16 Works

Data from: Sharing of clinical trial data among trialists: a cross sectional survey

Vinay Rathi, Kristina Dzara, Cary P. Gross, Iain Hrynaszkiewicz, Steven Joffe, Harlan M. Krumholz, Kelly M. Strait & Joseph S. Ross
Objective: To investigate clinical trialists’ opinions and experiences of sharing of clinical trial data with investigators who are not directly collaborating with the research team. Design and setting: Cross sectional, web based survey. Participants: Clinical trialists who were corresponding authors of clinical trials published in 2010 or 2011 in one of six general medical journals with the highest impact factor in 2011. Main outcome measures: Support for and prevalence of data sharing through data repositories...

A cross-sectional study of nemaline myopathy supplementary figures

Kimberly Amburgey, Meryl Acker, Samia Saeed, Reshma Amin, Alan H. Beggs, Carsten G. Bönneman, Michael Brudno, Andrei Constantinescu, Johannaz Dastgir, Mamadou Diallo, Casie A. Genetti, Michael Glueck, Stacy Hewson, Courtney Hum, Minal S. Jain, Michael W. Lawlor, Oscar H. Mayer, Leslie Nelson, Nicole Sultanum, Faiza Syed, Tuyen Tran, Ching H. Wang & James J. Dowling
Objective: Nemaline myopathy (NM) is a rare neuromuscular condition with clinical and genetic heterogeneity. To establish disease natural history, we performed a cross-sectional study of NM, complemented by longitudinal assessment and exploration of pilot outcome measures. Methods: Fifty-seven individuals with NM were recruited at two family workshops, including 16 examined at both time points. Subjects were evaluated by clinical history and physical examination. Functional outcome measures included the Motor Function Measure (MFM), pulmonary function tests...

Data from: A spatial genetics approach to inform vector control of tsetse flies (Glossina fuscipes fuscipes) in Northern Uganda

Norah Saarman, Mary Burak, Robert Opiro, Chaz Hyseni, Richard Echodu, Kirstin Dion, Elizabeth A. Opiyo, Augustine W. Dunn, Giuseppe Amatulli, Serap Aksoy & Adalgisa Caccone
Tsetse flies (genus Glossina) are the only vector for the parasitic trypanosomes responsible for sleeping sickness and nagana across sub-Saharan Africa. In Uganda, the tsetse fly Glossina fuscipes fuscipes is responsible for transmission of the parasite in 90% of sleeping sickness cases, and co-occurrence of both forms of human-infective trypanosomes makes vector control a priority. We use population genetic data from 38 samples from northern Uganda in a novel methodological pipeline that integrates genetic data,...

Data from: Association between aspirin dose and subarachnoid hemorrhage from saccular aneurysms: a case-control study

Anil Can, Robert F. Rudy, Victor M. Castro, Sheng Yu, Dmitriy Dligach, Sean Finan, Vivian Gainer, Nancy A. Shadick, Guergana Savova, Shawn Murphy, Tianxi Cai, Scott T. Weiss & Rose Du
Objective: We aimed to determine the association between ruptured saccular aneurysms and aspirin use/aspirin dose. Methods: 4,701 patients who were diagnosed at the Massachusetts General Hospital and Brigham and Women’s Hospital between 1990 and 2016 with 6,411 unruptured and ruptured saccular intracranial aneurysms were evaluated. Univariable and multivariable logistic regression analyses were performed to determine the association between aSAH and aspirin use, including aspirin dose. Inverse probability weighting using propensity scores was used to adjust...

Data from: GATA2 controls lymphatic endothelial cell junctional integrity and lymphovenous valve morphogenesis through miR-126

, Xin Geng, YenChun Ho, Boksik Cha, Yuenhee Kim, Jing Ma, Lijuan Chen, Greggory Myers, Sally Camper, Debbie Mustacich, Marlys Witte, Dongwon Choi, Young-Kwon Hong, Hong Chen, Gaurav Varshney, James D Engel, Shusheng Wang, Tae-Hoon Kim, Kim-Chew Lim & Sathish Srinivasan
Mutations in the transcription factor GATA2 cause lymphedema. GATA2 is necessary for the development of lymphatic valves (LVs) and lymphovenous valves (LVVs), and for the patterning of lymphatic vessels. Here, we report that GATA2 is not necessary for valvular endothelial cell (VEC) differentiation. Instead, GATA2 is required for VEC maintenance and morphogenesis. GATA2 is also necessary for the expression of cell junction molecules VE-Cadherin and Claudin5 in lymphatic vessels. We identified miR-126 as a target...

Sensory transduction is required for development of hair cell synapses

John Lee, Jeffrey Holt & Gwenaelle Geleoc
Acoustic overexposure and aging can damage auditory synapses in the inner ear by a process known as synaptopathy. These insults may also damage hair bundles and the sensory transduction apparatus in auditory hair cells. However, a connection between sensory transduction and synaptopathy has not been established. To evaluate potential contributions of sensory transduction to synapse formation and development, we assessed inner hair cell synapses in several genetic models of dysfunctional sensory transduction, including mice lacking...

Continuous glucose monitoring in cystic fibrosis: glycemic relationships, clinical correlations, and implications for CFRD diagnosis

Melissa Putman & Scully Kevin
Context: The clinical utility and implications of continuous glucose monitoring (CGM) in cystic fibrosis (CF) are unclear. Objective: We examined the correlation between CGM measures and clinical outcomes in adults with CF, investigated the relationship between hemoglobin A1c (HbA1c) and CGM-derived average glucose (AG), and explored CGM measures that distinguish cystic fibrosis–related diabetes (CFRD) from normal and abnormal glucose tolerance. Methods: This prospective observational study included 77 adults with CF who had CGM and HbA1c...

Data from: Forward genetic screen of human transposase genomic rearrangements

Anton G. Henssen, Eileen Jiang, Jiali Zhuang, Luca Pinello, Nicholas D. Socci, Richard Koche, Mithat Gonen, Camila M. Villasante, Scott A. Armstrong, Daniel E. Bauer, Zhiping Weng & Alex Kentsis
Background: Numerous human genes encode potentially active DNA transposases or recombinases, but our understanding of their functions remains limited due to shortage of methods to profile their activities on endogenous genomic substrates. Results: To enable functional analysis of human transposase-derived genes, we combined forward chemical genetic hypoxanthine-guanine phosphoribosyltransferase 1 (HPRT1) screening with massively parallel paired-end DNA sequencing and structural variant genome assembly and analysis. Here, we report the HPRT1 mutational spectrum induced by the human...

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: Transcriptional profiling at whole population and single cell levels reveals somatosensory neuron molecular diversity

Isaac M. Chiu, Lee B. Barrett, Erika Williams, David E. Strochlic, Seungkyu Lee, Andy D. Weyer, Shan Lou, Gregory Bryman, David P. Roberson, Nader Ghasemlou, Cara Piccoli, Ezgi Ahat, Victor Wang, Enrique J. Cobos, Cheryl L. Stucky, Qiufu Ma, Stephen D. Liberles, Clifford J. Woolf & Gregory S Bryman
The somatosensory nervous system is critical for the organism’s ability to respond to mechanical, thermal, and nociceptive stimuli. Somatosensory neurons are functionally and anatomically diverse but their molecular profiles are not well-defined. Here, we used transcriptional profiling to analyze the detailed molecular signatures of dorsal root ganglion (DRG) sensory neurons. We used two mouse reporter lines and surface IB4 labeling to purify three major non-overlapping classes of neurons: 1)IB4+SNS-Cre/TdTomato+, 2)IB4-SNS-Cre/TdTomato+, and 3)Parv-Cre/TdTomato+ cells, encompassing the...

MERFISH measurements in the mouse ileum

Jeffrey Moffitt, Rosalind Xu, Peter Kharchenko, Viktor Petukhov, Paolo Cadinu, Ruslan Soldatov & Konstantin Khodosevich
Spatial transcriptomics protocols based on in situ sequencing or multiplexed RNA fluorescent hybridization can reveal detailed tissue organization. However, distinguishing the boundaries of individual cells in such data is challenging, and can hamper downstream analysis. Current methods generally approximate cells positions using nuclei stains. We describe a segmentation method, Baysor, which optimizes 2D or 3D cell boundaries considering joint likelihood of transcriptional composition and cell morphology. While Baysor can take into account segmentation based on...

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...

Supplemental Data: Low bone mineral density in early pubertal transgender/gender diverse youth: Findings from the Trans Youth Care Study

Janet Y. Lee, Courtney Finlayson, Johanna Olson-Kennedy, Robert Garofalo, Yee-Ming Chan, David V. Glidden & Stephen M. Rosenthal
Context. Transgender youth may initiate gonadotropin-releasing hormone agonists (GnRHa) to suppress puberty, a critical period for bone-mass accrual. Low bone mineral density (BMD) has been reported in late-pubertal transgender girls prior to gender-affirming therapy, but little is known about BMD in early-pubertal transgender youth. Objective. To describe BMD in early-pubertal transgender youth. Design. Cross-sectional analysis of the prospective, observational, longitudinal Trans Youth Care Study cohort. Setting. Four multi-disciplinary academic pediatric gender centers in the United...

YAP and TAZ maintain PROX1 expression in the developing lymphatic and lymphovenous valves in response to VEGF-C signaling

Boksik Cha, Yen-Chun Ho, Xin Geng, , Lijuan Chen, Yeunhee Kim, Dongwon Choi, Tae Hoon Kim, Gwendalyn Randolph, Xinwei Cao, Hong Chen & R. Sathish Srinivasan
Lymphatic vasculature is an integral part of digestive, immune and circulatory systems. The homeobox transcription factor PROX1 is necessary for the development of lymphatic vessels, lymphatic valves (LVs) and lymphovenous valves (LVVs). We and others previously reported a feedback loop between PROX1 and Vascular Endothelial Growth Factor-C (VEGF-C) signaling. PROX1 promotes the expression of the VEGF-C receptor VEGFR3 in lymphatic endothelial cells (LECs). In turn, VEGF-C signaling maintains PROX1 expression in LECs. However, the mechanisms...

Data from: Identification of children with anaphylaxis at low risk of receiving acute inpatient therapies

Timothy E. Dribin, Kenneth A. Michelson, Michael C. Monuteaux, Anne M. Stack, Karen S. Farbman, Lynda C. Schneider & Mark I. Neuman
Objective: Opportunity exists to reduce unnecessary hospitalizations for children with anaphylaxis given wide variation in admission rates across U.S. emergency departments (EDs). We sought to identify children hospitalized with anaphylaxis at low risk of receiving epinephrine and other acute inpatient therapies, as these patients may be candidates for ED discharge rather than inpatient hospitalization. Methods: We conducted a single-center retrospective cohort study of children 1–21 years of age hospitalized with anaphylaxis from 2009 to 2016....

Data from: Genetic diversity and population structure of the tsetse fly Glossina fuscipes fuscipes (Diptera: Glossinidae) in Northern Uganda: implications for vector control

Robert Opiro, Norah P. Saarman, Richard Echodu, Elizabeth A. Opiyo, Kirstin Dion, Alexis Halyard, Augustine W. Dunn, Serap Aksoy, Adalgisa Caccone & Philippe Solano
Uganda is the only country where the chronic and acute forms of human African Trypanosomiasis (HAT) or sleeping sickness both occur and are separated by < 100 km in areas north of Lake Kyoga. In Uganda, Glossina fuscipes fuscipes is the main vector of the Trypanosoma parasites responsible for these diseases as well for the animal African Trypanosomiasis (AAT), or Nagana. We used highly polymorphic microsatellite loci and a mitochondrial DNA (mtDNA) marker to provide...

Registration Year

  • 2022
    1
  • 2021
    2
  • 2020
    4
  • 2019
    3
  • 2018
    3
  • 2016
    1
  • 2014
    1
  • 2012
    1

Resource Types

  • Dataset
    16

Affiliations

  • Boston Children's Hospital
    16
  • Massachusetts General Hospital
    4
  • Harvard Medical School
    3
  • Medical College of Wisconsin
    2
  • Oklahoma Medical Research Foundation
    2
  • University of Southern California
    2
  • Yale University
    2
  • Gulu University
    2
  • The University of Texas at Dallas
    2
  • The University of Texas Southwestern Medical Center
    2