| 1. |
- Allard, Christina, et al.
(author)
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Rasbiologiskt språkbruk i statens rättsprocess mot sameby : DN Debatt 2015-06-11
- 2015
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Other publication (pop. science, debate, etc.)abstract
- Statens hantering av forskningsresultat i rättsprocessen med Girjas sameby utgör ett hot mot Sverige som rättsstat och kunskapsnation. Åratal av svensk och internationell forskning underkänns och man använder ett språkbruk som skulle kunna vara hämtat från rasbiologins tid. Nu måste staten ta sitt ansvar och börja agera som en demokratisk rättsstat, skriver 59 forskare.
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| 2. |
- Allard, Christina, et al.
(author)
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Rasbiologiskt språkbruk i statens rättsprocess mot sameby
- 2015
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In: Dagens Nyheter. - 1101-2447.
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Journal article (pop. science, debate, etc.)abstract
- Statens hantering av forskningsresultat i rättsprocessen med Girjas sameby utgör ett hot mot Sverige som rättsstat och kunskapsnation. Åratal av svensk och internationell forskning underkänns och man använder ett språkbruk som skulle kunna vara hämtat från rasbiologins tid. Nu måste staten ta sitt ansvar och börja agera som en demokratisk rättsstat, skriver 59 forskare.
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| 3. |
- Östling, Jörgen, et al.
(author)
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IL-17-high asthma with features of a psoriasis immunophenotype
- 2019
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In: Journal of Allergy and Clinical Immunology. - : Elsevier. - 0091-6749 .- 1097-6825. ; 144:5, s. 1198-1213
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Journal article (peer-reviewed)abstract
- Background: The role of IL-17 immunity is well established in patients with inflammatory diseases, such as psoriasis and inflammatory bowel disease, but not in asthmatic patients, in whom further study is required.Objective: We sought to undertake a deep phenotyping study of asthmatic patients with upregulated IL-17 immunity.Methods: Whole-genome transcriptomic analysis was performed by using epithelial brushings, bronchial biopsy specimens (91 asthmatic patients and 46 healthy control subjects), and whole blood samples (n = 498) from the Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes (U-BIOPRED) cohort. Gene signatures induced in vitro by IL-17 and IL-13 in bronchial epithelial cells were used to identify patients with IL-17–high and IL-13–high asthma phenotypes.Results: Twenty-two of 91 patients were identified with IL-17, and 9 patients were identified with IL-13 gene signatures. The patients with IL-17–high asthma were characterized by risk of frequent exacerbations, airway (sputum and mucosal) neutrophilia, decreased lung microbiota diversity, and urinary biomarker evidence of activation of the thromboxane B2 pathway. In pathway analysis the differentially expressed genes in patients with IL-17-high asthma were shared with those reported as altered in psoriasis lesions and included genes regulating epithelial barrier function and defense mechanisms, such as IL1B, IL6, IL8, and β-defensin.Conclusion: The IL-17–high asthma phenotype, characterized by bronchial epithelial dysfunction and upregulated antimicrobial and inflammatory response, resembles the immunophenotype of psoriasis, including activation of the thromboxane B2 pathway, which should be considered a biomarker for this phenotype in further studies, including clinical trials targeting IL-17.
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| 4. |
- Abdel-Aziz, Mahmoud I., et al.
(author)
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A multi-omics approach to delineate sputum microbiome-associated asthma inflammatory phenotypes
- 2022
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In: European Respiratory Journal. - : European Respiratory Society. - 0903-1936 .- 1399-3003. ; 59:1
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Journal article (peer-reviewed)abstract
- A multi-omics approach revealed the underlying biological pathways in the microbiome-driven severe asthma phenotypes. This may help to elucidate new leads for treatment development, particularly for the therapeutically challenging neutrophilic asthma.
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| 5. |
- Bergman, Lina, 1982, et al.
(author)
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Study for Improving Maternal Pregnancy And Child ouTcomes (IMPACT): a study protocol for a Swedish prospective multicentre cohort study
- 2020
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In: BMJ Open. - : BMJ. - 2044-6055 .- 2044-6055. ; 10:9, s. e033851-e033851
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Journal article (peer-reviewed)abstract
- Introduction First-trimester pregnancy risk evaluation facilitates individualised antenatal care, as well as application of preventive strategies for pre-eclampsia or birth of a small for gestational age infant. A range of early intervention strategies in pregnancies identified as high risk at the end of the first trimester has been shown to decrease the risk of preterm pre-eclampsia (<37 gestational weeks). The aim of this project is to create the Improving Maternal Pregnancy And Child ouTcomes (IMPACT) database; a nationwide database with individual patient data, including predictors recorded at the end of the first trimester and later pregnancy outcomes, to identify women at high risk of pre-eclampsia. A second aim is to link the IMPACT database to a biobank with first-trimester blood samples. Methods and analysis This is a Swedish prospective multicentre cohort study. Women are included between the 11th and 14th weeks of pregnancy. At inclusion, pre-identified predictors are retrieved by interviews and medical examinations. Blood samples are collected and stored in a biobank. Additional predictors and pregnancy outcomes are retrieved from the Swedish Pregnancy Register. Inclusion in the study began in November 2018 with a targeted sample size of 45 000 pregnancies by end of 2021. Creation of a new risk prediction model will then be developed, validated and implemented. The database and biobank will enable future research on prediction of various pregnancy-related complications. Ethics and dissemination Confidentiality aspects such as data encryption and storage comply with the General Data Protection Regulation and with ethical committee requirements. This study has been granted national ethical approval by the Swedish Ethical Review Authority (Uppsala 2018-231) and national biobank approval at Uppsala Biobank (18237 2 2018 231). Results from the current as well as future studies using information from the IMPACT database will be published in peer-reviewed journals.
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| 6. |
- Burg, Dominic, et al.
(author)
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Large-Scale Label-Free Quantitative Mapping of the Sputum Proteome
- 2018
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In: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 17:6, s. 2072-2091
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Journal article (peer-reviewed)abstract
- Analysis of induced sputum supematant is a minimally invasive approach to study the epithelial lining fluid and, thereby, provide insight into normal lung biology and the pathobiology of lung diseases. We present here a novel proteomics approach to sputum analysis developed within the U-BIOPRED (unbiased biomarkers predictive of respiratory disease outcomes) international project. We present practical and analytical techniques to optimize the detection of robust biomarkers in proteomic studies. The normal sputum proteome was derived using data-independent HDMSE applied to 40 healthy nonsmoking participants, which provides an essential baseline from which to compare modulation of protein expression in respiratory diseases. The "core" sputum proteome (proteins detected in >= 40% of participants) was composed of 284 proteins, and the extended proteome (proteins detected in >= 3 participants) contained 1666 proteins. Quality control procedures were developed to optimize the accuracy and consistency of measurement of sputum proteins and analyze the distribution of sputum proteins in the healthy population. The analysis showed that quantitation of proteins by HDMSE is influenced by several factors, with some proteins being measured in all participants' samples and with low measurement variance between samples from the same patient. The measurement of some proteins is highly variable between repeat analyses, susceptible to sample processing effects, or difficult to accurately quantify by mass spectrometry. Other proteins show high interindividual variance. We also highlight that the sputum proteome of healthy individuals is related to sputum neutrophil levels, but not gender or allergic sensitization. We illustrate the importance of design and interpretation of disease biomarker studies considering such protein population and technical measurement variance.
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| 7. |
- Carlsson, Ylva, 1975, et al.
(author)
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Comparing the results from a Swedish pregnancy cohort using data from three automated placental growth factor immunoassay platforms intended for first-trimester preeclampsia prediction.
- 2023
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In: Acta Obstetricia et Gynecologica Scandinavica. - : Wiley. - 0001-6349 .- 1600-0412. ; :8, s. 1084-1091
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Journal article (peer-reviewed)abstract
- INTRODUCTION: Risk evaluation for preeclampsia in early pregnancy allows identification of women at high risk. Prediction models for preeclampsia often include circulating concentrations of placental growth factor (PlGF); however, the models are usually limited to a specific PlGF method of analysis. The aim of this study was to compare three different PlGF methods of analysis in a Swedish cohort to assess their convergent validity and appropriateness for use in preeclampsia risk prediction models in the first trimester of pregnancy.MATERIAL AND METHODS: First-trimester blood samples were collected in gestational week 11+0 to 13+6 from 150 pregnant women at Uppsala University Hospital during November 2018 until November 2020. These samples were analyzed using the different PlGF methods from Perkin Elmer, Roche Diagnostics, and Thermo Fisher Scientific.RESULTS: There were strong correlations between the PlGF results obtained with the three methods, but the slopes of the correlations clearly differed from 1.0: PlGFPerkinElmer = 0.553 (95% confidence interval [CI] 0.518-0.588) * PlGFRoche -1.112 (95% CI -2.773 to 0.550); r = 0.966, mean difference -24.6 (95% CI -26.4 to -22.8). PlGFPerkinElmer = 0.673 (95% CI 0.618-0.729) * PlGFThermoFisher -0.199 (95% CI -2.292 to 1.894); r = 0.945, mean difference -13.8 (95% CI -15.1 to -12.6). PlGFRoche = 1.809 (95% CI 1.694-1.923) * PlGFPerkinElmer +2.010 (95% CI -0.877 to 4.897); r = 0.966, mean difference 24.6 (95% CI 22.8-26.4). PlGFRoche = 1.237 (95% CI 1.113-1.361) * PlGFThermoFisher +0.840 (95% CI -3.684 to 5.363); r = 0.937, mean difference 10.8 (95% CI 9.4-12.1). PlGFThermoFisher = 1.485 (95% CI 1.363-1.607) * PlGFPerkinElmer +0.296 (95% CI -2.784 to 3.375); r = 0.945, mean difference 13.8 (95% CI 12.6-15.1). PlGFThermoFisher = 0.808 (95% CI 0.726-0.891) * PlGFRoche -0.679 (95% CI -4.456 to 3.099); r = 0.937, mean difference -10.8 (95% CI -12.1 to -9.4).CONCLUSION: The three PlGF methods have different calibrations. This is most likely due to the lack of an internationally accepted reference material for PlGF. Despite different calibrations, the Deming regression analysis indicated good agreement between the three methods, which suggests that results from one method may be converted to the others and hence used in first-trimester prediction models for preeclampsia.
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| 8. |
- Emma, Rosalia, et al.
(author)
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Enhanced oxidative stress in smoking and ex-smoking severe asthma in the U-BIOPRED cohort
- 2018
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In: PLOS ONE. - : Public Library Science. - 1932-6203. ; 13:9
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Journal article (peer-reviewed)abstract
- Oxidative stress is believed to be a major driver of inflammation in smoking asthmatics. The U-BIOPRED project recruited a cohort of Severe Asthma smokers/ex-smokers (SAs/ex) and non-smokers (SAn) with extensive clinical and biomarker information enabling characterization of these subjects. We investigated oxidative stress in severe asthma subjects by analysing urinary 8-iso-PGF(2 alpha) and the mRNA-expression of the main pro-oxidant (NOX2; NOSs) and anti-oxidant (SODs; CAT; GPX1) enzymes in the airways of SAs/ex and SAn. All the severe asthma U-BIOPRED subjects were further divided into current smokers with severe asthma (CSA), ex-smokers with severe asthma (ESA) and non-smokers with severe asthma (NSA) to deepen the effect of active smoking. Clinical data, urine and sputum were obtained from severe asthma subjects. A bronchoscopy to obtain bronchial biopsy and brushing was performed in a subset of subjects. The main clinical data were analysed for each subset of subjects (urine-8-iso-PGF(2 alpha); IS-transcriptomics; BB-transcriptomics; BBrtranscriptomics). Urinary 8-iso-PGF(2 alpha) was quantified using mass spectrometry. Sputum, bronchial biopsy and bronchial brushing were processed for mRNA expression microarray analysis. Urinary 8-iso-PGF(2 alpha) was increased in SAs/ex, median (IQR) = 31.7 (24.5 +/- 44.7) ng/mmol creatinine, compared to SAn, median (IQR) = 26.6 (19.6 +/- 36.6) ng/mmol creatinine (p< 0.001), and in CSA, median (IQR) = 34.25 (24.4 +/- 47.7), vs. ESA, median (IQR) = 29.4 (22.3 +/- 40.5), and NSA, median (IQR) = 26.5 (19.6 +/- 16.6) ng/mmol creatinine (p = 0.004). Sputum mRNA expression of NOX2 was increased in SAs/ex compared to SAn (probe sets 203922_PM_s_at fold-change = 1.05 p = 0.006; 203923_PM_s_at fold-change = 1.06, p = 0.003; 233538_PM_s_at fold-change = 1.06, p = 0.014). The mRNA expression of antioxidant enzymes were similar between the two severe asthma cohorts in all airway samples. NOS2 mRNA expression was decreased in bronchial brushing of SAs/ex compared to SAn (fold-change = -1.10; p = 0.029). NOS2 mRNA expression in bronchial brushing correlated with FeNO (Kendal's Tau = 0.535; p< 0.001). From clinical and inflammatory analysis, FeNO was lower in CSA than in ESA in all the analysed subject subsets (p< 0.01) indicating an effect of active smoking. Results about FeNO suggest its clinical limitation, as inflammation biomarker, in severe asthma active smokers. These data provide evidence of greater systemic oxidative stress in severe asthma smokers as reflected by a significant changes of NOX2 mRNA expression in the airways, together with elevated urinary 8-iso-PGF(2 alpha) in the smokers/ex-smokers group.
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| 9. |
- Hou, Ruihua, et al.
(author)
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The role of inflammation in anxiety and depression in the European U-BIOPRED asthma cohorts
- 2023
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In: Brain, behavior, and immunity. - : Academic Press. - 0889-1591 .- 1090-2139. ; 111, s. 249-258
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Journal article (peer-reviewed)abstract
- Background: Growing evidence indicates high comorbid anxiety and depression in patients with asthma. However, the mechanisms underlying this comorbid condition remain unclear. The aim of this study was to investigate the role of inflammation in comorbid anxiety and depression in three asthma patient cohorts of the Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes (U-BIOPRED) project. Methods: U-BIOPRED was conducted by a European Union consortium of 16 academic institutions in 11 European countries. A subset dataset from subjects with valid anxiety and depression measures and a large blood biomarker dataset were analysed, including 198 non-smoking patients with severe asthma (SAn), 65 smoking patients with severe asthma (SAs), 61 non-smoking patients with mild-to-moderate asthma (MMA), and 20 healthy non-smokers (HC). The Hospital Anxiety and Depression Scale was used to measure anxiety and depression and a series of inflammatory markers were analysed by the SomaScan v3 platform (SomaLogic, Boulder, Colo). ANOVA and the Kruskal-Wallis test were used for multiple-group comparisons as appropriate. Results: There were significant group effects on anxiety and depression among the four cohort groups (p < 0.05). Anxiety and depression of SAn and SAs groups were significantly higher than that of MMA and HC groups (p < 0.05. There were significant differences in serum IL6, MCP1, CCL18, CCL17, IL8, and Eotaxin among the four groups (p < 0.05). Depression was significantly associated with IL6, MCP1, CCL18 level, and CCL17; whereas anxiety was associated with CCL17 only (p < 0.05). Conclusions: The current study suggests that severe asthma patients are associated with higher levels of anxiety and depression, and inflammatory responses may underlie this comorbid condition.
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| 10. |
- Kuo, Chih-Hsi Scott, et al.
(author)
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A transcriptome-driven analysis of epithelial brushings and bronchial biopsies to define asthma phenotypes in U-BIOPRED
- 2017
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In: American Journal of Respiratory and Critical Care Medicine. - 1073-449X .- 1535-4970. ; 194:4, s. 443-455
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Journal article (peer-reviewed)abstract
- RATIONALE AND OBJECTIVES: Asthma is a heterogeneous disease driven by diverse immunologic and inflammatory mechanisms. We used transcriptomic profiling of airway tissues to help define asthma phenotypes.METHODS: The transcriptome from bronchial biopsies and epithelial brushings of 107 moderate-to-severe asthmatics were annotated by gene-set variation analysis (GSVA) using 42 gene-signatures relevant to asthma, inflammation and immune function. Topological data analysis (TDA) of clinical and histological data was used to derive clusters and the nearest shrunken centroid algorithm used for signature refinement.RESULTS: 9 GSVA signatures expressed in bronchial biopsies and airway epithelial brushings distinguished two distinct asthma subtypes associated with high expression of T-helper type 2 (Th-2) cytokines and lack of corticosteroid response (Group 1 and Group 3). Group 1 had the highest submucosal eosinophils, high exhaled nitric oxide (FeNO) levels, exacerbation rates and oral corticosteroid (OCS) use whilst Group 3 patients showed the highest levels of sputum eosinophils and had a high BMI. In contrast, Group 2 and Group 4 patients had an 86% and 64% probability of having non-eosinophilic inflammation. Using machine-learning tools, we describe an inference scheme using the currently-available inflammatory biomarkers sputum eosinophilia and exhaled nitric oxide levels along with OCS use that could predict the subtypes of gene expression within bronchial biopsies and epithelial cells with good sensitivity and specificity.CONCLUSION: This analysis demonstrates the usefulness of a transcriptomic-driven approach to phenotyping that segments patients who may benefit the most from specific agents that target Th2-mediated inflammation and/or corticosteroid insensitivity.
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