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- Kvedaraite, E, et al.
(författare)
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Notch-dependent cooperativity between myeloid lineages promotes Langerhans cell histiocytosis pathology
- 2022
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Ingår i: Science immunology. - : American Association for the Advancement of Science (AAAS). - 2470-9468. ; 7:78, s. eadd3330-
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Tidskriftsartikel (refereegranskat)abstract
- Langerhans cell histiocytosis (LCH) is a potentially fatal neoplasm characterized by the aberrant differentiation of mononuclear phagocytes, driven by mitogen-activated protein kinase (MAPK) pathway activation. LCH cells may trigger destructive pathology yet remain in a precarious state finely balanced between apoptosis and survival, supported by a unique inflammatory milieu. The interactions that maintain this state are not well known and may offer targets for intervention. Here, we used single-cell RNA-seq and protein analysis to dissect LCH lesions, assessing LCH cell heterogeneity and comparing LCH cells with normal mononuclear phagocytes within lesions. We found LCH discriminatory signatures pointing to senescence and escape from tumor immune surveillance. We also uncovered two major lineages of LCH with DC2- and DC3/monocyte-like phenotypes and validated them in multiple pathological tissue sites by high-content imaging. Receptor-ligand analyses and lineage tracing in vitro revealed Notch-dependent cooperativity between DC2 and DC3/monocyte lineages during expression of the pathognomonic LCH program. Our results present a convergent dual origin model of LCH with MAPK pathway activation occurring before fate commitment to DC2 and DC3/monocyte lineages and Notch-dependent cooperativity between lineages driving the development of LCH cells.
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- González-Gil, E. M., et al.
(författare)
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Reliability of primary caregivers reports on lifestyle behaviours of European pre-school children : the ToyBox-study
- 2014
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Ingår i: Obesity Reviews. - : Wiley-Blackwell. - 1467-7881 .- 1467-789X. ; 15:Suppl 3, s. 61-66
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Tidskriftsartikel (refereegranskat)abstract
- Reliable assessments of health-related behaviours are necessary for accurate evaluation on the efficiency of public health interventions. The aim of the current study was to examine the reliability of a self-administered primary caregivers questionnaire (PCQ) used in the ToyBox-intervention. The questionnaire consisted of six sections addressing sociodemographic and perinatal factors, water and beverages consumption, physical activity, snacking and sedentary behaviours. Parents/caregivers from six countries (Belgium, Bulgaria, Germany, Greece, Poland and Spain) were asked to complete the questionnaire twice within a 2-week interval. A total of 93 questionnaires were collected. Test-retest reliability was assessed using intra-class correlation coefficient (ICC). Reliability of the six questionnaire sections was assessed. A stronger agreement was observed in the questions addressing sociodemographic and perinatal factors as opposed to questions addressing behaviours. Findings showed that 92% of the ToyBox PCQ had a moderate-to-excellent test-retest reliability (defined as ICC values from 0.41 to 1) and less than 8% poor test-retest reliability (ICC < 0.40). Out of the total ICC values, 67% showed good-to-excellent reliability (ICC from 0.61 to 1). We conclude that the PCQ is a reliable tool to assess sociodemographic characteristics, perinatal factors and lifestyle behaviours of pre-school children and their families participating in the ToyBox-intervention.
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- Mouratidou, N., et al.
(författare)
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Identification of Childhood-Onset Inflammatory Bowel Disease in Swedish Healthcare Registers: A Validation Study
- 2022
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Ingår i: CLINICAL EPIDEMIOLOGY. - 1179-1349. ; 14, s. 591-600
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The Swedish National Patient Register (NPR) is often used in observational studies of childhood-onset inflammatory bowel disease (IBD) (<18 years of age) and its subtypes, but the validity of previously used register-based algorithms for capturing childhood-onset IBD has never been examined. Methods: We identified a random sample of 233 individuals with at least two first ever diagnostic listings of IBD in the NPR between 2002 and 2014. We calculated the test characteristics for different register-based definitions of IBD and its subtypes using the Copenhagen criteria and the revised Porto criteria as gold standard, both based on medical chart review. We made assumptions of the occurrence of undiagnosed IBD in the general child population based on available literature. Results: Out of 233 individuals with at least two diagnostic listings of IBD, 216 had true IBD, resulting in a positive predictive value (PPV) = 93% (95% confidence interval (CI) 89-96), sensitivity = 88% (95% CI 83-92), specificity = 100% (95% CI 100-100), and negative predictive value (NPV) = 100% (95% CI 100-100). The PPV for the NPR-based definitions of IBD subtypes at time of first IBD diagnosis and at end of follow-up were 78% (95% CI 69-86) and 88% (95% CI 80-94), respectively, for Crohn's disease and 74% (95% CI 63-83) and 71% (95% CI 60-80), respectively, for ulcerative colitis. Conclusion: The validity of register-based definitions of childhood-onset IBD in the Swedish NPR is high and can be used to identify patients in observational research.
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