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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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- Nichols, E, et al.
(författare)
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Use of multidimensional item response theory methods for dementia prevalence prediction: an example using the Health and Retirement Survey and the Aging, Demographics, and Memory Study
- 2021
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Ingår i: BMC medical informatics and decision making. - : Springer Science and Business Media LLC. - 1472-6947. ; 21:1, s. 241-
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundData sparsity is a major limitation to estimating national and global dementia burden. Surveys with full diagnostic evaluations of dementia prevalence are prohibitively resource-intensive in many settings. However, validation samples from nationally representative surveys allow for the development of algorithms for the prediction of dementia prevalence nationally.MethodsUsing cognitive testing data and data on functional limitations from Wave A (2001–2003) of the ADAMS study (n = 744) and the 2000 wave of the HRS study (n = 6358) we estimated a two-dimensional item response theory model to calculate cognition and function scores for all individuals over 70. Based on diagnostic information from the formal clinical adjudication in ADAMS, we fit a logistic regression model for the classification of dementia status using cognition and function scores and applied this algorithm to the full HRS sample to calculate dementia prevalence by age and sex.ResultsOur algorithm had a cross-validated predictive accuracy of 88% (86–90), and an area under the curve of 0.97 (0.97–0.98) in ADAMS. Prevalence was higher in females than males and increased over age, with a prevalence of 4% (3–4) in individuals 70–79, 11% (9–12) in individuals 80–89 years old, and 28% (22–35) in those 90 and older.ConclusionsOur model had similar or better accuracy as compared to previously reviewed algorithms for the prediction of dementia prevalence in HRS, while utilizing more flexible methods. These methods could be more easily generalized and utilized to estimate dementia prevalence in other national surveys.
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- Vetrano, Davide L., et al.
(författare)
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Hypertension and frailty : a systematic review and meta-analysis
- 2018
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Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 8:12
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Forskningsöversikt (refereegranskat)abstract
- Objective To review the association between hypertension and frailty in observational studies. Design A systematic review of the PubMed, Web of Science and Embase databases was performed. A meta-analysis was performed if at least three studies used the same definition of frailty and a dichotomous definition of hypertension. Setting, participants and measures Studies providing information on the association between frailty and hypertension in adult persons, regardless of the study setting, study design or definition of hypertension and frailty were included. Results Among the initial 964 articles identified, 27 were included in the review. Four longitudinal studies examined the incidence of frailty according to baseline hypertension status, providing conflicting results. Twenty-three studies assessed the cross-sectional association between frailty and hypertension: 13 of them reported a significantly higher prevalence of frailty in hypertensive participants and 10 found no significant association. The pooled prevalence of hypertension in frail individuals was 72% (95% CI 66% to 79%) and the pooled prevalence of frailty in individuals with hypertension was 14% (95% CI 12% to 17%). Five studies, including a total of 7656 participants, reported estimates for the association between frailty and hypertension (pooled OR 1.33; 95% CI 0.94 to 1.89). Conclusions Frailty is common in persons with hypertension. Given the possible influence of frailty on the risk-benefit ratio of treatment for hypertension and its high prevalence, it is important to assess the presence of this condition in persons with hypertension.
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