| 1. |
- Fernandez, J. L. Abelleira, et al.
(författare)
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A Large Hadron Electron Collider at CERN
- 2012
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Ingår i: Journal of Physics G. - : IOP Publishing. - 0954-3899 .- 1361-6471. ; 39:7
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Tidskriftsartikel (refereegranskat)
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| 2. |
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| 3. |
- Brito-Zeron, P., et al.
(författare)
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How immunological profile drives clinical phenotype of primary Sjögren's syndrome at diagnosis : analysis of 10,500 patients (Sjögren Big Data Project)
- 2018
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Ingår i: Clinical and Experimental Rheumatology. - : CLINICAL & EXPER RHEUMATOLOGY. - 0392-856X .- 1593-098X. ; 36:3, s. S102-S112
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To evaluate the influence of the main immunological markers on the disease phenotype at diagnosis in a large international cohort of patients with primary Sjogren's syndrome (SjS).Methods: The Big Data Sjogren Project Consortium is an international, multicentre registry created in 2014. As a first step, baseline clinical information from leading centres on clinical research in SjS of the 5 continents was collected. The centres shared a harmonised data architecture and conducted cooperative online efforts in order to refine collected data under the coordination of a big data statistical team. Inclusion criteria were the fulfillment of the 2002 classification criteria. Immunological tests were carried out using standard commercial assays.Results: By January 2018, the participant centres had included 10,500 valid patients from 22 countries. The cohort included 9,806 (93%) women and 694 (7%) men, with a mean age at diagnosis of primary SjS of 53 years, mainly White (78%) and included from European countries (71%). The frequency of positive immunological markers at diagnosis was 79.3% for ANA, 73.2% for anti-Ro, 48.6% for RF, 45.1% for anti-La, 13.4% for low C3 levels, 14.5% for low C4 levels and 7.3% for cryoglobulins. Positive autoantibodies (ANA, Ro, La) correlated with a positive result in salivary gland biopsy, while hypocomplementaemia and especially cryoglobulinaemia correlated with systemic activity (mean ESSDAI score of 17.7 for ctyoglobulins, 11.3 for low C3 and 9.2 for low C4, in comparison with 3.8 for negative markers). The immunological markers with a great number of statistically-significant associations (p<0.001) in the organ-by-organ ESSDAI evaluation were cryoglobulins (9 domains), low C3 (8 domains), anti-La (7 domains) and low C4 (6 domains).Conclusion: We confirm the strong influence of immunological markers on the phenotype of primary SjS at diagnosis in the largest multi-ethnic international cohort ever analysed, with a greater influence for cryoglobulinaemic-related markers in comparison with Ro/La autoantibodies and ANA. Immunological patterns play a central role in the phenotypic expression of the disease already at the time of diagnosis, and may guide physicians to design a specific personalised management during the follow-up of patients with primary SjS.
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| 4. |
- Retamozo, S., et al.
(författare)
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Influence of the age at diagnosis in the disease expression of primary Sjogren's syndrome : Analysis of 12,753 patients from the Sjogren Big Data Consortium
- 2021
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Ingår i: Clinical and Experimental Rheumatology. - : CLINICAL & EXPER RHEUMATOLOGY. - 0392-856X .- 1593-098X. ; 39:6, s. S166-S174
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Tidskriftsartikel (refereegranskat)abstract
- Objective. To analyse how the main components of the disease phenotype (sicca symptoms, diagnostic tests, immunological markers and systemic disease) can be driven by the age at diagnosis of primary Sjogren's syndrome (pSS).Methods. By January 2021, the participant centres had included 12,753 patients from 25 countries that fulfilled the 2002/2016 classification criteria for pSS. The age at diagnosis was defined as the time when the attending physician confirmed fulfilment of the criteria. Patients were clustered according to age at diagnosis. 50 clusters with more than 100 observations (from 27 to 76 years) were used to study the influence of the age at diagnosis in the disease expression.Results. There was a consistent increase in the frequency of oral dryness according to the age at diagnosis, with a frequency of <90% in patients diagnosed at the youngest ages and >95% in those diagnosed at the oldest ages. The smooth curves that best fitted a linear model were the frequency of dry mouth (adjusted R-2 0.87) and the frequency of abnormal oral tests (adjusted R-2 0.72). Therefore, for each 1-year increase in the age at diagnosis, the frequency of dry mouth increased by 0.13%, and the frequency of abnormal oral diagnostic tests by 0.11%. There was a consistent year-by-year decrease in the frequency of all autoantibodies and immunological markers except for cryoglobulins. According to the linear models, for each 1-year increase in the age at diagnosis, the frequency of a positive result decreased by 0.57% (for anti-Ro antibodies), 0.47% (for RF) and 0.42% (for anti-La antibodies). The ESSDAI domains which showed a more consistent decrease were glandular and lymph node involvement (for each 1-year increase in the age at diagnosis, the frequency of activity decreased by 0.18%), and constitutional, cutaneous, and haematological involvements (the frequency decreased by 0.09% for each 1-year increase). In contrast, other domains showed an ascending pattern, especially pulmonary involvement (for each 1-year increase in the age at diagnosis, the frequency of activity increased by 0.22%), and peripheral nerve involvement (the frequency increased by 0.09% for each 1-year increase).Conclusion. The influence of the age at diagnosis on the key phenotypic features of pSS is strong, and should be considered critical not only for designing a personalised diagnostic approach, but also to be carefully considered when analysing the results of diagnostic tests and immunological parameters, and when internal organ involvement is suspected at diagnosis.
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| 5. |
- Retamozo, S., et al.
(författare)
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Systemic manifestations of primary Sjogren's syndrome out of the ESSDAI classification : prevalence and clinical relevance in a large international, multi-ethnic cohort of patients
- 2019
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Ingår i: Clinical and Experimental Rheumatology. - : CLINICAL & EXPER RHEUMATOLOGY. - 0392-856X .- 1593-098X. ; 71
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To analyse the frequency and characterise the systemic presentation of primary Sjogren's syndrome (SS) out of the ESSDAI classification in a large international, multi-ethnic cohort of patients. Methods: The Big Data Sjogren Project Consortium is an international, multicentre registry based on world-wide data-sharing and cooperative merging of pre-existing clinical SS databases from leading centres in clinical research in SS from the five continents. A list of 26 organ-by-organ systemic features not currently included in the ESSDAI classification was defined according to previous studies; these features were retrospectively recorded. Results: Information about non-ESSDAI features was available in 6331 patients [5,917 female, mean age at diagnosis 52 years, mainly White (86.3%)]. A total of 1641 (26%) patients had at least one of the ESSDAI systemic features. Cardiovascular manifestations were the most frequent organ-specific group of non-ESSDAI features reported in our patients (17% of the total cohort), with Raynaud's phenomenon being reported in 15%. Patients with systemic disease due to non-ESSDAI features had a lower frequency of dry mouth (90.7% vs. 94.1%, p<0.001) and positive minor salivary gland biopsy (86.7% vs. 89%, p=0.033), a higher frequency of anti-Ro/SSA (74.7% vs. 68.7%, p<0.001), anti-La/SSB antibodies (44.5% vs. 40.4%, p=0.004), ANA (82.7% vs. 79.5%, p=0.006), low C3 levels (17.4% vs. 9.7%, p<0.001), low C4 levels (14.4% vs. 9.6%, p<0.001), and positive serum cryoglobulins (8.6% vs. 5.5%, p=0.001). Systemic activity measured by the ESSDAI, clinESSDAI and DAS was higher in patients with systemic disease out of the ESSDAI in comparison with those without these features (p<0.001 for all comparisons). Conclusions: More than a quarter of patients with primary SS may have systemic manifestations not currently included in the ESSDAI classification, with a wide variety of cardiovascular, digestive, pulmonary, neurological, ocular, ENT (ear, nose, and throat), cutaneous and urological features that increase the scope of the systemic phenotype of the disease. However, the individual frequency of each of these non-ESSDAI features was very low, except for Raynaud's phenomenon.
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| 6. |
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| 7. |
- Brito-Zeron, P., et al.
(författare)
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Exposure to air pollution as an environmental determinant of how Sjögren's disease is expressed at diagnosis
- 2023
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Ingår i: Clinical and Experimental Rheumatology. - : Clinical and Experimental Rheumatology. - 0392-856X .- 1593-098X. ; 41:12, s. 2448-2457
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveTo analyse how the potential exposure to air pollutants can influence the key components at the time of diagnosis of Sjogren's phenotype (epidemiological profile, sicca symptoms, and systemic disease). MethodsFor the present study, the following variables were selected for harmonisation and refinement: age, sex, country, fulfilment of 2002/2016 criteria items, dry eyes, dry mouth, and overall ESSDAI score. Air pollution indexes per country were defined according to the OECD (1990-2021), including emission data of nitrogen and sulphur oxides (NO/SO), particulate matter (PM2.5 and 1.0), carbon monoxide (CO) and volatile organic compounds (VOC) calculated per unit of GDP, Kg per 1000 USD.ResultsThe results of the chi-square tests of independence for each air pollutant with the frequency of dry eyes at diagnosis showed that, except for one, all variables exhibited p-values <0.0001. The most pronounced disparities emerged in the dry eye prevalence among individuals inhabiting countries with the highest NO/SO exposure, a surge of 4.61 percentage points compared to other countries, followed by CO (3.59 points), non-methane (3.32 points), PM2.5 (3.30 points), and PM1.0 (1.60 points) exposures. Concerning dry mouth, individuals residing in countries with worse NO/SO exposures exhibited a heightened frequency of dry mouth by 2.05 percentage points (p<0.0001), followed by non-methane exposure (1.21 percentage points increase, p=0.007). Individuals inhabiting countries with the worst NO/SO, CO, and PM2.5 pollution levels had a higher mean global ESSDAI score than those in lower-risk nations (all p-values <0.0001). When systemic disease was stratified according to DAS into low, moderate, and high systemic activity levels, a heightened proportion of individuals manifesting moderate/severe systemic activity was observed in countries with worse exposures to NO/SO, CO, and PM2.5 pollutant levels. ConclusionFor the first time, we suggest that pollution levels could influence how SjD appears at diagnosis in a large international cohort of patients. The most notable relationships were found between symptoms (dryness and general body symptoms) and NO/SO, CO, and PM2.5 levels.
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| 8. |
- Flores-Chavez, A., et al.
(författare)
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Influence of exposure to climate-related hazards in the phenotypic expression of primary Sjögren's syndrome
- 2023
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Ingår i: Clinical and Experimental Rheumatology. - : Clinical and Experimental Rheumatology. - 0392-856X .- 1593-098X. ; 41:12, s. 2437-2447
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Tidskriftsartikel (refereegranskat)abstract
- Objective To analyse how the key components at the time of diagnosis of the Sjogren's phenotype (epidemiological profile, sicca symptoms, and systemic disease) can be influenced by the potential exposure to climate-related natural hazards. Methods For the present study, the following variables were selected for harmonisation and refinement: age, sex, country, fulfilment of 2002/2016 criteria items, dry eyes, dry mouth, and overall ESSDAI score. Climate-related hazards per country were defined according to the OECD and included seven climate-related hazard types: extreme temperature, extreme precipitation, drought, wildfire, wind threats, river flooding, and coastal flooding. Climatic variables were defined as dichotomous variables according to whether each country is ranked among the ten countries with the most significant exposure. Results After applying data-cleaning techniques and excluding people from countries not included in the OECD climate rankings, the database study analysed 16,042 patients from 23 countries. The disease was diagnosed between 1 and 3 years earlier in people living in countries included among the top 10 worst exposed to extreme precipitation, wildfire, wind threats, river flooding, and coastal flooding. A lower frequency of dry eyes was observed in people living in countries exposed to wind threats, river flooding, and coastal flooding, with a level of statistical association being classified as strong (p<0.0001 for the three variables). The frequency of dry mouth was significantly lower in people living in countries exposed to river flooding (p<0.0001) and coastal flooding (p<0.0001). People living in countries included in the worse climate scenarios for extreme temperature (p<0.0001) and river flooding (p<0.0001) showed a higher mean ESSDAI score in comparison with people living in no-risk countries. In contrast, those living in countries exposed to worse climate scenarios for wind threats (p<0.0001) and coastal flooding (p<0.0001) showed a lower mean ESSDAI score in comparison with people living in no-risk countries. Conclusion Local exposure to extreme climate-related hazards plays a role in modulating the presentation of Sjogren across countries concerning the age at which the disease is diagnosed, the frequency of dryness, and the degree of systemic activity.
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| 10. |
- Bogdan, Cristian M, 1971-, et al.
(författare)
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Programming for Moving Bodies
- 2020
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Ingår i: ACM International Conference Proceeding Series. - New York, NY, USA : Association for Computing Machinery.
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Konferensbidrag (refereegranskat)abstract
- Movement plays an increasingly important role in interactive systems design, from users' physical engagement, to how designed artefacts can move or be moved, and to the concert between users and artefacts. Designers, as well as programmers, have to engage more and more in physical activities when they want to create appealing experiences involving movement. There is a need for articulating emerging dialogues between designers, developers, and their materials. We will explore such dialogues in a 2-half-day workshop, focusing on data and its challenges, on tools and methods, on sensing and actuation when designing or detecting subtle body movements, and on catering for bodily changes over time.
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| 15. |
- Kilic, O., et al.
(författare)
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Severe musculoskeletal time-loss injuries and symptoms of common mental disorders in professional soccer: a longitudinal analysis of 12-month follow-up data
- 2018
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Ingår i: Knee Surgery, Sports Traumatology, Arthroscopy. - : SPRINGER. - 0942-2056 .- 1433-7347. ; 26:3, s. 946-954
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Tidskriftsartikel (refereegranskat)abstract
- Psychological factors have shown to be predictors of injury in professional football. However, it seems that this is a two-way relationship, as severe musculoskeletal time-loss injuries have shown to be associated with the onset of symptoms of common mental disorders (CMD). There is no longitudinal study performed exploring this interaction between symptoms of CMD and injuries. The purpose of this study was to explore the interaction between severe musculoskeletal time-loss injuries and symptoms of CMD in professional football players over a 12-month period. Players were recruited by their national players unions in five European countries. Symptoms of CMD included in the study were related to distress, anxiety/depression, sleep disturbance and adverse alcohol use. A total of 384 professional football players were enrolled in the study, of whom 262 (68%) completed the 12-month follow-up period. The mean age of the participants at baseline was 27 +/- 5 years, and they had played professional football for 8 +/- 5 years on average. Symptoms of CMD at baseline were not associated with the onset of severe musculoskeletal time-loss injuries during the follow-up period with relative risks (and 95% CI) ranging from 0.6 (0.3-1.0) to 1.0 (0.5-2.2). In contrast, severe musculoskeletal time-loss injuries reported at baseline were associated with the onset of symptoms of CMD during the follow-up period with relative risks ranging from 1.8 (0.8-3.7) to 6.9 (4.0-11.9). No relationship was found between symptoms of CMD and the onset of severe musculoskeletal time-loss injuries. However, professional football players who suffered from severe musculoskeletal time-loss injuries are likely to develop subsequent symptoms of CMD. This study emphasizes the need for an interdisciplinary medical approach, which not only focuses on the physical but also on the mental health of professional football players. An early identification of players at risk of symptoms of CMD, such as those suffering from severe musculoskeletal injuries, creates the opportunity for an interdisciplinary clinical medical team to treat the players timely and adequately. Prospective cohort study, Level II.
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| 16. |
- Kilic, Ö., et al.
(författare)
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Exposure to physical and psychosocial stressors in relation to symptoms of common mental disorders among European professional football referees : A prospective cohort study
- 2018
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Ingår i: BMJ Open Sport and Exercise Medicine. - London : BMJ Publishing Group Ltd. - 2055-7647. ; 4:1
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Tidskriftsartikel (refereegranskat)abstract
- Objectives The study aim was to explore the association of physical and psychosocial stressors (severe injuries, surgeries, recent life events, social support) with one-season onset of symptoms of common mental disorders (CMDs) among European professional football referees. Methods An observational prospective cohort study over a follow-up period of one season (2015-2016) was conducted among professional football referees from Belgium, Finland, France, Germany, Norway, Russia, Scotland and Sweden. Based on physical and psychosocial stressors as well as symptoms of CMD, an electronic questionnaire in English and French was set up and distributed by eight football federations involved. Results The prevalence of symptoms of CMD ranged from 5.9% for distress to 19.2% for eating disorders. A higher number of severe injuries and a lower degree of satisfaction about social support were significantly related to the occurrence of symptoms of CMD with an OR of 2.63 and an OR of 1.10, respectively. Conclusion A higher number of severe injuries and a lower degree on satisfaction about social support were found to be significantly associated with the onset of symptoms of CMD among European professional football referees. Referees suffering from severe injuries were nearly three times more likely to report symptoms of anxiety and depression. Referees who reported a low satisfaction of social support were significantly more likely to report symptoms of eating disorder. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved.
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| 17. |
- Kreins, AY, et al.
(författare)
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Human TYK2 deficiency: Mycobacterial and viral infections without hyper-IgE syndrome
- 2015
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Ingår i: The Journal of experimental medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 212:10, s. 1641-1662
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Tidskriftsartikel (refereegranskat)abstract
- Autosomal recessive, complete TYK2 deficiency was previously described in a patient (P1) with intracellular bacterial and viral infections and features of hyper-IgE syndrome (HIES), including atopic dermatitis, high serum IgE levels, and staphylococcal abscesses. We identified seven other TYK2-deficient patients from five families and four different ethnic groups. These patients were homozygous for one of five null mutations, different from that seen in P1. They displayed mycobacterial and/or viral infections, but no HIES. All eight TYK2-deficient patients displayed impaired but not abolished cellular responses to (a) IL-12 and IFN-α/β, accounting for mycobacterial and viral infections, respectively; (b) IL-23, with normal proportions of circulating IL-17+ T cells, accounting for their apparent lack of mucocutaneous candidiasis; and (c) IL-10, with no overt clinical consequences, including a lack of inflammatory bowel disease. Cellular responses to IL-21, IL-27, IFN-γ, IL-28/29 (IFN-λ), and leukemia inhibitory factor (LIF) were normal. The leukocytes and fibroblasts of all seven newly identified TYK2-deficient patients, unlike those of P1, responded normally to IL-6, possibly accounting for the lack of HIES in these patients. The expression of exogenous wild-type TYK2 or the silencing of endogenous TYK2 did not rescue IL-6 hyporesponsiveness, suggesting that this phenotype was not a consequence of the TYK2 genotype. The core clinical phenotype of TYK2 deficiency is mycobacterial and/or viral infections, caused by impaired responses to IL-12 and IFN-α/β. Moreover, impaired IL-6 responses and HIES do not appear to be intrinsic features of TYK2 deficiency in humans.
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| 18. |
- Schneider, K. M., et al.
(författare)
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Gut microbiota depletion exacerbates cholestatic liver injury via loss of FXR signalling
- 2021
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Ingår i: Nature Metabolism. - : Springer Science and Business Media LLC. - 2522-5812. ; 3:9, s. 1228-1241
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Tidskriftsartikel (refereegranskat)abstract
- Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease of unknown aetiology for which there are no approved therapeutic options. Patients with PSC display changes in gut microbiota and in bile acid (BA) composition; however, the contribution of these alterations to disease pathogenesis remains controversial. Here we identify a role for microbiota-dependent changes in BA synthesis that modulates PSC pathophysiology. In a genetic mouse model of PSC, we show that loss of microbiota-mediated negative feedback control of BA synthesis results in increased hepatic BA concentrations, disruption of bile duct barrier function and, consequently, fatal liver injury. We further show that these changes are dependent on decreased BA signalling to the farnesoid X receptor, which modulates the activity of the rate-limiting enzyme in BA synthesis, CYP7A1. Moreover, patients with advanced stages of PSC show suppressed BA synthesis as measured by serum C4 levels, which is associated with poor disease prognosis. Our preclinical data highlight the microbiota-dependent dynamics of BA metabolism in cholestatic liver disease, which could be important for future therapies targeting BA and gut microbiome interactions, and identify C4 as a potential biomarker to functionally stratify patients with PSC and predict disease outcomes. Patients with primary sclerosing cholangitis (PSC), a chronic cholestatic liver disease, display changes in the gut microbiota and in bile acid composition. Schneider, Candels and colleagues identify a role for microbiota-dependent regulation of bile acid synthesis through farnesoid X receptor signalling, which is relevant for PSC disease progression.
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| 19. |
- Schneider, K. M., et al.
(författare)
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Imbalanced gut microbiota fuels hepatocellular carcinoma development by shaping the hepatic inflammatory microenvironment
- 2022
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths worldwide, and therapeutic options for advanced HCC are limited. Here, we observe that intestinal dysbiosis affects antitumor immune surveillance and drives liver disease progression towards cancer. Dysbiotic microbiota, as seen in Nlrp6(-/-) mice, induces a Toll-like receptor 4 dependent expansion of hepatic monocytic myeloid-derived suppressor cells (mMDSC) and suppression of T-cell abundance. This phenotype is transmissible via fecal microbiota transfer and reversible upon antibiotic treatment, pointing to the high plasticity of the tumor microenvironment. While loss of Akkermansia muciniphila correlates with mMDSC abundance, its reintroduction restores intestinal barrier function and strongly reduces liver inflammation and fibrosis. Cirrhosis patients display increased bacterial abundance in hepatic tissue, which induces pronounced transcriptional changes, including activation of fibro-inflammatory pathways as well as circuits mediating cancer immunosuppression. This study demonstrates that gut microbiota closely shapes the hepatic inflammatory microenvironment opening approaches for cancer prevention and therapy. Steatohepatitis is a chronic hepatic inflammation associated with increased risk of hepatocellular carcinoma progression. Here the authors show that intestinal dysbiosis in mice lacking the inflammasome sensor molecule NLRP6 aggravates steatohepatitis and accelerates liver cancer progression, a process that can be delayed by antibiotic treatment.
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| 20. |
- Shipilin, Mikhail, et al.
(författare)
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The influence of incommensurability on the long-range periodicity of the Pd(100)-(root 5 x root 5)R27 degrees-PdO(101)
- 2017
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Ingår i: Surface Science. - : Elsevier BV. - 0039-6028. ; 660, s. 1-8
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Tidskriftsartikel (refereegranskat)abstract
- The structural model of the (root 5 x root 5)R27 degrees PdO(101) surface oxide grown on Pd(100) has been proposed and refined by a number of authors over more than a decade. In the current contribution we discuss the long-range periodicity of this structure arising along one of the crystallographic directions due to its incommensurability with the substrate. Analyzing the results of surface sensitive diffraction studies, we determined a slight distortion of the previously reported perfect (root 5 x root 5)R27 degrees surface oxide unit cell. Considering it, we were able to achieve both qualitatively and quantitatively better fit to the experimental diffraction data than it was possible for the perfect structure. Further, taking into account the experimentally obtained scanning tunneling microscopy data and closely examining high-resolution patterns recorded by means of high-energy surface X-ray diffraction, we developed a qualitative structural model based on a larger non-orthogonal surface unit cell to shed more light on the long-range order of the PdO(101) surface oxide. The model comprises a shift of the atoms of the PdO perpendicularly to the direction of the incommensurability to correct for it. This structural model reproduces the fine details of the high-resolution diffraction patterns and qualitatively explains the periodic stripes of structural distortion observed in the images recorded by a scanning tunneling microscope.
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