| 1. |
- Arve-Butler, Sabine, et al.
(författare)
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Identification of novel autoantigens as potential biomarkers in juvenile idiopathic arthritis associated uveitis
- 2023
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Ingår i: Frontiers in Pediatrics. - : Frontiers Media SA. - 2296-2360. ; 10, s. 1-11
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Many children with juvenile idiopathic arthritis (JIA) have autoantibodies, targeting nuclear components (anti-nuclear antibodies, ANA). ANA in JIA is associated with uveitis, an eye inflammation which may cause permanent vision impairment if not detected and treated. However, ANA-testing is neither specific nor sensitive enough to be a clinically reliable predictor of uveitis risk, and the precise autoantigens targeted by ANA in JIA are largely unknown. If identified, specific autoantibodies highly associated with uveitis could be used as biomarkers to facilitate identification of JIA patients at risk.METHODS: Antibodies from six ANA-positive, oligoarticular JIA patients, with and without uveitis, were explored by two large-scale methods: (1) screening against 42,100 peptides on an autoimmunity profiling planar array, and (2) immunoprecipitations from cell lysates with antigen identification by mass spectrometry. Three hundred thirty-five peptide antigens, selected from proteins identified in the large-scale methods and the scientific literature were investigated using a bead-based array in a cohort of 56 patients with oligoarticular- or RF-negative polyarticular JIA, eight of which were having current or previous uveitis.RESULTS: In the planar array, reactivity was detected against 332 peptide antigens. The immunoprecipitations identified reactivity towards 131 proteins. Only two proteins were identified by both methods. In the bead-based array of selected peptide antigens, patients with uveitis had a generally higher autoreactivity, seen as higher median fluorescence intensity (MFI) across all antigens, compared to patients without uveitis. Reactivity towards 17 specific antigens was significantly higher in patients with uveitis compared to patients without uveitis. Hierarchical clustering revealed that patients with uveitis clustered together.CONCLUSION: This study investigated autoantigens in JIA and uveitis, by combining two exploratory methods and confirmation in a targeted array. JIA patients with current or a history of uveitis had significantly higher reactivity towards 17 autoantigens and a generally higher autoreactivity compared to JIA patients without uveitis. Hierarchical clustering suggests that a combination of certain autoantibodies, rather than reactivity towards one specific antigen, is associated with uveitis. Our analysis of autoantibodies associated with uveitis in JIA could be a starting point for identification of prognostic biomarkers useful in JIA clinical care.
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| 2. |
- Bhatti, Fiaz Ahmad, et al.
(författare)
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On the Extended Chen Distribution: Development, Properties, Characterizations and Applications
- 2021
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Ingår i: Annals of Data Science. - : Springer Science and Business Media LLC. - 2198-5804 .- 2198-5812. ; 8:1, s. 159-180
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Tidskriftsartikel (refereegranskat)abstract
- In this paper, a flexible model called extended Chen (EC) distribution is derived from the generalized Burr-Hatke differential equation and nexus between the exponential and gamma variables. The EC distribution is also derived from compounding mixture of the generalized Chen and gamma distributions. The EC distribution is very flexible and its hazard rate function accommodates various shapes such as increasing, decreasing, decreasing–increasing, increasing–decreasing–increasing, bathtub and modified bathtub. The density function of the EC model is arc, J, reverse-J, left-skewed, right-skewed and symmetrical shaped. Some structural and mathematical properties such as descriptive measures on the basis of quantiles, stochastic orderings, moments, order statistics and reliability measures are theoretically established. The EC distribution is characterized via various techniques. The maximum likelihood estimates for unknown parameters of the EC distribution are obtained. A simulation study is executed to assess the behavior of the maximum likelihood estimators. The EC distribution is applied to two real data sets to elucidate its potentiality and utility. The competence of the EC distribution is tested through various goodness of fit criteria.
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| 3. |
- Farrahi, Hassan, et al.
(författare)
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Psychometric properties of the Persian version of the overall anxiety severity and impairment scale (OASIS)
- 2020
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Ingår i: Iranian Journal of Psychiatry and Behavioral Sciences. - : Kowsar Medical Publishing Company. - 1735-8639. ; 14:4
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: This study was conducted to assess the psychometric properties of the Persian version of the overall anxiety severity and impairment scale (OASIS), a measure designed to evaluate the severity and functional impairments associated with clinical and subsyndromal anxiety.Methods: Using a descriptive-analytic framework, first, the OASIS was translated into Persian according to the forward-backward translation guidelines. Then, a total of 463 students of Guilan University of Medical Sciences in the academic year 2017 - 18 were selected using the convenience sampling method. Participants completed seven measures (i.e., OASIS, anxiety and stress subscales of depression anxiety stress scales-21, Beck anxiety inventory, openness subscale of NEO five-factor inventory, positive affect and negative affect scales, Connor-Davidson resilience scale, and state subscale of state-trait anxiety inventory), and the data were analyzed by SPSS V. 20.0 for windows and Lisrel V. 8.80.Results: Internal consistency reliability of the OASIS was acceptable (Cronbach’s α = 0.877). The exploratory factor analysis indicated that all items were loaded on a single factor (loadings = 0.799 - 0.849). The confirmatory factor analysis revealed that the single-factor model has resulted in an adequate model fit. The OASIS was positively correlated with the anxiety- and negative affect-related scales, whereas it was negatively correlated with the resilience- and positive affect-related scales. Correlations with the openness subscale were not significant.Conclusions: In line with previous studies, the findings showed that the psychometric properties of the Persian version of the OASIS are acceptable. Therefore, it seems that the measure can be used in clinical practices and research studies in Iran.
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| 4. |
- Haghbin, Hossein, et al.
(författare)
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Functional singular spectrum analysis
- 2021
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Ingår i: Stat. - : Wiley. - 2049-1573. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- In this paper, we develop a new extension of the singular spectrum analysis (SSA) called functional SSA to analyze functional time series. The new methodology is constructed by integrating ideas from functional data analysis and univariate SSA. Specifically, we introduce a trajectory operator in the functional world, which is equivalent to the trajectory matrix in the regular SSA. In the regular SSA, one needs to obtain the singular value decomposition (SVD) of the trajectory matrix to decompose a given time series. Since there is no procedure to extract the functional SVD (fSVD) of the trajectory operator, we introduce a computationally tractable algorithm to obtain the fSVD components. The effectiveness of the proposed approach is illustrated by an interesting example of remote sensing data. Also, we develop an efficient and user‐friendly R package and a shiny web application to allow interactive exploration of the results.
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| 5. |
- Haghi, Mehrnaz, et al.
(författare)
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Distinctive alteration in the expression of autophagy genes in Drosophila models of amyloidopathy and tauopathy
- 2020
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Ingår i: Upsala Journal of Medical Sciences. - : Uppsala Medical Society. - 0300-9734 .- 2000-1967. ; 125:4, s. 265-273
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Alzheimer's disease (AD) is one the most common types of dementia. Plaques of amyloid beta and neurofibrillary tangles of tau are two major hallmarks of AD. Metabolism of these two proteins, in part, depends on autophagy pathways. Autophagy dysfunction and protein aggregation in AD may be involved in a vicious circle. The aim of this study was to investigate whether tau or amyloid beta 42 (Aβ42) could affect expression of autophagy genes, and whether they exert their effects in the same way or not.METHODS: Expression levels of some autophagy genes, Hook, Atg6, Atg8, and Cathepsin D, were measured using quantitative PCR in transgenic Drosophila melanogaster expressing either Aβ42 or Tau R406W.RESULTS: We found that Hook mRNA levels were downregulated in Aβ42-expressing flies both 5 and 25 days old, while they were increased in 25-day-old flies expressing Tau R406W. Both Atg6 and Atg8 were upregulated at day 5 and then downregulated in 25-day-old flies expressing either Aβ42 or Tau R406W. Cathepsin D expression levels were significantly increased in 5-day-old flies expressing Tau R406W, while there was no significant change in the expression levels of this gene in 5-day-old flies expressing Aβ42. Expression levels of Cathepsin D were significantly decreased in 25-day-old transgenic flies expressing Tau R406W or Aβ42.CONCLUSION: We conclude that both Aβ42 and Tau R406W may affect autophagy through dysregulation of autophagy genes. Interestingly, it seems that these pathological proteins exert their toxic effects on autophagy through different pathways and independently.
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| 6. |
- Kahn, Robin, et al.
(författare)
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Capillary leak syndrome was associated with more severe multisystem inflammatory syndrome in children during the COVID-19 pandemic
- 2024
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Ingår i: Acta Paediatrica, International Journal of Paediatrics. - 0803-5253. ; 113:6, s. 1404-1411
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Tidskriftsartikel (refereegranskat)abstract
- Aim: This population-based study investigated the occurrence of capillary leak syndrome (CLS) in children with multisystem inflammatory syndrome in children (MIS-C), associated with COVID-19. We also examined associations between CLS and MIS-C disease severity. Methods: All eligible individuals aged 0–18 years, who were diagnosed with MIS-C in Skåne, southern Sweden, from 1 April 2020 to 31 July 2021, were studied. They were all included in the Pediatric Rheumatology Quality Register and clinical and laboratory data were compared between patients with and without CLS. Results: We included 31 patients (61% male) with MIS-C in the study. The median age at diagnosis was 10.6 years (range 1.99–17.15) and 45% developed CLS. All six patients who required intensive care had CLS. Patients with CLS also had a higher incidence of reduced cardiac function, measured as low ejection fraction. The CLS group exhibited significantly higher C-reactive protein values (p < 0.001) and N-terminal pro-B-type natriuretic peptide levels (p < 0.001), as well as lower platelet counts (p = 0.03), during the first week of treatment. Individuals with CLS also received more intense immunosuppression. Conclusion: CLS was a common complication of MIS-C in our study and these patients had a more severe disease course that required more intensive treatment.
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| 7. |
- Mayeli, Ahmad, et al.
(författare)
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Sleep abnormalities in Individuals at Clinical High Risk for Psychosis
- 2021
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Ingår i: Journal of Psychiatric Research. - : Elsevier BV. - 0022-3956. ; 137, s. 328-334
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Tidskriftsartikel (refereegranskat)abstract
- Youth at clinical high risk (CHR) represent a unique population enriched for precursors of major psychiatric disorders. Sleep disturbances are consistently reported in CHR individuals. However, there is a dearth of studies investigating quantifiable objective measures of sleep dysfunction in CHR youth. In this study, sleep high density (hd)-EEG recordings were collected in twenty-two CHR and twenty healthy control (HC) subjects. Sleep architecture parameters, as well as sleep EEG power spectra in five frequency bands, were computed and compared between CHR and HC groups during non-rapid eye movement (NREM) sleep. Furthermore, correlation analyses between sleep EEG power spectra, sleep architecture parameters, and clinical symptoms, assessed with the scale of prodromal symptoms (SOPS), were conducted in CHR participants. Our results show that CHR individuals had more wakefulness after sleep onset (WASO) compared to HC participants. CHR also showed a higher NREM sleep gamma EEG power, which was observed in a large fronto-parieto-occipital area, relative to HC. Additionally, higher NREM gamma activity in lateral fronto-occipital regions was associated with more WASO, and increased NREM gamma power in medial fronto/parietal areas correlated with worse SOPS negative symptoms. Altogether, these findings suggest that topographically specific increases in EEG gamma activity during NREM sleep represent neurophysiological signatures underlying some of the objectively assessed sleep disturbances and clinical symptoms of CHR individuals.
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| 8. |
- Naseri, Parisa, et al.
(författare)
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Functional brain response to emotional musical stimuli in depression, using INLA approach for approximate Bayesian inference
- 2021
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Ingår i: Basic and Clinical Neuroscience. - : Negah Scientific Publisher. - 2008-126X .- 2228-7442. ; 12:1, s. 95-104
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: One of the vital skills which has an impact on emotional health and well-being is the regulation of emotions. In recent years, the neural basis of this process has been considered widely. One of the powerful tools for eliciting and regulating emotion is music. The Anterior Cingulate Cortex (ACC) is part of the emotional neural circuitry involved in Major Depressive Disorder (MDD). The current study uses functional Magnetic Resonance Imaging (fMRI) to examine how neural processing of emotional musical auditory stimuli is changed within the ACC in depression. Statistical inference is conducted using a Bayesian Generalized Linear Model (GLM) approach with an Integrated Nested Laplace Approximation (INLA) algorithm. Methods: A new proposed Bayesian approach was applied for assessing functional response to emotional musical auditory stimuli in a block design fMRI data with 105 scans of two healthy and depressed women. In this Bayesian approach, Unweighted Graph-Laplacian (UGL) prior was chosen for spatial dependency, and autoregressive (AR) (1) process was used for temporal correlation via pre-weighting residuals. Finally, the inference was conducted using the Integrated Nested Laplace Approximation (INLA) algorithm in the R-INLA package. Results: The results revealed that positive music, as compared to negative music, elicits stronger activation within the ACC area in both healthy and depressed subjects. In comparing MDD and Never-Depressed (ND) individuals, a significant difference was found between MDD and ND groups in response to positive music vs negative music stimuli. The activations increase from baseline to positive stimuli and decrease from baseline to negative stimuli in ND subjects. Also, a significant decrease from baseline to positive stimuli was observed in MDD subjects, but there was no significant difference between baseline and negative stimuli. Conclusion: Assessing the pattern of activations within ACC in a depressed individual may be useful in retraining the ACC and improving its function, and lead to more effective therapeutic interventions.
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| 9. |
- Oliver, Ryan C, et al.
(författare)
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Assembly of Capsids from Hepatitis B Virus Core Protein Progresses through Highly Populated Intermediates in the Presence and Absence of RNA
- 2020
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Ingår i: ACS Nano. - : American Chemical Society (ACS). - 1936-086X .- 1936-0851. ; 14:8, s. 10226-10238
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Tidskriftsartikel (refereegranskat)abstract
- The genetic material of viruses is protected by protein shells that are assembled from a large number of subunits in a process that is efficient and robust. Many of the mechanistic details underpinning efficient assembly of virus capsids are still unknown. The assembly mechanism of hepatitis B capsids has been intensively researched using a truncated core protein lacking the C-terminal domain responsible for binding genomic RNA. To resolve the assembly intermediates of hepatitis B virus (HBV), we studied the formation of nucleocapsids and empty capsids from full-length hepatitis B core proteins, using time-resolved small-angle X-ray scattering. We developed a detailed structural model of the HBV capsid assembly process using a combination of analysis with multivariate curve resolution, structural modeling, and Bayesian ensemble inference. The detailed structural analysis supports an assembly pathway that proceeds through the formation of two highly populated intermediates, a trimer of dimers and a partially closed shell consisting of around 40 dimers. These intermediates are on-path, transient and efficiently convert into fully formed capsids. In the presence of an RNA oligo that binds specifically to the C-terminal domain the assembly proceeds via a similar mechanism to that in the absence of nucleic acids. Comparisons between truncated and full-length HBV capsid proteins reveal that the unstructured C-terminal domain has a significant impact on the assembly process and is required to obtain a more complete mechanistic understanding of HBV capsid formation. These results also illustrate how combining scattering information from different time-points during time-resolved experiments can be utilized to derive a structural model of protein self-assembly pathways.
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| 10. |
- Schmidt, Tobias, et al.
(författare)
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Synovial monocytes contribute to chronic inflammation in childhood-onset arthritis via IL-6/STAT signalling and cell-cell interactions
- 2023
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Ingår i: Frontiers in Immunology. - 1664-3224. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Monocytes are key effector cells in inflammatory processes. We and others have previously shown that synovial monocytes in childhood-onset arthritis are activated. However, very little is known about how they contribute to disease and attain their pathological features. Therefore, we set out to investigate the functional alterations of synovial monocytes in childhood-onset arthritis, how they acquire this phenotype, and whether these mechanisms could be used to tailorize treatment.METHODS: The function of synovial monocytes was analysed by assays believed to reflect key pathological events, such as T-cell activation-, efferocytosis- and cytokine production assays using flow cytometry in untreated oligoarticular juvenile idiopathic arthritis (oJIA) patients (n=33). The effect of synovial fluid on healthy monocytes was investigated through mass spectrometry and functional assays. To characterize pathways induced by synovial fluid, we utilized broad-spectrum phosphorylation assays and flow cytometry, as well as inhibitors to block specific pathways. Additional effects on monocytes were studied through co-cultures with fibroblast-like synoviocytes or migration in transwell systems.RESULTS: Synovial monocytes display functional alterations with inflammatory and regulatory features, e.g., increased ability to induce T-cell activation, resistance to cytokine production following activation with LPS and increased efferocytosis. In vitro, synovial fluid from patients induced the regulatory features in healthy monocytes, such as resistance to cytokine production and increased efferocytosis. IL-6/JAK/STAT signalling was identified as the main pathway induced by synovial fluid, which also was responsible for a majority of the induced features. The magnitude of synovial IL-6 driven activation in monocytes was reflected in circulating cytokine levels, reflecting two groups of low vs. high local and systemic inflammation. Remaining features, such as an increased ability to induce T-cell activation and markers of antigen presentation, could be induced by cell-cell interactions, specifically via co-culture with fibroblast-like synoviocytes. CONCLUSIONS: Synovial monocytes in childhood-onset arthritis are functionally affected and contribute to chronic inflammation, e.g., via promoting adaptive immune responses. These data support a role of monocytes in the pathogenesis of oJIA and highlight a group of patients more likely to benefit from targeting the IL-6/JAK/STAT axis to restore synovial homeostasis.
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