Medical Sciences Commons^™

De Novo Variants In The Splicing Factor Gene Sf3b1 Are Associated With Neurodevelopmental Disorders, Kevin Uguen, Tiffany Bergot, Marie-Pier Scott-Boyer, Solène Chapalain, Camille Desdouets, Séverine Commet, Changlian Zhu, Yiran Xu, Yangong Wang, Tony Roscioli, Frederic Tran-Mau-Them, Laurence Faivre, Julien Maraval, Julian Delanne, Anne-Sophie Denommé-Pichon, Antonio Vitobello, Céline Jost, Marc Planes, Susan Hiatt, Patricia Wheeler, Claudia Gonzaga-Jauregui, Heng Wang, Baozhong Xin, Valerie Sency, Michael C Kruer, Somayeh Bakhtiari, Patrick Sulem, Cynthia Curry, Trine Prescott, Gertrud Strobl-Wildemann, Theresa Brunet, Martine Doco Fenzy, Thomas Courtin, Céline Poirsier, Trine Bjørg Hammer, Christina D Fenger, Melissa Macpherson, Kosuke Izumi, Jacqueline Leonard, Dong Li, Elaine H Zackai, Ian A Glass, Scott Ward, Philippe M Campeau, Maria Carla Hermida Borroto, Laurence Le Moigno, Hilde Van Esch, Liesbeth De Waele, Daniel G Calame, James R Lupski, Giulia Barcia, Cristina Peduto, Pauline Planté-Bordeneuve, Lucie Dupuis, Roberto Mendoza-Londono, Dimitri J Stavropoulos, Jennifer Gillibert-Duplantier, Thomas Besnard, Laura Do Souto Ferreira, Benjamin Cogné, Stéphane Bézieau, Arnaud Droit, Laurent Corcos, Eric Lippert, Claude Férec, Sebastien Küry, Delphine G Bernard

Faculty, Staff and Students Publications

SF3B1 is an essential and ubiquitous splicing factor that plays a pivotal role in the early steps of pre-mRNA splicing. Recurrent somatic missense mutations in SF3B1 are frequent in cancers, but no constitutional variant has been reported so far. We describe here a cohort of 26 individuals with neurodevelopmental disorders, harbouring SF3B1 constitutional heterozygous variants that appeared mostly de novo. Patients present with a global developmental delay, associated with variable neurological and facial dysmorphic traits. A dichotomy may emerge between patients harbouring predicted loss of function (n = 9) and missense variants (n = 17), the latter being associated with …

Gh Alters Lymphatic Vessels In Female Mice And Stat5 Phosphorylation In Human Lymphatic Endothelial Cells, Christopher Walsh, Emily Scott, Elise Wagner, Jerome Walsh, Shashank Reddy, Arshad Ahmad, Reetobrata Basu, Eva Sevick-Muraca, Rich Brody, Uday Sandbhor, Sebastian Neggers, John J Kopchick

The Brown Foundation: Institute of Molecular Medicine

Disruption of lymphatic function underlies a broad spectrum of inflammatory and metabolic disorders, yet the hormonal pathways that regulate lymphatic biology remain poorly defined. GH, which is implicated in similar disease states, has an unclear role in lymphatic homeostasis. To address this gap, we investigated how chronic alterations in GH signaling alter lymphatic structure and function. Using transgenic mouse lines with increased, decreased, or absent GH action, we quantified the effect of GH on lymphatic pumping rate and lymphangiogenic remodeling during wound healing using near-infrared fluorescent imaging. We also measured markers of lymphatic endothelial cells using Western blot and immunohistochemistry …

Pathways, Outputs And Impact Of Nih-Supported Bioinformatics And Genomics Graduate Trainees In Africa, Daudi Jjingo, Andrew Walakira, Suhaila Hashim, Cisse Cheickna, Ronald Galiwango, Caleb Kibet, Florence N Kivunike, Gerald Mboowa, Fredrick Elishama Kakembo, Babajide Ayodele, Jean-Baka Domelevo Entfellner, Santie De Villiers, Karen Wambui, Segun Fatumo, Tinashe Chikowore, John Mukisa, Alfred Ssekagiri, Nicholas Bbosa, Julius Mulindwa, Samuel Kyobe, Mike Nsubuga, Grace Kebirungi, Eric Katagirya, Savannah Mwesigwa, Ibra Lujumba, Rogers Kamulegeya, Samuel Kirimunda, Stephen Kanyerezi, Shahiid Kiyaga, Ivan Sserwadda, Davis Kiberu, Bernard S Bagaya, Julius Okwir, Patricia Nabisubi, Grace Nabakooza, Mugume Twinamatsiko Atwine, Ricard Sserunjogi, Rolanda Julius, Mariam Quiñones, Meghan Mccarthy, Phillip Cruz, Karlynn Noble, Christopher J Whalen, Darrell Hurt, Maria Y Giovanni, Michael Tartakovsky, Deogratius Ssemwanga, John M Kitayimbwa, Steven J Reynolds, Christopher C Whalen, Andrew Kambugu, Neil A Hanchard, Li Jian, Peter Amoako-Yirenkyi, Graeme Mardon, I King Jordan, Samson Pandam Salifu, Mamadou Wele, Ezekiel Adebiyi, Jeffrey G Shaffer, Seydou Doumbia, David Patrick Kateete, Michelle Skelton, Nicola Mulder, Jonathan K Kayondo, Daniel Masiga, H3africa Consortium

Faculty, Staff and Students Publications

Global biomedical and health research is increasingly relying on genomic and computational approaches, largely driven by the increasing volumes of nucleic acid sequencing. Concurrently, epidemiological studies and clinical records are generating enormous amounts of data amenable to disease modeling, machine learning, and artificial intelligence techniques. Bioinformatics and data science expertise is therefore essential for improved population health. Accordingly, in 2012, the US National Institutes of Health (NIH) in partnership with the Wellcome Trust, and with support from the African Society for Human Genetics, initiated the H3Africa (Human Heredity and Health in Africa) consortium. One of its key goals was to …

Anti-Csf-1r Therapy With Combined Immuno-Chemotherapy Coordinate An Adaptive Immune Response To Eliminate Macrophage Enriched Triple Negative Breast Cancers, Diego A Pedroza, Xueying Yuan, Fengshuo Liu, Hilda L Chan, Christina Zhang, William Bowie, Alex J Smith, Sebastian J Calderon, Nadia Lieu, Weiguo Wu, Paul Porter, Poonam Sarkar, Na Zhao, Constanze V Oehler, Ondrej Peller, M Waleed Gaber, Qian Zhu, Charles M Perou, Xiang H-F Zhang, Jeffrey M Rosen

Faculty, Staff and Students Publications

Women diagnosed with metastatic triple negative breast cancer (mTNBC) have limited treatment options, are more prone to develop resistance and are associated with high mortality. A cold tumor immune microenvironment (TIME) characterized by low T cells and high tumor associated macrophages (TAMs) in mTNBC is associated with the failure of standard-of-care chemotherapy and immune checkpoint blockade (ICB) treatment. We demonstrate that the combination of immunomodulatory low-dose Cyclophosphamide (CTX) coupled with anti-CSF-1R antibody targeted therapy (SNDX-ms6352) and anti-PD-1 (ICB), was highly effective against aggressive metastatic Trp53 null TNBC transplantable syngeneic models that present with high macrophage infiltration. Mechanistically, CSF-1R inhibition along …

Slc22a3/Oct3 Drives Serotonin-Mediated Stemness In Pancreatic Cancer, Nivedeta Krishna Kumar, Venkatesh Varadharaj, Neelanjana Gayen, Annant Bir Kaur, Kirtana Arikath, Ashu Shah, Poompozhil Mathivanan, Palanisamy Nallasamy, Zahraa Wajih Alsafwani, Bhuvaneshwari Seshadri, Pratima Raut, Sanchita Rauth, Jimmie Persinger, Sandipan Brahma, Micah Schott, Rebecca E. Oberley-Deegan, Geoffrey A. Talmon, Jesse L. Cox, Surinder K. Batra, Moorthy P. Ponnusamy

Journal Articles: Biochemistry & Molecular Biology

Pancreatic cancer (PC) is a highly aggressive malignancy, with cancer stem cells (CSCs) playing a critical role in metastasis, therapy resistance, and recurrence, thereby presenting significant treatment challenges. Emerging evidence suggests that normal embryonic and adult progenitor stem cells share common gene signatures with CSCs. However, the early pluripotency-associated factors and stemness programs that become aberrantly reactivated during oncogenic transformation remain poorly defined. Here, we identify SLC22A3/OCT3 (Solute Carrier Family 22 Member 3) as a reactivated embryonic-associated signature that regulates PC stemness. SLC22A3 is markedly upregulated in CSC-enriched populations, and its silencing in PC cells grown in both 2D cultures …

From Fog To Function: An Occupational Therapist's Guide To Evaluating And Treating Cancer-Related Cognitive Impairments, Lauren E. Toner

Entry-Level Occupational Therapy Doctorate - Doctoral Capstone Symposium

Cancer – related cognitive impairment (CRCI) is a common side effect of cancer treatment that interferes with cancer survivors’ occupational performance, independence, and quality of life. Despite its high prevalence, CRCI remains under recognized and inconsistently addressed within oncology care. About 70% of individuals diagnosed with cancer report cognitive changes during or after treatment, yet many do not receive treatment. Occupational therapists are clinically trained to evaluate and treat functional cognition, activities of daily activities, instrumental activities of daily living, and client centered goals, positioning them as key providers in addressing CRCI. However, limited occupational therapy specific resources have hindered …

Sexually Dimorphic Effects Of Gpnmb Modulation On Vertebral Bone Mass Regulation And Intravertebral Disc Health, Hakem Altawil, Fayez Safadi

Williams Honors College, Honors Research Projects

Osteoporosis and vertebral degeneration are major contributors to musculoskeletal morbidity, yet the molecular mechanisms regulating vertebral bone and intervertebral disc (IVD) homeostasis remain incompletely understood. GPNMB (osteoactivin) has been identified as a regulator of bone remodeling, though its role in spine health is unclear. This study evaluated the effects of GPNMB deficiency on lumbar vertebral bone microarchitecture and IVD integrity in a sex-dependent context.

Six-month-old male and female wild-type (WT) and GPNMB knockout (KO) mice were analyzed using micro–computed tomography (µCT) of lumbar vertebrae (L4–L6) and histological assessment of the L5–L6 IVD. KO males exhibited increased bone volume fraction, bone …

Unlocking The Power Of Cxcr2 Inhibition To Overcome Gemcitabine Resistance In Pancreatic Cancer, Caitlin Molczyk, Reegan Sturgeon, Sugandha Saxena, Esther Johnson, Rakesh Bhatia, Namita Bhyravbhatla, Sushil Kumar, Surinder K. Batra, Rakesh K. Singh

Journal Articles: Biochemistry & Molecular Biology

Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related mortality, characterized by intrinsic resistance to conventional therapies and limited effective treatment options. In this study, we investigated the role of the CXCR2 axis in PDAC therapy resistance. CXCR2, a chemokine receptor, is actively involved in inflammation, tumor angiogenesis, and metastasis. Our working hypothesis is that CXCR2 contributes to PDAC chemotherapy resistance. To test this, we generated gemcitabine-resistant (GemR) lines using T3M4 and CD18/HPAF (CD18) cell lines. Baseline expression of CXCL1, CXCL5, and CXCL8 ligands was higher in GemR cells compared to parental cells. Upon gemcitabine treatment, parental cells …

Midkine (Mdk) As A Central Regulator Of The Tumor Microenvironment: From Developmental Cytokine To Therapeutic Target, Hareesh B. Nair, Ajay Nair, Ya-Guang Liu, Dileep K. Vijayan, Ramadevi Subramani, Rajkumar Lakshmanaswamy, Suryavathi Viswanadhapalli, Gangadhara R. Sareddy, Surinder K. Batra, Ratna K. Vadlamudi

Journal Articles: Biochemistry & Molecular Biology

Midkine (MDK) is an oncofetal, heparin-binding cytokine that is re-expressed across diverse cancers and correlates with aggressive disease and treatment resistance. This review synthesizes current evidence on MDK as a coordinator of tumor-intrinsic signaling and microenvironmental remodeling. We summarize MDK structural features, extracellular matrix interactions, and receptor systems that mediate MDK signaling, highlighting LRP1 and PTPRZ1 with context-dependent participation of ALK, nucleolin and integrins. Downstream, MDK engages MAPK, PI3K-AKT, STAT3 and NF-κB pathways to promote tumor cell survival, epithelial-mesenchymal plasticity, and therapeutic stress tolerance. We then focus on tumor microenvironment (TME) programs shaped by MDK, including angiogenesis, fibroblast activation and …

Mucin 5ac Modulates Cancer-Associated Fibroblast Heterogeneity Through Epigenetic Reprogramming Of Precursor Cells, Rachel J. Kehrberg, Namita Bhyravbhatla, Zahraa Wajih Alsafwani, Xiaoqi Li, Gopalakrishnan Natarajan, Imran Khan, Randall E. Brand, Maneesh Jain, Surinder K. Batra, Sushil Kumar

Journal Articles: Biochemistry & Molecular Biology

Pancreatic cancer (PC) is characterized by extensive desmoplasia, with heterogeneous cancer-associated fibroblasts (CAFs) as a major component. However, the contribution of distinct precursor cells to CAF heterogeneity remains poorly defined. This study investigated the role of Muc5ac in modulating CAF heterogeneity by maturing precursor cells, including adipose-derived mesenchymal stem cells (AD-MSCs), bone marrow-derived MSCs (BM-MSCs), and pancreatic stellate cells (PSCs), into different CAF subsets. RNA sequencing of precursor cells treated with conditioned media from Muc5ac-proficient or -deficient cancer cells revealed distinct transcriptional profiles. Muc5ac significantly modulated the expression of Dnmts and Tets in AD-MSCs, promoting the acquisition of extracellular matrix …

Extracellular Vesicles In Prostate Cancer: Current Understanding And Future Perspectives, Balaji Perumalsamy, Parthasarathy Seshacharyulu, Raghupathy Vengoji, Nicole Shonka, Benjamin A. Teply, Surinder K. Batra, Sakthivel Muniyan

Journal Articles: Biochemistry & Molecular Biology

Exosomes are nanoscale, lipid bilayer extracellular vesicles (EVs) actively secreted by cells under both physiological and pathological conditions. As key mediators of intercellular communication, exosomes carry a diverse array of molecular cargo, including nucleic acids, proteins, lipids, and metabolites, which can influence the function of recipient cells. Based on evidence from 2016–2025 across PubMed, Embase, the Cochrane Library, and clinicaltrials.org, this review consolidates current understanding of exosome biology in prostate cancer (PCa). We discuss exosome biogenesis, molecular cargo composition, and their functional roles in tumor progression, angiogenesis, immune evasion, metastasis, and therapy resistance of PCa. We emphasize the biomarker potential …

The Influence, Dependency, And Targeting Of Fatty Acid Uptake In Er+ Breast Cancer, Abigail E. Goen

Dartmouth College Ph.D Dissertations

Estrogen Receptor-positive/ Human Epidermal Growth Factor 2-negative, breast cancer (ER+/HER2- BC) is the most prevalent subtype of BC, impacting millions of individuals. Although early screening and treatment with endocrine therapy has greatly enhanced survival, this subtype sustains a steady increase of risk for recurrent disease for decades after diagnosis, indicating the persistence of residual cancer cells that are capable of maintaining dormancy for >20 years prior to metastatic outgrowth. Dormant cells reprogram metabolic pathways which can be profoundly influenced by the tumor microenvironment in promoting quiescence or proliferation. Fatty acid oxidation dependency has been noted as a hallmark of drug …

Exploring Anticholinergic Neurotoxicity: Diphenhydramine's Impact On Neuro-2a Cell Morphology, Expression, And Viability, Jordan B. Mcintyre

Honors Undergraduate Theses

Anticholinergic medications, such as diphenhydramine (commonly known as Benadryl), are increasingly recognized for their association with cognitive impairment and neurodegenerative disease. These medications, which inhibit the action of acetylcholine, a neurotransmitter essential for the formation and utilization of the central and peripheral nervous system, have been implicated in conditions such as dementia and may impact fundamental cellular processes like neurogenesis and cell proliferation. This study investigates the effects of diphenhydramine on neurogenesis when introduced to Neuro-2a cells during differentiation. For all studies cells were plated on coverslips or in 6-well plates with differentiation media containing 0 ng/mL, 50 ng/mL, …

Manuka Honey Modulates Oxidative Stress In Neuro2-A Cells Through Mitochondrial Regulation, Rachel Abramovici

Honors Undergraduate Theses

Manuka honey is known for its vital usage in wound healing, being an agonist towards fighting infections, and is an acting antioxidant [32]. Its main constituents are flavonoids and phenolic compounds, with methyl syringate (MSYR) being a major active ingredient. The specific compounds responsible for these antioxidant effects, particularly in the CNS, remain unclear. It is hypothesized that pre-treatment of mouse neuroblastoma cells with MSYR followed by hydrogen peroxide exposure will activate the AMPK/SIRT1/PGC-1a pathway, due to MSYR’s phenolic structure, and thus reduce oxidative stress and improve mitochondrial biogenesis. Hydrogen peroxide is a standard reactive oxygen species (ROS) treatment to …

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 …

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.

Case Series Of Nizon-Isidor Syndrome By Heterozygous Variants In Med12l With Further Evidence Of Mitotic Instability In One Case With Diploid-Triploid Mosaicism, Russell Stewart, Kimberly M Ezell, Deanna S Bell, Brian Corner, Ashley Mcminn, Joy D Cogan, Rizwan Hamid, Lynette Rives, John A Phillips, Nina Paddu, Gitanjali Srivastava, Ronit Marom, Farah A Ladha, Claudia Soler-Alfonso, Rachel Franciskovich, Mary Koziura, Sumit Pruthi, Gabriele Richard, Christina B Sheedy, Undiagnosed Diseases Network, Thomas Cassini

Faculty, Staff and Students Publications

Nizon-Isidor syndrome is a rare disorder caused by heterozygous variants in MED12L, with only eight documented cases in the literature. Here, we present three additional cases of this syndrome. Proband 1 was a 7-year-old female who presented with developmental delay, right-leg hemihypertrophy, laryngeal cleft, esotropia, abnormal skin pigmentation, sectoral iris hypopigmentation, dysphagia, periventricular nodular heterotopia, seizures, morbid obesity, and a pelvic kidney. Genome sequencing (GS) revealed a MED12L variant, NM_053002.5:c.3559+2T>G. Both computational models and transcriptomic analysis confirmed that this variant induced splice loss of MED12L exon 25. Probands 2 and 3 presented with overlapping phenotypes of developmental delay; sequencing …

Efficacy And Safety Of Pyrimidine Nucleos(T)Ide Therapy In Thymidine Kinase 2 Deficiency, Michio Hirano, Caterina Garone, Richard Haas, Carmen Paradas, Fernando Scaglia, Irene Rebollo Mesa, Carl Chiang, Anny-Odile Colson, Susan Vanmeter, Cristina Domínguez-González

Faculty, Staff and Students Publications

Thymidine kinase 2 deficiency (TK2d) (MIM 609560) is an ultra-rare, autosomal recessive mitochondrial myopathy caused by TK2 variants, leading to mitochondrial DNA depletion and/or multiple deletions. People with thymidine kinase 2 deficiency experience progressive myopathy, bulbar weakness and respiratory insufficiency, often losing the ability to walk, eat and breathe independently. Doxecitine and doxribtimine represents the first approved treatment for patients with thymidine kinase 2 deficiency with age of symptom onset ≤12 years by the US Food and Drug Administration and the European Medicines Agency; previously, disease management was limited to supportive care. We investigated the efficacy and safety of pyrimidine …

Highly Variable Expressivity Of A Cnv Deletion Involving Tbx4 In Three Deceased Siblings With Lung Developmental Disorder And Their Mildly Affected Mother And Grandfather, Przemyslaw Szafranski, Tomasz Gambin, Michal Kadlof, Michał Denkiewicz, Dariusz Plewczynski, Hyun Jeong Kim, Gail Deutsch, Nahir Cortes-Santiago, Salmo Raskin, Paweł Stankiewicz

Faculty, Staff and Students Publications

Single nucleotide variants (SNVs) and copy-number variant (CNV) deletions involving TBX4 have been associated with pulmonary arterial hypertension, ischiocoxopodopatellar syndrome, and lethal lung developmental disorders (LLDDs). Thus far, all large CNV deletions encompassing entire TBX4 have been found to have arisen de novo. Here, we present a three-generation family with three neonate siblings who died within 35-66 days due to histopathologically diagnosed LLDD. Whole-genome sequencing identified an ~108-kb CNV deletion encompassing TBX4 in all three infants. The deletion was also found in their mother with a history of pneumonia and persistent thick upper airway secretions and in the maternal grandfather …

A Nonlinear Relationship Of Evoked Responses Following Charge-Balanced Single-Pulse Electrical Stimulation With Varying Pulse Widths, Isabel A Danstrom, Joshua A Adkinson, Zoe Liu, Meghan E Robinson, Denise Oswalt, Garrett P Banks, Atul Maheshwari, Lu Lin, Ben Shofty, Mohammed Hasen, Alica Goldman, Eleonora Bartoli, Sarah R Heilbronner, Kelly R Bijanki

Faculty, Staff and Students Publications

Background: Single-pulse electrical stimulation (SPES) can help guide neuromodulation therapy in an iterative process to reveal ideal circuits and degrees of engagement. Understanding the relationship between parameter input and neural output will be necessary both to build informative models of the brain's functional connectivity and to improve responses to stimulation-based neuromodulation therapies. Modulating pulse width alters the total charge delivered to neural tissue and is thought to selectively activate fibers with different diameters, potentially shifting therapeutic thresholds. The anterior cingulate cortex (ACC) and orbitofrontal cortex (OFC) are of great clinical relevance to the pathophysiology and treatment of neuropsychiatric disorders.

Objective: …

Mark Hallett: Scientist And Humanitarian In Modern Movement Disorder Neurology, Daniel Truong, Joseph Jankovic

Faculty, Staff and Students Publications

Mark Hallett, MD (1943-2025) was a highly influential neurologist in the modern history of movement disorders. Over several decades, his work transformed the field from a predominantly descriptive clinical specialty into a neuroscientific discipline. Through pioneering investigations in neurophysiology, cortical excitability, dystonia, tremors, myoclonus, functional movement disorders, and transcranial magnetic stimulation, Hallett helped establish conceptual frameworks that continue to shape contemporary research and clinical practice. Beyond his scientific contributions, he is recognized as a global mentor and educational ambassador whose influence extended across generations of neurologists and neuroscientists worldwide. This article examines Hallett's dual legacy as both a transformative scientist …

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 …

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.

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 …

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 …

Case Report: Molecular Diagnostics And Clinical Courses Of Two Adult Spinal Pilocytic Astrocytoma Long-Term Survivors With Gtf2i::Braf Fusion, Lorenzo Argao, Pinar E Zerk, Hsiang-Chih Lu, Zied Abdullaev, Martha Quezado, Michelle L Cassidy, Bennett Mclver, Anna Choi, Marissa Panzer, Renee Tweneboah-Koduah, Lily Polskin, Marta Penas-Prado, Paul Park, Nathan Clarke, Kenneth Aldape, Jacob Mandel, Byram H Ozer

Faculty, Staff and Students Publications

Introduction: Pilocytic astrocytomas are driven by BRAF and mitogen-activated protein kinase (MAPK) alterations, typically KIAA1549::BRAF fusions. A rare GTF2I::BRAF fusion has been described, but little is known about these cases.

Case report: Here, we report two cases with GTF2I::BRAF fusions. Case 1 is a 36-year-old man initially diagnosed with myxopapillary ependymoma at the conus medullaris with three recurrences over 23 years requiring two surgeries, three rounds of radiation therapy, and one round of lapatinib/temozolomide. A distant disease focus in T3/T4 was sampled and tested with modern diagnostic techniques revealing a pilocytic astrocytoma on histology and methylation profiling. The patient has …

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, …

Wnt4 Deficiency Impacts Heart, Diaphragm, And Palate Development: Insights From Human Genetics, Machine Learning, And Mouse Models, Andrés Hernández-García, Bum Jun Kim, David Chitayat, Patrick Shannon, Stephanie Hedges, Maria Al Bandari, Maria J Guillen Sacoto, Emily Anne Bates, Yunus H Ozekin, Victor Faundes, Pamela N Luna, Chad A Shaw, Tara L Rasmussen, Chih-Wei Hsu, Daryl A Scott

Faculty, Staff and Students Publications

WNT4 is a secreted protein that plays a critical role in the regulation of cell fate and embryogenesis. Biallelic variants in WNT4 have been linked to SERKAL syndrome, an autosomal recessive disorder characterized by 46,XX sex reversal and dysgenesis of the kidneys, adrenals, and lungs. SERKAL syndrome has only been described in a single consanguineous kindred with four affected fetuses. Additional features seen in a subset of affected fetuses included ventricular septal defect (VSD), congenital diaphragmatic hernia (CDH), and orofacial clefting (OFC). To determine if these additional features were likely to be caused by WNT4 deficiency, we used machine learning …

The Underexplored Complexity Of Pancreatic Cancer: Early Dissemination And Quiescence, Nivedeta Krishna Kumar, Annant Bir Kaur, Surinder K. Batra, Moorthy P. Ponnusamy

Journal Articles: Biochemistry & Molecular Biology

Pancreatic cancer has been renowned for its aggressive nature and occasionally manifests periods of dormancy, presenting a perplexing challenge in studying disease progression. Despite surgery, many patients relapse due to dormancy and chemoresistance, resulting in recurrence and death within a few years. Studies also suggest that pancreatic cancer disseminates early on, spreading to secondary organs with no evidence of disease. The lingering question is: how, where, and when does pancreatic cancer recur and spread? Herein, we explore evidence for clinically dormant pancreatic cancer cells, examining the roles of quiescence and stemness populations and their interactions with the tumor microenvironment. Understanding …