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| 2. |
- Jain, Ruchi, et al.
(author)
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Liver nucleotide biosynthesis is linked to protection from vascular complications in individuals with long-term type 1 diabetes
- 2020
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In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
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Journal article (peer-reviewed)abstract
- Identification of biomarkers associated with protection from developing diabetic complications is a prerequisite for an effective prevention and treatment. The aim of the present study was to identify clinical and plasma metabolite markers associated with freedom from vascular complications in people with very long duration of type 1 diabetes (T1D). Individuals with T1D, who despite having longer than 30 years of diabetes duration never developed major macro- or microvascular complications (non-progressors; NP) were compared with those who developed vascular complications within 25 years from diabetes onset (rapid progressors; RP) in the Scandinavian PROLONG (n = 385) and DIALONG (n = 71) cohorts. The DIALONG study also included 75 healthy controls. Plasma metabolites were measured using gas and/or liquid chromatography coupled to mass spectrometry. Lower hepatic fatty liver indices were significant common feature characterized NPs in both studies. Higher insulin sensitivity and residual beta-cell function (C-peptide) were also associated with NPs in PROLONG. Protection from diabetic complications was associated with lower levels of the glycolytic metabolite pyruvate and APOCIII in PROLONG, and with lower levels of thiamine monophosphate and erythritol, a cofactor and intermediate product in the pentose phosphate pathway as well as higher phenylalanine, glycine and serine in DIALONG. Furthermore, T1D individuals showed elevated levels of picolinic acid as compared to the healthy individuals. The present findings suggest a potential beneficial shunting of glycolytic substrates towards the pentose phosphate and one carbon metabolism pathways to promote nucleotide biosynthesis in the liver. These processes might be linked to higher insulin sensitivity and lower liver fat content, and might represent a mechanism for protection from vascular complications in individuals with long-term T1D.
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| 3. |
- Efe, C., et al.
(author)
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Extrahepatic autoimmune diseases in primary biliary cholangitis: Prevalence and significance for clinical presentation and disease outcome
- 2021
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In: Journal of Gastroenterology and Hepatology. - : Wiley. - 0815-9319 .- 1440-1746. ; 36:4, s. 936-942
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Journal article (peer-reviewed)abstract
- Background and Aim The prevalence and clinical significance of extrahepatic autoimmune diseases (EHAIDs) have not been evaluated in a large cohort of primary biliary cholangitis (PBC). Methods The medical records of 1554 patients with PBC from 20 international centers were retrospectively reviewed. Development of decompensated cirrhosis (ascites, variceal bleeding, and/or hepatic encephalopathy) and hepatocellular carcinoma were considered clinical endpoints. Results A total of 35 different EHAIDs were diagnosed in 440 (28.3%) patients with PBC. Patients with EHAIDs were more often female (92.5%vs86.1%,P < 0.001) and seropositive for anti-mitochondrial antibodies (88%vs84%,P = 0.05) and antinuclear antibodies and/or smooth muscle antibodies (53.8%vs43.6%,P = 0.005). At presentation, patients with EHAIDs had significantly lower levels of alkaline phosphatase (1.76vs1.98 x upper limit of normal [ULN],P = 0.006), aspartate aminotransferase (1.29vs1.50 x ULN,P < 0.001), and total bilirubin (0.53vs0.58 x ULN,P = 0.002). Patients with EHAIDs and without EHAIDs had similar rates of GLOBE high-risk status (12.3%vs16.1%,P = 0.07) and Paris II response (71.4%vs69.4%,P = 0.59). Overall, event-free survival was not different in patients with and without EHAIDs (90.8%vs90.7%,P = 0.53, log rank). Coexistence of each autoimmune thyroid diseases (10.6%), Sjogren disease (8.3%), systemic sclerosis (2.9%), rheumatoid arthritis (2.7%), systemic lupus erythematosus (1.7%), celiac disease (1.7%), psoriasis (1.5%), and inflammatory bowel diseases (1.3%) did not influence the outcome. Conclusions Our study confirms that EHAIDs are frequently diagnosed in patients with PBC. The presence of EHAIDs may influence the clinical phenotype of PBC at presentation but has no impact on PBC outcome.
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| 4. |
- Goetz, C., et al.
(author)
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Cometary plasma science : Open science questions for future space missions
- 2021
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In: Experimental astronomy. - : Springer Nature. - 0922-6435 .- 1572-9508.
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Journal article (peer-reviewed)abstract
- Comets hold the key to the understanding of our Solar System, its formation and its evolution, and to the fundamental plasma processes at work both in it and beyond it. A comet nucleus emits gas as it is heated by the sunlight. The gas forms the coma, where it is ionised, becomes a plasma, and eventually interacts with the solar wind. Besides these neutral and ionised gases, the coma also contains dust grains, released from the comet nucleus. As a cometary atmosphere develops when the comet travels through the Solar System, large-scale structures, such as the plasma boundaries, develop and disappear, while at planets such large-scale structures are only accessible in their fully grown, quasi-steady state. In situ measurements at comets enable us to learn both how such large-scale structures are formed or reformed and how small-scale processes in the plasma affect the formation and properties of these large scale structures. Furthermore, a comet goes through a wide range of parameter regimes during its life cycle, where either collisional processes, involving neutrals and charged particles, or collisionless processes are at play, and might even compete in complicated transitional regimes. Thus a comet presents a unique opportunity to study this parameter space, from an asteroid-like to a Mars- and Venus-like interaction. The Rosetta mission and previous fast flybys of comets have together made many new discoveries, but the most important breakthroughs in the understanding of cometary plasmas are yet to come. The Comet Interceptor mission will provide a sample of multi-point measurements at a comet, setting the stage for a multi-spacecraft mission to accompany a comet on its journey through the Solar System. This White Paper, submitted in response to the European Space Agency’s Voyage 2050 call, reviews the present-day knowledge of cometary plasmas, discusses the many questions that remain unanswered, and outlines a multi-spacecraft European Space Agency mission to accompany a comet that will answer these questions by combining both multi-spacecraft observations and a rendezvous mission, and at the same time advance our understanding of fundamental plasma physics and its role in planetary systems.
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| 5. |
- Li, Chen, et al.
(author)
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Genome-wide Association Analysis in Humans Links Nucleotide Metabolism to Leukocyte Telomere Length
- 2020
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In: American Journal of Human Genetics. - : CELL PRESS. - 0002-9297 .- 1537-6605. ; 106:3, s. 389-404
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Journal article (peer-reviewed)abstract
- Leukocyte telomere length (LTL) is a heritable biomarker of genomic aging. In this study, we perform a genome-wide meta-analysis of LTL by pooling densely genotyped and imputed association results across large-scale European-descent studies including up to 78,592 individuals. We identify 49 genomic regions at a false dicovery rate (FDR) < 0.05 threshold and prioritize genes at 31, with five highlighting nucleotide metabolism as an important regulator of LTL. We report six genome-wide significant loci in or near SENP7, MOB1B, CARMIL1 , PRRC2A, TERF2, and RFWD3, and our results support recently identified PARP1, POT1, ATM, and MPHOSPH6 loci. Phenome-wide analyses in >350,000 UK Biobank participants suggest that genetically shorter telomere length increases the risk of hypothyroidism and decreases the risk of thyroid cancer, lymphoma, and a range of proliferative conditions. Our results replicate previously reported associations with increased risk of coronary artery disease and lower risk for multiple cancer types. Our findings substantially expand current knowledge on genes that regulate LTL and their impact on human health and disease.
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| 6. |
- Thieme, M. L., et al.
(author)
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Navigating trade-offs between dams and river conservation
- 2021
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In: Global Sustainability. - : Cambridge University Press. - 2059-4798. ; 4
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Research review (peer-reviewed)abstract
- Non-technical summary There has been a long history of conflicts, studies, and debate over how to both protect rivers and develop them sustainably. With a pause in new developments caused by the global pandemic, anticipated further implementation of the Paris Agreement and high-level global climate and biodiversity meetings in 2021, now is an opportune moment to consider the current trajectory of development and policy options for reconciling dams with freshwater system health. Technical summary We calculate potential loss of free-flowing rivers (FFRs) if proposed hydropower projects are built globally. Over 260,000 km of rivers, including Amazon, Congo, Irrawaddy, and Salween mainstem rivers, would lose free-flowing status if all dams were built. We propose a set of tested and proven solutions to navigate trade-offs associated with river conservation and dam development. These solution pathways are framed within the mitigation hierarchy and include (1) avoidance through either formal river protection or through exploration of alternative development options; (2) minimization of impacts through strategic or system-scale planning or re-regulation of downstream flows; (3) restoration of rivers through dam removal; and (4) mitigation of dam impacts through biodiversity offsets that include restoration and protection of FFRs. A series of examples illustrate how avoiding or reducing impacts on rivers is possible - particularly when implemented at a system scale - and can be achieved while maintaining or expanding benefits for climate resilience, water, food, and energy security. Social media summary Policy solutions and development pathways exist to navigate trade-offs to meet climate resilience, water, food, and energy security goals while safeguarding FFRs.
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| 7. |
- Nilsson Sommar, Johan, et al.
(author)
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Long-term exposure to particulate air pollution and black carbon in relation to natural and cause-specific mortality: a multicohort study in Sweden
- 2021
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In: Bmj Open. - : BMJ. - 2044-6055. ; 11:9
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Journal article (peer-reviewed)abstract
- Objectives To estimate concentration-response relationships for particulate matter (PM) and black carbon (BC) in relation to mortality in cohorts from three Swedish cities with comparatively low pollutant levels. Setting Cohorts from Gothenburg, Stockholm and Umea, Sweden. Design High-resolution dispersion models were used to estimate annual mean concentrations of PM with aerodynamic diameter <= 10 mu m (PM10) and <= 2.5 mu m (PM2.5), and BC, at individual addresses during each year of follow-up, 1990-2011. Moving averages were calculated for the time windows 1-5 years (lag1-5) and 6-10 years (lag6-10) preceding the outcome. Cause-specific mortality data were obtained from the national cause of death registry. Cohort-specific HRs were estimated using Cox regression models and then meta-analysed including a random effect of cohort. Participants During the study period, 7 340 cases of natural mortality, 2 755 cases of cardiovascular disease (CVD) mortality and 817 cases of respiratory and lung cancer mortality were observed among in total 68 679 individuals and 689 813 person-years of follow-up. Results Both PM10 (range: 6.3-41.9 mu g/m(3)) and BC (range: 0.2-6.8 mu g/m(3)) were associated with natural mortality showing 17% (95% CI 6% to 31%) and 9% (95% CI 0% to 18%) increased risks per 10 mu g/m(3) and 1 mu g/m(3) of lag1-5 exposure, respectively. For PM2.5 (range: 4.0-22.4 mu g/m(3)), the estimated increase was 13% per 5 mu g/m(3), but less precise (95% CI -9% to 40%). Estimates for CVD mortality appeared higher for both PM10 and PM2.5. No association was observed with respiratory mortality. Conclusion The results support an effect of long-term air pollution on natural mortality and mortality in CVD with high relative risks also at low exposure levels. These findings are relevant for future decisions concerning air quality policies.
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| 8. |
- Schmedes, Clare M., et al.
(author)
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Circulating extracellular vesicle tissue factor activity during orthohantavirus infection is associated with intravascular coagulation
- 2020
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In: Journal of Infectious Diseases. - : Oxford University Press. - 0022-1899 .- 1537-6613. ; 222:8, s. 1392-1399
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Journal article (peer-reviewed)abstract
- BACKGROUND: Puumala (PUUV) orthohantavirus causes hemorrhagic fever with renal syndrome (HFRS). HFRS patients have an activated coagulation system with increased risk of disseminated intravascular coagulation (DIC) and venous thromboembolism (VTE). The aim of the study was to determine if circulating extracellular vesicle tissue factor (EVTF) activity levels associates with DIC and VTE (grouped as intravascular coagulation) in HFRS patients.METHODS: Longitudinal samples were collected from 88 HFRS patients. Patients were stratified into groups of those with intravascular coagulation (n=27) and those who did not (n=61). We measured levels of circulating EVTF activity, fibrinogen, activated partial prothrombin time, prothrombin time international normalized ratio, D-dimer, tissue plasminogen activator (tPA), plasminogen activator inhibitor 1 (PAI-1) and platelets.RESULTS: Plasma EVTF activity was transiently increased during HFRS. Levels of EVTF activity significantly associated with plasma tPA and PAI-1, suggesting endothelial cells as a potential source. Patients with intravascular coagulation had significantly higher peak EVTF activity levels compared to those who did not. The peak EVTF activity value predicting intravascular coagulation was 0.51 ng/L with 63% sensitivity and 61% specificity with AUC 0.63 (95% CI 0.51 - 0.76), p-value 0.046.CONCLUSIONS: Increased circulating EVTF activity during HFRS is associated with intravascular coagulation.
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| 9. |
- Felton, Adam, et al.
(author)
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Correction to: Keeping pace with forestry : Multi-scale conservation in a changing production forest matrix (vol 49, pg 1050, 2020)
- 2020
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In: Ambio. - : Springer. - 0044-7447 .- 1654-7209. ; 49:5, s. 1065-1066
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Journal article (peer-reviewed)abstract
- In the original published article, the sentence “Nevertheless, semi-natural forest remnants continue to be harvested and fragmented (Svensson et al. 2018; Jonsson et al. 2019), and over 2000 forest-associated species (of 15 000 assessed) are listed as threatened on Sweden’s red-list, largely represented by macro-fungi, beetles, lichens and butterflies (Sandström 2015).”under the section Introduction was incorrect. The correct version of the sentence is “Nevertheless, semi-natural forest remnants continue to be harvested and fragmented (Svensson et al. 2018; Jonsson et al. 2019), and approximately 2000 forest-associated species (of 15 000 assessed) are on Sweden’s red-list, largely represented by macro-fungi, beetles, lichens and butterflies (Sandström 2015).”
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| 10. |
- Lundström, Mats, et al.
(author)
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Catquest-9SF functioning over a decade - a study from the Swedish National Cataract Register
- 2020
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In: Eye and Vision. - : Springer Science and Business Media LLC. - 2326-0254. ; 7:1
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Journal article (peer-reviewed)abstract
- BackgroundThe Swedish National Cataract Register (NCR) collects data on cataract surgery outcomes during March, including patient-reported outcomes using the Catquest-9SF questionnaire for over 11years. Previous studies from NCR have shown that the preoperative visual acuity has improved over time. The main purpose of this study was to evaluate the Catquest-9SF Rasch scoring performance in this changing environment. A second purpose was to describe clinical data over the same period for those who completed the questionnaire.MethodsThe performance of the Catquest-9SF was analysed by a separate Rasch analysis for each year, resulting in a preoperative and postoperative score for each participating patient in the annual cohorts. The clinical data and questionnaire scoring were analysed for each year in the period 2008-2018 inclusive.ResultsData were available for 42,023 eyes for 11 annual cohorts (2008-2018). The psychometric properties of the questionnaire were stable during the study period. Person separation (precision) for the whole period was 2.58 and varied between 2.45 and 2.72. The person reliability was 0.87 and varied between 0.86 and 0.88. The targeting of question difficulty to person ability became less accurate over time meaning that the item activities became easier to carry out without difficulty. The average targeting for the whole period was -2.06 and changed from -1.92 in 2008 to -2.31 in 2018. The person score improved both before surgery and after surgery, indicating that patients are undergoing surgery at a more able level and getting better outcomes. The average improvement by surgery decreased from 3.41 logits in 2008 to 3.21 logits in 2018 (p=0.003).Over time, patient age decreased from 75 to 74years (p<0.001) and the proportion of women decreased from 63.9 to 57.9% (p<0.001). The mean preoperative visual acuity in both the operated eye and the better eye improved over time (0.47 to 0.40 logMAR, p<0.001 and 0.22 to 0.19 logMAR, p<0.001, respectively), as did the mean postoperative visual acuity in the operated eye (0.14 to 0.09 logMAR, p<0.001).ConclusionsThe Catquest-9SF retained stable psychometric properties over this 11-year period although more recent cohorts included slightly younger patients with somewhat better vision.
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