62 Works

Rare missense functional variants at COL4A1 and COL4A2 in sporadic intracerebral hemorrhage

Jaeyoon Chung, Graham Hamilton, Minsup Kim, Sandro Marini, Bailey Montgomery, Jonathan Henry, Art Cho, Devin Brown, Bradford Worrall, James Meschia, Scott Silliman, Magdy Selim, David Tirschwell, Chelsea Kidwell, Brett Kissela, Steven Greenberg, Anand Viswanathan, Joshua Goldstein, Carl Langefeld, Kristiina Rannikmae, Catherine Sudlow, Neshika Samarasekera, Mark Rodrigues, Rustam Salman, James Prendergast … & Christopher Anderson
Objective To test the genetic contribution of rare missense variants in COL4A1 and COL4A2 in which common variants are genetically associated with sporadic intracerebral hemorrhage (ICH), we performed rare variant analysis in multiple sequencing data for the risk for sporadic ICH. Methods We performed sequencing across 559Kbp at 13q34 including COL4A1 and COL4A2 among 2,133 individuals (1,055 ICH cases; 1,078 controls) in US-based and 1,492 individuals (192 ICH cases; 1,300 controls) from Scotland-based cohorts, followed...

Large-scale neural recordings with single neuron resolution using Neuropixels probes in human cortex

Angelique C Paulk, Yoav Kfir, Arjun R Khanna, Martina L Mustroph, Eric M Trautmann, Dan J Soper, Sergey D Stavisky, Marleen Welkenhuysen, Barundeb Dutta, Krisha V Shenoy, Leigh R Hochberg, R. Mark Richardson, Ziv M Williams & Sydney S Cash
Recent advances in multi-electrode array technology have made it possible to monitor large neuronal ensembles at cellular resolution in animal models. In humans, however, current approaches restrict recordings to few neurons per penetrating electrode or combine the signals of thousands of neurons in local field potential (LFP) recordings. Here, we describe a new probe variant and set of techniques which enable simultaneous recording from over 200 well-isolated cortical single units in human participants during intraoperative...

Generalizable EHR-R-REDCap pipeline for a national multi-institutional rare tumor patient registry

Sophia Shalhout, Farees Saqlain, Kayla Wright, Oladayo Akinyemi & David Miller
Objective: To develop a clinical informatics pipeline designed to capture large-scale structured EHR data for a national patient registry. Materials and Methods: The EHR-R-REDCap pipeline is implemented using R-statistical software to remap and import structured EHR data into the REDCap-based multi-institutional Merkel Cell Carcinoma (MCC) Patient Registry using an adaptable data dictionary. Results: Clinical laboratory data were extracted from EPIC Clarity across several participating institutions. Labs were transformed, remapped and imported into the MCC registry...

Data from: Distinct epileptiform abnormalities are associated with clinical seizures in Alzheimer’s disease

Alice Lam, Rani Sarkis, Kyle R Pellerin, Jin Jing, Barbara A Dworetzky, Daniel B Hoch, Claire S Jacobs, Jong Woo Lee, Daniel S Weisholtz, Rodrigo Zepeda, M. Brandon Westover, Andrew J. Cole & Sydney S Cash
Objective: Examine the relationship between scalp EEG biomarkers of hyperexcitability in Alzheimer’s disease (AD) and determine how these electrical biomarkers relate to the clinical expression of seizures in AD. Methods: In this cross-sectional study, we performed 24-hour ambulatory scalp EEGs on 43 cognitively normal elderly healthy controls (HC), 41 early-stage AD participants with no history or risk factors for epilepsy (AD-NoEp), and 15 early-stage AD participants with late-onset epilepsy related to AD (AD-Ep). Two epileptologists,...

Implementing standardized provider documentation in a tertiary epilepsy clinic: supplemental material

Felipe J.S. Jones, Jason R. Smith, Neishay Ayub, Susan T. Herman, Jeffrey R. Buchhalter, Brandy E. Fureman, Sydney S. Cash, Daniel B. Hoch & Lidia M.V.R. Moura
Objective: To incorporate standardized documentation into an epilepsy clinic and use these standardized data to compare patients’ perception of epilepsy diagnosis to provider documentation. Methods: Using quality improvement methodology, we implemented interventions to increase documentation of epilepsy diagnosis, seizure frequency and type from 49.8% to 70% of adult non-employee patients seen by six providers over five months of routine clinical care. The main intervention consisted of an interactive SmartPhrase that mirrored a documentation template developed...

Data from: CAG repeat not polyglutamine length determines timing of Huntington’s disease onset

Jong-Min Lee
Variable, glutamine-encoding, CAA interruptions indicate that a property of the uninterrupted HTT CAG repeat sequence, distinct from the length of huntingtin’s polyglutamine segment, dictates the rate at which Huntington’s disease (HD) develops. The timing of onset shows no significant association with HTT cis-eQTLs but is influenced, sometimes in a sex-specific manner, by polymorphic variation at multiple DNA maintenance genes, suggesting that the special onset-determining property of the uninterrupted CAG repeat is a propensity for length...

Data from: Diffusion tensor imaging in patients with glioblastoma multiforme using the supertoroidal model

Choukri Mekkaoui, Philippe Metellus, William J. Kostis, Roberto Martuzzi, Fabricio R. Pereira, Jean-Paul Beregi, Timothy G. Reese, Todd R. Constable & Marcel P. Jackowski
Purpose: Diffusion Tensor Imaging (DTI) is a powerful imaging technique that has led to improvements in the diagnosis and prognosis of cerebral lesions and neurosurgical guidance for tumor resection. Traditional tensor modeling, however, has difficulties in differentiating tumor-infiltrated regions and peritumoral edema. Here, we describe the supertoroidal model, which incorporates an increase in surface genus and a continuum of toroidal shapes to improve upon the characterization of Glioblastoma multiforme (GBM). Materials and Methods: DTI brain...

Data from: Clinical spectrum of STX1B-related epileptic disorders

Stefan Wolking, Patrick May, Davide Mei, Rikke S. Møller, Simona Balestrini, Katherine L. Helbig, Cecilia Desmettre Altuzarra, Nicolas Chatron, Charu Kaiwar, Katharina Stoehr, Peter Widdess-Walsh, Bryce A. Mendelsohn, Adam Numis, Maria R. Cilio, Wim Van Paesschen, Lene L. Svendsen, Stephanie Oates, Elaine Hughes, Sushma Goyal, Kathleen Brown, Margarita Sifuentes Saenz, Thomas Dorn, Hiltrud Muhle, Alistair T. Pagnamenta, Dimitris V. Vavoulis … & Julian Schubert
Objective: The aim of this study was to expand the spectrum of epilepsy syndromes related to STX1B, encoding the presynaptic protein syntaxin-1B, and establish genotype-phenotype correlations by identifying further disease-related variants. Methods: We used next generation sequencing in the framework of research projects and diagnostic testing. Clinical data and EEGs were reviewed, including already published cases. To estimate the pathogenicity of the variants, we used established and newly developed in silico prediction tools. Results: We...

Data from: Abnormal thalamo-cortical network dynamics in migraine

Yiheng Tu, Zening Fu, Fang Zeng, Nasim Maleki, Lei Lan, Zhengjie Li, Joel Park, Georgia Wilson, Yujie Gao, Mailan Liu, Vince Calhoun, Fanrong Liang & Jian Kong
Objective: To investigate the dynamic functional connectivity of thalamo-cortical networks in interictal migraine patients and whether clinical features are associated with abnormal connectivity. Methods: We investigated dynamic functional network connectivity (dFNC) of the migraine brain in 89 interictal migraine patients and 70 healthy controls. We focused on the temporal properties of thalamocortical connectivity using sliding window cross-correlation, clustering state analysis, and graph-theory methods. Relationships between clinical symptoms and abnormal dFNC were evaluated using a multivariate...

Data from: Convergent evolution of phenotypic integration and its alignment with morphological diversification in Carribean Anolis ecomorphs

Jason J. Kolbe, Liam J. Revell, Brian Szekely, & Jonathan B Losos
The adaptive landscape and the G-matrix are keys concepts for understanding how quantitative characters evolve during adaptive radiation. In particular, whether the adaptive landscape can drive convergence of phenotypic integration (i.e., the pattern of phenotypic variation and covariation summarized in the P-matrix) is not well studied. We estimated and compared P for 19 morphological traits in eight species of Caribbean Anolis lizards, finding that similarity in P among species was not correlated with phylogenetic distance....

Data from: Activation of autophagy during normothermic machine perfusion of discarded livers is associated with improved hepatocellular function

Anders Ohman, Siavash Raigani, John Santiago, Megan Heaney, Joan Boylan, Nicola Parry, Cailah Carroll, Sofia Baptista, Korkut Uygun, Phillip Gruppuso, Jennifer Sanders & Heidi Yeh
Liver transplantation is hampered by a severe shortage of donor organs. Normothermic machine perfusion (NMP) of donor livers allows dynamic preservation in addition to viability assessment prior to transplantation. Little is known about the injury and repair mechanisms induced during NMP. To investigate these mechanisms, we examined gene and protein expression changes in a cohort of discarded human livers, stratified by hepatocellular function, during NMP. Six human livers acquired through donation after circulatory death (DCD)...

Data from: In vivo human whole-brain Connectom diffusion MRI dataset at 760 µm isotropic resolution (PART I)

Fuyixue Wang, Zijing Dong, Qiyuan Tian, Congyu Liao, Qiuyun Fan, W. Scott Hoge, Boris Keil, Jonathan R. Polimeni, Lawrence L. Wald, Susie Y. Huang & Kawin Setsompop
This whole-brain in vivo diffusion MRI dataset was acquired at 760 µm isotropic resolution and sampled at 1260 q-space points across 9 two-hour sessions on a single healthy subject. It was acquired using state-of-the-art acquisition hardware and advanced reconstruction to achieve high SNR at such resolution, including a high-gradient-strength Connectom scanner, a custom-built 64-channel phased-array coil, a personalized motion-robust head stabilizer, a recently developed SNR-efficient dMRI acquisition, and parallel imaging reconstruction with advanced ghost reduction...

Facemasks: Perceptions and use in an ED population during COVID-19

Vidya Eswaran, Anna Marie Chang, R Gentry Wilkerson, Kelli O'Laughlin, Brian Chinnock, Stephanie Eucker, Brigitte Baumann, Nancy Anaya, Daniel Miller, Adrianne Haggins, Jesus Torres, Erik Anderson, Stephen Lim, Martina Caldwell, Ali Raja & Robert Rodriguez
Study Objective: Facemask use is associated with reduced transmission of SARS-CoV-2. Most surveys assessing perceptions and practices of mask use miss the most vulnerable racial, ethnic, and socio-economic populations. These same populations have suffered disproportionate impacts from the pandemic. The purpose of this study was to assess beliefs, access, and practices of mask wearing across 15 urban emergency department (ED) populations. Methods: This was a secondary analysis of a cross-sectional study of ED patients from...

Data from: Revisiting protein aggregation as pathogenic in sporadic Parkinson’s and Alzheimer’s diseases

Alberto J. Espay, Joaquin A. Vizcarra, Luca Marsili, Anthony E. Lang, David K. Simon, Aristide Merola, Keith A. Josephs, Alfonso Fasano, Francesca Morgante, Rodolfo Savica, J. Timothy Greenamyre, Franca Cambi, Tritia R. Yamasaki, Caroline M. Tanner, Ziv Gan-Or, Irene Litvan, Ignacio F. Mata, Cyrus P. Zabetian, Patrik Brundin, Hubert H. Fernandez, David G. Standaert, Marcelo A. Kauffman, Michael A. Schwarzschild, S. Pablo Sardi, Todd Sherer … & James B. Leverenz
The gold standard for a definitive diagnosis of Parkinson’s disease (PD) is the pathologic finding of aggregated alpha-synuclein into Lewy bodies and for Alzheimer’s disease (AD) aggregated amyloid into plaques and hyperphosphorylated tau into tangles. Implicit in this clinico-pathologic-based nosology is the assumption that pathological protein aggregation at autopsy reflect pathogenesis at disease onset. While these aggregates may in exceptional cases be on a causal pathway in humans (e.g., aggregated alpha-synuclein in SNCA gene multiplication...

Data from: Succinate links atrial dysfunction and cardioembolic stroke

Sarah E. Nelson, Zsuzsanna Ament, Zoe Wolcott, Robert E. Gerszten & W. Taylor Kimberly
Objective: To determine whether altered metabolic profiles represent a link between atrial dysfunction and cardioembolic (CE) stroke, and thus whether underlying dysfunctional atrial substrate may contribute to thromboembolism risk in CE stroke. Methods: One hundred forty-four metabolites were measured using liquid chromatography-tandem mass spectrometry in plasma samples collected within 9 hours of stroke onset in 367 acute stroke patients. Stroke subtype was assigned using the causative classification of stroke, and CE stroke (n=181) was compared...

Data from: Alcoholism gender differences in brain responsivity to emotional stimuli

Kayle S Sawyer, Nasim Maleki, Trinity Urban, Marinkovic Ksenija, Karson Steven, Susan Mosher Ruiz, Gordon J Harris & Marlene Oscar-Berman
Men and women may use alcohol to regulate emotions differently, with corresponding differences in neural responses. We explored how the viewing of different types of emotionally salient stimuli impacted brain activity observed through functional magnetic resonance imaging (fMRI) from 42 long-term abstinent alcoholic (25 women) and 46 nonalcoholic (24 women) participants. Analyses revealed blunted brain responsivity in alcoholic compared to nonalcoholic groups, as well as gender differences in those activation patterns. Brain activation in alcoholic...

Data from: Multi-contrast submillimetric 3-Tesla hippocampal subfield segmentation protocol and dataset

Jessie Kulaga-Yoskovitz, Boris C. Bernhardt, Seok-Jun Hong, Tommaso Mansi, Kevin E. Liang, Andre J. W. Van Der Kouwe, Jonathan Smallwood, Andrea Bernasconi & Neda Bernasconi
The hippocampus is composed of distinct anatomical subregions that participate in multiple cognitive processes and are differentially affected in prevalent neurological and psychiatric conditions. Advances in high-field MRI allow for the non-invasive identification of hippocampal substructure. These approaches, however, demand time-consuming manual segmentation that relies heavily on anatomical expertise. Here, we share manual labels and associated high-resolution MRI data (MNI-HISUB25; submillimetric T1- and T2-weighted images, detailed sequence information, and stereotaxic probabilistic anatomical maps) based on...

Data from: Population-specific genetic modification of Huntington's disease in Venezuela

Michael J. Chao, Kyung-Hee Kim, Jun Wan Shin, Diane Lucente, Vanessa C. Wheeler, Hong Li, Jared C. Roach, Leroy Hood, Nancy S. Wexler, Laura B. Jardim, Peter Holmans, Lesley Jones, Michael Orth, Seung Kwak, James F. Gusella, Marcy E. MacDonald & Jong-Min Lee
Modifiers of Mendelian disorders can provide insights into disease mechanisms and guide therapeutic strategies. A recent genome-wide association (GWA) study discovered genetic modifiers of Huntington's disease (HD) onset in Europeans. Here, we performed whole genome sequencing and GWA analysis of a Venezuelan HD cluster whose families were crucial for the original mapping of the HD gene defect. The Venezuelan HD subjects develop motor symptoms earlier than their European counterparts, implying the potential for population-specific modifiers....

Data from: Effect of IV glyburide on adjudicated edema endpoints in the GAMES-RP Trial

W. Taylor Kimberly, Matthew B. Bevers, Rüdiger Von Kummer, Andrew M. Demchuk, Javier M. Romero, Jordan J. Elm, Holly E. Hinson, Bradley J. Molyneaux, J. Marc Simard & Kevin Navin Sheth
Objective: In this secondary analysis of the GAMES-RP trial, we report the effect of IV glyburide on adjudicated, edema-related endpoints. Methods: Blinded adjudicators assigned designations for hemorrhagic transformation, neurological deterioration, malignant edema and edema-related death to patients from the GAMES-RP Phase II randomized controlled trial of IV glyburide for large hemispheric infarct. Rates of these endpoints were compared between treatment arms in the per-protocol sample. In those participants with malignant edema, the effects of treatment...

Data from: Clinical trial registration, reporting, publication and FDAAA compliance: a cross-sectional analysis and ranking of new drugs approved by the FDA in 2012

Jennifer E. Miller, David Korn & Joseph S. Ross
Objective: To evaluate clinical trial registration, reporting and publication rates for new drugs by: (1) legal requirements and (2) the ethical standard that all human subjects research should be publicly accessible to contribute to generalisable knowledge. Design: Cross-sectional analysis of all clinical trials submitted to the Food and Drug Administration (FDA) for drugs approved in 2012, sponsored by large biopharmaceutical companies. Data sources: Information from Drugs@FDA, ClinicalTrials.gov, MEDLINE-indexed journals and drug company communications. Main outcome...

Data from: Quantification of motor speech impairment and its anatomic basis in primary progressive aphasia

Claire Cordella, Megan Quimby, Alexandra Touroutoglou, Michael Brickhouse, Bradford Clark Dickerson & Jordan R. Green
Objective: To evaluate whether a quantitative speech measure is effective in identifying and monitoring motor speech impairment (MSI) in patients with primary progressive aphasia (PPA), and to investigate the neuroanatomical basis of MSI in PPA. Methods: Sixty-four patients with PPA were evaluated at baseline, with a subset (N=39) evaluated longitudinally. Articulation rate (AR), a quantitative measure derived from spontaneous speech, was measured at each timepoint. MRI was collected at baseline. Differences in baseline AR were...

Data from: Neuropathy with vascular endothelial growth factor receptor tyrosine kinase inhibitors

Bhaskar Roy, Avash Das, Kumar Ashish, Dhrubajyoti Bandyopadhyay, Abhishek Maiti, Sandipan Chakraborty, Martha E. Stone, Lisa Liang Philpotts, Richard J. Nowak & Huned S. Patwa
Objective: To explore the association of peripheral neuropathy with vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) use in cancer patients. Methods: Published data search up to November 2018 reporting peripheral neuropathy in cancer patients treated with VEGFR-TKIs was performed. The primary outcome was presence of peripheral neuropathy at the end of the trial. Random-effects meta-analysis was performed to estimate Relative Risk (RR) of individual treatment. Results: Thirty Randomized Clinical Trials (RCTs) including 12,490...

Data from: The NBS-LRR architectures of plant R-proteins and metazoan NLRs evolved in independent events

Jonathan M. Urbach & Frederick M. Ausubel
There are intriguing parallels between plants and animals, with respect to the structures of their innate immune receptors, that suggest universal principles of innate immunity. The cytosolic nucleotide binding site–leucine rich repeat (NBS-LRR) resistance proteins of plants (R-proteins) and the so-called NOD-like receptors of animals (NLRs) share a domain architecture that includes a STAND (signal transduction ATPases with numerous domains) family NTPase followed by a series of LRRs, suggesting inheritance from a common ancestor with...

Skeletal Muscle and Peripheral Nerve Histopathology in COVID-19

Joome Suh, Shibani Mukerji, Sarah Collens, Robert Padera, Geraldine Pinkus, Anthony Amato & Isaac Solomon
To explore the spectrum of skeletal muscle and nerve pathology of patients who died following SARS-CoV-2 infection and assess for direct viral invasion of these tissues. Psoas muscle and femoral nerve were sampled from 35 consecutive autopsies of patients who died following SARS-CoV-2 infection and 10 SARS-CoV-2-negative controls were examined under light microscopy. Clinical and laboratory data were obtained by chart review. In SARS-CoV-2-positive patients, mean age at death was 67.8 years (range 43-90 years)...

Genetic overlap and causal inferences between kidney function and cerebrovascular disease

Sandro Marini, Marios Georgakis, Jaeyoon Chung, Jonathan Henry, Martin Dichgans, Jonathan Rosand, Christopher Anderson & Rainer Malik
Objective: Leveraging large-scale genetic data, we aimed to identify shared pathogenic mechanisms and causal relationships between impaired kidney function and cerebrovascular disease phenotypes. Methods: We used summary statistics from genome-wide association studies (GWAS) of kidney function traits (chronic kidney disease (CKD) diagnosis, estimated glomerular filtration rate (eGFR), and Urinary Albumin-to-Creatinine Ratio (UACR)), and of cerebrovascular disease phenotypes: ischemic stroke and its subtypes, intracerebral hemorrhage (ICH), white matter hyperintensities (WMH) on brain MRI. We (i) tested...

Registration Year

  • 2022
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  • 2011

Resource Types

  • Dataset


  • Massachusetts General Hospital
  • Brigham and Women's Hospital
  • Stanford University
  • University of Pittsburgh
  • Boston Children's Hospital
  • Columbia University
  • University of Virginia
  • McGill University
  • University of Southern California
  • University of Tennessee Health Science Center