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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TL;DR: Higher levels of blood lead at age 24 months, but not at other ages, were significantly associated with lower global scores on both the WISC-R and the K-TEA after adjustment for potential confounders.
Abstract: The implications of low-level lead exposure for children's intellectual and academic performance at school age are uncertain. This issue was investigated in a prospective study of middle-class and upper-middle-class children with low lifetime exposures to lead. A battery of neuropsychological tests was administered at age 10 years to 148 children whose lead exposure and cognitive function had been previously assessed at ages 6, 12, 18, 24, and 57 months. Primary endpoints were Wechsler Intelligence Scale for Children-Revised (WISC-R) and the Kaufman Test of Educational Achievement (K-TEA). Higher levels of blood lead at age 24 months, but not at other ages, were significantly associated with lower global scores on both the WISC-R and the K-TEA after adjustment for potential confounders. Over the range of approximately 0 to 25 micrograms/dL, a 0.48-mumol/L (10 micrograms/dL) increase in blood lead at 24 months was associated with a 5.8-point decline in WISC-R Full-Scale IQ (95% confidence interval: 1.7 to 9.9, P = .007) and an 8.9-point decline in K-TEA Battery Composite score (95% confidence interval: 4.2 to 13.6, P = .0003). Mean blood lead level at age 24 months was 0.31 mumol/L (6.5 micrograms/dL; SD: 4.9, 90% percentile: 12.5). Slightly elevated blood lead levels around the age of 24 months are associated with intellectual and academic performance deficits at age 10 years.
658 citations
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German Cancer Research Center1, Heidelberg University2, Max Planck Society3, University of Cambridge4, Russian Academy5, McGill University6, University of Amsterdam7, University of Würzburg8, University Hospital Heidelberg9, University of Tübingen10, Stanford University11, Broad Institute12, Harvard University13, University of Toronto14, New York University15, Johns Hopkins University16, Boston Children's Hospital17, University of Münster18, University of Düsseldorf19, McGill University Health Centre20
TL;DR: Recurrent activating mutations in FGFR1 and PTPN11 and new NTRK2 fusion genes in non-cerebellar tumors and new BRAF-activating changes were observed, indicating that pilocytic astrocytoma is predominantly a single-pathway disease.
Abstract: Pilocytic astrocytoma, the most common childhood brain tumor, is typically associated with mitogen-activated protein kinase (MAPK) pathway alterations. Surgically inaccessible midline tumors are therapeutically challenging, showing sustained tendency for progression and often becoming a chronic disease with substantial morbidities. Here we describe whole-genome sequencing of 96 pilocytic astrocytomas, with matched RNA sequencing (n = 73), conducted by the International Cancer Genome Consortium (ICGC) PedBrain Tumor Project. We identified recurrent activating mutations in FGFR1 and PTPN11 and new NTRK2 fusion genes in non-cerebellar tumors. New BRAF-activating changes were also observed. MAPK pathway alterations affected all tumors analyzed, with no other significant mutations identified, indicating that pilocytic astrocytoma is predominantly a single-pathway disease. Notably, we identified the same FGFR1 mutations in a subset of H3F3A-mutated pediatric glioblastoma with additional alterations in the NF1 gene. Our findings thus identify new potential therapeutic targets in distinct subsets of pilocytic astrocytoma and childhood glioblastoma.
657 citations
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Woolcock Institute of Medical Research1, University of Cape Town2, University of Manitoba3, Laval University4, Federal University of Bahia5, Harvard University6, Helsinki University Central Hospital7, Kagoshima University8, Erasmus University Rotterdam9, University of Wisconsin-Madison10, McMaster University11, University of Pisa12, University of Southern Denmark13, Universidade Federal de Santa Catarina14, University of Costa Rica15, Boston Children's Hospital16, The Chinese University of Hong Kong17, University of British Columbia18
TL;DR: The changes include a revised asthma definition, tools for assessing symptom control and risk factors for adverse outcomes, and updated strategies for adaptation and implementation of GINA recommendations.
Abstract: Over the past 20 years, the Global Initiative for Asthma (GINA) has regularly published and annually updated a global strategy for asthma management and prevention that has formed the basis for many national guidelines. However, uptake of existing guidelines is poor. A major revision of the GINA report was published in 2014, and updated in 2015, reflecting an evolving understanding of heterogeneous airways disease, a broader evidence base, increasing interest in targeted treatment, and evidence about effective implementation approaches. During development of the report, the clinical utility of recommendations and strategies for their practical implementation were considered in parallel with the scientific evidence.This article provides a summary of key changes in the GINA report, and their rationale. The changes include a revised asthma definition; tools for assessing symptom control and risk factors for adverse outcomes; expanded indications for inhaled corticosteroid therapy; a framework for targeted treatment based on phenotype, modifiable risk factors, patient preference, and practical issues; optimisation of medication effectiveness by addressing inhaler technique and adherence; revised recommendations about written asthma action plans; diagnosis and initial treatment of the asthma-chronic obstructive pulmonary disease overlap syndrome; diagnosis in wheezing pre-school children; and updated strategies for adaptation and implementation of GINA recommendations.
657 citations
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University of Texas Southwestern Medical Center1, University of California, San Diego2, Boston Children's Hospital3, Howard Hughes Medical Institute4, Baylor College of Medicine5, Washington University in St. Louis6, Reata Pharmaceuticals7, Utrecht University8, Cancer Research UK9, Harvard University10, Broad Institute11, Columbia University12, University of California, Berkeley13
TL;DR: Through the characterization of a domain of beclin 1 that interacts with HIV-1 Nef, an autophagy-inducing peptide is developed that has potential efficacy in the treatment of human diseases.
Abstract: The lysosomal degradation pathway of autophagy has a crucial role in defence against infection, neurodegenerative disorders, cancer and ageing. Accordingly, agents that induce autophagy may have broad therapeutic applications. One approach to developing such agents is to exploit autophagy manipulation strategies used by microbial virulence factors. Here we show that a peptide, Tat-beclin 1-derived from a region of the autophagy protein, beclin 1, which binds human immunodeficiency virus (HIV)-1 Nef-is a potent inducer of autophagy, and interacts with a newly identified negative regulator of autophagy, GAPR-1 (also called GLIPR2). Tat-beclin 1 decreases the accumulation of polyglutamine expansion protein aggregates and the replication of several pathogens (including HIV-1) in vitro, and reduces mortality in mice infected with chikungunya or West Nile virus. Thus, through the characterization of a domain of beclin 1 that interacts with HIV-1 Nef, we have developed an autophagy-inducing peptide that has potential efficacy in the treatment of human diseases.
656 citations
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TL;DR: Using a murine model of chronic myelogenous leukemia, it is shown that malignant and nonmalignant neutrophils are more prone to NET formation and an increased sensitivity toward NET generation is observed in mammary and lung carcinoma models, suggesting that cancers, through a systemic effect on the host, can induce an increase in peripheral blood neutophils, which are predisposed to NET Formation.
Abstract: Cancer-associated thrombosis often lacks a clear etiology. However, it is linked to a poor prognosis and represents the second-leading cause of death in cancer patients. Recent studies have shown that chromatin released into blood, through the generation of neutrophil extracellular traps (NETs), is procoagulant and prothrombotic. Using a murine model of chronic myelogenous leukemia, we show that malignant and nonmalignant neutrophils are more prone to NET formation. This increased sensitivity toward NET generation is also observed in mammary and lung carcinoma models, suggesting that cancers, through a systemic effect on the host, can induce an increase in peripheral blood neutrophils, which are predisposed to NET formation. In addition, in the late stages of the breast carcinoma model, NETosis occurs concomitant with the appearance of venous thrombi in the lung. Moreover, simulation of a minor systemic infection in tumor-bearing, but not control, mice results in the release of large quantities of chromatin and a prothrombotic state. The increase in neutrophil count and their priming is mediated by granulocyte colony-stimulating factor (G-CSF), which accumulates in the blood of tumor-bearing mice. The prothrombotic state in cancer can be reproduced by treating mice with G-CSF combined with low-dose LPS and leads to thrombocytopenia and microthrombosis. Taken together, our results identify extracellular chromatin released through NET formation as a cause for cancer-associated thrombosis and unveil a target in the effort to decrease the incidence of thrombosis in cancer patients.
656 citations
Authors
Showing all 165661 results
Name | H-index | Papers | Citations |
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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 |