| 220881. |
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| 220882. |
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| 220883. |
- Skau, Emma, et al.
(författare)
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Are the results from a multiplex proteomic assay and a conventional immunoassay for NT-proBNP and GDF-15 comparable?
- 2023
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Ingår i: Clinical Proteomics. - : BioMed Central (BMC). - 1542-6416 .- 1559-0275. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: We aimed to compare absolute plasma concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP) and growth differentiation factor 15 (GDF-15) obtained by a conventional immunoassay with the corresponding relative concentrations from a proximity extension assay (PEA) and compare the prognostic impact of the protein levels obtained from these assays.Methods: We evaluated 437 patients with peripheral arterial disease (PAD) and a population-based cohort of 643 individuals without PAD. Correlations were calculated using Spearman's rank correlation coefficients (rho). The discriminatory accuracy of the protein levels to predict future cardiovascular events was analyzed with Cox regression and presented as time-dependent areas under the receiver-operator-characteristic curves (tdAUCs).Results: For NT-proBNP, the two assays correlated with rho 0.93 and 0.93 in the respective cohort. The PEA values leveled off at higher values in both cohorts. The corresponding correlations for GDF-15 were 0.91 and 0.89. At 5 years follow-up, the tdAUCs in the patient cohort were similar for NT-proBNP and GDF-15 regardless of assay used (0.65-0.66). The corresponding tdAUCs in the population-based cohort were between 0.72 and 0.77.Conclusion: Except for the highest levels of NT-proBNP, we suggest that PEA data for NT-proBNP and GDF-15 reliably reflects absolute plasma levels and contains similar prognostic information.
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| 220884. |
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| 220885. |
- Skau, Emma, et al.
(författare)
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GDF-15 and TRAIL-R2 are powerful predictors of long-term mortality in patients with acute myocardial infarction
- 2017
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Ingår i: European Journal of Preventive Cardiology. - : Oxford University Press (OUP). - 2047-4873 .- 2047-4881. ; 24:15, s. 1576-1583
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Tidskriftsartikel (refereegranskat)abstract
- Background The Proximity Extension Assay proteomics chip provides a large-scale analysis of 92 biomarkers linked to cardiovascular disease or inflammation. We aimed to identify the biomarkers that best predicted long-term all-cause mortality in patients with acute myocardial infarction. Methods In this prospective cohort study, 92 biomarkers were analysed in 847 consecutive patients from the Vastmanland Myocardial Infarction Study with a median follow-up of 6.9 years. Results The mean ( standard deviation) age of the patients was 70 (11.8) years and 32.7% were female. Two hundred and seven patients had died after follow-up. The biomarkers most strongly linked to all-cause mortality were growth differentiation factor 15 (GDF-15) and tumour necrosis factor-related apoptosis-inducing ligand receptor 2 (TRAIL-R2). Cox regression analysis showed that GDF-15 (hazard ratio 1.25 per unit change, 95% confidence interval, 1.02-1.53, p=0.031) and TRAIL-R2 (hazard ratio 1.37 per unit change, 95% confidence interval 1.12-1.67, p=0.002) were independent predictors of long-term all-cause mortality after adjusting for age, gender, diabetes, previous myocardial infarction, stroke, heart failure, hypertension, smoking, hypercholesterolaemia, body mass index, ST-elevation myocardial infarction, left ventricular ejection fraction, troponin I, estimated glomerular filtration rate, N-terminal pro-brain natriuretic peptide and C-reactive protein. The combination of GDF-15 and TRAIL-R2 with established risk factors and biomarkers showed a discriminating accuracy of separating survivors from non-survivors with a cross-validated area under the receiving operating characteristics curve of 0.88 within five years. Conclusion GDF-15 and TRAIL-R2 were the most powerful Proximity Extension Assay chip biomarkers in predicting long-term all-cause mortality in patients with acute myocardial infarction.
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| 220886. |
- Skau, Emma, et al.
(författare)
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Targeted multiplex proteomics for prediction of all-cause mortality during long-term follow-up in outpatients with peripheral arterial disease
- 2020
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Ingår i: Atherosclerosis. - : Elsevier. - 0021-9150 .- 1879-1484. ; 311, s. 143-149
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Tidskriftsartikel (refereegranskat)abstract
- Background and aims: Patients with peripheral arterial disease (PAD) are at high risk for fatal events. We aimed to investigate the ability among several serum proteins to predict all-cause mortality in outpatients with PAD.Methods: Consecutive outpatients with carotid and/or lower extremity PAD were included in the discovery cohort (n = 436), and subjects with PAD from a population-based sample in the validation cohort (n = 129). Blood samples were analyzed for 81 proteins by a proximity extension assay. The proteins best predicting incident all-cause mortality were identified using L1-regularized Cox regression. The added value of the identified proteins to clinical risk markers was evaluated by Cox regression models and presented by the area under the receiver operator characteristics curves (AUC).Results: In the discovery cohort (mean age 70 years; 59% men), 195 died (4.8 events per 100 person-years) during a 10.3 years median follow-up. The clinical risk markers generated an AUC of 0.70 (95% confidence interval [95%CI] 0.65-0.76). The two serum protein biomarkers with best prediction of all-cause mortality were growth differentiation factor 15 and tumor necrosis factor-related apoptosis-inducing ligand receptor 2. Adding these proteins to the clinical risk markers significantly improved prediction (p < 0.001) and yielded an AUC of 0.76 (95%CI 0.71-0.80). A higher discriminatory performance was observed in the validation cohort (AUC 0.84; 95% CI 0.76-0.92).Conclusions: In a large-sample targeted proteomics assay, we identified two proteins that improved risk prediction beyond the COPART risk score. The use of high-throughput proteomics assays may identify potential biomarkers for improved risk prediction in patients with PAD.
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| 220887. |
- Skau, Emma
(författare)
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Targeted multiplex proteomics for risk stratification in patients with cardiovascular disease
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Risk stratification is valuable in patients with cardiovascular disease (CVD). Proteins involved in different pathophysiological processes in atherosclerosis have shown prognostic capacity. A new technology, Proximity Extension Assay (PEA), enables the simultaneous analysis of numerous plasma proteins from a minimal amount of plasma. In this thesis, the overall aim was to identify and study prognostic protein biomarkers that could become useful in risk stratification. We used PEA to identify the biomarkers with the best prediction of long-term mortality among patients with acute myocardial infarction (AMI) and peripheral arterial disease (PAD). The study populations included consecutive patients with AMI from the Västmanland Myocardial Infarction Study (VaMIS), outpatients with carotid or lower extremity PAD from the Peripheral Arterial Disease Study in Västmanland (PADVa), and a population-based control cohort. A set of 92 proteins was analysed with PEA and related to follow-up data in the populations. The biomarkers which were best at predicting all-cause mortality were identified using LASSO regression analyses. The added value of the identified biomarkers to clinical risk markers was evaluated by logistic or Cox regression models. The associations between the plasma concentrations of growth differentiation factor 15 (GDF-15) to clinical risk factors, indicators of atherosclerotic burden, and variables of cardiac geometry and function were analysed with linear regression models. Spearman’s rank correlation coefficients compared the plasma concentrations obtained from conventional immunoassays and PEA for GDF-15 and N-terminal pro-brain natriuretic peptide (NT-proBNP) in the PAD population and the population-based cohort without PAD. The association between the two assay data and outcome was evaluated separately with Cox regression.GDF-15 and tumour necrosis factor-related apoptosis-inducing ligand receptor 2 (TRAIL-R2) had the best prognostic performance for all-cause mortality among individuals with AMI, and PAD, and improved the risk prediction beyond the established risk markers.Circulating GDF-15 levels among individuals with PAD were independently associated with several of the clinical and biochemical risk variables, particularly diabetes and low low-density lipoprotein cholesterol.We demonstrated an excellent correlation and a similar prognostic performance of plasma levels of NT-proBNP and GDF-15 obtained by conventional assays compared with PEA in both cohorts. Except for high levels of NT-proBNP, the PEA reliably reflects the serum levels obtained from the conventional assay.Hopefully, our results can contribute to the finding of potential biomarkers useful in clinical practice in order to better identify subgroups among patients with CVD. In the long run, this might open up possibilities for individualised treatment and to more cost-effective follow-up routines, thus improving quality of life and longevity.
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| 220888. |
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| 220889. |
- Skawinski, Tomasz, et al.
(författare)
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A re-evaluation of the historical "dinosaur' remains from the Middle-Upper Triassic of Poland
- 2017
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Ingår i: Historical Biology. - : TAYLOR & FRANCIS LTD. - 0891-2963 .- 1029-2381. ; 29:4, s. 442-472
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Forskningsöversikt (refereegranskat)abstract
- The so-called historical Polish discoveries of Triassic dinosaurs' have been repeatedly cited in papers and popular science books. Here, we re-evaluate each historical and purported Triassic dinosaur find from Poland. Additionaly, we describe several supposed dinosaur' bones collected by Polish geologists but only briefly mentioned: in regional geological journals, on collection labels, or in field notes. We attempt to assign all investigated specimens to the least inclusive taxon possible. Our revision indicates that part of this material represents non-dinosaur archosauromorph taxa. Most of the analysed specimens are fragmentary bones or isolated teeth and are indistinguishable from skeletal elements described from other well-known Triassic archosauromorph taxa. We conclude that fossils of dinosauriforms are present in the Upper Triassic of Silesia and Holy Cross Mountains. New analysis of Velocipes guerichi von Huene, 1932 holotype specimen from Kocury shows that it is the proximal part of fibula of a medium-sized theropod (or even neotheropod). Formally undescribed part of dinosauriform limb bone from the Holy Cross Mountains and V. guerichi from Silesia are the only identifiable dinosauromorph skeletal remains recognised in the Polish Triassic discovered prior to the description of Silesaurus opolensis Dzik, 2003 from the Upper Carnian of Krasiejow.
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| 220890. |
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