| 1. |
- Thysell, Elin, et al.
(författare)
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Clinical and biological relevance of the transcriptomic-based prostate cancer metastasis subtypes MetA-C
- 2022
-
Ingår i: Molecular Oncology. - : Wiley. - 1574-7891 .- 1878-0261. ; 16:4, s. 846-859
-
Tidskriftsartikel (refereegranskat)abstract
- To improve treatment of metastatic prostate cancer, the biology of metastases needs to be understood. We recently described three subtypes of prostate cancer bone metastases (MetA-C), based on differential gene expression. The aim of this study was to verify the clinical relevance of these subtypes and to explore their biology and relations to genetic drivers. Freshly-frozen metastasis samples were obtained as hormone-naive (n = 17), short-term castrated (n = 21), or castration-resistant (n = 65) from a total of 67 patients. Previously published sequencing data from 573 metastasis samples were also analyzed. Through transcriptome profiling and sample classification based on a set of predefined MetA-C-differentiating genes, we found that most metastases were heterogeneous for the MetA-C subtypes. Overall, MetA was the most common subtype, while MetB was significantly enriched in castration-resistant samples and in liver metastases, and consistently associated with poor prognosis. By gene set enrichment analysis, the phenotype of MetA was described by high androgen response, protein secretion and adipogenesis, MetB by high cell cycle activity and DNA repair, and MetC by epithelial-to-mesenchymal transition and inflammation. The MetB subtype demonstrated single nucleotide variants of RB transcriptional corepressor 1 (RB1) and loss of 21 genes at chromosome 13, including RB1, but provided independent prognostic value to those genetic aberrations. In conclusion, a distinct set of gene transcripts can be used to classify prostate cancer metastases into the subtypes MetA-C. The MetA-C subtypes show diverse biology, organ tropism, and prognosis. The MetA-C classification may be used independently, or in combination with genetic markers, primarily to identify MetB patients in need of complementary therapy to conventional androgen receptor-targeting treatments.
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| 2. |
- Hellsmark, Hans, 1974, et al.
(författare)
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Teknologiska innovationssystem inom energiområdet: En praktisk vägledning till identifiering av systemsvagheter som motiverar särskilda politiska åtaganden
- 2014
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Syftet med denna rapport är att illustrera hur ett praktiskt inriktat ramverk, tekno- logiska innovationssystem (TIS), kan användas av analytiker och beslutsfattare vid departement och myndigheter för att analysera strategiskt viktiga teknikområden ?????????????????????????????????????????????????????????????????????????????I rapporten analyseras fem TIS centrerade kring havsbaserad vindkraft, marin energi, ????????????????????????????????????????????????????????????????????????????????????? systemsvagheter som bromsar områdets vidare utveckling, vilka som kan åtgärdas av systemets aktörer och vilka som motiverar särskilda politiska åtaganden. Rapporten utgör därmed ett underlag för att formulera åtgärder för att åstadkomma ökad innova- tion, teknikspridning och industrialisering inom ovan nämnda teknikområden.Studien har även möjliggjort en jämförande analys av likheter och skillnader ???????????????????????????????????????????????????????????????????????????????? ?????????????????????????????????????????????????????????????????????????????????????? mellan områdena – de är starka respektive svaga av olika orsaker. Detta visar att ???????????????????????????????????????????????????????????????????????Samtidigt har områdena gemensamma drag. Systemets aktörer, där även politiska ???????????????????????????????????????????????????????????????????????????????????? ?????????????????????????????????????????????????????????????????????????????- skapsnätverk. Men de har varit sämre på att skapa tidiga nischmarknader som ger utrymme för fortsatt lärande och kostnadsreduktion. Sådana nischer kan ibland skapas av marknadens aktörer, men ofta krävs politiska styrmedel. De behövs för att investeringar i kunskapsutveckling ska kunna nyttiggöras och för att en bred industriell utveckling inom nya områden skall göras möjlig i Sverige.Vidare presenteras lärdomar kring vad en aktiv teknikpolitik innebär. Två huvud- ??????????????????????????????????????????????????????????????????????????????- hällsbygget och därför bör vara ett politikområde bland många samt att den skarpa ??????????????????????????????????????????????????????????????????????????????- ?????????????????????????????????????????????????????????????????????????????????? ?????????????????????????????????????????????????????????????????????????????????? olika faser av innovationssystemets utveckling.För att lyckas med en aktiv teknikpolitik behövs en hög grad av koordinering ??????????????????????????????????????????????????????????????????????? teknikområden så att ”rätt” typ av åtgärder kan sättas in vid ”rätt” tidpunkt av ”rätt” aktör. TIS-ramverket lyfts här fram som en metod för att skapa ett sådant underlag. Slutligen presenteras en metod för projektbedömningar som syftar till att stötta handläggare i utvärderingar av projekt inom nya teknikområden.Rapporten i sin helhet riktar sig särskilt till beslutsfattare och handläggare vid myndigheter, departement och politiker, men även andra organisationer och indi- vider med intresse av att högt ställda klimatmål ska kunna nås samtidigt som en positiv näringslivsutveckling möjliggörs.
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| 3. |
- Woksepp, Hanna, et al.
(författare)
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Dissemination of carbapenemase-producing Enterobacterales through wastewater and gulls at a wastewater treatment plant in Sweden
- 2023
-
Ingår i: Science of the Total Environment. - : Elsevier. - 0048-9697 .- 1879-1026. ; 886
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Tidskriftsartikel (refereegranskat)abstract
- Here we report the detection of carbapenemase-producing Enterobacterales (CPE) isolated from Swedish wastewater and gull faeces. CPE have not been detected in samples from animals in Sweden preceding this report. Sampling of wastewater treatment plant (WWTP) inlet and outlet, sedimentation basins, surface seawater from key aquatic bird habitats and freshly deposited gull faeces was done on six separate occasions during May to September 2021. Following broth enrichment, selective screening of putative CPE was performed on mSuperCarbaTM (CHROMagar). Species identification was done with MALDI-TOF. Antimicrobial susceptibility testing was performed according to EUCAST. In total, seventeen CPE were verified by genome sequencing carrying blaGES-5, blaIMI-3, blaOXA-181 or blaOXA-244. The blaGES-5 was carried on IncP plasmids in four different species; Escherichia coli ST10 isolated from WWTP outlet, Raoultella ornithinolytica isolated from WWTP inlet, outlet and sedimentation basins as well as gull faeces collected at the WWTP and Klebsiella spp. isolates from WWTP inlet and outlet. The genetic environment surrounding blaGES-5 was similar in two Citrobacter freundii causing human infections. The blaIMI-3 was carried on IncFII(Yp) plasmids in four Enterobacter ludwigii, isolated from WWTP outlet and gull faeces collected at a recreational city park 2 km from the WWTP. The blaOXA-181 was located on a COLKP3 plasmid found in an E. coli, while blaOXA-244 was chromosomally located in an E. coli ST10, both isolated from WWTP inlet. Phylogenetic analysis of R. ornithinolytica and E. ludwigii isolates indicate that the gulls carried strains related to those identified in the WWTP samples. The results thus add to the increasing evidence of WWTPs as anthropogenic reservoirs for mobile genetic elements with antibiotic-resistance functionality. Such environments could profoundly impact the dissemination and spread of such genetic elements via for example aquatic birds, thereby warranting further study and surveillance.
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| 4. |
- Björk, Magnus, 1977, et al.
(författare)
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Exposed Datapath for Efficient Computing
- 2006
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- We introduce FlexCore, which is the first exemplar of a processor based on the FlexSoC processor paradigm. TheFlexCore utilizes an exposed datapath for increased performance. Microbenchmarks yield a performance boost of a factor of two over a traditional five-stage pipeline with the same functional units as the FlexCore.We describe our approach to compiling for the FlexCore.A flexible interconnect allows the FlexCore datapath to bedynamically reconfigured as a consequence of code generation. Additionally, specialized functional units may be introduced and utilized within the same architecture and compilation framework. The exposed datapath requires a wide control word. The conducted evaluation of two micro benchmarks confirms that this increases the instruction bandwidth and memory footprint. This calls for an efficient instruction decoding as proposed in the FlexSoC paradigm.
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| 5. |
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| 6. |
- Cappellini, Francesca, et al.
(författare)
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Dry Generation of CeO2 Nanoparticles and Deposition onto a Co-Culture of A549 and THP-1 Cells in Air-Liquid Interface-Dosimetry Considerations and Comparison to Submerged Exposure
- 2020
-
Ingår i: Nanomaterials. - : MDPI AG. - 2079-4991. ; 10:4
-
Tidskriftsartikel (refereegranskat)abstract
- Relevant in vitro assays that can simulate exposure to nanoparticles (NPs) via inhalation are urgently needed. Presently, the most common method employed is to expose lung cells under submerged conditions, but the cellular responses to NPs under such conditions might differ from those observed at the more physiological air-liquid interface (ALI). The aim of this study was to investigate the cytotoxic and inflammatory potential of CeO2 NPs (NM-212) in a co-culture of A549 lung epithelial cells and differentiated THP-1 cells in both ALI and submerged conditions. Cellular dose was examined quantitatively using inductively coupled plasma mass spectrometry (ICP-MS). The role of serum and LPS-priming for IL-1 beta release was further tested in THP-1 cells in submerged exposure. An aerosol of CeO2 NPs was generated by using the PreciseInhale (R) system, and NPs were deposited on the co-culture using XposeALI (R). No or minor cytotoxicity and no increased release of inflammatory cytokines (IL-1 beta, IL-6, TNF alpha, MCP-1) were observed after exposure of the co-culture in ALI (max 5 mu g/cm(2)) or submerged (max 22 mu g/cm(2)) conditions. In contrast, CeO2 NPs cause clear IL-1 beta release in monocultures of macrophage-like THP-1, independent of the presence of serum and LPS-priming. This study demonstrates a useful approach for comparing effects at various in-vitro conditions.
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| 7. |
- Cappellini, Francesca, et al.
(författare)
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Mechanistic insight into reactivity and (geno)toxicity of well-characterized nanoparticles of cobalt metal and oxides
- 2018
-
Ingår i: Nanotoxicology. - : Taylor & Francis. - 1743-5390 .- 1743-5404. ; 12:6, s. 602-620
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Tidskriftsartikel (refereegranskat)abstract
- An increasing use of cobalt (Co)-based nanoparticles (NPs) in different applications and exposures at occupational settings triggers the need for toxicity assessment. Improved understanding regarding the physiochemical characteristics of Co metal NPs and different oxides in combination with assessment of toxicity and mechanisms may facilitate decisions for grouping during risk assessment. The aim of this study was to gain mechanistic insights in the correlation between NP reactivity and toxicity of three different Co-based NPs (Co, CoO, and Co3O4) by using various tools for characterization, traditional toxicity assays, as well as six reporter cell lines (ToxTracker) for rapid detection of signaling pathways of relevance for carcinogenicity. The results showed cellular uptake of all NPs in lung cells and induction of DNA strand breaks and oxidative damage (comet assay) by Co and CoO NPs. In-depth studies on the ROS generation showed high reactivity of Co, lower for CoO, and no reactivity of Co3O4 NPs. The reactivity depended on the corrosion and transformation/dissolution properties of the particles and the media highlighting the role of the surface oxide and metal speciation as also confirmed by in silico modeling. By using ToxTracker, Co NPs were shown to be highly cytotoxic and induced reporters related to oxidative stress (Nrf2 signaling) and DNA strand breaks. Similar effects were observed for CoO NPs but at higher concentrations, whereas the Co3O4 NPs were inactive at all concentrations tested. In conclusion, our study suggests that Co and CoO NPs, but not Co3O4, may be grouped together for risk assessment.
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| 8. |
- Dahlin, Anna M., 1979-, et al.
(författare)
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Genetic Variants in the 9p21.3 Locus Associated with Glioma Risk in Children, Adolescents, and Young Adults : A Case-Control Study
- 2019
-
Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 28:7, s. 1252-1258
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Genome-wide association studies have identified germline genetic variants in 25 genetic loci that increase the risk of developing glioma in adulthood. It is not known if these variants increase the risk of developing glioma in children and adolescents and young adults (AYA). To date, no studies have performed genome-wide analyses to find novel genetic variants associated with glioma risk in children and AYA.Methods: We investigated the association between 8,831,628 genetic variants and risk of glioma in 854 patients diagnosed up to the age of 29 years and 3,689 controls from Sweden and Denmark. Recruitment of patients and controls was population based. Genotyping was performed using Illumina BeadChips, and untyped variants were imputed with IMPUTE2. We selected 41 established adult glioma risk variants for detailed investigation.Results: Three adult glioma risk variants, rs634537, rs2157719, and rs145929329, all mapping to the 9p21.3 (CDKN2B-AS1) locus, were associated with glioma risk in children and AYA. The strongest association was seen for rs634537 (odds ratioG = 1.21; 95% confidence interval = 1.09–1.35; P = 5.8 × 10−4). In genome-wide analysis, an association with risk was suggested for 129 genetic variants (P <1 × 10−5).Conclusions: Carriers of risk alleles in the 9p21.3 locus have an increased risk of glioma throughout life. The results from genome-wide association analyses require validation in independent cohorts.Impact: Our findings line up with existing evidence that some, although not all, established adult glioma risk variants are associated with risk of glioma in children and AYA. Validation of results from genome-wide analyses may reveal novel susceptibility loci for glioma in children and AYA.
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| 9. |
- Diswall, Mette, 1979, et al.
(författare)
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Structural characterization of alpha1,3-galactosyltransferase knockout pig heart and kidney glycolipids and their reactivity with human and baboon antibodies.
- 2010
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Ingår i: Xenotransplantation. - : Wiley. - 1399-3089 .- 0908-665X. ; 17:1, s. 48-60
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: alpha1,3-galactosyltranferase knockout (GalT-KO) pigs have been established to avoid hyperacute rejection in GalT-KO pig-to-human xenotransplantation. GalT-KO pig heart and kidney glycolipids were studied focusing on elimination of Gal-antigens and whether novel antigens would appear. Non-human primates are used as pre-clinical transplantation experimental models. Therefore, sera from baboons transplanted with GalT-KO hearts were compared with human serum regarding reactivity with pig glycolipids. METHODS: Neutral and acidic glycolipids were isolated from GalT-KO and WT pig hearts and kidneys. Glycolipid immune reactivity was tested on TLC plates using human affinity-purified anti-Gal Ig, anti-blood group monoclonal antibodies, lectins, and human serum as well as baboon serum collected before and after GalT-KO pig heart transplantations. Selected glycolipid fractions, isolated by HPLC, were structurally characterized by mass spectrometry and proton NMR spectroscopy. RESULTS: GalT-KO heart and kidney lacked alpha3Gal-terminated glycolipids completely. Levels of uncapped N-acetyllactosamine precursor compounds, blood group H type 2 core chain compounds, the P1 antigen and the x(2) antigen were increased. Human serum antibodies reacted with Gal-antigens and N-glycolylneuraminic acid (NeuGc) in WT organs of which only the NeuGc reactivity remained in the GalT-KO tissues. A clear difference in reactivity between baboon and human antibodies with pig glycolipids was found. This was most pronounced for acidic, not yet identified, compounds in GalT-KO organs which were less abundant or lacking in the corresponding WT tissues. CONCLUSIONS: GalT-KO pig heart and kidney completely lacked Gal glycolipid antigens whilst glycolipids synthesized by competing pathways were increased. Baboon and human serum antibodies showed a different reactivity pattern to pig glycolipid antigens indicating that non-human primates have limitations as a human pre-clinical model for immune rejection studies.
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| 10. |
- Einarsdottir, Berglind Osk, 1979, et al.
(författare)
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A patient-derived xenograft pre-clinical trial reveals treatment responses and a resistance mechanism to karonudib in metastatic melanoma
- 2018
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Ingår i: Cell Death & Disease. - : Springer Science and Business Media LLC. - 2041-4889. ; 9:8
-
Tidskriftsartikel (refereegranskat)abstract
- Karonudib (TH1579) is a novel compound that exerts anti-tumor activities and has recently entered phase I clinical testing. The aim of this study was to conduct a pre-clinical trial in patient-derived xenografts to identify the possible biomarkers of response or resistance that could guide inclusion of patients suffering from metastatic melanoma in phase II clinical trials. Patient-derived xenografts from 31 melanoma patients with metastatic disease were treated with karonudib or a vehicle for 18 days. Treatment responses were followed by measuring tumor sizes, and the models were categorized in the response groups. Tumors were harvested and processed for RNA sequencing and protein analysis. To investigate the effect of karonudib on T-cell-mediated anti-tumor activities, tumor-infiltrating T cells were injected in mice carrying autologous tumors and the mice treated with karonudib. We show that karonudib has heterogeneous anti-tumor effect on metastatic melanoma. Thus, based on the treatment responses, we could divide the 31 patient-derived xenografts in three treatment groups: progression group (32%), suppression group (42%), and regression group (26%). Furthermore, we show that karonudib has anti-tumor effect, irrespective of major melanoma driver mutations. Also, we identify high expression of ABCB1, which codes for p-gp pumps as a resistance biomarker. Finally, we show that karonudib treatment does not hamper T-cell-mediated anti-tumor responses. These findings can be used to guide future use of karonudib in clinical use with a potential approach as precision medicine.
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| 11. |
- Enebro, Jonas, 1979-, et al.
(författare)
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A New Approach for Studying Correlations between the Chemical Structure and the Rheological Properties in Carboxymethyl Cellulose
- 2007
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Ingår i: Biomacromolecules. - : American Chemical Society (ACS). - 1525-7797 .- 1526-4602. ; 8:10, s. 3253-3257
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Tidskriftsartikel (refereegranskat)abstract
- Two model sodium carboxymethyl celluloses (CMC) with similar monomer composition but with significant differences in the viscoelastic properties, that could not be assigned to variations in the average molar mass or molar mass distribution, were investigated with respect to the fraction of nonsubstituted cellulose segments in the polymers. The CMCs were hydrolyzed by a purified highly selective endoglucanase. The average molar mass and molar mass distribution of the enzyme products, as measured by size-exclusion chromatography with online multi-angle light scattering and refractive index detection (SEC/MALS/RI), revealed that the enzyme-catalyzed hydrolysis was more effective on one of the CMCs. To investigate whether this was due to a higher fraction of nonsubstituted cellulose segments in the polymer, the concentrations of nonsubstituted enzyme products, e.g., cellotetraose and cellopentaose, were measured by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS). It was concluded that the two CMCs displayed significant differences in the fraction of nonsubstituted cellulose segments. Furthermore, the CMC with the strongest attractive intermolecular interactions, according to rheometry, also contained the highest fraction of nonsubstituted cellulose segments.
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| 12. |
- Enebro, Jonas, 1979-, et al.
(författare)
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Investigation of endoglucanase selectivity on carboxymethyl cellulose by mass spectrometric techniques
- 2009
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Ingår i: Cellulose. - : Springer Science and Business Media LLC. - 0969-0239 .- 1572-882X. ; 16:2, s. 271-280
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Tidskriftsartikel (refereegranskat)abstract
- The benefits of applying cellulose selective enzymes as analytical tools for chemical structure characterization of cellulose derivatives have been frequently addressed over the years. In a recent study the high selectivity of cellulase Cel45A from Trichoderma reesei (Tr Cel45A) was utilized for relating the chemical structure to the flow properties of carboxymethyl cellulose (CMC). However, in order to take full advantage of the enzymatic hydrolysis the enzyme selectivity on the cellulose substrate must be further investigated. Therefore, the selectivity of Tr Cel45A on CMC was studied by chemical sample preparation of the enzyme products followed by mass spectrometric chemical structure characterization. The results strongly suggest that, in accordance with recent studies, also this highly selective endoglucanase is able to catalyze hydrolysis of glucosidic bonds adjacent to mono-substituted anhydroglucose units (AGUs). Furthermore, the results also indicate that substituents on the nearby AGUs will affect the hydrolysis.
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| 13. |
- Enebro, Jonas, 1979-, et al.
(författare)
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Liquid Chromatography combined with Mass Spectrometry for the Investigation of Endoglucanase Selectivity on Carboxymethyl Cellulose
- 2009
-
Ingår i: Carbohydrate Research. - : Elsevier BV. - 0008-6215 .- 1873-426X. ; 344:16, s. 2173-2181
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Tidskriftsartikel (refereegranskat)abstract
- Endoglucanases are useful tools in the chemical structure analysis of cellulose derivatives. However, knowledge on the endoglucanase selectivity, which is of central importance for data interpretation, is still limited. In this study, new reverse-phase liquid chromatography mass spectrometry (LC-MS) methods were developed to investigate the selectivity of the endoglucanases Cel5A, cel7B, Cel45A, and Cel74A from the filamentous fungus Trichoderma reesei. The aim was to improve the identification of the regioisomers in the complex mixtures that are obtained after enzymatic hydrolysis. Reduction followed by per-O-methylation was performed in order to improve the separation in reverse-phase LC, increase MS sensitivity, and to facilitate structure analysis by MS/MS of O-carboxymethyl glucose and cellooligosaccharides. The cellulose selective enzymes that were investigated displayed interesting differences in enzyme selectivity on CMC substrates.
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| 14. |
- Enebro, Jonas, 1979-
(författare)
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New Mass Spectrometric Methods for Structure Analysis of Carboxymethyl Cellulose
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Carboxymethyl cellulose (CMC) is a cellulose derivative, made from cellulose by introduction of carboxymethyl groups along the molecules. The properties of CMC are affected by several parameters where the molar mass and molar mass distribution, degree of substitution (DS) and the distribution pattern along, and between, the cellulose molecules are the most prominent. In the present thesis we have investigated the use of various mass spectrometric techniques, such as matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS) and electrospray ionization MS (ESI-MS), for characterization of the chemical structure of CMC. We here present a refined sample preparation procedure for MALDI that greatly facilitates the spectrum acquisition and improves the quality of the mass spectrum when analyzing partially hydrolyzed CMC. The refined method allows for estimation of the DS in CMC samples as a complement to more expensive and laborious methods. We also show that by combining MALDI-TOFMS with selective hydrolysis, by purified endoglucanase, and size-exclusion chromatography (SEC) it is possible to differentiate between CMCs of similar monomer composition but differences in the substitution pattern. Our findings show that the CMC containing longer non-substituted cellulose segments along the polymer backbone also displayed the highest intermolecular interactions in solution, as measured by rheometry. In order to take full advantage of the selective hydrolysis, provided by purified endoglucanases, more information regarding their selectivity on CMC must be investigated. We therefore present methods where chemical sample preparation of the oligomeric enzyme products is performed in order to facilitate the chemical structure characterization by ESI-MS/MS and liquid chromatography MS (LC-MS). These methods provides valuable information regarding the substituent distribution along the oligomeric enzyme products, and thereby gives indications regarding the selectivity of the endoglucanases on CMC substrates. From our finding we are able to present interesting information regarding the selectivity of four endoglucanases (Cel7B, Cel5A, Cel45A and Cel74A) from the filamentous fungus Trichoderma reesei and provide plausible explanations to their apparent differences in selectivity on CMC.
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| 15. |
- Feiz, Roozbeh, 1975-, et al.
(författare)
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Biogas Potential for Improved Sustainability in Guangzhou, China : A Study Focusing on Food Waste on Xiaoguwei Island
- 2019
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Ingår i: Sustainability. - : MDPI. - 2071-1050. ; 11:6
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Tidskriftsartikel (refereegranskat)abstract
- As a result of rapid development in China and the growth of megacities, large amounts of organic wastes are generated within relatively small areas. Part of these wastes can be used to produce biogas, not only to reduce waste-related problems, but also to provide renewable energy, recycle nutrients, and lower greenhouse gases and air polluting emissions. This article is focused on the conditions for biogas solutions in Guangzhou. It is based on a transdisciplinary project that integrates several approaches, for example, literature studies and lab analysis of food waste to estimate the food waste potential, interviews to learn about the socio-technical context and conditions, and life-cycle assessment to investigate the performance of different waste management scenarios involving biogas production. Xiaoguwei Island, with a population of about 250,000 people, was chosen as the area of study. The results show that there are significant food waste potentials on the island, and that all studied scenarios could contribute to a net reduction of greenhouse gas emissions. Several socio-technical barriers were identified, but it is expected that the forthcoming regulatory changes help to overcome some of them.
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| 16. |
- Hedberg, Yolanda, 1985-, et al.
(författare)
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Interaction of Albumin and Fibrinogen with Stainless Steel : Influence of Sequential Exposure and Protein Aggregation on Metal Release and Corrosion Resistance
- 2017
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Ingår i: Corrosion. - : NATL ASSOC CORROSION ENG. - 0010-9312 .- 1938-159X. ; 73:12
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Tidskriftsartikel (refereegranskat)abstract
- Corrosion and metal release mechanisms of the biomedical stainless steel grade Type 316L are at human-relevant biological conditions not fully understood. This study focuses on its corrosion properties and release of iron (Fe), chromium (Cr), manganese (Mn), and nickel (Ni) into simulated physiological solutions at pH 7.4 in the presence of proteins. Parallel studies were performed on stainless steel Type 303 containing a substantial amount of MnS inclusions. Metal release studies were performed in phosphate buffered saline (PBS) for 4 h and 24 h at 37 degrees C with or without different concentrations of bovine serum albumin (BSA), fibrinogen from bovine plasma (Fbn), or mixtures of the same. Studies were in addition performed after 1, 4, 6, and 24 h in solutions that were partially replenished after 5 h in order to investigate whether any Vroman effect (exchange of adsorbed proteins by proteins of higher binding affinity) could influence the extent of released metals in solution. This was performed at physiological concentrations of BSA (40 g/L) and Fbn (2.67 g/L) in PBS, and for reference solutions of PBS, PBS with 40 g/L BSA, and PBS with 2.67 g/L Fbn. Changes in open-circuit potential and linear polarization resistance were investigated for the same conditions. After exposure, the exposed surfaces were rinsed and investigated ex situ by means of x-ray photoelectron spectroscopy and infrared reflection absorption spectroscopy. Metal-protein complexation-induced metal release mechanisms were found to be most pronounced for Type 316L and the release of Fe, Cr, and Ni. Fibrinogen adsorbed differently onto Type 303 (thicker conformation of adsorbed proteins) as compared with Type 316L and occasionally induced corrosion events for Type 303. Mn was mostly released from inclusions present in the Type 303 alloy, most probably via non-electrochemical mechanisms. A Vroman effect was observed for both grades. A significant extent of precipitation of metal-rich protein aggregates influenced the metal release measurements in solution and resulted in an underestimation of the total amount of released metals from the stainless steel grades.
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| 17. |
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| 18. |
- Karlsson, Joakim, et al.
(författare)
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Molecular profiling of driver events in metastatic uveal melanoma
- 2020
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
-
Tidskriftsartikel (refereegranskat)abstract
- Metastatic uveal melanoma is less well understood than its primary counterpart, has a distinct biology compared to skin melanoma, and lacks effective treatments. Here we genomically profile metastatic tumors and infiltrating lymphocytes. BAP1 alterations are overrepresented and found in 29/32 of cases. Reintroducing a functional BAP1 allele into a deficient patient-derived cell line, reveals a broad shift towards a transcriptomic subtype previously associated with better prognosis of the primary disease. One outlier tumor has ahigh mutational burden associated with UV-damage. CDKN2A deletions also occur, which are rarely present in primaries. A focused knockdown screen is used to investigate overexpressed genesassociated withcopy number gains. Tumor-infiltrating lymphocytes are in several cases found tumor-reactive, but expression of the immune checkpoint receptors TIM-3, TIGIT and LAG3 is also abundant. This study represents the largest whole-genome analysis of uveal melanoma to date, and presents an updated view of the metastatic disease. © 2020, The Author(s).
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| 19. |
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| 20. |
- Karlsson, Oskar, et al.
(författare)
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The human exposome and health in the Anthropocene
- 2021
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Ingår i: International Journal of Epidemiology. - : Oxford University Press (OUP). - 0300-5771 .- 1464-3685. ; 50:2, s. 378-389
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Tidskriftsartikel (refereegranskat)
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| 21. |
- Karlsson, Simon, 1984-, et al.
(författare)
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Granö fiskavledare
- 2015
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Utvinning av vattenkraft från Granö kraftstation påbörjades på slutet av 1950-talet. Ålen har sedan dess varit hindrad att passera genom kraftverket av ett finmaskigt och höglutande nät under ålens vandringssäsonger. Den alternativa vägen runt stationen har varit med spillvatten eller ner i den gamla ålkistan placerad i intagskanalen. Det är okänt hur många ålar som faktiskt vandrat ut med spillvattnet, men fångsterna i den gamla ålkistan har varit begränsade och mängder med ålar har dött på nätet. Ålen är nu akut hotad och åtgärder att mildra kraftverkens negativa inverkan på utvandrande blankål har högsta prioritet.Till följd av problem med igensättning av den så kallade ålspärren uppstod ett dammbrott 2010. För att öka dammsäkerheten och effektiviteten för åluppsamling designades och uppfördes en ny fiskavledare med åluppsamlingsanläggning 2011. Granö fiskavledare är unik i sitt slag då den har intagsgaller av kompositmaterial, ställbara lutningar (30-40˚), samt flyktöppningar som leder till en uppsamlingsbur. Vattnet från uppsamlingen pumpas tillbaka till intagskanalen, för att undvika onödigt spill.En stor del av utvärderingen bestod i märkning och spårning av blankål i anslutning till avledaren. Märkningsförsöken under 2012 och 2013 visade att endast en liten proportion av fisken hittar flyktöppningarna och kommer till uppsamlingsburen, dessutom har skador på fisken kunna relateras till avledaren och uppsamlingsburen. Totalt har 284 ålar märkts och 475 har visuellt bedömts för skador efter passage genom avledaren eller referensfisket Havbältan. Trots två dåliga ålvandringsår har majoriteten av den radiomärkta fisken ankommit till avledaren och totalt har 15 fisk återfångades. Hydrauliska mätningar i flyktöppningarna visar att vattenflödena igenom avledarsystemet är låga och andelen (vatten genom avledaren/totalflöde) är långt under rekommenderat vilket kan vara en anledning till de få återfångsterna av fisk.
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| 22. |
- Karlsson, Tom S., 1979-
(författare)
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Manager and civil servant : exploring actors' taken-for-granted assumptions in public administration
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Manager and Civil Servant is an exploration of actors' taken-for-granted assumptions that govern perceptions concerning how public administration should be undertaken within contemporary welfare states. It is argued that more than 30 years of continuous reforms directed towards public administration have caused dilemmas to arise. These dilemmas have resulted in a shifting of balances regarding the underpinning pillars of public administration. These reforms have furthermore resulted in an emergence of challenging social systems, entailing new beliefs and practices. The question posited is "how do actors engaged in public administration make sense of the dilemma(s) they face". Theoretically, this dissertation entails institutional theory as well as Structuration Theory. These are combined in a framework, wherein agency and structure are used in order to characterise manifestations of taken-for-granted assumptions. The framework is furthermore elaborated through conceptual perspectives concerning Management as well as Civil Service in order to model a framework for public administration. Empirically, this dissertation entails a use of qualitative as well as quantitative methods. Open-ended interviews are combined with self-administered surveys, statistical analysis, and focus groups. Two important contributions are highlighted. Firstly, actors engaged in public administration reject the idea of polarisation concerning inherent public administrative activities and that the dilemma being accentuated within public administration. As such, instances of making sense are reduced due to an unconscious enactment of meanings and sanctions that reject the presence of dilemmas. Secondly, actors' ability to reject polarisation, and thus dilemma, can be explained through compartmentalising interdependent perspectives. On the one hand actors enact an internal perspective wherein instances of Management make sense. On the other hand actors enact an external perspective wherein instances of Civil Service make sense. The separation and compartmentalisation of these perspectives not only enable actors to reject dilemma, they are enabled to enact seemingly different roles at once. They become both Managers and Civil Servants.
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| 23. |
- Kessler, Amanda, et al.
(författare)
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Adsorption of Horseradish Peroxidase on Metallic Nanoparticles : Effects on Reactive Oxygen Species Detection Using 2′,7′-Dichlorofluorescin Diacetate
- 2021
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Ingår i: Chemical Research in Toxicology. - : American Chemical Society. - 0893-228X .- 1520-5010. ; 350, s. S215-S216
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Tidskriftsartikel (refereegranskat)abstract
- The fluorescent probe 2′,7′-dichlorofluorescein diacetate (DCFH-DA) together with the enzyme horseradish peroxidase (HRP) is widely used in nanotoxicology to study acellular reactive oxygen species (ROS) production from nanoparticles (NPs). This study examined whether HRP adsorbs onto NPs of Mn, Ni, and Cu and if this surface process influences the extent of metal release and hence the ROS production measurements using the DCFH assay in phosphate buffered saline (PBS), saline, or Dulbecco's modified Eagle's medium (DMEM). Adsorption of HRP was evident onto all NPs and conditions, except for Mn NPs in PBS. The presence of HRP resulted in an increased release of copper from the Cu NPs in PBS and reduced levels of nickel from the Ni NPs in saline. Both metal ions in solution and the adsorption of HRP onto the NPs can change the activity of HRP and thus influence the ROS results. The effect of HRP on the NP reactivity was shown to be solution chemistry dependent. Most notable was the evident affinity/adsorption of phosphate toward the metal NPs, followed by a reduced adsorption of HRP, the concomitant reduction in released manganese from the Mn NPs, and increased levels of released metals from the Cu NPs in PBS. Minor effects were observed for the Ni NPs. The solution pH should be monitored since the release of metals can change the solution pH and the activity of HRP is known to be pH-dependent. It is furthermore essential that solution pH adjustments are made following the addition of NaOH during diacetyl removal of DCFH-DA. Even though not observed for the given exposure conditions of this study, released metal ions could possibly induce agglomeration or partial denaturation of HRP, which in turn could result in steric hindrance for H2O2 to reach the active site of HRP. This study further emphasizes the influence of HRP on the background kinetics, its solution dependence, and effects on measured ROS signals. Different ways of correcting for the background are highlighted, as this can result in different interpretations of generated results. The results show that adsorption of HRP onto the metal NPs influenced the extent of metal release and may, depending on the investigated system, result in either under- or overestimated ROS signals if used together with the DCFH assay. HRP should hence be used with caution when measuring ROS in the presence of reactive metallic NPs. © 2021 The Authors.
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| 24. |
- Lisacek, F., et al.
(författare)
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Databases and associated tools for glycomics and glycoproteomics
- 2017
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Ingår i: High-Throughput Glycomics and Glycoproteomics. Eds: Gordan Lauc & Manfred Wuhrer. - New York : Springer. - 1064-3745. - 9781493964932 - 9781493964918 ; , s. 235-264
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- The access to biodatabases for glycomics and glycoproteomics has proven to be essential for current glycobiological research. This chapter presents available databases that are devoted to different aspects of glycobioinformatics. This includes oligosaccharide sequence databases, experimental databases, 3D structure databases (of both glycans and glycorelated proteins) and association of glycans with tissue, disease, and proteins. Specific search protocols are also provided using tools associated with experimental databases for converting primary glycoanalytical data to glycan structural information. In particular, researchers using glycoanalysis methods by U/HPLC (GlycoBase), MS (GlycoWorkbench, UniCarb-DB, GlycoDigest), and NMR (CASPER) will benefit from this chapter. In addition we also include information on how to utilize glycan structural information to query databases that associate glycans with proteins (UniCarbKB) and with interactions with pathogens (Sugar Bind). © Springer Science+Business Media New York 2017.
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| 25. |
- McCarrick, S., et al.
(författare)
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Toxtracker reporter cell lines as a tool for mechanism-based (Geno)toxicity screening of nanoparticles—metals, oxides and quantum dots
- 2020
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Ingår i: Nanomaterials. - : MDPI AG. - 2079-4991. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- The increased use of nanoparticles (NPs) requires efficient testing of their potential toxic effects. A promising approach is to use reporter cell lines to quickly assess the activation of cellular stress response pathways. This study aimed to use the ToxTracker reporter cell lines to investigate (geno)toxicity of various metal-or metal oxide NPs and draw general conclusions on NP-induced effects, in combination with our previous findings. The NPs tested in this study (n = 18) also included quantum dots (QDs) in different sizes. The results showed a large variation in cytotoxicity of the NPs tested. Furthermore, whereas many induced oxidative stress only few activated reporters related to DNA damage. NPs of manganese (Mn and Mn3O4) induced the most remarkable ToxTracker response with activation of reporters for oxidative stress, DNA damage, protein unfolding and p53-related stress. The QDs (CdTe) were highly toxic showing clearly size-dependent effects and calculations suggest surface area as the most relevant dose metric. Of all NPs investigated in this and previous studies the following induce the DNA damage reporter; CuO, Co, CoO, CdTe QDs, Mn, Mn3O4, V2O5, and welding NPs. We suggest that these NPs are of particular concern when considering genotoxicity induced by metal-and metal oxide NPs.
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| 26. |
- Nordanstig, Joakim, et al.
(författare)
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Mortality with Paclitaxel-Coated Devices in Peripheral Artery Disease.
- 2020
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Ingår i: The New England journal of medicine. - : Massachusetts Medical Society. - 1533-4406 .- 0028-4793. ; 383, s. 2538-46
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Tidskriftsartikel (refereegranskat)abstract
- The results of a recent meta-analysis aroused concern about an increased risk of death associated with the use of paclitaxel-coated angioplasty balloons and stents in lower-limb endovascular interventions for symptomatic peripheral artery disease.We conducted an unplanned interim analysis of data from a multicenter, randomized, open-label, registry-based clinical trial. At the time of the analysis, 2289 patients had been randomly assigned to treatment with drug-coated devices (the drug-coated-device group, 1149 patients) or treatment with uncoated devices (the uncoated-device group, 1140 patients). Randomization was stratified according to disease severity on the basis of whether patients had chronic limb-threatening ischemia (1480 patients) or intermittent claudication (809 patients). The single end point for this interim analysis was all-cause mortality.No patients were lost to follow-up. Paclitaxel was used as the coating agent for all the drug-coated devices. During a mean follow-up of 2.49 years, 574 patients died, including 293 patients (25.5%) in the drug-coated-device group and 281 patients (24.6%) in the uncoated-device group (hazard ratio, 1.06; 95% confidence interval, 0.92 to 1.22). At 1 year, all-cause mortality was 10.2% (117 patients) in the drug-coated-device group and 9.9% (113 patients) in the uncoated-device group. During the entire follow-up period, there was no significant difference in the incidence of death between the treatment groups among patients with chronic limb-threatening ischemia (33.4% [249 patients] in the drug-coated-device group and 33.1% [243 patients] in the uncoated-device group) or among those with intermittent claudication (10.9% [44 patients] and 9.4% [38 patients], respectively).In this randomized trial in which patients with peripheral artery disease received treatment with paclitaxel-coated or uncoated endovascular devices, the results of an unplanned interim analysis of all-cause mortality did not show a difference between the groups in the incidence of death during 1 to 4 years of follow-up. (Funded by the Swedish Research Council and others; ClinicalTrials.gov number, NCT02051088.).
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| 27. |
- Pettersson, Ingrid M, 1979, et al.
(författare)
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Living Room on the Move : Autonomous Vehicles and Social Experiences
- 2016
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Ingår i: Proceedings of the 9th Nordic Conference on Human-Computer Interaction. - New York, NY, USA : ACM. - 9781450347631 ; 23-27-October-2016
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Konferensbidrag (refereegranskat)abstract
- Developing autonomous vehicles is technically complex and up to now research has focused on technical improvement and operative safety. As the level of automation increases the role of the driver will change; from controlling every movement of the vehicle into becoming an operator/passenger. Little is known about how this new context will affect the social experiences with and within the vehicle. This workshop focuses on three different kinds of social experience and socializing, namely; between other road users and the autonomous car, the social activities taking place within the autonomous car, and lastly the relationship between the car and the operator. The workshop aims at exploring possible practices, research and design directions of autonomous vehicles in relation to these social experiences. A human-centered design approach is the core of the workshop, with playful field excursions and ideation sessions.
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| 28. |
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| 29. |
- Van Puyvelde, Heleen, et al.
(författare)
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Dietary methyl-group donor intake and breast cancer risk in the european prospective investigation into cancer and nutrition (EPIC)
- 2021
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Ingår i: Nutrients. - : MDPI AG. - 2072-6643. ; 13:6
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Tidskriftsartikel (refereegranskat)abstract
- (1) Background: Methyl-group donors (MGDs), including folate, choline, betaine, and methionine, may influence breast cancer (BC) risk through their role in one-carbon metabolism; (2) Methods: We studied the relationship between dietary intakes of MGDs and BC risk, adopting data from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort; (3) Results: 318,686 pre-and postmenopausal women were followed between enrolment in 1992–2000 and December 2013–December 2015. Dietary MGD intakes were estimated at baseline through food-frequency questionnaires. Multivariable Cox proportional hazards regression models were used to quantify the association between dietary intake of MGDs, measured both as a calculated score based on their sum and individually, and BC risk. Subgroup analyses were performed by hormone receptor status, menopausal status, and level of alcohol intake. During a mean follow-up time of 14.1 years, 13,320 women with malignant BC were identified. No associations were found between dietary intakes of the MGD score or individual MGDs and BC risk. However, a potential U-shaped relationship was observed between dietary folate intake and overall BC risk, suggesting an inverse association for intakes up to 350 µg/day compared to a reference intake of 205 µg/day. No statistically significant differences in the associations were observed by hormone receptor status, menopausal status, or level of alcohol intake; (4) Conclusions: There was no strong evidence for an association between MGDs involved in one-carbon metabolism and BC risk. However, a potential U-shaped trend was suggested for dietary folate intake and BC risk. Further research is needed to clarify this association.
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