| 1. |
- Moberg, Christina, et al.
(författare)
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De unga gör helt rätt när de stämmer staten
- 2022
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Ingår i: Aftonbladet. - 1103-9000.
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- 1 620 forskare och lärare i forskarvärlden: Vi ställer oss bakom Auroras klimatkrav
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| 2. |
- Welen, Karin, et al.
(författare)
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COVIDENZA - A prospective, multicenter, randomized PHASE II clinical trial of enzalutamide treatment to decrease the morbidity in patients with Corona virus disease 2019 (COVID-19): a structured summary of a study protocol for a randomised controlled trial.
- 2021
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Ingår i: Trials. - : Springer Science and Business Media LLC. - 1745-6215. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- The main goal of the COVIDENZA trial is to evaluate if inhibition of testosterone signalling by enzalutamide can improve the outcome of patients hospitalised for COVID-19. The hypothesis is based on the observation that the majority of patients in need of intensive care are male, and the connection between androgen receptor signalling and expression of TMPRSS2, an enzyme important for SARS-CoV-2 host cell internalization.Hospitalised COVID-19 patients will be randomised (2:1) to enzalutamide plus standard of care vs. standard of care designed to identify superiority.Included participants, men or women above 50 years of age, must be hospitalised for PCR confirmed COVID-19 symptoms and not in need of immediate mechanical ventilation. Major exclusion criteria are breast-feeding or pregnant women, hormonal treatment for prostate or breast cancer, treatment with immunosuppressive drugs, current symptomatic unstable cardiovascular disease (see Additional file 1 for further details). The trial is registered at Umeå University Hospital, Region Västerbotten, Sweden and 8 hospitals are approved for inclusion in Sweden.Patients randomised to the treatment arm will be treated orally with 160 mg (4x40 mg) enzalutamide (Xtandi®) daily, for five consecutive days. The study is not placebo controlled. The comparator is standard of care treatment for patients hospitalised with COVID-19.The primary endpoints of the study are (time to) need of mechanical ventilation or discharge from hospital as assessed by a clinical 7-point ordinal scale (up to 30 days after inclusion).Randomisation was stratified by center and sex. Each strata was randomized separately with block size six with a 2:1 allocation ratio (enzalutamide + "standard of care": "standard of care"). The randomisation list, with consecutive subject numbers, was generated by an independent statistician using the PROC PLAN procedure of SAS version 9.4 software (SAS Institute, Inc, Cary, North Carolina) BLINDING (MASKING): This is an open-label trial.The trial is designed to have three phases. The first, an exploration phase of 45 participants (30 treatment and 15 control) will focus on safety and includes a more extensive laboratory assessment as well as more frequent safety evaluation. The second prolongation phase, includes the first 100 participants followed by an interim analysis to define the power of the study. The third phase is the continuation of the study up to maximum 600 participants included in total.The current protocol version is COVIDENZA v2.0 as of September 10, 2020. Recruitment started July 29, 2020 and is presently in safety pause after the first exploration phase. Recruitment is anticipated to be complete by 31 December 2021.Eudract number 2020-002027-10 ClinicalTrials.gov Identifier: NCT04475601 , registered June 8, 2020 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.
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| 3. |
- Ekstrand, Eva-Maria, 1985-, et al.
(författare)
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Identifying targets for increased biogasproduction through chemical and organicmatter characterization of digestate from full‑scale biogas plants : what remains and why?
- 2022
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Ingår i: Biotechnology for Biofuels and Bioproducts. - London, United Kingdom : BioMed Central. - 2731-3654. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: This study examines the destiny of macromolecules in different full-scale biogas processes. From previousstudies it is clear that the residual organic matter in outgoing digestates can have significant biogas potential,but the factors dictating the size and composition of this residual fraction and how they correlate with the residualmethane potential (RMP) are not fully understood. The aim of this study was to generate additional knowledge of thecomposition of residual digestate fractions and to understand how they correlate with various operational and chemicalparameters. The organic composition of both the substrates and digestates from nine biogas plants operating onfood waste, sewage sludge, or agricultural waste was characterized and the residual organic fractions were linked tosubstrate type, trace metal content, ammonia concentration, operational parameters, RMP, and enzyme activity.Results: Carbohydrates represented the largest fraction of the total VS (32–68%) in most substrates. However, inthe digestates protein was instead the most abundant residual macromolecule in almost all plants (3–21 g/kg). Thedegradation efficiency of proteins generally lower (28–79%) compared to carbohydrates (67–94%) and fats (86–91%).High residual protein content was coupled to recalcitrant protein fractions and microbial biomass, either from thesubstrate or formed in the degradation process. Co-digesting sewage sludge with fat increased the protein degradationefficiency with 18%, possibly through a priming mechanism where addition of easily degradable substrates alsotriggers the degradation of more complex fractions. In this study, high residual methane production (> 140 L CH4/kgVS) was firstly coupled to operation at unstable process conditions caused mainly by ammonia inhibition (0.74 mgNH3-N/kg) and/or trace element deficiency and, secondly, to short hydraulic retention time (HRT) (55 days) relative tothe slow digestion of agricultural waste and manure.Conclusions: Operation at unstable conditions was one reason for the high residual macromolecule content andhigh RMP. The outgoing protein content was relatively high in all digesters and improving the degradation of proteinsrepresents one important way to increase the VS reduction and methane production in biogas plants. Post-treatment
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| 6. |
- Sotak, Matus, et al.
(författare)
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Intestinal sodium/glucose cotransporter 3 expression is epithelial and downregulated in obesity.
- 2021
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Ingår i: Life sciences. - : Elsevier BV. - 1879-0631 .- 0024-3205. ; 267
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Tidskriftsartikel (refereegranskat)abstract
- We aimed to determine whether the sodium/glucose cotransporter family member SGLT3, a proposed glucose sensor, is expressed in the intestine and/or kidney, and if its expression is altered in mouse models of obesity and in humans before and after weight-loss surgery.We used in-situ hybridization and quantitative PCR to determine whether the Sglt3 isoforms 3a and 3b were expressed in the intestine and kidney of C57, leptin-deficient ob/ob, and diabetic BTBR ob/ob mice. Western blotting and immunohistochemistry were also used to assess SGLT3 protein levels in jejunal biopsies from obese patients before and after weight-loss Roux-en-Y gastric bypass surgery (RYGB), and in lean healthy controls.Sglt3a/3b mRNA was detected in the small intestine (duodenum, jejunum and ileum), but not in the large intestine or kidneys of mice. Both isoforms were detected in epithelial cells (confirmed using intestinal organoids). Expression of Sglt3a/3b mRNA in duodenum and jejunum was significantly lower in ob/ob and BTBR ob/ob mice than in normal-weight littermates. Jejunal SGLT3 protein levels in aged obese patients before Roux-en-Y gastric bypass (RYGB) were lower than in lean individuals, but substantially upregulated 6months post-RYGB.Our study shows that Sglt3a/3b is expressed primarily in epithelial cells of the small intestine in mice. Furthermore, we observed an association between intestinal mRNA Sglt3a/3b expression and obesity in mice, and between jejunal SGLT3 protein levels and obesity in humans. Further studies are required to determine the possible role of SGLT3 in obesity.
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| 7. |
- Öfverholm, Anna, et al.
(författare)
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Extended genetic analysis and tumor characteristics in over 4600 women with suspected hereditary breast and ovarian cancer
- 2023
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Ingår i: BMC Cancer. - : BioMed Central (BMC). - 1471-2407. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundGenetic screening for pathogenic variants (PVs) in cancer predisposition genes can affect treatment strategies, risk prediction and preventive measures for patients and families. For decades, hereditary breast and ovarian cancer (HBOC) has been attributed to PVs in the genes BRCA1 and BRCA2, and more recently other rare alleles have been firmly established as associated with a high or moderate increased risk of developing breast and/or ovarian cancer. Here, we assess the genetic variation and tumor characteristics in a large cohort of women with suspected HBOC in a clinical oncogenetic setting.MethodsWomen with suspected HBOC referred from all oncogenetic clinics in Sweden over a six-year inclusion period were screened for PVs in 13 clinically relevant genes. The genetic outcome was compared with tumor characteristics and other clinical data collected from national cancer registries and hospital records.ResultsIn 4622 women with breast and/or ovarian cancer the overall diagnostic yield (the proportion of women carrying at least one PV) was 16.6%. BRCA1/2 PVs were found in 8.9% of women (BRCA1 5.95% and BRCA2 2.94%) and PVs in the other breast and ovarian cancer predisposition genes in 8.2%: ATM (1.58%), BARD1 (0.45%), BRIP1 (0.43%), CDH1 (0.11%), CHEK2 (3.46%), PALB2 (0.84%), PTEN (0.02%), RAD51C (0.54%), RAD51D (0.15%), STK11 (0) and TP53 (0.56%). Thus, inclusion of the 11 genes in addition to BRCA1/2 increased diagnostic yield by 7.7%. The yield was, as expected, significantly higher in certain subgroups such as younger patients, medullary breast cancer, higher Nottingham Histologic Grade, ER-negative breast cancer, triple-negative breast cancer and high grade serous ovarian cancer. Age and tumor subtype distributions differed substantially depending on genetic finding.ConclusionsThis study contributes to understanding the clinical and genetic landscape of breast and ovarian cancer susceptibility. Extending clinical genetic screening from BRCA1 and BRCA2 to 13 established cancer predisposition genes almost doubles the diagnostic yield, which has implications for genetic counseling and clinical guidelines. The very low yield in the syndrome genes CDH1, PTEN and STK11 questions the usefulness of including these genes on routine gene panels.
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| 9. |
- Assenhöj, Maria, et al.
(författare)
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Protein interaction, monocyte toxicity and immunogenic properties of cerium oxide crystals with 5% or 14% gadolinium, cobalt oxide and iron oxide nanoparticles–an interdisciplinary approach
- 2021
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Ingår i: Nanotoxicology. - : Taylor and Francis Ltd.. - 1743-5390 .- 1743-5404. ; 15:8, s. 1035-1038
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Tidskriftsartikel (refereegranskat)abstract
- Metal oxide nanoparticles are widely used in both consumer products and medical applications, but the knowledge regarding exposure-related health effects is limited. However, it is challenging to investigate nanoparticle interaction processes with biological systems. The overall aim of this project was to improve the possibility to predict exposure-related health effects of metal oxide nanoparticles through interdisciplinary collaboration by combining workflows from the pharmaceutical industry, nanomaterial sciences, and occupational medicine. Specific aims were to investigate nanoparticle-protein interactions and possible adverse immune reactions. Four different metal oxide nanoparticles; CeOx nanocrystals with 5% or 14% Gd, Co3O4, and Fe2O3, were characterized by dynamic light scattering and high-resolution transmission electron microscopy. Nanoparticle-binding proteins were identified and screened for HLA-binding peptides in silico. Monocyte interaction with nanoparticle–protein complexes was assessed in vitro. Herein, for the first time, immunogenic properties of nanoparticle-binding proteins have been characterized. The present study indicates that especially Co3O4-protein complexes can induce both ‘danger signals’, verified by the production of inflammatory cytokines and simultaneously bind autologous proteins, which can be presented as immunogenic epitopes by MHC class II. The clinical relevance of these findings should be further evaluated to investigate the role of metal oxide nanoparticles in the development of autoimmune disease. The general workflow identified experimental difficulties, such as nanoparticle aggregate formation and a lack of protein-free buffers suitable for particle characterization, protein analyses, as well as for cell studies. This confirms the importance of future interdisciplinary collaborations. © 2021 The Author(s).
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| 10. |
- Bondelind, Mia, 1980, et al.
(författare)
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Hydrodynamic modelling of traffic-related microplastics discharged with stormwater into the Göta River in Sweden
- 2020
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Ingår i: Environmental Science and Pollution Research. - : Springer Science and Business Media LLC. - 0944-1344 .- 1614-7499. ; 27:19, s. 24218-24230
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Tidskriftsartikel (refereegranskat)abstract
- Microplastics (MP) are transported from land-based sources from rivers to marine waters. However, there is currently little knowledge about MP fate from land sources to marine waters. Traffic is estimated to be one of the largest sources of MP; hence, stormwater is expected to be an important transportation route of MP to marine waters. The aim of this study was to investigate the effect of the size and density of tyre wear particles in road run-off on their fate in the Gota River in Sweden using hydrodynamic modelling. The model of the stretch of Gota River, Sweden's largest river, passing through Gothenburg (Sweden's second largest city) and out to the sea, was set up using MIKE 3 FM software. Literature data were used to define the MP characteristics: concentrations in stormwater, prevalent particle sizes, density of MP commonly occurring in road run-off and settling velocities. Results show that higher concentrations of MP are found on the south side of the river, compared with the north side, due to higher annual average daily traffic loads along the south side of the river. The mixing processes in the river and the MP concentrations were generally influenced by the vertical water density gradient caused by saline water from the Kattegat strait. While most MP with higher density and larger size settle in the river, smaller MP with density close to 1.0 g/cm(3) do not settle in the river and therefore reach the Kattegat strait and the marine environments. Further research is needed to describe the fate and transport of microplastics in the stormwater system, including treatment facilities, i.e. biofouling, aggregation, degradation and/or further fragmentation and settling.
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