| 1. |
- van Houten, C. B., et al.
(författare)
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Antibiotic misuse in respiratory tract infections in children and adultsa prospective, multicentre study (TAILORED Treatment)
- 2019
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Ingår i: European Journal of Clinical Microbiology & Infectious Diseases. - : Springer Science and Business Media LLC. - 0934-9723 .- 1435-4373. ; 38:3, s. 505-514
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Tidskriftsartikel (refereegranskat)abstract
- Respiratory tract infections (RTI) are more commonly caused by viral pathogens in children than in adults. Surprisingly, little is known about antibiotic use in children as compared to adults with RTI. This prospective study aimed to determine antibiotic misuse in children and adults with RTI, using an expert panel reference standard, in order to prioritise the target age population for antibiotic stewardship interventions. We recruited children and adults who presented at the emergency department or were hospitalised with clinical presentation of RTI in The Netherlands and Israel. A panel of three experienced physicians adjudicated a reference standard diagnosis (i.e. bacterial or viral infection) for all the patients using all available clinical and laboratory information, including a 28-day follow-up assessment. The cohort included 284 children and 232 adults with RTI (median age, 1.3years and 64.5years, respectively). The proportion of viral infections was larger in children than in adults (209(74%) versus 89(38%), p<0.001). In case of viral RTI, antibiotics were prescribed (i.e. overuse) less frequently in children than in adults (77/209 (37%) versus 74/89 (83%), p<0.001). One (1%) child and three (2%) adults with bacterial infection were not treated with antibiotics (i.e. underuse); all were mild cases. This international, prospective study confirms major antibiotic overuse in patients with RTI. Viral infection is more common in children, but antibiotic overuse is more frequent in adults with viral RTI. Together, these findings support the need for effective interventions to decrease antibiotic overuse in RTI patients of all ages.
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| 2. |
- Zhang, Haofei, et al.
(författare)
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Monoterpenes are the largest source of summertime organic aerosol in the southeastern United States
- 2018
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 115:9, s. 2038-2043
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Tidskriftsartikel (refereegranskat)abstract
- The chemical complexity of atmospheric organic aerosol (OA) has caused substantial uncertainties in understanding its origins and environmental impacts. Here, we provide constraints on OA origins through compositional characterization with molecular-level details. Our results suggest that secondary OA (SOA) from monoterpene oxidation accounts for approximately half of summertime fine OA in Centreville, AL, a forested area in the southeastern United States influenced by anthropogenic pollution. We find that different chemical processes involving nitrogen oxides, during days and nights, play a central role in determining the mass of monoterpene SOA produced. These findings elucidate the strong anthropogenic–biogenic interaction affecting ambient aerosol in the southeastern United States and point out the importance of reducing anthropogenic emissions, especially under a changing climate, where biogenic emissions will likely keep increasing.
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| 3. |
- Weinstein, John N., et al.
(författare)
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The cancer genome atlas pan-cancer analysis project
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:10, s. 1113-1120
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Forskningsöversikt (refereegranskat)abstract
- The Cancer Genome Atlas (TCGA) Research Network has profiled and analyzed large numbers of human tumors to discover molecular aberrations at the DNA, RNA, protein and epigenetic levels. The resulting rich data provide a major opportunity to develop an integrated picture of commonalities, differences and emergent themes across tumor lineages. The Pan-Cancer initiative compares the first 12 tumor types profiled by TCGA. Analysis of the molecular aberrations and their functional roles across tumor types will teach us how to extend therapies effective in one cancer type to others with a similar genomic profile. © 2013 Nature America, Inc. All rights reserved.
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| 4. |
- Borovok, I, et al.
(författare)
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Streptomyces spp. contain class Ia and class II ribonucleotide reductases: expression analysis of the genes in vegetative growth
- 2002
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Ingår i: Microbiology (Reading, England). - : Microbiology Society. - 1350-0872 .- 1465-2080. ; 148:Pt 2, s. 391-404
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Tidskriftsartikel (refereegranskat)abstract
- Genes encoding two ribonucleotide reductases (RNRs) were identified in members of the genusStreptomyces. One gene,nrdJ, encoded an oligomeric protein comprising four identical subunits each with a molecular mass of ∼108 kDa. The activity of this protein depended on the presence of 5′-deoxyadenosylcobalamine (coenzyme B12), establishing it as a class II RNR. TheStreptomyces clavuligerus nrdJgene was cloned, using internal peptide sequences from the purified protein, and was found to encode a polypeptide of 961 aa. Molecular phylogenetic analysis showed that theS. clavuligerusclass II RNR shares significant similarity with most other bacterial and archaeal class II RNRs. Two other genes,nrdAandnrdB, were initially identified in theStreptomyces coelicolorgenome database in unannotated ORFs as encoding a class Ia RNR. Southern analysis demonstrated that thenrdABgenes were present in differentStreptomycesspp. TheS. coelicolor nrdABgenes were cloned and expressed inEscherichia coli, and the recombinant proteins were shown to represent a class I RNR. It was shown, using quantitative real-time PCR, that theS. clavuligerusclass Ia and class II RNR genes were differentially transcribed during vegetative growth. The copy number of the class IInrdJtranscripts was approximately constant throughout the exponential phase of vegetative growth (3–5×105copies per 400 ng total RNA after reverse transcription). In contrast, the copy number of the class IanrdABtranscripts was some 10- to 20-fold less than that ofnrdJin the early-exponential growth phase (2·8×104copies), and decreased markedly at the mid-exponential (4×103copies) and late-exponential phases (1·1×103copies) of growth. A possible role for the involvement of two RNRs during vegetative growth is discussed.
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| 5. |
- Cohen, A., et al.
(författare)
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A multifaceted 'omics' approach for addressing the challenge of antimicrobial resistance
- 2015
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Ingår i: Future Microbiology. - : Future Medicine Ltd. - 1746-0913 .- 1746-0921. ; 10:3, s. 365-376
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Tidskriftsartikel (refereegranskat)abstract
- The inappropriate use of antibiotics has severe global health and economic consequences, including the emergence of antibiotic-resistant bacteria. A major driver of antibiotic misuse is the inability to accurately distinguish between bacterial and viral infections based on currently available diagnostic solutions. A multifaceted 'omics' approach that integrates personalized patient data such as genetic predisposition to infections (genomics), natural microbiota composition and immune response to infection (proteomics and transcriptomics) together with comprehensive pathogen profiling has the potential to help physicians improve their antimicrobial prescribing practices. In this respect, the EU has funded a multidisciplinary project (TAILORED-Treatment) that will develop novel omics-based personalized treatment schemes that have the potential to reduce antibiotic consumption, and help limiting the spread of antibiotic resistance.
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| 6. |
- Qin, Yue, et al.
(författare)
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A multi-scale map of cell structure fusing protein images and interactions
- 2021
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Ingår i: Nature. - : Springer Nature. - 0028-0836 .- 1476-4687. ; 600:7889, s. 536-
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Tidskriftsartikel (refereegranskat)abstract
- The cell is a multi-scale structure with modular organization across at least four orders of magnitude(1). Two central approaches for mapping this structure-protein fluorescent imaging and protein biophysical association-each generate extensive datasets, but of distinct qualities and resolutions that are typically treated separately(2,3). Here we integrate immunofluorescence images in the Human Protein Atlas(4) with affinity purifications in BioPlex(5) to create a unified hierarchical map of human cell architecture. Integration is achieved by configuring each approach as a general measure of protein distance, then calibrating the two measures using machine learning. The map, known as the multi-scale integrated cell (MuSIC 1.0), resolves 69 subcellular systems, of which approximately half are to our knowledge undocumented. Accordingly, we perform 134 additional affinity purifications and validate subunit associations for the majority of systems. The map reveals a pre-ribosomal RNA processing assembly and accessory factors, which we show govern rRNA maturation, and functional roles for SRRM1 and FAM120C in chromatin and RPS3A in splicing. By integration across scales, MuSIC increases the resolution of imaging while giving protein interactions a spatial dimension, paving the way to incorporate diverse types of data in proteome-wide cell maps.
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