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Sökning: WFRF:(Palm Lars)

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1.
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2.
  • Thorlacius, Guðný Ella, et al. (författare)
  • Genetic and clinical basis for two distinct subtypes of primary Sjögren's syndrome
  • 2021
  • Ingår i: Rheumatology. - : Oxford University Press. - 1462-0324 .- 1462-0332. ; 60:2, s. 837-848
  • Tidskriftsartikel (refereegranskat)abstract
    • ObjectivesClinical presentation of primary Sjögren’s syndrome (pSS) varies considerably. A shortage of evidence-based objective markers hinders efficient drug development and most clinical trials have failed to reach primary endpoints.MethodsWe performed a multicentre study to identify patient subgroups based on clinical, immunological and genetic features. Targeted DNA sequencing of 1853 autoimmune-related loci was performed. After quality control, 918 patients with pSS, 1264 controls and 107 045 single nucleotide variants remained for analysis. Replication was performed in 177 patients with pSS and 7672 controls.ResultsWe found strong signals of association with pSS in the HLA region. Principal component analysis of clinical data distinguished two patient subgroups defined by the presence of SSA/SSB antibodies. We observed an unprecedented high risk of pSS for an association in the HLA-DQA1 locus of odds ratio 6.10 (95% CI: 4.93, 7.54, P=2.2×10−62) in the SSA/SSB-positive subgroup, while absent in the antibody negative group. Three independent signals within the MHC were observed. The two most significant variants in MHC class I and II respectively, identified patients with a higher risk of hypergammaglobulinaemia, leukopenia, anaemia, purpura, major salivary gland swelling and lymphadenopathy. Replication confirmed the association with both MHC class I and II signals confined to SSA/SSB antibody positive pSS.ConclusionTwo subgroups of patients with pSS with distinct clinical manifestations can be defined by the presence or absence of SSA/SSB antibodies and genetic markers in the HLA locus. These subgroups should be considered in clinical follow-up, drug development and trial outcomes, for the benefit of both subgroups.
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3.
  • Appelberg, Jonas, 1985- (författare)
  • Gilla oss! : En studie av fyra svenska medieföretags arbete med sociala medier
  • 2018
  • Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • This dissertation contains an exploratory study of how four Swedish media companies has decided to use social media in their daily work, and also how they in fact use them. What are the goals with implementing social media, how do they differ between different companies and do the goals transfer into the newsrooms?The four companies studied are Sveriges Radio, Aftonbladet, Dalarnas Tidningar and Gotlands Media. Media companies that differ from one another both in size, geographical coverage and economy. They range from small local newspapers to national public service radio and the biggest tabloid on the Swedish market. The methods used are qualitative research interviews and field studies as well as quantitative data analysis. The theoretical chapter helps define traditional journalism and journalistic practice. The concepts of boundaries, participatory cultures and normalizing of work methods are also discussed and helps build a context for the analysis of the empirical data.Some key findings from the study are that there are more similarities than differences between the various companies in both how they aim to use social media and how they in fact use them. That the digital development in the surrounding society are much faster than the implementation of new technologies in the newsrooms. Also, that there are differences between how the companies aim to use social media and the actual usage. For instance, all companies strive for a more active dialog with the audience in their visionary work, but has a hard time turning this into reality.There is also notable that social media in this study do not change the journalistic fundamental routines and traditions. The studied journalists are still in control of their own content and they aim to meet the same standard in journalistic quality when working in social media. It is also evident that Facebook is invaluable for all the studied companies, which gives Facebook an interesting indirect power over the journalistic work process and product. Finally, the study finds that it is hard to engage the audience in an active collaboration even when working with social media.
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4.
  • Dahlqvist, Johanna, 1979-, et al. (författare)
  • Identification and functional characterization of a novel susceptibility locus for small vessel vasculitis with MPO-ANCA
  • 2022
  • Ingår i: Rheumatology. - Oxford, United Kingdom : Oxford University Press (OUP). - 1462-0324 .- 1462-0332. ; 61:8, s. 3461-3470
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective To identify and characterize genetic loci associated with the risk of developing ANCA-associated vasculitides (AAV). Methods Genetic association analyses were performed after Illumina sequencing of 1853 genes and subsequent replication with genotyping of selected single nucleotide polymorphisms in a total cohort of 1110 Scandinavian cases with granulomatosis with polyangiitis or microscopic polyangiitis, and 1589 controls. A novel AAV-associated single nucleotide polymorphism was analysed for allele-specific effects on gene expression using luciferase reporter assay. Results PR3-ANCA(+) AAV was significantly associated with two independent loci in the HLA-DPB1/HLA-DPA1 region [rs1042335, P = 6.3 x 10(-61), odds ratio (OR) 0.10; rs9277341, P = 1.5 x 10(-44), OR 0.22] and with rs28929474 in the SERPINA1 gene (P = 2.7 x 10(-10), OR 2.9). MPO-ANCA(+) AAV was significantly associated with the HLA-DQB1/HLA-DQA2 locus (rs9274619, P = 5.4 x 10(-25), OR 3.7) and with a rare variant in the BACH2 gene (rs78275221, P = 7.9 x 10(-7), OR 3.0), the latter a novel susceptibility locus for MPO-ANCA(+) granulomatosis with polyangiitis/microscopic polyangiitis. The rs78275221-A risk allele reduced luciferase gene expression in endothelial cells, specifically, as compared with the non-risk allele. Conclusion We identified a novel susceptibility locus for MPO-ANCA(+) AAV and propose that the associated variant is of mechanistic importance, exerting a regulatory function on gene expression in specific cell types.
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5.
  • Ekman, Diana, et al. (författare)
  • Stratified genetic analysis reveals sex differences in MPO-ANCA-associated vasculitis
  • 2023
  • Ingår i: Rheumatology. - : Oxford University Press. - 1462-0324 .- 1462-0332. ; 62:9, s. 3213-3218
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To identify and genetically characterize subgroups of patients with ANCA-associated vasculitides (AAV) based on sex and ANCA subtype. Methods: A previously established SNP dataset derived from DNA sequencing of 1853 genes and genotyping of 1088 Scandinavian cases with AAV and 1589 controls was stratified for sex and ANCA subtype and analysed for association with five top AAV SNPs. rs9274619, a lead variant at the HLA-DQB1/HLA-DQA2 locus previously associated with AAV positive for myeloperoxidase (MPO)-ANCA, was analysed for association with the cumulative disease involvement of ten different organ systems. Results: rs9274619 showed a significantly stronger association to MPO-ANCA-positive females than males [P = 2.0 × 10-4, OR = 2.3 (95% CI 1.5, 3.5)], whereas proteinase 3 (PR3)-ANCA-associated variants rs1042335, rs9277341 (HLA-DPB1/A1) and rs28929474 (SERPINA1) were equally associated with females and males with PR3-ANCA. In MPO-ANCA-positive cases, carriers of the rs9274619 risk allele were more prone to disease engagement of eyes [P = 0.021, OR = 11 (95% CI 2.2, 205)] but less prone to pulmonary involvement [P = 0.026, OR = 0.52 (95% CI 0.30, 0.92)]. Moreover, AAV with both MPO-ANCA and PR3-ANCA was associated with the PR3-ANCA lead SNP rs1042335 [P = 0.0015, OR = 0.091 (95% CI 0.0022, 0.55)] but not with rs9274619. Conclusions: Females and males with MPO-ANCA-positive AAV differ in genetic predisposition to disease, suggesting at least partially distinct disease mechanisms between the sexes. Double ANCA-positive AAV cases are genetically similar to PR3-ANCA-positive cases, providing clues to the clinical follow-up and treatment of these patients.
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6.
  • Khatri, B., et al. (författare)
  • Genome-wide association study identifies Sjogren's risk loci with functional implications in immune and glandular cells
  • 2022
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Sjogren's disease is a complex autoimmune disease with twelve established susceptibility loci. This genome-wide association study (GWAS) identifies ten novel genome-wide significant (GWS) regions in Sjogren's cases of European ancestry: CD247, NAB1, PTTG1-MIR146A, PRDM1-ATG5, TNFAIP3, XKR6, MAPT-CRHR1, RPTOR-CHMP6-BAIAP6, TYK2, SYNGR1. Polygenic risk scores yield predictability (AUROC = 0.71) and relative risk of 12.08. Interrogation of bioinformatics databases refine the associations, define local regulatory networks of GWS SNPs from the 95% credible set, and expand the implicated gene list to >40. Many GWS SNPs are eQTLs for genes within topologically associated domains in immune cells and/or eQTLs in the main target tissue, salivary glands. The genetic architecture underlying Sjogren's syndrome is not fully understood. Here, the authors perform a genome-wide association study to identify 10 new genetic risk regions, implicating genes involved in immune and salivary gland function.
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7.
  • Lundtoft, Christian, et al. (författare)
  • The HLA region in ANCA-associated vasculitis : characterisation of genetic associations in a Scandinavian patient population
  • 2024
  • Ingår i: RMD Open. - : BMJ PUBLISHING GROUP. - 2056-5933. ; 10:2, s. 1-10
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: The antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are inflammatory disorders with ANCA autoantibodies recognising either proteinase 3 (PR3-AAV) or myeloperoxidase (MPO-AAV). PR3-AAV and MPO-AAV have been associated with distinct loci in the human leucocyte antigen (HLA) region. While the association between MPO-AAV and HLA has been well characterised in East Asian populations where MPO-AAV is more common, studies in populations of European descent are limited. The aim of this study was to thoroughly characterise associations to the HLA region in Scandinavian patients with PR3-AAV as well as MPO-AAV.METHODS: Genotypes of single-nucleotide polymorphisms (SNPs) located in the HLA region were extracted from a targeted exome-sequencing dataset comprising Scandinavian AAV cases and controls. Classical HLA alleles were called using xHLA. After quality control, association analyses were performed of a joint SNP/classical HLA allele dataset for cases with PR3-AAV (n=411) and MPO-AAV (n=162) versus controls (n=1595). Disease-associated genetic variants were analysed for association with organ involvement, age at diagnosis and relapse, respectively.RESULTS: PR3-AAV was significantly associated with both HLA-DPB1*04:01 and rs1042335 at the HLA-DPB1 locus, also after stepwise conditional analysis. MPO-AAV was significantly associated with HLA-DRB1*04:04. Neither carriage of HLA-DPB1*04:01 alleles in PR3-AAV nor of HLA-DRB1*04:04 alleles in MPO-AAV were associated with organ involvement, age at diagnosis or relapse. CONCLUSIONS: The association to the HLA region was distinct in Scandinavian cases with MPO-AAV compared with cases of East Asian descent. In PR3-AAV, the two separate signals of association to the HLD-DPB1 region mediate potentially different functional effects.
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8.
  • Rosengren, Calle, et al. (författare)
  • Framtidens kontor
  • 2022
  • Ingår i: Framtidens arbetsliv: Arbetsvillkor och arbetsmiljö. - Lund : Studentlitteratur. - 9789144153100 - 9144153104 ; , s. 315-338
  • Bokkapitel (refereegranskat)
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10.
  • Abul-Kasim, Kasim, et al. (författare)
  • The Neuroanatomic Localization of Epstein-Barr Virus Encephalitis May Be a Predictive Factor for Its Clinical Outcome: A Case Report and Review of 100 Cases in 28 Reports.
  • 2009
  • Ingår i: Journal of Child Neurology. - : SAGE Publications. - 1708-8283 .- 0883-0738. ; 24, s. 720-726
  • Tidskriftsartikel (refereegranskat)abstract
    • Encephalitis is one of the manifestations of infection with Epstein-Barr virus with clinical outcome varying from complete recovery to death. A 16-year-old boy with Epstein-Barr virus encephalitis with global cortical and subcortical gray matter involvement and a full clinical recovery is reported. The case inspired a literature review which yielded 100 cases of Epstein-Barr virus encephalitis subjected to radiological investigation and published in 28 reports. Cerebellum and basal ganglia were reported to be equally involved by Epstein-Barr virus infection, next to cerebral hemisphere. Patients with isolated hemispheric gray or white matter involvement were reported to achieve good recovery while almost half of the patients with thalamic involvement developed sequelae. The highest mortality rate was among patients with isolated brain stem involvement. In conclusion, neuroanatomic distribution of the radiological abnormalities in Epstein-Barr virus encephalitis may be useful as a prognostic marker.
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