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- Moberg, Christina, et al.
(författare)
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De unga gör helt rätt när de stämmer staten
- 2022
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Ingår i: Aftonbladet. - 1103-9000.
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- 1 620 forskare och lärare i forskarvärlden: Vi ställer oss bakom Auroras klimatkrav
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| 4. |
- de Vries, Charlotte, et al.
(författare)
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Antibodies to Porphyromonas gingivalis Are Increased in Patients with Severe Periodontitis, and Associate with Presence of Specific Autoantibodies and Myocardial Infarction
- 2022
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Ingår i: Journal of Clinical Medicine. - : MDPI. - 2077-0383. ; 11:4
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Tidskriftsartikel (refereegranskat)abstract
- There is accumulating data suggesting that periodontitis is associated with increased risk of systemic and autoimmune diseases, including cardiovascular disease, rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), and there is an unmet need to identify these individuals early. With the periodontal bacteria Porphyromonas gingivalis (Pg) as one of the key drivers of periodontitis, we set out to investigate whether antibodies to Pg virulence factor arginine gingipain (Rgp) could serve as a biomarker for periodontitis patients at increased risk of autoimmunity and systemic disease. We measured serum anti-Rgp IgG in three study populations: PAROKRANK (779 individuals with myocardial infarction (MI); 719 controls), where 557 had periodontitis, and 312 were positive for autoantibodies associated with RA/SLE; the PerioGene North pilot (41 periodontitis; 39 controls); and an SLE case/control study (101 SLE; 100 controls). Anti-Rgp IgG levels were increased in severe periodontitis compared to controls (p < 0.0001), in individuals positive for anti-citrullinated protein antibodies (p = 0.04) and anti-dsDNA antibodies (p = 0.035), compared to autoantibody-negative individuals; and in MI patients versus matched controls (p = 0.035). Our data support longitudinal studies addressing the role of anti-Rgp antibodies as biomarkers for periodontitis patients at increased risk of developing autoimmunity linked to RA and SLE, and mechanisms underpinning these associations.
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- Reed, Evan, et al.
(författare)
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Presence of autoantibodies in "seronegative" rheumatoid arthritis associates with classical risk factors and high disease activity
- 2020
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Ingår i: Arthritis Research & Therapy. - : Springer Science and Business Media LLC. - 1478-6362. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundRheumatoid arthritis (RA) is classified as seropositive or seronegative, depending on the presence/absence of rheumatoid factor (RF), primarily IgM RF, and/or anti-citrullinated protein antibodies (ACPA), commonly detected using anti-cyclic citrullinated peptide (CCP) assays. Known risk factors associate with the more severe seropositive form of RA; less is known about seronegative RA. Here, we examine risk factors and clinical phenotypes in relation to presence of autoantibodies in the RA subset that is traditionally defined as seronegative.MethodsAnti-CCP2 IgG, 19 ACPA fine-specificities, IgM/IgG/IgA RF, anti-carbamylated-protein (CarP) antibodies, and 17 other autoantibodies, were analysed in 2755 RA patients and 370 controls. Antibody prevalence, levels, and co-occurrence were examined, and associations with risk factors and disease activity during 5 years were investigated for different antibody-defined RA subsets.ResultsAutoantibodies were detected in a substantial proportion of the traditionally defined seronegative RA subset, with ACPA fine-specificities found in 30%, IgA/IgG RF in 9.4%, and anti-CarP antibodies in 16%, with a 9.6% co-occurrence of at least two types of RA-associated autoantibodies. HLA-DRB1 shared epitope (SE) associated with the presence of ACPA in anti-CCP2-negative RA; in anti-CCP2-positive RA, the SE association was defined by six ACPA fine-specificities with high co-occurrence. Smoking associated with RF, but not with ACPA, in anti-CCP2-negative RA. Presence of ACPA and RF, but not anti-CarP antibodies, in conventionally defined “seronegative” RA, associated with worse clinical outcome.Conclusions“Seronegative” RA is not truly a seronegative disease subset. Additional screening for ACPA fine-specificities and IgA/IgG RF defines a group of patients that resembles seropositive patients with respect to risk factors and clinical picture and may contribute to earlier diagnosis for a subset of anti-CCP2−/IgM RF− patients with a high need for active treatment.
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| 7. |
- Abolhalaj, Milad, et al.
(författare)
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Transcriptional profiling demonstrates altered characteristics of CD8 + cytotoxic T-cells and regulatory T-cells in TP53-mutated acute myeloid leukemia
- 2022
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Ingår i: Cancer Medicine. - : Wiley. - 2045-7634. ; 11:15, s. 3023-3032
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Tidskriftsartikel (refereegranskat)abstract
- Background: Acute myeloid leukemia (AML) patients have limited effect from T-cell-based therapies, such as PD-1 and CTLA-4 blockade. However, recent data indicate that AML patients with TP53 mutation have higher immune infiltration and other immunomodulatory therapies could thus potentially be effective. Here, we performed the transcriptional analysis of distinct T-cell subpopulations from TP53-mutated AML to identify gene expression signatures suggestive of altered functional properties.Methods: CD8+ cytotoxic T lymphocytes (CTLs), conventional helper T cells (Th), and regulatory T cells (Tregs) were sorted from peripheral blood of AML patients with TP53 mutation (n = 5) and healthy donors (n = 3), using FACS, and the different subpopulations were subsequently subjected to RNA-sequencing. Differentially expressed genes were identified and gene set enrichment analysis (GSEA) was performed to outline altered pathways and exhaustion status. Also, expression levels for a set of genes encoding established and emerging immuno-oncological targets were defined.Results: The results showed altered transcriptional profiles for each of the T-cell subpopulations from TP53-mutated AML as compared to control subjects. IFN-α and IFN-γ signaling were stronger in TP53-mutated AML for both CTLs and Tregs. Furthermore, in TP53-mutated AML as compared to healthy controls, Tregs showed gene expression signatures suggestive of metabolic adaptation to their environment, whereas CTLs exhibited features of exhaustion/dysfunction with a stronger expression of TIM3 as well as enrichment of a gene set related to exhaustion.Conclusions: The results provide insights on mechanisms underlying the inadequate immune response to leukemic cells in TP53-mutated AML and open up for further exploration toward novel treatment regimens for these patients.
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| 8. |
- Bergström, Sara, et al.
(författare)
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Miljöbedömning och miljöbeskrivning i väg- och järnvägsprojekt : Vägledning
- 2022
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Denna vägledning förmedlar Trafikverkets syn på hur de båda processerna miljöbedömning och miljöbeskrivning bör tillämpas i planläggning och projektering av väg- och järnvägsprojekt, med utgångspunkt från lagkrav, praxis och Trafikverkets erfarenheter. Den tar även upp innehållet i de båda dokumenten miljökonsekvensbeskrivning och miljöbeskrivning som kommer ut av de båda processerna. Vägledningen syftar till att bidra till integrering av miljöaspekter i planläggning och projektering av vägar och järnvägar samt till en god kvalitet på genomförande och redovisning. Den syftar även till att miljöbedömningar och miljöbeskrivningar ska genomföras på ett likartat sätt i hela Trafikverket och få en jämn kvalitet. Vägledningen riktar sig främst till Trafikverkets konsulter och egna miljöspecialister som gör miljöbedömningar och miljöbeskrivningar i Trafikverkets väg- och järnvägsprojekt. Vägledningen ersätter Trafikverkets Handbok om metodik för miljökonsekvensbeskrivning för vägar och järnvägar (Trafikverket 2011:090). Den ersätter också texter om MKB och miljöbeskrivning i Trafikverkets Rapport planläggning av vägar och järnvägar. Vägledningen innehåller bland annat:relevant lagstiftning och målbeskrivning om hur miljö integreras samt miljöbedömningens roll och moment i planläggningens olika skedensamråd, samrådsunderlag, utredning om betydande miljöpåverkan och miljökonsekvensbeskrivningens (MKB) innehåll Trafikverkets syn på hantering av miljöaspekter, behov av att koppla dessa till miljöintressen för vilka konsekvenser beskrivs
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| 9. |
- Burnum-Johnson, Kristin E., et al.
(författare)
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New Views of Old Proteins : Clarifying the Enigmatic Proteome
- 2022
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Ingår i: Molecular & Cellular Proteomics. - : Elsevier BV. - 1535-9476 .- 1535-9484. ; 21:7
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Tidskriftsartikel (refereegranskat)abstract
- All human diseases involve proteins, yet our current tools to characterize and quantify them are limited. To better elucidate proteins across space, time, and molecular composition, we provide a >10 years of projection for technologies to meet the challenges that protein biology presents. With a broad perspective, we discuss grand opportunities to transition the science of proteomics into a more propulsive enterprise. Extrapolating recent trends, we describe a next generation of approaches to define, quantify, and visualize the multiple dimensions of the proteome, thereby transforming our understanding and interactions with human disease in the coming decade.
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| 10. |
- Dikaiou, Pigi, et al.
(författare)
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Obesity, overweight and risk for cardiovascular disease and mortality in young women
- 2021
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Ingår i: European Journal of Preventive Cardiology. - : Oxford University Press (OUP). - 2047-4873 .- 2047-4881. ; 28:12, s. 1351-1359
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Tidskriftsartikel (refereegranskat)abstract
- Aims The aim of this study was to investigate the relation between body mass index (BMI) in young women, using weight early in pregnancy as a proxy for pre-pregnancy weight, and risk for early cardiovascular disease (CVD) and mortality. Methods and results In this prospective, registry-based study, we used weight data in early pregnancy from women, registered in the Swedish Medical Birth Registry, and who gave birth between 1982 and 2014 (n = 1,495,499; median age 28.3 years). Of the women, 118,212 (7.9%) were obese (BMI >= 30 kg/m(2)) and 29,630 (2.0%) severely obese (BMI >= 35 kg/m(2)). After a follow-up of median 16.3 years, we identified 3295 and 4375 cases of acute myocardial infarction (AMI) and ischemic stroke (IS) corresponding to 13.4 and 17.8 per 100,000 observation years, respectively, occurring at mean ages of 49.8 and 47.3 years. Compared to women with a BMI 20-<22.5 kg/m(2), the hazard ratio (HR) of AMI increased with higher BMI from 1.40 (95% confidence interval (CI) 1.27-1.54) among women with BMI 22.5-<25.0 kg/m(2) to 4.71 (95% CI 3.88-5.72) among women with severe obesity, with similar findings for IS and CVD death, after adjustment for age, pregnancy year, parity and comorbidities at baseline. Women with BMI 30-<35.0 and >= 35 kg/m(2) had increased all-cause mortality with adjusted HR 1.53 (95% CI 1.43-1.63) and 1.83 (95% CI 1.63-2.05), respectively. Conclusion A significant increase in the risk for early AMI, IS and CVD death was noticeable in overweight young women, with a marked increase in obese women.
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