Neurosciences Commons^™

See Me, Hear Me, Know Me: Perspectives On Diet And Physical Activity Influences Among Teens Living In Rural Texas Communities, Debbe Thompson, Julie Miranda, Chishinga Callender, Jayna M Dave, Godlove Appiah, Salma M A Musaad

Faculty, Staff and Students Publications

Teens in rural communities are at greater risk of obesity than teens in urban areas. Diet and physical activity influence obesity risk. Understanding their perspectives is an important step in intervention design. This qualitative investigation explored teen perspectives on how living in a rural community influenced their diet and physical activity choices. Forty parent-teen pairs were recruited. Data collection included surveys and telephone interviews. This paper reports teen perspectives identified in the first interview. Thematic analysis was used to code and analyze the data. Findings revealed that the primary factor driving teens' diet and physical activity behaviors was the teens …

Therapeutic Implications Of Impaired Nuclear Receptor Function And Dysregulated Metabolism In Wilson’S Disease, Clavia Ruth Wooton-Kee

Faculty, Staff and Students Publications

Copper is an essential trace element that is required for the activity of many enzymes and cellular processes, including energy homeostasis and neurotransmitter biosynthesis; however, excess copper accumulation results in significant cellular toxicity. The liver is the major organ for maintaining copper homeostasis. Inactivating mutations of the copper-transporting P-type ATPase, ATP7B, result in Wilson’s disease, an autosomal recessive disorder that requires life-long medicinal therapy or liver transplantation. Current treatment protocols are limited to either sequestration of copper via chelation or reduction of copper absorption in the gut (zinc therapy). The goal of these strategies is to reduce free copper, redox …

Importance Of Health Policy And Systems Research For Strengthening Rehabilitation In Health Systems: A Call To Action To Accelerate Progress, Walter R Frontera, Wouter Degroote, Abdul Ghaffar, Health Policy & Systems Research For Rehabilitation Group

Faculty, Staff and Student Publications

No abstract provided.

The Development, Content And Response Process Validation Of A Caregiver-Reported Severity Measure For Cdkl5 Deficiency Disorder, Sonja I Ziniel, Alexandra Mackie, Jacinta Saldaris, Helen Leonard, Peter Jacoby, Eric D Marsh, Bernhard Suter, Elia Pestana-Knight, Heather E Olson, Dana Price, Judith Weisenberg, Rajsekar Rajaraman, Gina Vanderveen, Tim A Benke, Jenny Downs, Scott Demarest

Faculty, Staff and Students Publications

BACKGROUND: CDKL5 Deficiency Disorder (CDD) is a severe X-linked developmental and epileptic encephalopathy. Existing developmental outcome measures have floor effects and cannot capture incremental changes in symptoms. We modified the caregiver portion of a CDD clinical severity assessment (CCSA) and assessed content and response-process validity.

METHODS: We conducted cognitive interviews with 15 parent caregivers of 1-39-year-old children with CDD. Caregivers discussed their understanding and concerns regarding appropriateness of both questions and answer options. Item wording and questionnaire structure were adjusted iteratively to ensure questions were understood as intended.

RESULTS: The CCSA was refined during three rounds of cognitive interviews into …

Dicarboxylic Acylcarnitine Biomarkers In Peroxisome Biogenesis Disorders, Michael F Wangler, Barbara Lesko, Rejwi Dahal, Sharayu Jangam, Pradnya Bhadane, Theodore E Wilson, Molly Mcpheron, Marcus J Miller

Duncan NRI Faculty and Staff Publications

The peroxisome is an essential eukaryotic organelle with diverse metabolic functions. Inherited peroxisomal disorders are associated with a wide spectrum of clinical outcomes and are broadly divided into two classes, those impacting peroxisome biogenesis (PBD) and those impacting specific peroxisomal factors. Prior studies have indicated a role for acylcarnitine testing in the diagnosis of some peroxisomal diseases through the detection of long chain dicarboxylic acylcarnitine abnormalities (C16-DC and C18-DC). However, there remains limited independent corroboration of these initial findings and acylcarnitine testing for peroxisomal diseases has not been widely adopted in clinical laboratories. To explore the utility of acylcarnitine testing …

Untargeted Metabolomic Analysis Investigating Links Between Unprocessed Red Meat Intake And Markers Of Inflammation, Alexis C Wood, Goncalo Graca, Meghana Gadgil, Mackenzie K Senn, Matthew A Allison, Ioanna Tzoulaki, Philip Greenland, Timothy Ebbels, Paul Elliott, Mark O Goodarzi, Russell Tracy, Jerome I Rotter, David Herrington

Faculty, Staff and Students Publications

BACKGROUND: Whether red meat consumption is associated with higher inflammation or confounded by increased adiposity remains unclear. Plasma metabolites capture the effects of diet after food is processed, digested, and absorbed, and correlate with markers of inflammation, so they can help clarify diet-health relationships.

OBJECTIVE: To identify whether any metabolites associated with red meat intake are also associated with inflammation.

METHODS: A cross-sectional analysis of observational data from older adults (52.84% women, mean age 63 ± 0.3 y) participating in the Multi-Ethnic Study of Atherosclerosis (MESA). Dietary intake was assessed by food-frequency questionnaire, alongside C-reactive protein (CRP), interleukin-2, interleukin-6, fibrinogen, …

Anthocyanins: Molecular Aspects On Their Neuroprotective Activity, César A Zaa, Álvaro J Marcelo, Zhiqiang An, José L Medina-Franco, Marco A Velasco-Velázquez

Faculty, Staff and Student Publications

Anthocyanins are a type of flavonoids that give plants and fruits their vibrant colors. They are known for their potent antioxidant properties and have been linked to various health benefits. Upon consumption, anthocyanins are quickly absorbed and can penetrate the blood-brain barrier (BBB). Research based on population studies suggests that including anthocyanin-rich sources in the diet lower the risk of neurodegenerative diseases. Anthocyanins exhibit neuroprotective effects that could potentially alleviate symptoms associated with such diseases. In this review, we compiled and discussed a large body of evidence supporting the neuroprotective role of anthocyanins. Our examination encompasses human studies, animal models, …

Rna-Based Translation Activators For Targeted Gene Upregulation, Yang Cao, Huachun Liu, Shannon S Lu, Krysten A Jones, Anitha P Govind, Okunola Jeyifous, Christine Q Simmons, Negar Tabatabaei, William N Green, Jimmy L Holder, Soroush Tahmasebi, Alfred L George, Bryan C Dickinson

Duncan NRI Faculty and Staff Publications

Technologies capable of programmable translation activation offer strategies to develop therapeutics for diseases caused by insufficient gene expression. Here, we present "translation-activating RNAs" (taRNAs), a bifunctional RNA-based molecular technology that binds to a specific mRNA of interest and directly upregulates its translation. taRNAs are constructed from a variety of viral or mammalian RNA internal ribosome entry sites (IRESs) and upregulate translation for a suite of target mRNAs. We minimize the taRNA scaffold to 94 nucleotides, identify two translation initiation factor proteins responsible for taRNA activity, and validate the technology by amplifying SYNGAP1 expression, a haploinsufficiency disease target, in patient-derived cells. …

Neuromyelitis Optica Spectrum Disorder: Redefining An Old Disease Present And Future Challenges, Victor M Rivera

Faculty, Staff and Students Publications

No abstract provided.

Top Caregiver Concerns In Rett Syndrome And Related Disorders: Data From The Us Natural History Study, Jeffrey L Neul, Timothy A Benke, Eric D Marsh, Bernhard Suter, Lori Silveira, Cary Fu, Sarika U Peters, Alan K Percy

Faculty, Staff and Students Publications

OBJECTIVE: Recent advances in the understanding of neurodevelopmental disorders such as Rett syndrome (RTT) have enabled the discovery of novel therapeutic approaches that require formal clinical evaluation of efficacy. Clinical trial success depends on outcome measures that assess clinical features that are most impactful for affected individuals. To determine the top concerns in RTT and RTT-related disorders we asked caregivers to list the top caregiver concerns to guide the development and selection of appropriate clinical trial outcome measures for these disorders.

METHODS: Caregivers of participants enrolled in the US Natural History Study of RTT and RTT-related disorders (n = 925) …

Super-Enhancer Hijacking Drives Ectopic Expression Of Hedgehog Pathway Ligands In Meningiomas, Mark W Youngblood, Zeynep Erson-Omay, Chang Li, Hinda Najem, Süleyman Coșkun, Evgeniya Tyrtova, Julio D Montejo, Danielle F Miyagishima, Tanyeri Barak, Sayoko Nishimura, Akdes Serin Harmancı, Victoria E Clark, Daniel Duran, Anita Huttner, Timuçin Avşar, Yasar Bayri, Johannes Schramm, Julien Boetto, Matthieu Peyre, Maximilien Riche, Roland Goldbrunner, Nduka Amankulor, Angeliki Louvi, Kaya Bilgüvar, M Necmettin Pamir, Koray Özduman, Türker Kilic, James R Knight, Matthias Simon, Craig Horbinski, Michel Kalamarides, Marco Timmer, Amy B Heimberger, Ketu Mishra-Gorur, Jennifer Moliterno, Katsuhito Yasuno, Murat Günel

Faculty, Staff and Students Publications

Hedgehog signaling mediates embryologic development of the central nervous system and other tissues and is frequently hijacked by neoplasia to facilitate uncontrolled cellular proliferation. Meningiomas, the most common primary brain tumor, exhibit Hedgehog signaling activation in 6.5% of cases, triggered by recurrent mutations in pathway mediators such as SMO. In this study, we find 35.6% of meningiomas that lack previously known drivers acquired various types of somatic structural variations affecting chromosomes 2q35 and 7q36.3. These cases exhibit ectopic expression of Hedgehog ligands, IHH and SHH, respectively, resulting in Hedgehog signaling activation. Recurrent tandem duplications involving IHH permit de novo chromatin …

Comparative Genomic Landscape Of Urothelial Carcinoma Of The Bladder Among Patients Of East And South Asian Genomic Ancestry, Taylor Peak, Philippe E Spiess, Roger Li, Petros Grivas, Andrea Necchi, Dean Pavlick, Richard S P Huang, Douglas Lin, Natalie Danziger, Joseph M Jacob, Gennady Bratslavsky, Jeffrey S Ross

Faculty, Staff and Student Publications

BACKGROUND: Despite the low rate of urothelial carcinoma of the bladder (UCB) in patients of South Asian (SAS) and East Asian (EAS) descent, they make up a significant portion of the cases worldwide. Nevertheless, these patients are largely under-represented in clinical trials. We queried whether UCB arising in patients with SAS and EAS ancestry would have unique genomic features compared to the global cohort.

METHODS: Formalin-fixed, paraffin-embedded tissue was obtained for 8728 patients with advanced UCB. DNA was extracted and comprehensive genomic profiling was performed. Ancestry was classified using a proprietary calculation algorithm. Genomic alterations (GAs) were determined using a …

Cardiac Magnetic Resonance Imaging To Determine Single Ventricle Function In A Pediatric Population Is Feasible In A Large Trial Setting: Experience From The Single Ventricle Reconstruction Trial Longitudinal Follow Up, Jon Detterich, Michael D Taylor, Timothy C Slesnick, Michael Dilorenzo, Anthony Hlavacek, Christopher Z Lam, Shagun Sachdeva, Sean M Lang, M Jay Campbell, Jennifer Gerardin, Kevin K Whitehead, Rahul H Rathod, Mark Cartoski, Shaji Menon, Felicia Trachtenberg, Russell Gongwer, Jane Newburger, Caren Goldberg, Adam L Dorfman, The Pediatric Heart Network Investigators

Faculty, Staff and Students Publications

The Single Ventricle Reconstruction (SVR) Trial was a randomized prospective trial designed to determine survival advantage of the modified Blalock-Taussig-Thomas shunt (BTTS) vs the right ventricle to pulmonary artery conduit (RVPAS) for patients with hypoplastic left heart syndrome. The primary aim of the long-term follow-up (SVRIII) was to determine the impact of shunt type on RV function. In this work, we describe the use of CMR in a large cohort follow up from the SVR Trial as a focused study of single ventricle function. The SVRIII protocol included short axis steady-state free precession imaging to assess single ventricle systolic function …

Expert Panel Curation Of 113 Primary Mitochondrial Disease Genes For The Leigh Syndrome Spectrum, Elizabeth M Mccormick, Kierstin Keller, Julie P Taylor, Alison J Coffey, Lishuang Shen, Danuta Krotoski, Brian Harding, Xiaowu Gai, Marni J Falk, Zarazuela Zolkipli-Cunningham, Shamima Rahman

Children’s Nutrition Research Center Staff Publications

Objective: Primary mitochondrial diseases (PMDs) are heterogeneous disorders caused by inherited mitochondrial dysfunction. Classically defined neuropathologically as subacute necrotizing encephalomyelopathy, Leigh syndrome spectrum (LSS) is the most frequent manifestation of PMD in children, but may also present in adults. A major challenge for accurate diagnosis of LSS in the genomic medicine era is establishing gene-disease relationships (GDRs) for this syndrome with >100 monogenic causes across both nuclear and mitochondrial genomes.

Methods: The Clinical Genome Resource (ClinGen) Mitochondrial Disease Gene Curation Expert Panel (GCEP), comprising 40 international PMD experts, met monthly for 4 years to review GDRs for LSS. The GCEP …

Can Craniosynostosis Be Diagnosed On Physical Examination? A Retrospective Review, Carmen A Zavala, Laura A Zima, Matthew R Greives, Stephen A Fletcher, Manish N Shah, Brandon A Miller, David I Sandberg, Phuong D Nguyen

Faculty, Staff and Student Publications

Craniosynostosis is a developmental craniofacial defect in which one or more sutures of the skull fuse together prematurely. Uncorrected craniosynostosis may have serious complications including elevated intracranial pressure, developmental delay, and blindness. Proper diagnosis of craniosynostosis requires a physical examination of the head with assessment for symmetry and palpation of sutures for prominence. Often, if craniosynostosis is suspected, computed tomography (CT) imaging will be obtained. Recent literature has posited that this is unnecessary. This study aims to address whether physical examination alone is sufficient for the diagnosis and treatment planning of single suture craniosynostosis. Between 2015 and 2022, the Divisions …

A Cross-Species Proteomic Map Reveals Neoteny Of Human Synapse Development, Li Wang, Kaifang Pang, Li Zhou, Arantxa Cebrián-Silla, Susana González-Granero, Shaohui Wang, Qiuli Bi, Matthew L White, Brandon Ho, Jiani Li, Tao Li, Yonatan Perez, Eric J Huang, Ethan A Winkler, Mercedes F Paredes, Rothem Kovner, Nenad Sestan, Alex A Pollen, Pengyuan Liu, Jingjing Li, Xianhua Piao, José Manuel García-Verdugo, Arturo Alvarez-Buylla, Zhandong Liu, Arnold R Kriegstein

Faculty, Staff and Students Publications

The molecular mechanisms and evolutionary changes accompanying synapse development are still poorly understood1,2. Here we generate a cross-species proteomic map of synapse development in the human, macaque and mouse neocortex. By tracking the changes of more than 1,000 postsynaptic density (PSD) proteins from midgestation to young adulthood, we find that PSD maturation in humans separates into three major phases that are dominated by distinct pathways. Cross-species comparisons reveal that human PSDs mature about two to three times slower than those of other species and contain higher levels of Rho guanine nucleotide exchange factors (RhoGEFs) in the …

Clinical Genome Sequencing: Three Years’ Experience At A Tertiary Children’S Hospital, Runjun D Kumar, Lisa F Saba, Haley Streff, Chad A Shaw, Elizabeth Mizerik, Matthew T Snyder, Dolores Lopez-Terrada, Jennifer Scull

Duncan NRI Faculty and Staff Publications

Purpose: Genome sequencing (GS) may shorten the diagnostic odyssey for patients, but clinical experience with this assay in nonresearch settings remains limited. Texas Children's Hospital began offering GS as a clinical test to admitted patients in 2020, providing an opportunity to study GS utilization, possibilities for test optimization, and testing outcomes.

Methods: We retrospectively reviewed GS orders for admitted patients for a nearly 3-year period from March 2020 through December 2022. We gathered anonymized clinical data from the electronic health record to answer the study questions.

Results: The diagnostic yield over 97 admitted patients was 35%. The majority of GS …

Associations Between Metabolomic Biomarkers Of Avocado Intake And Glycemia In The Multi-Ethnic Study Of Atherosclerosis, Alexis C Wood, Mark O Goodarzi, Mackenzie K Senn, Meghana D Gadgil, Goncalo Graca, Matthew A Allison, Ioanna Tzoulaki, Michael Y Mi, Philip Greenland, Timothy Ebbels, Paul Elliott, Russell P Tracy, David M Herrington, Jerome I Rotter

Faculty, Staff and Students Publications

BACKGROUND: Avocado consumption is linked to better glucose homeostasis, but small associations suggest potential population heterogeneity. Metabolomic data capture the effects of food intake after digestion and metabolism, thus accounting for individual differences in these processes.

OBJECTIVES: To identify metabolomic biomarkers of avocado intake and to examine their associations with glycemia.

METHODS: Baseline data from 6224 multi-ethnic older adults (62% female) included self-reported avocado intake, fasting glucose and insulin, and untargeted plasma proton nuclear magnetic resonance metabolomic features (metabolomic data were available for a randomly selected subset; N = 3438). Subsequently, incident type 2 diabetes (T2D) was assessed over an …

Novel Genetic And Phenotypic Expansion In Gosr2-Related Progressive Myoclonus Epilepsy, Lea Hentrich, Mered Parnes, Timothy Edward Lotze, Rohini Coorg, Tom J De Koning, Kha M Nguyen, Calvin K Yip, Heinz Jungbluth, Anne Koy, Hormos Salimi Dafsari

Faculty, Staff and Students Publications

Biallelic variants in the Golgi SNAP receptor complex member 2 gene (GOSR2) have been reported in progressive myoclonus epilepsy with neurodegeneration. Typical clinical features include ataxia and areflexia during early childhood, followed by seizures, scoliosis, dysarthria, and myoclonus. Here, we report two novel patients from unrelated families with a GOSR2-related disorder and novel genetic and clinical findings. The first patient, a male compound heterozygous for the GOSR2 splice site variant c.336+1G>A and the novel c.364G>A,p.Glu122Lys missense variant showed global developmental delay and seizures at the age of 2 years, followed by myoclonus at the age …

Transcriptomic Analysis Of Stem Cells From Chorionic Villi Uncovers The Impact Of Chromosomes 2, 6 And 22 In The Clinical Manifestations Of Down Syndrome, Salvatore Vaiasicca, Gianmarco Melone, David W James, Marcos Quintela, Alessandra Preziuso, Richard H Finnell, Robert Steven Conlan, Lewis W Francis, Bruna Corradetti

Faculty, Staff and Students Publications

BACKGROUND: Down syndrome (DS) clinical multisystem condition is generally considered the result of a genetic imbalance generated by the extra copy of chromosome 21. Recent discoveries, however, demonstrate that the molecular mechanisms activated in DS compared to euploid individuals are more complex than previously thought. Here, we utilize mesenchymal stem cells from chorionic villi (CV) to uncover the role of comprehensive functional genomics-based understanding of DS complexity.

METHODS: Next-generation sequencing coupled with bioinformatic analysis was performed on CV obtained from women carrying fetuses with DS (DS-CV) to reveal specific genome-wide transcriptional changes compared to their euploid counterparts. Functional assays were …

Association Between Alcohol Consumption And Ectopic Fat In The Multi-Ethnic Study Of Atherosclerosis, Richard Kazibwe, Parag A Chevli, Joni K Evans, Matthew Allison, Erin D Michos, Alexis C Wood, Jingzhong Ding, Michael D Shapiro, Morgana Mongraw-Chaffin

Faculty, Staff and Students Publications

Background The relationship between alcohol consumption and ectopic fat distribution, both known factors for cardiovascular disease, remains understudied. Therefore, we aimed to examine the association between alcohol consumption and ectopic adiposity in adults at risk for cardiovascular disease. Methods and Results In this cross-sectional analysis, we categorized alcohol intake among participants in MESA (Multi-Ethnic Study of Atherosclerosis) as follows (drinks/day): <1 >(light drinking), 1 to 2 (moderate drinking), >2 (heavy drinking), former drinking, and lifetime abstention. Binge drinking was defined as consuming ≥5 drinks on 1 occasion in the past month. Visceral, subcutaneous, and intermuscular fat area, pericardial fat volume, and …

Decoding Depression Severity From Intracranial Neural Activity, Jiayang Xiao, Nicole R Provenza, Joseph Asfouri, John Myers, Raissa K Mathura, Brian Metzger, Joshua A Adkinson, Anusha B Allawala, Victoria Pirtle, Denise Oswalt, Ben Shofty, Meghan E Robinson, Sanjay J Mathew, Wayne K Goodman, Nader Pouratian, Paul R Schrater, Ankit B Patel, Andreas S Tolias, Kelly R Bijanki, Xaq Pitkow, Sameer A Sheth

Faculty, Staff and Students Publications

BACKGROUND: Disorders of mood and cognition are prevalent, disabling, and notoriously difficult to treat. Fueling this challenge in treatment is a significant gap in our understanding of their neurophysiological basis.

METHODS: We recorded high-density neural activity from intracranial electrodes implanted in depression-relevant prefrontal cortical regions in 3 human subjects with severe depression. Neural recordings were labeled with depression severity scores across a wide dynamic range using an adaptive assessment that allowed sampling with a temporal frequency greater than that possible with typical rating scales. We modeled these data using regularized regression techniques with region selection to decode depression severity from …

Beyond The Symptom: The Biology Of Fatigue, David M Raizen, Janet Mullington, Christelle Anaclet, Gerard Clarke, Hugo Critchley, Robert Dantzer, Ronald Davis, Kelly L Drew, Josh Fessel, Patrick M Fuller, Erin M Gibson, Mary Harrington, W Ian Lipkin, Elizabeth B Klerman, Nancy Klimas, Anthony L Komaroff, Walter Koroshetz, Lauren Krupp, Anna Kuppuswamy, Julie Lasselin, Laura D Lewis, Pierre J Magistretti, Heidi Y Matos, Christine Miaskowski, Andrew H Miller, Avindra Nath, Maiken Nedergaard, Mark R Opp, Marylyn D Ritchie, Dragana Rogulja, Asya Rolls, John D Salamone, Clifford Saper, Vicky Whittemore, Glenn Wylie, Jarred Younger, Phyllis C Zee, H Craig Heller

Faculty, Staff and Student Publications

A workshop titled "Beyond the Symptom: The Biology of Fatigue" was held virtually September 27-28, 2021. It was jointly organized by the Sleep Research Society and the Neurobiology of Fatigue Working Group of the NIH Blueprint Neuroscience Research Program. For access to the presentations and video recordings, see: https://neuroscienceblueprint.nih.gov/about/event/beyond-symptom-biology-fatigue. The goals of this workshop were to bring together clinicians and scientists who use a variety of research approaches to understand fatigue in multiple conditions and to identify key gaps in our understanding of the biology of fatigue. This workshop summary distills key issues discussed in this workshop and provides a …

Genetic Susceptibility To Cognitive Decline Following Craniospinal Irradiation For Pediatric Central Nervous System Tumors, Austin L Brown, Pagna Sok, Kimberly P Raghubar, Philip J Lupo, Melissa A Richard, Alanna C Morrison, Jun J Yang, Clinton F Stewart, Mehmet Fatih Okcu, Murali M Chintagumpala, Amar Gajjar, Lisa S Kahalley, Heather Conklin, Michael E Scheurer

Faculty, Staff and Student Publications

BACKGROUND: Survivors of pediatric central nervous system (CNS) tumors treated with craniospinal irradiation (CSI) exhibit long-term cognitive difficulties. Goals of this study were to evaluate longitudinal effects of candidate and novel genetic variants on cognitive decline following CSI.

METHODS: Intelligence quotient (IQ), working memory (WM), and processing speed (PS) were longitudinally collected from patients treated with CSI (n = 241). Genotype-by-time interactions were evaluated using mixed-effects linear regression to identify common variants (minor allele frequency > 1%) associated with cognitive performance change. Novel variants associated with cognitive decline (P < 5 × 10-5) in individuals of European ancestry (n = 163) were considered replicated if they demonstrated consistent genotype-by-time interactions (P < .05) in individuals of non-European ancestries (n = 78) and achieved genome-wide statistical significance (P < 5 × 10-8) in a meta-analysis across ancestry groups.

RESULTS: Participants were mostly males (65%) diagnosed with embryonal tumors (98%) at …

Abnormal Motion Capture In Acute Stroke (Bionics): A Low-Cost Tele-Evaluation Tool For Automated Assessment Of Upper Extremity Function In Stroke Patients, Syed A Zamin, Kaichen Tang, Emily A Stevens, Melissa Howard, Dorothea M Parker, Allyson Seals, Xiaoqian Jiang, Sean Savitz, Shayan Shams

Faculty, Staff and Student Publications

BACKGROUND: The incidence of stroke and stroke-related hemiparesis has been steadily increasing and is projected to become a serious social, financial, and physical burden on the aging population. Limited access to outpatient rehabilitation for these stroke survivors further deepens the healthcare issue and estranges the stroke patient demographic in rural areas. However, new advances in motion detection deep learning enable the use of handheld smartphone cameras for body tracking, offering unparalleled levels of accessibility.

METHODS: In this study we want to develop an automated method for evaluation of a shortened variant of the Fugl-Meyer assessment, the standard stroke rehabilitation scale …

Computational Modeling And Minimization Of Unintended Neuronal Excitation In A Lifu Stimulation, Boqiang Fan, Wayne Goodman, Raymond Y Cho, Sameer A Sheth, Richard R Bouchard, Behnaam Aazhang

Faculty, Staff and Student Publications

The neuromodulation effect of low-intensity focused ultrasound (LIFU) is highly target-specific. Unintended off-target neuronal excitation can be elicited when the beam focusing accuracy and resolution are limited, whereas the resulted side effect has not been evaluated quantitatively. There is also a lack of methods addressing the minimization of such side effects. Therefore, this work introduces a computational model of unintended neuronal excitation during LIFU neuromodulation, which evaluates the off-target activation area (OTAA) by integrating an ultrasound field model with the neuronal spiking model. In addition, a phased array beam focusing scheme called constrained optimal resolution beamforming (CORB) is proposed to …

Genome-Wide Association Studies And Fine-Mapping Identify Genomic Loci For N-3 And N-6 Polyunsaturated Fatty Acids In Hispanic American And African American Cohorts, Chaojie Yang, Jenna Veenstra, Traci M Bartz, Matthew C Pahl, Brian Hallmark, Yii-Der Ida Chen, Jason Westra, Lyn M Steffen, Christopher D Brown, David Siscovick, Michael Y Tsai, Alexis C Wood, Stephen S Rich, Caren E Smith, Timothy D O'Connor, Dariush Mozaffarian, Struan F A Grant, Floyd H Chilton, Nathan L Tintle, Rozenn N Lemaitre, Ani Manichaikul

Faculty, Staff and Students Publications

Omega-3 (n-3) and omega-6 (n-6) polyunsaturated fatty acids (PUFAs) play critical roles in human health. Prior genome-wide association studies (GWAS) of n-3 and n-6 PUFAs in European Americans from the CHARGE Consortium have documented strong genetic signals in/near the FADS locus on chromosome 11. We performed a GWAS of four n-3 and four n-6 PUFAs in Hispanic American (n = 1454) and African American (n = 2278) participants from three CHARGE cohorts. Applying a genome-wide significance threshold of P < 5 × 10

A Multiparameter Molecular Classifier To Predict Response To Neoadjuvant Lapatinib Plus Trastuzumab Without Chemotherapy In Her2+ Breast Cancer, Jamunarani Veeraraghavan, Carolina Gutierrez, Carmine De Angelis, Robert Davis, Tao Wang, Tomas Pascual, Pier Selenica, Katherine Sanchez, Hiroaki Nitta, Monesh Kapadia, Anne C Pavlick, Patricia Galvan, Brent Rexer, Andres Forero-Torres, Rita Nanda, Anna M Storniolo, Ian E Krop, Matthew P Goetz, Julie R Nangia, Antonio C Wolff, Britta Weigelt, Jorge S Reis-Filho, Susan G Hilsenbeck, Aleix Prat, C Kent Osborne, Rachel Schiff, Mothaffar F Rimawi

Faculty, Staff and Student Publications

PURPOSE: Clinical trials reported 25% to 30% pathologic complete response (pCR) rates in HER2+ patients with breast cancer treated with anti-HER2 therapies without chemotherapy. We hypothesize that a multiparameter classifier can identify patients with HER2-"addicted" tumors who may benefit from a chemotherapy-sparing strategy.

EXPERIMENTAL DESIGN: Baseline HER2+ breast cancer specimens from the TBCRC023 and PAMELA trials, which included neoadjuvant treatment with lapatinib and trastuzumab, were used. In the case of estrogen receptor-positive (ER+) tumors, endocrine therapy was also administered. HER2 protein and gene amplification (ratio), HER2-enriched (HER2-E), and PIK3CA mutation status were assessed by dual gene protein assay (GPA), research-based …

The Nurosleeve, A User-Centered 3d Printed Hybrid Orthosis For Individuals With Upper Extremity Impairment, Mehdi Khantan, Mikael Avery, Phyo Thuta Aung, Rachel M. Zarin, Emma Hammelef, Nabila Shawki, Mijail Demian Serruya, Alessandro Naopli

Farber Institute for Neuroscience Faculty Papers

BACKGROUND: Active upper extremity (UE) assistive devices have the potential to restore independent functional movement in individuals with UE impairment due to neuromuscular diseases or injury-induced chronic weakness. Academically fabricated UE assistive devices are not usually optimized for activities of daily living (ADLs), whereas commercially available alternatives tend to lack flexibility in control and activation methods. Both options are typically difficult to don and doff and may be uncomfortable for extensive daily use due to their lack of personalization. To overcome these limitations, we have designed, developed, and clinically evaluated the NuroSleeve, an innovative user-centered UE hybrid orthosis.

METHODS: This …

Novel Murine Glioblastoma Models That Reflect The Immunotherapy Resistance Profile Of A Human Disease, Chao-Hsien Chen, Renee L Chin, Genevieve P Hartley, Spencer T Lea, Brian J Engel, Cheng-En Hsieh, Rishika Prasad, Jason Roszik, Takashi Shingu, Gregory A Lizee, Amy B Heimberger, Steven W Millward, Jian Hu, David S Hong, Michael A Curran

Faculty, Staff and Student Publications

BACKGROUND: The lack of murine glioblastoma models that mimic the immunobiology of human disease has impeded basic and translational immunology research. We, therefore, developed murine glioblastoma stem cell lines derived from Nestin-CreERT2QkL/L; Trp53L/L; PtenL/L (QPP) mice driven by clinically relevant genetic mutations common in human glioblastoma. This study aims to determine the immune sensitivities of these QPP lines in immunocompetent hosts and their underlying mechanisms.

METHODS: The differential responsiveness of QPP lines was assessed in the brain and flank in untreated, anti-PD-1, or anti-CTLA-4 treated mice. The impact of genomic landscape on the responsiveness of each tumor was measured through …