Institution
Boston Children's Hospital
Healthcare•Boston, Massachusetts, United States•
About: Boston Children's Hospital is a healthcare organization based out in Boston, Massachusetts, United States. It is known for research contribution in the topics: Population & Transplantation. The organization has 165409 authors who have published 215589 publications receiving 6885627 citations.
Topics: Population, Transplantation, Poison control, Intensive care, Health care
Papers published on a yearly basis
Papers
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McGill University1, German Cancer Research Center2, Montreal Children's Hospital3, National Research Council4, Russian Academy5, Semmelweis University6, University of Debrecen7, University of Tübingen8, Boston Children's Hospital9, Augsburg College10, University of Würzburg11, Martin Luther University of Halle-Wittenberg12, Heidelberg University13, University of Toronto14, University of Düsseldorf15, University of Cambridge16, University Hospital Heidelberg17
TL;DR: The presence of H3F3A/ATRX-DAXX/TP53 mutations was strongly associated with alternative lengthening of telomeres and specific gene expression profiles, suggesting that defects of the chromatin architecture underlie paediatric and young adult GBM pathogenesis.
Abstract: Glioblastoma multiforme (GBM) is a lethal brain tumour in adults and children. However, DNA copy number and gene expression signatures indicate differences between adult and paediatric cases. To explore the genetic events underlying this distinction, we sequenced the exomes of 48 paediatric GBM samples. Somatic mutations in the H3.3-ATRX-DAXX chromatin remodelling pathway were identified in 44% of tumours (21/48). Recurrent mutations in H3F3A, which encodes the replication-independent histone 3 variant H3.3, were observed in 31% of tumours, and led to amino acid substitutions at two critical positions within the histone tail (K27M, G34R/G34V) involved in key regulatory post-translational modifications. Mutations in ATRX (α-thalassaemia/mental retardation syndrome X-linked) and DAXX (death-domain associated protein), encoding two subunits of a chromatin remodelling complex required for H3.3 incorporation at pericentric heterochromatin and telomeres, were identified in 31% of samples overall, and in 100% of tumours harbouring a G34R or G34V H3.3 mutation. Somatic TP53 mutations were identified in 54% of all cases, and in 86% of samples with H3F3A and/or ATRX mutations. Screening of a large cohort of gliomas of various grades and histologies (n = 784) showed H3F3A mutations to be specific to GBM and highly prevalent in children and young adults. Furthermore, the presence of H3F3A/ATRX-DAXX/TP53 mutations was strongly associated with alternative lengthening of telomeres and specific gene expression profiles. This is, to our knowledge, the first report to highlight recurrent mutations in a regulatory histone in humans, and our data suggest that defects of the chromatin architecture underlie paediatric and young adult GBM pathogenesis.
2,091 citations
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Seattle Children's1, Case Western Reserve University2, University of Maryland, Baltimore3, University of Missouri–Kansas City4, Indiana University5, University of Colorado Denver6, Boston Children's Hospital7, University of British Columbia8, Thomas Jefferson University9, American Academy of Pediatrics10, Alfred I. duPont Hospital for Children11, Morehouse College12, Harvard University13, University of Texas Health Science Center at Houston14, University of Pittsburgh15, Columbia University Medical Center16, Cincinnati Children's Hospital Medical Center17
TL;DR: These pediatric hypertension guidelines are an update to the 2004 report and include revised recommendations on when to perform echocardiography in the evaluation of newly diagnosed hypertensive pediatric patients (generally only before medication initiation), along with a revised definition of left ventricular hypertrophy.
Abstract: These pediatric hypertension guidelines are an update to the 2004 “Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents.” Significant changes in these guidelines include (1) the replacement of the term “prehypertension” with the term “elevated blood pressure,” (2) new normative pediatric blood pressure (BP) tables based on normal-weight children, (3) a simplified screening table for identifying BPs needing further evaluation, (4) a simplified BP classification in adolescents ≥13 years of age that aligns with the forthcoming American Heart Association and American College of Cardiology adult BP guidelines, (5) a more limited recommendation to perform screening BP measurements only at preventive care visits, (6) streamlined recommendations on the initial evaluation and management of abnormal BPs, (7) an expanded role for ambulatory BP monitoring in the diagnosis and management of pediatric hypertension, and (8) revised recommendations on when to perform echocardiography in the evaluation of newly diagnosed hypertensive pediatric patients (generally only before medication initiation), along with a revised definition of left ventricular hypertrophy. These guidelines include 30 Key Action Statements and 27 additional recommendations derived from a comprehensive review of almost 15 000 published articles between January 2004 and July 2016. Each Key Action Statement includes level of evidence, benefit-harm relationship, and strength of recommendation. This clinical practice guideline, endorsed by the American Heart Association, is intended to foster a patient- and family-centered approach to care, reduce unnecessary and costly medical interventions, improve patient diagnoses and outcomes, support implementation, and provide direction for future research.
2,082 citations
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TL;DR: The autoantigens of a new category of treatment‐responsive paraneoplastic encephalitis are reported, and it is proposed that this category should be combined with existing treatment-responsive encephalopathy categories.
Abstract: Objective
To report the autoantigens of a new category of treatment-responsive paraneoplastic encephalitis.
2,079 citations
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TL;DR: The molecular mechanisms by which Ser133-phosphorylated CREB activates transcription, intracellular signaling pathways that lead to phosphorylation ofCREB at Ser133, and features of each signaling pathway that impart specificity at the level of CREB activation are discussed.
Abstract: Extracellular stimuli elicit changes in gene expression in target cells by activating intracellular protein kinase cascades that phosphorylate transcription factors within the nucleus. One of the best characterized stimulus-induced transcription factors, cyclic AMP response element (CRE)-binding protein (CREB), activates transcription of target genes in response to a diverse array of stimuli, including peptide hormones, growth factors, and neuronal activity, that activate a variety of protein kinases including protein kinase A (PKA), pp90 ribosomal S6 kinase (pp90RSK), and Ca2+/calmodulin-dependent protein kinases (CaMKs)[corrected]. These kinases all phosphorylate CREB at a particular residue, serine 133 (Ser133), and phosphorylation of Ser133 is required for CREB-mediated transcription. Despite this common feature, the mechanism by which CREB activates transcription varies depending on the stimulus. In some cases, signaling pathways target additional sites on CREB or proteins associated with CREB, permitting CREB to regulate distinct programs of gene expression under different conditions of stimulation. This review discusses the molecular mechanisms by which Ser133-phosphorylated CREB activates transcription, intracellular signaling pathways that lead to phosphorylation of CREB at Ser133, and features of each signaling pathway that impart specificity at the level of CREB activation.
2,078 citations
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TL;DR: The amyloid beta protein could function as a neurotrophic factor for differentiating neurons, but at high concentrations in mature neurons, as in Alzheimer's disease, could cause neuronal degeneration.
Abstract: The amyloid beta protein is deposited in the brains of patients with Alzheimer's disease but its pathogenic role is unknown. In culture, the amyloid beta protein was neurotrophic to undifferentiated hippocampal neurons at low concentrations and neurotoxic to mature neurons at higher concentrations. In differentiated neurons, amyloid beta protein caused dendritic and axonal retraction followed by neuronal death. A portion of the amyloid beta protein (amino acids 25 to 35) mediated both the trophic and toxic effects and was homologous to the tachykinin neuropeptide family. The effects of the amyloid beta protein were mimicked by tachykinin antagonists and completely reversed by specific tachykinin agonists. Thus, the amyloid beta protein could function as a neurotrophic factor for differentiating neurons, but at high concentrations in mature neurons, as in Alzheimer's disease, could cause neuronal degeneration.
2,077 citations
Authors
Showing all 165661 results
Name | H-index | Papers | Citations |
---|---|---|---|
Walter C. Willett | 334 | 2399 | 413322 |
Frederick E. Shelton | 327 | 1485 | 295883 |
Robert Langer | 281 | 2324 | 326306 |
Graham A. Colditz | 261 | 1542 | 256034 |
Frank B. Hu | 250 | 1675 | 253464 |
George M. Whitesides | 240 | 1739 | 269833 |
Eugene Braunwald | 230 | 1711 | 264576 |
Ralph B. D'Agostino | 226 | 1287 | 229636 |
Mark J. Daly | 204 | 763 | 304452 |
Eric B. Rimm | 196 | 988 | 147119 |
Virginia M.-Y. Lee | 194 | 993 | 148820 |
Bernard Rosner | 190 | 1162 | 147661 |
Stuart H. Orkin | 186 | 715 | 112182 |
Mark Hallett | 186 | 1170 | 123741 |
Ralph Weissleder | 184 | 1160 | 142508 |