Institution
Utrecht University
Education•Utrecht, Utrecht, Netherlands•
About: Utrecht University is a education organization based out in Utrecht, Utrecht, Netherlands. It is known for research contribution in the topics: Population & Context (language use). The organization has 58176 authors who have published 139351 publications receiving 6214282 citations. The organization is also known as: UU & Universiteit Utrecht.
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TL;DR: In this article, the authors provide guidance on how to calculate the sample size required to develop a clinical prediction model.
Abstract: Clinical prediction models aim to predict outcomes in individuals, to inform diagnosis or prognosis in healthcare. Hundreds of prediction models are published in the medical literature each year, yet many are developed using a dataset that is too small for the total number of participants or outcome events. This leads to inaccurate predictions and consequently incorrect healthcare decisions for some individuals. In this article, the authors provide guidance on how to calculate the sample size required to develop a clinical prediction model.
646 citations
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United States Department of Health and Human Services1, Erasmus University Rotterdam2, University of California, Berkeley3, Johns Hopkins University4, Icahn School of Medicine at Mount Sinai5, University of Southern California6, Duke University7, University of Bristol8, University Medical Center Groningen9, University of California, San Francisco10, North Carolina State University11, Karolinska Institutet12, Pompeu Fabra University13, University of Paris14, University of Memphis15, Centre Hospitalier Universitaire de Grenoble16, University of Bergen17, Isfahan University of Medical Sciences18, Brigham and Women's Hospital19, Oslo University Hospital20, Utrecht University21, French Institute of Health and Medical Research22, Norwegian Institute of Public Health23, Johns Hopkins University School of Medicine24, Harvard University25, International Agency for Research on Cancer26, Paris Descartes University27, Michigan State University28, Centre national de la recherche scientifique29, Fred Hutchinson Cancer Research Center30, University of Basel31, Swiss Tropical and Public Health Institute32, Stockholm County Council33, University of Southampton34
TL;DR: This large scale meta-analysis of methylation data identified numerous loci involved in response to maternal smoking in pregnancy with persistence into later childhood and provide insights into mechanisms underlying effects of this important exposure.
Abstract: Epigenetic modifications, including DNA methylation, represent a potential mechanism for environmental impacts on human disease. Maternal smoking in pregnancy remains an important public health problem that impacts child health in a myriad of ways and has potential lifelong consequences. The mechanisms are largely unknown, but epigenetics most likely plays a role. We formed the Pregnancy And Childhood Epigenetics (PACE) consortium and meta-analyzed, across 13 cohorts (n = 6,685), the association between maternal smoking in pregnancy and newborn blood DNA methylation at over 450,000 CpG sites (CpGs) by using the Illumina 450K BeadChip. Over 6,000 CpGs were differentially methylated in relation to maternal smoking at genome-wide statistical significance (false discovery rate, 5%), including 2,965 CpGs corresponding to 2,017 genes not previously related to smoking and methylation in either newborns or adults. Several genes are relevant to diseases that can be caused by maternal smoking (e.g., orofacial clefts and asthma) or adult smoking (e.g., certain cancers). A number of differentially methylated CpGs were associated with gene expression. We observed enrichment in pathways and processes critical to development. In older children (5 cohorts, n = 3,187), 100% of CpGs gave at least nominal levels of significance, far more than expected by chance (p value < 2.2 × 10(-16)). Results were robust to different normalization methods used across studies and cell type adjustment. In this large scale meta-analysis of methylation data, we identified numerous loci involved in response to maternal smoking in pregnancy with persistence into later childhood and provide insights into mechanisms underlying effects of this important exposure.
646 citations
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TL;DR: It is demonstrated that bacteria directly activate nociceptors, and that the immune response mediated through TLR2, MyD88, T cells, B cells, and neutrophils and monocytes is not necessary for Staphylococcus aureus-induced pain in mice.
Abstract: Nociceptor sensory neurons are specialized to detect potentially damaging stimuli, protecting the organism by initiating the sensation of pain and eliciting defensive behaviours. Bacterial infections produce pain by unknown molecular mechanisms, although they are presumed to be secondary to immune activation. Here we demonstrate that bacteria directly activate nociceptors, and that the immune response mediated through TLR2, MyD88, T cells, B cells, and neutrophils and monocytes is not necessary for Staphylococcus aureus-induced pain in mice. Mechanical and thermal hyperalgesia in mice is correlated with live bacterial load rather than tissue swelling or immune activation. Bacteria induce calcium flux and action potentials in nociceptor neurons, in part via bacterial N-formylated peptides and the pore-forming toxin α-haemolysin, through distinct mechanisms. Specific ablation of Nav1.8-lineage neurons, which include nociceptors, abrogated pain during bacterial infection, but concurrently increased local immune infiltration and lymphadenopathy of the draining lymph node. Thus, bacterial pathogens produce pain by directly activating sensory neurons that modulate inflammation, an unsuspected role for the nervous system in host-pathogen interactions.
645 citations
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TL;DR: MS-based proteomics is starting to mature and to deliver through a combination of developments in instrumentation, sample preparation and computational analysis, and to highlight recent applications.
Abstract: Next-generation sequencing allows the analysis of genomes, including those representing disease states. However, the causes of most disorders are multifactorial, and systems-level approaches, including the analysis of proteomes, are required for a more comprehensive understanding. The proteome is extremely multifaceted owing to splicing and protein modifications, and this is further amplified by the interconnectivity of proteins into complexes and signalling networks that are highly divergent in time and space. Proteome analysis heavily relies on mass spectrometry (MS). MS-based proteomics is starting to mature and to deliver through a combination of developments in instrumentation, sample preparation and computational analysis. Here we describe this emerging next generation of proteomics and highlight recent applications.
645 citations
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TL;DR: If there are indeed two (or more) subtypes of asthma, and if non-eosinophilic (neutrophil mediated) asthma is relatively common, this would have major consequences for the treatment and Prevention of asthma since most treatment and prevention strategies are now almost entirely focused on allergic/eos inophilic asthma and allergen avoidance measures, respectively.
Abstract: There is increasing evidence that inflammatory mechanisms other than eosinophilic inflammation may be involved in producing the final common pathway of enhanced bronchial reactivity and reversible airflow obstruction that characterises asthma. A review of the literature has shown that, at most, only 50% of asthma cases are attributable to eosinophilic airway inflammation. It is hypothesised that a major proportion of asthma is based on neutrophilic airway inflammation, possibly triggered by environmental exposure to bacterial endotoxin, particulate air pollution, and ozone, as well as viral infections. If there are indeed two (or more) subtypes of asthma, and if non-eosinophilic (neutrophil mediated) asthma is relatively common, this would have major consequences for the treatment and prevention of asthma since most treatment and prevention strategies are now almost entirely focused on allergic/eosinophilic asthma and allergen avoidance measures, respectively. It is therefore important to study the aetiology of asthma further, including the underlying inflammatory profiles.
645 citations
Authors
Showing all 58756 results
Name | H-index | Papers | Citations |
---|---|---|---|
Ronald C. Kessler | 274 | 1332 | 328983 |
Albert Hofman | 267 | 2530 | 321405 |
Douglas G. Altman | 253 | 1001 | 680344 |
Hans Clevers | 199 | 793 | 169673 |
Craig B. Thompson | 195 | 557 | 173172 |
Patrick W. Serruys | 186 | 2427 | 173210 |
Ruedi Aebersold | 182 | 879 | 141881 |
Dennis S. Charney | 179 | 802 | 122408 |
Kenneth S. Kendler | 177 | 1327 | 142251 |
Jean Louis Vincent | 161 | 1667 | 163721 |
Vilmundur Gudnason | 159 | 837 | 123802 |
Monique M.B. Breteler | 159 | 546 | 93762 |
Lex M. Bouter | 158 | 767 | 103034 |
Elio Riboli | 158 | 1136 | 110499 |
Roy F. Baumeister | 157 | 650 | 132987 |