56 Works

Enhancing U.S. Surveillance of Laboratory Confirmed SARS-CoV-2, Influenza, and other Respiratory Viruses through a Network of Emergency Departments

Jeffrey Kline
This emergency department (ED) surveillance network comprises 24 nodes represented by site investigators at hospital systems in 21 states and the District of Columbia. This work is funded by a contract from the Centers for Disease Control with Wayne State as the prime. The goal of the network is to identify patients who present with acute respiratory illness (e.g. cough or fever). The network report demographic data, vaccination status as identified in the medical record,...

The STARS phase 2 study: a randomized controlled trial of gaboxadol in Angelman syndrome

Lynne Bird, Cesar Ochoa-Lubinoff, Wen-Hann Tan, Gali Heimer, Raun Melmed, Amit Rakhit, Jeannie Visootsak, Matthew During, Rebecca Burdine, Christina Holcroft, Alexander Kolevzon & Ronald Thibert
Objective: To evaluate safety and tolerability and exploratory efficacy endpoints for gaboxadol (OV101) compared with placebo in individuals with Angelman syndrome (AS). Methods: Gaboxadol is a highly selective orthosteric agonist that activates γ-subunit–containing extrasynaptic γ-aminobutyric acid type A (GABAA) receptors. In a multicenter, double-blind, placebo-controlled, parallel-group trial, adolescent and adult individuals with a molecular diagnosis of AS were randomized (1:1:1) to 1 of 3 dosing regimens for a duration of 12 weeks: placebo morning dose...

Data from: Nusinersen in later-onset spinal muscular atrophy: long-term results from the phase 1/2 studies

Basil T. Darras, Claudia A. Chiriboga, Susan T. Iannaccone, Kathryn J. Swoboda, Jacqueline Montes, Laurence Mignon, Shuting Xia, C. Frank Bennett, Kathie M. Bishop, Jeremy M. Shefner, Allison M. Green, Peng Sun, Ishir Bhan, Sarah Gheuens, Eugene Schneider, Wildon Farwell & Darryl C. De Vivo
Objective: Report results of intrathecal nusinersen in children with later-onset spinal muscular atrophy (SMA). Methods: Analyses included children from the phase 1b/2a study (ISIS-396443-CS2; NCT01703988) who first received nusinersen during that study and were eligible to continue treatment in the extension study (ISIS-396443-CS12; NCT02052791). The phase 1b/2a study was a 253-day, ascending dose (3, 6, 9, 12 mg), multiple-dose, open-label, multicenter study that enrolled children with SMA aged 2 to 15 years. The extension study...

Data from: Histopathology of diffusion imaging abnormalities in cerebral amyloid angiopathy

Susanne J. Van Veluw, Yael D. Reijmer, Andre J. Van Der Kouwe, Andreas Charidimou, Grace A. Riley, Alexander Leemans, Brian J. Bacskai, Matthew P. Frosch, Anand Viswanathan & Steven M. Greenberg
Objective: we sought to determine the underlying mechanism for altered white matter diffusion tensor imaging (DTI) measures at the histopathologic level in patients with cerebral amyloid angiopathy (CAA). Methods: formalin-fixed intact hemispheres from nine CAA cases and two elderly controls were scanned at 3 tesla MRI, including a diffusion-weighted sequence. DTI measures (i.e. fractional anisotropy (FA) and mean diffusivity (MD)) and histopathology measures were obtained from two tracts: the anterior thalamic radiation (ATR) and inferior...

Data from: A quantitative electrophysiological biomarker of duplication 15q11.2-q13.1 syndrome

Joel Frohlich, Damla Senturk, Vidya Saravanapandian, Peyman Golshani, Lawrence T. Reiter, Raman Sankar, Ronald Thibert, Charlotte Distefano, Scott Huberty, Edwin H. Cook & Shafali S. Jeste
Background: Duplications of 15q11.2-q13.1 (Dup15q syndrome) are highly penetrant for autism spectrum disorder (ASD). A distinct electrophysiological (EEG) pattern characterized by excessive activity in the beta band has been noted in clinical reports. We asked whether EEG power in the beta band, as well as in other frequency bands, distinguished children with Dup15q syndrome from those with non-syndromic ASD and then examined the clinical correlates of this electrophysiological biomarker in Dup15q syndrome. Methods: In the...

Data from: Clinical EEG slowing correlates with delirium severity and predicts poor clinical outcomes

Eyal Y Kimchi, Anudeepthi Neelagiri, Wade Whitt, Avinash Rao Sagi, Sophia L Ryan, Greta Gadbois, Daniël Groothuysen, Michael B Westover & Eyal Kimchi
Objective To determine which findings on routine clinical EEGs correlate with delirium severity across various presentations, and to determine whether EEG findings independently predict important clinical outcomes. Methods We prospectively studied a cohort of non-intubated inpatients undergoing EEG for evaluation of altered mental status. Patients were assessed for delirium within one hour of EEG using the 3-Minute Diagnostic Interview for Confusion Assessment Method (3D-CAM) and 3D-CAM severity score (3D-CAM-S). EEGs were interpreted clinically by neurophysiologists,...

Data from: Cholinergic modulation of hippocampal calcium activity across the sleep-wake cycle

Heng Zhou, Kevin R Neville, Nitsan Goldstein, Shushi Kabu, Naila Kausar, Rong Ye, Thuan Tinh Nguyen, Noah Gelwan, Bradley T Hyman & Stephen N Gomperts
Calcium is a critical second messenger in neurons that contributes to learning and memory, but how the coordination of action potentials of neuronal ensembles with the hippocampal local field potential (LFP) is reflected in dynamic calcium activity remains unclear. Here, we recorded hippocampal calcium activity with endoscopic imaging of the genetically encoded fluorophore GCaMP6 with concomitant LFP in freely behaving mice. Dynamic calcium activity was greater in exploratory behavior and REM sleep than in quiet...

Data from: Aberrant FGFR signaling mediates resistance to CDK4/6 inhibitors in ER+ breast cancer

Luigi Formisano, Yao Lu, Alberto Servetto, Ariella B. Hanker, Valerie M. Jansen, Joshua A. Bauer, Dhivya R. Sudhan, Angel L. Guerrero-Zotano, Sarah Croessmann, Yan Guo, Paula Gonzalez, Kyung-Min Lee, Melissa J. Nixon, Luis J. Schwarz, Melinda E. Sanders, Teresa C. Dugger, Marcelo Rocha Cruz, Amir Behdad, Massimo Cristofanilli, Aditya Bardia, Joyce O'Shaughnessy, Rebecca J. Nagy, Richard B. Lanman, Nadia Solovieff, Wei He … & Carlos L. Arteaga
Using an ORF kinome screen in MCF-7 cells treated with the CDK4/6 inhibitor ribociclib plus fulvestrant, we identified FGFR1 as a mechanism of drug resistance. FGFR1-amplified/ER+ breast cancer cells and MCF-7 cells transduced with FGFR1 were resistant to fulvestrant ± ribociclib or palbociclib. This resistance was abrogated by treatment with the FGFR tyrosine kinase inhibitor (TKI) lucitanib. Addition of the FGFR TKI erdafitinib to palbociclib/fulvestrant induced complete responses of FGFR1-amplified/ER+ patient-derived-xenografts. Next generation sequencing of...

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

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...

Cerebrovascular disease progression in patients with ACTA2 Arg179 pathogenic variants supplementary materials

Arne Lauer, Samantha Speroni, Jay Patel, Ellen Regalado, Myoung Choi, Edward Smith, Jayashree Kalpathy-Kramer, Paul Caruso, Dianna Milewicz & Patricia Musolino
Our study entitled “Cerebrovascular disease progression in patients with ACTA2 Arg179 Pathogenic Variants” examines progression of imaging biomarkers of stroke, arterial steno-occlusive disease and white matter injury in patients with smooth muscle dysfunction syndrome caused by mutations in the ACTA2 gene (ACTA2 Arg179 pathogenic variants). We found characteristic patterns of acute white matter ischemic injury and progressive internal carotid artery stenosis on MRI. Longitudinal analysis showed both stable and progressive lesion entities. The data was...

Data from: Clinical presentation and management of SMART syndrome

Sebastian F. Winter, Joshua P. Klein, Eugene J. Vaios, Philipp Karschnia, Eudocia Q. Lee, Helen A. Shih, Franziska Loebel & Jorg Dietrich
Stroke-like migraine attacks after radiation therapy (SMART) syndrome represents a rare but serious condition manifesting years after cranial radiation therapy (RT). Characterized by migraine-type headaches, stroke-like deficits and/or seizures and MR imaging abnormalities, including cortical gyriform enhancement in irradiated brain regions, SMART remains diagnostically and therapeutically challenging. Distinction from tumor progression is difficult and treatment options are limited. Although frequently reversible, SMART episodes can recur and effectuate persistent neurologic and/or imaging sequelae.

Data from: The Golgi-localized γ-ear-containing ARF-binding (GGA) proteins alter amyloid-β precursor protein (APP) processing through interaction of their GAE domain with the beta-site APP cleaving enzyme 1 (BACE1)

Bjoern Von Einem, Anke Wahler, Tobias Schips, Alberto Serrano-Pozo, Christian Proepper, Tobias M. Boeckers, Angelika Rueck, Thomas Wirth, Bradley T. Hyman, Karin M. Danzer, Dietmar R. Thal & Christine A. F. Von Arnim
Proteolytic processing of amyloid-β precursor protein (APP) by beta-site APP cleaving enzyme 1 (BACE1) is the initial step in the production of amyloid beta (Aβ), which accumulates in senile plaques in Alzheimer’s disease (AD). Essential for this cleavage is the transport and sorting of both proteins through endosomal/Golgi compartments. Golgi-localized γ-ear-containing ARF-binding (GGA) proteins have striking cargo-sorting functions in these pathways. Recently, GGA1 and GGA3 were shown to interact with BACE1, to be expressed in...

Data from: Longitudinal cognitive and biomarker changes in dominantly inherited Alzheimer disease

Eric McDade, Guoqiao Wang, Brian Andrew Gordon, Jason Hassenstab, Tammie L.S. Benzinger, Virginia Buckles, Anne M. Fagan, David M. Holtzman, Nigel J. Cairns, Alison M. Goate, Daniel S. Marcus, John C. Morris, Katrina Paumier, Chengjie Xiong, Ricardo Allegri, Sarah B. Berman, William Klunk, James Nobel, John Ringman, Bernardino Ghetti, Martin Farlow, Reisa Anne Sperling, Jasmeer Chhatwal, Stephen Salloway, Neil R. Graff-Radford … & Randall J. Bateman
Objective: To assess the onset, sequence and rate of progression of comprehensive biomarker and clinical measures across the spectrum of Alzheimer disease using the Dominantly Inherited Alzheimer Network (DIAN) study and compare these to cross-sectional estimates. Methods: We conducted longitudinal clinical, cognitive, cerebrospinal fluid (CSF) and neuroimaging assessments (mean of 2.7 (+/- 1.1) visits) in 217 DIAN participants. Linear mixed effects models were used to assess changes in each measure relative to individuals’ estimated years...

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: 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: 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: 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...

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: 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,...

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)...

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...

A Novel Cognition-Based Guidance System to Improve Surgical Safety

Lauren Kennedy-Metz
Medical errors causing preventable adverse events are the third leading cause of death in the U.S. The role of human cognition in contributing to errors in complex healthcare environments is increasingly being recognized. Many studies have demonstrated a direct relationship between cognitive performance metrics and patient outcomes. Notwithstanding, the role of cognition in improving safety has not received enough attention. Cardiac surgical OR is a high-impact area to improve patient safety and save lives. High...

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...

Data from: Revised Airlie House consensus guidelines for design and implementation of ALS clinical trials

Leonard H Van Den Berg, Eric Sorenson, Gary Gronseth, Eric A. Macklin, Jinsy Andrews, Robert H. Baloh, Michael Benatar, James D. Berry, Adriano Chio, Philippe Corcia, Angela Genge, Amelie K. Gubitz, Catherine Lomen-Hoerth, Christopher J. McDermott, Erik P. Pioro, Jeffrey Rosenfeld, Vincenzo Silani, Martin R. Turner, Markus Weber, Benjamin Rix Brooks, Robert G. Miller & Hiroshi Mitsumoto
Objective: To revise the 1999 Airlie House consensus guidelines for the design and implementation of preclinical therapeutic studies and clinical trials in amyotrophic lateral sclerosis (ALS). Methods: A consensus committee comprising 140 key members of the international ALS community (ALS researchers, clinicians, patient representatives, research funding representatives, industry and regulatory agencies) addressed nine areas of need within ALS research: 1. Pre-clinical studies; 2. Biological and phenotypic heterogeneity; 3. Outcome measures; 4. Disease-modifying and symptomatic interventions;...

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Resource Types

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Affiliations

  • Massachusetts General Hospital
    56
  • Brigham and Women's Hospital
    9
  • Stanford University
    5
  • University of Pittsburgh
    5
  • Columbia University
    4
  • Boston Children's Hospital
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    3
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    2
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    2