Neurology Commons^™

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 …

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 …

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) …

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. …

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 …

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 …

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 …

Lenalidomide In The Treatment Of Anti-Myelin-Associated Glycoprotein Neuropathy: A Phase 1 Study To Identify The Maximum Tolerated Dose., Amro M Stino, Naresh Bumma, Rachel Smith, Long Davalos, Jeff Allen, Jing Christine Ye, Matthew Pianko, Erica Campagnaro, Cassandra Fierro, Abdelrahman Awad, Ben Murdock, Maciej Pietrzak, Gerard Loszanski, David M Kline, Yvonne Efebera, Bakri Elsheikh

Neuroscience Articles

BACKGROUND: Anti-myelin-associated glycoprotein (MAG) neuropathy is a debilitating demyelinating polyneuropathy with no approved therapies. Our primary objective was to ascertain lenalidomide safety and maximum tolerated dose (MTD) in anti-MAG neuropathy.

METHODS: This phase 1b, open-label, single-arm, dose-finding trial was conducted from 2019 through 2022. The original design included a dose-escalation/extension phase followed by a dose-expansion phase. Three doses of lenalidomide were evaluated: 10, 15, and 25 mg. The main outcome was the MTD.

RESULTS: Eleven patients enrolled (10 men), with a mean age of 67.6 years (SD = 6.18, range 58-77 years) and mean disease duration of 8.5 years (SD …

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 …

Emotional, Behavioral, And Cognitive Symptom Associations With Community Participation In Chronic Traumatic Brain Injury, Shannon B Juengst, Brittany Wright, Leia Vos, Robert Perna, Michael Williams, Emily Dudek, Annalyn Demello, Zinat Taiwo, Luis Leon Novelo

Faculty, Staff and Student Publications

OBJECTIVES: To determine the association between self-reported emotional and cognitive symptoms and participation outcomes in chronic traumatic brain injury (TBI) and to explore the relative contribution of self-reported versus performance-based cognition to participation outcomes.

SETTING: Community.

PARTICIPANTS: Community-dwelling adults ( n = 135) with a lifetime history of mild to severe TBI.

DESIGN: Secondary analysis of a cross-sectional study on neurobehavioral symptoms in chronic TBI.

MAIN MEASURES: Behavioral Assessment Screening Tool (BAST) (Negative Affect, Fatigue, Executive Dysfunction, Impulsivity, Substance Abuse subscales) measured self-reported neurobehavioral symptoms; Participation Assessment with Recombined Tools (Productivity, Social Relations, and Out and About) measured self-reported participation …

The Use Of Optical Coherence Tomography (Oct) And Oct Angiography In Borderline Personality Disorder Compared To Health Control Subjects, Bei Xu, Fangling Li, Zhejia Zhang, Qian Xiao

Faculty, Staff and Student Publications

BACKGROUND: Optical coherence tomography (OCT) or OCT angiography (OCTA) has been investigated in few research studies of psychiatric disorders. No research has been done using OCT or OCTA in patients with borderline personality disorder (BPD).

METHODS: OCTA measured foveal avascular zone (FAZ), macular vessel density (MVD), and peripapillary vessel density (PVD). OCT measured the peripapillary retinal fiber layer (RNFL) and central retinal thickness (CRT). The study utilized the Ottawa Self-Injury Inventory, Hamilton Anxiety Rating Scale (HAMA), and Global Assessment of Functioning (GAF) to assess the symptom characteristics of individuals with BPD.

RESULTS: Fifty-nine eyes of BPD patients and 58 eyes …

Risk Of Alzheimer's Disease And Related Dementias In Persons With Glaucoma: A National Cohort Study, Casey Crump, Jan Sundquist, Weiva Sieh, Kristina Sundquist

Faculty, Staff and Student Publications

PURPOSE: Glaucoma is a heterogeneous group of optic neuropathies that potentially may be associated with other cerebral neurodegenerative processes leading to dementia. However, prior studies have been inconsistent. We examined dementia risks after glaucoma diagnosis in a large population-based cohort.

DESIGN: National matched cohort study.

PARTICIPANTS: A total of 324 730 persons diagnosed with glaucoma during 1995-2017 in Sweden and 3 247 300 age- and sex-matched population-based controls without prior dementia.

METHODS: Cox regression was used to compute hazard ratios (HRs) for Alzheimer's disease (AD), vascular dementia (VaD), and all-cause dementia in persons with glaucoma compared with controls, adjusting for …

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 …

Demographics And Paindetect As Predictors Of 24-Month Outcomes For 10 Khz Scs In Nonsurgical Refractory Back Pain, Leonardo Kapural, Chengyuan Wu, Aaron Calodney, Julie Pilitsis, Markus Bendel, Erika Petersen, Dawood Sayed, Colleen Kelly, Rose Province-Azalde, Naresh P. Patel

Department of Neurosurgery Faculty Papers

BACKGROUND: Nonsurgical refractory back pain (NSRBP) is broadly defined as chronic refractory back pain in patients who have not had previous spine surgery and, because they are deemed inappropriate candidates for surgery, are reliant on conventional medical management (CMM), which often provides poor long-term outcomes. High-frequency spinal cord stimulation (10kHz SCS) has demonstrated high rates of pain relief and improvements in functioning in patients with NSRBP. However, despite the use of temporary trial stimulation to select patients who will respond to therapy, some patients fail to achieve long-term therapy response with permanent implants. Prediction analysis founded on patients' baseline characteristics …

Comparative Efficacy, Quality Of Life, Safety, And Tolerability Of Atogepant And Rimegepant In Migraine Prevention: A Matching-Adjusted Indirect Comparison Analysis, Cristina Tassorelli, Kateryna Onishchenko, Rashmi B. Halker Singh, Molly Duan, Laure Dupont-Benjamin, Matthew Hemstock, Corey Voller, Peter Mcallister, Stephanie J. Nahas, Pranav Gandhi, Jessica Ailani

Department of Neurology Faculty Papers

BACKGROUND: Comparative evaluations of preventive migraine treatments can help inform clinical decision making for managing migraine in clinical practice.

METHODS: An anchored matching-adjusted indirect comparison analysis was conducted using pooled participant-level data from two phase 3 atogepant trials (ADVANCE and PROGRESS) and one phase 2/3 rimegepant trial (BHV3000-305) to evaluate the relative efficacy and safety/tolerability of atogepant and rimegepant as preventive migraine treatments. Participants receiving atogepant 60 mg once daily, rimegepant orally disintegrating tablet 75 mg once every other day, and placebo were included. Only participants meeting the BHV3000-305 inclusion/exclusion criteria were analyzed: ≥6 monthly migraine days and ≤18 monthly …

Association Of Plasma Ykl-40 With Mri, Csf, And Cognitive Markers Of Brain Health And Dementia, Matthew P Pase, Jayandra J Himali, Raquel Puerta, Alexa S Beiser, Mitzi M Gonzales, Claudia L Satizabal, Qiong Yang, Hugo J Aparicio, Daniel J Kojis, Charles S Decarli, Oscar L Lopez, Will Longstreth, Vilmundur Gudnason, Thomas H Mosley, Joshua C Bis, Alison Fohner, Bruce M Psaty, Mercè Boada, Pablo García-González, Sergi Valero, Marta Marquié, Russell Tracy, Lenore J Launer, Agustín Ruiz, Myriam Fornage, Sudha Seshadri

Faculty, Staff and Student Publications

BACKGROUND AND OBJECTIVES: Higher YKL-40 levels in the CSF are a known biomarker of brain inflammation. We explored the utility of plasma YKL-40 as a biomarker for accelerated brain aging and dementia risk.

METHODS: We performed cross-sectional and prospective analyses of 4 community-based cohorts in the United States or Europe: the Age, Gene/Environment Susceptibility-Reykjavik Study, Atherosclerosis Risk in the Communities study, Coronary Artery Risk Development in Young Adults study, and Framingham Heart Study (FHS). YKL-40 was measured from stored plasma by a single laboratory using Mesoscale Discovery with levels log transformed and standardized within each cohort. Outcomes included MRI total …

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 …

Comparing Anesthesia And Surgery Controlled Time For Primary Total Knee And Hip Arthroplasty Between An Academic Medical Center And A Community Hospital: Retrospective Cohort Study, Thy B Nguyen, Nathaen Weitzel, Craig Hogan, Rachel M Kacmar, Kayla M Williamson, Jack Pattee, Vesna Jevtovic-Todorovic, Colby G Simmons, Adeel Ahmad Faruki

Faculty, Staff and Student Publications

BACKGROUND: Osteoarthritis is a significant cause of disability, resulting in increased joint replacement surgeries and health care costs. Establishing benchmarks that more accurately predict surgical duration could help to decrease costs, maximize efficiency, and improve patient experience. We compared the anesthesia-controlled time (ACT) and surgery-controlled time (SCT) of primary total knee (TKA) and total hip arthroplasties (THA) between an academic medical center (AMC) and a community hospital (CH) for 2 orthopedic surgeons.

OBJECTIVE: This study aims to validate and compare benchmarking times for ACT and SCT in a single patient population at both an AMC and a CH.

METHODS: This …

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, …

Stereotactic Electroencephalogram Recordings In Temporal Lobectomy Patients Demonstrates The Predictive Value Of Interictal Cross-Frequency Correlations: A Retrospective Study, Anish Sathe, Mahdi Alizadeh, Emily Johannan, Christian Raimondo, Michael R Sperling, Ashwini Sharan, Michael Kogan

Department of Neurosurgery Faculty Papers

BACKGROUND: Positive correlations between low- and high-frequency spectra from stereotactic electroencephalogram (SEEG) recordings have been implicated in pathological brain activity interictally and have been used for ictal detection in both focal and network models.

OBJECTIVE: We evaluated SEEG signals in patients who ultimately underwent temporal lobectomy to evaluate their utility in seizure localization and prediction of seizure freedom post-resection.

METHODS: We retrospectively analyzed cross-frequency correlations between beta and high gamma (HG) interictal SEEG signals from 22 patients. We compared signals based on temporal versus extra-temporal locations, seizure-free (SF) versus non-seizure-free (NSF) outcomes, and mesial (M) versus mesial temporal-plus (M+) onset. …

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 …

Real-World Effectiveness Of Add-Onfremanezumab In Patients Receiving Onabotulinumtoxina For The Prevention Of Chronic Migraine In A Us Tertiary Headache Center: A Retrospective Chart Review Study, Hsiangkuo Yuan, Fred Cohen, Maurice T. Driessen, Lynda J. Krasenbaum, Mario Ortega, Mary Hopkins, Michael J. Marmura

Department of Jefferson Headache Center Papers and Presentations

Background: Concomitant fremanezumab, a calcitonin gene-related peptide (CGRP) pathway monoclonal antibody (mAb), and onabotulinumtoxinA (onabotA) improve treatment response compared with onabotA alone in patients with chronic migraine (CM). Methods: This was a single-center, retrospective, observational study that assessed treatment response (change over time in monthly headache days [MHD] and pain intensity [PI]) in adult patients with CM receiving fremanezumab as add-on therapy to onabotA for CM prevention. Results: In the study population (N = 116, age 50.0 ± 13.1, female 85.3%, pre-index onabotA use 46.5 ± 34.2 months) receiving concurrent onabotA and fremanezumab for 17.5 ± 11.6 months, MHD decreased …

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 …

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

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 …

Moving Toward Elucidating Alternative Motor Pathway Structures Post-Stroke: The Value Of Spinal Cord Neuroimaging, Ramiro Oquita, Victoria Cuello, Sarvani Uppati, Sravani Mannuru, Daniel Salinas, Michael R. Dobbs, Kelsey Potter-Baker

School of Medicine Publications

Stroke results in varying levels of motor and sensory disability that have been linked to the neurodegeneration and neuroinflammation that occur in the infarct and peri-infarct regions within the brain. Specifically, previous research has identified a key role of the corticospinal tract in motor dysfunction and motor recovery post-stroke. Of note, neuroimaging studies have utilized magnetic resonance imaging (MRI) of the brain to describe the timeline of neurodegeneration of the corticospinal tract in tandem with motor function following a stroke. However, research has suggested that alternate motor pathways may also underlie disease progression and the degree of functional recovery post-stroke. …

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 = …