| 1. |
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| 2. |
- Guman, M. S.S., et al.
(författare)
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Adipose Tissue, Bile Acids, and Gut Microbiome Species Associated With Gallstones After Bariatric Surgery
- 2022
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Ingår i: Journal of Lipid Research. - : Elsevier BV. - 0022-2275 .- 1539-7262. ; 63:11, s. 100280-
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Tidskriftsartikel (refereegranskat)abstract
- Several risk factors are associated with gallstone disease after bariatric surgery, but the underlying pathophysiological mechanisms of gallstone formation are unclear. We hypothesize that gallstone formation after bariatric surgery is induced by different pathways compared with gallstone formation in the general population, since postoperative formation occurs rapidly in patients who did not develop gallstones in preceding years. To identify both pathophysiological and potentially protective mechanisms against postoperative gallstone formation, we compared the preoperative fasting metabolome, fecal microbiome, and liver and adipose tissue transcriptome obtained before or during bariatric surgery of obese patients with and without postoperative gallstones. In total, 88 patients were selected from the BARIA longitudinal cohort study. Within this group, 32 patients had postoperative gallstones within 2 years. Gut microbiota metagenomic analyses showed group differences in abundance of 41 bacterial species, particularly abundance of Lactobacillaceae and Enterobacteriaceae in patients without gallstones. Subcutaneous adipose tissue transcriptomic analyses revealed four genes that were suppressed in gallstone patients compared with patients without gallstones. These baseline gene expression and gut microbiota composition differences might relate to protective mechanisms against gallstone formation after bariatric surgery. Moreover, baseline fasting blood samples of patients with postoperative gallstones showed increased levels of several bile acids. Overall, we revealed different genes and bacteria associated with gallstones than those previously reported in the general population, supporting the hypothesis that gallstone formation after bariatric surgery follows a different trajectory. Further research is necessary to confirm the involvement of the bile acids, adipose tissue activity, and microbial species observed here.
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| 3. |
- Knevel, R, et al.
(författare)
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Rheumatic?-A Digital Diagnostic Decision Support Tool for Individuals Suspecting Rheumatic Diseases: A Multicenter Pilot Validation Study
- 2022
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Ingår i: Frontiers in medicine. - : Frontiers Media SA. - 2296-858X. ; 9, s. 774945-
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Tidskriftsartikel (refereegranskat)abstract
- Digital diagnostic decision support tools promise to accelerate diagnosis and increase health care efficiency in rheumatology. Rheumatic? is an online tool developed by specialists in rheumatology and general medicine together with patients and patient organizations. It calculates a risk score for several rheumatic diseases. We ran a pilot study retrospectively testing Rheumatic? for its ability to differentiate symptoms from existing or emerging immune-mediated rheumatic diseases from other rheumatic and musculoskeletal complaints and disorders in patients visiting rheumatology clinics.Materials and MethodsThe performance of Rheumatic? was tested using in three university rheumatology centers: (A) patients at Risk for RA (Karolinska Institutet, n = 50 individuals with musculoskeletal complaints and anti-citrullinated protein antibody positivity) (B) patients with early joint swelling [dataset B (Erlangen) n = 52]. (C) Patients with early arthritis where the clinician considered it likely to be of auto-immune origin [dataset C (Leiden) n = 73]. In dataset A we tested whether Rheumatic? could predict the development of arthritis. In dataset B and C we tested whether Rheumatic? could predict the development of an immune-mediated rheumatic diseases. We examined the discriminative power of the total score with the Wilcoxon rank test and the area-under-the-receiver-operating-characteristic curve (AUC-ROC). Next, we calculated the test characteristics for these patients passing the first or second expert-based Rheumatic? scoring threshold.ResultsThe total test scores differentiated between: (A) Individuals developing arthritis or not, median 245 vs. 163, P < 0.0001, AUC-ROC = 75.3; (B) patients with an immune-mediated arthritic disease or not median 191 vs. 107, P < 0.0001, AUC-ROC = 79.0; but less patients with an immune-mediated arthritic disease or not amongst those where the clinician already considered an immune mediated disease most likely (median 262 vs. 212, P < 0.0001, AUC-ROC = 53.6). Threshold-1 (advising to visit primary care doctor) was highly specific in dataset A and B (0.72, 0.87, and 0.23, respectively) and sensitive (0.67, 0.61, and 0.67). Threshold-2 (advising to visit rheumatologic care) was very specific in all three centers but not very sensitive: specificity of 1.0, 0.96, and 0.91, sensitivity 0.05, 0.07, 0.14 in dataset A, B, and C, respectively.ConclusionRheumatic? is a web-based patient-centered multilingual diagnostic tool capable of differentiating immune-mediated rheumatic conditions from other musculoskeletal problems. The current scoring system needs to be further optimized.
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| 4. |
- Knevel, R, et al.
(författare)
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Rheumatic?-A Digital Diagnostic Decision Support Tool for Individuals Suspecting Rheumatic Diseases: A Multicenter Pilot Validation Study
- 2022
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Ingår i: Frontiers in medicine. - : Frontiers Media SA. - 2296-858X. ; 9, s. 774945-
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Tidskriftsartikel (refereegranskat)abstract
- Digital diagnostic decision support tools promise to accelerate diagnosis and increase health care efficiency in rheumatology. Rheumatic? is an online tool developed by specialists in rheumatology and general medicine together with patients and patient organizations. It calculates a risk score for several rheumatic diseases. We ran a pilot study retrospectively testing Rheumatic? for its ability to differentiate symptoms from existing or emerging immune-mediated rheumatic diseases from other rheumatic and musculoskeletal complaints and disorders in patients visiting rheumatology clinics.Materials and MethodsThe performance of Rheumatic? was tested using in three university rheumatology centers: (A) patients at Risk for RA (Karolinska Institutet, n = 50 individuals with musculoskeletal complaints and anti-citrullinated protein antibody positivity) (B) patients with early joint swelling [dataset B (Erlangen) n = 52]. (C) Patients with early arthritis where the clinician considered it likely to be of auto-immune origin [dataset C (Leiden) n = 73]. In dataset A we tested whether Rheumatic? could predict the development of arthritis. In dataset B and C we tested whether Rheumatic? could predict the development of an immune-mediated rheumatic diseases. We examined the discriminative power of the total score with the Wilcoxon rank test and the area-under-the-receiver-operating-characteristic curve (AUC-ROC). Next, we calculated the test characteristics for these patients passing the first or second expert-based Rheumatic? scoring threshold.ResultsThe total test scores differentiated between: (A) Individuals developing arthritis or not, median 245 vs. 163, P < 0.0001, AUC-ROC = 75.3; (B) patients with an immune-mediated arthritic disease or not median 191 vs. 107, P < 0.0001, AUC-ROC = 79.0; but less patients with an immune-mediated arthritic disease or not amongst those where the clinician already considered an immune mediated disease most likely (median 262 vs. 212, P < 0.0001, AUC-ROC = 53.6). Threshold-1 (advising to visit primary care doctor) was highly specific in dataset A and B (0.72, 0.87, and 0.23, respectively) and sensitive (0.67, 0.61, and 0.67). Threshold-2 (advising to visit rheumatologic care) was very specific in all three centers but not very sensitive: specificity of 1.0, 0.96, and 0.91, sensitivity 0.05, 0.07, 0.14 in dataset A, B, and C, respectively.ConclusionRheumatic? is a web-based patient-centered multilingual diagnostic tool capable of differentiating immune-mediated rheumatic conditions from other musculoskeletal problems. The current scoring system needs to be further optimized.
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| 5. |
- Knevel, R, et al.
(författare)
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RHEUMATIC? - A DIGITAL DIAGNOSTIC DECISION SUPPORT TOOL FOR INDIVIDUALS SUSPECTING RHEUMATIC DISEASES: A MULTICENTER VALIDATION STUDY
- 2021
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Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 80, s. 87-88
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Digital diagnostic decision support tools promise to accelerate diagnosis and increase health care efficiency in rheumatology. Rheumatic? is an online tool developed by specialists in rheumatology and general medicine together with patients and patient organizations for individuals suspecting a rheumatic disease.1,2 The tool can be used by people suspicious for rheumatic diseases resulting in individual advise on eventually seeking further health care.Objectives:We tested Rheumatic? for its ability to differentiate symptoms from immune-mediated diseases from other rheumatic and musculoskeletal complaints and disorders in patients visiting rheumatology clinics.Methods:The performance of Rheumatic? was tested using data from 175 patients from three university rheumatology centers covering two different settings:A.Risk-RA phase setting. Here, we tested whether Rheumatic? could predict the development of arthritis in 50 at risk-individuals with musculoskeletal complaints and anti-citrullinated protein antibody positivity from the KI (Karolinska Institutet)B.Early arthritis setting. Here, we tested whether Rheumatic? could predict the development of an immune-mediated rheumatic disease in i) EUMC (Erlangen) n=52 patients and ii) LUMC (Leiden) n=73 patients.In each setting, we examined the discriminative power of the total score with the Wilcoxon rank test and the area-under-the-receiver-operating-characteristic curve (AUC-ROC).Results:In setting A, the total test score clearly differentiated between individuals developing arthritis or not, median 245 versus 163, P < 0.0001, AUC-ROC = 75.3 (Figure 1). Also within patients with arthritis the Rheumatic? total score was significantly higher in patients developing an immune-mediated arthritic disease versus those who did not: median score EUMC 191 versus 107, P < 0.0001, AUC-ROC = 79.0, and LUMC 262 versus 212, P < 0.0001, AUC-ROC = 53.6.Figure 1.(Area under) the receiver operating curve for the total Rheumatic? scoreConclusion:Rheumatic? is a web-based patient-centered multilingual diagnostic tool capable of differentiating immune-mediated rheumatic conditions from other musculoskeletal problems. A following subject of research is how the tool performs in a population-wide setting.References:[1]Knitza J. et al. Mobile Health in Rheumatology: A Patient Survey Study Exploring Usage, Preferences, Barriers and eHealth Literacy. JMIR mHealth and uHealth. 2020.[2]https://rheumatic.elsa.science/en/Acknowledgements:This project has received funding from EIT Health. EIT Health is supported by the European Institute of Innovation and Technology (EIT), a body of the European Union that receives support from the European Union’s Horizon 2020 Research and Innovation program.This project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 777357, RTCure.Disclosure of Interests:Rachel Knevel: None declared, Johannes Knitza: None declared, Aase Hensvold: None declared, Alexandra Circiumaru: None declared, Tor Bruce Employee of: Ocean Observations, Sebastian Evans Employee of: Elsa Science, Tjardo Maarseveen: None declared, Marc Maurits: None declared, Liesbeth Beaart- van de Voorde: None declared, David Simon: None declared, Arnd Kleyer: None declared, Martina Johannesson: None declared, Georg Schett: None declared, Thomas Huizinga: None declared, Sofia Svanteson Employee of: Elsa Science, Alexandra Lindfors Employee of: Ocean Observations, Lars Klareskog: None declared, Anca Catrina: None declared
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| 6. |
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| 7. |
- Zapata, SJ, et al.
(författare)
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GENETIC SUSCEPTIBILITY VARIANTS FOR RHEUMATOID ARTHRITIS ARE NOT ASSOCIATED WITH EARLY REMISSION; A MULTI-COHORT STUDY
- 2021
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Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 80, s. 403-404
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Patients who achieve remission promptly could have a specific genetic risk profile that supports regaining immune tolerance. The identification of these genes could provide novel drug targets.Objectives:To test the association between RA genetic risk variants with achieving remission at 6 months.Methods:We computed genetic risk scores (GRS) comprising of the RA susceptibility variants1 and HLA-SE status separately in 4425 patients across eight datasets from inception cohorts. Remission was defined as DAS28CRP<2.6 at 6 months. Missing DAS28CRP values in patients were imputed using predictive mean matching by MICE. We first tested whether baseline DAS28CRP changed with increasing GRS using linear regression. Next, we calculated odds ratios for GRS and HLA-SE on remission using logistic regression. Heterogeneity of the outcome between datasets was mitigated by running inverse variance meta-analysis.Results:Evaluation of the complete dataset, baseline clinical variables did not differ between patients achieving remission and those who did not (Table 1). Distribution of GRS was consistent between datasets. Neither GRS nor HLA-SE was associated with baseline DAS2DAS (OR1.01; 95% CI 0.99-1.04). A fixed effect meta-analysis (Figure 1.) showed no significant effect of the GRS (OR 0.99; 95% CI 0.94-1.03) or HLA-SE (OR 0.8CRP87; 95% CI 0.75-1.01) on remission at 6 months.Table 1.Summary of the data separated by disease activity after 6 months.allRemission at 6 monthsNo remission at 6 monthsN4425*15582430Age, mean (sd)55.38 (13.87)5517 (14.09)55.62 (13.59)Female %68.98%65.43%70.73%ACPA+ %61.94%63.53%61.67%Baseline DAS28, mean (sd)4.76 (1.22)4.47 (1.23)5.1 (1.15)*not all patients had 6 months dataConclusion:In these combined cohorts, RA genetics risk variants are not associated with early disease remission. At baseline there was no difference in genetic risk between patients achieving remission or not. Studies encompassing other genetic variants are needed to elucidate the genetics of RA remission.References:[1]Knevel R et al. Sci Transl Med. 2020;12(545):eaay1548.Acknowledgements:This project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 777357, RTCure.This project has received funding from Pfizer Inc.Disclosure of Interests:Samantha Jurado Zapata: None declared, Marc Maurits: None declared, Yann Abraham Employee of: Pfizer, Erik van den Akker: None declared, Anne Barton: None declared, Philip Brown: None declared, Andrew Cope: None declared, Isidoro González-Álvaro: None declared, Carl Goodyear: None declared, Annette van der Helm - van Mil: None declared, Xinli Hu Employee of: Pfizer, Thomas Huizinga: None declared, Martina Johannesson: None declared, Lars Klareskog: None declared, Dennis Lendrem: None declared, Iain McInnes: None declared, Fraser Morton: None declared, Caron Paterson: None declared, Duncan Porter: None declared, Arthur Pratt: None declared, Luis Rodriguez Rodriguez: None declared, Daniela Sieghart: None declared, Paul Studenic: None declared, Suzanne Verstappen: None declared, Leonid Padyukov: None declared, Aaron Winkler Employee of: Pfizer, John D Isaacs: None declared, Rachel Knevel Grant/research support from: Pfizer
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| 8. |
- de Groot, Frank M. F., et al.
(författare)
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2p x-ray absorption spectroscopy of 3d transition metal systems
- 2021
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Ingår i: Journal of Electron Spectroscopy and Related Phenomena. - : Elsevier BV. - 0368-2048 .- 1873-2526. ; 249
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Tidskriftsartikel (refereegranskat)abstract
- This review provides an overview of the different methods and computer codes that are used to interpret 2p x-ray absorption spectra of 3d transition metal ions. We first introduce the basic parameters and give an overview of the methods used. We start with the semi-empirical multiplet codes and compare the different codes that are available. A special chapter is devoted to the user friendly interfaces that have been written on the basis of these codes. Next we discuss the first principle codes based on band structure, including a chapter on Density Functional theory based approaches. We also give an overview of the first-principle multiplet codes that start from a cluster calculation and we discuss the wavefunction based methods, including multi-reference methods. We end the review with a discussion of the link between theory and experiment and discuss the open issues in the spectral analysis.
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| 9. |
- Fijneman, Andreas J., et al.
(författare)
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Local quantification of mesoporous silica microspheres using multiscale electron tomography and lattice Boltzmann simulations
- 2020
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Ingår i: Microporous and Mesoporous Materials. - : Elsevier BV. - 1387-1811. ; 302
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Tidskriftsartikel (refereegranskat)abstract
- The multiscale pore structure of mesoporous silica microspheres plays an important role for tuning mass transfer kinetics in technological applications such as liquid chromatography. While local analysis of a pore network in such materials has been previously achieved, multiscale quantification of microspheres down to the nanometer scale pore level is still lacking. Here we demonstrate for the first time, by combining low convergence angle scanning transmission electron microscopy tomography (LC-STEM tomography) with image analysis and lattice Boltzmann simulations, that the multiscale pore network of commercial mesoporous silica microspheres can be quantified. This includes comparing the local tortuosity and intraparticle diffusion coefficients between different regions within the same microsphere. The results, spanning more than two orders of magnitude between nanostructures and entire object, are in good agreement with bulk characterization techniques such as nitrogen gas physisorption and add valuable local information for tuning mass transfer behavior (in liquid chromatography or catalysis) on the single microsphere level.
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| 10. |
- Kuhn, Joel, et al.
(författare)
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Tri-modal imaging of gold-dotted magnetic nanoparticles for magnetic resonance imaging, computed tomography and intravascular ultrasound : an in vitro study
- 2020
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Ingår i: Nanomedicine. - : Future Medicine Ltd. - 1743-5889 .- 1748-6963. ; 15:25
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To examine the multimodal contrasting ability of gold-dotted magnetic nanoparticles (Au*MNPs) for magnetic resonance (MR), computed tomography (CT) and intravascular ultrasound (IVUS) imaging.Materials & methods: Au*MNPs were prepared by adapting an impregnation method, without using surface capping reagents and characterized (transmission electron microscopy, x-ray diffraction and Fourier-transform infrared spectroscopy) with theirin vitrocytotoxicity assessed, followed by imaging assessments.Results: The contrast-enhancing ability of Au*MNPs was shown to be concentration-dependent across MR, CT and IVUS imaging. The Au content of the Au*MNP led to evident increases of the IVUS signal.Conclusion: We demonstrated that Au*MNPs showed concentration-dependent contrast-enhancing ability in MRI and CT imaging, and for the first-time in IVUS imaging due to the Au content. These Au*MNPs are promising toward solidifying tri-modal imaging-based theragnostics.
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