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| 2. |
- Alsterholm, Mikael, 1977, et al.
(författare)
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Establishment and utility of SwedAD : a nationwide Swedish registry for patients with atopic dermatitis receiving systemic pharmacotherapy
- 2023
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Ingår i: Acta Dermato-Venereologica. - : Medical Journals Sweden AB. - 0001-5555 .- 1651-2057. ; 103
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Tidskriftsartikel (refereegranskat)abstract
- SwedAD, a Swedish nationwide registry for patients with atopic dermatitis receiving systemic pharmacotherapy, was launched on 1 September 2019. We describe here the establishment of a user-friendly registry to the benefit of patients with atopic dermatitis. By 5 November 2022, 38 clinics had recorded 931 treatment episodes in 850 patients with an approximate national coverage rate of 40%. Characteristics at enrolment included median Eczema Area and Severity Index (EASI) 10.2 (interquartile range 4.0, 19.4), Patient-Oriented Eczema Measure (POEM) 18.0 (10.0, 24.0), Dermatology Life Quality Index (DLQI) 11.0 (5.0, 19.0) and Peak Itch Numerical Rating Scale-11 (NRS-11) 6.0 (3.0, 8.0). At 3 months, median EASI was 3.2 (1.0, 7.3) and POEM, DLQI, and NRS-11 were improved. Regional coverage varied, reflecting the distribution of dermatologists, the ratio of public to private healthcare, and difficulties in recruiting certain clinics. This study highlights the importance of a nationwide registry when managing systemic pharmacotherapy of atopic dermatitis.
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| 3. |
- Andersson, Tomas, et al.
(författare)
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Plasmon single- and multi-quantum excitation in free metal clusters as seen by photoelectron spectroscopy
- 2011
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Ingår i: Journal of Chemical Physics. - : AIP Publishing. - 0021-9606 .- 1089-7690. ; 134:9, s. 094511-
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Tidskriftsartikel (refereegranskat)abstract
- Plasmons are investigated in free nanoscale Na, Mg, and K metal clusters using synchrotron radiation-based x-ray photoelectron spectroscopy. The core levels for which the response from bulk and surface atoms can be resolved are probed over an extended binding energy range to include the plasmon loss features. In all species the features due to fundamental plasmons are identified, and in Na and K also those due to either the first order plasmon overtones or sequential plasmon excitation are observed. These features are discussed in view of earlier results for planar macroscopic samples and free clusters of the same materials.
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| 4. |
- Burn, Garth L., et al.
(författare)
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Superresolution imaging of the cytoplasmic phosphatase PTPN22 links integrin-mediated T cell adhesion with autoimmunity
- 2016
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Ingår i: Science Signaling. - : American Association for the Advancement of Science (AAAS). - 1945-0877 .- 1937-9145. ; 9:448
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Tidskriftsartikel (refereegranskat)abstract
- Integrins are heterodimeric transmembrane proteins that play a fundamental role in the migration of leukocytes to sites of infection or injury. We found that protein tyrosine phosphatase nonreceptor type 22 (PTPN22) inhibits signaling by the integrin lymphocyte function-associated antigen-1 (LFA-1) in effector T cells. PTPN22 colocalized with its substrates at the leading edge of cells migrating on surfaces coated with the LFA-1 ligand intercellular adhesion molecule-1 (ICAM-1). Knockout or knockdown of PTPN22 or expression of the autoimmune disease-associated PTPN22-R620W variant resulted in the enhanced phosphorylation of signaling molecules downstream of integrins. Superresolution imaging revealed that PTPN22-R620 (wild-type PTPN22) was present as large clusters in unstimulated T cells and that these disaggregated upon stimulation of LFA-1, enabling increased association of PTPN22 with its binding partners at the leading edge. The failure of PTPN22-R620W molecules to be retained at the leading edge led to increased LFA-1 clustering and integrin-mediated cell adhesion. Our data define a previously uncharacterized mechanism for fine-tuning integrin signaling in T cells, as well as a paradigm of auto-immunity in humans in which disease susceptibility is underpinned by inherited phosphatase mutations that perturb integrin function. 2016
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| 5. |
- Edfors, Fredrik, 1988-, et al.
(författare)
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A recombinant protein standard resource for targeted proteomics
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Here, we have used a resource of 26,000 recombinant protein fragments to create custom libraries of standards for targeted proteomics based on parallel reaction monitoring (PRM). The recombinant fragments can be produced in a bacterial cell factory to generate heavy isotope labeled standards for absolute quantification of the corresponding protein targets and be used to produce high- quality spectral libraries. Altogether, coordinates for 25,684 unique proteotypic peptide assays have been experimentally defined covering 10,163 human proteins. The protocol allows for precise monitoring of digestion kinetics and thus enables to select peptides that behave quantitative during the sample preparation process. We show that the quantification tag of each recombinant protein fragment can be used for accurate retention time prediction and allows for assay standardization across different method parameters. The use of this resource was illustrated by determining the absolute concentrations of selected protein targets using multiplex targeted proteomics assays for determination of quantitative assessment of 49 protein targets in serum samples.
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| 6. |
- Edfors, Fredrik, et al.
(författare)
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Screening a Resource of Recombinant Protein Fragments for Targeted Proteomics
- 2019
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Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 18:7, s. 2706-2718
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Tidskriftsartikel (refereegranskat)abstract
- The availability of proteomics resources hosting protein and peptide standards, as well as the data describing their analytical performances, will continue to enhance our current capabilities to develop targeted proteomics methods for quantitative biology. This study describes the analysis of a resource of 26,840 individually purified recombinant protein fragments corresponding to more than 16,000 human protein-coding genes. The resource was screened to identify proteotypic peptides suitable for targeted proteomics efforts, and we report LC-MS/MS assay coordinates for more than 25,000 proteotypic peptides, corresponding to more than 10,000 unique proteins. Additionally, peptide formation and digestion kinetics were, for a subset of the standards, monitored using a time-course protocol involving parallel digestion of isotope-labeled recombinant protein standards and endogenous human plasma proteins. We show that the strategy by adding isotope-labeled recombinant proteins before trypsin digestion enables short digestion protocols (<= 60 min) with robust quantitative precision. In a proof-of-concept study, we quantified 23 proteins in human plasma using assay parameters defined in our study and used the standards to describe distinct clusters of individuals linked to different levels of LPA, APOE, SERPINAS, and TFRC. In summary, we describe the use and utility of a resource of recombinant proteins to identify proteotypic peptides useful for targeted proteomics assay development.
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| 9. |
- Göranson, Lizel, et al.
(författare)
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Decision-Making Within Forensic Psychiatric Investigations: The Use of Various Information Sources by Different Expert Groups to Reach Conclusions on Legal Insanity
- 2022
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Ingår i: Frontiers in Psychiatry. - : Frontiers Media SA. - 1664-0640. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Background: Which type of information experts use to make decisions regarding legal insanity within forensic psychiatric investigations (FPI) is relatively unknown, both in general and when considering variations due to case context. It is important to explore this area to be able to counteract the effects of various kinds of cognitive bias. Method: The aim was to explore whether FPI expert groups differed regarding case-specific as well as general use of information types required to make decisions on severe mental disorder (SMD). Three FPI case vignettes were presented to three professional groups involved in FPIs in Sweden (n = 41): forensic psychiatrists (n = 15), psychologists (n = 15), and social workers (n = 11). The participants reported which types of information they required to reach conclusions regarding SMD in each case. They also reported which types of information they had used within general FPI praxis during the previous year and the information types’ perceived usefulness. Results: The expert groups differed somewhat regarding what type of information they required for the cases (e.g., results from cognitive testing), but some information was required in all cases (e.g., client’s self-report). Regarding the preliminary assessment of SMD in the three cases, minor differences were found. Within the general FPI praxis, experts reported using several information types, while the general perceived usefulness of these sources varied. Discussion: The professional groups relied partly on a “core” of information sources, but some case-specific adaptations were found. The professional groups’ inclination to suspect SMD also varied somewhat. This indicates a need to explore the potential consequences of these similarities and differences.
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| 10. |
- Hagvall, Lina, 1978, et al.
(författare)
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Fragrance compound geraniol forms contact allergens on air exposure. Identification and quantification of oxidation products and effect on skin sensitization
- 2007
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Ingår i: Chemical Research in Toxicology. - : American Chemical Society (ACS). - 0893-228X .- 1520-5010. ; 20:5, s. 807-814
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Tidskriftsartikel (refereegranskat)abstract
- Fragrances are common causes of contact allergy. Geraniol (trans-3,7-dimethyl-2,6-octadiene-1-ol) is an important fragrance terpene. It is considered a weak contact allergen and is used for fragrance allergy screening among consecutive dermatitis patients. Analogous to other monoterpenes studied, such as limonene and linalool, geraniol has the potential to autoxidize on air exposure and form highly allergenic compounds. The aim of the present study was to investigate and propose a mechanism for the autoxidation of geraniol at room temperature. To investigate whether allergenic compounds are formed, the sensitizing potency of geraniol itself, air-exposed geraniol, and its oxidation products was determined using the local lymph node assay in mice. The results obtained show that the allylic alcohol geraniol follows an oxidation pattern different from those of linalool and limonene, which autoxidize forming hydroperoxides as the only primary oxidation products. The autoxidation of geraniol follows two paths, originating from allylic hydrogen abstraction near the two double bonds. From geraniol, hydrogen peroxide is primarily formed together with aldehydes geranial and neral from a hydroxyhydroperoxide. In addition, small amounts of a hydroperoxide are formed, analogous to the formation of the major linalool hydroperoxide. The autoxidation of geraniol greatly influenced the sensitizing effect of geraniol. The oxidized samples had moderate sensitizing capacity, quite different from that of pure geraniol. The hydroperoxide formed is believed to be the major contributor to allergenic activity, together with the aldehydes geranial and neral. On the basis of the present study and previous experience, we recommend that the possibility of autoxidation and the subsequent formation of contact allergenic oxidation products are considered in risk assessments performed on fragrance terpenes.
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