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| 2. |
- Handin, Niklas, et al.
(författare)
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Proteome deconvolution of liver biopsies reveals hepatic cell composition as an important marker of fibrosis
- 2023
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Ingår i: Computational and Structural Biotechnology Journal. - : Elsevier. - 2001-0370. ; 21, s. 4361-4369
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Tidskriftsartikel (refereegranskat)abstract
- Human liver tissue is composed of heterogeneous mixtures of different cell types and their cellular stoichiometry can provide information on hepatic physiology and disease progression. Deconvolution algorithms for the identification of cell types and their proportions have recently been developed for transcriptomic data. However, no method for the deconvolution of bulk proteomics data has been presented to date. Here, we show that proteomes, which usually contain less data than transcriptomes, can provide useful information for cell type deconvolution using different algorithms. We demonstrate that proteomes from defined mixtures of cell lines, isolated primary liver cells, and human liver biopsies can be deconvoluted with high accuracy. In contrast to transcriptome-based deconvolution, liver tissue proteomes also provided information about extracellular compartments. Using deconvolution of proteomics data from liver biopsies of 56 patients undergoing Roux-en-Y gastric bypass surgery we show that proportions of immune and stellate cells correlate with inflammatory markers and altered composition of extracellular matrix proteins characteristic of early-stage fibrosis. Our results thus demonstrate that proteome deconvolution can be used as a molecular microscope for investigations of the composition of cell types, extracellular compartments, and for exploring cell-type specific pathological events. We anticipate that these findings will allow the refinement of retrospective analyses of the growing number of proteome datasets from various liver disease states and pave the way for AI-supported clinical and preclinical diagnostics.
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| 3. |
- Rossignol, P, et al.
(författare)
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NT-proBNP and stem cell factor plasma concentrations are independently associated with cardiovascular outcomes in end-stage renal disease hemodialysis patients
- 2022
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Ingår i: European Heart Journal Open. - : Oxford University Press. - 2752-4191. ; 2:6
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Tidskriftsartikel (refereegranskat)abstract
- Aimas: End-stage renal disease (ESRD) treated by chronic hemodialysis (HD) is associated with poor cardiovascular (CV) outcomes, with no available evidence-based therapeutics. A multiplexed proteomic approach may identify new pathophysiological pathways associated with CV outcomes, potentially actionable for precision medicine.Methods and Results: The AURORA trial was an international, multicentre, randomized, double-blind trial involving 2776 patients undergoing maintenance HD. Rosuvastatin vs. placebo had no significant effect on the composite primary endpoint of death from CV causes, nonfatal myocardial infarction or nonfatal stroke. We first compared CV risk-matched cases and controls (n = 410) to identify novel biomarkers using a multiplex proximity extension immunoassay (276 proteomic biomarkers assessed with OlinkTM). We replicated our findings in 200 unmatched cases and 200 controls. External validation was conducted from a multicentre real-life Danish cohort [Aarhus-Aalborg (AA), n = 331 patients] in which 92 OlinkTM biomarkers were assessed. In AURORA, only N-terminal pro-brain natriuretic peptide (NT-proBNP, positive association) and stem cell factor (SCF) (negative association) were found consistently associated with the trial's primary outcome across exploration and replication phases, independently from the baseline characteristics. Stem cell factor displayed a lower added predictive ability compared with NT-ProBNP. In the AA cohort, in multivariable analyses, BNP was found significantly associated with major CV events, while higher SCF was associated with less frequent CV deaths.Conclusions: Our findings suggest that NT-proBNP and SCF may help identify ESRD patients with respectively high and low CV risk, beyond classical clinical predictors and also point at novel pathways for prevention and treatment.
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| 4. |
- Subasic, M., et al.
(författare)
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Experimental investigation and numerical modelling of the cyclic plasticity and fatigue behavior of additively manufactured 316 L stainless steel
- 2024
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Ingår i: International Journal of Plasticity. - : Elsevier BV. - 0749-6419 .- 1879-2154. ; 176
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Tidskriftsartikel (refereegranskat)abstract
- This study addresses the critical need for a constitutive model to analyze the cyclic plasticity of additively manufactured 316L stainless steel. The anisotropic behavior at both room temperature and 300 °C is investigated experimentally based on cyclic hysteresis loops performed in different orientations with respect to the build direction. A comprehensive constitutive model is proposed, that integrates the Armstrong-Frederick nonlinear kinematic hardening, Voce nonlinear isotropic hardening and Hill's anisotropic yield criterion within a 3D return mapping algorithm. The model was calibrated to specimens in the 0° and 90° orientations and validated with specimens in the 45° orientation. A single set of hardening parameters successfully represented the elastoplastic response for all orientations at room temperature. The algorithm effectively captured the full cyclic hysteresis loops, including historical effects observed in experimental tests. A consistent trend of reduced hardening was observed at elevated temperature, while the 45° specimen orientation consistently exhibited the highest degree of strain hardening. The applicability of the model was demonstrated by computing energy dissipation for stabilized hysteresis loops, which was combined with fatigue tests to propose an energy-based fatigue life prediction model.
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| 6. |
- Åsberg, Signild, et al.
(författare)
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Ischemic Stroke and Secondary Prevention in Clinical Practice : A Cohort Study of 14 529 Patients in the Swedish Stroke Register
- 2010
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Ingår i: Stroke. - 0039-2499 .- 1524-4628. ; 41:7, s. 1338-1342
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Tidskriftsartikel (refereegranskat)abstract
- Background and Purpose Secondary prevention is recommended after stroke, but adherence to guidelines is unknown. We studied the prescription of antiplatelet drugs, angiotensin-converting enzyme inhibitors, statins, and anticoagulant drugs and their relation to risk of death. Methods Patients with first-ever ischemic stroke in 2005 were registered in the Swedish Stroke Register. Odds ratios, hazard ratios, and 95% CIs were calculated using logistic and Cox proportional hazard regression models. Adjustments were performed for age, sex, cardiovascular risk factors, other drug therapies, and activities of daily living function. Results In total, 14 529 patients with a mean age of 75.0 (±11.6) years were included. They were followed for 1.4 (±0.5) years: 52% had hypertension, 26% atrial fibrillation, 19% diabetes, and 15% were smokers. The odds ratio for prescription of antiplatelet was 2.20 (95% CI, 1.86 to 2.60) among the oldest patients (≥85 years of age) compared with the youngest (18 to 64 years of age). The corresponding odds ratio was 0.38 (0.32 to 0.45) for prescriptions of angiotensin-converting enzyme inhibitors, 0.09 (0.08 to 0.11) for statins, and 0.07 (0.05 to 0.09) for anticoagulant therapy. Prescription of statin and anticoagulant therapy was associated with reduced risk of death (hazard ratio, 0.78 [0.65 to 0.91] and hazard ratio, 0.58 [0.44 to 0.76], respectively) but not the prescription of antiplatelet drugs or angiotensin-converting enzyme inhibitors. Conclusions The prescription of antiplatelet, angiotensin-converting enzyme inhibitors, statins, and anticoagulant therapy was strongly age related. Statin and anticoagulant therapy was associated with reduced risk of death and seemed to be underused among elderly patients. These findings should encourage physicians to follow today's guidelines for stroke care.
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| 7. |
- Bergman, Eva-Mathilda, et al.
(författare)
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National registry-based case-control study : comorbidity and stroke in young adults
- 2015
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Ingår i: Acta Neurologica Scandinavica. - : Hindawi Limited. - 0001-6314 .- 1600-0404. ; 131:6, s. 394-399
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Tidskriftsartikel (refereegranskat)abstract
- ObjectivesStroke is overrepresented in cohorts of young adults with chronic diseases. The prevalence and impact of comorbidity among young stroke patients have not been compared with individuals without stroke. Our aim was to investigate the association between comorbidity and stroke in young adults. Materials and methodsA nationwide cohort of patients (aged 15-44years), registered in the Swedish Stroke Register, (Riksstroke) 2001-2009, was identified. Age- and sex-matched controls were randomly selected from the Population Register of Sweden. Discharge diagnoses were retrieved from the National Patient Register and grouped by chapter in the International Classification of Diseases 10th revision. Associations between ICD-10 chapters and stroke were stratified (age, sex, and stroke type) and analyzed by multivariable logistic regression. ResultsIn 2599 stroke patients analyzed, the prevalence of vascular risk factors (hypertension 25.3%, dyslipidemia 13.0%, diabetes 9.7%, heart failure 3.2%, and atrial fibrillation 2.8%), all ICD-10 chapters (except pregnancy) and prestroke hospitalizations were more frequent among cases than controls. Independent associations were found between stroke and eight ICD-10 chapters: neoplasms (odds ratios (OR) 1.53, 95% CI 1.15-2.05), blood (OR 1.61, 1.11-2.34), endocrine (OR 2.28, 1.77-2.93), psychiatric (OR 1.50, 1.24-1.81), nervous (OR 1.91, 1.46-2.50), eye (OR 1.67, 1.05-2.64), circulatory (OR 3.05, 2.45-3.80), and symptoms (OR 1.31, 1.13-1.52). The risk of stroke increased by 26% per ICD-10 chapter diagnosed. ConclusionsIn addition to vascular risk factors, comorbidity (represented by ICD-10 chapters) was associated with increased risk of stroke in young individuals. The risk of stroke was further increased with the number of diagnosed ICD-10 chapters.
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| 8. |
- Boenink, Rianne, et al.
(författare)
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Trends in kidney transplantation rate across Europe : a study from the ERA Registry
- 2023
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Ingår i: Nephrology Dialysis Transplantation. - : Oxford University Press (OUP). - 0931-0509 .- 1460-2385. ; 38:6, s. 1528-1539
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Tidskriftsartikel (refereegranskat)abstract
- Background. The aim of this study was to identify trends in total, deceased donor (DD) and living donor (LD) kidney transplantation (KT) rates in European countries. Methods. The European Renal Association (ERA) Registry and the Global Observatory on Donation and Transplantation (GODT) databases were used to obtain the number of KTs in individual European countries between 2010 and 2018. General population counts were obtained from Eurostat or the national bureaus of statistics. The KT rate per million population (p.m.p.) and the average annual percentage change (APC) were calculated. Results. The total KT rate in the 40 participating countries increased with 1.9% annually [95% confidence interval (CI) 1.5, 2.2] from 29.6 p.m.p. in 2010 to 34.7 p.m.p. in 2018, reflecting an increase of 3.4 p.m.p. in the DD-KT rate (from 21.6 p.m.p. to 25.0 p.m.p.; APC 1.9%; 95% CI 1.3, 2.4) and of 1.5 p.m.p. in the LD-KT rate (from 8.1 p.m.p. to 9.6 p.m.p.; APC 1.6%; 95% CI 1.0, 2.3). The trends in KT rate varied widely across European countries. An East-West gradient was observed for DD-KT rate, with Western European countries performing more KTs. In addition, most countries performed fewer LD-KTs. In 2018, Spain had the highest DD-KT rate (64.6 p.m.p.) and Turkey the highest LD-KT rate (37.0 p.m.p.). Conclusions. The total KT rate increased due to a rise in the KT rate from DDs and to a lesser extent from LDs, with large differences between individual European countries.
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| 9. |
- Chroinin, Danielle Ni, et al.
(författare)
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Statin Therapy and Outcome After Ischemic Stroke : Systematic Review and Meta-Analysis of Observational Studies and Randomized Trials
- 2013
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Ingår i: Stroke. - 0039-2499 .- 1524-4628. ; 44:2, s. 448-456
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Forskningsöversikt (refereegranskat)abstract
- Background and Purpose-Although experimental data suggest that statin therapy may improve neurological outcome after acute cerebral ischemia, the results from clinical studies are conflicting. We performed a systematic review and meta-analysis investigating the relationship between statin therapy and outcome after ischemic stroke. Methods-The primary analysis investigated statin therapy at stroke onset (prestroke statin use) and good functional outcome (modified Rankin score 0 to 2) and death. Secondary analyses included the following: (1) acute poststroke statin therapy (<= 72 hours after stroke), and (2) thrombolysis-treated patients. Results-The primary analysis included 113 148 subjects (27 studies). Among observational studies, statin treatment at stroke onset was associated with good functional outcome at 90 days (pooled odds ratio [OR], 1.41; 95% confidence interval [CI], 1.29-1.56; P<0.001), but not 1 year (OR, 1.12; 95% CI, 0.9-1.4; P=0.31), and with reduced fatality at 90 days (pooled OR, 0.71; 95% CI, 0.62-0.82; P<0.001) and 1 year (OR, 0.80;95% CI, 0.67-0.95; P=0.01). In the single randomized controlled trial reporting 90-day functional outcome, statin treatment was associated with good outcome (OR, 1.5; 95% CI, 1.0-2.24; P=0.05). No reduction in fatality was observed on meta-analysis of data from 3 randomized controlled trials (P=0.9). In studies restricted to of thrombolysis-treated patients, an association between statins and increased fatality at 90 days was observed (pooled OR, 1.25; 95% CI, 1.02-1.52; P=0.03, 3 studies, 4339 patients). However, this association was no longer present after adjusting for age and stroke severity in the largest study (adjusted OR, 1.14; 95% CI, 0.90-1.44; 4012 patients). Conclusion-In the largest meta-analysis to date, statin therapy at stroke onset was associated with improved outcome, a finding not observed in studies restricted to thrombolysis-treated patients. Randomized trials of statin therapy in acute ischemic stroke are needed.
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| 10. |
- Hajjari, Parisa, et al.
(författare)
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Paediatric Acute-onset Neuropsychiatric Syndrome (PANS) and intravenous immunoglobulin (IVIG): comprehensive open-label trial in ten children
- 2022
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Ingår i: Bmc Psychiatry. - : Springer Science and Business Media LLC. - 1471-244X. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Treatment with intravenous immunoglobulin (IVIG) in children with Paediatric Acute-onset Neuropsychiatric Syndrome (PANS) has for many years been used on clinical indications, but the research evidence for its efficacy is insufficient. Methods Open-label prospective in-depth trial including ten children (median age 10.3 years) with PANS, who received IVIG treatment 2 g/kg monthly for three months. Primary outcomes were changes in symptom severity and impairment from baseline to first and second follow-up visits one month after first and one month after third treatment, using three investigator-rated scales: Paediatric Acute Neuropsychiatric Symptom (PANS) scale, Clinical Global Impression - Severity and Improvement (CGI-S and CGI-I) scales. Secondary outcomes reported here were changes in Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS) scores, and side effects. Results All ten children received three treatments at one-month intervals according to study plan. From baseline to second follow-up marked reductions were seen in mean total PANS scale scores (p = .005), and CGI-S scores (p = .004). CGI-I ratings showed much to very much global improvement (mean CGI-I 1.8). Nine children had clinical response defined as > 30% reduction in PANS Scale scores. Improvements were also noted for CY-BOCS scores (p = .005), and in school attendance. Three children suffered moderate to severe temporary side effects after the first treatment, and the remaining seven had mild to moderate side effects. Side effects were much less severe after second and third treatments. Conclusions Considerable and pervasive improvements in symptoms and clinical impairments were seen in these ten children after three monthly IVIG treatments. Moderate to severe transient side effects occurred in three cases.
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