Neurology Commons^™

Acupuncture Treatment For Post-Stroke Depression: Intestinal Microbiota And Its Role, Hailun Jiang, Shizhe Deng, Jieying Zhang, Junjie Chen, Boxuan Li, Weiming Zhu, Menglong Zhang, Chao Zhang, Zhihong Meng

Faculty, Staff and Student Publications

Stroke-induced depression is a common complication and an important risk factor for disability. Besides psychiatric symptoms, depressed patients may also exhibit a variety of gastrointestinal symptoms, and even take gastrointestinal symptoms as the primary reason for medical treatment. It is well documented that stress may disrupt the balance of the gut microbiome in patients suffering from post-stroke depression (PSD), and that disruption of the gut microbiome is closely related to the severity of the condition in depressed patients. Therefore, maintaining the balance of intestinal microbiota can be the focus of research on the mechanism of acupuncture in the treatment of …

Using Artificial Intelligence To Improve Pain Assessment And Pain Management: A Scoping Review, Meina Zhang, Linzee Zhu, Shih-Yin Lin, Keela Herr, Chih-Lin Chi, Ibrahim Demir, Karen Dunn Lopez, Nai-Ching Chi

Faculty, Staff and Student Publications

CONTEXT: Over 20% of US adults report they experience pain on most days or every day. Uncontrolled pain has led to increased healthcare utilization, hospitalization, emergency visits, and financial burden. Recognizing, assessing, understanding, and treating pain using artificial intelligence (AI) approaches may improve patient outcomes and healthcare resource utilization. A comprehensive synthesis of the current use and outcomes of AI-based interventions focused on pain assessment and management will guide the development of future research.

OBJECTIVES: This review aims to investigate the state of the research on AI-based interventions designed to improve pain assessment and management for adult patients. We also …

Response Assessment In Pediatric Craniopharyngioma: Recommendations From The Response Assessment In Pediatric Neuro-Oncology (Rapno) Working Group, Lindsey M Hoffman, Camilo Jaimes, Kshitij Mankad, David M Mirsky, Benita Tamrazi, Christopher L Tinkle, Cassie Kline, Aparna Ramasubramanian, Fatema Malbari, Ross Mangum, Holly Lindsay, Vincent Horne, David J Daniels, Sameer Keole, David R Grosshans, Tina Young Poussaint, Roger Packer, Sergio Cavalheiro, Brigitte Bison, Todd C Hankinson, Hermann L Müller, Ute Bartels, Katherine E Warren, Murali Chintagumpala

Faculty, Staff and Student Publications

BACKGROUND: Craniopharyngioma is a histologically benign tumor of the suprasellar region for which survival is excellent but quality of life is often poor secondary to functional deficits from tumor and treatment. Standard therapy consists of maximal safe resection with or without radiation therapy. Few prospective trials have been performed, and response assessment has not been standardized.

METHODS: The Response Assessment in Pediatric Neuro-Oncology (RAPNO) committee devised consensus guidelines to assess craniopharyngioma response prospectively.

RESULTS: Magnetic resonance imaging is the recommended radiologic modality for baseline and follow-up assessments. Radiologic response is defined by 2-dimensional measurements of both solid and cystic tumor …

Safety And Tolerability Of Ser-109 As An Investigational Microbiome Therapeutic In Adults With Recurrent Clostridioides Difficile Infection: A Phase 3, Open-Label, Single-Arm Trial, Matthew D Sims, Sahil Khanna, Paul Feuerstadt, Thomas J Louie, Colleen R Kelly, Edward S Huang, Elizabeth L Hohmann, Elaine E L Wang, Caterina Oneto, Stuart H Cohen, Charles S Berenson, Louis Korman, Christine Lee, Bret Lashner, Colleen S Kraft, Mayur Ramesh, Michael Silverman, Darrell S Pardi, Ananya De, Asli Memisoglu, David A Lombardi, Brooke R Hasson, Barbara H Mcgovern, Lisa Von Moltke

Faculty, Staff and Student Publications

IMPORTANCE: A safe and effective treatment for recurrent Clostridioides difficile infection (CDI) is urgently needed. Antibiotics kill toxin-producing bacteria but do not repair the disrupted microbiome, which promotes spore germination and infection recurrence.

OBJECTIVES: To evaluate the safety and rate of CDI recurrence after administration of investigational microbiome therapeutic SER-109 through 24 weeks.

DESIGN, SETTING, AND PARTICIPANTS: This phase 3, single-arm, open-label trial (ECOSPOR IV) was conducted at 72 US and Canadian outpatient sites from October 2017 to April 2022. Adults aged 18 years or older with recurrent CDI were enrolled in 2 cohorts: (1) rollover patients from the ECOSPOR …

The Gdf15-Gfral Axis Mediates Chemotherapy-Induced Fatigue In Mice, Brandon Chelette, Chinenye L Chidomere, Robert Dantzer

Faculty, Staff and Student Publications

Cancer-related fatigue is defined as a distressing persistent subjective sense of physical, emotional, and/or cognitive tiredness or exhaustion related to cancer or cancer treatment that is not proportional to recent activity and that interferes with usual functioning. This form of fatigue is highly prevalent during cancer treatment and in some patients, it can persist for years after treatment has ended. An understanding of the mechanisms that drive cancer-related fatigue is still lacking, which hampers the identification of effective treatment options. Various chemotherapeutic agents including cisplatin are known to induce mitochondrial dysfunction and this effect is known to mediate chemotherapy-induced peripheral …

Genetics And Pathogenesis Of Parkinson's Syndrome, Hui Ye, Laurie A Robak, Meigen Yu, Matthew Cykowski, Joshua M Shulman

Faculty, Staff and Students Publications

Parkinson's disease (PD) is clinically, pathologically, and genetically heterogeneous, resisting distillation to a single, cohesive disorder. Instead, each affected individual develops a virtually unique form of Parkinson's syndrome. Clinical manifestations consist of variable motor and nonmotor features, and myriad overlaps are recognized with other neurodegenerative conditions. Although most commonly characterized by alpha-synuclein protein pathology throughout the central and peripheral nervous systems, the distribution varies and other pathologies commonly modify PD or trigger similar manifestations. Nearly all PD is genetically influenced. More than 100 genes or genetic loci have been identified, and most cases likely arise from interactions among many common …

Circadian Rhythms As Modulators Of Brain Health During Development And Throughout Aging, Rachel Van Drunen, Kristin Eckel-Mahan

Faculty, Staff and Student Publications

The circadian clock plays a prominent role in neurons during development and throughout aging. This review covers topics pertinent to the role of 24-h rhythms in neuronal development and function, and their tendency to decline with aging. Pharmacological or behavioral modification that augment the function of our internal clock may be central to decline of cognitive disease and to future chronotherapy for aging-related diseases of the central nervous system.

Single-Cell Multi-Omics Integration For Unpaired Data By A Siamese Network With Graph-Based Contrastive Loss, Chaozhong Liu, Linhua Wang, Zhandong Liu

Faculty, Staff and Students Publications

BACKGROUND: Single-cell omics technology is rapidly developing to measure the epigenome, genome, and transcriptome across a range of cell types. However, it is still challenging to integrate omics data from different modalities. Here, we propose a variation of the Siamese neural network framework called MinNet, which is trained to integrate multi-omics data on the single-cell resolution by using graph-based contrastive loss.

RESULTS: By training the model and testing it on several benchmark datasets, we showed its accuracy and generalizability in integrating scRNA-seq with scATAC-seq, and scRNA-seq with epitope data. Further evaluation demonstrated our model's unique ability to remove the batch …

The Kynurenine Pathway In Alzheimer’S Disease: A Meta-Analysis Of Central And Peripheral Levels, Brisa S Fernandes, Mehmet Enes Inam, Nitesh Enduru, Joao Quevedo, Zhongming Zhao

Faculty, Staff and Student Publications

OBJECTIVE: Changes in the kynurenine pathway are recognized in psychiatric disorders, but their role in Alzheimer's disease (AD) is less clear. We aimed to conduct a systematic review and meta-analysis to determine whether tryptophan and kynurenine pathway metabolites are altered in AD.

METHODS: We performed a systematic review and random-effects meta-analyses. Inclusion criteria were studies that compared AD and cognitively normal (CN) groups and assessed tryptophan or kynurenine pathway metabolites in cerebrospinal fluid or peripheral blood.

RESULTS: Twenty-two studies with a total of 1,356 participants (664 with AD and 692 CN individuals) were included. Tryptophan was decreased only in peripheral …

Pediatric Traumatic Brain Injury In The Middle East And North Africa Region: A Systematic Review And Meta-Analysis To Assess Characteristics, Mechanisms, And Risk Factors, Samar Al-Hajj, Sarah H Farran, Batoul Dekmak, Layal Hneiny, Hussein Abou Abbas, Aya Hassoun, Nadine Youness, Sarah Ghalayini, Nour Abou Khalil, Fiona Lecky, Shima Shahjouieh, Layal Ghamlouche, Zainab Nasrallah, Firas Kobeissy

Faculty, Staff and Student Publications

Pediatric traumatic brain injury (pTBI) represents a major cause of child injuries in the Middle East and North Africa (MENA) region. This review aims to assess pTBIs in the MENA region and reports their clinical severity and outcomes. A search was conducted using major electronic databases, including Medline/Ovid, PubMed, EMBASE, Web of Science, and SCOPUS. Abstracts were screened independently and in duplicate to detect original research. The objective and study findings for each article were recorded, along with the mechanism of pTBI, patient age and sex, injury assessment tool(s) used, and outcome. A total of 1345 articles were retrieved, of …

Segmentation Of Acute Stroke Infarct Core Using Image-Level Labels On Ct-Angiography, Luca Giancardo, Arash Niktabe, Laura Ocasio, Rania Abdelkhaleq, Sergio Salazar-Marioni, Sunil A Sheth

Faculty, Staff and Student Publications

Acute ischemic stroke is a leading cause of death and disability in the world. Treatment decisions, especially around emergent revascularization procedures, rely heavily on size and location of the infarct core. Currently, accurate assessment of this measure is challenging. While MRI-DWI is considered the gold standard, its availability is limited for most patients suffering from stroke. Another well-studied imaging modality is CT-Perfusion (CTP) which is much more common than MRI-DWI in acute stroke care, but not as precise as MRI-DWI, and it is still unavailable in many stroke hospitals. A method to determine infarct core using CT-Angiography (CTA), a much …

Frontostriatal And Limbic Contributions To Cognitive Decline In Parkinson’S Disease, Gregory Brown, Jonathan Hakun, Mechelle M Lewis, Sol De Jesus, Guangwei Du, Paul J Eslinger, Lan Kong, Xuemei Huang

Faculty, Staff and Student Publications

BACKGROUND AND PURPOSE: The circuitry underlying heterogenous cognitive profiles in Parkinson's disease (PD) remains unclear. The purpose of this study is to investigate whether structural changes in frontostriatal and limbic pathways contribute to different cognitive trajectories in PD.

METHODS: We obtained clinical and multimodal MRI data from 120 control and 122 PD subjects without dementia or severe motor disability. T1/T2-weighted images estimated volume, and diffusion imaging evaluated fractional anisotropy (FA) of frontostriatal (striatum and frontostriatal white matter [FSWM]) and limbic (hippocampus and fornix) structures. Montreal Cognitive Assessment (MoCA) gauged total and domain-specific (attention/executive and memory) cognitive function. Linear mixed-effects models …

Editorial: Big Data Analytics To Advance Stroke And Cerebrovascular Disease: A Tool To Bridge Translational And Clinical Research, Alexis Nétis Simpkins, Hari Kishan Reddy Indupuru, Sean Isaac Savitz

Faculty, Staff and Student Publications

No abstract provided.

Preoperative Tractography Algorithm For Safe Resection Of Tumors Located In The Descending Motor Pathways Zone, Edgar G Ordonez-Rubiano, Jason M Johnson, Nadin Abdalá-Vargas, Oscar F Zorro, Jorge H Marin-Munoz, Ricardo Álvarez-Tobián, Valeria Forlizzi, Carlos Castillo Rangel, Sabino Luzzi, Alvaro Campero, Javier G Patiño-Gómez, Matias Baldoncini

Faculty, Staff and Student Publications

BACKGROUND: Diffusion tensor imaging (DTI) tractography facilitates maximal safe resection and optimizes planning to avoid injury during subcortical dissection along descending motor pathways (DMPs). We provide an affordable, safe, and timely algorithm for preoperative DTI motor reconstruction for gliomas adjacent to DMPs.

METHODS: Preoperative DTI reconstructions were extracted from a prospectively acquired registry of glioma resections adjacent to DMPs. The surgeries were performed over a 7-year period. Demographic, clinical, and radiographic data were extracted from patients' electronic medical records.

RESULTS: Nineteen patients (12 male) underwent preoperative tractography between January 1, 2013, and May 31, 2020. The average age was 44.5 …

Artificial Intelligence-Driven Meta-Analysis Of Brain Gene Expression Identifies Novel Gene Candidates And A Role For Mitochondria In Alzheimer’S Disease, Caitlin A Finney, Fabien Delerue, Wendy A Gold, David A Brown, Artur Shvetcov

Faculty, Staff and Student Publications

Alzheimer's disease (AD) is the most common form of dementia. There is no treatment and AD models have focused on a small subset of genes identified in familial AD. Microarray studies have identified thousands of dysregulated genes in the brains of patients with AD yet identifying the best gene candidates to both model and treat AD remains a challenge. We performed a meta-analysis of microarray data from the frontal cortex (n = 697) and cerebellum (n = 230) of AD patients and healthy controls. A two-stage artificial intelligence approach, with both unsupervised and supervised machine learning, combined with a functional …

Reactome Pathway Analysis From Whole-Blood Transcriptome Reveals Unique Characteristics Of Systemic Sclerosis Patients At The Preclinical Stage, Chiara Bellocchi, Xuan Wang, Marka A Lyons, Maurizio Marchini, Maurizio Lorini, Vincenzo Carbonelli, Nicola Montano, Shervin Assassi, Lorenzo Beretta

Faculty, Staff and Student Publications

OBJECTIVE: This study aims to characterize differential expressed pathways (DEP) in subjects with preclinical systemic sclerosis (PreSSc) characterized uniquely by Raynaud phenomenon, specific autoantibodies, and/or capillaroscopy positive for scleroderma pattern.

METHODS: Whole-blood samples from 33 PreSSc with clinical prospective data (baseline and after 4 years of follow-up) and 16 matched healthy controls (HC) were analyzed for global gene expression transcriptome analysis via RNA sequencing. Functional Analysis of Individual Microarray Expression method annotated Reactome individualized pathways. ANOVA analysis identified DEP whose predictive capability were tested in logistic regression models after extensive internal validation.

RESULTS: At 4 years, 42.4% subjects progressed (evolving …

Frequency And Burden Of Neurological Manifestations Upon Hospital Presentation In Covid-19 Patients: Findings From A Large Brazilian Cohort, Milena Soriano Marcolino, Fernando Anschau, Luciane Kopittke, Magda Carvalho Pires, Izabela Guimarães Barbosa, Daniella Nunes Pereira, Lucas Emanuel Ferreira Ramos, Luís Fernando Israel Assunção, André Soares De Moura Costa, Matheus Carvalho Alves Nogueira, Helena Duani, Karina Paula Medeiros Prado Martins, Leila Beltrami Moreira, Carla Thais Cândida Alves Da Silva, Neimy Ramos De Oliveira, Patricia Klarmann Ziegelmann, Milton Henriques Guimarães-Júnior, Mauro Oscar Soares De Souza Lima, Rubia Laura Oliveira Aguiar, Luanna Silva Monteiro Menezes, Talita Fischer Oliveira, Maíra Dias Souza, Bárbara Lopes Farace, Christiane Corrêa Rodrigues Cimini, Amanda De Oliveira Maurílio, Silvana Mangeon Mereilles Guimarães, Silvia Ferreira Araújo, Guilherme Fagundes Nascimento, Daniel Vitório Silveira, Karen Brasil Ruschel, Thainara Conceição De Oliveira, Alexandre Vargas Schwarzbold, Luiz Antônio Nasi, Maiara Anschau Floriani, Veridiana Baldon Dos Santos, Carolina Marques Ramos, Joice Coutinho De Alvarenga, Ana Luiza Bahia Alves Scotton, Euler Roberto Fernandes Manenti, Gabriela Petry Crestani, Joanna D'Arc Lyra Batista, Daniela Ponce, Juliana Machado-Rugolo, Adriana Falangola Benjamin Bezerra, Petrônio José De Lima Martelli, Heloisa Reniers Vianna, Luís César De Castro, Cássia Regina Gotler Medeiros, Giovanna Grunewald Vietta, Elayne Crestani Pereira, José Miguel Chatkin, Mariana Frizzo De Godoy, Polianna Delfino-Pereira, Antonio Lucio Teixeira

Faculty, Staff and Student Publications

BACKGROUND: Scientific data regarding the prevalence of COVID-19 neurological manifestations and prognosis in Latin America countries is still lacking. Therefore, the study aims to understand neurological manifestations of SARS-CoV 2 infection and outcomes in the Brazilian population.

METHODS: This study is part of the Brazilian COVID-19 Registry, a multicentric cohort, including data from 37 hospitals. For the present analysis, patients were grouped according to the presence of reported symptoms (i.e., headache; anosmia and ageusia; syncope and dizziness) vs. clinically-diagnosed neurological manifestations (clinically-defined neurological syndrome: neurological signs or diagnoses captured by clinical evaluation) and matched with patients without neurological manifestations by …

Detection Of Stroke With Retinal Microvascular Density And Self-Supervised Learning Using Oct-A And Fundus Imaging, Samiksha Pachade, Ivan Coronado, Rania Abdelkhaleq, Juntao Yan, Sergio Salazar-Marioni, Amanda Jagolino, Charles Green, Mozhdeh Bahrainian, Roomasa Channa, Sunil A Sheth, Luca Giancardo

Faculty, Staff and Student Publications

Acute cerebral stroke is a leading cause of disability and death, which could be reduced with a prompt diagnosis during patient transportation to the hospital. A portable retina imaging system could enable this by measuring vascular information and blood perfusion in the retina and, due to the homology between retinal and cerebral vessels, infer if a cerebral stroke is underway. However, the feasibility of this strategy, the imaging features, and retina imaging modalities to do this are not clear. In this work, we show initial evidence of the feasibility of this approach by training machine learning models using feature engineering …

Consistency Of Efficacy Results Across Various Clinical Measures And Statistical Methods In The Lecanemab Phase 2 Trial Of Early Alzheimer’S Disease, Shobha Dhadda, Michio Kanekiyo, David Li, Chad J Swanson, Michael Irizarry, Scott Berry, Lynn D Kramer, Donald A Berry

Faculty, Staff and Student Publications

BACKGROUND: Lecanemab (BAN2401) is a humanized IgG1 monoclonal antibody that preferentially targets soluble aggregated Aβ species (protofibrils) with activity at insoluble fibrils and slowed clinical decline in an 18-month phase 2 proof-of-concept study (Study 201; ClinicalTrials.gov NCT01767311) in 856 subjects with early Alzheimer's disease (AD). In this trial, subjects were randomized to five lecanemab dose regimens or placebo. The primary efficacy endpoint was change from baseline in the Alzheimer's Disease Composite Score (ADCOMS) at 12 months with Bayesian analyses. The key secondary endpoints were ADCOMS at 18 months and Clinical Dementia Rating-Sum-of-Boxes (CDR-SB) and Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog14) …

Treatment Of Epilepsy Using A Targeted P38Γ Kinase Gene Therapy, Nicolle Morey, Magdalena Przybyla, Julia Van Der Hoven, Yazi D Ke, Fabien Delerue, Janet Van Eersel, Lars M Ittner

Faculty, Staff and Student Publications

Hyperphosphorylated microtubule-associated protein tau has been implicated in dementia, epilepsy, and other neurological disorders. In contrast, site-specific phosphorylation of tau at threonine 205 (T205) by the kinase p38γ was shown to disengage tau from toxic pathways, serving a neuroprotective function in Alzheimer's disease. Using a viral-mediated gene delivery approach in different mouse models of epilepsy, we show that p38γ activity-enhancing treatment reduces seizure susceptibility, restores neuronal firing patterns, reduces behavioral deficits, and ameliorates epilepsy-induced deaths. Furthermore, we show that p38γ-mediated phosphorylation of tau at T205 is essential for this protection in epilepsy, as a lack of this critical interaction reinstates …

Massive Macroglossia, A Rare Side Effect Of Covid-19: Clinical, Histologic, And Genomic Findings In Covid-19-Positive Versus Covid-19-Negative Patients, Victoria A Mañón, David Chubb, Laura S Farach, Rachid Karam, Mary C Farach-Carson, Nadarajah Vigneswaran, Karan Saluja, Simon Young, Mark Wong, James C Melville

Faculty, Staff and Student Publications

PURPOSE: The primary purpose of this study is to identify if there is an underlying genetic predisposition for COVID-related macroglossia and if this susceptibility is higher among individuals of African heritage. Secondary objectives include determining if genetic testing of COVID-infected patients who are intubated and prone could identify patients with higher susceptibility to the development of macroglossia.

METHODS: A retrospective chart review was completed for each patient, and prospectively, genetic and histopathologic analyses were completed. Whole-exome sequencing was completed on two patients; immunohistochemistry was completed on the COVID-positive tissue samples.

RESULTS: Histopathology of the COVID-positive patient revealed significant peri-lymphocytic infiltrate, …

Notch Missense Mutations In Drosophila Reveal Functions Of Specific Egf-Like Repeats In Notch Folding, Trafficking, And Signaling, Hilman Nurmahdi, Mao Hasegawa, Elzava Yuslimatin Mujizah, Takeshi Sasamura, Mikiko Inaki, Shinya Yamamoto, Tomoko Yamakawa, Kenji Matsuno

Duncan NRI Faculty and Staff Publications

Notch signaling plays various roles in cell-fate specification through direct cell–cell interactions. Notch receptors are evolutionarily conserved transmembrane proteins with multiple epidermal growth factor (EGF)-like repeats. Drosophila Notch has 36 EGF-like repeats, and while some play a role in Notch signaling, the specific functions of most remain unclear. To investigate the role of each EGF-like repeat, we used 19 previously identified missense mutations of Notch with unique amino acid substitutions in various EGF-like repeats and a transmembrane domain; 17 of these were identified through a single genetic screen. We assessed these mutants’ phenotypes in the nervous system and hindgut during …

Preconditioning By Voluntary Wheel Running Attenuates Later Neuropathic Pain Via Nuclear Factor E2-Related Factor 2 Antioxidant Signaling In Rats, Suzanne M Green-Fulgham, Michael E Harland, Jayson B Ball, Jiahe Li, Michael J Lacagnina, Heather D'Angelo, Renee A Dreher, Kendal F Willcox, Sabina A Lorca, Andrew J Kwilasz, Steven F Maier, Linda R Watkins, Peter M Grace

Faculty, Staff and Student Publications

Animal and human studies have shown that exercise prior to nerve injury prevents later chronic pain, but the mechanisms of such preconditioning remain elusive. Given that exercise acutely increases the formation of free radicals, triggering antioxidant compensation, we hypothesized that voluntary running preconditioning would attenuate neuropathic pain by supporting redox homeostasis after sciatic nerve injury in male and female rats. We show that 6 weeks of voluntary wheel running suppresses neuropathic pain development induced by chronic constriction injury across both sexes. This attenuation was associated with reduced nitrotyrosine immunoreactivity-a marker for peroxynitrite-at the sciatic nerve injury site. Our data suggest …

A Population-Based Meta-Analysis Of Circulating Gfap For Cognition And Dementia Risk, Mitzi M Gonzales, Crystal Wiedner, Chen-Pin Wang, Qianqian Liu, Joshua C Bis, Zhiguang Li, Jayandra J Himali, Saptaparni Ghosh, Emy A Thomas, Danielle M Parent, Tiffany F Kautz, Matthew P Pase, Hugo J Aparicio, Luc Djoussé, Kenneth J Mukamal, Bruce M Psaty, William T Longstreth, Thomas H Mosley, Vilmundur Gudnason, Djass Mbangdadji, Oscar L Lopez, Kristine Yaffe, Stephen Sidney, R Nick Bryan, Ilya M Nasrallah, Charles S Decarli, Alexa S Beiser, Lenore J Launer, Myriam Fornage, Russell P Tracy, Sudha Seshadri, Claudia L Satizabal

Faculty, Staff and Student Publications

Objective: Expression of glial fibrillary acidic protein (GFAP), a marker of reactive astrocytosis, colocalizes with neuropathology in the brain. Blood levels of GFAP have been associated with cognitive decline and dementia status. However, further examinations at a population-based level are necessary to broaden generalizability to community settings.

Methods: Circulating GFAP levels were assayed using a Simoa HD-1 analyzer in 4338 adults without prevalent dementia from four longitudinal community-based cohort studies. The associations between GFAP levels with general cognition, total brain volume, and hippocampal volume were evaluated with separate linear regression models in each cohort with adjustment for age, sex, education, …

Towards Quality Improvement Of Vaccine Concept Mappings In The Omop Vocabulary With A Semi-Automated Method, Rashmie Abeysinghe, Adam Black, Denys Kaduk, Yupeng Li, Christian Reich, Alexander Davydov, Lixia Yao, Licong Cui

Faculty, Staff and Student Publications

The Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM) provides a unified model to integrate disparate real-world data (RWD) sources. An integral part of the OMOP CDM is the Standardized Vocabularies (henceforth referred to as the OMOP vocabulary), which enables organization and standardization of medical concepts across various clinical domains of the OMOP CDM. For concepts with the same meaning from different source vocabularies, one is designated as the standard concept, while the others are specified as non-standard or source concepts and mapped to the standard one. However, due to the heterogeneity of source vocabularies, there may exist mapping …

Loss Of Lamp5 Interneurons Drives Neuronal Network Dysfunction In Alzheimer’S Disease, Yuanyuan Deng, Mian Bi, Fabien Delerue, Shelley L Forrest, Gabriella Chan, Julia Van Der Hoven, Annika Van Hummel, Astrid F Feiten, Seojin Lee, Ivan Martinez-Valbuena, Tim Karl, Gabor G Kovacs, Grant Morahan, Yazi D Ke, Lars M Ittner

Faculty, Staff and Student Publications

In Alzheimer's disease (AD), where amyloid-β (Aβ) and tau deposits in the brain, hyperexcitation of neuronal networks is an underlying disease mechanism, but its cause remains unclear. Here, we used the Collaborative Cross (CC) forward genetics mouse platform to identify modifier genes of neuronal hyperexcitation. We found LAMP5 as a novel regulator of hyperexcitation in mice, critical for the survival of distinct interneuron populations. Interestingly, synaptic LAMP5 was lost in AD brains and LAMP5 interneurons degenerated in different AD mouse models. Genetic reduction of LAMP5 augmented functional deficits and neuronal network hypersynchronicity in both Aβ- and tau-driven AD mouse models. …

Transcranial Magnetic Stimulation (Tms) Seeded Tractography Provides Superior Prediction Of Eloquence Compared To Anatomic Seeded Tractography, Matthew Muir, Sarah Prinsloo, Hayley Michener, Arya Shetty, Dhiego Chaves De Almeida Bastos, Jeffrey Traylor, Chibawanye Ene, Sudhakar Tummala, Vinodh A Kumar, Sujit S Prabhu

Faculty, Staff and Student Publications

BACKGROUND: For patients with brain tumors, maximizing the extent of resection while minimizing postoperative neurological morbidity requires accurate preoperative identification of eloquent structures. Recent studies have provided evidence that anatomy may not always predict eloquence. In this study, we directly compare transcranial magnetic stimulation (TMS) data combined with tractography to traditional anatomic grading criteria for predicting permanent deficits in patients with motor eloquent gliomas.

METHODS: We selected a cohort of 42 glioma patients with perirolandic tumors who underwent preoperative TMS mapping with subsequent resection and intraoperative mapping. We collected clinical outcome data from their chart with the primary outcome being …

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 …

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 …

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 …