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- Campbell, PJ, et al.
(författare)
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Pan-cancer analysis of whole genomes
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
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Tidskriftsartikel (refereegranskat)abstract
- Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1–3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10–18.
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- Hu, XS, et al.
(författare)
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Systemic evaluation of platelet and leukocyte activation and interaction in a rat model of pulmonary arterial hypertension
- 2010
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Ingår i: Cardiology. - : S. Karger AG. - 1421-9751 .- 0008-6312. ; 117:1, s. 44-53
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Tidskriftsartikel (refereegranskat)abstract
- <i>Objectives:</i> Thrombosis and inflammation are associated with the pathogenesis of pulmonary arterial hypertension (PAH). However, there are no solid data supporting the involvement of platelet and leukocyte activation and interaction in PAH. The present study thus investigated the activation and interaction of circulating platelets and leukocytes in a rat model of monocrotaline (MCT)-induced pulmonary hypertension. <i>Methods:</i> Mean pulmonary arterial pressure (mPAP) was monitored in rats (n = 24) before and 2, 3 and 7 weeks after MCT (60 mg/kg)injection. In parallel, activation of circulating platelets and leukocytes and platelet-leukocyte aggregates were measured by whole-blood flow cytometry. <i>Results:</i> Two weeks after MCT injection, mPAP had increased significantly, i.e. from 11.25 ± 0.92 mm Hg at baseline to 15.71 ± 1.66 mm Hg (p < 0.05), and it had increased even further at week 7 (26.83 ± 3.29 mm Hg; p < 0.01). Fibrinogen binding of circulating platelets had increased from the basal level of 1.45 ± 0.61 to 4.08 ± 1.59% 3 weeks after MCT injection (p < 0.01). Platelet responsiveness to ADP was also significantly enhanced. CD11b expression of circulating neutrophils was elevated; i.e. mean fluorescence intensity increased from 1.67 ± 0.38 before MCT injection to 2.37 ± 0.31 3 weeks after MCT injection (p < 0.01), and N-formyl-methionyl-leucyl-phenylalanine (1 × 10<sup>–7</sup><i>M</i>) stimulation induced more marked elevation of neutrophil CD11b expression in MCT-treated animals. Circulating platelet-neutrophil aggregates were already increased 2 weeks after MCT treatment (14.93 ± 4.22%; p < 0.01) compared to baseline (6.01 ± 2.91%) and remained elevated at 3 weeks (15.19 ± 4.78%; p < 0.01). <i>Conclusions:</i> MCT-induced PAH in rats is associated with increased platelet and leukocyte activation and platelet-leukocyte interaction in vivo, which may play an important role in the pathogenesis of PAH.
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- Abdoullaye, Doukary, et al.
(författare)
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Permanent genetic resources added to molecular ecology resources database 1 August 2009 - 30 September 2009
- 2010
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Ingår i: Molecular Ecology Resources. - : Wiley. - 1755-098X .- 1755-0998. ; 10:1, s. 232-236
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Tidskriftsartikel (refereegranskat)abstract
- This article documents the addition of 238 microsatellite marker loci and 72 pairs of Single Nucleotide Polymorphism (SNP) sequencing primers to the Molecular Ecology Resources Database. Loci were developed for the following species: Adelges tsugae, Artemisia tridentata, Astroides calycularis, Azorella selago, Botryllus schlosseri, Botrylloides violaceus, Cardiocrinum cordatum var. glehnii, Campylopterus curvipennis, Colocasia esculenta, Cynomys ludovicianus, Cynomys leucurus, Cynomys gunnisoni, Epinephelus coioides, Eunicella singularis, Gammarus pulex, Homoeosoma nebulella, Hyla squirella, Lateolabrax japonicus, Mastomys erythroleucus, Pararge aegeria, Pardosa sierra, Phoenicopterus ruber ruber and Silene latifolia. These loci were cross-tested on the following species: Adelges abietis, Adelges cooleyi, Adelges piceae, Pineus pini, Pineus strobi, Tubastrea micrantha, three other Tubastrea species, Botrylloides fuscus, Botrylloides simodensis, Campylopterus hemileucurus, Campylopterus rufus, Campylopterus largipennis, Campylopterus villaviscensio, Phaethornis longuemareus, Florisuga mellivora, Lampornis amethystinus, Amazilia cyanocephala, Archilochus colubris, Epinephelus lanceolatus, Epinephelus fuscoguttatus, Symbiodinium temperate-A clade, Gammarus fossarum, Gammarus roeselii, Dikerogammarus villosus and Limnomysis benedeni. This article also documents the addition of 72 sequencing primer pairs and 52 allele specific primers for Neophocaena phocaenoides.
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- Zhen, XM, et al.
(författare)
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Clinical and economic impact of methicillin-resistant Staphylococcus aureus: a multicentre study in China
- 2020
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1, s. 3900-
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Tidskriftsartikel (refereegranskat)abstract
- Methicillin-resistant Staphylococcus aureus (MRSA) has become a serious threat to global health. In China, the proportion of S. aureus isolates that were MRSA was 44.6% in 2014. The clinical and economic impact of MRSA in China remains largely uninvestigated. This study aims to compare the differences in hospital costs, length of hospital stay, and hospital mortality rate between MRSA and methicillin-susceptible S. aureus (MSSA) colonization or infection and between MRSA cases and those without an S. aureus infection. A retrospective and multicentre study was conducted in four tertiary hospitals in China between 2013 and 2015. Inpatient characteristics and hospital costs were collected from electronic medical records. We conducted propensity score matching (PSM) to eliminate selection bias by balancing the potential confounding variables between the two groups. The main indicators included hospital costs, length of hospital stay, and hospital mortality rate. A total of 1,335 inpatients with MRSA, 1,397 with MSSA, and 33,606 without an S. aureus infection were included. PSM obtained 954 and 1,313 pairs between the MRSA and MSSA groups and between the MRSA and S. aureus-free groups, respectively. After PSM, MRSA colonization or infection is associated with an increased total hospital cost ranging from $3,220 to $9,606, an excess length of hospital stay of 6 days–14 days, and an attributable hospital mortality rate of 0–3.58%. Between the MRSA and MSSA groups, MRSA colonization or infection was significantly associated with a higher total hospital cost and longer length of hospital stay among survivors but not among non-survivors; however, there were no differences in the hospital mortality rate between these two groups. Between the MRSA and the S. aureus-free groups, MRSA colonization or infection was significantly associated with an increased total hospital cost, a prolonged length of hospital stay and a higher hospital mortality rate among both survivors and non-survivors. It is critical to quantify the clinical and economic impact of MRSA to justify resource allocation for the development of strategies to improve clinical outcomes and to reduce the economic burden.
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- Zhen, XM, et al.
(författare)
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Clinical and Economic Impact of Third-Generation Cephalosporin-Resistant Infection or Colonization Caused by Escherichia coli and Klebsiella pneumoniae: A Multicenter Study in China
- 2020
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Ingår i: International journal of environmental research and public health. - : MDPI AG. - 1660-4601. ; 17:24
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Tidskriftsartikel (refereegranskat)abstract
- Quantifying economic and clinical outcomes for interventions could help to reduce third-generation cephalosporin resistance and Escherichia coli or Klebsiella pneumoniae. We aimed to compare the differences in clinical and economic burden between third-generation cephalosporin-resistant E. coli (3GCREC) and third-generation cephalosporin-susceptible E. coli (3GCSEC) cases, and between third-generation cephalosporin-resistant K. pneumoniae (3GCRKP) and third-generation cephalosporin-susceptible K. pneumoniae (3GCSKP) cases. A retrospective and multicenter study was conducted. We collected data from electronic medical records for patients who had clinical samples positive for E. coli or K. pneumoniae isolates during 2013 and 2015. Propensity score matching (PSM) was conducted to minimize the impact of potential confounding variables, including age, sex, insurance, number of diagnoses, Charlson comorbidity index, admission to intensive care unit, surgery, and comorbidities. We also repeated the PSM including length of stay (LOS) before culture. The main indicators included economic costs, LOS and hospital mortality. The proportions of 3GCREC and 3GCRKP in the sampled hospitals were 44.3% and 32.5%, respectively. In the two PSM methods, 1804 pairs and 1521 pairs were generated, and 1815 pairs and 1617 pairs were obtained, respectively. Compared with susceptible cases, those with 3GCREC and 3GCRKP were associated with significantly increased total hospital cost and excess LOS. Inpatients with 3GCRKP were significantly associated with higher hospital mortality compared with 3GCSKP cases, however, there was no significant difference between 3GCREC and 3GCSEC cases. Cost reduction and outcome improvement could be achieved through a preventative approach in terms of both antimicrobial stewardship and preventing the transmission of organisms.
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| 21. |
- Zhen, XM, et al.
(författare)
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The Clinical and Economic Impact of Antibiotic Resistance in China: A Systematic Review and Meta-Analysis
- 2019
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Ingår i: Antibiotics (Basel, Switzerland). - : MDPI AG. - 2079-6382. ; 8:3
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Tidskriftsartikel (refereegranskat)abstract
- Antibiotic resistance (ABR) is one of the biggest threats to global health, especially in China. This study aims to analyze the published literature on the clinical and economic impact of ABR or multi-drug resistant (MDR) bacteria compared to susceptible bacteria or non-infection, in mainland China. English and Chinese databases were searched to identify relevant studies evaluating mortality, hospital stay, and hospital costs of ABR. A meta-analysis of mortality was performed using a random effects model. The costs were converted into 2015 United States (US) dollars. Of 13,693 studies identified, 44 eligible studies were included. Twenty-nine investigated the impact of ABR on hospital mortality, 37 were focused on hospital stay, and 21 on hospital costs. Patients with ABR were associated with a greater risk of overall mortality compared to those with susceptibility or those without infection (odds ratio: 2.67 and 3.29, 95% confidence interval: 2.18–3.26 and 1.71–6.33, p < 0.001 and p < 0.001, respectively). The extra mean total hospital stay and total hospital cost were reported, ranging from 3 to 46 days, and from US$238 to US$16,496, respectively. Our study indicates that ABR is associated with significantly higher mortality. Moreover, ABR is not always, but usually, associated with significantly longer hospital stay and higher hospital costs.
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