancer.

Methods: Through the Genetic Overlap Between Anomalies and Cancer in Kids Study, we recruited 47 participants with anomalies and cancer, along with their biological families. Genome sequencing was performed, focusing on single-nucleotide variants, indels, and structural variants. Pathogenic or likely pathogenic variants were identified by the American College of Medical Genetics and Genomics classification.

Results: We identified pathogenic or likely pathogenic variants in 23.4% (11 of 47) of participants. …