Medical Specialties Commons^™

Removal Of Kcnq2 From Parvalbumin-Expressing Interneurons Improves Anti-Seizure Efficacy Of Retigabine, Junzhan Jing, Corrinne Dunbar, Alina Sonesra, Ana Chavez, Suhyeorn Park, Ryan Yang, Heun Soh, Maxwell Lee, Anastasios V Tzingounis, Edward C Cooper, Xiaolong Jiang, Atul Maheshwari

Duncan NRI Faculty and Staff Publications

Anti-seizure drug (ASD) targets are widely expressed in both excitatory and inhibitory neurons. It remains unknown if the action of an ASD upon inhibitory neurons could counteract its beneficial effects on excitatory neurons (or vice versa), thereby reducing the efficacy of the ASD. Here, we examine whether the efficacy of the ASD retigabine (RTG) is altered after removal of the Kv7 potassium channel subunit KCNQ2, one of its drug targets, from parvalbumin-expressing interneurons (PV-INs). Parvalbumin-Cre (PV-Cre) mice were crossed with Kcnq2-floxed (Kcnq2fl/fl) mice to conditionally delete Kcnq2 from PV-INs. In these conditional knockout mice (cKO, PV-Kcnq2 …

Evidence For An Association Between Coffin-Siris Syndrome And Congenital Diaphragmatic Hernia, Yoel Gofin, Xiaonan Zhao, Amanda Gerard, Fernando Scaglia, Michael F Wangler, Samantha A Schrier Vergano, Daryl A Scott

Duncan NRI Faculty and Staff Publications

Coffin-Siris syndrome (CSS) is an autosomal dominant neurodevelopmental syndrome that can present with a variety of structural birth defects. Pathogenic variants in 12 genes have been shown to cause CSS. Most of these genes encode proteins that are a part of the mammalian switch/sucrose non-fermentable (mSWI/SNF; BAF) complex. An association between genes that cause CSS and congenital diaphragmatic hernia (CDH) has been suggested based on case reports and the analysis of CSS and CDH cohorts. Here, we describe an unpublished individual with CSS and CDH, and we report additional clinical information on four published cases. Data from these individuals, and …

Duration Of Ischemia Affects Outcomes Independent Of Infarct Size In Stroke, Youngran Kim, Swapnil Khose, Osama O Zaidat, Ameer E Hassan, Johanna T Fifi, Ashish Nanda, Benjamin Atchie, Britton Woodward, Arnd Doerfler, Alejandro Tomasello, Albert J Yoo, Sunil A Sheth

Faculty, Staff and Student Publications

Background: Delays in endovascular reperfusion for patients with large vessel occlusion stroke are known to worsen outcomes, and the mechanism is believed to be time-dependent expansion of the ischemic infarction. In this study, we hypothesize that delays in onset to reperfusion (OTR) assert an effect on outcomes independent of effects of final infarct (FI).

Methods: We performed a subgroup analysis from the prospective multicenter COMPLETE (International Acute Ischemic Stroke Registry With the Penumbra System Aspiration Including the 3D Revascularization Device; Penumbra, Inc) registry for 257 patients with anterior circulation large vessel occlusion who underwent endovascular therapy with successful reperfusion (modified …

Treating Phantom Limb Pain: Cryoablation Of The Posterior Tibial Nerve, Matthew Fiala, Abana Azariah, Jean Woo, Ahmed Kamel Abdel Aal, Alexa Levey

Faculty, Staff and Student Publications

Phantom limb pain (PLP) is a complex pathophysiologic process involving both the central and peripheral nervous system for which there is no definitive treatment. The number of individuals living with amputated limbs is predicted to increase to 3.5 million by 2050, and up to 80% of these patients will have PLP. In this case report, we will demonstrate successful reduction of PLP in a patient with bilateral phantom toe pain utilizing nerve blockade and subsequent cryoablation of the posterior tibial nerves.

Altered Bladder-Related Brain Network In Multiple Sclerosis Women With Voiding Dysfunction, Zhaoyue Shi, Christof Karmonik, Amelia Soltes, Khue Tran, John A Lincoln, Timothy Boone, Rose Khavari

Faculty, Staff and Student Publications

Objectives:

A number of neuro-urology imaging studies have mainly focused on investigating the brain activations during micturition in healthy and neuropathic patients. It is, however, also necessary to study brain functional connectivity (FC) within bladder-related regions in order to understand the brain organization during the execution of bladder function. This study aims to identify the altered brain network associated with bladder function in multiple sclerosis (MS) women with voiding dysfunction through comparisons with healthy subjects via concurrent urodynamics (UDS)/fMRI.

Materials and Methods:

Ten healthy adult women and nine adult ambulatory women with clinically stable MS for ≥ 6 months and …

Mir-486 Is Essential For Muscle Function And Suppresses A Dystrophic Transcriptome, Adrienne Samani, Rylie M Hightower, Andrea L Reid, Katherine G English, Michael A Lopez, J Scott Doyle, Michael J Conklin, David A Schneider, Marcas M Bamman, Jeffrey J Widrick, David K Crossman, Min Xie, David Jee, Eric C Lai, Matthew S Alexander

Faculty, Staff and Student Publications

miR-486 is a muscle-enriched microRNA, or “myomiR,” that has reduced expression correlated with Duchenne muscular dystrophy (DMD). To determine the function of miR-486 in normal and dystrophin-deficient muscles and elucidate miR-486 target transcripts in skeletal muscle, we characterized mir-486 knockout mice (mir-486 KO). mir-486 KO mice developed disrupted myofiber architecture, decreased myofiber size, decreased locomotor activity, increased cardiac fibrosis, and metabolic defects were exacerbated in mir-486 KO:mdx5cv (DKO) mice. To identify direct in vivo miR-486 muscle target transcripts, we integrated RNA sequencing and chimeric miRNA eCLIP sequencing to identify key transcripts and pathways that contribute towards mir-486 …

Idh1 Pr132h Ctdna And D-2-Hydroxyglutarate As Csf Biomarkers In Patients With Idh-Mutant Gliomas, Yoko Fujita, Luis Nunez-Rubiano, Antonio Dono, Allison Bellman, Mauli Shah, Juan C Rodriguez, Vasanta Putluri, Abu Hena Mostafa Kamal, Nagireddy Putluri, Roy F Riascos, Jay-Jiguang Zhu, Yoshua Esquenazi, Leomar Y Ballester

Faculty, Staff and Student Publications

INTRODUCTION: We aimed to evaluate IDH1 p.R132H mutation and 2-hydroxyglutarate (2HG) in cerebrospinal fluid (CSF) as biomarkers for patients with IDH-mutant gliomas.

METHODS: CSF was collected from patients with infiltrating glioma, and 2HG levels were measured by liquid chromatography-mass spectrometry. IDH1 p.R132H mutant allele frequency (MAF) in CSF-ctDNA was measured by digital droplet PCR (ddPCR). Tumor volume was measured from standard-of-care magnetic resonance images.

RESULTS: The study included 48 patients, 6 with IDH-mutant and 42 with IDH-wildtype gliomas, and 57 samples, 9 from the patients with IDH-mutant and 48 from the patients with IDH-wildtype gliomas. ctDNA was detected in 7 …

Development Of A Novel Pharmacophore Model To Screen Specific Inhibitors For The Serine-Threonine Protein Phosphatase Calcineurin, Abhisek Mukherjee, Karina Cuanalo-Contreras, Abha Sood, Claudio Soto

Faculty, Staff and Student Publications

Calcineurin (CaN) is a calcium/calmodulin-dependent serine/threonine phosphatase with a crucial role in cellular homeostasis. It is also the target of the Food and Drug Administration (FDA) approved immunosuppressant drugs FK506 and cyclosporine A. Recent work from our group and others indicated that an uncontrolled increase in CaN activity causes synaptic dysfunction and neuronal death in various models of neurodegenerative diseases associated with calcium dysregulation. Furthermore, pharmacological normalization of CaN activity can prevent disease progression in animal models. However, none of the FDA-approved CaN inhibitors bind CaN directly, leading to adverse side effects. The development of direct CaN inhibitors is required …

Pharmacokinetic Evaluation Of Intravenous Vitamin C: A Classic Pharmacokinetic Study., Ping Chen, Greg Reed, Joyce Jiang, Yaohui Wang, Jean Sunega, Ruochen Dong, Yan Ma, Anna E. Esparham, Ryan Ferrell, Mark Levine, Jeanne Drisko, Qi Chen

Manuscripts, Articles, Book Chapters and Other Papers

Purpose: Intravenous vitamin C (IVC) is used in a variety of disorders with limited supporting pharmacokinetic data. Herein we report a pharmacokinetic study in healthy volunteers and cancer participants with IVC doses in the range of 1-100 g.

Methods: A pharmacokinetic study was conducted in 21 healthy volunteers and 12 oncology participants. Healthy participants received IVC infusions of 1-100 g; oncology participants received IVC infusions of 25-100 g. Serial blood and complete urine samples were collected pre-infusion and for 24 h post-infusion. Pharmacokinetic parameters were computed using noncompartmental methods. Adverse events were monitored during the study.

Results: In both cohorts, …

Limited Utility Of Structural Mri To Identify The Epileptogenic Zone In Young Children With Tuberous Sclerosis, Maaike Nijman, Edward Yang, Camilo Jaimes, Anna K Prohl, Mustafa Sahin, Darcy A Krueger, Joyce Y Wu, Hope Northrup, Scellig S D Stone, Joseph R Madsen, Aria Fallah, Jeffrey P Blount, Howard L Weiner, Leslie Grayson, E Martina Bebin, Brenda E Porter, Simon K Warfield, Sanjay P Prabhu, Jurriaan M Peters, Tacern Study Group

Faculty, Staff and Students Publications

BACKGROUND AND PURPOSE: The success of epilepsy surgery in children with tuberous sclerosis complex (TSC) hinges on identification of the epileptogenic zone (EZ). We studied structural MRI markers of epileptogenic lesions in young children with TSC.

METHODS: We included 26 children with TSC who underwent epilepsy surgery before the age of 3 years at five sites, with 12 months or more follow-up. Two neuroradiologists, blinded to surgical outcome data, reviewed 10 candidate lesions on preoperative MRI for characteristics of the tuber (large affected area, calcification, cyst-like properties) and of focal cortical dysplasia (FCD) features (cortical malformation, gray-white matter junction blurring, …

Somatic Variants In Diverse Genes Leads To A Spectrum Of Focal Cortical Malformations, Dulcie Lai, Meethila Gade, Edward Yang, Hyun Yong Koh, Jinfeng Lu, Nicole M Walley, Anne F Buckley, Tristan T Sands, Cigdem I Akman, Mohamad A Mikati, Guy M Mckhann, James E Goldman, Peter Canoll, Allyson L Alexander, Kristen L Park, Gretchen K Von Allmen, Olga Rodziyevska, Meenakshi B Bhattacharjee, Hart G W Lidov, Hannes Vogel, Gerald A Grant, Brenda E Porter, Annapurna H Poduri, Peter B Crino, Erin L Heinzen

Faculty, Staff and Student Publications

Post-zygotically acquired genetic variants, or somatic variants, that arise during cortical development have emerged as important causes of focal epilepsies, particularly those due to malformations of cortical development. Pathogenic somatic variants have been identified in many genes within the PI3K-AKT-mTOR-signalling pathway in individuals with hemimegalencephaly and focal cortical dysplasia (type II), and more recently in SLC35A2 in individuals with focal cortical dysplasia (type I) or non-dysplastic epileptic cortex. Given the expanding role of somatic variants across different brain malformations, we sought to delineate the landscape of somatic variants in a large cohort of patients who underwent epilepsy surgery with hemimegalencephaly …

Phenotypic And Genetic Spectrum Of Atp6v1a Encephalopathy: A Disorder Of Lysosomal Homeostasis, Renzo Guerrini, Davide Mei, Katalin Kerti-Szigeti, Sara Pepe, Mary Kay Koenig, Gretchen Von Allmen, Megan T Cho, Kimberly Mcdonald, Janice Baker, Vikas Bhambhani, Zöe Powis, Lance Rodan, Rima Nabbout, Giulia Barcia, Jill A Rosenfeld, Carlos A Bacino, Cyril Mignot, Lillian H Power, Catharine J Harris, Dragan Marjanovic, Rikke S Møller, Trine B Hammer, Riikka Keski Filppula, Päivi Vieira, Clara Hildebrandt, Stephanie Sacharow, Luca Maragliano, Fabio Benfenati, Katherine Lachlan, Andreas Benneche, Florence Petit, Jean Madeleine De Sainte Agathe, Barbara Hallinan, Yue Si, Ingrid M Wentzensen, Fanggeng Zou, Vinodh Narayanan, Naomichi Matsumoto, Alessandra Boncristiano, Giancarlo La Marca, Mitsuhiro Kato, Kristin Anderson, Carmen Barba, Luisa Sturiale, Domenico Garozzo, Roberto Bei, Laura Masuelli, Valerio Conti, Gaia Novarino, Anna Fassio

Faculty, Staff and Student Publications

Vacuolar-type H+-ATPase (V-ATPase) is a multimeric complex present in a variety of cellular membranes that acts as an ATP-dependent proton pump and plays a key role in pH homeostasis and intracellular signalling pathways. In humans, 22 autosomal genes encode for a redundant set of subunits allowing the composition of diverse V-ATPase complexes with specific properties and expression. Sixteen subunits have been linked to human disease. Here we describe 26 patients harbouring 20 distinct pathogenic de novo missense ATP6V1A variants, mainly clustering within the ATP synthase α/β family-nucleotide-binding domain. At a mean age of 7 years (extremes: 6 weeks, youngest deceased …

Cancer-Driving Mutations Are Enriched In Genic Regions Intolerant To Germline Variation, Dimitrios Vitsios, Ryan S Dhindsa, Dorota Matelska, Jonathan Mitchell, Xuequing Zou, Joshua Armenia, Fengyuan Hu, Quanli Wang, Ben Sidders, Andrew R Harper, Slavé Petrovski

Duncan NRI Faculty and Staff Publications

Large reference datasets of protein-coding variation in human populations have allowed us to determine which genes and genic subregions are intolerant to germline genetic variation. There is also a growing number of genes implicated in severe Mendelian diseases that overlap with genes implicated in cancer. We hypothesized that cancer-driving mutations might be enriched in genic subregions that are depleted of germline variation relative to somatic variation. We introduce a new metric, OncMTR (oncology missense tolerance ratio), which uses 125,748 exomes in the Genome Aggregation Database (gnomAD) to identify these genic subregions. We demonstrate that OncMTR can significantly predict driver mutations …

A Patient With Erdheim-Chester Disease Limited To Central Nervous System, Rajesh K Gupta, Anam Haque, Thejasvi A Reddy, Carlos A Pérez

Faculty, Staff and Student Publications

Erdheim-Chester disease (ECD) is a rare, sporadic, non-Langerhans cell histiocytosis, a multisystem disorder, which has higher mortality when presented with CNS involvement. We report a 46-year-old woman who has ECD with exclusive CNS involvement. She presented with intracranial hemorrhage and had a poor response to corticosteroid and interferon. She required multiple debulking procedures and eventually responded well to cobimetinib. She has not had any other organ involvement thus far. This report highlights that CNS involvement may be the only manifestation of ECD and sometimes may require a repeat biopsy with IHC testing for excellent treatment outcomes.

Modeling Neonatal Intraventricular Hemorrhage Through Intraventricular Injection Of Hemoglobin, Brandon A Miller, Shelei Pan, Peter H Yang, Catherine Wang, Amanda L Trout, Dakota Defreitas, Sruthi Ramagiri, Scott D Olson, Jennifer M Strahle

Faculty, Staff and Student Publications

Neonatal intraventricular hemorrhage (IVH) is a common consequence of premature birth and leads to brain injury, posthemorrhagic hydrocephalus (PHH), and lifelong neurological deficits. While PHH can be treated by temporary and permanent cerebrospinal fluid (CSF) diversion procedures (ventricular reservoir and ventriculoperitoneal shunt, respectively), there are no pharmacological strategies to prevent or treat IVH-induced brain injury and hydrocephalus. Animal models are needed to better understand the pathophysiology of IVH and test pharmacological treatments. While there are existing models of neonatal IVH, those that reliably result in hydrocephalus are often limited by the necessity for large-volume injections, which may complicate modeling of …

The Microrna Processor Drosha Is A Candidate Gene For A Severe Progressive Neurological Disorder, Scott Barish, Mumine Senturk, Kelly Schoch, Amanda L Minogue, Diego Lopergolo, Chiara Fallerini, Jake Harland, Jacob H Seemann, Nicholas Stong, Peter G Kranz, Sujay Kansagra, Mohamad A Mikati, Joan Jasien, Mays El-Dairi, Paolo Galluzzi, Francesca Ariani, Alessandra Renieri, Francesca Mari, Michael F Wangler, Swathi Arur, Yong-Hui Jiang, Shinya Yamamoto, Vandana Shashi, Hugo J Bellen

Faculty, Staff and Students Publications

DROSHA encodes a ribonuclease that is a subunit of the Microprocessor complex and is involved in the first step of microRNA (miRNA) biogenesis. To date, DROSHA has not yet been associated with a Mendelian disease. Here, we describe two individuals with profound intellectual disability, epilepsy, white matter atrophy, microcephaly and dysmorphic features, who carry damaging de novo heterozygous variants in DROSHA. DROSHA is constrained for missense variants and moderately intolerant to loss-of-function (o/e = 0.24). The loss of the fruit fly ortholog drosha causes developmental arrest and death in third instar larvae, a severe reduction in brain size and loss …

Number-Time Interaction: Search For A Common Magnitude System In A Cross-Modal Setting, Anuj Shukla, Raju S Bapi

Faculty, Staff and Student Publications

A theory of magnitude (ATOM) suggests that a generalized magnitude system in the brain processes magnitudes such as space, time, and numbers. Numerous behavioral and neurocognitive studies have provided support to ATOM theory. However, the evidence for common magnitude processing primarily comes from the studies in which numerical and temporal information are presented visually. Our current understanding of such cross-dimensional magnitude interactions is limited to visual modality only. However, it is still unclear whether the ATOM-framework accounts for the integration of cross-modal magnitude information. To examine the cross-modal influence of numerical magnitude on temporal processing of the tone, we conducted …

A Sparse Representation Strategy To Eliminate Pseudo-Hfo Events From Intracranial Eeg For Seizure Onset Zone Localization, Behrang Fazli Besheli, Zhiyi Sha, Jay R Gavvala, Candan Gurses, Sacit Karamursel, Michael M Quach, Daniel J Curry, Sameer A Sheth, David J Francis, Thomas R Henry, Nuri F Ince

Faculty, Staff and Student Publications

Objective.

High-frequency oscillations (HFOs) are considered a biomarker of the epileptogenic zone in intracranial EEG recordings. However, automated HFO detectors confound true oscillations with spurious events caused by the presence of artifacts.

Approach.

We hypothesized that, unlike pseudo-HFOs with sharp transients or arbitrary shapes, real HFOs have a signal characteristic that can be represented using a small number of oscillatory bases. Based on this hypothesis using a sparse representation framework, this study introduces a new classification approach to distinguish true HFOs from the pseudo-events that mislead seizure onset zone (SOZ) localization. Moreover, we further classified the HFOs into ripples and …

Novel Dominant And Recessive Variants In Human Robo1 Cause Distinct Neurodevelopmental Defects Through Different Mechanisms, Yan Huang, Mengqi Ma, Xiao Mao, Davut Pehlivan, Oguz Kanca, Feride Un-Candan, Li Shu, Gulsen Akay, Tadahiro Mitani, Shenzhao Lu, Sukru Candan, Hua Wang, Bo Xiao, James R Lupski, Hugo J Bellen

Duncan NRI Faculty and Staff Publications

The Roundabout (Robo) receptors, located on growth cones of neurons, induce axon repulsion in response to the extracellular ligand Slit. The Robo family of proteins controls midline crossing of commissural neurons during development in flies. Mono- and bi-allelic variants in human ROBO1 (HGNC: 10249) have been associated with incomplete penetrance and variable expressivity for a breath of phenotypes, including neurodevelopmental defects such as strabismus, pituitary defects, intellectual impairment, as well as defects in heart and kidney. Here, we report two novel ROBO1 variants associated with very distinct phenotypes. A homozygous missense p.S1522L variant in three affected siblings with nystagmus; and …

Immunohistochemical Detection And Prognostic Significance Of P53, Epidermal Growth Factor Receptor, Murine Double Minute 2, And Isocitrate Dehydrogenase 1 In Glioblastoma Multiforme Patients Of Pakistan, Syed Muhammad Adnan Ali, Muhammad Shahzad Shamim, Syed Ather Enam, Zubair Ahmad, Yumna Adnan, Hasnain Ahmed Farooqui

Department of Surgery Docs

Introduction: Glioblastoma multiforme (GBM) is one of the deadliest cranial tumors occurring in adults. Various biomarkers have been tested for their significance in diagnosis, prognosis, and treatment of GBM. Some well-studied markers in GBM are Isocitrate dehydrogenase 1 (IDH1), Murine double minute 2 (MDM2), Epidermal Growth Factor Receptor (EGFR), and p53. The aim of this study was to investigate the protein expression of these markers in GBM patients of Pakistan.
Methods: A total of 102 surgically resected formalin-fixed paraffin-embedded specimens from patients diagnosed and treated at Aga Khan University Hospital were included in this study. Immunohistochemistry (IHC) for IDH1, MDM2, …

Regulation Of Drosophila Oviduct Muscle Contractility By Octopamine, Sonali A Deshpande, Ethan W Rohrbach, James D Asuncion, Jenna Harrigan, Aditya Eamani, Ellery H Schlingmann, Daniel J Suto, Pei-Tseng Lee, Felix E Schweizer, Hugo J Bellen, David E Krantz

Duncan NRI Faculty and Staff Publications

Octopamine is essential for egg-laying in

Investigation Of The Hydrogen Sulfide Signaling Pathway In Schwann Cells During Peripheral Nerve Degeneration: Multi-Omics Approaches, Yoo Lim Chun, Won-Joon Eom, Jun Hyung Lee, Thy N C Nguyen, Ki-Hoon Park, Hyung-Joo Chung, Han Seo, Youngbuhm Huh, Sang Hoon Kim, Seung Geun Yeo, Wonseok Park, Geul Bang, Jin Young Kim, Min-Sik Kim, Na Young Jeong, Junyang Jung

Faculty, Staff and Student Publications

No abstract provided.

Genetic Impairment Of Succinate Metabolism Disrupts Bioenergetic Sensing In Adrenal Neuroendocrine Cancer, Priyanka Gupta, Keehn Strange, Rahul Telange, Ailan Guo, Heather Hatch, Amin Sobh, Jonathan Elie, Angela M Carter, John Totenhagen, Chunfeng Tan, Yogesh A Sonawane, Jiri Neuzil, Amarnath Natarajan, Ashley J Ovens, Jonathan S Oakhill, Thorsten Wiederhold, Karel Pacak, Hans K Ghayee, Laurent Meijer, Sushanth Reddy, James A Bibb

Faculty, Staff and Student Publications

Metabolic dysfunction mutations can impair energy sensing and cause cancer. Loss of function of the mitochondrial tricarboxylic acid (TCA) cycle enzyme subunit succinate dehydrogenase B (SDHB) results in various forms of cancer typified by pheochromocytoma (PC). Here we delineate a signaling cascade where the loss of SDHB induces the Warburg effect, triggers dysregulation of [Ca

Genetic Impairment Of Succinate Metabolism Disrupts Bioenergetic Sensing In Adrenal Neuroendocrine Cancer, Priyanka Gupta, Keehn Strange, Rahul Telange, Ailan Guo, Heather Hatch, Amin Sobh, Jonathan Elie, Angela M Carter, John Totenhagen, Chunfeng Tan, Yogesh A Sonawane, Jiri Neuzil, Amarnath Natarajan, Ashley J Ovens, Jonathan S Oakhill, Thorsten Wiederhold, Karel Pacak, Hans K Ghayee, Laurent Meijer, Sushanth Reddy, James A Bibb

Faculty, Staff and Student Publications

Metabolic dysfunction mutations can impair energy sensing and cause cancer. Loss of function of the mitochondrial tricarboxylic acid (TCA) cycle enzyme subunit succinate dehydrogenase B (SDHB) results in various forms of cancer typified by pheochromocytoma (PC). Here we delineate a signaling cascade where the loss of SDHB induces the Warburg effect, triggers dysregulation of [Ca2+]i, and aberrantly activates calpain and protein kinase Cdk5, through conversion of its cofactor from p35 to p25. Consequently, aberrant Cdk5 initiates a phospho-signaling cascade where GSK3 inhibition inactivates energy sensing by AMP kinase through dephosphorylation of the AMP kinase γ subunit, PRKAG2. Overexpression of p25-GFP …

Poziotinib Inhibits Her2-Mutant-Driven Therapeutic Resistance And Multiorgan Metastasis In Breast Cancer, Rashi Kalra, Ching Hui Chen, Junkai Wang, Ahmad Bin Salam, Lacey E Dobrolecki, Alaina Lewis, Christina Sallas, Clayton C Yates, Carolina Gutierrez, Balasubramanyam Karanam, Meenakshi Anurag, Bora Lim, Matthew J Ellis, Shyam M Kavuri

Faculty, Staff and Student Publications

The pan-HER tyrosine kinase inhibitor (TKI) neratinib is therapeutically active against metastatic breast cancers harboring activating HER2 mutations, but responses are variable and often not durable. Here we demonstrate that recurrent HER2 mutations have differential effects on endocrine therapy responsiveness, metastasis, and pan-HER TKI therapeutic sensitivity. The prevalence and prognostic significance may also depend on whether the HER2 mutant has arisen in the context of lobular versus ductal histology. The most highly recurrent HER2 mutant, L755S, was particularly resistant to neratinib but sensitive to the pan-HER TKI poziotinib, alone or in combination with fulvestrant. Poziotinib reduced tumor growth, diminished multiorgan …

Effect Of The Covid-19 Pandemic On Seizure Control Status In Patients With Epilepsy, A A Asadi-Pooya, Seyed Ali Nabavizadeh, Mohsen Farazdaghi

Department of Neurology Faculty Papers

Background: Previous studies have shown that patients with epilepsy (PWE) perceived significant disruption in the quality and provision of care due to the coronavirus disease 2019 (COVID-19) pandemic. The present study aimed to investigate the effect of this pandemic on seizure control status and changes in seizure frequency in PWE.

Methods:A consecutive sample of adult PWE registered in the database of Shiraz Epilepsy Center (Shiraz, Iran) was included in the study. In July 2021, phone interviews were conducted with all selected patients. Information such as age, sex, last seizure, seizure type, and frequency during the 12 months before the …

Secure Human Action Recognition By Encrypted Neural Network Inference, Miran Kim, Xiaoqian Jiang, Kristin Lauter, Elkhan Ismayilzada, Shayan Shams

Faculty, Staff and Student Publications

Advanced computer vision technology can provide near real-time home monitoring to support "aging in place" by detecting falls and symptoms related to seizures and stroke. Affordable webcams, together with cloud computing services (to run machine learning algorithms), can potentially bring significant social benefits. However, it has not been deployed in practice because of privacy concerns. In this paper, we propose a strategy that uses homomorphic encryption to resolve this dilemma, which guarantees information confidentiality while retaining action detection. Our protocol for secure inference can distinguish falls from activities of daily living with 86.21% sensitivity and 99.14% specificity, with an average …

Good Scientific Practice In Eeg And Meg Research: Progress And Perspectives, Guiomar Niso, Laurens R Krol, Etienne Combrisson, A Sophie Dubarry, Madison A Elliott, Clément François, Yseult Héjja-Brichard, Sophie K Herbst, Karim Jerbi, Vanja Kovic, Katia Lehongre, Steven J Luck, Manuel Mercier, John C Mosher, Yuri G Pavlov, Aina Puce, Antonio Schettino, Daniele Schön, Walter Sinnott-Armstrong, Bertille Somon, Anđela Šoškić, Suzy J Styles, Roni Tibon, Martina G Vilas, Marijn Van Vliet, Maximilien Chaumon

Faculty, Staff and Student Publications

Good scientific practice (GSP) refers to both explicit and implicit rules, recommendations, and guidelines that help scientists to produce work that is of the highest quality at any given time, and to efficiently share that work with the community for further scrutiny or utilization. For experimental research using magneto- and electroencephalography (MEEG), GSP includes specific standards and guidelines for technical competence, which are periodically updated and adapted to new findings. However, GSP also needs to be regularly revisited in a broader light. At the LiveMEEG 2020 conference, a reflection on GSP was fostered that included explicitly documented guidelines and technical …

Relevance Of Medullary Vein Sign In Neurosarcoidosis, Richard Liberio, Emily Kramer, Anza B Memon, Ryan Reinbeau, Parissa Feizi, Joe Joseph, Janet Wu, Shitiz Sriwastava

Faculty, Staff and Student Publications

BACKGROUND: Central nervous system involvement is uncommon in patients with sarcoidosis. It remains a diagnostic challenge for clinicians, as there is a broad differential diagnosis that matches the presenting neurological signs. Often, the imaging findings also overlap with other disease entities. One understudied finding in patients with neurosarcoidosis is the presence of medullary vein engorgement on SWI imaging, termed the "medullary vein sign", which has been postulated to be a specific sign for neurosarcoidosis. This study aims to provide an understanding of the diagnostic potential of the medullary vein sign.

METHODS: Thirty-two patients who presented with neurologic signs concerning for …

Identification Of Missing Hierarchical Relations In The Vaccine Ontology Using Acquired Term Pairs, Warren Manuel, Rashmie Abeysinghe, Yongqun He, Cui Tao, Licong Cui

Faculty, Staff and Student Publications

Background

The Vaccine Ontology (VO) is a biomedical ontology that standardizes vaccine annotation. Errors in VO will affect a multitude of applications that it is being used in. Quality assurance of VO is imperative to ensure that it provides accurate domain knowledge to these downstream tasks. Manual review to identify and fix quality issues (such as missing hierarchical is-a relations) is challenging given the complexity of the ontology. Automated approaches are highly desirable to facilitate the quality assurance of VO.

Methods

We developed an automated lexical approach that identifies potentially missing is-a relations in VO. First, we construct two types …