Medical Genetics Commons^™

Development Of An H&E On-Block Staining Technique For Collagen Detection In Cryo-Fluorescence Tomography Imaging Of Frozen Breast Tissue Samples, Erin P Snoddy, Tien T Tang, Natalie Fowlkes, Thomas Huynh, Kari J Brewer Savannah, Alejandro Contreras, Gregory Reece, Kristy K Brock

Faculty, Staff and Student Publications

Hematoxylin and eosin (H&E) staining is widely considered to be the gold-standard diagnostic tool for histopathology evaluation. However, the fatty nature of some tissue types, such as breast tissue, presents challenges with cryo-sectioning, often resulting in artifacts that can make histopathologic interpretation and correlation with other imaging modalities virtually impossible. We present an optimized on-block H&E staining technique that improves contrast for identifying collagenous stroma during cryo-fluorescence tomography (CFT) sectioning. In this prospective study, we embedded four breast specimens with confirmed ligaments from a bilateral mastopexy in an optimal cutting temperature block. Two of the samples were processed on a …

Partial Agonism In Heteromeric Gluk2/Gluk5 Kainate Receptor, Nabina Paudyal, Anindita Das, Elisa Carrillo, Vladimir Berka, Vasanthi Jayaraman

Faculty, Staff and Student Publications

Kainate receptors are a subtype of ionotropic glutamate receptors that form transmembrane channels upon binding glutamate. Here, we have investigated the mechanism of partial agonism in heteromeric GluK2/K5 receptors, where the GluK2 and GluK5 subunits have distinct agonist binding profiles. Using single-molecule Förster resonance energy transfer, we found that at the bi-lobed agonist-binding domain, the partial agonist AMPA-bound receptor occupied intermediate cleft closure conformational states at the GluK2 cleft, compared to the more open cleft conformations in apo form and more closed cleft conformations in the full agonist glutamate-bound form. In contrast, there is no significant difference in cleft closure …

Late Diagnosis Of Klinefelter Syndrome: Overcoming Phenotypic Variability And Diagnostic Oversights, Amna Kamran, Chinelo Okigbo

Department of Medicine Faculty Publications

We report a case of Klinefelter syndrome (KS) diagnosed in adulthood, emphasizing the impact of phenotypic variability and the declining reliance on physical examination in delayed recognition. A 27-year-old male with obesity, low libido, and biochemical and clinical primary hypogonadism was found to have 47, XXY karyotype, consistent with KS. His hypogonadism was initially attributed to obesity and overlooked, despite classic signs of a micropenis and small testes. The case highlights the importance of physical examination, comprehensive history, and clinician awareness in diagnosing KS, particularly in atypical presentations. KS is associated with increased risks of osteoporosis, cardiovascular disease, and psychosocial …

Organ Of Corti Macrophages: A Distinct Group Of Cochlear Macrophages With Potential Roles In Supporting Cell Degeneration And Survival, Mengxiao Ye, Celia Zhang, Dalian Ding, Guang-Di Chen, Henry J Adler, Rania Sharaf, Bo Hua Hu

Faculty, Staff and Student Publications

Macrophages are the primary immune cells in the cochlea, essential for maintaining cochlear homeostasis and orchestrating inflammatory responses to pathological events. Although these cells have been found in various parts of the cochlea, their presence in the organ of Corti, a critical structure for acoustic sensing, remains poorly understood. The present study was designed to examine macrophage responses to ototoxic drug-induced cochlear damage and age-related cochlear degeneration, with a particular focus on the pathological conditions that trigger macrophage recruitment into the organ of Corti. We used a model of ototoxicity induced by cyclodextrin, a cyclic oligosaccharide known for its ability …

Burden Of Seasonal Human Coronavirus Infections In Hematopoietic Cell Transplant Recipients, Fareed Khawaja, Terri Lynn Shigle, Layale Yaghi, May Daher, Jeremy L Ramdial, Ella Ariza-Heredia, Ying Jiang, Roy F Chemaly

Faculty, Staff and Student Publications

Background: Community respiratory viruses, such as seasonal human coronavirus (HCoV), commonly infect hematopoietic cell transplant (HCT) recipients. Recognizing the risk factors and outcomes of HCoV infections in HCT recipients is essential for the future development of potentially lifesaving therapeutics.

Methods: We performed a retrospective review of all HCoV-infected HCT recipients from September 1, 2015 to August 31, 2017, at our institution. Patients were classified with upper respiratory tract infection (URI) or lower respiratory infection (LRI) based on predefined definitions for respiratory viral infections in HCT recipients. Patient data were collected to identify risk factors for HCoV LRI, and to calculate …

Erratum: Melatonin Enhances Sorafenib-Induced Cytotoxicity In Flt3-Itd Acute Myeloid Leukemia Cells By Redox Modification: Erratum, Tian Tian, Jiajun Li, Yizhuo Li, Yun-Xin Lu, Yan-Lai Tang, Hua Wang, Fufu Zheng, Dingbo Shi, Qian Long, Miao Chen, Guillermo Garcia-Manero, Yumin Hu, Lijun Qin, Wuguo Deng

Faculty, Staff and Student Publications

No abstract provided.

Disparities In Breast Cancer Detection Modalities And Outcomes Among Geriatric Female Cancer Patients, Zhaoli Liu, Mathilda Nicot-Cartsonis, Biai D E Digbeu, Daoqi Gao, Sharon H Giordano, Yong-Fang Kuo

Faculty, Staff and Student Publications

This study examined racial and geographic disparities in breast cancer detection modalities (screening-, diagnostic-, or non-mammography) with cancer stage and mortality. A retrospective cohort study was conducted using Texas Cancer Registry-Medicare linkage data for geriatric women. Cancers detected through screening and diagnostic mammography had 43 % (95 % CI, 39 %-46 %, p < .0001) and 31 % (95 % CI, 27 %-35 %, p < .0001) lower all-cause mortality, and 49 % (95 % CI, 41 %-54 %, p < .0001) and 37 % (95 % CI, 32 %-43 %, p < .0001) lower cancer-specific mortality, respectively, compared to non-mammography-detected breast cancers. Patients from rural areas were 17 % (95 % CI, 1.06 - 1.29) more likely to be diagnosed with mid- (p = .0023) and advanced stage (p = .003) cancers compared to their urban counterparts. Racial or geographic disparities in cancer detection modalities with associated mortality no longer exist after adjusting for covariates. Healthcare professionals can leverage these findings to promote rural cancer health equity.

Mechanical Regulation Of Macrophage Metabolism By Allograft Inflammatory Factor 1 Leads To Adverse Remodeling After Cardiac Injury, Matthew Deberge, Kristofor Glinton, Connor Lantz, Zhi-Dong Ge, David P Sullivan, Swapna Patil, Bo Ryung Lee, Minori I Thorp, Adam Mullick, Steve Yeh, Shuling Han, Anja M Van Der Laan, Hans W M Niessen, Xunrong Luo, Nicholas E S Sibinga, Edward B Thorp

Faculty, Staff and Student Publications

Myocardial infarction (MI) mobilizes macrophages, the central protagonists of tissue repair in the infarcted heart. Although necessary for repair, macrophages also contribute to adverse remodeling and progression to heart failure. In this context, specific targeting of inflammatory macrophage activation may attenuate maladaptive responses and enhance cardiac repair. Allograft inflammatory factor 1 (AIF1) is a macrophage-specific protein expressed in a variety of inflammatory settings, but its function after MI is unknown. Here we identify a maladaptive role for macrophage AIF1 after MI in mice. Mechanistic studies show that AIF1 increases actin remodeling in macrophages to promote reactive oxygen species-dependent activation of …

Effect Of Digital Health Coaching On Self-Efficacy And Patient-Reported Outcomes In Individuals With Acute Myeloid And Chronic Lymphocytic Leukemia: A Pilot Randomized Controlled Trial, Jennifer Marvin-Peek, Valerie Shelton, Kelly Brassil, Bryan Fellman, Austin Barr, Kelly Sharon Chien, Danielle Hammond, Mahesh Swaminathan, Nitin Jain, William Wierda, Alessandra Ferrajoli, Courtney Dinardo

Faculty, Staff and Student Publications

Introduction: Promotion of self-efficacy can enhance engagement with health care and treatment adherence in patients with cancer. We report the outcomes of a pilot trial of a digital health coach intervention in patients with leukemia with the aim of improving self-efficacy.

Methods: Adult patients with newly diagnosed acute myeloid leukemia (AML) and chronic lymphocytic leukemia (CLL) were randomized 1:1 to a digital health coach intervention or standard of care. The primary outcome of self-efficacy was measured by the Cancer Behavior Inventory (CBI) score.

Results: A total of 147 patients (37 AML, 110 CLL) were enrolled from July 2020 to December …

Geographic Disparities In Access To Outpatient Stroke Rehabilitation In Texas, Joseph Wozny, Melissa Howard, Susan Doherty, Yenan Zhu, Kalyani Sonawane, Dorothea Parker, Lisa W Thomas, Bukola Azeez, Ndi Chukwumerije, Susan Varghese, Nicholas Hoang, Suja S Rajan, Charles Green, Vahed Maroufy, Trudy Millard Krause, Sean I Savitz

Faculty, Staff and Student Publications

Background: Outpatient rehabilitation plays a vital role in providing post-discharge care for stroke survivors' optimum recovery. Geographic variability in access to post-stroke rehabilitation care in rural areas is poorly understood.

Methods: This study used Medicare claims from 2016 to 2019 to estimate incidence of stroke discharges home and compared rehabilitation utilization rates after discharge from acute hospitalization in the state of Texas. We also examined spatial accessibility to post-discharge outpatient rehabilitation centers between rural and urban areas. We supplemented claims results with a survey to better understand locations where outpatient rehabilitation clinics provided services to stroke patients.

Results: After discharge …

Fraud In Genetic Testing: Swindling The System, Rachel Notestine, Claire N Singletary, Meagan Choates, Stephanie Gandomi, Molly Daniels, Rebecca Lunstroth, Quinn Stein

Faculty, Staff and Student Publications

Purpose: Health care fraud comprises a sizable portion of United States health care expenditure and inflicts undue burden on payors, patients, and the health care system overall. The genetic testing industry is rapidly growing, which propagates opportunities for health care fraud. Although federal organizations have highlighted it as an issue, there is limited research exploring genetic testing fraud.

Methods: A retrospective review of federal websites, news articles, and a legal database resulted in 42 cases of fraud involving outpatient genetic testing published between February 2019 and December 2023. These cases were analyzed for themes via inductive conventional content analysis.

Results: …

Impact Of Active Surveillance On Nephrometric Scores Of Bosniak Iii And Iv Renal Cysts, Roberto Dias Machado, Leonardo Bernardes De Amaro, Alessandro Prudente, Eliney Ferreira Faria, Antonio Antunes Rodrigues Júnior, Aradhana M Venkatesan, Jose A Karam, Valdair F Muglia, Leonardo O Reis, Rodolfo Borges Dos Reis

Faculty, Staff and Student Publications

Purpose: Active surveillance (AS) has been widely explored for small renal masses, but its role in complex renal cysts (CRCs) categorized as Bosniak (Bk) III and IV remains unclear. This study aims to evaluate changes in nephrometry scores (s-RENAL and s-PADUA) during AS and their potential impact on surgical complexity.

Methods: A retrospective, multicentric, observational study was conducted, analyzing 101 CRCs from 95 patients across three institutions. Nephrometry scores were evaluated at baseline and after a minimum follow-up of two years using computed tomography (CT) and magnetic resonance imaging (MRI). Statistical analysis included chi-square and marginal homogeneity tests, with data …

Micrornas As Key Regulators Of Cancer Drug Resistance: Insights And Future Directions In Chemotherapy, Targeted-Therapy, Radiotherapy, And Immunotherapy, Michael Attathikhun, Ancuta Jurj, George A Calin

Faculty, Staff and Student Publications

Cancer therapy remains an active field of investigation, particularly in understanding and overcoming therapy resistance. Small non-coding RNAs, such as microRNAs (miRNAs), are emerging as key regulators of cancer survival, progression, proliferation, invasion, migration, and metastasis. Although many studies have linked miRNAs to cancer therapy outcomes, significant questions remain regarding their precise molecular and cellular roles in therapy resistance. Increasing evidence shows that miRNAs influence critical pathways such as apoptosis, immune evasion, and other signaling cascades. However, there have been many setbacks because of the limitations in knowledge of each specific miRNA's function. A deeper understanding of miRNA expression and …

Corrigendum To Exosomal Mirna Confers Chemo Resistance Via Targeting Cav1/P-Gp/M2-Type Macrophage Axis In Ovarian Cancer, Pinar Kanlikilicer, Recep Bayraktar, Merve Denizli, Mohammed H Rashed, Cristina Ivan, Burcu Aslan, Rahul Mitra, Kubra Karagoz, Emine Bayraktar, Xinna Zhang, Cristian Rodriguez-Aguayo, Amr Ahmed El-Arabey, Nermin Kahraman, Seyda Baydogan, Ozgur Ozkayar, Michael L Gatza, Bulent Ozpolat, George A Calin, Anil K Sood, Gabriel Lopez-Berestein

Faculty, Staff and Student Publications

No abstract provided.

Icos And Icos Ligand: Expression Patterns And Outcomes In Oncology Patients, Mina Nikanjam, Shumei Kato, Daisuke Nishizaki, Donald A Barkauskas, Sarabjot Pabla, Mary K Nesline, Jeffrey M Conroy, Aung Naing, Razelle Kurzrock

Faculty, Staff and Student Publications

Background: Inducible T-cell co-stimulator (ICOS) and its ligand (ICOSL) form a complex, two-faced immune machinery that can lead to both immune stimulation and inhibition.

Objective: We explored ICOS transcriptomic expression patterns and their relationship with other checkpoints and with outcomes in patients with advanced/metastatic cancers.

Design: This was a retrospective cohort study.

Methods: RNA expression for ICOS and other immune checkpoints was quantified by RNA sequencing and stratified by rank values into high (75-100 percentiles) and low (0-24 percentiles). Fischer's exact tests were used for univariate analyses to evaluate independent predictors of ICOS high and logistic regression was used for …

Isatuximab For The Treatment Of Multiple Myeloma: Current Clinical Advances And Future Directions, Paul G Richardson, Elisabeth K O'Donnell, Peter O'Gorman, Lisa B Leypoldt, Jacob Laubach, Francesca Gay, Xavier Leleu, Thierry Facon, Philippe Moreau, Meletios A Dimopoulos, Hartmut Goldschmidt, Elias K Mai, Michele Cavo, Katja C Weisel, Jesus G Berdeja, Robert Z Orlowski, Meral Beksaç, Aurore Perrot, Joseph Mikhael, Thomas Martin

Faculty, Staff and Student Publications

Introduction: The addition of the anti-CD38 monoclonal antibody isatuximab to standard therapies is transforming the care of patients with newly diagnosed multiple myeloma (NDMM), as previously seen in the relapsed/refractory setting. This is particularly important for patients with NDMM as early treatment with effective, well tolerated therapies may ensure better clinical outcomes.

Areas covered: Here, we examine recent results from pivotal Phase 3 and 2 clinical trials that demonstrate efficacy and safety of isatuximab across multiple combinations, for both transplant-ineligible and transplant-eligible NDMM patients. We then evaluate long-term outcomes from the IKEMA and ICARIA-MM trials as well as real-world evidence …

Continued Positive Job Search Experience For New Pathologists Seeking First Employment During The Covid-19 Pandemic (2020-2022), Julie Katz Karp, Amanda Lofgreen, Kristen Johnson, Melissa R George, Stephanie Barak, Bronwyn H Bryant, Mary P Berg, John M Childs, Barbara E C Knollman-Ritschel, Victor G Prieto, Kristie L White, Cindy B Mccloskey

Faculty, Staff and Student Publications

Context.—: As pathologists retire and leave the field, it is critical to accurately capture employment trends for new-in-practice pathologists. There is always interest in the job market for newly graduated pathology trainees and prospective pathology trainees, but it is unclear how the COVID-19 pandemic may have affected the job search experience.

Objective.—: To provide an update on trends gleaned from a survey of pathology graduates' job search experiences during the COVID-19 pandemic.

Design.—: We analyzed data from an annual job search survey sent by the College of American Pathologists Graduate Medical Education Committee between 2020 and 2022 to College of …

Effectiveness And Acceptability Of Ventilation Modifications In Healthcare Facilities, Liberia 2022–2023, Ronan F Arthur, Ashley Styczynski, Krithika Srinivasan, Amos Tandanpolie, Philip Bemah, Ethan Bell, Jason R Andrews, Tom Baer, Jorge L Salinas

Faculty, Staff and Student Publications

Objective: To evaluate the effectiveness and acceptability of ventilation interventions in naturally ventilated hospitals in Liberia.

Design: Difference-in-differences analysis of pre- and post-air changes per hour of intervention and control spaces.

Setting: Hospitals in Bong and Montserrado Counties, Liberia.

Participants: Seventy patient care spaces were evaluated at baseline. Six spaces underwent physical intervention modifications, while 2 spaces were assessed for indirect effects and 2 others used as controls. Healthcare workers were interviewed to assess ventilation knowledge and acceptability.

Interventions: Ventilation interventions included the installation of window screens, louvered doors and windows, and wind turbines.

Methods: We measured carbon dioxide levels …

Wnt7a, Naomi M Calhoun, Richard R Behringer

Faculty, Staff and Student Publications

WNT7A regulates numerous developmental processes. It can activate canonical and non-canonical signaling depending on context. It is expressed in the developing central nervous system, limb buds, reproductive organs, and other tissues. Spontaneous and targeted Wnt7a mutations in mouse models resulted in abnormal limbs, defects in male and female reproductive tract organs, infertility, and defects in cerebellar axon remodeling. In zebrafish, wnt7aa mutants exhibited neurogenesis and angiogenesis defects in the central nervous system. In humans, recessive WNT7A missense and nonsense mutations resulted in severe limb and pelvic bone defects. Alterations in WNT7A expression correlated with multiple types of cancer.

Bismuth-Infused Perivascular Wrap Facilitates Delivery Of Mesenchymal Stem Cells And Attenuation Of Neointimal Hyperplasia In Rat Arteriovenous Fistulas, Allan John R Barcena, Joy Vanessa D Perez, Marvin R Bernardino, Jossana A Damasco, Erin Marie D San Valentin, Carleigh Klusman, Benjamin Martin, Gino Martin Canlas, Francisco M Heralde, Natalie Fowlkes, Richard R Bouchard, Jizhong Cheng, Steven Y Huang, Marites P Melancon

Faculty, Staff and Student Publications

BACKGROUND: Mesenchymal stem cells (MSCs) have emerged as novel therapies for supporting arteriovenous fistula (AVF) maturation, and bioresorbable polymeric scaffolds have enabled sustained MSC delivery into maturing AVFs. However, the radiolucency of biopolymeric wraps prevents in vivo monitoring of their integrity and location, hindering long-term preclinical investigations.

METHODS: We infused bismuth nanoparticles (BiNPs) into polycaprolactone (PCL) to fabricate an electrospun perivascular wrap capable of MSC delivery and conducive to longitudinal monitoring using conventional imaging. We tested the wraps' effects on the attenuation of markers of neointimal hyperplasia (i.e., endothelial dysfunction, hypoxia, and inflammation), the leading cause of AVF failure, in …

Delayed Tooth Eruption As An Early Clinical Indicator Of Genetical Tooth Agenesis: A Family-Based Study Of Cases With Whole-Exome Sequencing, Yu-Chen Jeng, I-Ting Chen, Hui-Ching Cheng, Hsin-Yu Huang, Chao-Kai Hsu, Yu-Fen Yen

Journal of Dental Sciences

Delayed tooth eruption is frequently considered a benign developmental variation but may represent an early sign of genetically driven tooth agenesis. We evaluated a 22-month-old female presenting with markedly delayed eruption (only eight primary teeth) and a positive family history of ectodermal features. Given the inconclusive early radiographic findings, whole-exome sequencing (WES) was utilized. WES revealed the proband carried a heterozygous EDARADD variant (NM_080738:c.328G>T; p.Asp110Tyr). Subsequent familial segregation analysis identified an additional heterozygous WNT10A variant (NM_025216:c.637G>A; p.Gly213Ser) within the broader family. The EDARADD variant alone was associated with varying presentations from normal dentition to delayed eruption. Furthermore, the …

Longitudinal Host Transcriptional Responses To Sars-Cov-2 Infection In Adults With Extremely High Viral Load, Vasanthi Avadhanula, Chad J Creighton, Laura Ferlic-Stark, Divya Nagaraj, Yiqun Zhang, Richard Sucgang, Erin G Nicholson, Anubama Rajan, Vipin Kumar Menon, Harshavardhan Doddapaneni, Donna Marie Muzny, Ginger A Metcalf, Sara Joan Javornik Cregeen, Kristi Louise Hoffman, Richard A Gibbs, Joseph F Petrosino, Pedro A Piedra

Faculty, Staff and Students Publications

Current understanding of viral dynamics of SARS-CoV-2 and host responses driving the pathogenic mechanisms in COVID-19 is rapidly evolving. Here, we conducted a longitudinal study to investigate gene expression patterns during acute SARS-CoV-2 illness. Cases included SARS-CoV-2 infected individuals with extremely high viral loads early in their illness, individuals having low SARS-CoV-2 viral loads early in their infection, and individuals testing negative for SARS-CoV-2. We could identify widespread transcriptional host responses to SARS-CoV-2 infection that were initially most strongly manifested in patients with extremely high initial viral loads, then attenuating within the patient over time as viral loads decreased. Genes …

Research For All: Building A Diverse Researcher Community For The All Of Us Research Program, Rubin Baskir, Minnkyong Lee, Sydney J Mcmaster, Jessica Lee, Faith Blackburne-Proctor, Romuladus Azuine, Nakia Mack, Sheri D Schully, Martin Mendoza, Janeth Sanchez, Yong Crosby, Erica Zumba, Michael Hahn, Naomi Aspaas, Ahmed Elmi, Shanté Alerté, Elizabeth Stewart, Danielle Wilfong, Meag Doherty, Margaret M Farrell, Grace B Hébert, Sula Hood, Cheryl M Thomas, Debra D Murray, Brendan Lee, Louisa A Stark, Megan A Lewis, Jen D Uhrig, Laura R Bartlett, Edgar Gil Rico, Adolph Falcón, Elizabeth Cohn, Mitchell R Lunn, Juno Obedin-Maliver, Linda Cottler, Milton Eder, Fornessa T Randal, Jason Karnes, Kitani Lemieux, Nelson Lemieux, Nelson Lemieux, Lilanta Bradley, Ronnie Tepp, Meredith Wilson, Monica Rodriguez, Chris Lunt, Karriem Watson

Faculty, Staff and Students Publications

OBJECTIVES: The NIH All of Us Research Program (All of Us) is engaging a diverse community of more than 10 000 registered researchers using a robust engagement ecosystem model. We describe strategies used to build an ecosystem that attracts and supports a diverse and inclusive researcher community to use the All of Us dataset and provide metrics on All of Us researcher usage growth.

MATERIALS AND METHODS: Researcher audiences and diversity categories were defined to guide a strategy. A researcher engagement strategy was codeveloped with program partners to support a researcher engagement ecosystem. An adapted ecological model guided the ecosystem …

Bayesian Covariate-Dependent Circadian Modeling Of Rest-Activity Rhythms, Beniamino Hadj-Amar, Vaishnav Krishnan, Marina Vannucci

Faculty, Staff and Students Publications

We propose a Bayesian covariate-dependent anti-logistic circadian model for analyzing activity data collected via wrist-worn wearable devices. The proposed approach integrates covariates into the modeling of the amplitude and phase parameters, facilitating cohort-level analysis with enhanced flexibility and interpretability. To promote model sparsity, we employ an l1-ball projection prior, enabling precise control over complexity while identifying significant predictors. We assess performances on simulated data and then apply the method to real-world actigraphy data from people with epilepsy. Our results demonstrate the model’s effectiveness in uncovering complex relationships among demographic, psychological, and medical factors influencing rest-activity rhythms, offering insights for …

Paternal Upd (15) With Disease-Causing Mutation And Small Supernumerary Ring Chromosome 15: A Case Report, David Lee Curtis, Nasim Bekheirnia, Lorraine Potocki, Ludmila Matyakhina, Mir Reza Bekheirnia

Faculty, Staff and Students Publications

Uniparental disomy (UPD) constitutes an unconventional mode of inheritance that disrupts the typical biparental genetic contribution and may result in phenotypic abnormalities. This report centers on a patient diagnosed with Bartter syndrome Type 1, attributed to a homozygous pathogenic variant in SLC12A1 unmasked by mosaic paternal UPD of chromosome 15. We hypothesize that this pattern (or constellation) emerged from a trisomy rescue event, resulting in two distinct cell lines. Concurrently, the unmasking of a pathogenic paternal SLC12A1 variant by trisomy rescue resulted in the manifestation of Bartter syndrome Type 1. The maternally derived ring chromosome 15 and its impact on …

Variants In Washc3, A Component Of The Wash Complex, Cause Short Stature, Variable Neurodevelopmental Abnormalities, And Distinctive Facial Dysmorphism, Youn Hee Jee, Julian C Lui, Dana Marafi, Zhi-Jie Xia, Ruchika Bhatia, Elaine Zhou, Isabella Herman, Adrian Temnycky, Philip Whalen, Gene Elliot, Ellen W Leschek, Robin Wijngaard, Ronald Van Beek, Annemarie De Vreugd, Maaike C De Vries, Clara D M Van Karnebeek, Machteld M Oud, Thomas C Markello, Kevin M Barnes, Hadil Alrohaif, Hudson H Freeze, William A Gahl, May Christine V Malicdan, Jennifer E Posey, James R Lupski, Jeffrey Baron

Faculty, Staff and Students Publications

Purpose: Genetic defects that impair growth plate chondrogenesis cause a phenotype that varies from skeletal dysplasia to mild short stature with or without other syndromic features. In many individuals with impaired skeletal growth, the genetic causes remain unknown.

Method: Exome sequence was performed in 3 unrelated families with short stature, distinctive facies, and neurodevelopmental abnormalities. The impact of identified variants was studied in vitro.

Results: Exome sequencing identified variants in WASHC3, a component of the WASH complex. In the first family, a de-novo-dominant missense variant (p.L69F) impaired WASHC3 participation in the WASH complex, altered PTH1R endosomal trafficking, diminished PTH1R …

Genetic Landscape Of Hypertrophic Cardiomyopathy In Hong Kong Chinese Population, Derek P H Lee, Ye Cao, Lilei Zhang

Faculty, Staff and Students Publications

Introduction: Asian populations are underrepresented in the hypertrophic cardiomyopathy (HCM) genomic databases, which are currently largely dominated by Caucasian population. We aim to characterize the genetic landscape of HCM in patients from Hong Kong Chinese population.

Methods: From March 2023 to March 2024, fifty-three unrelated patients with an unequivocal clinical diagnosis of HCM were enrolled at a single tertiary center in Hong Kong and underwent genetic testing using a standardized 19-gene panel.

Results: In this cohort study, we identified 13 patients (24.5%) with a predominant pathogenic or likely pathogenic (P/LP) variant and 12 patients (22.6%) with a predominant variant of …

Correction: Genetic Landscape Of Hypertrophic Cardiomyopathy In Hong Kong Chinese Population, Derek P H Lee, Ye Cao, Lilei Zhang

Faculty, Staff and Students Publications

[This corrects the article DOI: 10.3389/fgene.2025.1583838.].

Enhancing Clinical Trial Matching In Molecular Diagnostics: Using Natural Language Processing And Clustering Approaches In Hematological Malignancies, Gillian Fanning

Theses and Dissertations

Clinical trial matching is a critical component of personalized medicine, particularly in the management of hematologic malignancies. At Virginia Commonwealth University (VCU) Health, the Molecular Diagnostics (MDX) Lab produces somatic variant reports and recommends clinical trials based on the presence of clinically significant mutations. However, the current manual trial recommendation process is time-intensive and lacks scalability.

This study introduces a computational framework to streamline and standardize clinical trial matching using natural language processing (NLP) and unsupervised clustering. Trial brief descriptions were analyzed to extract frequent terms, and trials were grouped based on term similarity using joint dimensionality reduction and clustering. …

Adolescent And Caregiver Preparation For Legal Changes At Age 18, Blanca Sanchez-Fournier, Jordyn Babla, Mary Majumder, Beth H Garland, Constance M Wiemann, Albert C Hergenroeder

Center for Medical Ethics and Health Policy Staff Publications

Background: Most adolescents with special healthcare needs (ASHCN) will assume legal responsibility for making decisions about their medical treatment at age 18. Simultaneously, parents or other legal representatives (Caregivers) will lose ASHCN medical record access. This study examined ASHCN and Caregiver knowledge of, satisfaction with, and suggestions for improvement in preparing for these changes.

Methods: Eighty-three dyads (18-year-old ASHCN and Caregivers) completed an assessment to evaluate their knowledge about changes in responsibility for decision making with a focus on consent, satisfaction with the preparation received, and recommendations for improved preparation. Descriptive statistics and mean comparisons were used. Responses to open-ended …