Digital Commons Network^™

Transient Disruption Of Bladder Control Linked To Periaqueductal Gray Fibers Following Deep Brain Stimulation For Psychiatric Disorders, Thomas Hamre, Hideo Suzuki, Sarah Soubra, Reem El Jammal, Melissa A Ryan, Sanjay J Mathew, Jeffrey A Herron, Nidal Moukaddam, Eric A Storch, Nora Vanegas Arroyave, Kara L Marshall, Garrett P Banks, Nader Pouratian, Wayne K Goodman, Nicole R Provenza, Sameer A Sheth, Sarah R Heilbronner

Faculty, Staff and Students Publications

No abstract provided.

Validation Of The Norwegian Version Of The Movement Disorder Society-Unified Parkinson's Disease Rating Scale, Guido Alves, Yvonne Stavland Sørenes, Veslemøy Hamre Frantzen, Michaela Dreetz Gjerstad, Anders Ledaal Bjørnestad, Jodi Maple-Grødem, Elin Bjelland Forsaa, Ylva Hivand Hiorth, Karen Herlofson, Espen Benjaminsen, Kari Anne Bjørnarå, Espen Dietrichs, Roberta Balestrino, Carmen Gasca-Salas, Chi-Ying R Lin, Alvaro Sanchez-Ferro, Michelle H S Tosin, Tiago A Mestre, Monica M Kurtis, Pablo Martinez-Martin, Sheng Luo, Luowen Yu, Glenn T Stebbins, Christopher G Goetz, Mds Coa Translation Steering Committee

Faculty, Staff and Students Publications

Introduction: The Movement Disorder Society-revised version of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) is the gold standard assessment for evaluating Parkinson's disease (PD) symptoms and severity, but a validated Norwegian version is not yet available. We translated the original English MDS-UPDRS into Norwegian and tested the clinimetrics of the translated version following the MDS-established protocol for non-English language translations.

Methods: Two independent teams translated the English version of the MDS-UPDRS into Norwegian. After review of the back-translated English version, cognitive pretesting was performed in twelve PD patients at one study site. This was followed by large-scale testing completed by …

Suicidal Ideation In Spinocerebellar Ataxia, Levi Peppel, Ruo-Yah Lai, Christian Rummey, Puneet Opal, Jeremy D Schmahmann, Christopher M Gomez, Henry Paulson, Theresa A Zesiewicz, Susan Perlman, George Wilmot, Sarah H Ying, Chiadi U Onyike, Khalaf O Bushara, Michael D Geschwind, Karla P Figueroa, Stefan M Pulst, Sub H Subramony, Antoine Duquette, Tetsuo Ashizawa, Ali G Hamedani, Marie Y Davis, Sharan R Srinivasan, Matthew R Burns, Nadia Amokrane, Lauren R Moore, Vikram G Shakkottai, Liana S Rosenthal, Sheng-Han Kuo, Chi-Ying R Lin

Faculty, Staff and Students Publications

Objective: Suicidal ideation has not been extensively studied in spinocerebellar ataxias (SCAs). The authors examined whether individuals with SCAs have increased suicidal ideation and related factors.

Methods: The authors studied patients with genetically confirmed SCAs enrolled in the Clinical Research Consortium for the Study of Cerebellar Ataxia cohort, examining the percentages of patients with SCA subtypes 1, 2, 3, and 6 who reported suicidal ideation and comparing findings with nationally representative data from the National Survey on Drug Use and Health (NSDUH). Clinical characteristics that may contribute to suicidal ideation in SCAs, including age, disease duration, sex, ataxia severity, depression, …

Age-Related Variations Of The Hemodynamic Response Function Spatially Resolved Across Human Cerebral Cortex, Nooshin J Fesharaki, Amanda Taylor, David Ress

Faculty, Staff and Students Publications

Normal aging leads to regional vascular and neural alterations. Age-related impairments in neurovascular coupling (NVC) affect the blood-oxygen-level-dependent (BOLD) hemodynamic response function (HRF) measured with functional magnetic resonance imaging, causing changes in both amplitude and temporal dynamics. Previously, global, systematic age-related changes in HRF characteristics were demonstrated, consistent with known microvascular aging effects. In this follow-up study, a standard space was used to compare spatially resolved cortical HRF dynamics between sex-balanced groups of young and older adults. The results showed substantial age-related differences in both HRF amplitude and timing across distinct cortical regions. Nearly twice as much cortical area exhibited …

Platelet Extravasation In The Microvasculature: An Under-Appreciated Role For Platelets, Justin A Courson, Vahid Afshar-Kharghan, Alan R Burns, Rolando E Rumbaut

Faculty, Staff and Students Publications

In recent years, evidence has accumulated highlighting the presence and role of platelet extravasation - wherein platelets accumulate in tissue parenchyma - at a variety of sites throughout the body. While platelets are traditionally known for their roles in hemostasis and thrombosis, it is evident that platelets are potent mediators of inflammation across an array of physiological and pathological contexts. While anucleate and small in size, platelets contain a rich diversity of molecules in their granules capable of modulating cell proliferation, tissue repair, and a host of immune responses. There is growing evidence that platelet extravasation out of the vascular …

Survodutide For Treatment Of Obesity: Baseline Characteristics Of Participants In A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Trial (Synchronize™-1), Carel W Le Roux, Sean Wharton, Biykem Bozkurt, Elke Platz, Gabriele Bleckert, Samina Ajaz Hussain, Martina Brueckmann, Elena Startseva, Isabel M Kloer, Lee M Kaplan

Faculty, Staff and Students Publications

Aims: Survodutide, a novel glucagon receptor and glucagon-like peptide-1 (GLP-1) receptor dual agonist, elicited significant weight loss in a phase 2 trial in individuals with obesity without type 2 diabetes (T2D). Two multinational phase 3 trials are investigating survodutide for obesity management in individuals with or without T2D. We report the baseline characteristics of participants in the SYNCHRONIZE-1 trial in adults with obesity without T2D (ClinicalTrials.gov: NCT06066515).

Materials and methods: Participants aged ≥18 years with BMI ≥30 or ≥27 kg/m2 with ≥1 obesity complication without T2D were randomized 1:1:1 to double-blind, once-weekly, subcutaneous injections of survodutide (up-titrated to 3.6 …

Psychometric Properties Of A Novel Affective Bias Task And Its Application In Clinical And Nonclinical Populations, Prathik Kalva, Kourtney Kanja, Brian A Metzger, Xiaoxu Fan, Brian Cui, Bailey Pascuzzi, John Magnotti, Madaline Mocchi, Raissa Mathura, Kelly R Bijanki

Faculty, Staff and Students Publications

To mitigate limitations in self-reported mood assessments, we introduce a novel affective bias task (ABT). The task quantifies instantaneous emotional state by leveraging the phenomenon of affective bias, in which people interpret external emotional stimuli in a manner consistent with their current emotional state. This study establishes task stability in measuring and tracking depressive symptoms in clinical and non-clinical populations. Initial assessment in a large non-clinical sample established normative ratings. Depressive symptoms were tracked relative to task performance in a non-clinical sample, as well as in a clinical cohort undergoing surgical evaluation for severe epilepsy. In both cohorts, a stronger …

Esophageal Myotomy And Risk Of Esophageal Cancer And Mortality In Achalasia: Real-World Cohort Study, Fouad Jaber, Mohamad Ali Ibrahim, Mohammed Jaber, Youssef Soliman, Mai A Khalaf, Tara Keihanian, Fares Ayoub, Mohamed O Othman, Salmaan Jawaid

Faculty, Staff and Students Publications

Background and study aims: Achalasia is associated with increased risk of esophageal cancer, particularly squamous cell carcinoma. Although esophageal myotomy improves dysphagia, its impact on cancer risk and mortality remains unclear.

Patients and methods: We conducted a retrospective cohort study using the TriNetX research network, including adults (≥ 18 years) with achalasia confirmed by esophageal manometry. Patients were categorized based on treatment of those undergoing esophageal myotomy (peroral endoscopic myotomy [POEM] or laparoscopic Heller myotomy [LHM]) and those managed without myotomy. Patients with prior esophagectomy or malignancies associated with increased esophageal cancer risk were excluded. The primary outcome was incident …

Intercornual Distance And Postoperative Reproductive Outcomes In Moderate-To-Severe Intrauterine Adhesions: A Retrospective Cohort Study, Yifu He, Xingping Zhao, Huan Huang, Changfa Shu, Xiaoming Guan, Jia Guo, Dabao Xu

Faculty, Staff and Students Publications

Study question: Does intercornual distance (ICD), as reflected by intrauterine stent size during hysteroscopic adhesiolysis, have an association with reproductive outcomes and provide information for postoperative risk stratification in women with moderate-to-severe intrauterine adhesions?

Summary answer: A smaller ICD was independently associated with a lower likelihood of clinical pregnancy within 1 year of the final hysteroscopy and may offer additional information for postoperative risk stratification in women with moderate-to-severe intrauterine adhesions.

What is known already: Reproductive outcomes following treatment for moderate-to-severe intrauterine adhesions vary considerably. Existing severity classifications offer limited discrimination within this group. The potential association between ICD and …

Disrupted Intrathalamic And Thalamocortical Structural Covariance Networks In Posttraumatic Stress Disorder, Nick Steele, Ahmed Hussain, Delin Sun, C Lexi Baird, Courtney Russell, Neda Jahanshad, Lauren E Salminen, Miranda Olff, Jessie L Frijling, Dick J Veltman, Saskia B J Koch, Laura Nawijn, Mirjam Van Zuiden, Li Wang, Ye Zhu, Gen Li, Dan J Stein, Jonathan Ipser, Sheri Koopowitz, Yuval Neria, Xi Zhu, Orren Ravid, Sigal Zilcha-Mano, Amit Lazarov, Benjamin Suarez-Jimenez, Ashley A Huggins, Jennifer Stevens, Kerry Ressler, Tanja Jovanovic, Sanne J H Van Rooij, Negar Fani, Emily L Dennis, David F Tate, David X Cifu, William C Walker, Elisabeth A Wilde, Ivan Rektor, Pavel Říha, Milissa L Kaufman, Lauren A M Lebois, Justin T Baker, Anthony King, Israel Liberzon, Mike Angstadt, Nicholas D Davenport, Seth G Disner, Scott R Sponheim, Thomas Straube, David Hofmann, Guang Ming Lu, Rongfeng Qi, Amit Etkin, Adi Maron-Katz, Xin Wang, Austin Kunch, Hong Xie, Yann Quidé, Wissam El-Hage, Shmuel Lissek, Hannah Berg, Steven E Bruce, Josh Cisler, Marisa Ross, Ryan Herringa, Daniel W Grupe, Jack B Nitschke, Richard J Davidson, Christine Larson, Terri A Deroon-Cassini, Carissa W Tomas, Jacklynn M Fitzgerald, Brandee Feola, Jennifer U Blackford, Bunmi O Olatunji, Geoffrey May, Steven M Nelson, Evan M Gordon, Chadi G Abdallah, Ruth Lanius, Maria Densmore, Jean Théberge, Richard W J Neufeld, Paul M Thompson, Rajendra A Morey

Faculty, Staff and Students Publications

The thalamus is a heterogeneous structure crucial for corticocortical communication, affective–perceptual integration, motor preparation, and memory-related functions. Posttraumatic stress disorder (PTSD) is characterized by various symptoms that likely relate to thalamic functions. Group-level and individual differential structural covariance (SC) analyses were conducted on intrathalamic, thalamocortical, and thalamosubcortical volumetric networks by segmenting structural MRI data from 2,784 subjects (PTSD n = 1,306; controls n = 1,478) into 25 thalamic nuclei per hemisphere. We found that PTSD was associated with stronger intrathalamic and thalamocortical network strength and stronger SC between the limbic thalamus and the somatomotor and auditory thalamus. PTSD severity was …

Utilizing A Culture System For Horizontal Cells To Study Neural Circuit Assembly In The Developing Mouse Retina, Ross M Perez, Yong H Park, Ajeet Singh, Collin Todora, Marlon F Mattos, Daniela Becerril, Rajashree Venkatraman, Arlene A Hirano, Nicholas C Brecha, Rinki Ratnapriya, Benjamin J Frankfort, Elizabeth Zuniga-Sanchez

Faculty, Staff and Students Publications

The precise wiring of the nervous system relies on neurons extending their processes at the right time and place to find their appropriate synaptic partner. The mechanisms that determine when and where neurons extend their neurites during synaptogenesis remains a central question in the field. In the present study, we used a cell culture system coupled with live imaging to investigate the wiring mechanisms in the developing mouse retina. We focused on horizontal cells which are a class of interneurons in the outer mouse retina known to synapse selectively to the distinct types of photoreceptors. Previous research has shown horizontal …

Using Lotilaner Ophthalmic Solution, 0.25% To Treat Demodex Blepharitis In Patients Who Were Initially Misdiagnosed: A Case Series, Laura M Periman, Richard Lindstrom, Paul Karpecki, Brandon Ayres, Eric Donnenfeld, Marjan Farid, Ian Benjamin Gaddie, Preeya K Gupta, Selina Mcgee, Kelly K Nichols, Stephen Pflugfelder, Christopher E Starr, Nandini Venkateswaran, Elizabeth Yeu, Cecelia Koetting

Faculty, Staff and Students Publications

Introduction: Demodex blepharitis (DB) is a chronic ocular inflammation caused by Demodex mite infestation of the eyelid. DB is often misdiagnosed, as some of its clinical findings and patient-reported outcomes overlap with those of other ocular surface diseases. The Demodex Expert Panel on Treatment and Eyelid Health (DEPTH) has reached consensus on the symptomatology, diagnosis, and treatment of DB. Consensus findings from the DEPTH group include that collarettes are pathognomonic for DB and that lotilaner ophthalmic solution, 0.25%, the first and only FDA-approved treatment for DB, should be the first-line treatment for the disease. This case series highlights two instances …

The All Of Us Evenings With Genetics Research Program, Stacy M Lloyd, Jasmine Baker, Carolina Jorgez, Julie Coleman, Laterrica Williams, April Adams, Ashley Butler, Elizabeth Atkinson, Shamika Ketkar, Steven Scherer, Kim Worley, Susan Fernbach, Keasia Daniels, Latanya Hammonds-Odie, Laura Rosales, Brendan Lee, Debra Murray

Faculty, Staff and Students Publications

The All of Us Evenings with Genetics (All of Us EwG) Research Program, funded in part by the National Institute of Health’s All of Us Research Program, engages researchers to utilize the All of Us Researcher Workbench to advance precision medicine. The All of Us EwG program has two core aims: (1) address barriers to research productivity for minorities, disadvantaged, and persons with disabilities aspiring to enter STEM fields; and (2) promote the use of the All of Us Researcher Workbench to develop research focused on health equity. To achieve these goals, the program implements three key activities: (1) …

Senolytic-Resistant Senescent Cells Have A Distinct Sasp Profile And Functional Impact: The Path To Developing Senosensitizers, Utkarsh Tripathi, Masayoshi Suda, Vagisha Kulshreshtha, Bryan T Piatkowski, Allyson K Palmer, Nino Giorgadze, Christina Inman, Nathan Gasek, Ming Xu, Kurt O Johnson, Tamar Pirtskhalava, Selim Chaib, Larissa P G Langhi Prata, Yi Zhu, Renuka Kandhaya-Pillai, Stefan G Tullius, Saranya P Wyles, Rambabu Majji, Hari Krishna Yalamanchili, David B Allison, Tamar Tchkonia, James L Kirkland

Faculty, Staff and Students Publications

The senescent cell (SC) fate is linked to aging, multiple disorders and diseases, and physical dysfunction. Senolytics, agents that selectively eliminate 30%-70% of SCs, act by transiently disabling the senescent cell antiapoptotic pathways (SCAPs), which defend those SCs that are proapoptotic and pro-inflammatory from their own senescence-associated secretory phenotype (SASP). Consistent with this, a JAK/STAT inhibitor, Ruxolitinib, which attenuates the pro-inflammatory SASP of senescent human preadipocytes, caused them to become "senolytic-resistant". Administering senolytics to obese mice selectively decreased the abundance of the subset of SCs that is pro-inflammatory. In cell cultures, the 30%-70% of human senescent preadipocytes or human umbilical …

Correction: Establishing Standardized Transthoracic Echocardiography Reference Ranges For Mouse Models: Insights Into The Impact Of Anesthesia, Sex, And Age, Manuela A Oestereicher, Christopher S Ward, Elida Schneltzer, Susan Marschall, Helmut Fuchs, Valerie Gailus-Durner, Ghina Bou About, Mohammed Selloum, Hamid Meziane, Michelle Stewart, Lydia Teboul, Clare Norris, Dale Pimm, Marina Kan, Federico López Gómez, Robert Wilson, Mayra Monroy, Sheraz Pasha, Eva Zabrodska, Jan Prochazka, David Pajuelo Reguera, Zuzana Nichtova, Yann Herault, Sara Wells, Helen Parkinson, Jason D Heaney, Radislav Sedlacek, Xiang Gao, Martin Hrabe De Angelis, Nadine Spielmann

Faculty, Staff and Students Publications

This corrects the article "Establishing standardized transthoracic echocardiography reference ranges for mouse models: insights into the impact of anesthesia, sex, and age" in volume 12, 1695034.

Highly Effective Combination Of Brg1/Brm Inhibitor With Bet Inhibitor Or Decitabine For High-Risk Mecom-Rearranged Aml, Warren Fiskus, Christopher P Mill, Jessica Piel, Mike Collins, Murphy Hentemann, Branko Cuglievan, Christine E Birdwell, Kaberi Das, John A Davis, Hanxi Hou, Antrix Jain, Anna Malovannaya, Lauren B Flores, Tapan M Kadia, Naval Daver, Koji Sasaki, Koichi Takahashi, Danielle Hammond, Jian Wang, Sanam Loghavi, Xiaoping Su, Courtney D Dinardo, Ruud Delwel, Kapil N Bhalla

Faculty, Staff and Students Publications

In AML with 3q26.2 rearrangements (r) the distal GATA2 hematopoietic enhancer becomes aberrantly relocated leading to activation of EVI1 expression. EVI1 is a transcriptional regulator that plays a role in proliferation and maintenance of a stem cell-like phenotype in AML. BRG1 (SMARCA4) and BRM (SMARCA2) are the mutually exclusive ATPases of the BAF (BRG1/BRM-associated factor) chromatin remodeling complexes. They regulate access to enhancers/promoters and gene-expressions orchestrating AML stem/progenitor cell proliferation and differentiation. AML with 3q26.2 rearrangements are clinically challenging and prognosis remains very poor. FHD-286 is an orally bioavailable, selective inhibitor of BRG1/BRM under clinical development in AML. Present studies …

School-Level Gaps In Mmr Coverage As The Fuel For Measles Outbreaks, Meagan C Fitzpatrick, Chad R Wells, Abhishek Pandey, Lamia Ayaz, Peter J Hotez, Seyed M Moghadas, Alison P Galvani

Faculty, Staff and Students Publications

No abstract provided.

Unraveling Posttranslational Modification Complexity: Advances In Quantitative Histone Proteoform Mass Spectrometry, Karl F Poncha, Alyssa T Paparella, Nicolas L Young

Faculty, Staff and Students Publications

Histone proteins and their posttranslational modifications are central to chromatin structure and function. These modifications often occur in combinations, generating a diverse array of histone proteoforms that contribute to the dynamic regulation of chromatin architecture. Advancements in mass spectrometry-based proteomics, particularly top-down and middle-down approaches, have significantly enhanced our ability to characterize these proteoforms and elucidate PTM crosstalk. This review provides an analysis of the epigenetic machinery involved in the addition, recognition, and removal of histone PTMs, emphasizing the complexity introduced by histone variants and combinatorial PTM patterns. We examine the challenges and limitations of traditional antibody-based methods for PTM …

In Vivo Volumetric Visualization And Quantification Of Cumulus Expansion In Mice With Intravital Optical Coherence Tomography, Kohei Umezu, Frank J Brooks, Irina Larina

Faculty, Staff and Students Publications

Ovulation is preceded by a critical physiological process known as cumulus expansion, during which the cumulus cell layer surrounding the oocyte undergoes structural remodeling. Despite the recognized importance of this process for reproductive success, live quantitative imaging of cumulus expansion has not been previously achieved due to limitations of current imaging technologies for deeply located ovaries. In this study, we employed intravital optical coherence tomography for three-dimensional visualization of mouse follicles containing cumulus-oocyte complexes (COC) within the physiological context of the ovary, both ex vivo and in vivo. This method enabled time-lapse measurement of cumulus layer thickness and COC …

Long Covid And Cardiovascular Diseases Among U.S. Adults: Results From The U.S. Medical Expenditure Panel Survey, Geoffrey Y Zhang, John C Lin, Dang Nguyen, Sameed Ahmed M Khatana, Thomas P Giordano

Faculty, Staff and Students Publications

Objective: Long COVID is associated with persistent symptoms including cardiovascular complications; however, the epidemiology and directionality of this association remain unclear.

Methods: Utilizing a retrospective cohort study design with cross-sectional analyses, 8,332 respondents aged 18 and older from the 2022 Medical Expenditure Panel Survey (MEPS) who had a prior COVID-19 infection, were analyzed to determine the temporal association between long COVID and cardiovascular disease (CVD), modeling each as both outcome and exposure in separate analyses.

Results: Long COVID was associated with any CVD diagnosis (OR 1.37; 95% CI: 1.05-1.80), specifically angina (OR 1.81; 95% CI: 1.18-2.77) and myocardial infarction (OR …

Ptpn1 Regulation Via Ybx1-Ptbp1 Interaction Promotes Fibroblast Activation And Fibrotic Remodeling In The Lung, Huibing Liu, Cong Xia, Yingying Zhang, Yulong Gan, Lianhui Cheng, Xuqian Wang, Airu Chang, Wenyu Zhao, Bin Li, Yaxuan Wang, Yajun Li, Ivan Rosas, Juntang Yang, Guoying Yu, Lan Wang

Faculty, Staff and Students Publications

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial pneumonia of unknown etiology. Its pathogenesis involves complex multicellular interactions and signaling pathways, with fibroblast-to-myofibroblast transition (FMT) being critical for fibrogenesis. Although the transcription factor Y-box binding protein 1 (YBX1) regulates processes such as cell proliferation, transcription, translation, and DNA repair, its role in IPF remains undefined. Here, we demonstrate that YBX1 overexpression significantly promotes transforming growth factor-β1 (TGF-β1)-induced pulmonary FMT, leading to substantially increased extracellular matrix (ECM) deposition in primary human (PHLFs) and mouse (PMLFs) lung fibroblasts. Conversely, YBX1 inhibition markedly suppresses TGF-β1-driven aberrant fibroblast migration and activation. Mechanistically, YBX1 …

Molecular Heterogeneity Of Hpv-Associated Cancers And Strategies To Overcome Treatment Resistance, Sara Rasouli, Weiyi Gong, Raegan Wood, Danyal Daneshdoust, Anam Khan, Rani Mahyoob, Chongwen Cao, Zihao Yu, Nagireddy Putluri, Gennady Shvets, Haichang Li, Bo Zhao, Xuefeng Liu, Jenny Li

Faculty, Staff and Students Publications

Human papillomavirus (HPV) is a major driver of global cancer incidence, responsible for nearly all cervical cancers and a significant proportion of oropharyngeal, anal, and other anogenital cancers. Despite the availability of effective vaccines, HPV-associated cancers persist due to persistent infection, immune evasion, and the virus's ability to integrate into the host genome, contributing to molecular heterogeneity and therapeutic resistance. Here, we summarize molecular heterogeneity and the emerging combined therapeutic strategies. High-risk HPV types, notably HPV16 and HPV18, initiate carcinogenesis through persistent infection of epithelial basal cells and through the actions of the E6 and E7 oncoproteins, which disrupt the …

Investigating Food-Related Behaviors In Smith-Magenis Syndrome: Tailoring A Questionnaire For A Rare Disease, Citrine Elatrash, Theresa A Wilson, Alexis C Wood, Sarah H Elsea, Stephanie Sisley

Faculty, Staff and Students Publications

Purpose: Accurate measurement is essential for tracking changes in clinical outcomes. Individuals with Smith-Magenis syndrome (SMS) exhibit challenging and unique food-related behaviors. We sought to determine the best tool to capture their unique food-related behaviors.

Methods: We conducted focus groups with caregivers of individuals with SMS to evaluate two commonly used questionnaires for food-related behaviors- the Food Related Problems Questionnaire (FRPQ) and the Hyperphagia Questionnaire for Clinical Trials (HQ-CT). Based on caregiver input and clinical expertise, we adapted these existing measures into a new tool: the SMS-FRPQ. We then validated this instrument for internal consistency and concurrent validity using online …

Acmg Medical Directors’ Special Interest Group Survey: Current Challenges For Medical Genetics Clinics, Mark Dulchavsky, Catherine E Keegan, Nathaniel H Robin, Chad Haldeman-Englert, Shweta U Dhar, Fuki M Hisama

Faculty, Staff and Students Publications

Purpose: The American College of Medical Genetics and Genomics Medical Directors' Special Interest Group (SIG) began in 2021 as a forum for directors of medical genetics clinical groups to share questions, concerns, current practices, and solutions regarding clinical operations. We report on the first 4 years of the SIG-its membership growth and SIG activities. We also present quantitative and qualitative results of a nationwide survey of 66 SIG members addressing recurrent questions from members regarding: wait times, volume of referrals, clinical workload expectations, and independent practice of genetic counselors (GCs) and advanced practice providers.

Methods: Cross-sectional survey of American College …

Latent Factor Modeling Reveals Unexpected Spatial Heterogeneity In Human Alzheimer's Disease Brain Transcriptomes, Rami Al-Ouran, Chaozhong Liu, Linhua Wang, Zhijian Yu, Ying-Wooi Wan, Chaohao Gu, Xiqi Li, Gerarda Cappuccio, Mirjana Maletic-Savatic, Aleksandar Milosavljevic, Joshua M Shulman, Hu Chen, Zhandong Liu

Faculty, Staff and Students Publications

Alzheimer's disease is characterized by complex molecular and cellular heterogeneity, which complicates efforts to identify consistent biomarkers and therapeutic targets. To better characterize the heterogeneity, we applied latent factor modeling to RNA sequencing data from approximately 2,500 human Alzheimer's disease brain samples, uncovering underlying patterns in gene expression. These transcriptional groups demonstrated unique gene expression profiles related to synaptic and neuronal pathways, vasculature development, and protein folding and antigen processing. Notably, this latent factor reflects variation in spatial sampling. Adjusting for the latent factor improved the identification of differentially expressed genes in disease samples. This finding suggests that spatial heterogeneity …

Rare But Relevant? Assessing Variants In Dystonia-Linked Genes In Parkinson's Disease, Lara M Lange, Zih-Hua Fang, Laurel Screven, Ai Huey Tan, Roy N Alcalay, Rim Amouri, Roberta Bovenzi, Matilda Fenn, Joshua L I Frost, Joseph Jankovic, Simona Jasaityte, Zane Jaunmuktane, Beomseok Jeon, Ignacio Juan Keller Sarmiento, Rejko Krüger, Gregor Kuhlenbäumer, Chin-Hsien Lin, Lukas Pavelka, Maria Teresa Periñan, Samia Ben Sassi, Tommaso Schirinzi, Jung Hwan Shin, Joshua M Shulman, Yi Wen Tay, Ryan Uitti, Tom Warner, Zbigniew K Wszolek, Lesley Wu, Ruey-Meei Wu, Kirsten E Zeuner, Cornelis Blauwendraat, Andrew Singleton, Niccolò E Mencacci, Huw R Morris, Shen-Yang Lim, Katja Lohmann, Christine Klein

Faculty, Staff and Students Publications

Background: Dystonia and Parkinson's disease (PD) exhibit clinical and genetic overlap, but the relevance of dystonia gene variants in PD remains unclear.

Objective: The aim was to assess the frequency of dystonia-linked pathogenic variants in PD.

Methods: We screened sequencing data from 15,684 individuals (8272 PD, 3200 atypical parkinsonism, and 4212 unaffected) from the Global Parkinson's Genetics Program (GP2) and Accelerating Medicines Partnership-Parkinson's Disease (AMP-PD) for variants in genes linked to isolated dystonia, dystonia-parkinsonism, and myoclonus-dystonia.

Results: Pathogenic variants were identified only in PD patients. Forty-five PD individuals (0.54%) carried 26 distinct (likely) pathogenic variants in nine dystonia-linked genes, most …

The Words Community Dwelling, Spanish-Preferring Mexican/Mexican American Adults Use To Talk About Alzheimer’S Disease And Genetic Testing: Implications For Education And Outreach, Jamie C Fong, Fatima I Chavez, Karla Silos, Mirna L Arroyo-Miranda, Gabriela Castro Castro, Mark E Kunik, Joshua M Shulman, Luis D Medina

Faculty, Staff and Students Publications

Introduction: Hispanic/Latino (H/L) adults are more likely than non-Hispanic White individuals to have Alzheimer's disease (AD), yet fewer than one in five H/L adults has apolipoprotein E (APOE) Ɛ4, underscoring gaps in understanding genetic risk across H/L heritage groups. H/L adults remain underrepresented in AD research that uses genetic data for participant stratification. To inform culturally appropriate educational materials for 16 million U.S. Spanish speakers, we identified culturally salient words Spanish-preferring H/L adults use to describe AD and genetic testing beyond APOE.

Methods: Community-residing, Spanish-preferring Mexican/Mexican American adults (n = 14) completed freelisting interviews, a method eliciting …

Driving Impairment In Patients With Movement Disorders: Examining The Baylor Driving Questionnaire By Objective Driving Assessment, Abhishek Lenka, Ruosha Li, Karim Makhoul, Alan Gonzalez, Rory D Mahabir, Joseph Jankovic

Faculty, Staff and Students Publications

Background: The development of a screening tool to identify driving impairment in patients with movement disorders is an unmet need.

Objective: To validate Baylor Driving Questionnaire for Movement Disorders (BDQMD) by objective driving assessment (ODA).

Methods: In this cross-sectional study, 142 patients with various movement disorders completed the 10-item BDQMD and of those, 25 completed ODA using the driver performance analysis system (DPAS).

Results: The mean total BDQMD score for the whole cohort was 14.7 ± 5.6 (range 10-47). Patients who underwent ODA had a mean BDQMD score of 12.8 ± 2.9. Four had minimum driving skill, 20 had average, …

Transition To Tenecteplase Is Associated With Shorter Door-To-Puncture Times: A Retrospective Study From The Lone Star Stroke Consortium Tnk Registry, Anqi Luo, Sujani Bandela, Gretchel Gealogo-Brown, Mark P Goldberg, Andrew Slusher, Reza Behrouz, Alibay Jafarli, Siddarth Prasad, Daiwai Olson, Maria Denbow, Mehari Gebreyohanns, Asmiet Techan, Chethan P Venkatasubba Rao, Jane A Anderson, Barbara Kimmel, Anette Ovalle, Michele Patterson, Sean I Savitz, Salvador Cruz-Flores, Steven Warach, Lee Birnbaum

Faculty, Staff and Students Publications

Background: Intravenous thrombolytic (IVT) and mechanical thrombectomy (MT) therapies are the current standard of care for large vessel occlusion (LVO) stroke. Multiple studies emphasized the impact of time metrics on patient outcomes, particularly door-to-needle (DTN) and door-to-puncture (DTP) times. Tenecteplase (TNK) offers potential advantages over alteplase (ALT), including a simplified one-time bolus administration, which may reduce DTP time. Results suggest TNK is non-inferior to ALT in terms of clinical outcomes, but few large cohort studies have compared DTP time for patients receiving TNK vs. ALT prior to thrombectomy. This real-world study aimed to compare DTP times and discharge outcomes in …

Proceedings Of The 13th Annual Deep Brain Stimulation Think Tank: The Evolving Landscape, Chance R Fleeting, Eduardo M Moraud, Kamil Uğurbil, Doris D Wang, Wolf-Julian Neumann, Andrea A Kühn, Valerie Voon, Victor Pikov, Marie-Laure Welter, Michael D Fox, John D Rolston, Mahsa Malekmohammadi, Yagna J Pathak, Lyndahl M Himes, David Greene, Abbey S Holt-Becker, Gabriel Lázaro-Muñoz, Alexander W Charney, Amanda R Merner, Martijn Figee, Katherine W Scangos, Timothy Denison, Kent Leyde, Aysegul Gunduz, Helen M Bronte-Stewart, James C Beck, Nora Vanegas-Arroyave, Marta San Luciano, Norbert Brüggemann, Kelly D Foote, Michael S Okun, Joshua K Wong

Faculty, Staff and Students Publications

The Deep Brain Stimulation (DBS) Think Tank XIII was held September 2-4th, 2025, in Gainesville, Florida, at the Norman Fixel Institute for Neurological Diseases at the University of Florida. The theme was "The Evolving Landscape of DBS: New Indications, New Goals." This theme was a continuation of the DBS Think Tank XI and XII, which were focused on emerging technology and pushing the horizon of indications. Since its founding in 2012, the DBS Think Tank has provided a global forum for leading clinicians, engineers, and researchers in both in industry and academia to present, discuss, and debate the current state …