| 1. |
- Niemi, MEK, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 2. |
- Kanai, M, et al.
(författare)
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- 2023
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swepub:Mat__t
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| 3. |
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| 4. |
- Sliz, E., et al.
(författare)
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Evidence of a causal effect of genetic tendency to gain muscle mass on uterine leiomyomata
- 2023
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Uterine leiomyomata (UL) are the most common tumours of the female genital tract and the primary cause of surgical removal of the uterus. Genetic factors contribute to UL susceptibility. To add understanding to the heritable genetic risk factors, we conduct a genome-wide association study (GWAS) of UL in up to 426,558 European women from FinnGen and a previous UL meta-GWAS. In addition to the 50 known UL loci, we identify 22 loci that have not been associated with UL in prior studies. UL-associated loci harbour genes enriched for development, growth, and cellular senescence. Of particular interest are the smooth muscle cell differentiation and proliferation-regulating genes functioning on the myocardin-cyclin dependent kinase inhibitor 1A pathway. Our results further suggest that genetic predisposition to increased fat-free mass may be causally related to higher UL risk, underscoring the involvement of altered muscle tissue biology in UL pathophysiology. Overall, our findings add to the understanding of the genetic pathways underlying UL, which may aid in developing novel therapeutics.
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| 5. |
- Pezzotta, A., et al.
(författare)
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Euclid preparation XLI. Galaxy power spectrum modelling in real space
- 2024
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 687
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Tidskriftsartikel (refereegranskat)abstract
- We investigate the accuracy of the perturbative galaxy bias expansion in view of the forthcoming analysis of the Euclid spectroscopic galaxy samples. We compare the performance of a Eulerian galaxy bias expansion using state-of-the-art prescriptions from the effective field theory of large-scale structure (EFTofLSS) with a hybrid approach based on Lagrangian perturbation theory and high-resolution simulations. These models are benchmarked against comoving snapshots of the flagship I N-body simulation at z = (0.9, 1.2, 1.5, 1.8), which have been populated with H alpha galaxies leading to catalogues of millions of objects within a volume of about 58 h(-3) Gpc(3). Our analysis suggests that both models can be used to provide a robust inference of the parameters (h, omega c) in the redshift range under consideration, with comparable constraining power. We additionally determine the range of validity of the EFTofLSS model in terms of scale cuts and model degrees of freedom. From these tests, it emerges that the standard third-order Eulerian bias expansion - which includes local and non-local bias parameters, a matter counter term, and a correction to the shot-noise contribution - can accurately describe the full shape of the real-space galaxy power spectrum up to the maximum wavenumber of k(max) = 0.45 h Mpc(-1), and with a measurement precision of well below the percentage level. Fixing either of the tidal bias parameters to physically motivated relations still leads to unbiased cosmological constraints, and helps in reducing the severity of projection effects due to the large dimensionality of the model. We finally show how we repeated our analysis assuming a volume that matches the expected footprint of Euclid, but without considering observational effects, such as purity and completeness, showing that we can get constraints on the combination (h, omega c) that are consistent with the fiducial values to better than the 68% confidence interval over this range of scales and redshifts.
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| 6. |
- Hamaus, N., et al.
(författare)
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Euclid : Forecasts from redshift-space distortions and the Alcock-Paczynski test with cosmic voids
- 2022
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 658
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Tidskriftsartikel (refereegranskat)abstract
- Euclid is poised to survey galaxies across a cosmological volume of unprecedented size, providing observations of more than a billion objects distributed over a third of the full sky. Approximately 20 million of these galaxies will have their spectroscopy available, allowing us to map the three-dimensional large-scale structure of the Universe in great detail. This paper investigates prospects for the detection of cosmic voids therein and the unique benefit they provide for cosmological studies. In particular, we study the imprints of dynamic (redshift-space) and geometric (Alcock-Paczynski) distortions of average void shapes and their constraining power on the growth of structure and cosmological distance ratios. To this end, we made use of the Flagship mock catalog, a state-of-the-art simulation of the data expected to be observed with Euclid. We arranged the data into four adjacent redshift bins, each of which contains about 11000 voids and we estimated the stacked void-galaxy cross-correlation function in every bin. Fitting a linear-theory model to the data, we obtained constraints on f/b and DMH, where f is the linear growth rate of density fluctuations, b the galaxy bias, D-M the comoving angular diameter distance, and H the Hubble rate. In addition, we marginalized over two nuisance parameters included in our model to account for unknown systematic effects in the analysis. With this approach, Euclid will be able to reach a relative precision of about 4% on measurements of f/b and 0.5% on DMH in each redshift bin. Better modeling or calibration of the nuisance parameters may further increase this precision to 1% and 0.4%, respectively. Our results show that the exploitation of cosmic voids in Euclid will provide competitive constraints on cosmology even as a stand-alone probe. For example, the equation-of-state parameter, w, for dark energy will be measured with a precision of about 10%, consistent with previous more approximate forecasts.
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| 7. |
- Pöntinen, M., et al.
(författare)
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Euclid: Identification of asteroid streaks in simulated images using deep learning
- 2023
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 679
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Tidskriftsartikel (refereegranskat)abstract
- The material composition of asteroids is an essential piece of knowledge in the quest to understand the formation and evolution of the Solar System. Visual to near-infrared spectra or multiband photometry is required to constrain the material composition of asteroids, but we currently have such data, especially in the near-infrared wavelengths, for only a limited number of asteroids. This is a significant limitation considering the complex orbital structures of the asteroid populations. Up to 150 000 asteroids will be visible in the images of the upcoming ESA Euclid space telescope, and the instruments of Euclid will offer multiband visual to near-infrared photometry and slitless near-infrared spectra of these objects. Most of the asteroids will appear as streaks in the images. Due to the large number of images and asteroids, automated detection methods are needed. A non-machine-learning approach based on the Streak Det software was previously tested, but the results were not optimal for short and/or faint streaks. We set out to improve the capability to detect asteroid streaks in Euclid images by using deep learning. We built, trained, and tested a three-step machine-learning pipeline with simulated Euclid images. First, a convolutional neural network (CNN) detected streaks and their coordinates in full images, aiming to maximize the completeness (recall) of detections. Then, a recurrent neural network (RNN) merged snippets of long streaks detected in several parts by the CNN. Lastly, gradient-boosted trees (XGBoost) linked detected streaks between different Euclid exposures to reduce the number of false positives and improve the purity (precision) of the sample. The deep-learning pipeline surpasses the completeness and reaches a similar level of purity of a non-machine-learning pipeline based on the StreakDet software. Additionally, the deep-learning pipeline can detect asteroids 0.25–0.5 magnitudes fainter than StreakDet. The deep-learning pipeline could result in a 50% increase in the number of detected asteroids compared to the StreakDet software. There is still scope for further refinement, particularly in improving the accuracy of streak coordinates and enhancing the completeness of the final stage of the pipeline, which involves linking detections across multiple exposures.
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| 8. |
- Contarini, S., et al.
(författare)
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Euclid : cosmological forecasts from the void size function
- 2022
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 667
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Tidskriftsartikel (refereegranskat)abstract
- The Euclid mission - with its spectroscopic galaxy survey covering a sky area over 15 000 deg(2) in the redshift range 0.9 < z < 1.8 - will provide a sample of tens of thousands of cosmic voids. This paper thoroughly explores for the first time the constraining power of the void size function on the properties of dark energy (DE) from a survey mock catalogue, the official Euclid Flagship simulation. We identified voids in the Flagship light-cone, which closely matches the features of the upcoming Euclid spectroscopic data set. We modelled the void size function considering a state-of-the art methodology: we relied on the volume-conserving (Vdn) model, a modification of the popular Sheth & van de Weygaert model for void number counts, extended by means of a linear function of the large-scale galaxy bias. We found an excellent agreement between model predictions and measured mock void number counts. We computed updated forecasts for the Euclid mission on DE from the void size function and provided reliable void number estimates to serve as a basis for further forecasts of cosmological applications using voids. We analysed two different cosmological models for DE: the first described by a constant DE equation of state parameter, w, and the second by a dynamic equation of state with coefficients w(0) and w(a). We forecast 1 sigma errors on w lower than 10% and we estimated an expected figure of merit (FoM) for the dynamical DE scenario FoM(w0,wa) = 17 when considering only the neutrino mass as additional free parameter of the model. The analysis is based on conservative assumptions to ensure full robustness, and is a pathfinder for future enhancements of the technique. Our results showcase the impressive constraining power of the void size function from the Euclid spectroscopic sample, both as a stand-alone probe, and to be combined with other Euclid cosmological probes.
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| 9. |
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| 10. |
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| 11. |
- Kurki, MI, et al.
(författare)
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FinnGen provides genetic insights from a well-phenotyped isolated population
- 2023
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 613:7944, s. 508-
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Tidskriftsartikel (refereegranskat)abstract
- Population isolates such as those in Finland benefit genetic research because deleterious alleles are often concentrated on a small number of low-frequency variants (0.1% ≤ minor allele frequency < 5%). These variants survived the founding bottleneck rather than being distributed over a large number of ultrarare variants. Although this effect is well established in Mendelian genetics, its value in common disease genetics is less explored1,2. FinnGen aims to study the genome and national health register data of 500,000 Finnish individuals. Given the relatively high median age of participants (63 years) and the substantial fraction of hospital-based recruitment, FinnGen is enriched for disease end points. Here we analyse data from 224,737 participants from FinnGen and study 15 diseases that have previously been investigated in large genome-wide association studies (GWASs). We also include meta-analyses of biobank data from Estonia and the United Kingdom. We identified 30 new associations, primarily low-frequency variants, enriched in the Finnish population. A GWAS of 1,932 diseases also identified 2,733 genome-wide significant associations (893 phenome-wide significant (PWS), P < 2.6 × 10–11) at 2,496 (771 PWS) independent loci with 807 (247 PWS) end points. Among these, fine-mapping implicated 148 (73 PWS) coding variants associated with 83 (42 PWS) end points. Moreover, 91 (47 PWS) had an allele frequency of <5% in non-Finnish European individuals, of which 62 (32 PWS) were enriched by more than twofold in Finland. These findings demonstrate the power of bottlenecked populations to find entry points into the biology of common diseases through low-frequency, high impact variants.
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| 12. |
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| 13. |
- Cooper-DeHoff, Rhonda M., et al.
(författare)
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The Clinical Pharmacogenetics Implementation Consortium Guideline for SLCO1B1, ABCG2, and CYP2C9 genotypes and Statin-Associated Musculoskeletal Symptoms
- 2022
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Ingår i: Clinical Pharmacology and Therapeutics. - : John Wiley & Sons. - 0009-9236 .- 1532-6535. ; 111:5, s. 1007-1021
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Tidskriftsartikel (refereegranskat)abstract
- Statins reduce cholesterol, prevent cardiovascular disease, and are among the most commonly prescribed medications in the world. Statin-associated musculoskeletal symptoms (SAMS) impact statin adherence and ultimately can impede the long-term effectiveness of statin therapy. There are several identified pharmacogenetic variants that impact statin disposition and adverse events during statin therapy. SLCO1B1 encodes a transporter (SLCO1B1; alternative names include OATP1B1 or OATP-C) that facilitates the hepatic uptake of all statins. ABCG2 encodes an efflux transporter (BCRP) that modulates the absorption and disposition of rosuvastatin. CYP2C9 encodes a phase I drug metabolizing enzyme responsible for the oxidation of some statins. Genetic variation in each of these genes alters systemic exposure to statins (i.e., simvastatin, rosuvastatin, pravastatin, pitavastatin, atorvastatin, fluvastatin, lovastatin), which can increase the risk for SAMS. We summarize the literature supporting these associations and provide therapeutic recommendations for statins based on SLCO1B1, ABCG2, and CYP2C9 genotype with the goal of improving the overall safety, adherence, and effectiveness of statin therapy. This document replaces the 2012 and 2014 Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for SLCO1B1 and simvastatin-induced myopathy.
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| 14. |
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| 15. |
- Nakanishi, T, et al.
(författare)
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Age-dependent impact of the major common genetic risk factor for COVID-19 on severity and mortality
- 2021
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Ingår i: medRxiv : the preprint server for health sciences. - : Cold Spring Harbor Laboratory.
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- BackgroundThere is considerable variability in COVID-19 outcomes amongst younger adults—and some of this variation may be due to genetic predisposition. We characterized the clinical implications of the major genetic risk factor for COVID-19 severity, and its age-dependent effect, using individual-level data in a large international multi-centre consortium.MethodThe major common COVID-19 genetic risk factor is a chromosome 3 locus, tagged by the marker rs10490770. We combined individual level data for 13,424 COVID-19 positive patients (N=6,689 hospitalized) from 17 cohorts in nine countries to assess the association of this genetic marker with mortality, COVID-19-related complications and laboratory values. We next examined if the magnitude of these associations varied by age and were independent from known clinical COVID-19 risk factors.FindingsWe found that rs10490770 risk allele carriers experienced an increased risk of all-cause mortality (hazard ratio [HR] 1·4, 95% confidence interval [CI] 1·2–1·6) and COVID-19 related mortality (HR 1·5, 95%CI 1·3–1·8). Risk allele carriers had increased odds of several COVID-19 complications: severe respiratory failure (odds ratio [OR] 2·0, 95%CI 1·6-2·6), venous thromboembolism (OR 1·7, 95%CI 1·2-2·4), and hepatic injury (OR 1·6, 95%CI 1·2-2·0). Risk allele carriers ≤ 60 years had higher odds of death or severe respiratory failure (OR 2·6, 95%CI 1·8-3·9) compared to those > 60 years OR 1·5 (95%CI 1·3-1·9, interaction p-value=0·04). Amongst individuals ≤ 60 years who died or experienced severe respiratory COVID-19 outcome, we found that 31·8% (95%CI 27·6-36·2) were risk variant carriers, compared to 13·9% (95%CI 12·6-15·2%) of those not experiencing these outcomes. Prediction of death or severe respiratory failure among those ≤ 60 years improved when including the risk allele (AUC 0·82 vs 0·84, p=0·016) and the prediction ability of rs10490770 risk allele was similar to, or better than, most established clinical risk factors.InterpretationThe major common COVID-19 risk locus on chromosome 3 is associated with increased risks of morbidity and mortality—and these are more pronounced amongst individuals ≤ 60 years. The effect on COVID-19 severity was similar to, or larger than most established risk factors, suggesting potential implications for clinical risk management.FundingFunding was obtained by each of the participating cohorts individually.
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| 16. |
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| 17. |
- Hakkinen, K, et al.
(författare)
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Implementation of CYP2D6 copy-number imputation panel and frequency of key pharmacogenetic variants in Finnish individuals with a psychotic disorder
- 2022
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Ingår i: The pharmacogenomics journal. - : Springer Science and Business Media LLC. - 1473-1150 .- 1470-269X. ; 22:3, s. 166-172
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Tidskriftsartikel (refereegranskat)abstract
- We demonstrate that CYP2D6 copy-number variation (CNV) can be imputed using existing imputation algorithms. Additionally, we report frequencies of key pharmacogenetic variants in individuals with a psychotic disorder from the genetically bottle-necked population of Finland. We combined GWAS chip and CYP2D6 CNV data from the Breast Cancer Pain Genetics study to construct an imputation panel (n = 902) for CYP2D6 CNV. The resulting data set was used as a CYP2D6 CNV imputation panel in 9262 non-related individuals from the SUPER-Finland study. Based on imputation of 9262 individuals we confirm the higher frequency of CYP2D6 ultrarapid metabolizers and a 22-fold enrichment of the UGT1A1 decreased function variant rs4148323 (UGT1A1*6) in Finland compared with non-Finnish Europeans. Similarly, the NUDT15 variant rs116855232 was highly enriched in Finland. We demonstrate that imputation of CYP2D6 CNV is possible and the methodology enables studying CYP2D6 in large biobanks with genome-wide data.
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| 18. |
- Lopes, T. S., et al.
(författare)
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Cu(In,Ga)Se2 based ultrathin solar cells the pathway from lab rigid to large scale flexible technology
- 2023
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Ingår i: npj Flexible Electronics. - : Springer Nature. - 2397-4621. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- The incorporation of interface passivation structures in ultrathin Cu(In,Ga)Se2 based solar cells is shown. The fabrication used an industry scalable lithography technique—nanoimprint lithography (NIL)—for a 15 × 15 cm2 dielectric layer patterning. Devices with a NIL nanopatterned dielectric layer are benchmarked against electron-beam lithography (EBL) patterning, using rigid substrates. The NIL patterned device shows similar performance to the EBL patterned device.The impact of the lithographic processes in the rigid solar cells’ performance were evaluated via X-ray Photoelectron Spectroscopy and through a Solar Cell Capacitance Simulator. The device on stainless-steel showed a slightly lower performance than the rigid approach, due to additional challenges of processing steel substrates, even though scanning transmission electron microscopy did not show clear evidence of impurity diffusion. Notwithstanding, time-resolved photoluminescence results strongly suggested elemental diffusion from the flexible substrate. Nevertheless, bending tests on the stainless-steel device demonstrated the mechanical stability of the CIGS-based device.
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| 19. |
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| 20. |
- Huhtanen, JT, et al.
(författare)
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Deep learning accurately classifies elbow joint effusion in adult and pediatric radiographs
- 2022
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 12:1, s. 11803-
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Tidskriftsartikel (refereegranskat)abstract
- Joint effusion due to elbow fractures are common among adults and children. Radiography is the most commonly used imaging procedure to diagnose elbow injuries. The purpose of the study was to investigate the diagnostic accuracy of deep convolutional neural network algorithms in joint effusion classification in pediatric and adult elbow radiographs. This retrospective study consisted of a total of 4423 radiographs in a 3-year period from 2017 to 2020. Data was randomly separated into training (n = 2672), validation (n = 892) and test set (n = 859). Two models using VGG16 as the base architecture were trained with either only lateral projection or with four projections (AP, LAT and Obliques). Three radiologists evaluated joint effusion separately on the test set. Accuracy, precision, recall, specificity, F1 measure, Cohen’s kappa, and two-sided 95% confidence intervals were calculated. Mean patient age was 34.4 years (1–98) and 47% were male patients. Trained deep learning framework showed an AUC of 0.951 (95% CI 0.946–0.955) and 0.906 (95% CI 0.89–0.91) for the lateral and four projection elbow joint images in the test set, respectively. Adult and pediatric patient groups separately showed an AUC of 0.966 and 0.924, respectively. Radiologists showed an average accuracy, sensitivity, specificity, precision, F1 score, and AUC of 92.8%, 91.7%, 93.6%, 91.07%, 91.4%, and 92.6%. There were no statistically significant differences between AUC's of the deep learning model and the radiologists (p value > 0.05). The model on the lateral dataset resulted in higher AUC compared to the model with four projection datasets. Using deep learning it is possible to achieve expert level diagnostic accuracy in elbow joint effusion classification in pediatric and adult radiographs. Deep learning used in this study can classify joint effusion in radiographs and can be used in image interpretation as an aid for radiologists.
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| 21. |
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| 22. |
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| 23. |
- Nakanishi, Tomoko, et al.
(författare)
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Age-dependent impact of the major common genetic risk factor for COVID-19 on severity and mortality
- 2021
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Ingår i: Journal of Clinical Investigation. - : American Society For Clinical Investigation. - 0021-9738 .- 1558-8238. ; 131:23
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND. There is considerable variability in COVID-19 outcomes among younger adults, and some of this variation may be due to genetic predisposition. METHODS. We combined individual level data from 13,888 COVID-19 patients (n = 7185 hospitalized) from 17 cohorts in 9 countries to assess the association of the major common COVID-19 genetic risk factor (chromosome 3 locus tagged by rs10490770) with mortality, COVID-19-related complications, and laboratory values. We next performed metaanalyses using FinnGen and the Columbia University COVID-19 Biobank. RESULTS. We found that rs10490770 risk allele carriers experienced an increased risk of all-cause mortality (HR, 1.4; 95% CI, 1.2-1.7). Risk allele carriers had increased odds of several COVID-19 complications: severe respiratory failure (OR, 2.1; 95% CI, 1.6-2.6), venous thromboembolism (OR, 1.7; 95% CI, 1.2-2.4), and hepatic injury (OR, 1.5; 95% CI, 1.2-2.0). Risk allele carriers age 60 years and younger had higher odds of death or severe respiratory failure (OR, 2.7; 95% CI, 1.8-3.9) compared with those of more than 60 years (OR, 1.5; 95% CI, 1.2-1.8; interaction, P = 0.038). Among individuals 60 years and younger who died or experienced severe respiratory failure, 32.3% were risk-variant carriers compared with 13.9% of those not experiencing these outcomes. This risk variant improved the prediction of death or severe respiratory failure similarly to, or better than, most established clinical risk factors. CONCLUSIONS. The major common COVID-19 genetic risk factor is associated with increased risks of morbidity and mortality, which are more pronounced among individuals 60 years or younger. The effect was similar in magnitude and more common than most established clinical risk factors, suggesting potential implications for future clinical risk management.
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| 24. |
- Osika, W, et al.
(författare)
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Early findings from periscope (Pan-European response to the impacts of COVID-19 and future pandemics and epidemics)
- 2021
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Ingår i: EUROPEAN PSYCHIATRY. - : Royal College of Psychiatrists. - 0924-9338 .- 1778-3585. ; 64, s. S34-S34
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- The H2020/PERISCOPE project, including 32 partners from European universities & agencies, began 1st November 2020 and will last 36 months. The overarching objectives of PERISCOPE are to map and analyse the unintended impacts of the COVID-19 outbreak; develop solutions and guidance for policymakers and health authorities on how to mitigate the impact of the outbreak; enhance Europe’s preparedness for future similar events; and reflect on the future multi-level governance in the health as well as other domains affected by the outbreak. During this session we will report about early lessons learnt from the mapping and assessments of the impacts of the COVID-19 outbreak on mental health at national and subnational level in the EU with respect to individuals, communities and societies. Further, we will comment on their comparability. The aim is to explore differences between countries regarding the occurrence of mental ill health, and especially the impact on vulnerable groups, and how this is related to exposure to SARS-CoV-2, differences in policies over time, and effects on the economy. We will reflect on the short- and long-term consequences on mental health and health inequalities, report on the ongoing development of holistic policy guidelines for health authorities & other authorities, and from the analysis of multilevel governance, at local, regional and national level, memberstate – EU-level, and EU - global governance level. PERISCOPE will continue collecting data and updating a common data ”Atlas”, which would lead the consortium to engage in modelling and experiments to provide “continuous nowcasting” of the outbreak.DisclosureNo significant relationships.
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| 25. |
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| 26. |
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| 27. |
- Abadpour, Shadab, et al.
(författare)
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Adipose-Derived Stromal Cells Preserve Pancreatic Islet Function in a Transplantable 3D Bioprinted Scaffold
- 2023
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Ingår i: Advanced healthcare materials. - 2192-2640 .- 2192-2659. ; 12:32
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Tidskriftsartikel (refereegranskat)abstract
- Intra-portal islet transplantation is currently the only clinically approved beta cell replacement therapy, but its outcome is hindered by limited cell survival due to a multifactorial reaction against the allogeneic tissue in liver. Adipose-derived stromal cells (ASCs) can potentially improve the islet micro-environment by their immunomodulatory action. The challenge is to combine both islets and ASCs in a relatively easy and consistent long-term manner in a deliverable scaffold. Manufacturing the 3D bioprinted double-layered scaffolds with primary islets and ASCs using a mix of alginate/nanofibrillated cellulose (NFC) bioink is reported. The diffusion properties of the bioink and the supportive effect of human ASCs on islet viability, glucose sensing, insulin secretion, and reducing the secretion of pro-inflammatory cytokines are demonstrated. Diabetic mice transplanted with islet-ASC scaffolds reach normoglycemia seven days post-transplantation with no significant difference between this group and the group received islets under the kidney capsules. In addition, animals transplanted with islet-ASC scaffolds stay normoglycemic and show elevated levels of C-peptide compared to mice transplanted with islet-only scaffolds. The data present a functional 3D bioprinted scaffold for islets and ASCs transplanted to the extrahepatic site and suggest a possible role of ASCs on improving the islet micro-environment.
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| 28. |
- Andermo, S, et al.
(författare)
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The Implementation of Mindfulness-Based Programs in the Swedish Healthcare System-A Qualitative Study
- 2021
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Ingår i: Global advances in health and medicine. - : SAGE Publications. - 2164-957X .- 2164-9561. ; 10, s. 21649561211058698-
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Tidskriftsartikel (refereegranskat)abstract
- As the provision of Mindfulness-Based Programs (MBPs) in health care settings progresses, more research is needed to develop guidelines and structures for implementation in various contexts. This study is part of a larger project were MBP provision in Sweden is explored. Objective: The objective is to provide knowledge for the next steps of MBP implementation both in Sweden and internationally. The specific aim of the study is to explore how MBP teachers and other relevant stakeholders experience the implementation of MBP. Methods: Qualitative in-depth interviews were conducted with 15 MBP providers and 2 other stakeholders from a range of health care settings in Sweden. Results: The results, presented in 3 themes, provide insights into the factors that are crucial for facilitating or hindering MBP implementation; (1) MBP teachers and their training, including the importance of champion individuals and the benefit and shortcomings of various forms of MBP; (2) Patients and patient referrals, including patient characteristics and referral pathways; (3) Organizational prerequisites to successful implementation, highlighting the importance of financial factors and managers’ and colleagues’ knowledge and acceptance of MBP; and (4) the need for structural changes, including future recommendations on quality assessment and guidelines. Conclusion: This study highlights the need for national guidelines for MBP provision and teacher training pathways, as well as improved availability of teacher training. Also, the benefit of a stepped-care model of MBP provision is indicated by the findings. Finally, increasing awareness of MBPs among referrers, managers, and the public may enable successful implementation.
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| 29. |
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| 30. |
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| 31. |
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| 32. |
- Carlson-Nilsson, Ulrika, et al.
(författare)
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Trait Expression and Environmental Responses of Pea (Pisum sativum L.) Genetic Resources Targeting Cultivation in the Arctic
- 2021
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Ingår i: Frontiers in Plant Science. - : Frontiers Media SA. - 1664-462X. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- In the Arctic part of the Nordic region, cultivated crops need to specifically adapt to adverse and extreme climate conditions, such as low temperatures, long days, and a short growing season. Under the projected climate change scenarios, higher temperatures and an earlier spring thaw will gradually allow the cultivation of plants that could not be previously cultivated there. For millennia, Pea (Pisum sativum L.) has been a major cultivated protein plant in Nordic countries but is currently limited to the southern parts of the region. However, response and adaptation to the Arctic day length/light spectrum and temperatures are essential for the productivity of the pea germplasm and need to be better understood. This study investigated these factors and identified suitable pea genetic resources for future cultivation and breeding in the Arctic region. Fifty gene bank accessions of peas with a Nordic landrace or cultivar origin were evaluated in 2-year field trials at four Nordic locations in Denmark, Finland, Sweden, and Norway (55 degrees to 69 degrees N). The contrasting environmental conditions of the trial sites revealed differences in expression of phenological, morphological, crop productivity, and quality traits in the accessions. The data showed that light conditions related to a very long photoperiod partly compensated for the lack of accumulated temperature in the far north. A critical factor for cultivation in the Arctic is the use of cultivars with rapid flowering and maturation times combined with early sowing. At the most extreme site (69 degrees N), no accession reached full maturation. Nonetheless several accessions, predominantly landraces of a northern origin, reached a green harvest state. All the cultivars reached full maturation at the sub-Arctic latitude in northern Sweden (63 degrees N) when plants were established early in the season. Seed yield correlated positively with seed number and aboveground biomass, but negatively with flowering time. A high yield potential and protein concentration of dry seed were found in many garden types of pea, confirming their breeding potential for yield. Overall, the results indicated that pea genetic resources are available for breeding or immediate cultivation, thus aiding in the northward expansion of pea cultivation. Predicted climate changes would support this expansion.
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| 33. |
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| 34. |
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| 35. |
- Lepistö, Teemu, et al.
(författare)
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Particle lung deposited surface area (LDSAal) size distributions in different urban environments and geographical regions : Towards understanding of the PM2.5 dose–response
- 2023
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Ingår i: Environment International. - : Elsevier. - 0160-4120 .- 1873-6750. ; 180
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Tidskriftsartikel (refereegranskat)abstract
- Recent studies indicate that monitoring only fine particulate matter (PM2.5) may not be enough to understand and tackle the health risk caused by particulate pollution. Health effects per unit PM2.5 seem to increase in countries with low PM2.5, but also near local pollution sources (e.g., traffic) within cities. The aim of this study is to understand the differences in the characteristics of lung-depositing particles in different geographical regions and urban environments. Particle lung deposited surface area (LDSAal) concentrations and size distributions, along with PM2.5, were compared with ambient measurement data from Finland, Germany, Czechia, Chile, and India, covering traffic sites, residential areas, airports, shipping, and industrial sites. In Finland (low PM2.5), LDSAal size distributions depended significantly on the urban environment and were mainly attributable to ultrafine particles (<100 nm). In Central Europe (moderate PM2.5), LDSAal was also dependent on the urban environment, but furthermore heavily influenced by the regional aerosol. In Chile and India (high PM2.5), LDSAal was mostly contributed by the regional aerosol despite that the measurements were done at busy traffic sites. The results indicate that the characteristics of lung-depositing particles vary significantly both within cities and between geographical regions. In addition, ratio between LDSAal and PM2.5 depended notably on the environment and the country, suggesting that LDSAal exposure per unit PM2.5 may be multiple times higher in areas having low PM2.5 compared to areas with continuously high PM2.5. These findings may partly explain why PM2.5 seems more toxic near local pollution sources and in areas with low PM2.5. Furthermore, performance of a typical sensor based LDSAal measurement is discussed and a new LDSAal2.5 notation indicating deposition region and particle size range is introduced. Overall, the study emphasizes the need for country-specific emission mitigation strategies, and the potential of LDSAal concentration as a health-relevant pollution metric.
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| 36. |
- Lok, Veeleah, et al.
(författare)
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Changes in anxiety and depression during the COVID-19 pandemic in the European population : A meta-analysis of changes and associations with restriction policies
- 2023
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Ingår i: European psychiatry. - 0924-9338 .- 1778-3585. ; 66:1
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Forskningsöversikt (refereegranskat)abstract
- Background. Early studies of common mental disorders (CMDs) during the COVID-19 pandemic mainly report increases; however, more recent findings have been mixed. Also, studies assessing the effects of restriction measures on CMDs show varied results. The aim of this meta-analysis was to assess changes in levels of CMDs from pre-/early to during the pandemic and the effects of restriction policies in the European population.Methods. We searched for studies assessing both pre-pandemic and peri-pandemic self-reported emotional distress and symptoms of depression or anxiety among nationally/regionally representative samples in Europe and collected microdata from those studies. Estimates of corona containment index were related to changes in CMDs using random-effects meta-regression.Results. Our search strategy resulted in findings from 15 datasets drawn from 8 European countries being included in the meta-analysis. There was no evidence of change in the prevalence of emotional distress, anxiety, or depression from before to during the pandemic; but from early pandemic periods to later periods, there were significant decreases in emotional distress and anxiety. Increased school restrictions and social distancing were associated with small increases in self-reported emotional distress.Conclusions. Despite initial concerns of increased emotional distress and mental illness due to the COVID-19 pandemic, the results from this meta-analysis indicate that there was a decrease in emotional distress and no change in anxiety or depression in the general population in Europe. Overall, our findings support the importance of strong governance when implementing periodic and robust restriction measures to combat the spread of COVID-19.
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| 37. |
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| 38. |
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| 39. |
- Moghadasi, Ramin, et al.
(författare)
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Pore-scale characterization of residual gas remobilization in CO2 geological storage
- 2023
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Ingår i: Advances in Water Resources. - : Elsevier. - 0309-1708 .- 1872-9657. ; 179
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Tidskriftsartikel (refereegranskat)abstract
- A decrease in reservoir pressure can lead to remobilization of residually trapped CO2. In this study, the pore-scale processes related to trapped CO2 remobilization under pressure depletion were investigated with the use of highresolution 3D X-ray microtomography. The distribution of CO2 in the pore space of Bentheimer sandstone was measured after waterflooding at a fluid pressure of 10 MPa, and then at pressures of 8, 6 and 5 MPa. At each stage CO2 was produced, implying that swelling of the gas phase and exsolution allowed the gas to reconnect and flow. After production, the gas reached a new position of equilibrium where it may be trapped again. At the end of the experiment, we imaged the sample again after 30 hours. Firstly, the results showed that an increase in saturation beyond the residual value was required to remobilize the gas, which is consistent with earlier field-scale results. Additionally, Ostwald ripening and continuing exsolution lead to a significant change in fluid saturation: transport of dissolved gas in the aqueous phase to equilibriate capillary pressure led to reconnection of the gas and its flow upwards under gravity. The implications for CO2 storage are discussed: an increase in saturation beyond the residual value is required to mobilize the gas, but Ostwald ripening can allow local reconnection of hitherto trapped gas, thus enhancing migration and may reduce the amount of CO2 that can be capillary trapped in storage operations.
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| 40. |
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| 41. |
- Niemelä, E., et al.
(författare)
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Nanoparticles carrying fingolimod and methotrexate enables targeted induction of apoptosis and immobilization of invasive thyroid cancer
- 2020
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Ingår i: European journal of pharmaceutics and biopharmaceutics. - : ELSEVIER. - 0939-6411 .- 1873-3441. ; 148, s. 1-9
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Tidskriftsartikel (refereegranskat)abstract
- Metastatic tumors are the main cause of cancer-related death, as the invading cancer cells disrupt normal functions of distant organs and are nearly impossible to eradicate by traditional cancer therapeutics. This is of special concern when the cancer has created multiple metastases and extensive surgery would be too dangerous to execute. Therefore, combination chemotherapy is often the selected treatment form. However, drug cocktails often have severe adverse effects on healthy cells, whereby the development of targeted drug delivery could minimize side-effects of drugs and increase the efficacy of the combination therapy. In this study, we utilized the folate antagonist methotrexate (MTX) as targeting ligand conjugated onto mesoporous silica nanoparticles (MSNs) for selective eradication of folate receptor-expressing invasive thyroid cancer cells. The MSNs was subsequently loaded with the drug fingolimod (FTY720), which has previously been shown to efficiently inhibit proliferation and invasion of aggressive thyroid cancer cells. To assess the efficiency of our carrier system, comprehensive in vitro methods were employed; including flow cytometry, confocal microscopy, viability assays, invasion assay, and label-free imaging techniques. The in vitro results show that MTX-conjugated and FTY720-loaded MSNs potently attenuated both the proliferation and invasion of the cancerous thyroid cells while keeping the off-target effects in normal thyroid cells reasonably low. For a more physiologically relevant in vivo approach we utilized the chick chorioallantoic membrane (CAM) assay, showing decreased invasive behavior of the thyroid derived xenografts and an increased necrotic phenotype compared to tumors that received the free drug cocktail. Thus, the developed multidrug-loaded MSNs effectively induced apoptosis and immobilization of invasive thyroid cancer cells, and could potentially be used as a carrier system for targeted drug delivery for the treatment of diverse forms of aggressive cancers that expresses folate receptors.
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| 42. |
- Niemi, M, et al.
(författare)
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The Implementation of Mindfulness-Based Programs in the Swedish Healthcare System - A Survey Study of Service Providers
- 2021
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Ingår i: Global advances in health and medicine. - : SAGE Publications. - 2164-957X .- 2164-9561. ; 10, s. 21649561211049154-
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Tidskriftsartikel (refereegranskat)abstract
- The burden of depression and anxiety is on the rise globally. Mindfulness-Based Programs (MBPs) are a particular group of psychosocial programs targeting depression and anxiety. There is growing research and practice interest in MBPs internationally, and they are becoming more commonly implemented in a number of countries’ healthcare services. Objective To systematically map the existing provision of MBPs in the Swedish healthcare sector, in order to understand facilitators and barriers to uptake, and so inform future implementation efforts. Methods We assessed the experiences of MBP implementation among relevant stakeholders in Swedish healthcare settings through an online survey. The survey was designed to gather data on (1) the evidence-base of practice being implemented; (2) the context in which implementation was taking place and (3) the process of facilitation. Respondents were identified through snowball sampling of key stakeholders. Results In total, 129 individuals from 20 of the 21 healthcare regions in Sweden responded to the survey. Our findings showed that there is variation in the types of MBP models being implemented, and that the delivery structure of evidence-based programs were often being modified for implementation. We found some divergence from international guidance on good practice standards for the training of MBP teachers within Swedish implementation processes. The main service context for implementation is primary care; the most important facilitating factors for successful MBP implementation were the presence of a championing individual and support from leadership. The most influential hindering factors for implementation were lack of time, and lack of funding. Conclusion To support integrity and fidelity of MBP implementation in Sweden, a strategic plan and good practice guidelines seem necessary. Also, an evidence-based stepped care model for implementation may work to ensure intervention fidelity in cases where time and funding constraints permit.
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| 43. |
- Nummela, Aleksi J., et al.
(författare)
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Effects of dexmedetomidine, propofol, sevoflurane and S-ketamine on the human metabolome : A randomised trial using nuclear magnetic resonance spectroscopy
- 2022
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Ingår i: European Journal of Anaesthesiology. - : Wolters Kluwer. - 0265-0215 .- 1365-2346. ; 39:6, s. 521-532
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Pharmacometabolomics uses large-scale data capturing methods to uncover drug-induced shifts in the metabolic profile. The specific effects of anaesthetics on the human metabolome are largely unknown.OBJECTIVE: We aimed to discover whether exposure to routinely used anaesthetics have an acute effect on the human metabolic profile.DESIGN: Randomised, open-label, controlled, parallel group, phase IV clinical drug trial.SETTING: The study was conducted at Turku PET Centre, University of Turku, Finland, 2016 to 2017.PARTICIPANTS: One hundred and sixty healthy male volunteers were recruited. The metabolomic data of 159 were evaluable.INTERVENTIONS: Volunteers were randomised to receive a 1-h exposure to equipotent doses (EC50 for verbal command) of dexmedetomidine (1.5 ng ml-1; n = 40), propofol (1.7 μg ml-1; n = 40), sevoflurane (0.9% end-tidal; n = 39), S-ketamine (0.75 μg ml-1; n = 20) or placebo (n = 20).MAIN OUTCOME MEASURES: Metabolite subgroups of apolipoproteins and lipoproteins, cholesterol, glycerides and phospholipids, fatty acids, glycolysis, amino acids, ketone bodies, creatinine and albumin and the inflammatory marker GlycA, were analysed with nuclear magnetic resonance spectroscopy from arterial blood samples collected at baseline, after anaesthetic administration and 70 min postanaesthesia.RESULTS: All metabolite subgroups were affected. Statistically significant changes vs. placebo were observed in 11.0, 41.3, 0.65 and 3.9% of the 155 analytes in the dexmedetomidine, propofol, sevoflurane and S-ketamine groups, respectively. Dexmedetomidine increased glucose, decreased ketone bodies and affected lipoproteins and apolipoproteins. Propofol altered lipoproteins, fatty acids, glycerides and phospholipids and slightly increased inflammatory marker glycoprotein acetylation. Sevoflurane was relatively inert. S-ketamine increased glucose and lactate, whereas branched chain amino acids and tyrosine decreased.CONCLUSION: A 1-h exposure to moderate doses of routinely used anaesthetics led to significant and characteristic alterations in the metabolic profile. Dexmedetomidine-induced alterations mirror α2-adrenoceptor agonism. Propofol emulsion altered the lipid profile. The inertness of sevoflurane might prove useful in vulnerable patients. S-ketamine induced amino acid alterations might be linked to its suggested antidepressive properties.TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02624401. URL: https://clinicaltrials.gov/ct2/show/NCT02624401.
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| 44. |
- Oskarsdotter, Kristin, 1995, et al.
(författare)
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Autologous endothelialisation by the stromal vascular fraction on laminin-bioconjugated nanocellulose-alginate scaffolds
- 2023
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Ingår i: Biomedical Materials (Bristol). - 1748-605X .- 1748-6041. ; 18:4
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Tidskriftsartikel (refereegranskat)abstract
- Establishing a vascular network in biofabricated tissue grafts is essential for ensuring graft survival. Such networks are dependent on the ability of the scaffold material to facilitate endothelial cell adhesion; however, the clinical translation potential of tissue-engineered scaffolds is hindered by the lack of available autologous sources of vascular cells. Here, we present a novel approach to achieving autologous endothelialisation in nanocellulose-based scaffolds by using adipose tissue-derived vascular cells on nanocellulose-based scaffolds. We used sodium periodate-mediated bioconjugation to covalently bind laminin to the scaffold surface and isolated the stromal vascular fraction and endothelial progenitor cells (EPCs; CD31+CD45−) from human lipoaspirate. Additionally, we assessed the adhesive capacity of scaffold bioconjugation in vitro using both adipose tissue-derived cell populations and human umbilical vein endothelial cells. The results showed that the bioconjugated scaffold exhibited remarkably higher cell viability and scaffold surface coverage by adhesion regardless of cell type, whereas control groups comprising cells on non-bioconjugated scaffolds exhibited minimal cell adhesion across all cell types. Furthermore, on culture day 3, EPCs seeded on laminin-bioconjugated scaffolds showed positive immunofluorescence staining for the endothelial markers CD31 and CD34, suggesting that the scaffolds promoted progenitor differentiation into mature endothelial cells. These findings present a possible strategy for generating autologous vasculature and thereby increase the clinical relevance of 3D-bioprinted nanocellulose-based constructs.
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| 45. |
- Sämfors, Sanna, 1987, et al.
(författare)
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Design and biofabrication of a leaf-inspired vascularized cell-delivery device
- 2022
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Ingår i: Bioprinting. - : Elsevier BV. - 2405-8866. ; 26
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Tidskriftsartikel (refereegranskat)abstract
- We designed and biofabricated a channeled construct as a possible cell-delivery device that can be endothelialized to overcome size limitations due to oxygen diffusion. The channeled device mimicking a leaf was designed using computer-aided design software, with fluid flow through the channels visualized using simulation studies. The device was fabricated either by form casting using a custom 3D-printed plastic mold or by 3D-bioprinting using Pluronic F-127 as sacrificial ink to print the channels. The actual leaf was cast or bioprinted using hydrogel made from a mixture of tunicate cellulose nanofibers and alginate that was cross-linked in calcium chloride solution to allow a stable device. The resulting device was a 20 × 8 × 3 mm or 35 × 18 × 3 mm (length × width × height) leaf with one main channel connected to several side channels. Surface modification using periodate oxidation, followed by laminin bioconjugation, was performed to enhance endothelial cell adhesion in the channels. We subsequently used human umbilical vein endothelial cells to demonstrate the efficacy of the device for promoting endothelialization. These results indicated that the biofabricated device has great potential for use in tissue-engineering for various applications associated with the need of perfusable vasculature.
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