| 1. |
- Ahlén Bergman, Emma, et al.
(författare)
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Increased CD4+ T cell lineage commitment determined by CpG methylation correlates with better prognosis in urinary bladder cancer patients
- 2018
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Ingår i: Clinical Epigenetics. - : BMC. - 1868-7083 .- 1868-7075. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Urinary bladder cancer is a common malignancy worldwide. Environmental factors and chronic inflammation are correlated with the disease risk. Diagnosis is performed by transurethral resection of the bladder, and patients with muscle invasive disease preferably proceed to radical cystectomy, with or without neoadjuvant chemotherapy. The anti-tumour immune responses, known to be initiated in the tumour and draining lymph nodes, may play a major role in future treatment strategies. Thus, increasing the knowledge of tumour-associated immunological processes is important. Activated CD4+ T cells differentiate into four main separate lineages: Th1, Th2, Th17 and Treg, and they are recognized by their effector molecules IFN-γ, IL-13, IL-17A, and the transcription factor Foxp3, respectively. We have previously demonstrated signature CpG sites predictive for lineage commitment of these four major CD4+ T cell lineages. Here, we investigate the lineage commitment specifically in tumour, lymph nodes and blood and relate them to the disease stage and response to neoadjuvant chemotherapy.RESULTS: Blood, tumour and regional lymph nodes were obtained from patients at time of transurethral resection of the bladder and at radical cystectomy. Tumour-infiltrating CD4+ lymphocytes were significantly hypomethylated in all four investigated lineage loci compared to CD4+ lymphocytes in lymph nodes and blood (lymph nodes vs tumour-infiltrating lymphocytes: IFNG -4229 bp p < 0.0001, IL13 -11 bp p < 0.05, IL17A -122 bp p < 0.01 and FOXP3 -77 bp p > 0.05). Examination of individual lymph nodes displayed different methylation signatures, suggesting possible correlation with future survival. More advanced post-cystectomy tumour stages correlated significantly with increased methylation at the IFNG -4229 bp locus. Patients with complete response to neoadjuvant chemotherapy displayed significant hypomethylation in CD4+ T cells for all four investigated loci, most prominently in IFNG p < 0.0001. Neoadjuvant chemotherapy seemed to result in a relocation of Th1-committed CD4+ T cells from blood, presumably to the tumour, indicated by shifts in the methylation patterns, whereas no such shifts were seen for lineages corresponding to IL13, IL17A and FOXP3.CONCLUSION: Increased lineage commitment in CD4+ T cells, as determined by demethylation in predictive CpG sites, is associated with lower post-cystectomy tumour stage, complete response to neoadjuvant chemotherapy and overall better outcome, suggesting epigenetic profiling of CD4+ T cell lineages as a useful readout for clinical staging.
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| 2. |
- Asad, Samina, et al.
(författare)
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HTR1A a Novel Type 1 Diabetes Susceptibility Gene on Chromosome 5p13-q13
- 2012
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Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 7:5
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Tidskriftsartikel (refereegranskat)abstract
- Background: We have previously performed a genome-wide linkage study in Scandinavian Type 1 diabetes (T1D) families. In the Swedish families, we detected suggestive linkage (LOD less than= 2.2) to the chromosome 5p13-q13 region. The aim of our study was to investigate the linked region in search for possible T1D susceptibility genes. Methodology/Principal Findings: Microsatellites were genotyped in the Scandinavian families to fine-map the previously linked region. Further, SNPs were genotyped in Swedish and Danish families as well as Swedish sporadic cases. In the Swedish families we detected genome-wide significant linkage to the 5-hydroxytryptamine receptor 1A (HTR1A) gene (LOD 3.98, pless than9.8x10(-6)). Markers tagging two separate genes; the ring finger protein 180 (RNF180) and HTR1A showed association to T1D in the Swedish and Danish families (pless than0.002, pless than0.001 respectively). The association was not confirmed in sporadic cases. Conditional analysis indicates that the primary association was to HTR1A. Quantitative PCR show that transcripts of both HTR1A and RNF180 are present in human islets of Langerhans. Moreover, immunohistochemical analysis confirmed the presence of the 5-HTR1A protein in isolated human islets of Langerhans as well as in sections of human pancreas. Conclusions: We have identified and confirmed the association of both HTR1A and RFN180, two genes in high linkage disequilibrium (LD) to T1D in two separate family materials. As both HTR1A and RFN180 were expressed at the mRNA level and HTR1A as protein in human islets of Langerhans, we suggest that HTR1A may affect T1D susceptibility by modulating the initial autoimmune attack or either islet regeneration, insulin release, or both.
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| 3. |
- Engström, Gunnar, et al.
(författare)
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The Swedish CArdioPulmonary BioImage Study : objectives and design
- 2015
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 278:6, s. 645-659
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Tidskriftsartikel (refereegranskat)abstract
- Cardiopulmonary diseases are major causes of death worldwide, but currently recommended strategies for diagnosis and prevention may be outdated because of recent changes in risk factor patterns. The Swedish CArdioPulmonarybioImage Study (SCAPIS) combines the use of new imaging technologies, advances in large-scale 'omics' and epidemiological analyses to extensively characterize a Swedish cohort of 30 000 men and women aged between 50 and 64 years. The information obtained will be used to improve risk prediction of cardiopulmonary diseases and optimize the ability to study disease mechanisms. A comprehensive pilot study in 1111 individuals, which was completed in 2012, demonstrated the feasibility and financial and ethical consequences of SCAPIS. Recruitment to the national, multicentre study has recently started.
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| 4. |
- Hansson, Anna, et al.
(författare)
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Characteristics, complications, and a comparison between early and late tracheostomy: A retrospective observational study on tracheostomy in patients with COVID‐19‐related acute respiratory distress syndrome
- 2022
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Ingår i: Health Science Reports. - Hoboken, NJ, United States : John Wiley & Sons. - 2398-8835. ; 5:3
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Tidskriftsartikel (refereegranskat)abstract
- Background and AimsAs the coronavirus disease 2019 (COVID-19) pandemic spread worldwide in 2020, the number of patients requiring intensive care and invasive mechanical ventilation (IMV) has increased rapidly. During the pandemic, early recommendations suggested that tracheostomy should be postponed, as the potential benefits were not certain to exceed the risk of viral transmission to healthcare workers. The aim of this study was to assess the utility of tracheostomy in patients with COVID-19-related acute respiratory distress syndrome, in terms of patient and clinical characteristics, outcomes, and complications, by comparing between early and late tracheostomy.MethodsA multicenter, retrospective observational study was conducted in Jönköping County, Sweden. Between 14 March 2020 and 13 March 2021, 117 patients were included. All patients ≥18 years of age with confirmed COVID-19, who underwent tracheostomy were divided into two groups based on the timing of the procedure (≤/>7 days). Outcomes including the time on IMV, intensive care unit (ICU) length of stay, and mortality 30 days after ICU admission, as well as complications due to tracheostomy were compared between the groups.ResultsEarly tracheostomy (<7 days, n = 56) was associated with a shorter median duration of mechanical ventilation (7 [12], p = 0.001) as well as a shorter median ICU stay (8 [14], p = 0.001). The most frequent complication of tracheostomy was minor bleeding. With the exception of a higher rate of obesity in the group receiving late tracheostomy, the patient characteristics were similar between the groups.ConclusionThis study showed that early tracheostomy was safe and associated with a shorter time on IMV as well as a shorter ICU length of stay, implicating possible clinical benefits in critically ill COVID-19 patients. However, it is necessary to verify these findings in a randomized controlled trial.
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| 5. |
- Norin, Stefan, et al.
(författare)
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Severe infusion-related reactions are uncommon in rituximab-treated CLL patients in clinical practice: Results from a Swedish national observational study
- 2015
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Ingår i: Leukemia Research. - : Elsevier. - 0145-2126 .- 1873-5835. ; 39:1, s. 33-37
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Tidskriftsartikel (refereegranskat)abstract
- There have been concerns about serious infusion-related adverse drug reactions (ADR) with rituximabin chronic lymphocytic leukemia (CLL). We therefore conducted an observational trial in which CLL patients planned for rituximab-containing therapy were eligible. Ninety-six patients from 19 centers were enrolled. The most common regimen was rituximab, fludarabine and cyclophosphamide. Fifty-six patients experienced ADR during rituximab infusion. Reactions greater than= grade 3 occurred in five patients and no cases of tumor lysis syndrome were recorded. Despite a high number of circulating tumor cells few severe ADR were noted. Thus, rituximab containing regimens can be considered safe for CLL patients in general practice.
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| 6. |
- Sylvan, Sandra Eketorp, et al.
(författare)
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First-line therapy in chronic lymphocytic leukemia : a Swedish nation-wide real-world study on 1053 consecutive patients treated between 2007 and 2013
- 2019
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Ingår i: Haematologica. - : FERRATA STORTI FOUNDATION. - 0390-6078 .- 1592-8721. ; 104:4, s. 797-805
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to investigate long-term outcome following first-line therapy in consecutive chronic lymphocytic leukemia (CLL) patients in a well-defined geographic area: Sweden. All patients diagnosed with CLL (2007-2013) (n=3672) were identified from national registries, screening of patient files identified all (100%) treated first line (n=1053) and for those, an in-depth analysis was performed. End points were overall response rate, progression-free survival (PFS), overall survival (OS), and safety. Median age was 71 years; 53% had Rai stage III-IV and 97% had performance status grade 0-2. Fluorescence in situ hybridization (FISH) was performed in 57% of patients: 15% had del(17p). Chlorambucil + prednisone was used in 39% (5% also received rituximab). Fludarabine+cyclophosphamide+rituximab or fludarabine+cyclophosphamide was used in 43% and bendamustine + rituximab in 6%. Overall response rate was 64%; chlorambucil 43%, fludarabine+cyclophosphamide+rituximab 84%, fludarabine+cyclophosphamide 75% and bendamustine + rituximab 75%. Median PFS and OS was 24 and 58 months, respectively, both were significantly associated (multivariate analysis) with type of treatment, del(17p), performance status, gender, age and geographical region (OS only). Chlorambucil-treated patients had a median PFS and OS of only 9 and 33 months, respectively. Chlorambucil usage declined gradually throughout the study period, but one-third of patients still received chlorambucil + rituximab in 2013. Infections >= grade III were significantly associated with treatment; chlorambucil 19% versus fludarabine+cyclophosphamide+rituximab 30%. Richter transformation occurred in 5.5% of the patients, equally distributed across therapies. This is the largest retrospective, real-world cohort of consecutive first-line treated CLL patients with a complete follow up. In elderly patients, an unmet need for more effective, well-tolerated therapies was identified.
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| 7. |
- Wibeck, Victoria, et al.
(författare)
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Policy brief on climate engineering
- 2016
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Climate engineering (geoengineering) has been widely discussed as a potential instrument for curbing global warming if politics fails to deliver green house gas emission reductions. This debate has lost momentum over the last couple of years, but is now being renewed in the wake of the December 2015 Paris climate change agreement. Resurgent interest primarily stems from two elements of the Paris agreement. First, by defining the long term goal as “achiev[ing] a balance between anthropogenic emissions by sources and removals by sinks of greenhouse gases” instead of decarbonization, the agreement can be interpreted as providing leeway for climate engineering proposals. Second, the agreement formulated a temperature goal of “well below 2°C above pre-industrial levels and pursuing efforts to limit the temperature increase to 1.5°C”. In response, several scientists argued that these goals may require climate engineering.As these discussions will affect the forthcoming review of pathways toward 1.5°C warming, this policy brief takes stock of climate engineering. It draws on the expertise of Linköping University’s Climate Engineering (LUCE) interdisciplinary research programme. The brief provides an overview of the status of academic debate on climate engineering regarding bioenergy with carbon capture and storage (BECCS); stratospheric aerosol injection; and mass media reporting and public engagement.
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