| 1. |
- Alvez, Maria Bueno, et al.
(författare)
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Next generation pan-cancer blood proteome profiling using proximity extension assay
- 2023
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- A comprehensive characterization of blood proteome profiles in cancer patients can contribute to a better understanding of the disease etiology, resulting in earlier diagnosis, risk stratification and better monitoring of the different cancer subtypes. Here, we describe the use of next generation protein profiling to explore the proteome signature in blood across patients representing many of the major cancer types. Plasma profiles of 1463 proteins from more than 1400 cancer patients are measured in minute amounts of blood collected at the time of diagnosis and before treatment. An open access Disease Blood Atlas resource allows the exploration of the individual protein profiles in blood collected from the individual cancer patients. We also present studies in which classification models based on machine learning have been used for the identification of a set of proteins associated with each of the analyzed cancers. The implication for cancer precision medicine of next generation plasma profiling is discussed.
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| 2. |
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| 3. |
- Willgren, David, et al.
(författare)
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Adventsuppropet problematiskt
- 2012
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Ingår i: Dagen. - 1652-5264.
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- "Vi har problem med Adventsuppropet och den privilegierade ställning som den kristna tron förutsätts ha i det, skriver 18 pastorer och församlingsledare."
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| 4. |
- Willgren, David, et al.
(författare)
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Ett annat sätt att se på makt
- 2013
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Ingår i: Dagen. - 1652-5264.
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Tidskriftsartikel (populärvet., debatt m.m.)
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| 5. |
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| 6. |
- Åberg, N David, 1970, et al.
(författare)
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Insulin-like growth factor-I increases astrocyte intercellular gap junctional communication and connexin43 expression in vitro.
- 2003
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Ingår i: Journal of neuroscience research. - : Wiley. - 0360-4012. ; 74:1, s. 12-22
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Tidskriftsartikel (refereegranskat)abstract
- Connexin43 (cx43) forms gap junctions in astrocytes, and these gap junctions mediate intercellular communication by providing transport of low-molecular-weight metabolites and ions. We have recently shown that systemic growth hormone increases cx43 in the brain. One possibility was that local brain insulin-like growth factor-I (IGF-I) could mediate the effect by acting directly on astrocytes. In the present study, we examined the effects of direct application of recombinant human IGF-I (rhIGF-I) on astrocytes in primary culture concerning cx43 protein expression and gap junctional communication (GJC). After 24 hr of stimulation with rhIGF-I under serum-free conditions, the GJC and cx43 protein were analyzed. Administration of 30 ng/ml rhIGF-I increased the GJC and the abundance of cx43 protein. Cell proliferation of the astrocytes was not significantly increased by rhIGF-I at this concentration. However, a higher concentration of rhIGF-I (150 ng/ml) had no effect on GJC/cx43 but increased cell proliferation. Because of the important modulatory role of IGF binding proteins (IGFBPs) on IGF-I action, we analyzed IGFBPs in conditioned media. In cultures with a low abundance of IGFBPs (especially IGFBP-2), the GJC response to 30 ng/ml rhIGF-I was 81%, compared with the average of 25%. Finally, as a control, insulin was given in equimolar concentrations. However, GJC was not affected, which suggests that rhIGF-I acted via IGF-I receptors. In summary, the data show that rhIGF-I may increase GJC/cx43, whereas a higher concentration of rhIGF-I--at which stimulation of proliferation occurred--did not affect GJC/cx43. Furthermore, IGFBP-2 appeared to modulate the action of rhIGF-I on GJC in astrocytes by a paracrine mechanism.
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| 7. |
- Åberg, Veronica, 1976-, et al.
(författare)
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Microwave-assisted decarboxylation of bicyclic 2-pyridone scaffolds and identification of A beta-peptide aggregation inhibitors
- 2005
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Ingår i: Organic and biomolecular chemistry. - London, U.K. : Royal Society of Chemistry. - 1477-0520 .- 1477-0539. ; 3:15, s. 2817-2823
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Tidskriftsartikel (refereegranskat)abstract
- A reagent-free microwave-assisted decarboxylation procedure for carboxylic acid functionalized bicyclic 2-pyridones has been developed. This new method, based on microwave heating at 220 degrees C for 600 seconds in N-methyl pyrrolidone (NMP), proved to be practical and very efficient, resulting in decarboxylated 2-pyridones in near-quantitative yields. The decarboxylated products and the intermediate 2-pyridones in the form of carboxylic acid methyl esters and carboxylic acids were screened for their effect on A beta-peptide aggregation. Two out of the 21 2-pyridones described in this study inhibited amyloid formation of the Alzheimer A beta(1-40) peptide. The effect was seen even at a 4 : 1 ratio of 2-pyridone and monomeric A beta-peptide.
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| 8. |
- Åkerfeldt, Anna, et al.
(författare)
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"Fridolin backar in i framtiden om digitala läromedel"
- 2021
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Ingår i: Dagens Nyheter. - 1101-2447. ; :2021-12-16
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- Ingress: 23 forskare inom it- och utbildningsområdet: Regeringens utredare borde inte lyfta fram läsning på skärm som något negativt.Forskning visar att både tryckta och digitala läromedel behövs i skolan.
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| 9. |
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| 10. |
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| 11. |
- Ahlberg, Mats Steinholtz, et al.
(författare)
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PCASTt/SPCG-17-A randomised trial of active surveillance in prostate cancer: Rationale and design
- 2019
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Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Overtreatment of localised prostate cancer is substantial despite increased use of active surveillance. No randomised trials help define how to monitor patients or when to initiate treatment with curative intent. Methods and analysis A randomised, multicentre, intervention trial designed to evaluate the safety of an MRI-based active surveillance protocol, with standardised triggers for repeated biopsies and radical treatment. The aim is to reduce overtreatment of prostate cancer. 2000 men will be randomly allocated to either surveillance according to current practice or to standardised triggers at centres in Sweden, Norway, Finland and the UK. Men diagnosed in the past 12 months with prostate cancer, ≤T2a, prostate-specific antigen (PSA) <15 ng/mL, PSA density ≤0.2 ng/mL/cc, any International Society of Urological Pathology (ISUP) grade 1 are eligible. Men with ISUP grade 2 in <30% of cores on systematic biopsy and <10 mm cancer in one core on systematic or targeted biopsy are also eligible. Men diagnosed on systematic biopsy should have an MRI and targeted biopsies against Prostate Imaging and Reporting Data System V.2 3-5 lesions before inclusion. Identical follow-up in the two study arms: biannual PSA testing, yearly clinical examination and MRI every second year. In the experimental arm, standardised triggers based on MRI and PSA density elicit repeated biopsies. MRI and histopathological progression trigger radical treatment. Primary outcome measure is progression-free survival. Secondary outcome measures are cumulative incidence of metastatic disease, treatments with curative intent, pT3-4 at radical prostatectomy, switch to watchful waiting, prostate cancer mortality and quality of life. Inclusion started in October 2016 and in October 2018; 275 patients have been enrolled. Ethics and dissemination Ethical approval was obtained in each participating country. Results for the primary and secondary outcome measures will be submitted for publication in peer-reviewed journals. Trial registration number NCT02914873.
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| 12. |
- Balkhed, Wile, et al.
(författare)
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Repeated measurements of non-invasive fibrosis tests to monitor the progression of non-alcoholic fatty liver disease : A long-term follow-up study
- 2022
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Ingår i: Liver international (Print). - Chichester, United Kingdom : John Wiley & Sons. - 1478-3223 .- 1478-3231. ; 42:7, s. 1546-1556
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Tidskriftsartikel (refereegranskat)abstract
- Background and Aims: The presence of advanced hepatic fibrosis is the prime marker for the prediction of liver-related complications in non-alcoholic fatty liver disease (NAFLD). Blood-based non-invasive tests (NITs) have been developed to evaluate fibrosis and identify patients at risk. Current guidelines propose monitoring the progression of NAFLD using repeated NITs at 2-3-year intervals. The aim of this study was to evaluate the association of changes in NITs measured at two time points with the progression of NAFLD.Methods. We retrospectively included NAFLD patients with NIT measurements in whom the baseline hepatic fibrosis stage had been assessed by biopsy or transient elastography (TE). Subjects underwent follow-up visits at least 1 year from baseline to evaluate the progression of NAFLD. NAFLD progression was defined as the development of end-stage liver disease or fibrosis progression according to repeat biopsy or TE. The following NITs were calculated at baseline and follow-up: Fibrosis-4 (FIB-4), NAFLD fibrosis score (NFS), aspartate aminotransferase to platelet ratio index (APRI) and dynamic aspartate-to-alanine aminotransferase ratio (dAAR).Results: One hundred and thirty-five patients were included with a mean follow-up of 12.6 +/- 8.5 years. During follow-up, 41 patients (30%) were diagnosed with progressive NAFLD. Change in NIT scores during follow-up was significantly associated with disease progression for all NITs tested except for NFS. However, the diagnostic precision was suboptimal with area under the receiver operating characteristics 0.56-0.64 and positive predictive values of 0.28-0.36 at sensitivity fixed at 90%.Conclusions: Change of FIB-4, NFS, APRI, and dAAR scores is only weakly associated with disease progression in NAFLD. Our findings do not support repeated measurements of these NITs for monitoring the course of NAFLD.
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| 13. |
- Blomstrand, Fredrik, 1969, et al.
(författare)
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Extent of intercellular calcium wave propagation is related to gap junction permeability and level of connexin-43 expression in astrocytes in primary cultures from four brain regions.
- 1999
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Ingår i: Neuroscience. - 0306-4522. ; 92:1, s. 255-65
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Tidskriftsartikel (refereegranskat)abstract
- Astrocytes are coupled via gap junctions, predominantly formed by connexin-43 proteins, into cellular networks. This coupling is important for the propagation of intercellular calcium waves and for the spatial buffering of K+. Using the scrape-loading/dye transfer technique, we studied gap junction permeability in rat astrocytes cultured from four different brain regions. The cultures were shown to display regional heterogeneity with the following ranking of the gap junction coupling strengths: hippocampus = hypothalamus > cerebral cortex = brain stem. Similar relative patterns were found in connexin-43 messenger RNA and protein levels using solution hybridization/RNase protection assay and western blots, respectively. The percentages of the propagation area of mechanically induced intercellular calcium waves for cortical, brain stem and hypothalamic astrocytes compared with hippocampal astrocytes were approximately 77, 42, and 52, respectively. Thus, the extent of calcium wave propagation was due to more than just gap junctional permeability as highly coupled hypothalamic astrocytes displayed relatively small calcium wave propagation areas. Incubation with 5-hydroxytryptamine decreased and incubation with glutamate increased the calcium wave propagation area in hippocampal (67% and 170% of the control, respectively) and in cortical astrocytes (82% and 163% of the control, respectively). Contrary to hippocampal and cortical astrocytes, the calcium wave propagation in brain stem astrocytes was increased by 5-hydroxytryptamine incubation (158% of control), while in hypothalamic astrocytes, no significant effects were seen. Similar effects from 5-hydroxytryptamine or glutamate treatments were observed on dye transfer, indicating an effect on the junctional coupling strength. These results demonstrate a strong relationship between connexin-43 messenger RNA levels, protein expression, and gap junction permeability among astroglial cells. Furthermore, our results suggest heterogeneity among astroglial cells from different brain regions in intercellular calcium signaling and in its differential modulation by neurotransmitters, probably reflecting functional requirements in various brain regions.
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| 14. |
- Cederborg, Anna, 1976, et al.
(författare)
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Renal function after liver transplantation: Real-world experience with basiliximab induction and delayed reduced-dose tacrolimus
- 2022
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Ingår i: Digestive and Liver Disease. - : Elsevier BV. - 1590-8658. ; 54:8, s. 1076-1083
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Tidskriftsartikel (refereegranskat)abstract
- Background: Routine use of delayed reduced-dose calcineurin-inhibitor treatment with induction immunosuppression in liver transplantation to minimize post-operative kidney injury is still scarce. Aim: To evaluate real-world experience of basiliximab induction with delayed reduced-dose tacrolimus. Methods: In a retrospective cohort study, kidney function was evaluated pre- and postoperatively by measured glomerular filtration rate (mGFR). Adult patients undergoing liver transplantation between 2000 and 2017 were divided into a conventional treatment group (immediate-introduction of tacrolimus, target trough levels 10–15 ng/mL, and corticosteroids, n = 203) and a revised treatment group (basiliximab induction, reduced-dose tacrolimus, target through levels 5–8 ng/mL, delayed until day three, and mycophenolate mofetil 2000 mg/day, n = 343). Results: Mean mGFR was similar between groups at wait-listing (85.3 vs 84.1 ml/min/1.73m², p = 0.60), but higher in the revised treatment group at 3 (56.8 vs 63.4 ml/min/1.73m², p = 0.004) and 12 months post-transplant (60.9 vs 69.7 ml/min/1.73m², p<0.001); this difference remained after correcting for multiple confounders and was independent of pre-transplant mGFR. In the revised treatment group, biopsy proven acute rejection rate was lower (38% vs. 21%, p<0.001), and graft-survival better (p = 0.01). Conclusion: Basiliximab induction with delayed reduced-dose tacrolimus is associated with less kidney injury when compared to standard-dose tacrolimus, without increased risk of rejection, graft loss or death. © 2021
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| 15. |
- Cedervall, Ylva, et al.
(författare)
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Timed Up-and-Go Dual-Task Testing in the Assessment of Cognitive Function : A Mixed Methods Observational Study for Development of the UDDGait Protocol
- 2020
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Ingår i: International Journal of Environmental Research and Public Health. - : MDPI. - 1661-7827 .- 1660-4601. ; 17:5
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Tidskriftsartikel (refereegranskat)abstract
- New methods to screen for and identify early-stage dementia disorders are highly sought after. The purpose of this pilot study is to develop a study protocol for a dual-task test aimed at aiding the early detection of dementia disorders. We used the Timed Up-and-Go (TUG) test, which is a mobility task involving starting in a sitting position, standing up, walking three meters to cross a line on the floor, turning around, walking back and sitting down again. We combined TUG with the verbal task of naming different animals. Pilot study participants were 43 individuals with and without established dementia diagnoses who attended a clinic for memory assessment. Video-recorded test performances were systematically analysed. Deviant test performances concerning the interplay between test administration and participants' responses to the assessment instructions were revealed and led to refinements being made to the final study protocol. Exploration of the dual-task test outcome measures in a sub-sample of 22 persons, ten with and twelve without dementia, indicated that step-length and number of named animals after the turning point of the dual-task test might constitute appropriate measures for examining this kind of sample. We concluded that the refined study protocol is feasible for testing individuals undergoing initial memory assessments and healthy controls. Follow-up studies with larger samples are being carried out and will bring new knowledge to this area of research. It may also provide an opportunity for further studies exploring possibilities for broad clinical implementation.
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| 16. |
- Cegelski, Lynette, et al.
(författare)
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Small-molecule inhibitors target Escherichia coli amyloid biogenesis and biofilm formation
- 2009
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Ingår i: Nature Chemical Biology. - : Nature Publishing Group. - 1552-4450 .- 1552-4469. ; 5:12, s. 913-919
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Tidskriftsartikel (refereegranskat)abstract
- Curli are functional extracellular amyloid fibers produced by uropathogenic Escherichia coli (UPEC) and other Enterobacteriaceae. Ring-fused 2-pyridones, such as FN075 and BibC6, inhibited curli biogenesis in UPEC and prevented the in vitro polymerization of the major curli subunit protein CsgA. The curlicides FN075 and BibC6 share a common chemical lineage with other ring-fused 2-pyridones termed pilicides. Pilicides inhibit the assembly of type1pili, which are required for pathogenesis during urinary tract infection. Notably, the curlicides retained pilicide activities and inhibited both curli-dependent and type 1–dependent biofilms. Furthermore, pretreatment of UPEC with FN075 significantly attenuated virulence in a mouse model of urinary tract infection. Curli and type 1pili exhibited exclusive and independent roles in promoting UPEC biofilms, and curli provided a fitness advantage in vivo. Thus, the ability of FN075 to block the biogenesis of both curli and type 1pili endows unique anti-biofilm and anti-virulence activities on these compounds.
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| 17. |
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| 18. |
- Ek, Fredrik, et al.
(författare)
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Behavioral Analysis of Dopaminergic Activation in Zebrafish and Rats Reveals Similar Phenotypes
- 2016
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Ingår i: Acs Chemical Neuroscience. - : American Chemical Society (ACS). - 1948-7193. ; 7:5, s. 633-646
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Tidskriftsartikel (refereegranskat)abstract
- Zebrafish is emerging as a complement to mammals in behavioral studies; however, there is a lack of comparative studies with rodents and humans to establish the zebrafish as a predictive translational model. Here we present a detailed phenotype evaluation of zebrafish larvae, measuring 300-3000 variables and analyzing them using multivariate analysis to identify the most important ones for further evaluations. The dopamine agonist apomorphine has previously been shown to have a complex U-shaped dose response relationship in the variable distance traveled. In this study, we focused on breaking down distance traveled into more detailed behavioral phenotypes for both zebrafish and rats and identified in the multivariate analysis low and high dose phenotypes with characteristic behavioral features. Further analysis of single parameters also identified an increased activity at the lowest concentration indicative of a U-shaped dose response. Apomorphine increased the distance of each swim movement (bout) at both high and low doses, but the underlying behavior of this increase is different; at high dose, both bout duration and frequency increased whereas bout max speed was higher at low dose. Larvae also displayed differences in place preference. The low dose phenotype spent more time in the center, indicative of an anxiolytic effect, while the high-dose phenotype had a wall preference. These dose-dependent effects corroborated findings in a parallel rat study and previous observations in humans. The translational value of pharmacological zebrafish studies was further evaluated by comparing the amino acid sequence of the dopamine receptors (D-1-D-4), between zebrafish, rats and humans. Humans and zebrafish share 100% of the amino acids in the binding site for D-1 and D-3 whereas D-2 and D-4 receptors share 85-95%. Molecular modeling of dopamine D2 and D4 receptors indicated that nonconserved amino acids have limited influence on important ligand receptor interactions.
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| 19. |
- Forsell, Anders, 1978-
(författare)
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Kommunala ideal och politisk verklighet. : En jämförande fallstudie av frisinnad politisk organisering i Filipstad och Skövde, ca 1880-1920.
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Most studies of emerging Swedish parties and politics have mainly focused on the Swedish Social Democrats and their struggle for democracy and political power, most as a prelude to the so called ”Swedish Model”. Competing parties have received attention from historians on the national level, but their local origin remains to large extent an open field.The aim of this study is to investigate how local political factors shaped the emerging liberal party organizations in two small Swedish towns. By a case-oriented comparison two towns are contrasted, Skövde in Skaraborg county and Filipstad in Värmland.This thesis suggests that the distinction between national politics and municipal government, based on the interests of economic elites, was transformed during the period 1880-1920. During this period local elections and local government became increasingly sites for political struggle between different parties, with new agendas.With a framework that considered parties in light of their functions rather than organizational types and theoretical concepts borrowed from the sociology of social movements, the thesis main results suggest that political mobilization and liberal party-formation was depending on the local political traditions.The theoretical framework made it possible to pinpoint both similarities and differences between the cases. The results of the study indicate that the historical tradition is central to parties to emerge and flourish. This suggests that it is more meaningful to focus attention on local and regional processes to understand the historical development than has previously been done.
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| 20. |
- Grönqvist, Johan, et al.
(författare)
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Strain in semiconductor core-shell nanowires
- 2009
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Ingår i: Applied Physics Reviews. - : AIP Publishing. - 1931-9401. ; 106:5
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Tidskriftsartikel (refereegranskat)abstract
- We compute strain distributions in core-shell nanowires of zinc blende structure. We use both continuum elasticity theory and an atomistic model, and consider both finite and infinite wires. The atomistic valence force-field (VFF) model has only few assumptions. But it is less computationally efficient than the finite-element (FE) continuum elasticity model. The generic properties of the strain distributions in core-shell nanowires obtained based on the two models agree well. This agreement indicates that although the calculations based on the VFF model are computationally feasible in many cases, the continuum elasticity theory suffices to describe the strain distributions in large core-shell nanowire structures. We find that the obtained strain distributions for infinite wires are excellent approximations to the strain distributions in finite wires, except in the regions close to the ends. Thus, our most computationally efficient model, the FE continuum elasticity model developed for infinite wires, is sufficient, unless edge effects are important. We give a comprehensive discussion of strain profiles. We find that the hydrostatic strain in the core is dominated by the axial strain-component, epsilon(ZZ). We also find that although the individual strain components have a complex structure, the hydrostatic strain shows a much simpler structure. All in-plane strain components are of similar magnitude. The nonplanar off-diagonal strain components (epsilon(XZ) and epsilon(YZ)) are small but nonvanishing. Thus the material is not only stretched and compressed but also warped. The models used can be extended for the study of wurtzite nanowire structures, as well as nanowires with multiple shells.
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| 21. |
- Hedenström, Mattias, et al.
(författare)
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NMR studies of interactions between periplasmic chaperones from uropathogenic E-coli and pilicides that interfere with chaperone function and pilus assembly
- 2005
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Ingår i: ORGANIC & BIOMOLECULAR CHEMISTRY. - : Royal Society of Chemistry (RSC). - 1477-0520 .- 1477-0539. ; 3:23, s. 4193-4200
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Tidskriftsartikel (refereegranskat)abstract
- Adherence of uropathogenic Escherichia coli to host tissue is mediated by pili, which are hair-like protein structures extending from the outer cell membrane of the bacterium. The chaperones FimC and PapD are key components in pilus assembly since they catalyse folding of subunits that are incorporated in type 1 and P pili, respectively, and also transport the subunits across the periplasmic space. Recently, compounds that inhibit pilus biogenesis and interfere with chaperone-subunit interactions have been discovered and termed pilicides. In this paper NMR spectroscopy was used to study the interaction of different pilicides with PapD and FimC in order to gain structural knowledge that would explain the effect that some pilicides have on pilus assembly. First relaxation-edited NMR experiments revealed that the pilicides bound to the PapD chaperone with mM affinity. Then the pilicide-chaperone interaction surface was investigated through chemical shift mapping using N-15-labelled FimC. Principal component analysis performed on the chemical shift perturbation data revealed the presence of three binding sites on the surface of FimC, which interacted with three different classes of pilicides. Analysis of structure-activity relationships suggested that pilicides reduce pilus assembly in E. coli either by binding in the cleft of the chaperone, or by influencing the orientation of the flexible F1-G1 loop, both of which are part of the surface by which the chaperone forms complexes with pilus subunits. It is suggested that binding to either of these sites interferes with folding of the pilus subunits, which occurs during formation of the chaperone-subunit complexes. In addition, pilicides that influence the F1-G1 loop also appear to reduce pilus formation by their ability to dissociate chaperone-subunit complexes.
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| 22. |
- Johnson, Randi K., et al.
(författare)
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Metabolite-related dietary patterns and the development of islet autoimmunity
- 2019
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- The role of diet in type 1 diabetes development is poorly understood. Metabolites, which reflect dietary response, may help elucidate this role. We explored metabolomics and lipidomics differences between 352 cases of islet autoimmunity (IA) and controls in the TEDDY (The Environmental Determinants of Diabetes in the Young) study. We created dietary patterns reflecting pre-IA metabolite differences between groups and examined their association with IA. Secondary outcomes included IA cases positive for multiple autoantibodies (mAb+). The association of 853 plasma metabolites with outcomes was tested at seroconversion to IA, just prior to seroconversion, and during infancy. Key compounds in enriched metabolite sets were used to create dietary patterns reflecting metabolite composition, which were then tested for association with outcomes in the nested case-control subset and the full TEDDY cohort. Unsaturated phosphatidylcholines, sphingomyelins, phosphatidylethanolamines, glucosylceramides, and phospholipid ethers in infancy were inversely associated with mAb+ risk, while dicarboxylic acids were associated with an increased risk. An infancy dietary pattern representing higher levels of unsaturated phosphatidylcholines and phospholipid ethers, and lower sphingomyelins was protective for mAb+ in the nested case-control study only. Characterization of this high-risk infant metabolomics profile may help shape the future of early diagnosis or prevention efforts. © 2019, The Author(s).
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| 23. |
- Krischer, Jeffrey P, et al.
(författare)
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Predicting Islet Cell Autoimmunity and Type 1 Diabetes : An 8-Year TEDDY Study Progress Report
- 2019
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Ingår i: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 42:6, s. 1051-1060
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Assessment of the predictive power of The Environmental Determinants of Diabetes in the Young (TEDDY)-identified risk factors for islet autoimmunity (IA), the type of autoantibody appearing first, and type 1 diabetes (T1D).RESEARCH DESIGN AND METHODS: A total of 7,777 children were followed from birth to a median of 9.1 years of age for the development of islet autoantibodies and progression to T1D. Time-dependent sensitivity, specificity, and receiver operating characteristic (ROC) curves were calculated to provide estimates of their individual and collective ability to predict IA and T1D.RESULTS: HLA genotype (DR3/4 vs. others) was the best predictor for IA (Youden's index J = 0.117) and single nucleotide polymorphism rs2476601, in PTPN22, was the best predictor for insulin autoantibodies (IAA) appearing first (IAA-first) (J = 0.123). For GAD autoantibodies (GADA)-first, weight at 1 year was the best predictor (J = 0.114). In a multivariate model, the area under the ROC curve (AUC) was 0.678 (95% CI 0.655, 0.701), 0.707 (95% CI 0.676, 0.739), and 0.686 (95% CI 0.651, 0.722) for IA, IAA-first, and GADA-first, respectively, at 6 years. The AUC of the prediction model for T1D at 3 years after the appearance of multiple autoantibodies reached 0.706 (95% CI 0.649, 0.762).CONCLUSIONS: Prediction modeling statistics are valuable tools, when applied in a time-until-event setting, to evaluate the ability of risk factors to discriminate between those who will and those who will not get disease. Although significantly associated with IA and T1D, the TEDDY risk factors individually contribute little to prediction. However, in combination, these factors increased IA and T1D prediction substantially.
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| 24. |
- Liedberg, Fredrik, et al.
(författare)
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Fast-track access to urologic care for patients with macroscopic haematuria is efficient and cost-effective : results from a prospective intervention study
- 2016
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 115, s. 770-775
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Tidskriftsartikel (refereegranskat)abstract
- Background:The delay between onset of macroscopic haematuria and diagnosis of bladder cancer is often long.Methods:We evaluated timely diagnosis and health-care costs for patients with macroscopic haematuria given fast-track access to diagnostics. During a 15-month period, a telephone hotline for fast-track diagnostics was provided in nine Swedish municipalities for patients aged ⩾50 years with macroscopic haematuria. The control group comprised 101 patients diagnosed with bladder cancer in the same catchment area with macroscopic haematuria who underwent regular diagnostic process.Results:In all 275 patients who called ‘the Red Phone’ hotline were investigated, and 47 of them (17%) were diagnosed with cancer and 36 of those had bladder cancer. Median time from patient-reported haematuria to diagnosis was 29 (interquartile range (IQR) 14−104) days and 50 (IQR 27−165) days in the intervention and the control group, respectively (P=0.03). The median health-care costs were lower in the intervention group (655 (IQR 655−655) EUR) than in the control group (767 (IQR 490−1096) EUR) (P=0.002).Conclusions:Direct access to urologic expertise and fast-track diagnostics is motivated for patients with macroscopic haematuria to reduce diagnostic intervals and lower health-care expenditures.British Journal of Cancer advance online publication, 25 August 2016; doi:10.1038/bjc.2016.265 www.bjcancer.com.
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| 25. |
- Lindenger, C, et al.
(författare)
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Long-term survival and predictors of relapse and survival after liver transplantation for alcoholic liver disease
- 2018
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 53:12, s. 1553-1561
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Studies of predictive factors of alcohol recidivism and survival post-LT are not up-to-date. With evolving LT activity and with longer-term outcomes becoming increasingly available, re-evaluating post-LT outcomes is imperative. We analyzed recent data on survival, alcohol recurrence and predictive factors. Methods: We compared long-term survival among 159 consecutive ALD patients transplanted 2003-2016 with 159 propensity-score matched controls transplanted for non-ALD. Alcohol 'slips' (occasional lapse) and relapse to moderate or harmful drinking were assessed from medical records and structured forms filled in by home-district physicians, and analyzed by competing-risk and multivariate Cox regression analyses. Results: Patient and graft survival at 10 years were 75 and 69% in the ALD group and 65 and 63% in the control group (p=.06 and .36). In ALD patients, the 10-year cumulative rate of alcohol slip was 52% and of relapse, 37%. Duration of pre-LT abstinence (HR 0.97, 95% CI 0.94-0.99) and a history of prior alcohol relapses (HR 3.05, 95% CI 1.41-6.60) were significant predictors of relapse, but failed to predict death/graft loss. Patients with <6 months abstinence relapsed sooner than those with 7-24 months abstinence, but 10-year relapse rates were similar (40-50%). Ten-year relapse rate with 2-5-year pre-LT abstinence was 21%, and with >5-year abstinence, 0%. In patients with <6 months pre-LT abstinence, years of heavy drinking, prior addiction treatments, and lack of children predicted inferior survival. Conclusions: Although 37% of our ALD patients relapsed to drinking by 10 years post-LT, 14-year survival was not significantly different from survival in non-ALD patients. Short duration of pre-LT abstinence and prior relapses predicted post-LT relapse.
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| 26. |
- Lundgren, Markus, et al.
(författare)
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Analgesic antipyretic use among young children in the TEDDY study : No association with islet autoimmunity
- 2017
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Ingår i: BMC Pediatrics. - : Springer Science and Business Media LLC. - 1471-2431. ; 17:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The use of analgesic antipyretics (ANAP) in children have long been a matter of controversy. Data on their practical use on an individual level has, however, been scarce. There are indications of possible effects on glucose homeostasis and immune function related to the use of ANAP. The aim of this study was to analyze patterns of analgesic antipyretic use across the clinical centers of The Environmental Determinants of Diabetes in the Young (TEDDY) prospective cohort study and test if ANAP use was a risk factor for islet autoimmunity. Methods: Data were collected for 8542 children in the first 2.5 years of life. Incidence was analyzed using logistic regression with country and first child status as independent variables. Holm's procedure was used to adjust for multiplicity of intercountry comparisons. Time to autoantibody seroconversion was analyzed using a Cox proportional hazards model with cumulative analgesic use as primary time dependent covariate of interest. For each categorization, a generalized estimating equation (GEE) approach was used. Results: Higher prevalence of ANAP use was found in the U.S. (95.7%) and Sweden (94.8%) compared to Finland (78.1%) and Germany (80.2%). First-born children were more commonly given acetaminophen (OR 1.26; 95% CI 1.07, 1.49; p = 0.007) but less commonly Non-Steroidal Anti-inflammatory Drugs (NSAID) (OR 0.86; 95% CI 0.78, 0.95; p = 0.002). Acetaminophen and NSAID use in the absence of fever and infection was more prevalent in the U.S. (40.4%; 26.3% of doses) compared to Sweden, Finland and Germany (p < 0.001). Acetaminophen or NSAID use before age 2.5 years did not predict development of islet autoimmunity by age 6 years (HR 1.02, 95% CI 0.99-1.09; p = 0.27). In a sub-analysis, acetaminophen use in children with fever weakly predicted development of islet autoimmunity by age 3 years (HR 1.05; 95% CI 1.01-1.09; p = 0.024). Conclusions: ANAP use in young children is not a risk factor for seroconversion by age 6 years. Use of ANAP is widespread in young children, and significantly higher in the U.S. compared to other study sites, where use is common also in absence of fever and infection.
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| 27. |
- Malmberg, Lisa, 1982-
(författare)
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Building Design Capability in the Public Sector : Expanding the Horizons of Development
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Public sector organizations are in need of new approaches to development and innovation. There is a need to develop a capability to better understand priorities, needs and wishes of public sector service users and become more proactive, in order to meet the demands on keeping costs down and quality high.Design is increasingly put forward as a potential answer to this need and there are many initiatives taken across the world to encourage the use of a design approach to development and innovation within public sector. In relation to this trend there is a need to improve the understanding of how public sector organizations develop ability to exploit design; how they develop design capability. This is the focus of this thesis, which through an exploratory study has observed the two initiatives aiming to introduce design and develop design capability within healthcare and social service organizations.One main contribution of this work is an understanding of the design capability concept based on a structured review of the use of the design capability concept in the literature. The concept has previously been used in relation to different aspects of designs in organizations.Another important contribution is the development of an understanding for how design capability is developed based on interpretations founded in the organizational learning perspective of absorptive capacity. The study has identified how different antecedents to development of design capability have influenced this development in the two cases. The findings have identified aspects that both support and impede the development of design capability which are important to acknowledge and address when aiming to develop design capability within a public sector organization.In both cases, the set up of the knowledge transferring efforts focus mainly on developing awareness of design. Similar patterns are seen in other prior and parallel initiatives. The findings however suggest that it is also important to ensure that the organization have access to design competence and that structures like routines, processes and culture support and enable the use of design practice, in order to make design a natural part of the continuous development work.
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| 28. |
- Mattsson Hultén, Lillemor, 1951, et al.
(författare)
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15-Lipoxygenase-2 is expressed in macrophages in human carotid plaques and regulated by hypoxia-inducible factor-1 alpha
- 2010
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Ingår i: European Journal of Clinical Investigation. - : Wiley. - 1365-2362 .- 0014-2972. ; 40:1, s. 11-17
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Tidskriftsartikel (refereegranskat)abstract
- Background Macrophages are prominent in hypoxic areas of atherosclerotic lesions and their secreted cytokines, growth factors and activity of enzymes are involved in atherogenesis. Previously, we showed that 15-lipoxygenase (LOX)-2 is expressed in human monocyte-derived macrophages and that hypoxia increases 15-LOX-2 expression and secretion of pro-inflammatory molecules. Here we investigated whether human carotid plaque macrophages express 15-LOX-2 and whether its expression in macrophages is regulated by hypoxia through hypoxia-inducible factor 1α (HIF-1α). Materials and methods Carotid plaques from 47 patients with high-grade symptomatic carotid artery stenosis were analysed using immunohistochemistry, and stained areas were quantified by digital image analysis. Carotid plaque macrophages were isolated with anti-CD14 immunobeads using an immunomagnetic bead technique. Primary macrophages were transfected with HIF-1α siRNA or control siRNA before extraction of RNA and medium analysis. Results In paired tissue sections, the extent of staining for CD68 correlated with staining for 15-LOX-2 but not for 15-LOX-1. In carotid plaque macrophages isolated with anti-CD14 immunobeads, 15-LOX-2 mRNA was expressed at high levels. In primary macrophages, 15-LOX-2 expression was significantly increased by incubation with the HIF-1α stabilizer dimethyloxalylglycine. Knockdown of HIF-1α significantly decreased production of the 15-LOX-2 enzyme products 12- and 15-hydroxyeicosatetraenoic acid. In carotid plaques, HIF-1α staining correlated with staining for 15-LOX-2. Conclusions These results demonstrate that 15-LOX-2 is highly expressed in human plaques and is correlated with the presence of macrophages and HIF-1α. 15-LOX-2 enzyme activity can be modulated by HIF-1α. Thus, increased expression of 15-LOX-2 in macrophages in hypoxic atherosclerotic plaque may enhance inflammation and the recruitment of inflammatory cells.
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| 29. |
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| 30. |
- Olsson, Fredrik, et al.
(författare)
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Neuromuscular Controller Models for Quantifying Standing Balance in Older People : A Systematic Review
- 2023
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Ingår i: IEEE Reviews in Biomedical Engineering. - : Institute of Electrical and Electronics Engineers (IEEE). - 1941-1189 .- 1937-3333. ; 16, s. 560-578
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Forskningsöversikt (refereegranskat)abstract
- Objective quantification of the balancing mechanisms in humans is strongly needed in health care of older people, yet is largely missing among current clinical balance assessment methods. Hence, the main goal of this literature review is to identify methods that have the potential to meet that need. We searched in the PubMed and IEEE Xplore databases using predefined criteria, screened 1064 articles, and systematically reviewed and categorized methods from 73 studies that deal with identification of neuromuscular controller models of human upright standing from empirical data. These studies were then analyzed with the particular aim to understand to what degree such methods would be useful solutions for assessing the balance of older individuals aged above 60 years. The 16 studies that included an older subject population were especially examined with this in mind. The majority of the reviewed articles focused on research questions related to the general function of human balance control rather than clinical applicability. Further efforts need to be made to adapt these methods for more accessible and mobile technologies and to ensure that the outcomes are valid for balance assessment of a general older population.
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| 31. |
- Pemberton, Nils, et al.
(författare)
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Microwave-assisted synthesis of highly substituted aminomethylated 2-pyridones
- 2004
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Ingår i: Journal of Organic Chemistry. - Easton, Pa. : American Chemical Society. - 0022-3263 .- 1520-6904. ; 69:23, s. 7830-7835
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Tidskriftsartikel (refereegranskat)abstract
- By employing microwave-assisted organic synthesis (MAOS) efficient conditions to introduce aminomethylene substituents in highly substituted bicyclic 2-pyridones have been established. Primary amino methylene substituents were introduced via a cyanodehalogenation followed by a borane dimethyl sulfide reduction of the afforded nitrile. In both of these transformations, microwave irradiation proved to be superior to traditional conditions and the primary amines were obtained in good overall yields (55-58% over three steps). To incorporate tertiary aminomethylene substituents in the 2-pyridone framework, a microwave-assisted Mannich reaction using preformed iminium salts proved to be effective. Thus highly substituted 2-pyridones were obtained in 48-93% yields.
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| 32. |
- Persson, Anders I., 1973, et al.
(författare)
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Expression of delta opioid receptor mRNA and protein in the rat cerebral cortex and cerebellum is decreased by growth hormone.
- 2003
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Ingår i: Journal of neuroscience research. - : Wiley. - 0360-4012 .- 1097-4547. ; 71:4, s. 496-503
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Tidskriftsartikel (refereegranskat)abstract
- Hormones released from the pituitary have been shown to regulate the expression of different proteins in the central nervous system. We wanted to examine whether peripheral administration of bovine growth hormone (bGH) regulates the expression of delta-opioid receptor (DOR) in the cerebral cortex and cerebellum. Expression of the DOR protein was quantified using Western blot densitometry. DOR mRNA was quantified with a solution hybridization RNase protection assay. Hypophysectomized (Hx) and untreated normal female rats were included in the study. All Hx rats were hormonally treated with cortisol (400 microg/kg/day) and L-thyroxine (10 microg/kg/day) for 19 days. Hypophysectomy resulted in a threefold increase in cerebral cortex and a twofold increase in cerebellum of the DOR protein compared with normal rats. One subgroup of Hx rats received bGH (1 mg/kg body weight) as a daily subcutaneous injection for 19 days. This treatment normalized the levels of DOR protein in the cerebral cortex and cerebellum. Immunohistochemical experiments showed that GH decreased DOR expression especially in layers II-VI in cerebral cortex and in stratum moleculare in cerebellum. Quantification of DOR mRNA by solution hybridization RNase protection assay corresponded to the DOR protein measurements. We conclude that the expression of DORs in cerebral cortex and cerebellum is regulated by GH.
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| 33. |
- Pinkner, Jerome S., et al.
(författare)
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Rationally designed small compounds inhibit pilus biogenesis in uropathogenic bacteria
- 2006
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - Washtington : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 103:47, s. 17897-17902
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Tidskriftsartikel (refereegranskat)abstract
- A chemical synthesis platform with broad applications and flexibility was rationally designed to inhibit biogenesis of adhesive pili assembled by the chaperone–usher pathway in Gram-negative pathogens. The activity of a family of bicyclic 2-pyridones, termed pilicides, was evaluated in two different pilus biogenesis systems in uropathogenic Escherichia coli. Hemagglutination mediated by either type 1 or P pili, adherence to bladder cells, and biofilm formation mediated by type 1 pili were all reduced by 90% in laboratory and clinical E. coli strains. The structure of the pilicide bound to the P pilus chaperone PapD revealed that the pilicide bound to the surface of the chaperone known to interact with the usher, the outer-membrane assembly platform where pili are assembled. Point mutations in the pilicide-binding site dramatically reduced pilus formation but did not block the ability of PapD to bind subunits and mediate their folding. Surface plasmon resonance experiments confirmed that the pilicide interfered with the binding of chaperone–subunit complexes to the usher. These pilicides thus target key virulence factors in pathogenic bacteria and represent a promising proof of concept for developing drugs that function by targeting virulence factors.
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| 34. |
- Rosenmüller, Mats H., et al.
(författare)
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Costs and quality of life of small-incision open cholecystectomy and laparoscopic cholecystectomy : an expertise-based randomised controlled trial
- 2017
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Ingår i: BMC Gastroenterology. - : BIOMED CENTRAL LTD. - 1471-230X. ; 17
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Tidskriftsartikel (refereegranskat)abstract
- Background: Health care providers need solid evidence based data on cost differences between alternative surgical procedures for common surgical disorders. We aimed to compare small-incision open cholecystectomy (SIOC) and laparoscopic cholecystectomy (LC) concerning costs and health-related quality of life using data from an expertise-based randomised controlled trial. Methods: Patients scheduled for cholecystectomy were assigned to undergo LC or SIOC performed by surgeons in two different expert groups. Total costs were calculated in USD. Reusable instruments were assumed for the cost analysis. Quality of life was measured using the EuroQol 5-D 3-L (EQ 5-D-3L), at five postoperative time points and calculated to Area Under Curve (AUC) for 1 year postoperatively. Two hospitals participated in the trial, which included both emergency and elective surgery. Results: Of 477 patients that underwent a cholecystectomy during the study period, 355 (74.9%) were randomised and 323 analysed, 172 LC and 151 SIOC patients. Both direct and total costs were less for SIOC than for LC patients. The total costs were 5429 (4293-6932) USD for LC and 4636 (3905-5746) USD for SIOC, P = 0.001. The quality of life index did not differ between the LC and SIOC groups at any time. Median values (25th and 75th percentiles (p25-p75)) for AUC at 1 year were as follows: 349 (337-351) for LC and 349 (338-350) for SIOC. Conclusions: In this expertise-based randomised controlled trial LC was a more costly procedure and quality of life did not differ after SIOC and LC. (ClinicalTrials.gov Identifier: NCT00370344, August 30, 2006).
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| 35. |
- Selander, Sara, et al.
(författare)
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When weaker brands prevail
- 2003
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Ingår i: Journal of Product and Brand Management. - : Emerald. - 1061-0421. ; 12:1, s. 6-21
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- When consumers fulfill consumption goals they make decisions on first, from which product category to buy, and second, which brand to purchase within the product category. In this article, the relative effects of product-level typicality and brand-level typicality on goal-driven consumer choice are examined. Which level of typicality is more diagnostic of choice? Empirical results show that consumers are, in goal-derived usage contexts, more likely to choose a less typical and less favored brand from a typical product category than a typical and more favored brand from a less typical product category. Consequently, brands that consumers perceive as inferior may be chosen over superior brands because of the link between product categories and usage contexts. Our results indicate that it may be fruitful for marketers to associate brands and product categories with usage contexts, and that they need to consider brand competitors from other product categories.
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| 36. |
- Smith, Laura B., et al.
(författare)
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Psychological manifestations of celiac disease autoimmunity in young children
- 2017
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Ingår i: Pediatrics. - : American Academy of Pediatrics (AAP). - 0031-4005 .- 1098-4275. ; 139:3
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND OBJECTIVES: Psychological symptoms can be associated with celiac disease; abstract however, this association has not been studied prospectively in a pediatric cohort. We examined mother report of psychological functioning in children persistently positive for tissue transglutaminase autoantibodies (tTGA), defined as celiac disease autoimmunity (CDA), compared with children without CDA in a screening population of genetically at-risk children. We also investigated differences in psychological symptoms based on mothers' awareness of their child's CDA status. METHODS: The Environmental Determinants of Diabetes in the Young study followed 8676 children to identify triggers of type 1 diabetes and celiac disease. Children were tested for tTGA beginning at 2 years of age. The Achenbach Child Behavior Checklist assessed child psychological functioning at 3.5 and 4.5 years of age. RESULTS: At 3.5 years, 66 mothers unaware their child had CDA reported more child anxiety and depression, aggressive behavior, and sleep problems than 3651 mothers of children without CDA (all Ps ≤ .03). Unaware-CDA mothers also reported more child anxiety and depression, withdrawn behavior, aggressive behavior, and sleep problems than 440 mothers aware of their child's CDA status (all Ps ≤.04). At 4.5 years, there were no differences. CONCLUSIONS: In 3.5-year-old children, CDA is associated with increased reports of child depression and anxiety, aggressive behavior, and sleep problems when mothers are unaware of their child's CDA status. Mothers' knowledge of their child's CDA status is associated with fewer reports of psychological symptoms, suggesting that awareness of the child's tTGA test results affects reporting of symptoms.
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| 37. |
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| 38. |
- Thornberg, Fredrik, 1971-
(författare)
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Kompetens i klassrumsbedömning – en studie av lärares reflektioner om videodokumenterad undervisning
- 2015
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- There is a tendency to view teachers´ assessment literacy from a deficit perspective, and teachers existing practices are rarely used as a source of knowledge about assessment. Instead of treating teachers as being to some extent experts on assessment, the domain of assessment literacy is primarily represented by viewing researchers as “experts”. In this study teachers´ assessment literacy is approached from an asset perspective. The knowledge and skills that teachers possess can contribute to the description and understanding of classroom assessment literacy.The overall aim of the study is to develop knowledge about teachers’ classroom assessment literacy. Studying teachers' collective reflections about assessment, in relation to video-recorded teaching situations, is used to approach the question of what classroom assessment and assessment literacy actually mean. Three primary schools and eleven teachers, heterogeneous regarding age, sex, education and experience, are involved in the study. The results indicate three themes to describe teachers´ classroom assessment literacy: focus on the intention of assessment, focus on the enactment of assessment and focus on the conclusion of assessment. The study shows that teachers have the competence to conduct and use assessment as an integral part of teaching. An overall conclusion is that assessment literate teachers invite students to share power and responsibility in assessment processes. The three themes can be seen as a process of developing, implementing and using assessments, which requires a holistic approach to learning, teaching and assessment.
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| 39. |
- Törn, Carina, et al.
(författare)
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Complement gene variants in relation to autoantibodies to beta cell specific antigens and type 1 diabetes in the TEDDY Study
- 2016
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
-
Tidskriftsartikel (refereegranskat)abstract
- A total of 15 SNPs within complement genes and present on the ImmunoChip were analyzed in The Environmental Determinants of Diabetes in the Young (TEDDY) study. A total of 5474 subjects were followed from three months of age until islet autoimmunity (IA: n = 413) and the subsequent onset of type 1 diabetes (n = 115) for a median of 73 months (IQR 54-91). Three SNPs within ITGAM were nominally associated (p < 0.05) with IA: rs1143678 [Hazard ratio; HR 0.80; 95% CI 0.66-0.98; p = 0.032], rs1143683 [HR 0.80; 95% CI 0.65-0.98; p = 0.030] and rs4597342 [HR 1.16; 95% CI 1.01-1.32; p = 0.041]. When type 1 diabetes was the outcome, in DR3/4 subjects, there was nominal significance for two SNPs: rs17615 in CD21 [HR 1.52; 95% CI 1.05-2.20; p = 0.025] and rs4844573 in C4BPA [HR 0.63; 95% CI 0.43-0.92; p = 0.017]. Among DR4/4 subjects, rs2230199 in C3 was significantly associated [HR 3.20; 95% CI 1.75-5.85; p = 0.0002, uncorrected] a significance that withstood Bonferroni correction since it was less than 0.000833 (0.05/60) in the HLA-specific analyses. SNPs within the complement genes may contribute to IA, the first step to type 1 diabetes, with at least one SNP in C3 significantly associated with clinically diagnosed type 1 diabetes.
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| 40. |
- Vessby, Johan, 1972-, et al.
(författare)
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A two-step proteomic approach identifies candidate biomarker in ulcerative colitis with concomitant primary sclerosing cholangitis.
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: Ulcerative colitis (UC) with concomitant primary sclerosing cholangitis (PSC-UC or PSC-IBD) is today considered a unique IBD entity, including a more malignant disease course compared with classical UC. Biomarkers for identifying UC patients at risk of developing PSC is lacking, which may delay the onset of endoscopy surveillance. Mass spectrometric development has enabled the use of formalin-fixed paraffin embedded tissue (FFPE) for high resolution proteome analysis. In this study, we search for PSC-IBD proteomic fingerprints in FFPE by utilizing mass spectrometry.Methods: Protein was extracted out of FFPE colon archival samples from PSC-IBD (n=9), UC (n=7), and healthy controls (n=7). IBD-patients were all in clinical remission, without biologics or steroids, and all UC patients had a history of pancolitis. Samples were processed by the Multienzyme Digestion FASP and were analysed by liquid chromatography tandem mass spectrometry (LC-MS/MS). Proteins were quantified using the Total Protein Approach. Data was analysed using linear regression and in a multiple manner using random forest algorithms. Candidate findings were validated in a second cohort (n: PSC-IBD=16 UC=21) using the same proteomic technique. To make an over-all proteome comparison, we performed principal component analysis, as well as a meta-analysis for the most prominent findings.Results: In the exploratory proteomic step, 7279 unique proteins were detected. After statistical analysis including multiple testing, the top-5 proteins (CD47, LSM7, NDUFAF4, AGPAT1 and THEM192) were selected as candidate proteins. When validating these findings in a confirmatory cohort, AGPAT1 was verified (p=0.009). According to meta-analysis, AGPAT1 was also found to be the most distinctive protein between PSC-IBD and UC. The overall proteomic profiles in step 1 and step 2 (7706 proteins) confirmed small biologic variations between the IBD-groups.Conclusions: In this two-step proteomic study on remissive IBD, we were able to verify AGPAT1 as a colonic PSC-IBD biomarker. We found high overall proteome resemblance, in contrast to the phenotypical differences existing between PSC-IBD and UC. Our findings have possible implication in future PSC-IBD diagnostics, and adds further knowledge to the evasive PSC-IBD phenotype.
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| 41. |
- Vessby, Johan, 1972-, et al.
(författare)
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AGPAT1 as a Novel Colonic Biomarker for Discriminating Between Ulcerative Colitis With and Without Primary Sclerosing Cholangitis
- 2022
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Ingår i: Clinical and Translational Gastroenterology. - : Ovid Technologies (Wolters Kluwer Health). - 2155-384X. ; 13:5
-
Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Ulcerative colitis (UC) associated with primary sclerosing cholangitis (PSC-UC) is considered a unique inflammatory bowel disease (IBD) entity. PSC diagnosis in an IBD individual entails a significantly higher risk of gastrointestinal cancer; however, biomarkers for identifying patients with UC at risk for PSC are lacking. We, therefore, performed a thorough PSC-UC biomarker study, starting from archived colonic tissue.METHODS: Proteins were extracted out of formalin-fixed paraffin-embedded proximal colon samples from PSC-UC (n = 9), UC (n = 7), and healthy controls (n = 7). Patients with IBD were in clinical and histological remission, and all patients with UC had a history of pancolitis. Samples were processed by the multienzyme digestion FASP and subsequently analyzed by liquid chromatography-tandem mass spectrometry. Candidate proteins were replicated in an independent cohort (n: PSC-UC = 16 and UC = 21) and further validated by immunohistochemistry.RESULTS: In the discovery step, 7,279 unique proteins were detected. The top 5 most differentiating proteins (PSC-UC vs UC) based on linear regression analysis were selected for replication. Of these, 1-acetylglycerol-3-phosphate O-acyltransferase 1 (AGPAT1) was verified as higher in PSC-UC than UC (P = 0.009) in the replication cohort. A difference on the group level was also confirmed by immunohistochemistry, showing more intense AGPAT1 staining in patients with PSC-UC compared with UC.DISCUSSION: We present AGPAT1 as a potential colonic biomarker for differentiating PSC-UC from UC. Our findings have possible implication for future PSC-IBD diagnostics and surveillance.
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| 42. |
- Vessby, Johan, 1972-
(författare)
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Studies of ulcerative colitis with concomitant primary sclerosing cholangitis : Beyond the clinical phenotype
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Inflammatory bowel disease (IBD) is a group of chronically relapsing immune-related disorders, engaging the gastrointestinal tract. Symptoms vary depending on inflammatory phenotype, but may include diarrhoea, bowel pain and weight loss. The two most common entities are Crohn's disease and ulcerative colitis (UC). A minority of IBD patients, particularly UC, is concomitantly affected by primary sclerosing cholangitis (PSC) – an inflammatory bile duct disease with dismal prognosis. IBD with associated PSC has distinct clinical features, and is regarded a unique IBD phenotype (PSC-IBD or PSC-UC). These features include higher rates of pancolitis, a milder clinical course, and an unexplained increased risk of colorectal neoplasia.This thesis aimed to compare immunological conditions in PSC-UC and UC, but also to search for molecular differences, potentially facilitating PSC-UC diagnosis.In paper I and II, we compared eosinophil and lymphocyte activation and regulation. PSC-UC had down-regulated mucosal eosinophil activity, during both flare and remission. Compared with UC, PSC-UC had a dampened, and less Th2 dominated mucosal immune response. This was evident by a low quote of CRTH2/CXCR3 CD4+ cells and a cytokine milieu with no upregulated Th2 cytokines. In contrast, PSC-UC had highly up-regulated cytokines in peripheral blood. Among these, sCD40 stood out as being most important for inter-group separation according to multivariate analysis.In paper III, we gave a detailed description of colonic tissue factor (TF) expression. We found discrepancies in TF depending on UC subtype and inflammatory status, where inflammation- associated TF up-regulation was detected in UC only. Also, we identified stromal TF deposition as a sensitive indicator of acute colitis.In paper IV, PSC-UC and UC intestinal proteomes were compared using LC-MS/MS. After detecting more than 7200 unique proteins in the discovery step, the top-five most distinctive findings were chosen for verification. Of these, AGPAT1 was verified, being significantly higher in PSC-UC. Despite phenotypical differences, the overall colonic proteome comparison showed high degree of concordance.In summary, this thesis demonstrates distinct immunological and molecular properties in PSC-UC, implying phenotypical features beyond clinical observations. Moreover, serum sCD40 and colonic AGPAT1 are suggested possible PSC-UC biomarkers.
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| 43. |
- Vessby, Johan, 1972-, et al.
(författare)
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Tissue factor in ulcerative colitis, with and without concomitant primary sclerosing cholangitis
- 2019
-
Ingår i: Upsala Journal of Medical Sciences. - : Taylor & Francis Group. - 0300-9734 .- 2000-1967. ; 124:4, s. 238-245
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Tidskriftsartikel (refereegranskat)abstract
- Background: Ulcerative colitis (UC) in patients with the severe disease primary sclerosing cholangitis (PSC) constitutes a distinct clinical phenotype (PSC-UC) with a high incidence of colorectal cancer. Today, PSC-UC diagnosis is built on clinical observations only. Tissue factor (TF) has a potential use in UC diagnostics, and also in colorectal cancer prognostication. Here we evaluate TF expression in an inflammatory bowel disease (IBD) cohort, with special focus on differences between UC and PSC-UC patients.Materials and methods: Colonic biopsies from UC (n = 23), PSC (n = 24), and healthy controls (n = 11) were stained for TF by immunohistochemistry. Mononuclear cell contribution to TF expression was verified using flow cytometry.Results: TF was distributed at three distinct colonic locations: in subepithelial pericryptal sheath cells, in mononuclear cells, and in the intestinal stroma. In contrast to UC-where inflammation was accompanied with TF up-regulation-PSC-UC activity remained low during inflammation. Stromal TF positivity was found exclusively in ongoing inflammation.Conclusion: Our study provides additional support for a divergent pathogenesis in PSC-UC, with an inflammatory environment that differs from classical UC. Stromal TF emerges as a new marker of colonic inflammation.
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| 44. |
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| 45. |
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| 46. |
- Wijk, Katarina, et al.
(författare)
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Perceived enabling factors and barriers for the implementation of improvements in health care in order to achieve patient-centred care : A case report from Sweden
- 2020
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Ingår i: Journal of Evaluation In Clinical Practice. - : John Wiley & Sons. - 1356-1294 .- 1365-2753. ; 26:3, s. 791-800
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Rationale, aim, and objectives More knowledge is needed regarding the complex factors and perceptions that enable the implementation of change in health care. The study aimed to examine the enabling factors and barriers encountered in the implementation of improvements in health care in order to achieve patient-centred care (PCC) and to study if there was a correlation in the extent the improvements were perceived to be implemented and the preconditions that were considered to affect them. Methods Using a mixed method design, data were gathered via a questionnaire and individual interviews with health care personnel, clinic managers, and first-line managers. The data collection and analyses were based on the framework for Promoting Action on Research Implementation in Health Services (PARiHS). Correlations between PCC improvements and preconditions for improvements were performed. Results A high level of involvement, knowledge, and adequate resources were considered important to achieve an implementation of PCC with joint responsibility. Leadership and management need to be explicit and promote continuous follow-up and feedback. Preconditions for improvement had a linear correlation with the perceived level of implementation. Knowledge-related preconditions had greatest impact on implementation. Conclusions The PARiHS framework was appropriate to use since the three components of evidence, context, and facilitation present different important preconditions in the implementation process. Evidence was the highest rated contributor since evidence-based practices in health care are necessary. It is vital that the important role of the context and facilitators is acknowledged in the implementation process to enable a successful implementation of change. There is a need to incorporate a clear strategy involving all levels in the organization. Furthermore, leaders play an important role in the implementation by facilitating communication and support and by having trust in facilitators and health care personnel. The results are applicable to other interventions implementing change in health care.
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| 47. |
- Yrjänäinen, Väinö, et al.
(författare)
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The Swedish parliament corpus 1867–2022
- 2024
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Ingår i: Proceedings of the 2024 Joint International Conference on Computational Linguistics, Language Resources and Evaluation (LREC-COLING 2024). - : ELRA Language Resource Association. - 9782493814104 ; , s. 16100-16112
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Konferensbidrag (refereegranskat)abstract
- The Swedish parliamentary records are an important source material for social science and humanities researchers. We introduce a new research corpus, the Swedish Parliament Corpus, which is larger and more developed than previously available research corpora for the Swedish parliament. The corpus contains annotated and structured parliamentary records over more than 150 years, through the bicameral parliament (1867–1970) and the unicameral parliament (1971–). In addition to the records, which contain all speeches in the parliament, we also provide a database of all members of parliament over the same period. Along with the corpus, we describe procedures to ensure data quality. The corpus facilitates detailed analysis of parliamentary speeches in several research fields.
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| 48. |
- Zamani, Leila, et al.
(författare)
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High cell density perfusion culture has a maintained exoproteome and metabolome
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Chinese hamster ovary (CHO) cells are the workhorse to produce recombinant proteins in the biopharmaceutical industry using mammalian cells and are commonly cultured in either fed-batch or perfusion mode. The optimization of the complex biological systems used in such processes is extremely challenging. Multi-omics approaches can reveal otherwise unknown characteristics of these systems and identify culture parameters that can be manipulated to optimize the cultivation process. Here we have ap- plied both metabolomic and proteomic profiling to a monoclonal antibody (mAb) production operated in perfusion mode to explore how cell biology and reactor environment change as the cell density reaches ≥ 200 x 106 cells/mL. The extracellular metabolic composition obtained in perfusion mode was also com- pared to fed-batch, which showed a more stable profile for perfusion despite a far larger range of viable cell densities. The proteomics data showed an increase of structural proteins as the cell density increased, and both the proteomic and metabolic results showed signs of oxidative stress and changes in glutathione metabolism at very high cell densities. The methodology presented herein could be a powerful tool for optimizing cultivation processes and recombinant protein production.
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| 49. |
- Zamani, Leila, et al.
(författare)
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High Cell Density Perfusion Culture has a Maintained Exoproteome and Metabolome
- 2018
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Ingår i: Biotechnology Journal. - : Wiley. - 1860-6768 .- 1860-7314. ; 13:10
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Tidskriftsartikel (refereegranskat)abstract
- The optimization of bioprocesses for biopharmaceutical manufacturing by Chinese hamster ovary (CHO) cells can be a challenging endeavor and, today, heavily relies on empirical methods treating the bioreactor process and the cells as black boxes. Multi-omics approaches have the potential to reveal otherwise unknown characteristics of these systems and identify culture parameters to more rationally optimize the cultivation process. Here, the authors have applied both metabolomic and proteomic profiling to a perfusion process, using CHO cells for antibody production, to explore how cell biology and reactor environment change as the cell density reaches 200x10(6)cellsmL(-1). The extracellular metabolic composition obtained in perfusion mode shows a markedly more stable profile in comparison to fed-batch, despite a far larger range of viable cell densities in perfusion. This stable profile is confirmed in the extracellular proteosome. Furthermore, the proteomics data shows an increase of structural proteins as cell density increases, which could be due to a higher shear stress and explain the decrease in cell diameter at very high cell densities. Both proteomic and metabolic results shows signs of oxidative stress and changes in glutathione metabolism at very high cell densities. The authors suggest the methodology presented herein to be a powerful tool for optimizing processes of recombinant protein production.
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| 50. |
- Zhang, Huai, et al.
(författare)
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A global survey on the use of the international classification of diseases codes for metabolic dysfunction-associated fatty liver disease.
- 2024
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Ingår i: Hepatology international. - 1936-0541.
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Tidskriftsartikel (refereegranskat)abstract
- With the implementation of the 11th edition of the International Classification of Diseases (ICD-11) and the publication of the metabolic dysfunction-associated fatty liver disease (MAFLD) nomenclature in 2020, it is important to establish consensus for the coding of MAFLD in ICD-11. This will inform subsequent revisions of ICD-11.Using the Qualtrics XM and WJX platforms, questionnaires were sent online to MAFLD-ICD-11 coding collaborators, authors of papers, and relevant association members.A total of 890 international experts in various fields from 61 countries responded to the survey. We also achieved full coverage of provincial-level administrative regions in China. 77.1% of respondents agreed that MAFLD should be represented in ICD-11 by updating NAFLD, with no significant regional differences (77.3% in Asia and 76.6% in non-Asia, p=0.819). Over 80% of respondents agreed or somewhat agreed with the need to assign specific codes for progressive stages of MAFLD (i.e. steatohepatitis) (92.2%), MAFLD combined with comorbidities (84.1%), or MAFLD subtypes (i.e., lean, overweight/obese, and diabetic) (86.1%).This global survey by a collaborative panel of clinical, coding, health management and policy experts, indicates agreement that MAFLD should be coded in ICD-11. The data serves as a foundation for corresponding adjustments in the ICD-11 revision.
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