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- Domsgen, E, et al.
(author)
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An IFIH1 gene polymorphism associated with risk for autoimmunity regulates canonical antiviral defence pathways in Coxsackievirus infected human pancreatic islets
- 2016
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In: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6, s. 39378-
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Journal article (peer-reviewed)abstract
- The IFIH1 gene encodes the pattern recognition receptor MDA5. A common polymorphism in IFIH1 (rs1990760, A946T) confers increased risk for autoimmune disease, including type 1-diabetes (T1D). Coxsackievirus infections are linked to T1D and cause beta-cell damage in vitro. Here we demonstrate that the rs1990760 polymorphism regulates the interferon (IFN) signature expressed by human pancreatic islets following Coxsackievirus infection. A strong IFN signature was associated with high expression of IFNλ1 and IFNλ2, linking rs1990760 to the expression of type III IFNs. In the high-responding genotype, IRF-1 expression correlated with that of type III IFN, suggesting a positive-feedback on type III IFN transcription. In summary, our study uncovers an influence of rs1990760 on the canonical effector function of MDA5 in response to an acute infection of primary human parenchymal cells with a clinically relevant virus linked to human T1D. It also highlights a previously unrecognized connection between the rs1990760 polymorphism and the expression level of type III IFNs.
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- Fritzell, Peter, et al.
(author)
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Cost-effectiveness of lumbar fusion and nonsurgical treatment for chronic low back pain in the Swedish lumbar spine study : A multicenter, randomized, controlled trial from the Swedish Lumbar Spine Study Group
- 2004
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In: Spine. - : Lippincott Williams & Wilkins. - 0362-2436 .- 1528-1159. ; 29:4, s. 421-434
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Journal article (peer-reviewed)abstract
- Study Design. A cost-effectiveness study was performed from the societal and health care perspectives. Objective. To evaluate the costs-effectiveness of lumbar fusion for chronic low back pain (CLBP) during a 2-year follow-up. Summary of Background Data. A full economic evaluation comparing costs related to treatment effects in patients with CLBP is lacking. Patients and Methods. A total of 284 of 294 patients with CLBP for at least 2 years were randomized to either lumbar fusion or a nonsurgical control group. Costs for the health care sector ( direct costs), and costs associated with production losses ( indirect costs) were calculated. Societal total costs were identified as the sum of direct and indirect costs. Treatment effects were measured using patient global assessment of improvement, back pain ( VAS), functional disability (Owestry), and return to work. Results. The societal total cost per patient ( standard deviations) in the surgical group was significantly higher than in the nonsurgical group: Swedish kroner (SEK) 704,000 ( 254,000) vs. SEK 636,000 ( 208,000). The cost per patient for the health care sector was significantly higher for the surgical group, SEK 123,000 ( 60,100) vs. 65,200 ( 38,400) for the control group. All treatment effects were significantly better after surgery. The incremental cost-effectiveness ratio ( ICER), illustrating the extra cost per extra effect unit gained by using fusion instead of nonsurgical treatment, were for improvement: SEK 2,600 ( 600 - 5,900), for back pain: SEK 5,200 ( 1,100 - 11,500), for Oswestry: SEK 11,300 ( 1,200 - 48,000), and for return to work: SEK 4,100 ( 100 21,400). Conclusion. For both the society and the health care sectors, the 2-year costs for lumbar fusion was significantly higher compared with nonsurgical treatment but all treatment effects were significantly in favor of surgery. The probability of lumbar fusion being cost-effective increased with the value put on extra effect units gained by using surgery.
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- Grundy, Myriam M.L., et al.
(author)
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INFOGEST inter-laboratory recommendations for assaying gastric and pancreatic lipases activities prior to in vitro digestion studies
- 2021
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In: Journal of Functional Foods. - : Elsevier BV. - 1756-4646. ; 82
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Journal article (peer-reviewed)abstract
- In vitro digestion studies often use animal digestive enzyme extracts as substitutes of human gastric and pancreatic secretions. Pancreatin from porcine origin is thus commonly used to provide relevant pancreatic enzymes such as proteases, amylase and lipase. Rabbit gastric extracts (RGE) have been recently introduced to provide gastric lipase in addition to pepsin. Before preparing simulated gastric and pancreatic extracts with targeted enzyme activities as described in in vitro digestion protocols, it is important to determine the activities of enzyme preparations using validated methods. The purpose of this inter-laboratory study within the INFOGEST network was to test the repeatability and reproducibility of lipase assays using the pH-stat technique for measuring the activities of gastric and pancreatic lipases from various sources. Twenty-one laboratories having different pH-stat devices received the same protocol with identical batches of RGE and two pancreatin sources. Lipase assays were performed using tributyrin as a substrate and three different amounts (50, 100 and 200 µg) of each enzyme preparation. The repeatability results within individual laboratories were satisfactory with coefficients of variation (CVs) ranging from 4 to 8% regardless of the enzyme amount tested. However, the inter-laboratory variability was high (CV > 15%) compared to existing standards for bioanalytical assays. We identified and weighted the contributions to inter-laboratory variability of several parameters associated with the various pH-stat equipment used in this study (e.g. reaction vessel volume and shape, stirring mode and rate, burette volume for the automated delivery of sodium hydroxide). Based on this, we established recommendations for improving the reproducibility of lipase assays using the pH-stat technique. Defining accurate and complete recommendations on how to correctly quantify activity levels of enzyme preparations is a gateway to promising comparison of in vitro data obtained from different laboratories following the same in vitro digestion protocol.
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- Hankaniemi, MM, et al.
(author)
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Structural Insight into CVB3-VLP Non-Adjuvanted Vaccine
- 2020
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In: Microorganisms. - : MDPI AG. - 2076-2607. ; 8:9
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Journal article (peer-reviewed)abstract
- Coxsackievirus B (CVB) enteroviruses are common pathogens that can cause acute and chronic myocarditis, dilated cardiomyopathy, aseptic meningitis, and they are hypothesized to be a causal factor in type 1 diabetes. The licensed enterovirus vaccines and those currently in clinical development are traditional inactivated or live attenuated vaccines. Even though these vaccines work well in the prevention of enterovirus diseases, new vaccine technologies, like virus-like particles (VLPs), can offer important advantages in the manufacturing and epitope engineering. We have previously produced VLPs for CVB3 and CVB1 in insect cells. Here, we describe the production of CVB3-VLPs with enhanced production yield and purity using an improved purification method consisting of tangential flow filtration and ion exchange chromatography, which is compatible with industrial scale production. We also resolved the CVB3-VLP structure by Cryo-Electron Microscopy imaging and single particle reconstruction. The VLP diameter is 30.9 nm on average, and it is similar to Coxsackievirus A VLPs and the expanded enterovirus cell-entry intermediate (the 135s particle), which is ~2 nm larger than the mature virion. High neutralizing and total IgG antibody levels, the latter being a predominantly Th2 type (IgG1) phenotype, were detected in C57BL/6J mice immunized with non-adjuvanted CVB3-VLP vaccine. The structural and immunogenic data presented here indicate the potential of this improved methodology to produce highly immunogenic enterovirus VLP-vaccines in the future.
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| 7. |
- Medina, LMP, et al.
(author)
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Targeted plasma proteomics reveals signatures discriminating COVID-19 from sepsis with pneumonia
- 2023
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In: Respiratory research. - : Springer Science and Business Media LLC. - 1465-993X. ; 24:1, s. 62-
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Journal article (peer-reviewed)abstract
- BackgroundCOVID-19 remains a major public health challenge, requiring the development of tools to improve diagnosis and inform therapeutic decisions. As dysregulated inflammation and coagulation responses have been implicated in the pathophysiology of COVID-19 and sepsis, we studied their plasma proteome profiles to delineate similarities from specific features.MethodsWe measured 276 plasma proteins involved in Inflammation, organ damage, immune response and coagulation in healthy controls, COVID-19 patients during acute and convalescence phase, and sepsis patients; the latter included (i) community-acquired pneumonia (CAP) caused by Influenza, (ii) bacterial CAP, (iii) non-pneumonia sepsis, and (iv) septic shock patients.ResultsWe identified a core response to infection consisting of 42 proteins altered in both COVID-19 and sepsis, although higher levels of cytokine storm-associated proteins were evident in sepsis. Furthermore, microbiologic etiology and clinical endotypes were linked to unique signatures. Finally, through machine learning, we identified biomarkers, such as TRIM21, PTN and CASP8, that accurately differentiated COVID-19 from CAP-sepsis with higher accuracy than standard clinical markers.ConclusionsThis study extends the understanding of host responses underlying sepsis and COVID-19, indicating varying disease mechanisms with unique signatures. These diagnostic and severity signatures are candidates for the development of personalized management of COVID-19 and sepsis.
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| 8. |
- Osseiran, Afif, et al.
(author)
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Scenarios for 5G mobile and wireless communications : The vision of the METIS project
- 2014
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In: IEEE Communications Magazine. - 0163-6804 .- 1558-1896. ; 52:5, s. 26-35
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Journal article (peer-reviewed)abstract
- METIS is the EU flagship 5G project with the objective of laying the foundation for 5G systems and building consensus prior to standardization. The METIS overall approach toward 5G builds on the evolution of existing technologies complemented by new radio concepts that are designed to meet the new and challenging requirements of use cases today¿s radio access networks cannot support. The integration of these new radio concepts, such as massive MIMO, ultra dense networks, moving networks, and device-to-device, ultra reliable, and massive machine communications, will allow 5G to support the expected increase in mobile data volume while broadening the range of application domains that mobile communications can support beyond 2020. In this article, we describe the scenarios identified for the purpose of driving the 5G research direction. Furthermore, we give initial directions for the technology components (e.g., link level components, multinode/multiantenna, multi-RAT, and multi-layer networks and spectrum handling) that will allow the fulfillment of the requirements of the identified 5G scenarios.
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| 10. |
- Roupé, Mattias, 1975, et al.
(author)
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Perceived meaning in virtual reality architectural models
- 2001
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In: Conference on Applied Virtual Reality in Engineering & Construction Applications of Virtual Reality: Current Initiatives and Future Challenges. ; , s. 117-127, s. 117-127
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Conference paper (peer-reviewed)abstract
- This explorative study investigated how the participants experienced a VR-presentation of an office building. Three office types (landscape, mixed and traditional) were presented in a between-subjects experimental design to employees at the Ericsson company in Sweden. The effects on the participants’ experience were measured using the Semantic Environ¬mental Scale (the SMB-scale, Küller 1975; 1991), a standardised instrument consisting of eight meaning dimensions, each measured using four to eight adjectives on seven-step scales. The SMB-results showed that the participants’ experience of the three office types differed with regard to the dimensions, pleasantness, enclosedness and social status. We also found effects of gender on the meaning dimensions affection, potency and unity. Our research, conducted in an ecologically valid context, suggests that the VR-model tested produces realistic effects on the participants’ experience.
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