Medical Genetics Commons^™

Impact Of Personalized Risk Scores On Shared Decision Making In Left Ventricular Assist Device Implantation: Findings From A Qualitative Study, Holland Kaplan, Kristin Kostick-Quenet, Benjamin Lang, Robert J Volk, Jennifer Blumenthal-Barby

Center for Medical Ethics and Health Policy Staff Publications

Objective: To assess stakeholders' perspectives on integrating personalized risk scores (PRS) into left ventricular assist device (LVAD) implantation decisions and how these perspectives might impact shared decision making (SDM).

Methods: We conducted 40 in-depth interviews with physicians, nurse coordinators, patients, and caregivers about integrating PRS into LVAD implantation decisions. A codebook was developed to identify thematic patterns, and quotations were consolidated for analysis. We used Thematic Content Analysis in MAXQDA software to identify themes by abstracting relevant quotes.

Results: Clinicians had varying preferences regarding PRS integration into LVAD decision making, while patients and caregivers preferred real-time discussions about PRS with …

Deep Brain Stimulation For Childhood Treatment-Resistant Obsessive-Compulsive Disorder: Mental Health Clinician Views On Candidacy Factors, Ilona Cenolli, Tiffany A Campbell, Natalie Dorfman, Meghan Hurley, Jared N Smith, Kristin Kostick-Quenet, Eric A Storch, Jennifer Blumenthal-Barby, Gabriel Lázaro-Muñoz

Center for Medical Ethics and Health Policy Staff Publications

Introduction: Deep brain stimulation (DBS) is approved under a humanitarian device exemption to manage treatment-resistant obsessive-compulsive disorder (TR-OCD) in adults. It is possible that DBS may be trialed or used clinically off-label in children and adolescents with TR-OCD in the future. DBS is already used to manage treatment-resistant childhood dystonia. Evidence suggests it is a safe and effective intervention for certain types of dystonia. Important questions remain unanswered about the use of DBS in children and adolescents with TR-OCD, including whether mental health clinicians would refer pediatric patients for DBS, and who would be a good candidate for DBS.

Objectives: …

The Human Spinothalamic Tract: Lessons From Cordotomy, Anthony K Allam, Michael Benjamin Larkin, Ishan A Patel, Mohammed Hasen, David Mears, Patrick Dougherty, Ashwin Viswanathan

Faculty, Staff and Student Publications

The spinothalamic tract has long been known as a primary conductor of nociceptive information, with its anatomical and physiological understanding evolving over centuries of research. This comprehensive review traces the history of the spinothalamic tract beginning with Brown-Sequard’s 1860 report of contralateral analgesia following a hemisection of the spinal cord. As clinical and surgical interventions, such as cordotomies have advanced, so did our understanding of the spinothalamic tract’s function and anatomy. The spinothalamic tract’s role as a crossed pathway conducting pain and temperature sensations was solidified by the mid-20th century. However, intricate details of its somatotopic arrangement, anatomical distributions and …

Recurrent Carotid Paragangliomas In A Syndromic Patient With A Heterozygous Missense Variant In Dna Methyltransferase 3 Alpha, Ryan J German, Blake Vuocolo, Liesbeth Vossaert, Lisa Saba, Robin Fletcher, Matthew L Tedder, Bekim Sadikovic, Jennifer Kerkhof, Michael Wangler, Carlos A Bacino

Duncan NRI Faculty and Staff Publications

We report a 40-year-old African American female with a novel variant in exon 8 of DNA methyltransferase 3 alpha (DNMT3A), (NM_022552.4: c.905G>C, p.G302A) who presented with a history of recurrent carotid paragangliomas, mediastinal mass, intellectual disability, dysarthria, cholelithiasis, diabetes mellitus, hypertension, and dysmorphic features. We interpret this novel variant as likely pathogenic and causative for the patient's syndromic features of Heyn-Sproul-Jackson syndrome. Heyn-Sproul-Jackson syndrome is a condition caused by gain-of-function genetic changes in DNMT3A. Paragangliomas have also been observed in non-syndromic patients with genetic alterations in DNMT3A. We describe a patient with clinical features of Heyn-Sproul-Jackson syndrome such as …

Rare Variant Analysis Of Electronic Health Record-Defined Major Depressive Disorder In The All Of Us Research Program, Stephen Emil Vieno

Theses and Dissertations

The underlying pathogenesis of MDD remains poorly understood, with multiple competing hypotheses regarding its exact etiology. As a heterogeneous disorder with relatively low heritability, large-scale genome-wide association studies of MDD have relied on increasingly large sample sizes to identify common genetic variants associated with the disorder. However, the rare variant genetic architecture of MDD is still largely unknown. The aim of the present analysis was to use the AoU—a United States-based biobank that integrates healthcare records from over 50 healthcare systems and possesses whole genome sequencing data for participants—to perform a gene set–based analysis of MDD. This analysis presented several …

Examining Parents’ Perceptions Of Their Children’S Autism And Completion Of Genetic Testing, Georgina J Sakyi, Sarah S Mire, Robin P Goin-Kochel, Chaya N Murali, Susan X Day

Faculty, Staff and Students Publications

Though genetic testing is recommended for children diagnosed with autism spectrum disorder (ASD), both internal (e.g. parents’ and providers’ valuation of genetic testing) and external (e.g. insurance coverage) barriers exist, and exploration of these factors is required to close the gap between provider recommendations and parent follow-through. In a sample of 290 parents, we explored (a) how parents’ ASD-related etiological beliefs and symptom attributions, as well as income, affected genetic testing completion; and (b) whether these factors influence parents’ hopes or concerns about genetic testing. Principal component analysis (PCA) was used to investigate the factor structure of the ASD attribution …

Heterologous Prime-Pull Mucosal Vaccination With An Adjuvanted Rbd Vaccine Elicits Robust Iga Production And Protects Against Sars-Cov-2, Allyson H Hirsch, Calder R Ellsworth, William A Lewis, Ryan Craig, Amy E Meyer, Jonatan Maldonado, Frania Ramirez Lopez, Syamala Rani Thimmiraju, James B Mclachlan, Xuebin Qin, Nicholas J Maness, Jeroen Pollet, Ulrich Strych, Maria Elena Bottazzi, Peter J Hotez, Lisa A Morici

Faculty, Staff and Students Publications

Despite the efficacy of approved severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in preventing severe disease and death, breakthrough infections continue to occur in vaccinated individuals, contributing to further viral mutation and spread. These limitations may be attributable to the poor induction of mucosal immunity by parenteral vaccination. Mucosal adjuvants, such as T-vant, can enhance vaccine-induced immune responses through the generation of antigen-specific antibodies and T cells in the respiratory tract. In this study, we evaluated the protective efficacy of adjuvanted SARS-CoV-2 receptor binding domain (RBD) subunit vaccines administered by homologous and heterologous routes. Immunized mice were challenged with …

A Hybrid Cloud Data Lake Architecture Supporting The Integration Of Clinical And Genomics Data, Apollo Mcowiti, Heidi Dowst, Fei Zheng, Susan Hilsenbeck, Christopher Amos

Center for Medical Ethics and Health Policy Staff Publications

Objective: Cancer centers must quickly integrate clinical genomics data from different vendors for oncology operations and research. Clinical data warehouse architectures are costly to construct and brittle, and they are not readily amenable to the rapid changes in oncology research. We introduce a cost-effective hybrid cloud Data Lake architecture for storing clinical genomic data from different vendors, aiding both clinical and research workflows.

Methods: We created a Data Lake architecture based on the zone architecture, with four layers: ingestion, storage, transformation, and interaction. The layers are implemented with a hybrid cloud architecture. Rich metadata created from patient and genomic data …

A Landscape Analysis Of Psychedelic Retreat Organizations Advertising Online, Logan Neitzke-Spruill, Caroline S Beit, Jill Oliver Robinson, Nikita Singh, Srijith Kambala, Rishi Ramesh, Amy L Mcguire

Center for Medical Ethics and Health Policy Staff Publications

Research into psychedelics' clinical potential has corresponded to a growth in public interest and adult use. One common pathway to accessing psychedelics is through psychedelic retreats. While individual retreats have been characterized in the anthropological literature, no systematic evaluation of the psychedelic retreat industry exists. Assessing the characteristics of the psychedelic retreat industry is critical to understanding the associated ethical, legal, and social implications and ensuring consumer safety. To this end, we conducted a landscape analysis of online, publicly available information to capture and characterize a broad range of organizations offering psychedelic retreats and marketing to English-speaking consumers. From July …

Patient-Centric Federated Learning: Automating Meaningful Consent To Health Data Sharing With Smart Contracts, Kristin M Kostick-Quenet, Marcelo Corrales Compagnucci, Mateo Aboy, Timo Minssen

Center for Medical Ethics and Health Policy Staff Publications

Federated Learning (FL) promises to enhance data-driven health research by enabling collaborative machine learning across distributed datasets without direct data exchange. However, current FL implementations primarily reflect the data-sharing interests of institutional controllers rather than those of individual patients whose data are at stake. Existing consent mechanisms-like broad consent under HIPAA or explicit consent under the GDPR-fail to provide patients with control over how their data is used. This article explores the integration of smart contracts (SCs) into FL as a mechanism for automating, enforcing, and documenting consent in data transactions. SCs, encoded in decentralized ledger technologies, can ensure that …

Refining The Interpretation Of Variants Of Uncertain Significance In Hereditary Cancer Screening Through Integrated Rna Sequencing, Youbao Sha, J Bryce Ortiz, Sara L Bristow, Kate Loranger, Linyan Meng, Xiaonan Zhao, Fan Xia, Sheetal Parmar, Adam C Elnaggar, Wenbo Xu

Faculty, Staff and Students Publications

Purpose: Although up to 25% of germline variants are predicted to affect splicing, most are classified as variants of uncertain significance (VUS) because of the limited understanding of their functional consequences. Here, we investigated the impact of RNA sequencing (RNA-seq) data on the ability to resolve splicing-related VUS.

Methods: Patients with VUS predicted to alter splicing identified through commercial hereditary cancer testing between October 2021 to July 2023 were included. RNA-seq was used to compare splicing patterns between patient blood samples and normal controls. VUS reclassification rates were calculated.

Results: In total, 411 VUS in 52 genes predicted to affect …

Whole Exome Sequencing As A Screening Tool In Dogs: A Pilot Study, Fréderique Boeykens, Evelien Bogaerts, Liesbeth Vossaert, Luc Peelman, Filip Van Nieuwerburgh, Jimmy H Saunders, Bart J G Broeckx

Faculty, Staff and Students Publications

Background: Whole-exome sequencing (WES) is used to selectively sequence all exons of protein-coding genes. WES is considered as a cost-effective and direct approach for identifying phenotype-associated variants in protein-coding regions and is as such situated between the traditional Sanger sequencing and whole genome sequencing (WGS). While WES is already widely used as a clinical tool in human and medical genetics, its use in veterinary medicine is currently restricted to research purposes. In this article, we aimed to provide baseline performance characteristics of a WES design to assess its suitability with future applications in veterinary clinical genetics in mind.

Methods: To …

To Discard Or Not To Discard 1pns? A Systematic Review And Meta-Analysis On 291,474 Embryos, T. Lee, F. Qi, K. Peirce, J. Natalwala, V. Chapple, P. J. Mark, K. Sanders, Y. Liu

Research outputs 2022 to 2026

Unlike embryos that display two pronuclei (2PN), monopronucleated (1PN) embryos are assumed to be haploid and can be routinely discarded. Although there are reports of live births after 1PN embryo transfer, the developmental and clinical prognosis of 1PN embryos has not been systematically evaluated. The aim of this review was to elucidate the developmental, clinical and neonatal outcomes of 1PN embryos compared with 2PN embryos. Twenty-four studies met the inclusion criteria. The blastulation rate was lower in 1PN embryos compared with 2PN embryos [risk ratio (RR) 0.50, 95% CI 0.48–0.51]. The live birth rate was lower in 1PN blastocysts when …

Circulating Lipocalin-2 Across The Adult Lifespan, Carlie Bauer, Cassandra Smith, Sara Vogrin, Andrew S. Palmer, Mary Woessner, Shanie Landen, Macsue Jacques, Elizabeth Byrnes, Nir Eynon, Marc Sim, Joshua R. Lewis, Itamar Levinger

Research outputs 2022 to 2026

Lipocalin-2 (LCN2), a hormone produced by adipocytes, osteoblasts and renal tubular cells, is implicated in age-related diseases, including cardio-metabolic disease. To understand the role LCN2 may play in pathological states, we first need to elucidate the relationship between circulating LCN2 with indices of cardio-metabolic health during “normal” ageing. This study examined the relationship between serum levels of LCN2, age and cardio-metabolic measures across the adult lifespan in males and females. We conducted a pooled cohort analysis including 124 community-dwelling males (n = 52) and females (n = 72) (age 20 - 87 years, median BMI 25.92 (23.04, 29.81) kg/m2). Serum …

Experiences From Dual Genome Next-Generation Sequencing Panel Testing For Mitochondrial Disorders: A Comprehensive Molecular Diagnosis, Elizabeth Gorman, Hongzheng Dai, Yanming Feng, William James Craigen, David C Y Chen, Fan Xia, Linyan Meng, Pengfei Liu, Robert Rigobello, Arpita Neogi, Christine M Eng, Yue Wang

Faculty, Staff and Students Publications

Introduction: The molecular diagnosis of mitochondrial disorders is complicated by phenotypic variability, genetic heterogeneity, and the complexity of mitochondrial heteroplasmy. Next-generation sequencing (NGS) of the mitochondrial genome in combination with a targeted panel of nuclear genes associated with mitochondrial disease provides the highest likelihood of obtaining a comprehensive molecular diagnosis. To assess the clinical utility of this approach, we describe the results from a retrospective review of patients having dual genome panel testing for mitochondrial disease.

Methods: Dual genome panel testing by NGS was performed on a cohort of 1,509 unrelated affected individuals with suspected mitochondrial disorders. This test included …

Autosomal Dominant Hk1-Related Neurodevelopmental Disorder With Visual Defects And Brain Anomalies (Nedviba): An Emerging Mitochondrial Disorder, Bobby G Ng, Erik A Eklund, Jill A Rosenfeld, Abdallah F Elias, Aya Abu-El-Haija, Celine Bris, Magalie Barth, Jong-Hee Chae, Murim Choi, Holly A Dubbs, Carl Fratter, Nicola Foulds, Candace Gamble, Ralitza H Gavrilova, Jaclyn Haven, Trevor L Hoffman, Jill V Hunter, Austin Larson, Timothy Edward Lotze, Pilar Magoulas, Emily C Magness, Debra M Bootin, Eric D Marsh, Victoria Nesbitt, Matthew T Pastore, Joanna Poulton, Shamima Rahman, Fernando Scaglia, Chaya Murali, Jennifer Posey, Joshua Rotenberg, Betsy Schmalz, Deepali N Shinde, Zöe Powis, Rivka Sukenik-Halevy, Kristen V Truxal, Tami Uster, Matheus Vernet Machado Bressan Wilke, Erik Klee, Hyewon Woo, Donald Younkin, Jianhua Zhao, Jorge Granadillo, Seema Lalani, David Chitayat, Wendy K Chung, Hudson H Freeze, Volkan Okur

Faculty, Staff and Students Publications

Purpose: Hexokinase 1 (HK1) encodes a ubiquitously expressed hexokinase, which is responsible for the first step of glycolysis, phosphorylation of glucose to glucose-6-phosphate. Both autosomal recessive and dominant variants in this gene have previously been shown to cause human disease, and presently, there are clinical data available for 27 individuals with the monoallelic neurodevelopmental disorder with visual defects and brain anomalies. Delineation of the entire phenotypic spectrum and genotype-phenotype relations will aid in management and counseling decisions.

Methods: We present molecular and clinical data on 22 additional individuals with heterozygous, mostly de novo, variants in HK1. We …

The Dna Demethylase Tet1 Modifies The Impact Of Maternal Folic Acid Status On Embryonic Brain Development, Lehua Chen, Bernard K Van Der Veer, Qiuying Chen, Spyridon Champeris Tsaniras, Wannes Brangers, Harm H M Kwak, Rita Khoueiry, Yunping Lei, Robert Cabrera, Steven S Gross, Richard H Finnell, Kian Peng Koh

Faculty, Staff and Students Publications

Folic acid (FA) is well known to prevent neural tube defects (NTDs), but we do not know why many human NTD cases still remain refractory to FA supplementation. Here, we investigate how the DNA demethylase TET1 interacts with maternal FA status to regulate mouse embryonic brain development. We determined that cranial NTDs display higher penetrance in non-inbred than in inbred Tet1−/− embryos and are resistant to FA supplementation across strains. Maternal diets that are either too rich or deficient in FA are linked to an increased incidence of cranial deformities in wild type and Tet1+/− offspring and to …

Mixed-Methods Evaluation And Behavior Change Interventions To Improve Hand Hygiene Resources And Practices Among Healthcare Workers In Polyclinics And Health Centers In Belize, 2023, Anh N Ly, Kelsey Mcdavid, Christina Craig, Rosalva Blanco, Vickie Romero, Melissa Diaz-Musa, Francis Morey, Russell Manzanero, Gerhaldine Morazan, Makenzie Towery, Anna Impellitteri, Matthew Lozier, Kristy O Murray

Faculty, Staff and Students Publications

Background: Hand hygiene (HH) is an effective public health measure to prevent the spread of infections in healthcare settings. A previous study in Belize showed gaps in HH practices in hospitals and large polyclinics; however, there are limited national data assessing access to and use of HH resources in smaller outpatient primary care facilities, especially in rural areas.

Methods: In February 2023, facility assessments were conducted at 26 health centers and polyclinics in Belize to assess the availability of HH resources. Of these, 12 pilot healthcare facilities (HCF) were selected for additional evaluation, which included observation of HH practices, hand …

Determining Essential Regulatory Factors In Extravillous-Trophoblast Differentiation And Splice Variants Associated With The Development Of Preeclampsia, Brandt Hugh Beck

Electronic Theses & Dissertations (2024 - present)

Preeclampsia is a common condition affecting mothers across the world. Rates for preeclampsia have been rising in the past years due to factors such as obesity and diabetes. Since this condition has been more prevalent, a better understanding of the factors surrounding the preeclamptic state are needed. Core cell types and biological functions of placenta development are known but the cause behind the preeclamptic environment is not well understood. This research aims to investigate the potential causes behind preeclampsia by first reviewing Extravillous-Trophoblast differentiation factors in the context of differential gene expression and alternative splicing then evaluate towards preeclamptic tissue. …

Refining The Interpretation Of Variants Of Uncertain Significance In Hereditary Cancer Screening Through Integrated Rna Sequencing, Youbao Sha, J Bryce Ortiz, Sara L Bristow, Kate Loranger, Linyan Meng, Xiaonan Zhao, Fan Xia, Sheetal Parmar, Adam C Elnaggar, Wenbo Xu

Faculty, Staff and Students Publications

Purpose: Although up to 25% of germline variants are predicted to affect splicing, most are classified as variants of uncertain significance (VUS) because of the limited understanding of their functional consequences. Here, we investigated the impact of RNA sequencing (RNA-seq) data on the ability to resolve splicing-related VUS.

Methods: Patients with VUS predicted to alter splicing identified through commercial hereditary cancer testing between October 2021 to July 2023 were included. RNA-seq was used to compare splicing patterns between patient blood samples and normal controls. VUS reclassification rates were calculated.

Results: In total, 411 VUS in 52 genes predicted to affect …

Goldenbraid20 E Coli: A Comprehensive And Characterized Toolkit For Enterics, Matthew B Cooke, Kobie T Welch, Laura D Ramirez, Alice X Wen, David C Marciano, Christophe Herman

Faculty, Staff and Students Publications

Modular cloning systems streamline laboratory workflows by consolidating genetic 'parts' into reusable and modular collections, enabling researchers to fast-track strain construction. The GoldenBraid 2.0 modular cloning system utilizes the cutting property of type IIS restriction enzymes to create defined genetic 'grammars', which facilitate the reuse of standardized genetic parts and assembly of genetic parts in the right order. Here, we present a GoldenBraid 2.0 toolkit of genetic parts designed to accelerate cloning in the model bacterium

Zic1 Is A Context-Dependent Medulloblastoma Driver In The Rhombic Lip, John J Y Lee, Ran Tao, Zhen You, Parthiv Haldipur, Anders W Erickson, Hamza Farooq, Liam D Hendriske, Namal Abeysundara, Cory M Richman, Evan Y Wang, Neha Das Gupta, Jennifer Hadley, Melissa Batts, Christopher W Mount, Xiaochong Wu, Alex Rasnitsyn, Swneke Bailey, Florence M G Cavalli, Sorana Morrissy, Livia Garzia, Kulandaimanuvel Antony Michealraj, Abhi Visvanathan, Vernon Fong, Jonelle Palotta, Raul Suarez, Bryn G Livingston, Miao Liu, Betty Luu, Craig Daniels, James Loukides, Anne Bendel, Pim J French, Johan M Kros, Andrey Korshunov, Marcel Kool, Fernando Chico Ponce De León, Mario Perezpeña-Diazconti, Boleslaw Lach, Sheila K Singh, Sarah E S Leary, Byung-Kyu Cho, Seung-Ki Kim, Kyu-Chang Wang, Ji-Yeoun Lee, Teiji Tominaga, William A Weiss, Joanna J Phillips, Shizhong Dai, Gelareh Zadeh, Ali G Saad, László Bognár, Almos Klekner, Ian F Pollack, Ronald L Hamilton, Young-Shin Ra, Wieslawa A Grajkowska, Marta Perek-Polnik, Reid C Thompson, Anna M Kenney, Michael K Cooper, Stephen C Mack, Nada Jabado, Mathieu Lupien, Marco Gallo, Vijay Ramaswamy, Mario L Suva, Hiromichi Suzuki, Kathleen J Millen, L Frank Huang, Paul A Northcott, Michael D Taylor

Faculty, Staff and Students Publications

Transcription factors are frequent cancer driver genes, exhibiting noted specificity based on the precise cell of origin. We demonstrate that ZIC1 exhibits loss-of-function (LOF) somatic events in group 4 (G4) medulloblastoma through recurrent point mutations, subchromosomal deletions and mono-allelic epigenetic repression (60% of G4 medulloblastoma). In contrast, highly similar SHH medulloblastoma exhibits distinct and diametrically opposed gain-of-function mutations and copy number gains (20% of SHH medulloblastoma). Overexpression of ZIC1 suppresses the growth of group 3 medulloblastoma models, whereas it promotes the proliferation of SHH medulloblastoma precursor cells. SHH medulloblastoma ZIC1 mutants show increased activity versus wild-type ZIC1, whereas G4 medulloblastoma …

Epilepsy Clinic Analytics: Leveraging Emr Reporting Tools To Characterize Center Volume And Complexity, Vanuli Arya, Arindam Ghosh Mazumder, Muna Nnamani, Mark A Abboud, Samuel C Lee, Michael S Guzman, Vaishnav Krishnan

Faculty, Staff and Students Publications

Introduction: Epilepsy centers connect patients to multidisciplinary provider groups that can coordinate surgical interventions and/or investigational treatments. Automated techniques to cross-sectionally review patient volume and complexity may reveal objective metrics to assign appropriate personnel and resources. Here, we leveraged an electronic medical record (EMR) reporting tool to examine how patient and visit volumes, antiseizure medication (ASM) prescriptions and neuromodulation use evolved over an 11-year epoch at a single level 4 adult epilepsy center in Texas, USA.

Methods: Using Epic Workbench Reporting, we acquired the dates of (i) all clinic visits (office or telemedicine), (ii) CPT codes for neuromodulation interrogation/programming, and …

Monoallelic Expression Can Govern Penetrance Of Inborn Errors Of Immunity, O'Jay Stewart, Conor Gruber, Haley E Randolph, Roosheel Patel, Meredith Ramba, Enrica Calzoni, Lei Haley Huang, Jay Levy, Sofija Buta, Angelica Lee, Christos Sazeides, Zoe Prue, David P Hoytema Van Konijnenburg, Ivan K Chinn, Luis A Pedroza, James R Lupski, Erica G Schmitt, Megan A Cooper, Anne Puel, Xiao Peng, Stéphanie Boisson-Dupuis, Jacinta Bustamante, Satoshi Okada, Marta Martin-Fernandez, Jordan S Orange, Jean-Laurent Casanova, Joshua D Milner, Dusan Bogunovic

Faculty, Staff and Students Publications

Inborn errors of immunity (IEIs) are genetic disorders that underlie susceptibility to infection, autoimmunity, autoinflammation, allergy and/or malignancy1. Incomplete penetrance is common among IEIs despite their monogenic basis2. Here we investigate the contribution of autosomal random monoallelic expression (aRMAE), a somatic commitment to the expression of one allele3,4, to phenotypic variability observed in families with IEIs. Using a clonal primary T cell system to assess aRMAE status of genes in healthy individuals, we find that 4.30% of IEI genes and 5.20% of all genes undergo aRMAE. Perturbing H3K27me3 and DNA methylation alters …

Establishment Of Reference Intervals For Serum Immunoglobulin G N-Glycosylation Features In Healthy Chinese Adults: A Nationwide Survey In The Framework Of Predictive, Preventive, And Personalized Medicine, Changyu Liu, Yinghao Wang, Xingang Li, Xiaojia Xu, Ruirui Xu, Cuihong Tian, Zhixian Chen, Xinxia Lu, Yuejin Li, Meng Wang, Zhaoyang Tang, Xueyu Chen, Guoyong Ding, Xuerui Tan, Dong Li, Haifeng Hou, Wei Wang

Research outputs 2022 to 2026

Background: Immunoglobulin G (IgG) N-glycosylation plays a vital role in the pathogenesis of autoimmune disorders, inflammatory diseases, and viral infections. While various models of serum IgG N-glycosylation have been developed to identify individuals at high risk for relevant diseases, reference intervals (RIs) for the levels of IgG N-glycans have not been established yet. Identifying RIs for serum IgG N-glycans closely associated with biological aging and disease risk contributes to predictive, preventive, and personalized medicine (PPPM/3PM), which results in improvement of patients’ outcomes, enhancement of healthcare efficiency, and in reducing burden of chronic diseases. This study is aimed at defining the …

Ethical, Legal, And Social Issues In Metaverse-Enabled Healthcare, Kristin M Kostick-Quenet, Vasiliki Rahimzadeh

Center for Medical Ethics and Health Policy Staff Publications

Metaverse is heralded by some as the next iteration of the internet. It offers three-dimensional, immersive virtual spaces, where users, represented as avatars, can synchronously work, play, interact, and transact. Initially developed within the realm of massive multiplayer online role-playing games, the metaverse now extends into sectors such as music, entertainment, retail, real estate, and, more recently, healthcare. Users engage in the metaverse using augmented reality or virtual reality (AR/VR) headsets that interoperate with other sensory devices to integrate biofeedback and multimodal data streams.1 In this article, the authors offer a conceptual synthesis and anticipatory policy analysis grounded in …

Glutamatergic Lateral Habenula Neurons Modulate Consolidation Of Associative Memories, Snigdha Srivastava, I-Ching Wang, Mikhail Y Kochukov, Jessica L Swanson, Mauro Costa-Mattioli, Benjamin R Arenkiel

Duncan NRI Faculty and Staff Publications

INTRODUCTION: Despite the rise in psychiatric disorders worldwide, the underlying brain circuits responsible for these devastating conditions remain elusive. The lateral habenula (LHb) has emerged as a key brain structure in depression studies due to its hyperactive state in both patients and animal models. While this aligns with known roles in driving aversive states and regulating serotonin release, it is still unclear how acute and transient activity changes in the LHb can influence higher order cognitive processes such as learning, memory, and behavioral adaptation. Given the importance of these processes to psychiatric conditions, understanding how LHb activity impacts cognitive function …

Resort Enhances Reference-Based Cell Type Deconvolution For Spatial Transcriptomics Through Regional Information Integration, Linhua Wang, Ling Wu, Guantong Qi, Chaozhong Liu, Wanli Wang, Xiang H-F Zhang, Zhandong Liu

Duncan NRI Faculty and Staff Publications

Motivation: Spatial transcriptomics (ST) captures positional gene expression within tissues but lacks single-cell resolution. Reference-based cell type deconvolution methods were developed to understand cell type distributions for ST. However, batch/platform discrepancies between references and ST impact their accuracy.

Results: We present Region-based Cell Sorting (ReSort), which utilizes ST's region-level data to lessen reliance on reference data and alleviate these technical issues. In simulation studies, ReSort enhances reference-based deconvolution methods. Applying ReSort to a mouse breast cancer model highlights macrophages M0 and M2 enrichment in the epithelial clone, revealing insights into epithelial-mesenchymal transition and immune infiltration.

Availability and implementation: Source codes …

Drosophila Models Uncover Substrate Channeling Effects On Phospholipids And Sphingolipids In Peroxisomal Biogenesis Disorders, Michael F Wangler, Yu-Hsin Chao, Mary Roth, Ruth Welti, James A Mcnew

Duncan NRI Faculty and Staff Publications

Peroxisomal Biogenesis Disorders Zellweger Spectrum (PBD-ZSD) disorders are a group of autosomal recessive defects in peroxisome formation that produce a multi-systemic disease presenting at birth or in childhood. Well documented clinical biomarkers such as elevated very long chain fatty acids (VLCFA) are key biochemical diagnostic findings in these conditions. Additional, secondary biochemical alterations such as elevated very long chain lysophosphatidylcholines are allowing newborn screening for peroxisomal disease. In addition, a more widespread impact on metabolism and lipids is increasingly being documented by metabolomic and lipidomic studies. Here we utilize Drosophila models of pex2 and pex16 as well as human plasma …

When Families Bridge The Research-Clinical Divide: An Exploration Of Values Regarding Cascade Screening In Genomic Research, Katherine E Bonini, Lauren R Desrosiers-Battu, Ann Katherine M Foreman, Nuriye N Sahin-Hodoglugil, Mary A Majumder, Candice R Finnila, Stephanie A Kraft, Laura M Amendola, Eimear E Kenny, Stephanie M Fullerton, Sara L Ackerman, Benjamin S Wilfond, Amy L Mcguire, Hadley Stevens Smith

Center for Medical Ethics and Health Policy Staff Publications

Purpose: Genetic results are important for both patients and their biological relatives. However, cascade screening (CS) uptake is low, especially when testing occurs through research programs and not clinical care. Ethical guidance is needed for CS implementation when individuals receive clinical genetic results through research.

Methods: We conducted focus groups with 3 groups of individuals in the Clinical Sequencing Evidence-Generating Research Consortium: clinicians, patient representatives, and scholars of the ethical, legal, and social implications of genomics. We used inductive thematic and comparative analyses to analyze data within and across the groups.

Results: All participants (n = 27) agreed that …