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- Andernord, D., et al.
(författare)
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Contact allergy to haptens in the Swedish baseline series: Results from the Swedish Patch Test Register (2010 to 2017)
- 2022
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Ingår i: Contact Dermatitis. - : Wiley. - 0105-1873 .- 1600-0536. ; 86:3, s. 175-188
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Tidskriftsartikel (refereegranskat)abstract
- Background Allergic contact dermatitis has considerable public health impact and causative haptens vary over time. Objectives To report the prevalence of contact allergy to allergens in the Swedish baseline series 2010 to 2017, as registered in the Swedish Patch Test Register. Methods Results and demographic information for patients tested with the Swedish baseline series in 2010 to 2017 were analysed. Results Data for 21 663 individuals (females 69%) were included. Females had significantly more positive patch tests (54% vs 40%). The reaction prevalence rates were highest for nickel sulfate (20.7%), fragrance mix I (7.1%), Myroxylon pereirae (6.9%), potassium dichromate (6.9%), cobalt chloride (6.8%), methylchloroisothiazolinone/methylisothiazolinone (MCI/MI; 6.4%), MI (3.7%), colophonium (3.5%), fragrance mix II (3.2%), and formaldehyde (3.2%). Myroxylon pereirae reaction prevalence increased from 5% in 2010 to 9% in 2017 and that for methyldibromo glutaronitrile from 3.1% to 4.6%. MCI/MI and MI reactions decreased in prevalence after 2014. Nickel reaction prevalence decreased among females aged 10 to 19 years. Conclusions Nickel remains the most common sensitizing agent, with reaction prevalence decreasing among females younger than 20 years. The changes in MCI/MI and MI reaction prevalence mirrored those in Europe. The register can reveal changes in contact allergy prevalence over time among patients patch tested in Sweden.
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- Backman, Max, et al.
(författare)
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Extending the immune phenotypes of lung cancer: Oasis in the desert
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: Tumor infiltrating immune cells are key elements of the tumor microenvironment and mediate the anti-tumor effects of immunotherapy. The aim of the study was to characterize patterns of immune cell infiltration in non-small cell lung cancer (NSCLC) in relation to tumor mutations and clinicopathological parameters. Methods: Lymphocytes (CD4+, CD8+, CD20+, FOXP3+, CD45RO+), macrophages (CD163+), plasma cells (CD138+), NK cells (NKp46+) and PD-L1+ were annotated on a tissue microarray including 357 operated NSCLC cases. Somatic mutations and tumor mutational burden were analyzed by targeted sequencing for 82 genes, and transcriptomic immune patterns were established in 197 patients based on RNAseq data. Results: We identified somatic mutations (TP53, NF1, KEAP1, CSMD3, LRP1B) that correlated with specific immune cell infiltrates. Hierarchical clustering revealed four immune classes: with (1) high immune cell infiltration (“inflamed”), (2) low immune cell infiltration (“desert”), (3) a mixed phenotype, and (4) a new phenotype with an overall muted inflammatory cell pattern but with an imprint of NK and plasma cells. This latter class exhibited low expression of immune response-related genes (e.g. CXCL9, GZMB, INFG, TGFB1), but was linked to better survival and therefore designated “oasis”. Otherwise, the four immune classes were not related to the presence of specific mutations (EGFR, KRAS, TP53) or histologic subtypes. Conclusion: We present a compartment-specific immune cell analysis in the context of the molecular and clinical background of NSCLC and identified the novel immune class “oasis”. The immune classification helps to better define the immunogenic potency of NSCLC in the era of immunotherapy.
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- Backman, Max, et al.
(författare)
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Infiltration of NK and plasma cells is associated with a distinct immune subset in non‐small cell lung cancer
- 2021
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Ingår i: Journal of Pathology. - : John Wiley & Sons. - 0022-3417 .- 1096-9896. ; 255:3, s. 243-256
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Tidskriftsartikel (refereegranskat)abstract
- Immune cells of the tumor microenvironment are central but erratic targets for immunotherapy. The aim of this study was to characterize novel patterns of immune cell infiltration in non-small cell lung cancer (NSCLC) in relation to its molecular and clinicopathologic characteristics. Lymphocytes (CD3+, CD4+, CD8+, CD20+, FOXP3+, CD45RO+), macrophages (CD163+), plasma cells (CD138+), NK cells (NKp46+), PD1+, and PD-L1+ were annotated on a tissue microarray including 357 NSCLC cases. Somatic mutations were analyzed by targeted sequencing for 82 genes and a tumor mutational load score was estimated. Transcriptomic immune patterns were established in 197 patients based on RNA sequencing data. The immune cell infiltration was variable and showed only poor association with specific mutations. The previously defined immune phenotypic patterns, desert, inflamed, and immune excluded, comprised 30, 13, and 57% of cases, respectively. Notably, mRNA immune activation and high estimated tumor mutational load were unique only for the inflamed pattern. However, in the unsupervised cluster analysis, including all immune cell markers, these conceptual patterns were only weakly reproduced. Instead, four immune classes were identified: (1) high immune cell infiltration, (2) high immune cell infiltration with abundance of CD20+ B cells, (3) low immune cell infiltration, and (4) a phenotype with an imprint of plasma cells and NK cells. This latter class was linked to better survival despite exhibiting low expression of immune response-related genes (e.g. CXCL9, GZMB, INFG, CTLA4). This compartment-specific immune cell analysis in the context of the molecular and clinical background of NSCLC reveals two previously unrecognized immune classes. A refined immune classification, including traits of the humoral and innate immune response, is important to define the immunogenic potency of NSCLC in the era of immunotherapy. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.
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- Braesch-Andersen, Anna, et al.
(författare)
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Application of phase-field fracture theories and digital volume correlation to synchrotron X-ray monitored fractures in human trabecular bone : A case study
- 2022
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Ingår i: Journal of The Mechanical Behavior of Biomedical Materials. - : Elsevier. - 1751-6161 .- 1878-0180. ; 135
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Tidskriftsartikel (refereegranskat)abstract
- Fracture processes of trabecular bone have been studied using various approaches over the years. However, reliable methods to analyse fracture at the single trabecula level are limited. In this study, a digital volume correlation (DVC) and a phase-field fracture model are applied and contrasted for human trabecular bone to analyse its failure under global compression at high resolution.A human trabecular bone sample was fractured in situ under synchrotron-based X-ray micro computed to-mography (CT). Reconstructed CT data was then used in DVC algorithms to obtain high-resolution displacement fields in the bone at different load steps. A high-resolution specimen-specific structural mesh was discretized from the CT data and used for the phase-field simulation of the fracturing bone.The DVC analysis showed opening mode cracks as well as shear mode cracks. Strains in cracked regions were analysed. The load distribution in the trabecular structure resulted in two completely separated fracture regions in the sample body. A phenomenon that was also captured in the phase-field model. The results encourage us to believe improvements in boundary conditions and material models are worthwhile pursuing. Findings in this study support further development of a phase-field method to analyse fracture in samples with complex morphology, such as trabecular bone, and the capacity of DVC to quantify strains and slowly growing stable fractures during step-wise loading of trabecular bone.
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- Burman, Joachim, et al.
(författare)
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Autologous haematopoietic stem cell transplantation for aggressive multiple sclerosis : the Swedish experience
- 2014
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Ingår i: Journal of Neurology, Neurosurgery and Psychiatry. - London, United Kingdom : BMJ Publishing Group Ltd. - 0022-3050 .- 1468-330X. ; 85:10, s. 1116-1121
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Tidskriftsartikel (refereegranskat)abstract
- Background: Autologous haematopoietic stem cell transplantation (HSCT) is a viable option for treatment of aggressive multiple sclerosis (MS). No randomised controlled trial has been performed, and thus, experiences from systematic and sustained follow-up of treated patients constitute important information about safety and efficacy. In this observational study, we describe the characteristics and outcome of the Swedish patients treated with HSCT for MS.Methods: Neurologists from the major hospitals in Sweden filled out a follow-up form with prospectively collected data. Fifty-two patients were identified in total; 48 were included in the study and evaluated for safety and side effects; 41 patients had at least 1 year of follow-up and were further analysed for clinical and radiological outcome. In this cohort, 34 patients (83%) had relapsing-remitting MS, and mean follow-up time was 47 months.Results: At 5 years, relapse-free survival was 87%; MRI event-free survival 85%; expanded disability status scale (EDSS) score progression-free survival 77%; and disease-free survival (no relapses, no new MRI lesions and no EDSS progression) 68%. Presence of gadolinium-enhancing lesions prior to HSCT was associated with a favourable outcome (disease-free survival 79% vs 46%, p=0.028). There was no mortality. The most common long-term side effects were herpes zoster reactivation (15%) and thyroid disease (8.4%).Conclusions: HSCT is a very effective treatment of inflammatory active MS and can be performed with a high degree of safety at experienced centres.
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- Carlsson, Jenny, 1984-
(författare)
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On Crack Dynamics in Brittle Heterogeneous Materials
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Natural variation, sub-structural features, heterogeneity and porosity make fracture modelling of wood and many other heterogeneous and cellular materials challenging. In this thesis, fracture in such complicated materials is simulated using phase field methods for fracture. Phase field methods have shown promise in simulations of complex geometries as well as dynamics and require few additional parameters; only the material toughness and a length parameter, determining the width of a regularised crack, are needed.First, a dynamic phase field model is developed and validated against experiments performed on homogeneous brittle polymeric materials, wood fibre composites and polymeric materials with different hole patterns. Then, a high-resolution model of wood is developed and related to experiments, this time without considering fracture. Attention is finally focussed on high-resolution numerical analyses of fracture in wood and other cellular microstructures, considering both heterogeneity and relative density.The phase field model is found to reproduce crack paths, velocities and energy release rates well in homogeneous samples both with and without holes. In more complicated heterogeneous and porous materials, the model is also able to simulate crack paths, but the interpretation of the length scale is complicated by the inherent lengths of the micro-structural geometry. In sum, the thesis points to possibilities with the proposed method, as well as limitations in our current understanding of both quasistatic and dynamic fracture of heterogeneous and cellular materials. The findings of this thesis can contribute to an improved understanding of fracture in such materials.
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