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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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- Duo, Y, et al.
(författare)
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Noncancerous disease-targeting AIEgens
- 2023
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Ingår i: Chemical Society reviews. - : Royal Society of Chemistry (RSC). - 1460-4744 .- 0306-0012. ; 52:3, s. 1024-1067
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Tidskriftsartikel (refereegranskat)abstract
- Schematic diagram of noncancerous disease-targeting AIEgens.
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- Khatri, C, et al.
(författare)
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Outcomes after perioperative SARS-CoV-2 infection in patients with proximal femoral fractures: an international cohort study
- 2021
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Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 11:11, s. e050830-
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Tidskriftsartikel (refereegranskat)abstract
- Studies have demonstrated high rates of mortality in people with proximal femoral fracture and SARS-CoV-2, but there is limited published data on the factors that influence mortality for clinicians to make informed treatment decisions. This study aims to report the 30-day mortality associated with perioperative infection of patients undergoing surgery for proximal femoral fractures and to examine the factors that influence mortality in a multivariate analysis.SettingProspective, international, multicentre, observational cohort study.ParticipantsPatients undergoing any operation for a proximal femoral fracture from 1 February to 30 April 2020 and with perioperative SARS-CoV-2 infection (either 7 days prior or 30-day postoperative).Primary outcome30-day mortality. Multivariate modelling was performed to identify factors associated with 30-day mortality.ResultsThis study reports included 1063 patients from 174 hospitals in 19 countries. Overall 30-day mortality was 29.4% (313/1063). In an adjusted model, 30-day mortality was associated with male gender (OR 2.29, 95% CI 1.68 to 3.13, p<0.001), age >80 years (OR 1.60, 95% CI 1.1 to 2.31, p=0.013), preoperative diagnosis of dementia (OR 1.57, 95% CI 1.15 to 2.16, p=0.005), kidney disease (OR 1.73, 95% CI 1.18 to 2.55, p=0.005) and congestive heart failure (OR 1.62, 95% CI 1.06 to 2.48, p=0.025). Mortality at 30 days was lower in patients with a preoperative diagnosis of SARS-CoV-2 (OR 0.6, 95% CI 0.6 (0.42 to 0.85), p=0.004). There was no difference in mortality in patients with an increase to delay in surgery (p=0.220) or type of anaesthetic given (p=0.787).ConclusionsPatients undergoing surgery for a proximal femoral fracture with a perioperative infection of SARS-CoV-2 have a high rate of mortality. This study would support the need for providing these patients with individualised medical and anaesthetic care, including medical optimisation before theatre. Careful preoperative counselling is needed for those with a proximal femoral fracture and SARS-CoV-2, especially those in the highest risk groups.Trial registration numberNCT04323644
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- Ye, Q, et al.
(författare)
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A novel pattern of pp65-positive cytomegalic endothelial cells circulating in peripheral blood from a renal transplant recipient
- 2004
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Ingår i: Acta Histochemica. - : Elsevier BV. - 0065-1281. ; 106:2, s. 107-110
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Tidskriftsartikel (refereegranskat)abstract
- The present study reports a novel pattern of cytomegalic endothelial cells (CEC) in peripheral blood from a female renal transplant recipient infected with human cytomegalovirus (HCMV), which has not been reported previously. Localization of specific early antigen of HCMV, pp65 antigen, was examined by immunohistochemistry. Staining of an endothelial cell marker (CD34) was used to characterize endothelial cells. It is demonstrated that many leukocytes surrounded and adhered to a protein-like material, in which pp65-positive CEC were detected. The composition and function of this protein-like material are yet unknown. The patient tacked clinical symptoms of HCMV disease. Furthermore, similar localization patterns were found in other renal. transplant recipients suffering from HCMV infections as determined by real-time PCR to detect HCMV DNA in blood. These patients showed no or only minor clinical symptoms of HCMV infection. It is suggested that these novel Localization patterns of CEC may play a role in the host defense in patients infected with HCMV, but the exact relation between HCMV infection and CEC formation needs further investigation. (C) 2004 Elsevier GmbH. All rights reserved.
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- Zhang, XY, et al.
(författare)
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Expression pattern of apolipoprotein M during mouse and human embryogenesis
- 2004
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Ingår i: Acta Histochemica. - : Elsevier BV. - 0065-1281. ; 106:2, s. 123-128
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Tidskriftsartikel (refereegranskat)abstract
- Apolipoprotein M (apoM) is a recently discovered human apolipoprotein predominantly present in high-density lipoprotein (HDL), and in minor proportions in triglyceride-rich lipoprotein (TGRLP) and low-density lipoprotein (LDL). The gene encoding apoM is present in all mammalian genomes. The identity of the apoM gene of human, rat and mouse is over 80%. However, the (patho)physiological functions of apoM are unknown yet. In the present study, we investigated apoM expression patterns during mouse and human embryogenesis. ApoM transcripts were detectable in mouse embryos from day 7.5 to day 18.5. ApoM was expressed at low levels at day 7.5, its expression increased significantly at day 9.7, decreased at day 10.5, and then increased continually up to day 18.5. ApoM-positive cells appeared mainly in liver of day-12 embryos as detected by in situ hybridization. In day-15 embryos, apoM was expressed in both liver and kidney. During human embryogenesis, apoM was mainly expressed in liver and kidney and little was found in small intestine as determined by mRNA array of human fetal. normal tissues. ApoM was also detected in stomach and skeletal muscle in early stages of embryogenesis (3-5 months). (C) 2004 Elsevier GmbH. All rights reserved.
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| 27. |
- Zhang, XY, et al.
(författare)
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Specific tissue expression and cellular localization of human apolipoprotein M as determined by in situ hybridization
- 2003
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Ingår i: Acta Histochemica. - : Elsevier BV. - 0065-1281. ; 105:1, s. 67-72
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Tidskriftsartikel (refereegranskat)abstract
- Apolipoprotein M (apoM) is a recently discovered human apolipoprotein predominantly present in high-density lipoprotein (HDL), and in minor proportion in triglyceride-rich lipoprotein (TGRLP) and low-density lipoprotein (LDL). The gene coding for apoM has been detected in all mammal genomes. The function of apoM is unknown yet. In the present study, we demonstrated that apoM is exclusively expressed in a strong manner in adult liver and kidney, and is expressed weakly in fetal liver and kidney as detected with human multiple tissue expression array. Both immumohistochemical staining and apoM mRNA in situ hybridization demonstrated that apoM was exclusively expressed in hepatocytes in human liver and in tubular epithelial cells in human kidney. The present study helps to elucidate the pathophysiological functions of apoM in vivo.
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