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Sökning: WFRF:(Marsal L)

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1.
  • Kanai, M, et al. (författare)
  • 2023
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  • Niemi, MEK, et al. (författare)
  • 2021
  • swepub:Mat__t
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  • Blokland, G. A. M., et al. (författare)
  • Sex-Dependent Shared and Nonshared Genetic Architecture Across Mood and Psychotic Disorders
  • 2022
  • Ingår i: Biological Psychiatry. - : Elsevier BV. - 0006-3223 .- 1873-2402. ; 91:1, s. 102-117
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Sex differences in incidence and/or presentation of schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BIP) are pervasive. Previous evidence for shared genetic risk and sex differences in brain abnormalities across disorders suggest possible shared sex-dependent genetic risk. Methods: We conducted the largest to date genome-wide genotype-by-sex (G×S) interaction of risk for these disorders using 85,735 cases (33,403 SCZ, 19,924 BIP, and 32,408 MDD) and 109,946 controls from the PGC (Psychiatric Genomics Consortium) and iPSYCH. Results: Across disorders, genome-wide significant single nucleotide polymorphism–by-sex interaction was detected for a locus encompassing NKAIN2 (rs117780815, p = 3.2 × 10−8), which interacts with sodium/potassium-transporting ATPase (adenosine triphosphatase) enzymes, implicating neuronal excitability. Three additional loci showed evidence (p < 1 × 10−6) for cross-disorder G×S interaction (rs7302529, p = 1.6 × 10−7; rs73033497, p = 8.8 × 10−7; rs7914279, p = 6.4 × 10−7), implicating various functions. Gene-based analyses identified G×S interaction across disorders (p = 8.97 × 10−7) with transcriptional inhibitor SLTM. Most significant in SCZ was a MOCOS gene locus (rs11665282, p = 1.5 × 10−7), implicating vascular endothelial cells. Secondary analysis of the PGC-SCZ dataset detected an interaction (rs13265509, p = 1.1 × 10−7) in a locus containing IDO2, a kynurenine pathway enzyme with immunoregulatory functions implicated in SCZ, BIP, and MDD. Pathway enrichment analysis detected significant G×S interaction of genes regulating vascular endothelial growth factor receptor signaling in MDD (false discovery rate-corrected p < .05). Conclusions: In the largest genome-wide G×S analysis of mood and psychotic disorders to date, there was substantial genetic overlap between the sexes. However, significant sex-dependent effects were enriched for genes related to neuronal development and immune and vascular functions across and within SCZ, BIP, and MDD at the variant, gene, and pathway levels. © 2021 Society of Biological Psychiatry
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  • Munn-Chernoff, M. A., et al. (författare)
  • Shared genetic risk between eating disorder- and substance-use-related phenotypes: Evidence from genome-wide association studies
  • 2021
  • Ingår i: Addiction Biology. - : Wiley. - 1355-6215 .- 1369-1600. ; 26:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Eating disorders and substance use disorders frequently co-occur. Twin studies reveal shared genetic variance between liabilities to eating disorders and substance use, with the strongest associations between symptoms of bulimia nervosa and problem alcohol use (genetic correlation [r(g)], twin-based = 0.23-0.53). We estimated the genetic correlation between eating disorder and substance use and disorder phenotypes using data from genome-wide association studies (GWAS). Four eating disorder phenotypes (anorexia nervosa [AN], AN with binge eating, AN without binge eating, and a bulimia nervosa factor score), and eight substance-use-related phenotypes (drinks per week, alcohol use disorder [AUD], smoking initiation, current smoking, cigarettes per day, nicotine dependence, cannabis initiation, and cannabis use disorder) from eight studies were included. Significant genetic correlations were adjusted for variants associated with major depressive disorder and schizophrenia. Total study sample sizes per phenotype ranged from similar to 2400 to similar to 537 000 individuals. We used linkage disequilibrium score regression to calculate single nucleotide polymorphism-based genetic correlations between eating disorder- and substance-use-related phenotypes. Significant positive genetic associations emerged between AUD and AN (r(g) = 0.18; false discovery rate q = 0.0006), cannabis initiation and AN (r(g) = 0.23; q < 0.0001), and cannabis initiation and AN with binge eating (r(g) = 0.27; q = 0.0016). Conversely, significant negative genetic correlations were observed between three nondiagnostic smoking phenotypes (smoking initiation, current smoking, and cigarettes per day) and AN without binge eating (r(gs) = -0.19 to -0.23; qs < 0.04). The genetic correlation between AUD and AN was no longer significant after co-varying for major depressive disorder loci. The patterns of association between eating disorder- and substance-use-related phenotypes highlights the potentially complex and substance-specific relationships among these behaviors.
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  • Bryois, J., et al. (författare)
  • Genetic identification of cell types underlying brain complex traits yields insights into the etiology of Parkinson’s disease
  • 2020
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 52:5, s. 482-493
  • Tidskriftsartikel (refereegranskat)abstract
    • Genome-wide association studies have discovered hundreds of loci associated with complex brain disorders, but it remains unclear in which cell types these loci are active. Here we integrate genome-wide association study results with single-cell transcriptomic data from the entire mouse nervous system to systematically identify cell types underlying brain complex traits. We show that psychiatric disorders are predominantly associated with projecting excitatory and inhibitory neurons. Neurological diseases were associated with different cell types, which is consistent with other lines of evidence. Notably, Parkinson’s disease was genetically associated not only with cholinergic and monoaminergic neurons (which include dopaminergic neurons) but also with enteric neurons and oligodendrocytes. Using post-mortem brain transcriptomic data, we confirmed alterations in these cells, even at the earliest stages of disease progression. Our study provides an important framework for understanding the cellular basis of complex brain maladies, and reveals an unexpected role of oligodendrocytes in Parkinson’s disease. © 2020, The Author(s), under exclusive licence to Springer Nature America, Inc.
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  • 2019
  • Tidskriftsartikel (refereegranskat)
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  • Watson, H. J., et al. (författare)
  • Genome-wide association study identifies eight risk loci and implicates metabo-psychiatric origins for anorexia nervosa
  • 2019
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 51:8
  • Tidskriftsartikel (refereegranskat)abstract
    • Characterized primarily by a low body-mass index, anorexia nervosa is a complex and serious illness(1), affecting 0.9-4% of women and 0.3% of men(2-4), with twin-based heritability estimates of 50-60%(5). Mortality rates are higher than those in other psychiatric disorders(6), and outcomes are unacceptably poor(7). Here we combine data from the Anorexia Nervosa Genetics Initiative (ANGI)(8,9) and the Eating Disorders Working Group of the Psychiatric Genomics Consortium (PGC-ED) and conduct a genome-wide association study of 16,992 cases of anorexia nervosa and 55,525 controls, identifying eight significant loci. The genetic architecture of anorexia nervosa mirrors its clinical presentation, showing significant genetic correlations with psychiatric disorders, physical activity, and metabolic (including glycemic), lipid and anthropometric traits, independent of the effects of common variants associated with body-mass index. These results further encourage a reconceptualization of anorexia nervosa as a metabo-psychiatric disorder. Elucidating the metabolic component is a critical direction for future research, and paying attention to both psychiatric and metabolic components may be key to improving outcomes.
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  • Watson, Hunna J., et al. (författare)
  • Common Genetic Variation and Age of Onset of Anorexia Nervosa
  • 2022
  • Ingår i: BIOLOGICAL PSYCHIATRY: GLOBAL OPEN SCIENCE. - : Elsevier BV. - 2667-1743. ; 2:4, s. 368-378
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Genetics and biology may influence the age of onset of anorexia nervosa (AN). The aims of this study were to determine whether common genetic variation contributes to age of onset of AN and to investigate the genetic associations between age of onset of AN and age at menarche.METHODS: A secondary analysis of the Psychiatric Genomics Consortium genome-wide association study (GWAS) of AN was performed, which included 9335 cases and 31,981 screened controls, all from European ancestries. We conducted GWASs of age of onset, early-onset AN (,13 years), and typical-onset AN, and genetic correlation, genetic risk score, and Mendelian randomization analyses.RESULTS: Two loci were genome-wide significant in the typical-onset AN GWAS. Heritability estimates (single nucleotide polymorphism-h2) were 0.01-0.04 for age of onset, 0.16-0.25 for early-onset AN, and 0.17-0.25 for typical-onset AN. Early-and typical-onset AN showed distinct genetic correlation patterns with putative risk factors for AN. Specifically, early-onset AN was significantly genetically correlated with younger age at menarche, and typical-onset AN was significantly negatively genetically correlated with anthropometric traits. Genetic risk scores for age of onset and early-onset AN estimated from independent GWASs significantly predicted age of onset. Mendelian randomization analysis suggested a causal link between younger age at menarche and early -onset AN.CONCLUSIONS: Our results provide evidence consistent with a common variant genetic basis for age of onset and implicate biological pathways regulating menarche and reproduction.
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  • Hobbins, John C., et al. (författare)
  • Antibiotic prophylaxis before amniocentesis
  • 2011
  • Ingår i: Prenatal Diagnosis. - : Wiley. - 1097-0223 .- 0197-3851. ; 31:12, s. 1213-1214
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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  • Linder, L, et al. (författare)
  • Clinical aspects of osseointegration in joint replacement. A histological study of titanium implants
  • 1988
  • Ingår i: Journal of Bone and Joint Surgery: British Volume. - 2044-5377. ; 70-B:4, s. 550-555
  • Tidskriftsartikel (refereegranskat)abstract
    • In an experimental clinical study, 25 implants of pure titanium were inserted into the proximal tibia of 11 volunteer patients, four with rheumatoid arthritis and seven with osteoarthritis. The implants were removed from five weeks to 24 months later and detailed histological analysis was performed. The implants generally healed with direct bone-metal contact, showing so-called osseointegration. Only one of the 21 implants which had been in place for over five months did not show osseointegration, probably because of inadequate primary contact with bone. The presence of rheumatoid disease did not prevent osseointegration, but accompanying osteoporosis seemed to be a risk factor.
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  • Ayres-de-Campos, D, et al. (författare)
  • Can the reproducibility of fetal heart rate baseline estimation be improved?
  • 2004
  • Ingår i: European Journal of Obstetrics, Gynecology, and Reproductive Biology. - 0301-2115. ; 112:1, s. 49-54
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To evaluate the reproducibility of fetal heart rate (FHR) baseline estimation according to an objective and detailed definition presented in this article, by comparison with the FIGO guidelines' definition. Study design: Three hundred consecutively acquired FHR tracings, 150 from antepartum high-risk pregnancies and 150 from unselected intrapartum cases, were presented to nine experienced clinicians included in three different groups, for an estimation of the FHR baseline. The first group consisted of clinicians using the proposed definition, without previous training in its use. The second group consisted of clinicians using the proposed definition, where a previous training session was promoted. The third group consisted of clinicians using the FIGO guidelines' definition. Agreement in baseline estimation was evaluated using the kappa statistic, the proportions of agreement and the intra-class correlation coefficient. Results: Using the baseline definition proposed in this article, agreement was significantly higher in the group with prior training in its use. This group also showed a trend towards a higher agreement than the one using the FIGO guidelines. Conclusion: The FHR baseline definition proposed in this article provides an extremely reproducible estimation when associated with prior training in its use.
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  • Bergström, Ulf, et al. (författare)
  • Lower disease activity and disability in Swedish patients with rheumatoid arthritis in 1995 compared with 1978
  • 1999
  • Ingår i: Scandinavian Journal of Rheumatology. - 1502-7732. ; 28, s. 160-165
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of this study was to evaluate differences in disease activity, disability, and medical treatment in consecutive patients with rheumatoid arthritis seen at the outpatient clinics in Malmö, in 1978 (n=148) and 1995 (n=164). The groups were similar with regard to age, gender, disease duration, and the proportion having had hip or knee replacement surgery. The patients in 1995 had lower values for CRP (p<0.001), Ritchie Articular Index (mean values: 5.5 vs. 9.9, p<0.001), and Steinbrocker functional class index (mean values: 1.96 vs. 2.16, p<0.001) than the 1978 group. The 1995 patient group was also more extensively treated with DMARD:s (68 vs. 51%, p<0.01) and glucocorticosteroids (23 vs. 12%, p<0.02) and had historically been treated with almost twice as many DMARD:s (2.7 vs. 1.5, p<0.001). Similar findings regarding disease activity and disability were made when restricting the analysis to subgroups of patients that were seropositive or had a shorter disease duration (<5 yrs). The lower disease severity in the 1995 group may be secondary to a more active medical treatment, although other possibilities such as differences in selection and secular changes in disease severity unrelated to medication cannot be excluded.
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  • Granqvist, Claes Göran, et al. (författare)
  • Electrochromic foil-based devices : Optical transmittance and modulation range, effect of ultravioled irradiation, and quality assessment by 1/f current noise
  • 2008
  • Ingår i: Thin Solid Films. - : Elsevier BV. - 0040-6090 .- 1879-2731. ; 516:17, s. 5921-5926
  • Tidskriftsartikel (refereegranskat)abstract
    • We introduce electrochromic (EC) technology for modulating the transmittance of visible light and solar radiation in window apertures, with focus on recent work on foil-type devices embodying sputter deposited WO3 and NiO films joined by a polymer electrolyte. The purpose of this paper is to present a number of new and preliminary results showing that (i) double-sided antireflection coatings based on dip coating can enhance the transmittance significantly, (ii) tandem foils can yield a ratio between bleached-state and colored-state transmittance exceeding fifty, (iii) solar irradiance onto the EC device can enhance its charge insertion dynamics and thereby its optical modulation, and (iv) electromagnetic noise spectroscopy may serve as quality assessment of EC devices.
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  • Holmkvist, Petra, et al. (författare)
  • A major population of mucosal memory CD4(+) T cells, coexpressing IL-18Rα and DR3, display innate lymphocyte functionality.
  • 2015
  • Ingår i: Mucosal Immunology. - : Elsevier BV. - 1933-0219. ; 8:3, s. 545-558
  • Tidskriftsartikel (refereegranskat)abstract
    • Mucosal tissues contain large numbers of memory CD4(+) T cells that, through T-cell receptor-dependent interactions with antigen-presenting cells, are believed to have a key role in barrier defense and maintenance of tissue integrity. Here we identify a major subset of memory CD4(+) T cells at barrier surfaces that coexpress interleukin-18 receptor alpha (IL-18Rα) and death receptor-3 (DR3), and display innate lymphocyte functionality. The cytokines IL-15 or the DR3 ligand tumor necrosis factor (TNF)-like cytokine 1A (TL1a) induced memory IL-18Rα(+)DR3(+)CD4(+) T cells to produce interferon-γ, TNF-α, IL-6, IL-5, IL-13, granulocyte-macrophage colony-stimulating factor (GM-CSF), and IL-22 in the presence of IL-12/IL-18. TL1a synergized with IL-15 to enhance this response, while suppressing IL-15-induced IL-10 production. TL1a- and IL-15-mediated cytokine induction required the presence of IL-18, whereas induction of IL-5, IL-13, GM-CSF, and IL-22 was IL-12 independent. IL-18Rα(+)DR3(+)CD4(+) T cells with similar functionality were present in human skin, nasal polyps, and, in particular, the intestine, where in chronic inflammation they localized with IL-18-producing cells in lymphoid aggregates. Collectively, these results suggest that human memory IL-18Rα(+)DR3(+) CD4(+) T cells may contribute to antigen-independent innate responses at barrier surfaces.Mucosal Immunology advance online publication, 1 October 2014; doi:10.1038/mi.2014.87.
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  • Jacobsson, Lennart, et al. (författare)
  • Rheumatoid arthritis: what does it cost and what factors are driving those costs? Results of a survey in a community-derived population in Malmo, Sweden
  • 2007
  • Ingår i: Scandinavian Journal of Rheumatology. - : Informa UK Limited. - 1502-7732 .- 0300-9742. ; 36:3, s. 179-183
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: We sought to investigate the cost of living with rheumatoid arthritis (RA) and evaluate the influence of both demographics and specific disease characteristics on these costs. Methods: We used a population-based questionnaire to survey 895 patients living in the city of Malmo, Sweden, during 2002. Data were obtained on direct resource consumption, investments, informal care and work capacity, as well as utility, function and patients' assessment of disease severity and pain. Results: The survey was completed by 613 patients (68%). Their mean age was 66 years, 74% were female and the mean duration of disease was 16.7 years. The total mean annual cost per patient was 108 370 SEK (12 020 EUR). Direct costs represented 41% of that amount and were predominantly for drugs [141% of the participants were receiving treatment with tumour necrosis factor (TNF) blockers], community services and hospitalisation. Function measured with the Health Assessment Questionnaire (HAQ) was the main statistical predictor for all types of costs except sick leave, which was most strongly associated with patients' perception of global health. Conclusion: This is the first study in Sweden to include all costs incurred by a group representative of RA in the community. In comparison with previous studies, total costs had increased by more than 40%. Furthermore, direct costs were higher and constituted a great proportion of total costs because of more intensive treatments (i.e. the use of TNF blockers). Future comparisons will enable health economic evaluations on a community level.
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  • Jakobsson, Fredrik L. E., 1974-, et al. (författare)
  • Tuning the energy levels of photochromic diarylethene compounds for optoelectronic switch devices
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • Photochromic diarylethene molecules (PC) is investigated for use in opticalwrite/electrical read memory applications. The frontier energy levels and dipolemoment is calculated using density functional theory. Good agreement is foundbetween calculated electronic structure and measured ultraviolet photoelectronspectra. The changes in frontier energy levels and dipole moment are scrutinizedupon two different approaches for chemical modification: (i) adding substituentsto the ethylene bridge; or (ii) changing the chemical nature of the aryl rings.Through the chemical modification the frontier energy levels can be tuned bymore than 2 eV. The calculated molecular properties are used in charge transportmodels to predict the behavior of devices based on these molecules. By using thePC in combination with an organic semiconductor (in bilayer or blend) goodswitching behavior can be achieved in a device. The switch effect is predicted tobe mainly due to switch in frontier energy levels rather than switch of dipolemoment. This is concluded since the dipole moment is either too small (< 5 D) orthe switch effect to small (less than a factor of two).
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  • Nyberg, L., et al. (författare)
  • Observational study of tofacitinib in ulcerative colitis in Sweden (ODEN) - Interim analysis of clinical and biomarker data
  • 2024
  • Ingår i: Journal of Crohn's & Colitis. - : Oxford University Press. - 1873-9946 .- 1876-4479. ; 18:Suppl. 1, s. I1703-I1704
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Background: Tofacitinib is a Janus kinase (JAK) inhibitor for the treatment of moderate to severe ulcerative colitis (UC). ODEN is an ongoing Swedish multicentre prospective observational study regarding effectiveness of tofacitinib in UC. In this interim analysis, we aimed to assess the clinical outcomes during the first 16 weeks.Methods: Patients with active UC were enrolled 2020-2023 when starting tofacitinib as per clinical indication. Inclusion criteria were fecal (F) calprotectin >250 mg/kg or Mayo endoscopic score ≥2. Data were collected using an electronic case report form linked to the Swedish National Quality Registry for Inflammatory Bowel Disease (SWIBREG). Data concerning inflammatory markers, endoscopic activity, partial (p) Mayo, extra intestinal manifestations, health-related quality of life measures, corticosteroid use, and colectomy rates were collected regardless of tofacitinib discontinuation. Information collected at week 8 and 16 is presented here. Intention-to-treat (ITT) analysis was applied and tofacitinib discontinuation was considered as treatment failure (i.e., no tofacitinib-induced clinical or laboratory response or remission). McNemar’s test was used for proportion differences.Results: The proportion of patients who previously had failed at least one biologic was 95% and at least two biologics, 62%. At inclusion, median p-Mayo was 5 and 39% of patients were on corticosteroids (Table 1a). Patients’ survival on drug is shown in Figure 1a. At week 8 and 16, 42% and 43%, respectively, achieved corticosteroid free clinical remission, Figure 1b. A 50% reduction in F-calprotectin was seen in 54% and 49% at week 8 and 16, respectively. The endpoint of Mayo endoscopic score 0 and/or F-calprotectin <100 mg/kg was achieved by 30% and 38% at week 8 and 16, respectively. Arthralgia frequency decreased significantly from baseline from 29% at inclusion to 13% and 11% at week 8 and 16 respectively. Three patients underwent colectomy the first 16 weeks (Table 1b).Conclusion: After 16 weeks of treatment with tofacitinib, a substantial proportion of previously treatment refractory UC patients were in clinical and endoscopic corticosteroid-free remission, and a distinct improvement in F-calprotectin levels was observed. In addition, a significant reduction in arthralgia was noted.
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  • Nyberg, L., et al. (författare)
  • Observational study of tofacitinib in Ulcerative Colitis in Sweden (ODEN) - Interim analysis of health-related quality of life and fatigue
  • 2024
  • Ingår i: Journal of Crohn's & Colitis. - : Oxford University Press. - 1873-9946 .- 1876-4479. ; 18:Suppl. 1, s. I1887-I1889
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Background: Ulcerative colitis (UC) has a major impact on daily life. The Janus Kinas (JAK) inhibitor tofacitinib is effective in achieving remission in UC, but prospective real-world evidence concerning the effect on health-related quality of life (HRQoL) and fatigue are still scarce. Fatigue is a component of UC that is notoriously difficult to treat and not unambiguously related to inflammatory activity. ODEN is an ongoing Swedish multicentre prospective observational study of tofacitinib in UC. In this interim analysis, we assessed the effectiveness on HRQoL and fatigue during the first 16 weeks.Methods: Patients with UC and active inflammation were enrolled 2020-2023 when starting tofacitinib as per clinical indication. To measure various aspects of impairment of daily life, the validated questionnaires Short Health Scale (SHS), EQ-5D-5L [Swedish value set], and IBD-fatigue scale (IBD-F) were used. These data and information concerning clinical, biochemical, and endoscopic outcomes were collected in an e-CRF linked to the Swedish National Quality Registry for Inflammatory Bowel Disease (SWIBREG). For HRQoL outcomes, per protocol analysis was applied. Paired t-test and Wilcoxon’s signed-rank test were used for mean and median differences, respectively.Results: In total, 103 patients were included. Baseline data are shown in Table 1a. For patients still on tofacitinib treatment, all four dimensions of the SHS (symptoms, social function, disease related worry, and general well-being) improved significantly, Table 1b. A median decrease of one point from baseline was seen at week 8 in each of the parameters, which was maintained through week 16 with a tendency towards further improvement. EQ-5D-5L showed an impairment mainly in the aspects of pain/discomfort and ability to participate in common daily activities. Improvement in these dimensions was seen from baseline to week 16. The overall EQ-5D-5L index improved significantly from baseline (0.80) to week 8 (0.86) and week 16 (0.89), as did the EQ VAS 0-100 reflecting overall health (58, 71, and 74, respectively). A significant improvement in IBD-F part 1 and 2 was seen at week 8 and 16, Figure 1.Conclusion: This study demonstrates that tofacitinib treatment covariates with positive changes in a variety of measures of patients’ quality of life, including improvements in self-assessed overall wellbeing. Finally, fatigue significantly improved during tofacitinib treatment. Thus, tofacitinib treatment shows association with meaningful improvements in multiple aspects of quality of life during the first 16 weeks of treatment.
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  • Pehlivan, Ilknur Bayrak, et al. (författare)
  • Electrochromic Devices with Polymer Electrolytes Functionalized by SiO2 and In2O3:Sn Nanoparticles : Rapid Coloring/Bleaching Dynamics and Strong Near-Infrared Absorption
  • 2014
  • Ingår i: Solar Energy Materials and Solar Cells. - : Elsevier BV. - 0927-0248 .- 1879-3398. ; 126, s. 241-247
  • Tidskriftsartikel (refereegranskat)abstract
    • We studied the optical properties and coloring/bleaching dynamics of electrochromic devices based on tungsten oxide and nickel oxide and incorporating polymer electrolytes functionalized by adding about one percent of nanoparticles of SiO2 (fumed silica) or In2O3:Sn. SiO2 improved the coloring/bleaching dynamics and In2O3:Sn quenched the near-infrared transmittance. Both of these effects can be important in electrochromic smart windows, and our results point at the advantage of a polymer laminated construction over a monolithic one.
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  • Salomon, Benita, 1993-, et al. (författare)
  • Prognostic potential of mucosal proteins in Ulcerative Colitis
  • 2024
  • Ingår i: Journal of Crohn's & Colitis. - : Oxford University Press. - 1873-9946 .- 1876-4479. ; 18:Suppl. 1, s. I544-I545
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Background: Better prognostic measures for ulcerative colitis (UC) could significantly advance patient care. While the prognostic capacity of circulating proteins in UC has been explored, the role of mucosal proteins remains largely unknown. We examined mucosal protein markers in patients with incident ulcerative colitis and evaluated their prognostic value.Methods: Biopsies from macroscopically inflamed colonic/rectal mucosa of adult patients in the Swedish inception cohort of IBD (SIC IBD) were obtained at diagnosis of UC. Patients were followed prospectively, and clinical data were recorded after 3 and 12 months. Disease course was categorised as indolent or aggressive at 12 months, based on a composite outcome of colectomy, hospital admission for active disease, treatment refractoriness towards ≥2 biological agents; the use of >2 courses of corticosteroids, or a cumulative dose of >2.5 g. Relative estimates of 162 protein markers were assessed in homogenised tissue supernatants, using proximity extension assay technology (Olink Proteomics, Uppsala, Inflammation and Oncology II panel). Mann-Whitney U test, with Benjamini-Hochberg correction was used to identify differentially regulated mucosal proteins in aggressive vs indolent disease course, with a 5% false discovery rate (FDR). Smoothly clipped absolute deviation regularised logistic regression models were used to identify prognostic signatures distinguishing aggressive from indolent disease course. Performance was estimated in a leave-one-out cross-validation and reported as the area under the receiver operating characteristic (ROC) curve (AUC).Results: 117 patients provided a macroscopically inflamed colonic/rectal biopsy at diagnosis of UC. Basic demographics and clinical characteristics are presented in Table 1. Relative protein levels of WFdc2 and CCL20 were significantly lower in lysates from patients developing an aggressive course vs patients developing an indolent course, while estimates of MMP1, CCL11, WISP-1, OPG, RSPO3 and VEGFR2 were higher (Figure 1A). Regularized logistic regression identified signatures restricted to 28 proteins, distinguishing aggressive from indolent UC courses, yielding an AUC of 0.68 (95% confidence interval (CI): 0.56-0.80) for left-out samples (Figure 1B). Incorporating extent of inflammation at diagnosis in the model improved the AUC to 0.71 (95% CI: 0.60-0.83).Conclusion: We identified prognostic mucosal protein signatures associated with future course of ulcerative colitis by analysing inflamed mucosal biopsies that were obtained at diagnosis. These protein markers may highlight pathways of relevance for ulcerative colitis outcomes.
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