Neurology Commons^™

The Relationship Of Health Literacy To Health Outcomes Among Individuals With Traumatic Brain Injury: A Traumatic Brain Injury Model Systems Study, Monique R Pappadis, Angelle M Sander, Shannon B Juengst, Luis Leon-Novelo, Esther Ngan, Kathleen R Bell, John D Corrigan, Simon Driver, Laura E Dreer, Anthony H Lequerica

Faculty, Staff and Student Publications

OBJECTIVE: To examine the associations between health literacy and health outcomes among individuals with traumatic brain injury (TBI) at least a year post-injury.

SETTING: Community following discharge from inpatient rehabilitation.

PARTICIPANTS: A total of 205 individuals with complicated mild to severe TBI who completed a TBI Model Systems National Database follow-up interview and a web-based health literacy measure.

DESIGN: A multicenter, cross-sectional, observational study.

MAIN MEASURES: The Health Literacy Assessment Using Talking Touchscreen Technology (Health LiTT), number of comorbid conditions (Medical and Mental Health Comorbidities Interview [MMHCI]), perceived physical and mental health (PROMIS Global Physical and Mental Health subscales), Patient …

Imaging Predictors Of 4q12 Amplified And Rb1 Mutated Glioblastoma Idh-Wildtype, Antonio Dono, Jose Torres, Luis Nunez, Octavio Arevalo, Juan Carlos Rodriguez-Quinteros, Roy F Riascos, Arash Kamali, Nitin Tandon, Leomar Y Ballester, Yoshua Esquenazi

Faculty, Staff and Student Publications

Introduction: Recent studies have identified that glioblastoma IDH-wildtype consists of different molecular subgroups with distinct prognoses. In order to accurately describe and classify gliomas, the Visually AcceSAble Rembrandt Images (VASARI) system was developed. The goal of this study was to evaluate the VASARI characteristics in molecular subgroups of IDH-wildtype glioblastoma.

Methods: A retrospective analysis of glioblastoma IDH- wildtype with comprehensive next-generation sequencing and pre-operative and post-operative MRI was performed. VASARI characteristics and 205 genes were evaluated. Multiple comparison adjustment by the Bejamin-Hochberg false discovery rate (BH-FDR) was performed. A 1:3 propensity score match (PSM) with a Caliper of 0.2 was …

Interventions To Optimize Spinal Cord Perfusion In Patients With Acute Traumatic Spinal Cord Injury: An Updated Systematic Review, Nathan Evaniew, Benjamin Davies, Farzin Farahbakhsh, Michael G Fehlings, Mario Ganau, Daniel Graves, James D Guest, Radha Korupolu, Allan R Martin, Stephen L Mckenna, Lindsay A Tetreault, Aditya Vedantam, Erika D Brodt, Andrea C Skelly, Brian K Kwon

Faculty, Staff and Student Publications

STUDY DESIGN: Systematic review update.

OBJECTIVES: Interventions that aim to optimize spinal cord perfusion are thought to play an important role in minimizing secondary ischemic damage and improving outcomes in patients with acute traumatic spinal cord injuries (SCIs). However, exactly how to optimize spinal cord perfusion and enhance neurologic recovery remains controversial. We performed an update of a recent systematic review (Evaniew et al, J. Neurotrauma 2020) to evaluate the effects of Mean Arterial Pressure (MAP) support or Spinal Cord Perfusion Pressure (SCPP) support on neurological recovery and rates of adverse events among patients with acute traumatic SCI.

METHODS: We …

Techniques In Medicine: Ipsilateral Transforaminal Epidural Steroid Injection In Bertolotti’S Syndrome, Peter D Vu, Christopher L Robinson, Omar Viswanath, Ivan Urits, Jamal Hasoon

Faculty, Staff and Student Publications

Bertolotti's syndrome, also known as lumbosacral transitional vertebrae, is a relatively rare spinal condition characterized by an anatomical variation in the lower spine. Conservative approaches such as physical therapy, anti-inflammatory medications and lifestyle modifications may be recommended for mild cases. In more severe cases or when conservative measures fail to provide relief, injections such as may be considered to alleviate pain. This case is unique in that we document a challenging technique of ipsilateral transforaminal epidural steroid injection in a patient with Bertolotti's syndrome.

Association Of Timely Comprehensive Genomic Profiling With Precision Oncology Treatment Use And Patient Outcomes In Advanced Non-Small-Cell Lung Cancer, Jeff Yorio, Katherine T Lofgren, Jessica K Lee, Khaled Tolba, Geoffrey R Oxnard, Alexa B Schrock, Richard S P Huang, Lorraine Brisbin

Faculty, Staff and Student Publications

PURPOSE: Timely biomarker testing remains out of reach for many patients with advanced non-small-cell lung cancer (aNSCLC). Here, we studied the quality-of-care implications of closing the gap in timely receipt of comprehensive genomic profiling (CGP) to inform first-line (1L) decisions.

METHODS: Using a real-world clinicogenomic database, we studied testing and 1L treatment patterns in aNSCLC after the approval of pembrolizumab in combination with pemetrexed and carboplatin (May 10, 2017). To estimate the association of timely CGP results with therapy selection and patient outcomes, we identified patients with no previous genomic testing beyond PD-L1 immunohistochemistry and dichotomized patients by whether CGP …

A Clinical Practice Guideline For The Management Of Patients With Acute Spinal Cord Injury: Recommendations On Hemodynamic Management, Brian K Kwon, Lindsay A Tetreault, Allan R Martin, Paul M Arnold, Rex A W Marco, Virginia F J Newcombe, Carl M Zipser, Stephen L Mckenna, Radha Korupolu, Chris J Neal, Rajiv Saigal, Nina E Glass, Sam Douglas, Mario Ganau, Vafa Rahimi-Movaghar, James S Harrop, Bizhan Aarabi, Jefferson R Wilson, Nathan Evaniew, Andrea C Skelly, Michael G Fehlings

Faculty, Staff and Student Publications

STUDY DESIGN: Clinical practice guideline development following the GRADE process.

OBJECTIVES: Hemodynamic management is one of the only available treatment options that likely improves neurologic outcomes in patients with acute traumatic spinal cord injury (SCI). Augmenting mean arterial pressure (MAP) aims to improve blood perfusion and oxygen delivery to the injured spinal cord in order to minimize secondary ischemic damage to neural tissue. The objective of this guideline was to update the 2013 AANS/CNS recommendations on the hemodynamic management of patients with acute traumatic SCI, acknowledging that much has been published in this area since its publication. Specifically, we sought …

First Pass Effect As An Independent Predictor Of Functional Outcomes In Medium Vessel Occlusions: An Analysis Of An International Multicenter Study, Răzvan Alexandru Radu, Vincent Costalat, Robert Fahed, Sherief Ghozy, James E Siegler, Hamza Shaikh, Jane Khalife, Mohamad Abdalkader, Piers Klein, Thanh N Nguyen, Jeremy J Heit, Ahmad Sweid, Kareem El Naamani, Robert W Regenhardt, Jose Danilo Bengzon Diestro, Nicole M Cancelliere, Abdelaziz Amllay, Lukas Meyer, Anne Dusart, Flavio Bellante, Géraud Forestier, Aymeric Rouchaud, Suzana Saleme, Charbel Mounayer, Jens Fiehler, Anna Luisa Kühn, Ajit S Puri, Christian Dyzmann, Peter T Kan, Marco Colasurdo, Gaultier Marnat, Jérôme Berge, Xavier Barreau, Igor Sibon, Simona Nedelcu, Nils Henninger, Maéva Kyheng, Thomas R Marotta, Christopher J Stapleton, James D Rabinov, Takahiro Ota, Shogo Dofuku, Leonard Ll Yeo, Benjamin Yq Tan, Juan Carlos Martinez-Gutierrez, Sergio Salazar-Marioni, Sunil Sheth, Leonardo Renieri, Carolina Capirossi, Ashkan Mowla, Stavropoula I Tjoumakaris, Pascal Jabbour, Priyank Khandelwal, Arundhati Biswas, Frédéric Clarençon, Mahmoud Elhorany, Kevin Premat, Iacopo Valente, Alessandro Pedicelli, João Pedro Filipe, Ricardo Varela, Miguel Quintero-Consuegra, Nestor R Gonzalez, Markus A Möhlenbruch, Jessica Jesser, Illario Tancredi, Adrien Ter Schiphorst, Vivek Yedavalli, Pablo Harker, Lina M Chervak, Yasmin Aziz, Benjamin Gory, Christian Paul Stracke, Constantin Hecker, Monika Killer-Oberpfalzer, Christoph J Griessenauer, Ajith J Thomas, Cheng-Yang Hsieh, David S Liebeskind, Andrea M Alexandre, Tobias D Faizy, Charlotte Weyland, Aman B Patel, Vitor Mendes Pereira, Boris Lubicz, Adam A Dmytriw, Adrien Guenego

Faculty, Staff and Student Publications

Introduction: First pass effect (FPE), achievement of complete recanalization (mTICI 2c/3) with a single pass, is a significant predictor of favorable outcomes for endovascular treatment (EVT) in large vessel occlusion stroke (LVO). However, data concerning the impact on functional outcomes and predictors of FPE in medium vessel occlusions (MeVO) are scarce.

Patients and methods: We conducted an international retrospective study on MeVO cases. Multivariable logistic modeling was used to establish independent predictors of FPE. Clinical and safety outcomes were compared between the two study groups (FPE vs non-FPE) using logistic regression models. Good outcome was defined as modified Rankin Scale …

Education Research: Epilepsy Monitoring Unit Staff Education Using A High-Fidelity Manikin: A Pre-Post Intervention Study, John R Mclaren, Fábio A Nascimento, Joshua Chakranarayan, Marcia Olandoski, Poornachand Veerapaneni, Jay R Gavvala

Faculty, Staff and Student Publications

Background and objectives: Given the inherent risks of seizure provocation in the epilepsy monitoring unit (EMU), both miscommunication and incomplete training about the importance of when and why certain measures are taken can cause critical gaps in care for patients in an especially vulnerable state. To provide a framework that would help minimize these potential pitfalls, our objectives were 2-fold: (1) identify deficits in EMU safety and assessment using a checklist of predetermined items, including key measures essential to the care of EMU patients and (2) develop a simulation training program to address these deficits with education for staff on …

Novel Avenues Of Tau Research, Claire E Sexton, Gal Bitan, Kathryn R Bowles, Miroslaw Brys, Luc Buée, Mahmoud Bukar Maina, Claire D Clelland, Ann D Cohen, John F Crary, Jeffrey L Dage, Kristophe Diaz, Bess Frost, Li Gan, Alison M Goate, Lawrence I Golbe, Oskar Hansson, Celeste M Karch, Hartmuth C Kolb, Renaud La Joie, Suzee E Lee, Diana Matallana, Bruce L Miller, Chiadi U Onyike, Yakeel T Quiroz, Jessica E Rexach, Jonathan D Rohrer, Amy Rommel, Ghazaleh Sadri-Vakili, Suzanne E Schindler, Julie A Schneider, Reisa A Sperling, Charlotte E Teunissen, Stacie C Weninger, Susan L Worley, Hui Zheng, Maria C Carrillo

Faculty, Staff and Students Publications

INTRODUCTION: The pace of innovation has accelerated in virtually every area of tau research in just the past few years.

METHODS: In February 2022, leading international tau experts convened to share selected highlights of this work during Tau 2022, the second international tau conference co-organized and co-sponsored by the Alzheimer's Association, CurePSP, and the Rainwater Charitable Foundation.

RESULTS: Representing academia, industry, and the philanthropic sector, presenters joined more than 1700 registered attendees from 59 countries, spanning six continents, to share recent advances and exciting new directions in tau research.

DISCUSSION: The virtual meeting provided an opportunity to foster cross-sector collaboration …

Retinal Thickness In Essential Tremor And Early Parkinson Disease: Exploring Diagnostic Insights, Claudio Terravecchia, Giovanni Mostile, Clara G Chisari, Cristina Rascunà, Roberta Terranova, Calogero E Cicero, Loretta Giuliano, Giulia Donzuso, Giorgia Sciacca, Antonina Luca, Pierre-Marie Preux, Joseph Jankovic, Mario Zappia, Alessandra Nicoletti

Faculty, Staff and Students Publications

BACKGROUND: Essential tremor (ET) represents a heterogeneous condition which may overlap with Parkinson disease (PD) even at early stages, by sharing some subtle clinical aspects. Longstanding ET demonstrated also higher risk of developing PD, especially with a Tremor-dominant (TD-PD) phenotype. Therefore, differential diagnosis between ET and early PD could be quite challenging. Optical coherence tomography (OCT) has been recognized as a reliable tool to assess the retina as a proxy of neurodegeneration. We aimed to explore the possible role of retinal assessment in differential diagnosis between ET and early PD.

METHODS: Macular layers and peripapillary retinal nerve fiber layer (RNFL) …

Quantification And Visualization Of Cis-Regulatory Dynamics In Single-Cell Multi-Omics Data With Treasmo, Chaozhong Liu, Linhua Wang, Zhandong Liu

Faculty, Staff and Students Publications

Recent advances in single-cell multi-omics technologies have provided unprecedented insights into regulatory processes. We introduce TREASMO, a versatile Python package designed to quantify and visualize transcriptional regulatory dynamics in single-cell multi-omics datasets. TREASMO has four modules, spanning data preparation, correlation quantification, downstream analysis and visualization, enabling comprehensive dataset exploration. By introducing a novel single-cell gene-peak correlation strength index, TREASMO facilitates accurate identification of regulatory changes at single-cell resolution. Validation on a hematopoietic stem and progenitor cell dataset showcases TREASMO's capacity in quantifying the gene-peak correlation strength at the single-cell level, identifying regulatory markers and discovering temporal regulatory patterns along the …

Heterozygous Map3k20 Variants Cause Ectodermal Dysplasia, Craniosynostosis, Sensorineural Hearing Loss, And Limb Anomalies, Daniel Brooks, Elizabeth Burke, Sukyeong Lee, Tanya N Eble, Melanie O'Leary, Ikeoluwa Osei-Owusu, Heidi L Rehm, Shweta U Dhar, Lisa Emrick, David Bick, Michelle Nehrebecky, Ellen Macnamara, Dídac Casas-Alba, Judith Armstrong, Carolina Prat, Antonio F Martínez-Monseny, Francesc Palau, Pengfei Liu, David Adams, Undiagnosed Diseases Network, Seema Lalani, Jill A Rosenfeld, Lindsay C Burrage

Faculty, Staff and Students Publications

Biallelic pathogenic variants in MAP3K20, which encodes a mitogen-activated protein kinase, are a rare cause of split-hand foot malformation (SHFM), hearing loss, and nail abnormalities or congenital myopathy. However, heterozygous variants in this gene have not been definitively associated with a phenotype. Here, we describe the phenotypic spectrum associated with heterozygous de novo variants in the linker region between the kinase domain and leucine zipper domain of MAP3K20. We report five individuals with diverse clinical features, including craniosynostosis, limb anomalies, sensorineural hearing loss, and ectodermal dysplasia-like phenotypes who have heterozygous de novo variants in this specific region of the gene. …

Bi-Allelic Variants In Celsr3 Are Implicated In Central Nervous System And Urinary Tract Anomalies, Jil D Stegmann, Jeshurun C Kalanithy, Gabriel C Dworschak, Nina Ishorst, Enrico Mingardo, Filipa M Lopes, Yee Mang Ho, Phillip Grote, Tobias T Lindenberg, Öznur Yilmaz, Khadija Channab, Steve Seltzsam, Shirlee Shril, Friedhelm Hildebrandt, Felix Boschann, André Heinen, Angad Jolly, Katherine Myers, Kim Mcbride, Mir Reza Bekheirnia, Nasim Bekheirnia, Marcello Scala, Manuela Morleo, Vincenzo Nigro, Annalaura Torella, Tudp Consortium, Michele Pinelli, Valeria Capra, Andrea Accogli, Silvia Maitz, Alice Spano, Rory J Olson, Eric W Klee, Brendan C Lanpher, Se Song Jang, Jong-Hee Chae, Philipp Steinbauer, Dietmar Rieder, Andreas R Janecke, Julia Vodopiutz, Ida Vogel, Jenny Blechingberg, Jennifer L Cohen, Kacie Riley, Victoria Klee, Laurence E Walsh, Matthias Begemann, Miriam Elbracht, Thomas Eggermann, Arzu Stoppe, Kyra Stuurman, Marjon Van Slegtenhorst, Tahsin Stefan Barakat, Maureen S Mulhern, Tristan T Sands, Cheryl Cytrynbaum, Rosanna Weksberg, Federica Isidori, Tommaso Pippucci, Giulia Severi, Francesca Montanari, Michael C Kruer, Somayeh Bakhtiari, Hossein Darvish, Heiko Reutter, Gregor Hagelueken, Matthias Geyer, Adrian S Woolf, Jennifer E Posey, James R Lupski, Benjamin Odermatt, Alina C Hilger

Faculty, Staff and Students Publications

CELSR3 codes for a planar cell polarity protein. We describe twelve affected individuals from eleven independent families with bi-allelic variants in CELSR3. Affected individuals presented with an overlapping phenotypic spectrum comprising central nervous system (CNS) anomalies (7/12), combined CNS anomalies and congenital anomalies of the kidneys and urinary tract (CAKUT) (3/12) and CAKUT only (2/12). Computational simulation of the 3D protein structure suggests the position of the identified variants to be implicated in penetrance and phenotype expression. CELSR3 immunolocalization in human embryonic urinary tract and transient suppression and rescue experiments of Celsr3 in fluorescent zebrafish reporter lines further support an …

Efficacy And Safety Of Daxibotulinumtoxina For Injection In Cervical Dystonia: Aspen-1 Phase 3 Randomized Controlled Trial, Cynthia L Comella, Joseph Jankovic, Robert A Hauser, Atul T Patel, Marta D Banach, Edvard Ehler, Domenico Vitarella, Roman G Rubio, Todd M Gross, Aspen-1 Study Group

Faculty, Staff and Students Publications

BACKGROUND AND OBJECTIVES: ASPEN-1 was a phase 3, randomized, double-blind, placebo-controlled study to evaluate the efficacy, duration of response, and safety of 2 doses of DaxibotulinumtoxinA for Injection (DAXI), a novel botulinum toxin type A formulation in participants with cervical dystonia (CD).

METHODS: Adults (aged 18-80 years) with moderate-to-severe CD (Toronto Western Spasmodic Torticollis Rating Scale [TWSTRS] total score ≥20) were enrolled at 60 sites across 9 countries in Europe and North America. Participants were randomized (3:3:1) to single-dose intramuscular DAXI 125U, 250U, or placebo and followed for up to 36 weeks after injection. The primary end point was change …

Polyaminer-Bulk Is A Deep Learning-Based Algorithm That Decodes Alternative Polyadenylation Dynamics From Bulk Rna-Seq Data, Venkata Soumith Jonnakuti, Eric J Wagner, Mirjana Maletić-Savatić, Zhandong Liu, Hari Krishna Yalamanchili

Faculty, Staff and Students Publications

Alternative polyadenylation (APA) is a key post-transcriptional regulatory mechanism; yet, its regulation and impact on human diseases remain understudied. Existing bulk RNA sequencing (RNA-seq)-based APA methods predominantly rely on predefined annotations, severely impacting their ability to decode novel tissue- and disease-specific APA changes. Furthermore, they only account for the most proximal and distal cleavage and polyadenylation sites (C/PASs). Deconvoluting overlapping C/PASs and the inherent noisy 3' UTR coverage in bulk RNA-seq data pose additional challenges. To overcome these limitations, we introduce PolyAMiner-Bulk, an attention-based deep learning algorithm that accurately recapitulates C/PAS sequence grammar, resolves overlapping C/PASs, captures non-proximal-to-distal APA changes, …

The Optimization Of A Natural Language Processing Approach For The Automatic Detection Of Alzheimer’S Disease Using Gpt Embeddings, Benjamin S. Runde, Ajit Alapati, Nicolas G. Bazan

School of Medicine Faculty Publications

The development of noninvasive and cost-effective methods of detecting Alzheimer’s disease (AD) is essential for its early prevention and mitigation. We optimize the detection of AD using natural language processing (NLP) of spontaneous speech through the use of audio enhancement techniques and novel transcription methodologies. Specifically, we utilized Boll Spectral Subtraction to improve audio fidelity and created transcriptions using state-of-the-art AI services—locally-based Wav2Vec and Whisper, alongside cloud-based IBM Cloud and Rev AI—evaluating their performance against traditional manual transcription methods. Support Vector Machine (SVM) classifiers were then trained and tested using GPT-based embeddings of transcriptions. Our findings revealed that AI-based transcriptions …

Factors Affecting Selection Of Trainee For Neurointervention (Fasten), Mohamed Elfil, Rami Z Morsi, Sherief Ghozy, Ahmed Elmashad, Adnan Siddiqui, Alhamza R Al-Bayati, Ali Alaraj, Allan Brook, Anthony W Kam, Arindam Rano Chatterjee, Athos Patsalides, Ben Waldau, Charles J Prestigiacomo, Charles Matouk, Clemens M Schirmer, David Altschul, David T Parrella, Gabor Toth, Gaurav Jindal, Hamza A Shaikh, Jaydevsinh N Dolia, Johanna T Fifi, Justin F Fraser, Justin Thomas Do, Krishna Amuluru, Louis J Kim, Mark Harrigan, Matthew R Amans, Max Kole, Max Mokin, Michael Abraham, Mouhammad Jumaa, Nazli Janjua, Osama Zaidat, Patrick P Youssef, Priyank Khandelwal, Qingliang Tony Wang, Ramesh Grandhi, Ricardo Hanel, Ryan T Kellogg, Santiago Ortega-Gutierrez, Sunil Sheth, Thanh N Nguyen, Viktor Szeder, Yin C Hu, Albert J Yoo, Omar Tanweer, Brian Jankowitz, Jeremy J Heit, Richard Williamson, Tareq Kass-Hout, Richard W Crowley, Mohammad El-Ghanem, Fawaz Al-Mufti

Faculty, Staff and Students Publications

BACKGROUND AND IMPORTANCE: Neurointervention is a very competitive specialty in the United States due to the limited number of training spots and the larger pool of applicants. The training standards are continuously updated to ensure solid training experiences. Factors affecting candidate(s) selection have not been fully established yet. Our study aims to investigate the factors influencing the selection process.

METHODS: A 52-question survey was distributed to 93 program directors (PDs). The survey consisted of six categories: (a) Program characteristics, (b) Candidate demographics, (c) Educational credentials, (d) Personal traits, (e) Research and extracurricular activities, and (f) Overall final set of characteristics. …

The Effects Of Covid-19 Mrna Vaccine On Adolescence Gynecological Well-Being, Shih-Chiao Tseng, Dana Cherry, Mansoo Ko, Steven R Fisher, Michael Furtado, Shuo-Hsiu Chang

Faculty, Staff and Student Publications

PURPOSE: Evidence suggests that transcranial direct current stimulation (tDCS) can enhance motor performance and learning of hand tasks in persons with chronic stroke (PCS). However, the effects of tDCS on the locomotor tasks in PCS are unclear. This pilot study aimed to: (1) determine aggregate effects of anodal tDCS combined with step training on improvements of the neural and biomechanical attributes of stepping initiation in a small cohort of persons with chronic stroke (PCS) over a 4-week training program; and (2) assess the feasibility and efficacy of this novel approach for improving voluntary stepping initiation in PCS.

METHODS: A total …

Progestin-Associated Meningiomatosis With Unusual Schwannoma-Like Morphology, Katherine A Krause, Jared K Woods, Alexandra J Golby, Eudocia Q Lee, Shyam Tanguturi, Zachary Spigelman, Azra H Ligon, Umberto De Girolami, Matthew Torre

Duncan NRI Faculty and Staff Publications

No abstract provided.

Uchl1 Is A Potential Molecular Indicator And Therapeutic Target For Neuroendocrine Carcinomas, Shiqin Liu, Timothy Chai, Fernando Garcia-Marques, Qingqing Yin, En-Chi Hsu, Michelle Shen, Angus Martin Shaw Toland, Abel Bermudez, Alifiani B Hartono, Christopher F Massey, Chung S Lee, Liwei Zheng, Maya Baron, Caden J Denning, Merve Aslan, Holly M Nguyen, Rosalie Nolley, Amina Zoubeidi, Millie Das, Christian A Kunder, Brooke E Howitt, H Tom Soh, Irving L Weissman, Michael A Liss, Arnold I Chin, James D Brooks, Eva Corey, Sharon J Pitteri, Jiaoti Huang, Tanya Stoyanova

Faculty, Staff and Student Publications

Neuroendocrine carcinomas, such as neuroendocrine prostate cancer and small-cell lung cancer, commonly have a poor prognosis and limited therapeutic options. We report that ubiquitin carboxy-terminal hydrolase L1 (UCHL1), a deubiquitinating enzyme, is elevated in tissues and plasma from patients with neuroendocrine carcinomas. Loss of UCHL1 decreases tumor growth and inhibits metastasis of these malignancies. UCHL1 maintains neuroendocrine differentiation and promotes cancer progression by regulating nucleoporin, POM121, and p53. UCHL1 binds, deubiquitinates, and stabilizes POM121 to regulate POM121-associated nuclear transport of E2F1 and c-MYC. Treatment with the UCHL1 inhibitor LDN-57444 slows tumor growth and metastasis across neuroendocrine carcinomas. The combination of …

Piriformis Syndrome With A Variant Presentation, Roberto Chuapoco, Ryan E. Linford

Annual Research Symposium

Piriformis syndrome has long been a diagnostic quandary due to its tendency to present as other nerve-related conditions. Piriformis syndrome is commonly caused by entrapment of the sciatic nerve as it travels through the greater sciatic foramen due to hypertrophy of the piriformis muscle. However, its constellation of symptoms, including radiating pain down the thigh, can easily be mistaken for lumbosacral radiculopathy. This case report aims to address the misdiagnosis of piriformis syndrome which has prolonged pain for many patients and increased the cost of medical care. It demonstrates a 76-year-old female with a confounding presentation of piriformis syndrome: buttock …

Cpsf3 Inhibition Blocks Pancreatic Cancer Cell Proliferation Through Disruption Of Core Histone Mrna Processing, Abdulrahman A Alahmari, Aditi H Chaubey, Venkata S Jonnakuti, Arwen A Tisdale, Carla D Schwarz, Abigail C Cornwell, Kathryn E Maraszek, Emily J Paterson, Minsuh Kim, Swati Venkat, Eduardo Cortes Gomez, Jianmin Wang, Katerina V Gurova, Hari Krishna Yalamanchili, Michael E Feigin

Duncan NRI Faculty and Staff Publications

Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease with limited effective treatment options, potentiating the importance of uncovering novel drug targets. Here, we target cleavage and polyadenylation specificity factor 3 (CPSF3), the 3′ endonuclease that catalyzes mRNA cleavage during polyadenylation and histone mRNA processing. We find that CPSF3 is highly expressed in PDAC and is associated with poor prognosis. CPSF3 knockdown blocks PDAC cell proliferation and colony formation in vitro and tumor growth in vivo. Chemical inhibition of CPSF3 by the small molecule JTE-607 also attenuates PDAC cell proliferation and colony formation, while it has no effect on cell proliferation …

Cpsf3 Inhibition Blocks Pancreatic Cancer Cell Proliferation Through Disruption Of Core Histone Mrna Processing, Abdulrahman A Alahmari, Aditi H Chaubey, Venkata S Jonnakuti, Arwen A Tisdale, Carla D Schwarz, Abigail C Cornwell, Kathryn E Maraszek, Emily J Paterson, Minsuh Kim, Swati Venkat, Eduardo Cortes Gomez, Jianmin Wang, Katerina V Gurova, Hari Krishna Yalamanchili, Michael E Feigin

Faculty, Staff and Students Publications

Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease with limited effective treatment options, potentiating the importance of uncovering novel drug targets. Here, we target cleavage and polyadenylation specificity factor 3 (CPSF3), the 3′ endonuclease that catalyzes mRNA cleavage during polyadenylation and histone mRNA processing. We find that CPSF3 is highly expressed in PDAC and is associated with poor prognosis. CPSF3 knockdown blocks PDAC cell proliferation and colony formation in vitro and tumor growth in vivo. Chemical inhibition of CPSF3 by the small molecule JTE-607 also attenuates PDAC cell proliferation and colony formation, while it has no effect on cell proliferation …

Effects Of Metformin On Glucose Metabolism And Mitochondrial Function In Patients With Obstructive Sleep Apnea: A Pilot Randomized Trial, Elizabeth R.M. Zunica, Elizabeth C. Heintz, Wagner S. Dantas, R. Caitlin Hebert, Ma Kayla Tanksley, Robbie A. Beyl, Edward C. Mader, John P. Kirwan, Christopher L. Axelrod, Prachi Singh

School of Medicine Faculty Publications

Obstructive sleep apnea (OSA) is associated with increased risk for diabetes, and standard treatment with positive airway pressure (PAP) device shows inconsistent effects on glucose metabolism. Metformin is known to treat and prevent diabetes, but its effects on skeletal muscle mitochondrial function are not completely understood. Here, we evaluate the effects of metformin on glucose metabolism and skeletal muscle mitochondrial function in patients with OSA. Sixteen adults with obesity (50.9 ± 6.7 years, BMI: 36.5 ± 2.9 kg/m2) and moderate-to-severe OSA were provided with PAP treatment and randomized to 3 months of placebo (n = 8) or metformin (n = …

Development And Validation Of Parent-Reported Gastrointestinal Health Scale In Mecp2 Duplication Syndrome, Davut Pehlivan, Sukru Aras, Daniel G Glaze, Muharrem Ak, Bernhard Suter, Kathleen J Motil

Faculty, Staff and Students Publications

BACKGROUND/AIMS: We aimed to develop a validated patient-reported Gastrointestinal Health Scale (GHS) specific to MECP2 Duplication Syndrome (MDS) to be used in clinical trials.

METHODS: MDS parents completed a Gastrointestinal Health Questionnaire (GHQ) to investigate the most relevant and important items associated with gastrointestinal problems in MECP2-related disorders. Item reduction was executed according to EORTC guidelines. We performed reliability and validity studies for the finalized scale.

RESULTS: A total of 106 surveys were eligible for item reduction and validation processes. The initial 55 items were reduced to 38 items based on parent responses, expert opinion, and initial confirmatory factor analysis …

Impact Of An Integrated Health, Nutrition, And Early Child Stimulation And Responsive Care Intervention Package Delivered To Preterm Or Term Small For Gestational Age Babies During Infancy On Growth And Neurodevelopment: Study Protocol Of An Individually Randomized Controlled Trial In India (Small Babies Trial), Ranadip Chowdhury, Rukman Manapurath, Ingvild Fossgard Sandøy, Ravi Prakash Upadhyay, Neeta Dhabhai, Saijuddin Shaikh, Harish Chellani, Tarun Shankar Choudhary, Abhinav Jain, Jose Martines, Nita Bhandari, Tor A Strand, Sunita Taneja

Faculty, Staff and Student Publications

BACKGROUND: Preterm and term small for gestational age (SGA) babies are at high risk of experiencing malnutrition and impaired neurodevelopment. Standalone interventions have modest and sometimes inconsistent effects on growth and neurodevelopment in these babies. For greater impact, intervention may be needed in multiple domains-health, nutrition, and psychosocial care and support. Therefore, the combined effects of an integrated intervention package for preterm and term SGA on growth and neurodevelopment are worth investigating.

METHODS: An individually randomized controlled trial is being conducted in urban and peri-urban low to middle-socioeconomic neighborhoods in South Delhi, India. Infants are randomized (1:1) into two strata …

Endovascular Thrombectomy Treatment Effect In Direct Vs Transferred Patients With Large Ischemic Strokes: A Prespecified Analysis Of The Select2 Trial, Amrou Sarraj, Michael D Hill, M Shazam Hussain, Michael G Abraham, Santiago Ortega-Gutierrez, Michael Chen, Scott E Kasner, Leonid Churilov, Deep K Pujara, Hannah Johns, Spiros Blackburn, Sophia Sundararajan, Yin C Hu, Nabeel A Herial, Ronald F Budzik, William J Hicks, Juan F Arenillas, Jenny P Tsai, Osman Kozak, Dennis J Cordato, Ricardo A Hanel, Teddy Y Wu, Pere Cardona Portela, Chirag D Gandhi, Fawaz Al-Mufti, Laith Maali, Daniel Gibson, Natalia Pérez De La Ossa, Joanna D Schaafsma, Jordi Blasco, Navdeep Sangha, Steven Warach, Timothy J Kleinig, Faris Shaker, Clark W Sitton, Thanh Nguyen, Johanna T Fifi, Pascal Jabbour, Anthony Furlan, Maarten G Lansberg, Georgios Tsivgoulis, Cathy Sila, Nicholas Bambakidis, Stephen Davis, Lawrence Wechsler, Greg W Albers, James C Grotta, Marc Ribo, Bruce C Campbell, Ameer E Hassan, Nirav Vora, Nathan W Manning, Andrew Cheung, Amin N Aghaebrahim, Andres J Paipa Merchán, Daniel Sahlein, Manuel Requena Ruiz, Lucas Elijovich, Adam Arthur, Faisal Al-Shaibi, Edgar A Samaniego, Kelsey R Duncan, Amanda Opaskar, Abhishek Ray, Wei Xiong, Jeffery Sunshine, Michael Degeorgia, Stavropoula Tjoumakaris, Vitor Mendes Pereira

Faculty, Staff and Student Publications

Importance: Patients with large ischemic core stroke have poor clinical outcomes and are frequently not considered for interfacility transfer for endovascular thrombectomy (EVT).

Objective: To assess EVT treatment effects in transferred vs directly presenting patients and to evaluate the association between transfer times and neuroimaging changes with EVT clinical outcomes.

Design, setting, and participants: This prespecified secondary analysis of the SELECT2 trial, which evaluated EVT vs medical management (MM) in patients with large ischemic stroke, evaluated adults aged 18 to 85 years with acute ischemic stroke due to occlusion of the internal carotid or middle cerebral artery (M1 segment) as …

Longitudinal Single-Cell Transcriptional Dynamics Throughout Neurodegeneration In Sca1, Leon Tejwani, Neal G Ravindra, Changwoo Lee, Yubao Cheng, Billy Nguyen, Kimberly Luttik, Luhan Ni, Shupei Zhang, Logan M Morrison, John Gionco, Yangfei Xiang, Jennifer Yoon, Hannah Ro, Fatema Haidery, Rosalie M Grijalva, Eunwoo Bae, Kristen Kim, Regina T Martuscello, Harry T Orr, Huda Y Zoghbi, Hayley S Mcloughlin, Laura P W Ranum, Vikram G Shakkottai, Phyllis L Faust, Siyuan Wang, David Van Dijk, Janghoo Lim

Duncan NRI Faculty and Staff Publications

Neurodegeneration is a protracted process involving progressive changes in myriad cell types that ultimately results in the death of vulnerable neuronal populations. To dissect how individual cell types within a heterogeneous tissue contribute to the pathogenesis and progression of a neurodegenerative disorder, we performed longitudinal single-nucleus RNA sequencing of mouse and human spinocerebellar ataxia type 1 (SCA1) cerebellar tissue, establishing continuous dynamic trajectories of each cell population. Importantly, we defined the precise transcriptional changes that precede loss of Purkinje cells and, for the first time, identified robust early transcriptional dysregulation in unipolar brush cells and oligodendroglia. Finally, we applied a …

Parenting Influences On Frontal Lobe Gray Matter And Preterm Toddlers' Problem-Solving Skills, Josselyn S Muñoz, Megan E Giles, Kelly A Vaughn, Ying Wang, Susan H Landry, Johanna R Bick, Dana M Demaster

Faculty, Staff and Student Publications

Children born preterm often face challenges with self-regulation during toddlerhood. This study examined the relationship between prematurity, supportive parent behaviors, frontal lobe gray matter volume (GMV), and emotion regulation (ER) among toddlers during a parent-assisted, increasingly complex problem-solving task, validated for this age range. Data were collected from preterm toddlers (n = 57) ages 15–30 months corrected for prematurity and their primary caregivers. MRI data were collected during toddlers’ natural sleep. The sample contained three gestational groups: 22–27 weeks (extremely preterm; EPT), 28–33 weeks (very preterm; VPT), and 34–36 weeks (late preterm; LPT). Older toddlers became more compliant as …

Insights Of Clinical Significance From 109 695 Solid Tumor Tissue-Based Comprehensive Genomic Profiles, Andreas M Heilmann, Jonathan W Riess, Margaret Mclaughlin-Drubin, Richard S P Huang, Meghann Hjulstrom, James Creeden, Brian M Alexander, Rachel L Erlich

Faculty, Staff and Student Publications

BACKGROUND: FoundationOneCDx is approved in the US and Japan as a companion diagnostic test to identify patients with cancer who may benefit from treatment with 30 drug therapies in the US and 23 in Japan. Tumor profiling with FoundationOneCDx also detects genomic findings with evidence of clinical significance that may inform clinical care decisions beyond companion diagnostic claims. This observational study reports the breadth and impact of clinical decision insights from FoundationOneCDx solid tumor profiles.

MATERIALS AND METHODS: Consecutive test result reports for patients with solid tumor diagnoses (n = 109 695) were retrospectively analyzed for clinically significant predictive, prognostic, …