Host-Virus Interaction Dynamics Using Sulfolobus Spindle-Shaped Virus And Host Sulfolobales System, Yeasin Ahmed

Graduate Theses and Dissertations

The Sulfolobus Spindle-shaped virus (SSV) is among the most studied archaeal viruses, particularly in extreme environments. This virus predominantly infects multiple Crenarchaea from the Sulfolobaceae family. These hosts thrive in extreme environmental conditions, such as sulfuric hot springs, with a pH of 2 to 4 and a temperature of 76-80˚C. Sulfolobales exhibit a wide geographical distribution across volcanic hot springs. The Sulfolobus Spindle-shaped Virus (SSV), encompassing strains such as SSV1 and SSV8, employs a non-lytic replication strategy in hosts belonging to the order Sulfolobales. The SSV-Sulfolobales system can be cultured in liquid and gellan gum solid media. A comprehensive study …

Identifying Critical Evidence Gaps In Wound Closure And Incision Management After Total Hip Arthroplasty: Delphi Panel Insights, Margaret Ainslie-Garcia, Lucas Anderson, Benjamin Bloch, Tim N Board, Antonia Chen, Samantha Craigie, Walter Danker, Najmuddin Gunja, James Harty, Victor Hernandez, Kate Lebedeva, Mitchell Ng, Daniel Hameed, Michael Mont, Ryan Nunley, Javad Parvizi, Sean Sequeira, Carsten Perka, Nicolas Piuzzi, Ola Rolfson, Joshua Rychlik, Emilio Romanini, Pablo Sanz-Ruiz, Rafael Sierra, Linda Suleiman, Eleftherios Tsiridis, Pascal-André Vendittoli, Helge Wangen, Luigi Zagra

Department of Orthopaedic Surgery Faculty Papers

BACKGROUND: In total hip arthroplasty (THA), proper management of surgical incisions is essential for optimal wound healing and patient outcomes. Despite advances in surgical techniques, significant challenges remain in preventing complications and infections. This study aimed to identify evidence gaps in THA wound care, including presurgical preparation, intraoperative practices, and postsurgical complications.

METHODS: Using a modified Delphi method, 20 expert orthopedic surgeons from Europe and North America participated in a 3-phase consensus process from April 1 to September 30, 2023. This included a preliminary questionnaire, a remote conference, and a final online survey. The panel reviewed literature and achieved agreement …

Adolescent E-Cigarette Expectancies: Measure Development And Preliminary Validity Of The Electronic Nicotine Vaping Outcomes Measure For Youth, Paul T. Harrell, Kelli J. England, Tracey E. Barnett, Vani N. Simmons, Richard W. Handel, Amy C. Paulson

Department of Pediatrics Faculty Publications

BACKGROUND: Electronic nicotine delivery systems (“e-cigarettes”) are the nicotine product most commonly used by adolescents. Research, treatment, and policy could benefit from measures of adolescent e-cigarette beliefs about outcomes of use (ie, expectancies). In the current study, we developed and tested an adolescent electronic nicotine vaping expectancy measure.

METHODS: A focus group with adolescents evaluated potential e-cigarette expectancy items. A panel of national experts assisted in revision of these items. Finally, items were administered to a sample of adolescents 14-17 years old (N = 267, Mean age 15.6, SD = 1.1, 50.9% Female, 50.2% Non-Hispanic White, 22.5% Non-Hispanic Black, 14.2% …

Study Of Ai Applications In Biomedical Data Acquisition, Communication, And Analysis: Cest Mri Acceleration And Ecg Transmissions, Adarsha Bhattarai

Dissertations and Doctoral Documents, University of Nebraska-Lincoln, 2023–

This dissertation investigates the application of artificial intelligence in biomedical data acquisition, communication, and analysis to advance neurological research and to enable the early detection of cardiovascular conditions. Despite significant advances in imaging and physiological modalities, challenges persist. Imaging modalities, such as the chemical exchange saturation transfer magnetic resonance imaging (CEST MRI) technique are challenged by a prolonged data acquisition time and high operational costs. In addition, physiological modalities such as electrocardiogram (ECG) sensors face constraints in providing uninterrupted signal monitoring which is crucial for the timely detection of premature cardiac abnormalities. The primary goal of this work is to …

Hormonal Modulation Of Sexual Approach And Avoidance Among Women With A History Of Sexual Trauma, Anneliis Susan Sartin-Tarm

Dissertations and Doctoral Documents, University of Nebraska-Lincoln, 2023–

A history of sexual trauma places women at a high risk for sexual dysfunction and other health sequelae, yet the influence of ovarian hormones in this population is poorly understood. This dissertation tested the theory that the effects of ovarian hormones are mediated by cognitive approach-avoidance systems to shape sexual well-being, and that this process is moderated by sexual trauma history. This was investigated across three studies examining the menstrual cycle, hormonal contraceptive use, and menopause. Across each chapter, I present complementary evidence demonstrating that hormones interact with the interpretation of ambiguous internal and external cues with respect to sexual …

Egg White Hydrolysate In Hypertension: A Mechanistic Investigation Of Gut Microbiota Dependent And Independent Pathways, Emerson David Nolasco

Dissertations and Doctoral Documents, University of Nebraska-Lincoln, 2023–

Cardiovascular diseases are one of the leading causes of mortality worldwide in which hypertension is a risk factor. Present pharmacological interventions require long-term adherence to the therapy and are often associated with undesirable side effects. Moreover, treatments have overlooked the role of the microbiome in the development of hypertension. Egg white hydrolysate (EWH) has exhibited antihypertensive properties with potential to be used as a natural alternative for the prevention and management of hypertension. However, EWH peptide’s effect on the gut microbiome remains yet to be elucidated. Studies have described that a portion of the ingested protein can remain undigested as …

Anxiety During Perimenopause: A Narrative Qualitative Study Of The Women’S Lived Experiences, Kayla Mcelhany

Dissertations and Theses (Open Access)

Abstract

Objectives: Perimenopause has been associated with increased anxiety symptoms. However, data is lacking regarding the experiences of women with perimenopausal anxiety and the contributing factors to worsening anxiety symptoms. We explored the experiences of women with self-reported new onset or worsening of anxiety symptoms during perimenopause to better understand contributing factors.

Study design: Twenty women participated in one-on-one interviews to explore experiences of perimenopausal anxiety in the context of their daily lives and perimenopausal physical changes. Inductive thematic analysis was used to develop codes and themes from the transcribed interview data. Analysis was done using MAXQDA software.

Main …

Association Of Epigenetic Aging With Plasma Cbiomarkers Of Amyloid, Tau, Neurodegeneration, And Neuroinflammation In Hispanic/Latino Adults, Myriam Fornage, Wassim Tarraf, Martha L Daviglus, Charles Decarli, Kevin A Gonzalez, Carmen R Isasi, Sayaka Kuwayama, Melissa Lamar, Bonnie E Levin, Humberto Parada, Alberto R Ramos, Tatjana Rundek, Bharat Thyagarajan, Hector M González

The Brown Foundation: Institute of Molecular Medicine

Background: Blood-based biomarkers hold significant promise for the early detection and diagnosis of Alzheimer's disease (AD) and other dementias. Age-related changes in blood levels of AD biomarkers are well-documented but poorly understood. Epigenetic clocks are mathematical models based on DNA methylation patterns that reflect various aspects of the multidimensional aging process. We investigated the associations of epigenetic aging with five blood-based AD biomarkers in 2656 Hispanic/Latino adults (mean age 62.5 years; 65% females) from the Hispanic Community Health Study/Study of Latinos. We used multivariable linear regression models to estimate the associations of acceleration in each of five epigenetic clocks with …

Antithrombotic Strategies And Outcomes In Neonates And Infants With Cardiac Shunts: A Systematic Review And Meta-Analysis., Amy L. Kiskaddon, Neil A. Goldenberg, Marisol Betensky, Joshua W. Branstetter, Dina Ashour, Pamela Williams, Arabela C. Stock, Michael Silvey, Therese M. Giglia, Nhue L. Do, Cardiac Disease Thrombosis And Hemostasis Working Party Of The Isth Ssc Subcommittee On Pediatric And Neonatal Thrombosis And Hemostasis

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Cardiac shunt thrombosis in neonates and infants remains a concern for shunt failure and mortality. The optimal strategy for thromboprophylaxis remains unknown.

OBJECTIVES: This systematic review aims to characterize antithrombotic strategies and outcomes in neonates and infants with a cardiac shunt.

METHODS: MEDLINE, Embase, and Cochrane CENTRAL were searched from inception through July 2024 for studies reporting shunt thrombosis prevalence among infants who received a cardiac shunt. We estimated the pooled prevalence of shunt thrombosis using random-effects meta-analysis. In the subgroup analysis, we evaluated the effects of shunt type and antithrombotic strategies on shunt thrombosis prevalence.

RESULTS: A total …

Dean's Research Newsletter, August 2025, Neil W. Schluger

SOM Dean's Research Newsletter

No abstract provided.

A Tale Of Two Toxicants: Investigating The Interaction Between Hexavalent Chromium And Perfluorooctane Sulfonic Acid., Morgan Elizabeth Delnicki

Electronic Theses and Dissertations

Hexavalent chromium [Cr(VI)] and per- and polyfluoroalkyl substances (PFAS) are environmental contaminants of major public health concern. Despite commonly being found together in contaminated drinking water, no studies have considered the concomitant health effects of Cr(VI) and PFAS, specifically perfluorooctane sulfonic acid (PFOS). In vitro studies using CHO cells assessed the cytotoxicity and genotoxicity of Cr(VI) and PFAS both individually and in combination. Intracellular and extracellular Cr levels were measured with Atomic Absorption Spectrometry. PFOS was found to exacerbate Cr(VI) induced cytotoxicity and genotoxicity. Additionally, a novel in vivo model of studying the hepatotoxicity of Cr(VI) was established. Adult Hartley …

Exploring Hexavalent Chromium Exposure And Lipid Accumulation In Liver Disease., Gabrielle Celine Griffin

Electronic Theses and Dissertations

The prevalence of MASLD has doubled over the past 20 years and continues to rise. Hexavalent chromium [Cr(VI)], a top chemical hazard in U.S. drinking water, is emerging as potential risk factor for liver disease. To study the impact of Cr(VI) and high-fat diet on MASLD, we developed an in vivo model using Sprague-Dawley rats exposed to Cr(VI) in drinking water (0, 0.05, or 0.1 mg/L) and fed normal or high-fat diet for 90 days. High-fat diet significantly increased body mass, plasma lipoproteins, cholesterol, liver injury, and hepatic triglycerides, which were exacerbated by Cr(VI) exposure. Cr(VI) alone increased hepatic chromium …

Integrating Bulk And Single-Cell Transcriptomics To Investigate Intratumor Heterogeneity, Shuai Guo

Dissertations and Theses (Open Access)

Cancers are heterogeneous mixtures of tumor and surrounding cells, where each component comprises multiple distinct sub-types and/or states. Understanding the cell-type-specific contributions is critical for advancing cancer biology, yet high-throughput expression profiles from tumor tissues only represent combined signals from all diverse cellular sources. Bulk deconvolution with single-cell/nucleus (sc/sn) RNA-seq data has emerged as a powerful approach to dissect both cellular composition and cell-type-specific expression patterns, yet the technological discrepancy across sequencing platforms limits accuracy.

To systematically evaluate the impact of platform discrepancies on bulk deconvolution, we first generated a benchmark dataset of 24 healthy retinas with paired bulk and …

Chronic Cluster Headache Is A Rare Disease: Implications For Diagnosis, Treatment And Public Health, Hsiangkuo Yuan, Jan Hoffmann, Elena Ruiz De La Torre, Michael J. Marmura, Mario F. P. Peres

Department of Jefferson Headache Center Papers and Presentations

Cluster headache (CH) is a rare and painful primary headache disorder characterized by severe unilateral pain and cranial autonomic symptoms. This perspective examines the epidemiological evidence supporting the classification of chronic cluster headache (CCH) as a rare disease, noting a prevalence of CH of approximately 124 per 100,000 individuals, with only 3.5-13.7% manifesting CCH. This prevalence meets criteria established by both the US Food and Drug Administration and European Medicines Agency for rare disease designation. The rarity of CCH creates substantial clinical and research challenges, including prolonged diagnostic delays, limited research funding and a dearth of approved treatments. The economic …

Detection Of Activity Cliffs Produced By Anti-Cancer Drugs And An Algorithm For Reliable Predictions In Affected Areas, Sarah Josephine Aurit

Department of Statistics: Dissertations, Theses, and Student Research

An activity cliff (AC) occurs when drugs close in chemical space produce dissimilar biological results. We focus on developing an inferential procedure to detect the presence of ACs in a chemical landscape. If detected, we provide a distance-based procedure that can be used to identify regions of stability in the chemical landscape of interest and generate prediction with higher precision in those areas of stability. We conceptualize the chemical landscape as a spatial random field and use spatial models for prediction of efficacy for new drugs based on “distance” in chemical space. We argue that an AC manifests itself by …

Applications Of Preclinical Magnetic Resonance Imaging In The Treatment Of Traumatic Brain Injury And Understanding Carotid Artery Atherosclerosis, Evan Timothy Curtis

Dissertations and Doctoral Documents, University of Nebraska-Lincoln, 2023–

Advances in magnetic resonance imaging (MRI) provide the opportunity to investigate research questions that have been left unanswered. In the cases of traumatic brain injury (TBI) and carotid artery atherosclerosis, MRI is a resource for non-invasively viewing the phenomena taking place. Additionally, potential interventions and treatments can be observed without harm to the subject. This dissertation expands the understanding of two preclinical applications of MRI: traumatic brain injury and carotid artery atherosclerosis in mouse models.

TBI is a leading cause of death and disability for individuals between 15–45 years of age and effective pharmaceutical interventions for treating the secondary damage …

The Lived Experiences Of Fathers With Postpartum Depression: A Qualitative Study, Rachael Elizabeth Schmitz

Nursing and Health Sciences

Background:

Although parents may joyfully anticipate the birth of a child, it's impossible for them to know ahead of time just how profoundly their lives will change. Postpartum depression (PPD) can result. While there is a substantial body of research regarding maternal PPD, paternal PPD has received far less attention and is neither adequately understood nor diagnosed. This is exacerbated by outdated but persistent sociocultural masculinity norms and the stigmas around mental health issues.

Purpose:

This study sought to explore the lived experiences of new fathers with PPD in order to provide greater insight into their experiences.

Methods:

This qualitative …

The Effect Of An Acute Bout Of Rock Climbing On Cognitive Functioning And Cortisol Levels, Vanessa Steigauf

All NMU Master's Theses

Rock climbing is an understudied physical activity (PA) that demands active decision-making, integration of sensory and visual input, and continuous regulation of nervous system activity to produce complex motor outputs. The unique psychological demands of climbing warrant studying its effect on cognition and brain health. I recruited 26 generally healthy adults for a randomized-controlled study. Climbing experience, PA and perceived stress were self-reported. Each participant was randomly assigned to a climbing (10x2 minutes climb, moderate intensity) or control group (seated, watching climbing-related video). The primary outcomes, cognitive performance and salivary cortisol levels were assessed by the Stroop test. A linear …

The Importance Of Imperfect Pre-Clinical Models In Adolescent Idiopathic Scoliosis, Diane S Sepich, Ryan S Gray, Nadav Ahituv, Christina A Gurnett, Jonathan J Rios, Lila Solnica-Krezel, Carol A Wise

2020-Current year OA Pubs

Adolescent idiopathic scoliosis (AIS) is a twisting spinal deformity that occurs in otherwise healthy children at the time of rapid pre-pubescent growth. AIS affects ∼3% of children worldwide and is the most common musculoskeletal diagnosis in pediatric populations, posing a significant physiological, psychosocial and financial burden to patients. Genetic predisposition is a clear and major contributor to AIS, and insights from genomic discoveries are inspiring translational studies ultimately aimed at developing novel diagnostics and therapies. Pre-clinical animal models of AIS are now essential to validate human genetic findings, understand gene-by-environment interactions, and speed etiologic and therapeutic discovery. In this Perspective, …

If Alcohol Consumption Were Eliminated, Which Us Counties Would Still Experience High Rates Of Breast Cancer Among Women?, Hina Javed

Boise State University Theses and Dissertations

Background

Breast cancer is the most prevalent cancer among women in the United States, accounting for roughly one-third of all newly diagnosed female cancers (American Cancer Society, 2024). The risk factors for breast cancer include both non-modifiable and modifiable factors. Non-modifiable factors include age at menarche, early menstrual cycles and late menopause. Modifiable factors include smoking, diabetes, obesity and environmental factors such as air pollution. The interplay between lifestyle factors and environmental exposures in cancer development has long been debated. While alcohol consumption is widely recognized as a major breast cancer risk factor, the role of environmental exposure such as …

Supervised Machine-Based Learning And Computational Analysis To Reveal Unique Molecular Signatures Associated With Wound Healing And Fibrotic Outcomes To Lens Injury, Catherine Lalman, Kylie R. Stabler, Yimin Yang, Janice L Walker

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Posterior capsule opacification (PCO), a frequent complication of cataract surgery, arises from dysregulated wound healing and fibrotic transformation of residual lens epithelial cells. While transcriptomic and machine learning (ML) approaches have elucidated fibrosis-related pathways in other tissues, the molecular divergence between regenerative and fibrotic outcomes in the lens remains unclear. Here, we used an ex vivo chick lens injury model to simulate post-surgical conditions, collecting RNA from lenses undergoing either regenerative wound healing or fibrosis between days 1–3 post-injury. Bulk RNA sequencing data were normalized, log-transformed, and subjected to univariate filtering prior to training LASSO, SVM, and RF ML models …

Analysis Of The Clinical, Socioeconomic, And Sociodemographic Characteristics Of Virally Unsuppressed Children Aged 2-14 Living With Hiv/Aids In The Region Of Abidjan 2 – Côte D’Ivoire (Region Supported By Usaid), Maman Fathim Kamagate

Capstone Experience: Master of Public Health

Background: Viral suppression among children living with HIV (CLHIV) remains suboptimal in Côte d’Ivoire. This study assessed clinical, socioeconomic, and demographic characteristics associated with viral non-suppression among CLHIV aged 2–14 years in Abidjan 2 to inform targeted interventions under the U.S. Agency for International Development (USAID)-supported Reaching Impact, Saturation, and Epidemic Control (RISE) project.

Methods: A retrospective analysis was conducted using routine program data from 1,203 CLHIV across 73 health facilities. Descriptive, bivariate, and multivariate analyses were performed to examine associations with viral load suppression status. Findings guided the development of a multi-level implementation plan using Kotter’s Change Management Framework, …

Gastric Sarcina Ventriculi: A Report On Two Cases, Yaomin Chen, Yu Liu, Zhiyan Fu

School of Medicine Faculty Publications

: Sarcina ventriculi is a rare Gram-positive coccus that thrives in acidic environments such as the human stomach. It has been increasingly identified in individuals with delayed gastric emptying and has been reported in association with various gastric disorders. However, its exact pathogenic role is not fully understood and remains controversial. : We present two cases of patients, one with a small bowel obstruction and the other with epigastric pain, both diagnosed with Sarcina ventriculi infection by histological examination of gastric biopsies. The patients were managed with a combination of antibiotics and a proton pump inhibitor, resulting in symptom resolution …

The Impact Of Gender, Training Year, Medical Specialty And The Covid-19 Pandemic On Resident Wellness, Sara Beachy, Jessica Luzier, Chantel Weisenmuller, Kathleen Bors, Mary Ann Maurer, Amna Anees, Tiffany Lasky, Lisa Calderwood

Department of Family & Community Medicine Faculty Papers

INTRODUCTION: Data are limited as to which factors most strongly impact medical trainees' well-being, and few studies have assessed trainee's wellness at multiple time points during the COVID-19 pandemic. Additionally, much research has not taken an intersectional approach to understanding the ways in which different facets of a resident's identity impact their wellness. Thus, more person-centred, probability-driven statistical approaches that can produce distinct heterogenous groups of individuals are warranted to understand the way in which different identities are associated with resident wellness scores.

METHODS: A latent profile analysis was conducted using institutional data from resident surveys administered from 2019 to …

Sarcoplasmic Reticulum-Mitochondria Microdomains: Hugging And Kissing In The Heart, Bong Sook Jhun, Jin O-Uchi, Brian Rhee, Ameneh Ahrari, Nathan Demichaelis, Kye-Im Jeon, David M. Booth, Shey-Shing Sheu

Center for Translational Medicine Faculty Papers

Endoplasmic reticulum (ER)-mitochondrial (ER-Mito) interface, termed mitochondrial-ER contacts (MERCs), plays significant roles in the maintenance of bioenergetics and basal cell functions via the exchange of lipids, Ca 2 þ , and reactive oxygen species (ROS) in various cell types/tissues. Genetic deletion of mitofusin 2 (Mfn2), one of the key components of ER-Mito tethering, in cardiomy- ocytes (CMs) in vivo revealed the importance of the microdomains between mitochondria and sarcoplasmic reticulum (SR), a dif- ferentiated form of ER in muscle cells, for maintaining normal mitochondrial Ca 2 þ (mtCa 2 þ ) handling and bioenergetics in the adult heart. However, key …

Medical Surveillance In Custodial Jsas: Preventing Bloodborne Pathogen Exposure, Kiara Gadea

Electronic Theses, Projects, and Dissertations

Custodians play an important role in maintaining our surroundings safe and sanitary. However, in doing so, they are their exposure to health hazards that put them at risk, yet these exposures are often overlooked. One major risk they face is contact with bloodborne pathogens, which put custodial staff at risk for infections such as hepatitis B. While Job Safety Analyses (JSA’s) outline various protective measures, many fail to incorporate medical surveillance as part of their risk management program. Overlooking this important detail leaves custodians vulnerable to health risks that can be prevented.

Adding a medical surveillance section to custodial JSA’s, …

Mx1-Labeled Pulp Progenitor Cells Are The Main Contributors Of Odontoblast And Dentin Regeneration In Murine Molars, Dongwook Yang, Youngjae Jeong, Laura Ortinau, Jea Giezl Solidum, Dongsu Park

Faculty, Staff and Students Publications

Regeneration of dentin and odontoblasts from dental pulp progenitor cells is essential for the maintenance of permanent tooth. However, the in vivo identity of endogenous pulp progenitor cells and how they contribute to reparative dentinogenesis remain elusive. Here we show that comparative single-cell analysis of pulp cells before and after molar eruption reveal that endogenous pulp progenitor cells are enriched in coronal papilla-like cells with Mx1-Cre and Cxcl12–GFP expression. Further, lineage tracing and fluorescence-activated cell sorting analysis indicated that Mx1-labeled (Mx1+) pulp cells include long-term repopulating progenitor cells with higher expression of stem cell markers. Notably, …

Differences In Wait-List Mortality: Temporary Vs Durable Circulatory Support Devices, Mahwash Kassi, Salma Zook, Duc Nguyen, Katelyn Ingram, Sapna Legha, Rayan Yousefzai, Ju Kim, Imad Hussain, Cindy M Martin, Janardhana Gorthi, Adeel Ahsan Syed, Nadia Fida, Arvind Bhimaraj, Edward A Graviss, Ashrith Guha

Faculty, Staff and Students Publications

Background: In 2018, changes in the United Network for Organ Sharing (UNOS) allocation system led to a shift in practices, making durable left ventricular assist devices less desirable as a bridge to transplantation compared to temporary mechanical circulatory support. This study compares the composite outcome of waitlist mortality and delisting incidence at 1 year between these two support types.

Methods: All actively listed adult patients on mechanical circulatory support listed for heart transplantation under the current UNOS system from October 2018 to October 2021 were included, excluding those with right ventricular devices, biventricular devices, total artificial hearts, and extracorporeal membrane …

Exploring Transgender And Gender Expansive Youth's Experiences With Vicarious Minority Stress, Erin T. Pereida

Graduate Doctoral Dissertations

In the United States (U.S.), transgender and gender expansive (TGE) youth experience elevated rates of depressive symptoms, self-harm behaviors, and suicidality compared to cisgender peers. Mental health professionals and researchers often use the gender minority stress model to explain these elevated rates, positing that stressors related to minority identity experienced above and beyond normative daily stress contribute to adverse mental health outcomes. One emerging component of the model requiring further investigation is vicarious minority stress; stress experienced indirectly through witnessing or learning of gender minority stressors affecting other TGD individuals or the community more broadly. The present study explored this …

Genetic Diversity And Expanded Phenotypes In Dystonia: Insights From Large-Scale Exome Sequencing, Mirja Thomsen, Fabian Ott, Sebastian Loens, Gamze Kilic-Berkmen, Ai Huey Tan, Shen-Yang Lim, Ebba Lohmann, Kaja M Schröder, Lea Ipsen, Lena A Nothacker, Linn Welzel, Alexandra S Rudnik, Frauke Hinrichs, Thorsten Odorfer, Kirsten E Zeuner, Friederike Schumann, Andrea A Kühn, Simone Zittel, Marius Moeller, Robert Pfister, Christoph Kamm, Anthony E Lang, Yi Wen Tay, Ana Luísa De Almeida Marcelino, Marie Vidailhet, Emmanuel Roze, Joel S Perlmutter, Jeanne S Feuerstein, Victor S C Fung, Florence Chang, Richard L Barbano, Steven Bellows, Aparna A Wagle Shukla, Alberto J Espay, Mark S Ledoux, Brian D Berman, Stephen Reich, Andres Deik, Andre Franke, Michael Wittig, Sören Franzenburg, Jens Volkmann, Norbert Brüggemann, H A Jinnah, Tobias Bäumer, Christine Klein, Hauke Busch, Katja Lohmann

Faculty, Staff and Students Publications

Objective: Dystonia is one of the most prevalent movement disorders, characterized by significant clinical and etiological heterogeneity. Despite considerable heritability (~25%), the etiology in most patients remains elusive. Moreover, understanding correlations between clinical manifestations and genetic variants has become increasingly complex.

Methods: Exome sequencing was conducted on 1924 genetically unsolved, mainly late-onset isolated dystonia patients, recruited primarily from two dystonia registries (DysTract and the Dystonia Coalition). Rare variants in genes previously linked to dystonia (n = 406) were examined, confirmed via Sanger sequencing, and analyzed for segregation when possible.

Results: We identified 137 distinct likely pathogenic/pathogenic variants (according to ACMG …