| 1. |
- Palmer, Nicholette D, et al.
(författare)
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A genome-wide association search for type 2 diabetes genes in African Americans.
- 2012
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Ingår i: PloS one. - San Francisco : Public Library of Science (PLoS). - 1932-6203. ; 7:1, s. e29202-
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Tidskriftsartikel (refereegranskat)abstract
- African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P<0.0071), were directionally consistent in the Replication cohort and were associated with T2DM in subjects without nephropathy (P<0.05). Meta-analysis in all cases and controls revealed a single SNP reaching genome-wide significance (P<2.5×10(-8)). SNP rs7560163 (P = 7.0×10(-9), OR (95% CI) = 0.75 (0.67-0.84)) is located intergenically between RND3 and RBM43. Four additional loci (rs7542900, rs4659485, rs2722769 and rs7107217) were associated with T2DM (P<0.05) and reached more nominal levels of significance (P<2.5×10(-5)) in the overall analysis and may represent novel loci that contribute to T2DM. We have identified novel T2DM-susceptibility variants in the African-American population. Notably, T2DM risk was associated with the major allele and implies an interesting genetic architecture in this population. These results suggest that multiple loci underlie T2DM susceptibility in the African-American population and that these loci are distinct from those identified in other ethnic populations.
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| 2. |
- Duffy, J. Emmett, et al.
(författare)
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Toward a Coordinated Global Observing System for Seagrasses and Marine Macroalgae
- 2019
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Ingår i: Frontiers in Marine Science. - : Frontiers Media S.A.. - 2296-7745. ; 6
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Forskningsöversikt (refereegranskat)abstract
- In coastal waters around the world, the dominant primary producers are benthic macrophytes, including seagrasses and macroalgae, that provide habitat structure and food for diverse and abundant biological communities and drive ecosystem processes. Seagrass meadows and macroalgal forests play key roles for coastal societies, contributing to fishery yields, storm protection, biogeochemical cycling and storage, and important cultural values. These socio-economically valuable services are threatened worldwide by human activities, with substantial areas of seagrass and macroalgal forests lost over the last half-century. Tracking the status and trends in marine macrophyte cover and quality is an emerging priority for ocean and coastal management, but doing so has been challenged by limited coordination across the numerous efforts to monitor macrophytes, which vary widely in goals, methodologies, scales, capacity, governance approaches, and data availability. Here, we present a consensus assessment and recommendations on the current state of and opportunities for advancing global marine macrophyte observations, integrating contributions from a community of researchers with broad geographic and disciplinary expertise. With the increasing scale of human impacts, the time is ripe to harmonize marine macrophyte observations by building on existing networks and identifying a core set of common metrics and approaches in sampling design, field measurements, governance, capacity building, and data management. We recommend a tiered observation system, with improvement of remote sensing and remote underwater imaging to expand capacity to capture broad-scale extent at intervals of several years, coordinated with strati fied in situ sampling annually to characterize the key variables of cover and taxonomic or functional group composition, and to provide ground-truth. A robust networked system of macrophyte observations will be facilitated by establishing best practices, including standard protocols, documentation, and sharing of resources at all stages of work flow, and secure archiving of open-access data. Because such a network is necessarily distributed, sustaining it depends on close engagement of local stakeholders and focusing on building and long-term maintenance of local capacity, particularly in the developing world. Realizing these recommendations will producemore effective, efficient, and responsive observing, a more accurate global picture of change in vegetated coastal systems, and stronger international capacity for sustaining observations.
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| 3. |
- Kalinen, Sofia, et al.
(författare)
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Differences in Gut Microbiota Profiles and Microbiota Steroid Hormone Biosynthesis in Men with and Without Prostate Cancer.
- 2024
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Ingår i: European urology open science. - 2666-1683. ; 62, s. 140-150
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Tidskriftsartikel (refereegranskat)abstract
- Although prostate cancer (PCa) is the most common cancer in men in Western countries, there is significant variability in geographical incidence. This might result from genetic factors, discrepancies in screening policies, or differences in lifestyle. Gut microbiota has recently been associated with cancer progression, but its role in PCa is unclear.Characterization of the gut microbiota and its functions associated with PCa.In a prospective multicenter clinical trial (NCT02241122), the gut microbiota profiles of 181 men with a clinical suspicion of PCa were assessed utilizing 16S rRNA sequencing.Sequences were assigned to operational taxonomic units, differential abundance analysis, and α- and β-diversities, and predictive functional analyses were performed. Plasma steroid hormone levels corresponding to the predicted microbiota steroid hormone biosynthesis profiles were investigated.Of 364 patients, 181 were analyzed, 60% of whom were diagnosed with PCa. Microbiota composition and diversity were significantly different in PCa, partially affected by Prevotella 9, the most abundant genus of the cohort, and significantly higher in PCa patients. Predictive functional analyses revealed higher 5-α-reductase, copper absorption, and retinol metabolism in the PCa-associated microbiome. Plasma testosterone was associated negatively with the predicted microbial 5-α-reductase level.Gut microbiota of the PCa patients differed significantly compared with benign individuals. Microbial 5-α-reductase, copper absorption, and retinol metabolism are potential mechanisms of action. These findings support the observed association of lifestyle, geography, and PCa incidence.In this report, we found that several microbes and potential functions of the gut microbiota are altered in prostate cancer compared with benign cases. These findings suggest that gut microbiota could be the link between environmental factors and prostate cancer.
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| 4. |
- Saxena, Richa, et al.
(författare)
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Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels
- 2007
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 316:5829, s. 1331-1336
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Tidskriftsartikel (refereegranskat)abstract
- New strategies for prevention and treatment of type 2 diabetes (T2D) require improved insight into disease etiology. We analyzed 386,731 common single-nucleotide polymorphisms (SNPs) in 1464 patients with T2D and 1467 matched controls, each characterized for measures of glucose metabolism, lipids, obesity, and blood pressure. With collaborators (FUSION and WTCCC/UKT2D), we identified and confirmed three loci associated with T2D - in a noncoding region near CDKN2A and CDKN2B, in an intron of IGF2BP2, and an intron of CDKAL1 - and replicated associations near HHEX and in SLC30A8 found by a recent whole-genome association study. We identified and confirmed association of a SNP in an intron of glucokinase regulatory protein (GCKR) with serum triglycerides. The discovery of associated variants in unsuspected genes and outside coding regions illustrates the ability of genome-wide association studies to provide potentially important clues to the pathogenesis of common diseases.
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| 5. |
- Zhu, Youjian, et al.
(författare)
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Cogasification of Australian Brown Coal with Algae in a Fluidized Bed Reactor
- 2015
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Ingår i: Energy & Fuels. - : American Chemical Society (ACS). - 0887-0624 .- 1520-5029. ; 29:3, s. 1686-1700
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Tidskriftsartikel (refereegranskat)abstract
- Recently, the use of algae for CO2 abatement, wastewater treatment, and energy production has increasingly gained attention worldwide. In order to explore the potential of using algae as an alternative fuel as well as the possible challenges related to the algae gasification process, two species of macroalgae, Derbesia tenuissima and Oedogonium sp., and one type of microalgae, Scenedesmus sp. were studied in this research. In this work, Oedogonium sp. was cultivated with two protocols: producing biomass with both high and low levels of nitrogen content. Cogasification of 10 wt % algae with an Australian brown coal was performed in a fluidized bed reactor, and the effects of algae addition on syngas yield, ash composition, and bed agglomeration were investigated. It was found that CO and H-2 yield increased and CO2 yield decreased after adding three types of macroalgae in the coal, with a slight increase of carbon conversion rate, compared to the coal alone experiment. In the case of coal/Scenedesmus sp, the carbon conversion rate decreased with lower CO/CO2/H-2 yield as compared to coal alone. Samples of fly ash, bed ash, and bed material agglomerates were analyzed using scanning electron microscopy combined with an energy dispersive X-ray detector (SEM-EDX) and X-ray diffraction (XRD). It was observed that both the fly ash and bed ash samples from all coal/macroalgae tests contained more Na and K as compared to the coal test. High Ca and Fe contents were also found in the fly ash and bed ash from the coal/Scenedesmus sp. test. Significant differences in the characteristics and compositions of the ash layer on the bed particles were observed from the different tests. Agglomerates were found in the bed material samples after the cogasification tests of coal/Oedogonium N+ and coal/Oedogonium N. The formation of liquid alkalisilicates on the sand particles was considered to be the main reason for agglomeration for the coal/Oedogonium N+ and coal/Oedogonium N tests. Agglomerates of fused ash and tiny silica sand particles were also found in the coal/Scenedesmus sp. test. In this case, however, the formation of a Fe-Al silicate eutectic mixture was proposed to be the main reason for agglomeration. Debersia was suggested to be a potential alternative fuel, which can be cogasified with brown coal without any significant operating problems under the current experimental conditions. However, for the other algae types, appropriate countermeasures are needed to avoid agglomeration and defluidization in the cogasification process.
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| 6. |
- De las Cuevas, Carlos, et al.
(författare)
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Revealing the reporting disparity : VigiBase highlights underreporting of clozapine in other Western European countries compared to the UK
- 2023
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Ingår i: Schizophrenia Research. - : Elsevier. - 0920-9964 .- 1573-2509.
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Tidskriftsartikel (refereegranskat)abstract
- Background: Pharmacovigilance studies indicate clozapine history is marked by adverse drug reactions (ADRs).Objective: In a 2021 article, the United Kingdom (UK) had >90 % of European clozapine-related fatal outcomes in VigiBase, the World Health Organization's pharmacovigilance database. Two possibly opposing hypotheses could explain this disparity: 1) fewer reported fatal outcomes in other Western European countries mainly reflect underreporting to VigiBase, and 2) the higher number of UK reports reflects higher real relative mortality.Methods: VigiBase reports from clozapine's introduction to December 31, 2022, were studied for ADRs and the top 10 causes of fatal outcomes. The UK was compared with 11 other top reporting Western countries (Germany, Denmark, France, Finland, Ireland, Italy, Netherlands, Norway, Spain, Sweden and Switzerland). Nine countries (except Ireland and Switzerland) were compared after controlling for population and clozapine prescriptions.Results: The UK accounted for 29 % of worldwide clozapine-related fatal outcomes, Germany 2 % and <1 % in each of the other countries. The nonspecific label “death” was the top cause in the world (46 %) and in the UK (33 %). “Pneumonia” was second in the world (8 %), the UK (12 %), Ireland (8 %) and Finland (14 %). Assuming that our corrections for population and clozapine use are correct, other countries underreported only 1–10 % of the UK clozapine fatal outcome number.Conclusions: Different Western European countries consistently underreport to VigiBase compared to the UK, but have different reporting/publishing styles for clozapine-related ADRs/fatal outcomes. Three Scandinavian registries suggest lives are saved as clozapine use increases, but this cannot be studied in pharmacovigilance databases.
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| 7. |
- Strauss, Leena, et al.
(författare)
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Seminal vesicles and urinary bladder as sites of aromatization of androgens in men, evidenced by a CYP19A1-driven luciferase reporter mouse and human tissue specimens.
- 2013
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Ingår i: The FASEB Journal. - : Wiley. - 0892-6638 .- 1530-6860. ; 27:4, s. 1342-50
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Tidskriftsartikel (refereegranskat)abstract
- The human CYP19A1 gene is expressed in various tissues by the use of tissue-specific promoters, whereas the rodent cyp19a1 gene is expressed mainly in the gonads and brain. We generated a transgenic mouse model containing a >100-kb 5' region of human CYP19A1 gene connected to a luciferase reporter gene. The luciferase activity in mouse tissues mimicked the CYP19A1 gene expression pattern in humans. Interestingly, the reporter gene activity was 16 and 160 times higher in the urinary bladder and seminal vesicles, respectively, as compared with the activity in the testis. Accordingly, CYP19A1 gene and P450arom protein expression was detected in those human tissues. Moreover, the data revealed that the expression of CYP19A1 gene is driven by promoters PII, I.4, and I.3 in the seminal vesicles, and by promoters PII and I.4 in the urinary bladder. Furthermore, the reporter gene expression in the seminal vesicles was androgen dependent: Castration decreased the expression ∼20 times, and testosterone treatment restored it to the level of an intact mouse. This reporter mouse model facilitates studies of tissue-specific regulation of the human CYP19A1 gene, and our data provide evidence for seminal vesicles as important sites for estrogen production in males.-Strauss, L., Rantakari, P., Sjögren, K., Salminen, A., Lauren, E., Kallio, J., Damdimopoulou, P., Boström, M., Boström, P. J., Pakarinen, P., Zhang, F. P., Kujala, P., Ohlsson, C., Mäkelä, S., Poutanen, M. Seminal vesicles and urinary bladder as sites of aromatization of androgens in men, evidenced by a CYP19A1-driven luciferase reporter mouse and human tissue specimens.
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| 8. |
- Zhu, Youjian, et al.
(författare)
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Fluidized bed co-gasification of algae and wood pellets : gas yields and bed agglomeration analysis
- 2016
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Ingår i: Energy & Fuels. - : American Chemical Society (ACS). - 0887-0624 .- 1520-5029. ; 30:3, s. 1800-1809
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Tidskriftsartikel (refereegranskat)abstract
- Algae utilization in energy production has gained increasing attention as a result of its characteristics, such as high productivity, rapid growth rate, and flexible cultivation environment. In this paper, three species of algae, including a fresh water macroalgae, Oedogonium sp., a saltwater macroalgae, Derbersia tenuissima, and a microalgae species, Scenedesmus sp., were studied to explore the potential of using smaller amounts of algae fuels in blends with traditional woody biomasses in the gasification processes. Co-gasification of 10 wt % algae and 90 wt % Swedish wood pellets was performed in a fluidized bed reactor. The effects of algae addition on the syngas yield and carbon conversion rate were investigated. The addition of 10 wt % algae in wood increased the CO, H2, and CH4 yields by 3–20, 6–31, and 9–20%, respectively. At the same time, it decreased the CO2 yield by 3–18%. The carbon conversion rates were slightly increased with the addition of 10 wt % macroalgae in wood, but the microalgae addition resulted in a decrease of the carbon conversion rate by 8%. Meanwhile, the collected fly ash and bed material samples were analyzed using scanning electron microscopy combined with an energy-dispersive X-ray detector (SEM–EDX) and X-ray diffraction (XRD) technique. The fly ashes of wood/marcoalgae tests showed a higher Na content with lower Si and Ca contents compared to the wood test. The gasification tests were scheduled to last 4 h; however, only wood and wood/Derbersia gasification experiments were carried out without significant operational problems. The gasification of 10 wt % Oedogonium N+ and Oedogonium N– led to defluidization of the bed in less than 1 h, and the wood/Scenedesmus (WD/SA) test was stopped after 1.8 h as a result of severe agglomeration. It was found that the algae addition had a remarkable influence on the characteristics and compositions of the coating layer. The coating layer formation and bed agglomeration mechanism of wood/macroalgae was initiated by the reaction of alkali compounds with the bed particles to form low-temperature melting silicates (inner layer). For the WD/SA test, the agglomeration was influenced by both the composition of the original algae fuel as well as the external mineral contaminations. In summary, the operational problems experienced during the co-gasification tests of different algae–wood mixtures were assigned to the specific ash compositions of the different fuel mixtures. This showed the need for countermeasures, specifically to balance the high alkali content, to reach stable operation in a fluidized bed gasifier.
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| 9. |
- Zhu, Youjian, et al.
(författare)
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Preliminary understanding on the ash behavior of algae during co-gasification in an entrained flow reactor
- 2018
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Ingår i: Fuel processing technology. - : Elsevier. - 0378-3820 .- 1873-7188. ; 175, s. 26-34
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Tidskriftsartikel (refereegranskat)abstract
- Algae are considered as a promising alternative fuel to produce energy due to its advantages such as high production yield, short growth cycle and flexible growing environment. Unfortunately, ash-related issues restrict its thermochemical utilization due to the high ash content and especially the high alkali metal concentration. In this paper, the gasification performance and ash behavior were experimentally analysed for three macro- and micro-algal species. Clear differences in the proximate and ultimate compositions were found between the cultivated algae used in this study and macroalgae (seaweed) harvested from the marine environments. Algal biomass generally contained higher Na and P contents than lignocellulosic biomass. Microalgae also had a relatively high mineral content due to the impurities in the harvesting process which included centrifugal pumping followed by sedimentation. Co-gasification of 20 wt% algae with softwood was investigated using an entrained flow reactor. The addition of both macroalgal species Derbersia tenuissima and Oedogonium to softwood had a limited influence on the gas yields and carbon conversion. On the other hand, the addition of the microalgal species Scenedesmus significantly decreased the main gas yields and carbon conversion. Moreover, the addition of algae clearly changed the residual ash composition of the base fuel. Finally, a preliminary understanding of the ash behavior of the tested algae blends was obtained through the analysis of the fuel ashes and the collected residual ashes. Fouling and corrosion were presumably occurred during the co-gasification of wood/macroalgae blends in view of the high alkali metal content. Microalga Scenedesmus had a high mineral content which could potentially capture the alkali metal in the ash and mitigate fouling when gasified with softwood. The growing environment and harvesting method were found to be significantly affecting the ash behavior implying the need for careful consideration regarding co-gasification process.
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| 10. |
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| 11. |
- Alinezhad, Saeid, et al.
(författare)
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Validation of novel biomarkers for prostate cancer progression by the combination of bioinformatics, clinical and functional studies
- 2016
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:5
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Tidskriftsartikel (refereegranskat)abstract
- The identification and validation of biomarkers for clinical applications remains an important issue for improving diagnostics and therapy in many diseases, including prostate cancer. Gene expression profiles are routinely applied to identify diagnostic and predictive biomarkers or novel targets for cancer. However, only few predictive markers identified in silico have also been validated for clinical, functional or mechanistic relevance in disease progression. In this study, we have used a broad, bioinformatics-based approach to identify such biomarkers across a spectrum of progression stages, including normal and tumor-adjacent, premalignant, primary and late stage lesions. Bioinformatics data mining combined with clinical validation of biomarkers by sensitive, quantitative reverse-transcription PCR (qRT-PCR), followed by functional evaluation of candidate genes in disease-relevant processes, such as cancer cell proliferation, motility and invasion. From 300 initial candidates, eight genes were selected for validation by several layers of data mining and filtering. For clinical validation, differential mRNA expression of selected genes was measured by qRT-PCR in 197 clinical prostate tissue samples including normal prostate, compared against histologically benign and cancerous tissues. Based on the qRT-PCR results, significantly different mRNA expression was confirmed in normal prostate versus malignant PCa samples (for all eight genes), but also in cancer-adjacent tissues, even in the absence of detectable cancer cells, thus pointing to the possibility of pronounced field effects in prostate lesions. For the validation of the functional properties of these genes, and to demonstrate their putative relevance for disease-relevant processes, siRNA knock-down studies were performed in both 2D and 3D organotypic cell culture models. Silencing of three genes (DLX1, PLA2G7 and RHOU) in the prostate cancer cell lines PC3 and VCaP by siRNA resulted in marked growth arrest and cytotoxicity, particularly in 3D organotypic cell culture conditions. In addition, silencing of PLA2G7, RHOU, ACSM1, LAMB1 and CACNA1D also resulted in reduced tumor cell invasion in PC3 organoid cultures. For PLA2G7 and RHOU, the effects of siRNA silencing on proliferation and cell-motility could also be confirmed in 2D monolayer cultures. In conclusion, DLX1 and RHOU showed the strongest potential as useful clinical biomarkers for PCa diagnosis, further validated by their functional roles in PCa progression. These candidates may be useful for more reliable identification of relapses or therapy failures prior to the recurrence local or distant metastases.
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| 12. |
- Boström, Peter J., et al.
(författare)
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Clinical markers of morbidity, mortality and survival in bladder cancer patients treated with radical cystectomy : A systematic review
- 2020
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Ingår i: Scandinavian journal of urology. - : Taylor & Francis. - 2168-1805 .- 2168-1813. ; 54:4, s. 267-276
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Forskningsöversikt (refereegranskat)abstract
- Context: Radical cystectomy and pelvic lymph node dissection (RC and PLND) are an essential part of the treatment paradigm in high risk bladder cancer. However, these patients have high rates of morbidity and mortality related both to the treatment and to the disease.Objective:To provide overview of current literature about clinical markers that can be used to predict and improve BC-patient outcomes at the time of RC and PLND and to study if they are properly validated.Evidence acquisition: A systematic literature search was conducted according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) criteria between January 1990 and October 2018 to identify English written original and review articles relevant to this topic. Prospective and retrospective studies were included.Evidence synthesis: There are several risk factors identified from non-randomised trials that can be improved before surgery to reduce perioperative mortality and morbidity. These include poor nutritional status, anaemia, renal function and smoking. Preoperative nomograms have also been developed to help decision-making and to inform patients about the risks of surgery. They can be used to estimate risk of postoperative mortality after RC and PLND with accuracy varying from 70 to 86%. These nomograms are largely based on retrospective data. Likewise, nomograms developed to calculate estimates about patient's overall and cancer specific survival have the same limitations.Conclusion: Clinical markers to predict morbidity, mortality and survival in patients with bladder cancer treated with RC and PLND may help to improve patient outcomes and treatment decision-making, but available data come from small retrospective trials and have not been properly validated. Prospective, multi-centre studies are needed to implement and disseminate predictive clinical markers and nomograms such that they can be utilised in treatment decision-making in daily practice.
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| 13. |
- Boström, Peter J, et al.
(författare)
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Genomic Predictors of Outcome in Prostate Cancer.
- 2015
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Ingår i: European Urology. - : Elsevier BV. - 1873-7560 .- 0302-2838. ; 68:6, s. 1033-1044
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Forskningsöversikt (refereegranskat)abstract
- Given the highly variable behavior and clinical course of prostate cancer (PCa) and the multiple available treatment options, a personalized approach to oncologic risk stratification is important. Novel genetic approaches offer additional information to improve clinical decision making.
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| 14. |
- de Fouw, Jimmy, et al.
(författare)
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A facultative mutualism facilitates European seagrass meadows
- 2023
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Ingår i: Ecography. - 0906-7590 .- 1600-0587. ; 2023:5
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Tidskriftsartikel (refereegranskat)abstract
- Coastal ecosystem functioning often hinges on habitat-forming foundation species that engage in positive interactions (e.g. facilitation and mutualism) to reduce environmental stress. Seagrasses are important foundation species in coastal zones but are rapidly declining with losses typically linked to intensifying global change-related environmental stress. There is growing evidence that loss or disruption of positive interactions can amplify coastal ecosystem degradation as it compromises its stress mitigating capacity. Multiple recent studies highlight that seagrass can engage in a facultative mutualistic relationship with lucinid bivalves that alleviate sulphide toxicity. So far, however, the generality of this mutualism, and how its strength and relative importance depend on environmental conditions, remains to be investigated. Here we study the importance of the seagrass-lucinid mutualistic interaction on a continental-scale using a field survey across Europe. We found that the lucinid bivalve Loripes orbiculatus is associated with the seagrasses Zostera noltii and Zostera marina across a large latitudinal range. At locations where the average minimum temperature was above 1 °C, L. orbiculatus was present in 79% of the Zostera meadows; whereas, it was absent below this temperature. At locations above this minimum temperature threshold, mud content was the second most important determinant explaining the presence or absence of L. orbiculatus. Further analyses suggest that the presence of the lucinids have a positive effect on seagrass biomass by mitigating sulphide stress. Finally, results of a structural equation model (SEM) support the existence of a mutualistic feedback between L. orbiculatus and Z. noltii. We argue that this seagrass-lucinid mutualism should be more solidly integrated into management practices to improve seagrass ecosystem resilience to global change as well as the success of restoration efforts.
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| 15. |
- Diligent, O, et al.
(författare)
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The low-frequency reflection and scattering of the S0 Lamb mode from a circular through-thickness hole in a plate: Finite Element, analytical and experimental studies
- 2002
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Ingår i: Journal of the Acoustical Society of America. - : Acoustical Society of America (ASA). - 1520-8524 .- 0001-4966. ; 112:6, s. 2589-2601
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Tidskriftsartikel (refereegranskat)abstract
- A study of the interaction of the S0 Lamb wave with a circular through-thickness hole in a plate is presented. The study is limited to the nondispersive frequency range of this wave, in which the distributions of stress and displacement are simple. This allows a Finite Element analysis to be undertaken using a two-dimensional membrane discretization. Predictions of the direct reflection of the S0 mode and the lateral scattering of the SH0 mode are made for a range of diameters of the hole. At the same time, an analytical solution based on modal superposition is developed, and this is also used to predict the reflection and scattering coefficients. Both sets of predictions are validated by experimental measurements. It is found that the trends of the reflection coefficients for different hole diameters, frequencies and distances from the hole satisfy a simple normalization. On a detailed scale, the functions exhibit undulations which are shown to result from the interference of the direct reflection with secondary reflections which arrive slightly later.
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| 16. |
- Florez, Jose C., et al.
(författare)
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The Kruppel-like factor 11 (KLF11) Q62R polymorphism is not associated with type 2 diabetes in 8,676 people
- 2006
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Ingår i: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 55:12, s. 3620-3624
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Tidskriftsartikel (refereegranskat)abstract
- Kruppel-like factor 11 is a pancreatic transcription factor whose activity induces the insulin gene. A common glutamine-to-arginine change at codon 62 (Q62R) in its gene KLF11 has been recently associated with type 2 diabetes in two independent samples. Q62R and two other rare missense variants (A347S and T220M) were also shown to affect the function of KLF11 in vitro, and insulin levels were lower in carriers of the minor allele at Q62R. We therefore examined their impact on common type 2 diabetes in several family-based and case-control samples of northern-European ancestry, totaling 8,676 individuals. We did not detect the rare A347S and T220M variants in our samples. With respect to Q62R, despite > 99% power to detect an association of the previously published magnitude, Q62R was not associated with type 2 diabetes (pooled odds ratio 0.97 [95% Cl 0.88-1.08], P = 0.63). In a subset of normoglycemic individuals, we did not observe significant differences in various insulin traits according to genotype at KLF11 Q62R. We conclude that the KLF11 A347S and T220M mutations do not contribute to increased risk of diabetes in European-derived populations and that the Q62R polymorphism has, at best, a minor effect on diabetes risk.
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| 17. |
- Körner, Stefanie Korsgaard, et al.
(författare)
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Which data are available in central registries on bladder cancer patients in the five Nordic countries
- 2021
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Ingår i: Scandinavian journal of urology. - : Taylor & Francis. - 2168-1805 .- 2168-1813. ; 55:2, s. 135-141
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The aim of this study was to give a collective overview on all available data sources on bladder cancer patients in the Nordic countries including the amount of detail and coverage.METHODS: National representatives from five Nordic countries were asked to fill out a questionnaire on available information regarding bladder cancer patients from databases in their respective countries. Additional information was retrieved from descriptions of the relevant registries.RESULTS: : Information on overall survival was available in all countries whereas recurrence-free survival and cancer-specific survival were available for some but not all patients depending on treatment modality.CONCLUSIONS: Despite limitations, we found that it was possible to retrieve detailed information on diagnostics, treatment, and outcome for most aspects of bladder cancer in the Nordic countries on a population based, non-selected patient cohort.
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| 18. |
- Malmström, Per-Uno, et al.
(författare)
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Non-muscle-invasive bladder cancer : a vision for the future
- 2017
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Ingår i: Scandinavian journal of urology. - : Medical Journals Sweden AB. - 2168-1805 .- 2168-1813. ; 51:2, s. 87-94
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Forskningsöversikt (refereegranskat)abstract
- The management of non-muscle-invasive bladder cancer (NMIBC) has evolved from the first reports on bladder endoscopy and transurethral resection to the introduction of adjuvant intravesical treatment. However, disease recurrence and progression remain an ongoing risk, placing a heavy burden on healthcare resources and on patients' quality of life. Deeper understanding of the molecular basis of the disease and developments in optics, lasers and computer science are already offering opportunities to revolutionize care and improve long-term prognosis. This article discusses developments likely to cause a paradigm shift towards the delivery of personalized care and reduced burden of disease in NMIBC.
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| 19. |
- Malmström, Per-Uno, et al.
(författare)
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Progress towards a Nordic standard for the investigation of hematuria : 2019
- 2019
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Ingår i: Scandinavian journal of urology. - : Medical Journals Sweden AB. - 2168-1805 .- 2168-1813. ; 53:1, s. 1-6
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To describe the management of patients with hematuria in the Nordic countries in relation to bladder cancer epidemiology, especially in the context of introducing fast track pathways with the aim of proposing a common guideline.Materials and methods: Epidemiological data on bladder cancer from each country, and the combined cancer registry, Nordcan, were analyzed. The evolution of the different national recommendations and the introduction of fast track pathways were assessed. Patients' demographics, type of hematuria and cancer detection rates were analysed if available.Results: The crude incidence of bladder cancer has increased substantially since the 1960s, while the age standardized incidence has been stable during recent decades. The relative survival has increased in all countries, while the mortality has been stable. For those with microscopic hematuria there has been a clear trend towards less rigorous investigations. In the fast track pathways, introduced in three of five countries, about one in five patients with macroscopic hematuria had a cancer diagnosis. Data show that time to diagnosis has been reduced.Conclusions: The number of patients with bladder cancer is increasing in the Nordic region. The introduction of fast track pathways has been important in improving the management of patients with suspicion of the disease. Our recommendation is to focus on macroscopic hematuria in the fast track pathways. Microhematuria without any symptoms should not be an indication for cystoscopy. However, urinary tract symptoms accompanied by microhematuria can still be investigated according to respective guidelines but not necessarily within fast track pathways.
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| 20. |
- Oedorf, Kimie, et al.
(författare)
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Perioperative management of upper tract urothelial carcinoma in the Nordic countries
- 2024
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Ingår i: BMC Urology. - : BioMed Central (BMC). - 1471-2490. ; 24:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Upper tract urothelial carcinoma (UTUC) is a rare malignancy, with typically only few new cases annually per urological department. Adherence to European association of urology (EAU) guidelines on UTUC in the Nordic countries is unknown. The objective of this survey was to examine the implementation of EAU guidelines, the perioperative management and organization of the treatment of UTUC in the Nordic countries.METHODS: The electronic survey was distributed to 93 hospitals in the Nordic countries performing radical nephroureterectomy (NU). The survey consisted of 57 main questions and data was collected between December 1st, 2021 and April 23rd, 2022.RESULTS: Overall response rate was 47/93 (67%) with a completion rate of 98%. Five out of the 6 examined subjects on diagnostic practice are applied by ≥ 72% of the participating centers. NU as treatment for high-risk UTUC is performed by 37/47 (79%), and 91% include a bladder cuff excision.CONCLUSIONS: Adherence to EAU guidelines is high on diagnostic practice in the Nordic countries, whereas disease management is less coherent.
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| 21. |
- Pemberton, Nils, et al.
(författare)
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Cycloaddition of 2-thiazolines and acyl ketenes under acidic conditions results in bicyclic 1,3-oxazinones and not 6-acylpenams as earlier reported
- 2005
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Ingår i: Organic Letters. - Washington, D.C. : American Chemical Society. - 1523-7060 .- 1523-7052. ; 7:6, s. 1019-1021
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Tidskriftsartikel (refereegranskat)abstract
- Optically active 2-thiazolines 4 were previously reported to react with acyl Meldrum's acid derivatives 5 under acidic conditions (HCl (g) in benzene) to stereoselectively give 6-acylpenams 1. Recently we have discovered that the structure elucidation of these compounds was incorrect. Thus, we report new data showing that instead of acyl -lactams, the optically active isomers 3R,9R-1,3-oxazinones 3a-g are obtained stereoselectively in 38-93% yields.
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| 22. |
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| 23. |
- Wahlström, Gudrun, et al.
(författare)
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The variant rs77559646 associated with aggressive prostate cancer disrupts ANO7 mRNA splicing and protein expression.
- 2022
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Ingår i: Human molecular genetics. - 1460-2083. ; 31:12, s. 2063-2077
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Tidskriftsartikel (refereegranskat)abstract
- Prostate cancer is among the most common cancers in men, with a large fraction of the individual risk attributable to heritable factors. A majority of the diagnosed cases does not lead to a lethal disease, and hence biological markers that can distinguish between indolent and fatal forms of the disease are of great importance for guiding treatment decisions. Although over 300 genetic variants are known to be associated with prostate cancer risk, few have been associated with the risk of an aggressive disease. One such variant is rs77559646 located in ANO7. This variant has a dual function. It constitutes a missense mutation in the short isoform of ANO7 and a splice region mutation in full-length ANO7. In this study, we have analyzed the impact of the variant allele of rs77559646 on ANO7 mRNA splicing using a minigene splicing assay and by performing splicing analysis with the tools IRFinder (intron retention finder), rMATS (replicate multivariate analysis of transcript splicing) and LeafCutter on RNA sequencing data from prostate tissue of six rs77559646 variant allele carriers and 43 non-carriers. The results revealed a severe disruption of ANO7 mRNA splicing in rs77559646 variant allele carriers. Immunohistochemical analysis of prostate samples from patients homozygous for the rs77559646 variant allele demonstrated a loss of apically localized ANO7 protein. Our study is the first to provide a mechanistic explanation for the impact of a prostate cancer risk SNP on ANO7 protein production. Furthermore, the rs77559646 variant is the first known germline loss-of-function mutation described for ANO7. We suggest that loss of ANO7 contributes to prostate cancer progression.
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| 24. |
- Winckler, Wendy, et al.
(författare)
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Evaluation of common variants in the six known maturity-onset diabetes of the young (MODY) genes for association with type 2 diabetes
- 2007
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Ingår i: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 56:3, s. 685-693
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Tidskriftsartikel (refereegranskat)abstract
- An important question in human genetics is the extent to which genes causing monogenic forms of disease harbor common variants that may contribute to the more typical form of that disease. We aimed to comprehensively evaluate the extent to which common variation irk the six known maturity-onset diabetes of the young (MODY) genes, which cause a monogenic form of type 2 diabetes, is associated with type 2 diabetes. Specifically, we determined patterns of common sequence variation in the genes encoding Gck, lpf1, Tcf2, and NeuroD1 (MODY2 and MODY4-MODY6, respectively), selected a comprehensive set of 107 tag single nucleotide polymorphisms (SNPs) that captured common variation, and genotyped each in 4,206 patients and control subjects from Sweden, Finland, and Canada (including family-based studies and unrelated case-control subjects). All SNPs with a nominal P value < 0.1 for association to type 2 diabetes in this initial screen were then genotyped in an additional 4,470 subjects from North America and Poland. Of 30 nominally significant SNPs from the initial sample, 8 achieved consistent results in the replication sample. We found the strongest effect at rs757210 in intron 2 of TCF2, with corrected P values < 0.01 for an odds ratio (OR) of 1.13. This association was observed again in an independent sample of 5,891 unrelated case and control subjects and 500 families from the U.K., for an overall OR of 1.12 and a P value < 10(-6) in > 15,000 samples. We combined these results with our previous studies on HNF4 alpha and TCF1 and explicitly tested for gene-gene interactions among these variants and with several known type 2 diabetes susceptibility loci, and we found no genetic interactions between these six genes. We conclude that although rare variants in these six genes explain most cases of MODY, common variants in these same genes contribute very modestly, if at all, to the common form of type 2 diabetes.
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