| 1. |
- Bernal, Ximena E., et al.
(författare)
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Empowering Latina scientists
- 2019
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 363:6429, s. 825-826
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 2. |
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| 3. |
- Shumilova, Oleksandra, et al.
(författare)
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Simulating rewetting events in intermittent rivers and ephemeral streams : A global analysis of leached nutrients and organic matter
- 2019
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Ingår i: Global Change Biology. - : WILEY. - 1354-1013 .- 1365-2486. ; 25:5, s. 1591-1611
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Tidskriftsartikel (refereegranskat)abstract
- Climate change and human pressures are changing the global distribution and the extent of intermittent rivers and ephemeral streams (IRES), which comprise half of the global river network area. IRES are characterized by periods of flow cessation, during which channel substrates accumulate and undergo physico-chemical changes (preconditioning), and periods of flow resumption, when these substrates are rewetted and release pulses of dissolved nutrients and organic matter (OM). However, there are no estimates of the amounts and quality of leached substances, nor is there information on the underlying environmental constraints operating at the global scale. We experimentally simulated, under standard laboratory conditions, rewetting of leaves, riverbed sediments, and epilithic biofilms collected during the dry phase across 205 IRES from five major climate zones. We determined the amounts and qualitative characteristics of the leached nutrients and OM, and estimated their areal fluxes from riverbeds. In addition, we evaluated the variance in leachate characteristics in relation to selected environmental variables and substrate characteristics. We found that sediments, due to their large quantities within riverbeds, contribute most to the overall flux of dissolved substances during rewetting events (56%-98%), and that flux rates distinctly differ among climate zones. Dissolved organic carbon, phenolics, and nitrate contributed most to the areal fluxes. The largest amounts of leached substances were found in the continental climate zone, coinciding with the lowest potential bioavailability of the leached OM. The opposite pattern was found in the arid zone. Environmental variables expected to be modified under climate change (i.e. potential evapotranspiration, aridity, dry period duration, land use) were correlated with the amount of leached substances, with the strongest relationship found for sediments. These results show that the role of IRES should be accounted for in global biogeochemical cycles, especially because prevalence of IRES will increase due to increasing severity of drying events.
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| 4. |
- Baenas, Isabel, et al.
(författare)
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Impact of COVID-19 Lockdown in Eating Disorders : A Multicentre Collaborative International Study
- 2022
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Ingår i: Nutrients. - : MDPI AG. - 2072-6643. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Background. The COVID-19 lockdown has had a significant impact on mental health. Patients with eating disorders (ED) have been particularly vulnerable. Aims. (1) To explore changes in eating-related symptoms and general psychopathology during lockdown in patients with an ED from various European and Asian countries; and (2) to assess differences related to diagnostic ED subtypes, age, and geography. Methods. The sample comprised 829 participants, diagnosed with an ED according to DSM-5 criteria from specialized ED units in Europe and Asia. Participants were assessed using the COVID-19 Isolation Scale (CIES). Results. Patients with binge eating disorder (BED) experienced the highest impact on weight and ED symptoms in comparison with other ED subtypes during lockdown, whereas individuals with other specified feeding and eating disorders (OFSED) had greater deterioration in general psychological functioning than subjects with other ED subtypes. Finally, Asian and younger individuals appeared to be more resilient. Conclusions. The psychopathological changes in ED patients during the COVID-19 lockdown varied by cultural context and individual variation in age and ED diagnosis. Clinical services may need to target preventive measures and adapt therapeutic approaches for the most vulnerable patients.
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| 5. |
- Gomez-Velazquez, Melisa, et al.
(författare)
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CTCF counter-regulates cardiomyocyte development and maturation programs in the embryonic heart
- 2017
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Ingår i: PLOS Genetics. - : PUBLIC LIBRARY SCIENCE. - 1553-7390 .- 1553-7404. ; 13:8
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Tidskriftsartikel (refereegranskat)abstract
- Cardiac progenitors are specified early in development and progressively differentiate and mature into fully functional cardiomyocytes. This process is controlled by an extensively studied transcriptional program. However, the regulatory events coordinating the progression of such program from development to maturation are largely unknown. Here, we show that the genome organizer CTCF is essential for cardiogenesis and that it mediates genomic interactions to coordinate cardiomyocyte differentiation and maturation in the developing heart. Inactivation of Ctcf in cardiac progenitor cells and their derivatives in vivo during development caused severe cardiac defects and death at embryonic day 12.5. Genome wide expression analysis in Ctcf mutant hearts revealed that genes controlling mitochondrial function and protein production, required for cardiomyocyte maturation, were upregulated. However, mitochondria from mutant cardiomyocytes do not mature properly. In contrast, multiple development regulatory genes near predicted heart enhancers, including genes in the IrxA cluster, were downregulated in Ctcf mutants, suggesting that CTCF promotes cardiomyocyte differentiation by facilitating enhancer-promoter interactions. Accordingly, loss of CTCF disrupts gene expression and chromatin interactions as shown by chromatin conformation capture followed by deep sequencing. Furthermore, CRISPR-mediated deletion of an intergenic CTCF site within the IrxA cluster alters gene expression in the developing heart. Thus, CTCF mediates local regulatory interactions to coordinate transcriptional programs controlling transitions in morphology and function during heart development.
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| 6. |
- Pastor, Ada, et al.
(författare)
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Local and regional drivers of headwater streams metabolism : insights from the first AIL collaborative project
- 2017
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Ingår i: LIMNETICA. - : Asociacion Iberica de Limnologia. - 0213-8409 .- 1989-1806. ; 36:1, s. 67-85
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Tidskriftsartikel (refereegranskat)abstract
- Streams play a key role in the global biogeochemical cycles, processing material from adjacent terrestrial systems and transporting it downstream. However, the drivers of stream metabolism, especially those acting at broad spatial scales, are still not well understood. Moreover, stream metabolism can be affected by hydrological changes associated with seasonality, and thus, assessing the temporality of metabolic rates is a key question to understand stream function. This study aims to analyse the geographical and temporal patterns in stream metabolism and to identify the main drivers regulating the whole ecosystem metabolic rates at local and regional scales. Using a coordinated distributed experiment, we studied ten headwaters streams located across five European ecoregions during summer and fall 2014. We characterized the magnitude and variability of gross primary production (GPP) and ecosystem respiration (ER) with the open-channel method. Moreover, we examined several climatic, geographical, hydrological, morphological, and physicochemical variables that can potentially control stream metabolic rates. Daily rates of stream metabolism varied considerately across streams, with GPP and ER ranging from 0.06 to 4.33 g O-2 m(-2) d(-1) and from 0.72 to 14.20 g O-2 m(-2) d(-1), respectively. All streams were highly heterotrophic (P/R < 1), except the southernmost one. We found that the drier climates tended to have the highest GPP, while humid regions presented the highest ER. Between the sampling periods no statistical differences were found. Partial-least squares models (PLS) explained similar to 80% of the variance in GPP and ER rates across headwater streams and included both local and regional variables. Rates of GPP varied primarily in response to the local variables, such as streambed substrate and stream water temperature. In contrast, regional variables, such as the mean annual temperature or the land use of the catchment, had more relevance to explain ER. Overall, our results highlight that stream metabolism depends on both local and regional drivers and show the positive experience of a young network of researchers to assess scientific challenges across large-scale geographic areas.
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| 7. |
- Sternby, Hanna, et al.
(författare)
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Determinants of Severity in Acute Pancreatitis : A Nation-wide Multicenter Prospective Cohort Study
- 2019
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Ingår i: Annals of Surgery. - 1528-1140. ; 270:2, s. 348-355
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The aim of this study was to compare and validate the different classifications of severity in acute pancreatitis (AP) and to investigate which characteristics of the disease are associated with worse outcomes. SUMMARY OF BACKGROUND DATA: AP is a heterogeneous disease, ranging from uneventful cases to patients with considerable morbidity and high mortality rates. Severity classifications based on legitimate determinants of severity are important to correctly describe the course of disease. METHODS: A prospective multicenter cohort study involving patients with AP from 23 hospitals in Spain. The Atlanta Classification (AC), Revised Atlanta Classification (RAC), and Determinant-based Classification (DBC) were compared. Binary logistic multivariate analysis was performed to investigate independent determinants of severity. RESULTS: A total of 1655 patients were included; 70 patients (4.2%) died. RAC and DBC were equally superior to AC for describing the clinical course of AP. Although any kind of organ failure was associated with increased morbidity and mortality, persistent organ failure (POF) was the most significant determinant of severity. All local complications were associated with worse outcomes. Infected pancreatic necrosis correlated with high morbidity, but in the presence of POF, it was not associated to higher mortality when compared with sterile necrotizing pancreatitis. Exacerbation of previous comorbidity was associated with increased morbidity and mortality. CONCLUSION: The RAC and DBC both signify an advance in the description and differentiation of AP patients. Herein, we describe the complications of the disease independently associated to morbidity and mortality. Our findings are valuable not only when designing future studies on AP but also for the improvement of current classifications.
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| 8. |
- Swift, Imogen J, et al.
(författare)
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A systematic review of progranulin concentrations in biofluids in over 7,000 people-assessing the pathogenicity of GRN mutations and other influencing factors.
- 2024
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Ingår i: Alzheimer's Research & Therapy. - 1758-9193. ; 16:1
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Tidskriftsartikel (refereegranskat)abstract
- Pathogenic heterozygous mutations in the progranulin gene (GRN) are a key cause of frontotemporal dementia (FTD), leading to significantly reduced biofluid concentrations of the progranulin protein (PGRN). This has led to a number of ongoing therapeutic trials aiming to treat this form of FTD by increasing PGRN levels in mutation carriers. However, we currently lack a complete understanding of factors that affect PGRN levels and potential variation in measurement methods. Here, we aimed to address this gap in knowledge by systematically reviewing published literature on biofluid PGRN concentrations.Published data including biofluid PGRN concentration, age, sex, diagnosis and GRN mutation were collected for 7071 individuals from 75 publications. The majority of analyses (72%) had focused on plasma PGRN concentrations, with many of these (56%) measured with a single assay type (Adipogen) and so the influence of mutation type, age at onset, sex, and diagnosis were investigated in this subset of the data.We established a plasma PGRN concentration cut-off between pathogenic mutation carriers and non-carriers of 74.8ng/mL using the Adipogen assay based on 3301 individuals, with a CSF concentration cut-off of 3.43ng/mL. Plasma PGRN concentration varied by GRN mutation type as well as by clinical diagnosis in those without a GRN mutation. Plasma PGRN concentration was significantly higher in women than men in GRN mutation carriers (p=0.007) with a trend in non-carriers (p=0.062), and there was a significant but weak positive correlation with age in both GRN mutation carriers and non-carriers. No significant association was seen with weight or with TMEM106B rs1990622 genotype. However, higher plasma PGRN levels were seen in those with the GRN rs5848 CC genotype in both GRN mutation carriers and non-carriers.These results further support the usefulness of PGRN concentration for the identification of the large majority of pathogenic mutations in the GRN gene. Furthermore, these results highlight the importance of considering additional factors, such as mutation type, sex and age when interpreting PGRN concentrations. This will be particularly important as we enter the era of trials for progranulin-associated FTD.
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| 9. |
- Abelev, Betty, et al.
(författare)
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Measurement of prompt J/psi and beauty hadron production cross sections at mid-rapidity in pp collisions at root s=7 TeV
- 2012
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Ingår i: Journal of High Energy Physics. - 1029-8479. ; :11
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Tidskriftsartikel (refereegranskat)abstract
- The ALICE experiment at the LHC has studied J/psi production at mid-rapidity in pp collisions at root s = 7 TeV through its electron pair decay on a data sample corresponding to an integrated luminosity L-int = 5.6 nb(-1). The fraction of J/psi from the decay of long-lived beauty hadrons was determined for J/psi candidates with transverse momentum p(t) > 1,3 GeV/c and rapidity vertical bar y vertical bar < 0.9. The cross section for prompt J/psi mesons, i.e. directly produced J/psi and prompt decays of heavier charmonium states such as the psi(2S) and chi(c) resonances, is sigma(prompt J/psi) (p(t) > 1.3 GeV/c, vertical bar y vertical bar < 0.9) = 8.3 +/- 0.8(stat.) +/- 1.1 (syst.)(-1.4)(+1.5) (syst. pol.) mu b. The cross section for the production of b-hadrons decaying to J/psi with p(t) > 1.3 GeV/c and vertical bar y vertical bar < 0.9 is a sigma(J/psi <- hB) (p(t) > 1.3 GeV/c, vertical bar y vertical bar < 0.9) = 1.46 +/- 0.38 (stat.)(-0.32)(+0.26) (syst.) mu b. The results are compared to QCD model predictions. The shape of the p(t) and y distributions of b-quarks predicted by perturbative QCD model calculations are used to extrapolate the measured cross section to derive the b (b) over bar pair total cross section and d sigma/dy at mid-rapidity.
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| 10. |
- Abelev, Betty, et al.
(författare)
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Underlying Event measurements in pp collisions at root s=0.9 and 7 TeV with the ALICE experiment at the LHC
- 2012
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Ingår i: Journal of High Energy Physics. - 1029-8479. ; :7
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Tidskriftsartikel (refereegranskat)abstract
- We present measurements of Underlying Event observables in pp collisions at root s = 0 : 9 and 7 TeV. The analysis is performed as a function of the highest charged-particle transverse momentum p(T),L-T in the event. Different regions are defined with respect to the azimuthal direction of the leading (highest transverse momentum) track: Toward, Transverse and Away. The Toward and Away regions collect the fragmentation products of the hardest partonic interaction. The Transverse region is expected to be most sensitive to the Underlying Event activity. The study is performed with charged particles above three different p(T) thresholds: 0.15, 0.5 and 1.0 GeV/c. In the Transverse region we observe an increase in the multiplicity of a factor 2-3 between the lower and higher collision energies, depending on the track p(T) threshold considered. Data are compared to PYTHIA 6.4, PYTHIA 8.1 and PHOJET. On average, all models considered underestimate the multiplicity and summed p(T) in the Transverse region by about 10-30%.
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| 11. |
- Aguiar, Diana, et al.
(författare)
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Transforming critical agrarian studies: : Solidarity, scholar-activism and emancipatory agendas in and from the Global South
- 2023
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Ingår i: Journal of Peasant Studies. - 0306-6150. ; 50:2, s. 758-786
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Tidskriftsartikel (refereegranskat)abstract
- This paper examines the challenges and opportunities faced bycritical agrarian scholars in and from the Global South. We arguethat despite the historical and structural limitations, the criticaljuncture of convergence of crises and renewed interest inagrarian political economies offers an opportunity for fostering adiverse research agenda that opens space for critical perspectivesabout, from and by the Global South, which is mostly absent inmainstream scholarship dominated by the Global North. We alsopropose doing so by enhancing solidarity to transform injusticeswithin academia and other spaces of knowledge production anddissemination. To develop the argument,first, we reflect on themultiplicity of crises in rural areas and the changing character ofsocial struggles, as well as the interlinkages betweenenvironmental crises and the re-emergence of critical agrarianstudies that are reshaping the agrarian question. Then, we discussthe implications and conditions of the political agenda carriedout by a scholar-activist movement working on agrarian studiesfrom the Global South. Drawing on our experience as theCollective of Agrarian Scholar-Activists from the South (CASAS),we conclude by proposing three ways forward for enhancingsolidarity through networks of scholar-activists: knowledgeaccessibility, cooperative organization, and co-production ofknowledge
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| 12. |
- Agustin, Sanchez-Arcilla, et al.
(författare)
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Introduction
- 2008
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Ingår i: Journal of Hydraulic Research. - 0022-1686. ; 46:2, s. 179-182
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 13. |
- Antoniou, Antonis C., et al.
(författare)
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A locus on 19p13 modifies risk of breast cancer in BRCA1 mutation carriers and is associated with hormone receptor-negative breast cancer in the general population
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 42:10, s. 885-892
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Tidskriftsartikel (refereegranskat)abstract
- Germline BRCA1 mutations predispose to breast cancer. To identify genetic modifiers of this risk, we performed a genome-wide association study in 1,193 individuals with BRCA1 mutations who were diagnosed with invasive breast cancer under age 40 and 1,190 BRCA1 carriers without breast cancer diagnosis over age 35. We took forward 96 SNPs for replication in another 5,986 BRCA1 carriers (2,974 individuals with breast cancer and 3,012 unaffected individuals). Five SNPs on 19p13 were associated with breast cancer risk (P-trend = 2.3 x 10(-9) to Ptrend = 3.9 x 10(-7)), two of which showed independent associations (rs8170, hazard ratio (HR) = 1.26, 95% CI 1.17-1.35; rs2363956 HR = 0.84, 95% CI 0.80-0.89). Genotyping these SNPs in 6,800 population-based breast cancer cases and 6,613 controls identified a similar association with estrogen receptor-negative breast cancer (rs2363956 per-allele odds ratio (OR) = 0.83, 95% CI 0.75-0.92, P-trend = 0.0003) and an association with estrogen receptor-positive disease in the opposite direction (OR = 1.07, 95% CI 1.01-1.14, P-trend = 0.016). The five SNPs were also associated with triple-negative breast cancer in a separate study of 2,301 triple-negative cases and 3,949 controls (Ptrend = 1 x 10(-7) to Ptrend = 8 x 10(-5); rs2363956 per-allele OR = 0.80, 95% CI 0.74-0.87, P-trend = 1.1 x 10(-7)).
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| 14. |
- Baenas, Isabel, et al.
(författare)
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Does Confinement Affect Treatment Dropout Rates in Patients With Gambling Disorder? A Nine-Month Observational Study
- 2021
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Ingår i: Frontiers in Psychology. - : Frontiers Media SA. - 1664-1078. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Background and Aims: COVID-19 pandemic and confinement have represented a challenge for patients with gambling disorder (GD). Regarding treatment outcome, dropout may have been influenced by these adverse circumstances. The aims of this study were: (a) to analyze treatment dropout rates in patients with GD throughout two periods: during and after the lockdown and (b) to assess clinical features that could represent vulnerability factors for treatment dropout. Methods: The sample consisted of n=86 adults, mostly men (n=79, 91.9%) and with a mean age of 45years old (SD=16.85). Patients were diagnosed with GD according to DSM-5 criteria and were undergoing therapy at a Behavioral Addiction Unit when confinement started. Clinical data were collected through a semi-structured interview and protocolized psychometric assessment. A brief telephone survey related to COVID-19 concerns was also administered at the beginning of the lockdown. Dropout data were evaluated at two moments throughout a nine-month observational period (T1: during the lockdown, and T2: after the lockdown). Results: The risk of dropout during the complete observational period was R=32/86=0.372 (37.2%), the Incidence Density Rate (IDR) ratio T2/T1 being equal to 0.052/0.033=1.60 (p=0.252). Shorter treatment duration (p=0.007), lower anxiety (p=0.025), depressive symptoms (p=0.045) and lower use of adaptive coping strategies (p=0.046) characterized patients who abandoned treatment during the lockdown. Briefer duration of treatment (p=0.001) and higher employment concerns (p=0.044) were highlighted in the individuals who dropped out after the lockdown. Treatment duration was a predictor of dropout in both periods (p=0.005 and p<0.001, respectively). Conclusion: The present results suggest an impact of the COVID-19 pandemic on treatment dropout among patients with GD during and after the lockdown, being treatment duration a predictor of dropout. Assessing vulnerability features in GD may help clinicians identify high-risk individuals and enhance prevention and treatment approaches in future similar situations.
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| 15. |
- Berglund, Lisa, et al.
(författare)
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Glucose-Dependent Insulinotropic Polypeptide (GIP) Stimulates Osteopontin Expression in the Vasculature via Endothelin-1 and CREB.
- 2016
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Ingår i: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 65:1, s. 239-254
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Tidskriftsartikel (refereegranskat)abstract
- Glucose-dependent insulinotropic polypeptide (GIP) is an incretin hormone with extrapancreatic effects beyond glycemic control. Here we demonstrate unexpected effects of GIP signaling in the vasculature. GIP induces the expression of the pro-atherogenic cytokine osteopontin (OPN) in mouse arteries, via local release of endothelin-1 (ET-1) and activation of cAMP response element binding protein (CREB). Infusion of GIP increases plasma OPN levels in healthy individuals. Plasma ET-1 and OPN levels are positively correlated in patients with critical limb ischemia. Fasting GIP levels are higher in individuals with a history of cardiovascular disease (myocardial infarction, stroke) when compared to controls. GIP receptor (GIPR) and OPN mRNA levels are higher in carotid endarterectomies from patients with symptoms (stroke, transient ischemic attacks, amaurosis fugax) than in asymptomatic patients; and expression associates to parameters characteristic of unstable and inflammatory plaques (increased lipid accumulation, macrophage infiltration and reduced smooth muscle cell content). While GIPR expression is predominantly endothelial in healthy arteries from human, mouse, rat and pig; remarkable up-regulation is observed in endothelial and smooth muscle cells upon culture conditions yielding a "vascular disease-like" phenotype. Moreover, a common variant rs10423928 in the GIPR gene associated with increased risk of stroke in type 2 diabetes patients.
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| 16. |
- Berglund, Lisa, et al.
(författare)
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NFAT regulates the expression of AIF-1 and IRT-1: Yin and yang splice variants of neointima formation and atherosclerosis.
- 2012
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Ingår i: Cardiovascular Research. - : Oxford University Press (OUP). - 1755-3245 .- 0008-6363. ; 93, s. 414-423
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Tidskriftsartikel (refereegranskat)abstract
- Aims Alternative transcription and splicing of the allograft inflammatory factor-1 (AIF-1) gene results in the expression of two different proteins: AIF-1 and interferon responsive transcript-1 (IRT-1). Here we explore the impact of AIF-1 and IRT-1 on vascular smooth muscle cell (VSMC) activation and neointima formation, the mechanisms underlying their alternative splicing, and associations of AIF-1 and IRT-1 mRNA with parameters defining human atherosclerotic plaque phenotype.Methods and results Translation of AIF-1 and IRT-1 results in different products with contrasting cellular distribution and functions. Overexpression of AIF-1 stimulates migration and proliferation of human VSMCs, whereas IRT-1 exerts opposite effects. Adenoviral infection of angioplasty-injured rat carotid arteries with AdAIF-1 exacerbates intima hyperplasia, whereas infection with AdIRT-1 reduces neointima. Expression of these variants is modulated by changes in nuclear factor of activated T-cells (NFAT) activity. Pharmacological inhibition of NFAT or targeting of NFATc3 with siRNA lowers the AIF-1/IRT-1 ratio and favors an anti-proliferative outcome. NFAT acts as a repressor on the IRT-1 transcriptional start site, which is also sensitive to interferon-γ stimulation. Expression of AIF-1 mRNA in human carotid plaques associates with less extracellular matrix and a more pro-inflammatory plaque and plasma profile, features that may predispose to plaque rupture. In contrast, expression of IRT-1 mRNA associates with a less aggressive phenotype and less VSMCs at the most stenotic region of the plaque.Conclusions Inhibition of NFAT signaling, by shifting the AIF-1/IRT-1 ratio, may be an attractive target to regulate the VSMC response to injury and manipulate plaque stability in atherosclerosis.
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| 17. |
- Carsin, Anne-Elie, et al.
(författare)
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Spirometric patterns in young and middle-aged adults : a 20-year European study
- 2024
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Ingår i: Thorax. - : BMJ Publishing Group Ltd. - 0040-6376 .- 1468-3296. ; 79:2, s. 153-162
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Tidskriftsartikel (refereegranskat)abstract
- Background Understanding the natural history of abnormal spirometric patterns at different stages of life is critical to identify and optimise preventive strategies. We aimed to describe characteristics and risk factors of restrictive and obstructive spirometric patterns occurring before 40 years (young onset) and between 40 and 61 years (mid-adult onset). Methods We used data from the population- based cohort of the European Community Respiratory Health Survey (ECRHS). Prebronchodilator forced expiratory volume in one second (FEV 1) and forced vital capacity (FVC) were assessed longitudinally at baseline (ECRHS1, 1993-1994) and again 20 years later ( ECRHS3, 2010-2013). Spirometry patterns were defined as: restrictive if FEV1/ FVC >= LLN and FVC<10th percentile, obstructive if FEV1/FVC
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| 18. |
- Conte, Benedetta, et al.
(författare)
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A 14-gene B-cell immune signature in early-stage triple-negative breast cancer (TNBC) : a pooled analysis of seven studies
- 2024
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Ingår i: EBioMedicine. - 2352-3964. ; 102
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Tidskriftsartikel (refereegranskat)abstract
- Background: Early-stage triple-negative breast cancer (TNBC) displays clinical and biological diversity. From a biological standpoint, immune infiltration plays a crucial role in TNBC prognosis. Currently, there is a lack of genomic tools aiding in treatment decisions for TNBC. This study aims to assess the effectiveness of a B-cell/immunoglobulin signature (IGG) alone, or in combination with tumor burden, in predicting prognosis and treatment response in patients with TNBC. Methods: Genomic and clinical data were retrieved from 7 cohorts: SCAN-B (N = 874), BrighTNess (n = 482), CALGB-40603 (n = 389), METABRIC (n = 267), TCGA (n = 118), GSE58812 (n = 107), GSE21653 (n = 67). IGG and a risk score integrating IGG with tumor/nodal staging (IGG-Clin) were assessed for event-free survival (EFS) and overall survival (OS) in each cohort. Random effects model was used to derive pooled effect sizes. Association of IGG with pathological complete response (pCR) was assessed in CALGB-40603 and BrighTNess. Immune significance of IGG was estimated through CIBERSORTx and EcoTyper. Findings: IGG was associated with improved EFS (pooled HR = 0.77, [95% CI = 0.70–0.85], I2 = 18%) and OS (pooled HR = 0.79, [0.73–0.85], I2 = 0%) across cohorts, and was predictive of pCR in CALGB-40603 (OR 1.25, [1.10–1.50]) and BrighTNess (OR 1.57 [1.25–1.98]). IGG-Clin was predictive of recurrence (pooled HR = 2.11, [1.75–2.55], I2 = 0%) and death (pooled HR = 1.99, 95% [0.84–4.73], I2 = 79%) across cohorts. IGG was associated with adaptive immune response at CIBERSORTx and EcoTyper analysis. Interpretation: IGG is linked to improved prognosis and pCR in early-stage TNBC. The integration of IGG alongside tumor and nodal staging holds promise as an approach to identify patients benefitting from intensified or de-intensified treatments. Funding: This study received funding from: Associació Beca Marta Santamaria, European Union's Horizon 2020 research and innovation and Marie Skłodowska–Curie Actions programs, Fundación FERO, Fundación CRIS contra el cáncer, Agència de Gestó d'Ajuts Universitaris i de Recerca, Instituto de Salud Carlos III, Fundación Contigo, Asociación Cáncer de Mama Metastásico IV, Breast Cancer Research Foundation, RESCUER, Fundación científica AECC and FSEOM.
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| 19. |
- De Winther, Menno P.J., et al.
(författare)
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Translational opportunities of single-cell biology in atherosclerosis
- 2023
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 44:14, s. 1216-1230
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Forskningsöversikt (refereegranskat)abstract
- The advent of single-cell biology opens a new chapter for understanding human biological processes and for diagnosing, monitoring, and treating disease. This revolution now reaches the field of cardiovascular disease (CVD). New technologies to interrogate CVD samples at single-cell resolution are allowing the identification of novel cell communities that are important in shaping disease development and direct towards new therapeutic strategies. These approaches have begun to revolutionize atherosclerosis pathology and redraw our understanding of disease development. This review discusses the state-of-the-art of single-cell analysis of atherosclerotic plaques, with a particular focus on human lesions, and presents the current resolution of cellular subpopulations and their heterogeneity and plasticity in relation to clinically relevant features. Opportunities and pitfalls of current technologies as well as the clinical impact of single-cell technologies in CVD patient care are highlighted, advocating for multidisciplinary and international collaborative efforts to join the cellular dots of CVD.
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| 20. |
- Ellison, Stephen, et al.
(författare)
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Attenuation of Experimental Atherosclerosis by Interleukin-19.
- 2013
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Ingår i: Arteriosclerosis, Thrombosis and Vascular Biology. - 1524-4636. ; 33:10, s. 2316-2324
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Tidskriftsartikel (refereegranskat)abstract
- Interleukin-19 (IL-19) is a putative Th2, anti-inflammatory interleukin. Its expression and potential role in atherogenesis are unknown. IL-19 is not detected in normal artery and is expressed to a greater degree in plaque from symptomatic versus asymptomatic patients, suggesting a compensatory counter-regulatory function. We tested whether IL-19 could reduce atherosclerosis in susceptible mice and identified plausible mechanisms.
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| 21. |
- Gómez-Gener, Lluís, et al.
(författare)
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Hot spots for carbon emissions from Mediterranean fluvial networks during summer drought
- 2015
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Ingår i: Biogeochemistry. - : Springer Science and Business Media LLC. - 0168-2563 .- 1573-515X. ; 125:3, s. 409-426
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Tidskriftsartikel (refereegranskat)abstract
- During summer drought, Mediterranean fluvial networks are transformed into highly heterogeneous landscapes characterized by different environments (i.e., running and impounded waters, isolated river pools and dry beds). This hydrological setting defines novel biogeochemically active areas that could potentially increase the rates of carbon emissions from the fluvial network to the atmosphere. Using chamber methods, we aimed to identify hot spots for carbon dioxide (CO2) and methane (CH4) emissions from two typical Mediterranean fluvial networks during summer drought. The CO2 efflux from dry beds (mean ± SE = 209 ± 10 mmol CO2 m−2 d−1) was comparable to that from running waters (120 ± 33 mmol m−2 d−1) and significantly higher than from impounded waters (36.6 ± 8.5 mmol m−2 d−1) and isolated pools (17.2 ± 0.9 mmol m−2 d−1). In contrast, the CH4 efflux did not significantly differ among environments, although the CH4 efflux was notable in some impounded waters (13.9 ± 10.1 mmol CH4 m−2 d−1) and almost negligible in the remaining environments (mean <0.3 mmol m−2 d−1). Diffusion was the only mechanism driving CO2 efflux in all environments and was most likely responsible for CH4 efflux in running waters, isolated pools and dry beds. In contrast, the CH4 efflux in impounded waters was primarily ebullition-based. Using a simple heuristic approach to simulate potential changes in carbon emissions from Mediterranean fluvial networks under future hydrological scenarios, we show that an extreme drying out (i.e., a four-fold increase of the surface area of dry beds) would double the CO2 efflux from the fluvial network. Correspondingly, an extreme transformation of running waters into impounded waters (i.e., a twofold increase of the surface area of impounded waters) would triple the CH4 efflux. Thus, carbon emissions from dry beds and impounded waters should be explicitly considered in carbon assessments of fluvial networks, particularly under predicted global change scenarios, which are expected to increase the spatial and temporal extent of these environments.
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| 22. |
- Gomez-Gener, Lluis, et al.
(författare)
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When Water Vanishes : Magnitude and Regulation of Carbon Dioxide Emissions from Dry Temporary Streams
- 2016
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Ingår i: Ecosystems (New York. Print). - : Springer Science and Business Media LLC. - 1432-9840 .- 1435-0629. ; 19:4, s. 710-723
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Tidskriftsartikel (refereegranskat)abstract
- Most fluvial networks worldwide include watercourses that recurrently cease to flow and run dry. The spatial and temporal extent of the dry phase of these temporary watercourses is increasing as a result of global change. Yet, current estimates of carbon emissions from fluvial networks do not consider temporary watercourses when they are dry. We characterized the magnitude and variability of carbon emissions from dry watercourses by measuring the carbon dioxide (CO2) flux from 10 dry streambeds of a fluvial network during the dry period and comparing it to the CO2 flux from the same streambeds during the flowing period and to the CO2 flux from their adjacent upland soils. We also looked for potential drivers regulating the CO2 emissions by examining the main physical and chemical properties of dry streambed sediments and adjacent upland soils. The CO2 efflux from dry streambeds (mean +/- A SD = 781.4 +/- A 390.2 mmol m(-2) day(-1)) doubled the CO2 efflux from flowing streambeds (305.6 +/- A 206.1 mmol m(-2) day(-1)) and was comparable to the CO2 efflux from upland soils (896.1 +/- A 263.2 mmol m(-2) day(-1)). However, dry streambed sediments and upland soils were physicochemically distinct and differed in the variables regulating their CO2 efflux. Overall, our results indicate that dry streambeds constitute a unique and biogeochemically active habitat that can emit significant amounts of CO2 to the atmosphere. Thus, omitting CO2 emissions from temporary streams when they are dry may overlook the role of a key component of the carbon balance of fluvial networks.
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| 23. |
- Jansen, Iris E, et al.
(författare)
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Genome-wide meta-analysis for Alzheimer's disease cerebrospinal fluid biomarkers.
- 2022
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Ingår i: Acta neuropathologica. - : Springer Science and Business Media LLC. - 1432-0533 .- 0001-6322. ; 144:5, s. 821-842
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Tidskriftsartikel (refereegranskat)abstract
- Amyloid-beta 42 (Aβ42) and phosphorylated tau (pTau) levels in cerebrospinal fluid (CSF) reflect core features of the pathogenesis of Alzheimer's disease (AD) more directly than clinical diagnosis. Initiated by the European Alzheimer & Dementia Biobank (EADB), the largest collaborative effort on genetics underlying CSF biomarkers was established, including 31 cohorts with a total of 13,116 individuals (discovery n=8074; replication n=5042 individuals). Besides the APOE locus, novel associations with two other well-established AD risk loci were observed; CR1 was shown a locus for Aβ42 and BIN1 for pTau. GMNC and C16orf95 were further identified as loci for pTau, of which the latter is novel. Clustering methods exploring the influence of all known AD risk loci on the CSF protein levels, revealed 4 biological categories suggesting multiple Aβ42 and pTau related biological pathways involved in the etiology of AD. In functional follow-up analyses, GMNC and C16orf95 both associated with lateral ventricular volume, implying an overlap in genetic etiology for tau levels and brain ventricular volume.
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| 24. |
- Jansen, Willemijn J, et al.
(författare)
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Prevalence Estimates of Amyloid Abnormality Across the Alzheimer Disease Clinical Spectrum.
- 2022
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Ingår i: JAMA neurology. - : American Medical Association (AMA). - 2168-6157 .- 2168-6149. ; 79:3, s. 228-243
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Tidskriftsartikel (refereegranskat)abstract
- One characteristic histopathological event in Alzheimer disease (AD) is cerebral amyloid aggregation, which can be detected by biomarkers in cerebrospinal fluid (CSF) and on positron emission tomography (PET) scans. Prevalence estimates of amyloid pathology are important for health care planning and clinical trial design.To estimate the prevalence of amyloid abnormality in persons with normal cognition, subjective cognitive decline, mild cognitive impairment, or clinical AD dementia and to examine the potential implications of cutoff methods, biomarker modality (CSF or PET), age, sex, APOE genotype, educational level, geographical region, and dementia severity for these estimates.This cross-sectional, individual-participant pooled study included participants from 85 Amyloid Biomarker Study cohorts. Data collection was performed from January 1, 2013, to December 31, 2020. Participants had normal cognition, subjective cognitive decline, mild cognitive impairment, or clinical AD dementia. Normal cognition and subjective cognitive decline were defined by normal scores on cognitive tests, with the presence of cognitive complaints defining subjective cognitive decline. Mild cognitive impairment and clinical AD dementia were diagnosed according to published criteria.Alzheimer disease biomarkers detected on PET or in CSF.Amyloid measurements were dichotomized as normal or abnormal using cohort-provided cutoffs for CSF or PET or by visual reading for PET. Adjusted data-driven cutoffs for abnormal amyloid were calculated using gaussian mixture modeling. Prevalence of amyloid abnormality was estimated according to age, sex, cognitive status, biomarker modality, APOE carrier status, educational level, geographical location, and dementia severity using generalized estimating equations.Among the 19097 participants (mean [SD] age, 69.1 [9.8] years; 10148 women [53.1%]) included, 10139 (53.1%) underwent an amyloid PET scan and 8958 (46.9%) had an amyloid CSF measurement. Using cohort-provided cutoffs, amyloid abnormality prevalences were similar to 2015 estimates for individuals without dementia and were similar across PET- and CSF-based estimates (24%; 95% CI, 21%-28%) in participants with normal cognition, 27% (95% CI, 21%-33%) in participants with subjective cognitive decline, and 51% (95% CI, 46%-56%) in participants with mild cognitive impairment, whereas for clinical AD dementia the estimates were higher for PET than CSF (87% vs 79%; mean difference, 8%; 95% CI, 0%-16%; P=.04). Gaussian mixture modeling-based cutoffs for amyloid measures on PET scans were similar to cohort-provided cutoffs and were not adjusted. Adjusted CSF cutoffs resulted in a 10% higher amyloid abnormality prevalence than PET-based estimates in persons with normal cognition (mean difference, 9%; 95% CI, 3%-15%; P=.004), subjective cognitive decline (9%; 95% CI, 3%-15%; P=.005), and mild cognitive impairment (10%; 95% CI, 3%-17%; P=.004), whereas the estimates were comparable in persons with clinical AD dementia (mean difference, 4%; 95% CI, -2% to 9%; P=.18).This study found that CSF-based estimates using adjusted data-driven cutoffs were up to 10% higher than PET-based estimates in people without dementia, whereas the results were similar among people with dementia. This finding suggests that preclinical and prodromal AD may be more prevalent than previously estimated, which has important implications for clinical trial recruitment strategies and health care planning policies.
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| 25. |
- Jansen, Willemijn J, et al.
(författare)
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Prevalence of cerebral amyloid pathology in persons without dementia: a meta-analysis.
- 2015
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Ingår i: JAMA. - : American Medical Association (AMA). - 1538-3598 .- 0098-7484. ; 313:19, s. 1924-38
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Tidskriftsartikel (refereegranskat)abstract
- Cerebral amyloid-β aggregation is an early pathological event in Alzheimer disease (AD), starting decades before dementia onset. Estimates of the prevalence of amyloid pathology in persons without dementia are needed to understand the development of AD and to design prevention studies.
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| 26. |
- Jiménez-Balado, Joan, et al.
(författare)
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DNA methylation and stroke prognosis : an epigenome-wide association study
- 2024
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Ingår i: Clinical Epigenetics. - : BioMed Central (BMC). - 1868-7083. ; 16:1
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Tidskriftsartikel (refereegranskat)abstract
- Background and aimsStroke is the leading cause of adult-onset disability. Although clinical factors influence stroke outcome, there is a significant variability among individuals that may be attributed to genetics and epigenetics, including DNA methylation (DNAm). We aimed to study the association between DNAm and stroke prognosis.Methods and resultsTo that aim, we conducted a two-phase study (discovery-replication and meta-analysis) in Caucasian patients with ischemic stroke from two independent centers (BasicMar [discovery, N = 316] and St. Pau [replication, N = 92]). Functional outcome was assessed using the modified Rankin Scale (mRS) at three months after stroke, being poor outcome defined as mRS > 2. DNAm was determined using the 450K and EPIC BeadChips in whole-blood samples collected within the first 24 h. We searched for differentially methylated positions (DMPs) in 370,344 CpGs, and candidates below p-value < 10–5 were subsequently tested in the replication cohort. We then meta-analyzed DMP results from both cohorts and used them to identify differentially methylated regions (DMRs).After doing the epigenome-wide association study, we found 29 DMPs at p-value < 10–5 and one of them was replicated: cg24391982, annotated to thrombospondin-2 (THBS2) gene (p-valuediscovery = 1.54·10–6; p-valuereplication = 9.17·10–4; p-valuemeta-analysis = 6.39·10–9). Besides, four DMRs were identified in patients with poor outcome annotated to zinc finger protein 57 homolog (ZFP57), Arachidonate 12-Lipoxygenase 12S Type (ALOX12), ABI Family Member 3 (ABI3) and Allantoicase (ALLC) genes (p-value < 1·10–9 in all cases).DiscussionPatients with poor outcome showed a DMP at THBS2 and four DMRs annotated to ZFP57, ALOX12, ABI3 and ALLC genes. This suggests an association between stroke outcome and DNAm, which may help identify new stroke recovery mechanisms.
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| 27. |
- Jimenez-Murcia, Susana, et al.
(författare)
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Gambling Habits in Spanish Women : The Social Gambling Questionnaire for Women (SGQW-47), A new screening instrument.
- 2017. - 1
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Ingår i: Gambling disorders in women. - London : Routledge. - 9781315627625 ; , s. 22-34
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Gambling has been a common activity across societies and cultures. To better understand gambling gender differences in Spain it is important to consider cultural aspects as well as the epidemiology of gambling and pathological gambling in this country. However, it is important to highlight that no national epidemiological studies have yet been conducted in Spain as a whole and the estimated prevalence results from regional studies carried out in Catalonia, Andalusia and Galicia. Few studies have explored gender differences and very few have been conducted so far in Spain. When focusing on gambling behavior during treatment, a recent study describes different gambling patterns between the sexes in a Spanish population. Given the low number of studies exploring female gambling behaviors, the aim of the study was to provide a self-report questionnaire to assess responsible gambling behaviors in Spanish females. As for predictors of gambling behavior, low socioeconomic status emerged as the unique socio-demographic factor for problematic gambling.
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| 28. |
- Jones, Benedict C, et al.
(författare)
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To which world regions does the valence-dominance model of social perception apply?
- 2021
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Ingår i: Nature Human Behaviour. - : Springer Science and Business Media LLC. - 2397-3374. ; 5:1, s. 159-169
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Tidskriftsartikel (refereegranskat)abstract
- Over the past 10 years, Oosterhof and Todorov's valence-dominance model has emerged as the most prominent account of how people evaluate faces on social dimensions. In this model, two dimensions (valence and dominance) underpin social judgements of faces. Because this model has primarily been developed and tested in Western regions, it is unclear whether these findings apply to other regions. We addressed this question by replicating Oosterhof and Todorov's methodology across 11 world regions, 41 countries and 11,570 participants. When we used Oosterhof and Todorov's original analysis strategy, the valence-dominance model generalized across regions. When we used an alternative methodology to allow for correlated dimensions, we observed much less generalization. Collectively, these results suggest that, while the valence-dominance model generalizes very well across regions when dimensions are forced to be orthogonal, regional differences are revealed when we use different extraction methods and correlate and rotate the dimension reduction solution. PROTOCOL REGISTRATION: The stage 1 protocol for this Registered Report was accepted in principle on 5 November 2018. The protocol, as accepted by the journal, can be found at https://doi.org/10.6084/m9.figshare.7611443.v1 .
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| 29. |
- Kuppler, Jonas, et al.
(författare)
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Global gradients in intraspecific variation in vegetative and floral traits are partially associated with climate and species richness
- 2020
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Ingår i: Global Ecology and Biogeography. - : Wiley. - 1466-822X .- 1466-8238. ; 29:6, s. 992-1007
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Tidskriftsartikel (refereegranskat)abstract
- AimIntraspecific trait variation (ITV) within natural plant communities can be large, influencing local ecological processes and dynamics. Here, we shed light on how ITV in vegetative and floral traits responds to large‐scale abiotic and biotic gradients (i.e., climate and species richness). Specifically, we tested whether associations of ITV with temperature, precipitation and species richness were consistent with any of four hypotheses relating to stress tolerance and competition. Furthermore, we estimated the degree of correlation between ITV in vegetative and floral traits and how they vary along the gradients.LocationGlobal.Time period1975–2016.Major taxa studiedHerbaceous and woody plants.MethodsWe compiled a dataset of 18,401 measurements of the absolute extent of ITV (measured as the coefficient of variation) in nine vegetative and seven floral traits from 2,822 herbaceous and woody species at 2,372 locations.ResultsLarge‐scale associations between ITV and climate were trait specific and more prominent for vegetative traits, especially leaf morphology, than for floral traits. The ITV showed pronounced associations with climate, with lower ITV values in colder areas and higher values in drier areas. The associations of ITV with species richness were inconsistent across traits. Species‐specific associations across gradients were often idiosyncratic, and covariation in ITV was weaker between vegetative and floral traits than within the two trait groups.Main conclusionsOur results show that, depending on the traits considered, ITV either increased or decreased with climate stress and species richness, suggesting that both factors can constrain or enhance ITV, which might foster plant‐population persistence in stressful conditions. Given the species‐specific responses and covariation in ITV, associations can be hard to predict for traits and species not yet studied. We conclude that consideration of ITV can improve our understanding of how plants cope with stressful conditions and environmental change across spatial and biological scales.
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| 30. |
- Ludvigsson, Johnny, et al.
(författare)
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GAD65 antigen therapy in recently diagnosed type 1 diabetes mellitus
- 2012
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Ingår i: New England Journal of Medicine. - : Massachusetts Medical Society. - 0028-4793 .- 1533-4406. ; 366:5, s. 433-442
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The 65-kD isoform of glutamic acid decarboxylase (GAD65) is a major autoantigen in type 1 diabetes. We hypothesized that alum-formulated GAD65 (GAD-alum) can preserve beta-cell function in patients with recent-onset type 1 diabetes.METHODS: We studied 334 patients, 10 to 20 years of age, with type 1 diabetes, fasting C-peptide levels of more than 0.3 ng per milliliter (0.1 nmol per liter), and detectable serum GAD65 autoantibodies. Within 3 months after diagnosis, patients were randomly assigned to receive one of three study treatments: four doses of GAD-alum, two doses of GAD-alum followed by two doses of placebo, or four doses of placebo. The primary outcome was the change in the stimulated serum C-peptide level (after a mixed-meal tolerance test) between the baseline visit and the 15-month visit. Secondary outcomes included the glycated hemoglobin level, mean daily insulin dose, rate of hypoglycemia, and fasting and maximum stimulated C-peptide levels.RESULTS: The stimulated C-peptide level declined to a similar degree in all study groups, and the primary outcome at 15 months did not differ significantly between the combined active-drug groups and the placebo group (P=0.10). The use of GAD-alum as compared with placebo did not affect the insulin dose, glycated hemoglobin level, or hypoglycemia rate. Adverse events were infrequent and mild in the three groups, with no significant differences.CONCLUSIONS: Treatment with GAD-alum did not significantly reduce the loss of stimulated C peptide or improve clinical outcomes over a 15-month period.
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| 31. |
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| 32. |
- Marcé, Rafael, et al.
(författare)
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Emissions from dry inland waters are a blind spot in the global carbon cycle
- 2019
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Ingår i: Earth-Science Reviews. - : Elsevier. - 0012-8252 .- 1872-6828. ; 188, s. 240-248
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Forskningsöversikt (refereegranskat)abstract
- A large part of the world's inland waters, including streams, rivers, ponds, lakes and reservoirs is subject to occasional, recurrent or even permanent drying. Moreover, the occurrence and intensity of drying events are increasing in many areas of the world because of climate change, water abstraction, and land use alteration. Yet, information on the gaseous carbon (C) fluxes from dry inland waters is scarce, thus precluding a comprehensive assessment of C emissions including all, also intermittently dry, inland waters. Here, we review current knowledge on gaseous C fluxes from lotic (streams and rivers) and lentic (ponds, lakes, and reservoirs) inland waters during dry phases and the response to rewetting, considering controls and sources as well as implications of including 'dry' fluxes for local and global scale estimates. Moreover, knowledge gaps and research needs are discussed. Our conservative estimates indicate that adding emissions from dry inland waters to current global estimates of CO2 emissions from inland waters could result in an increase of 0.22 Pg C year(-1), or similar to 10% of total fluxes. We outline the necessary conceptual understanding to successfully include dry phases in a more complete picture of inland water C emissions and identify potential implications for global C cycle feedbacks.
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| 33. |
- Maxwell, Christopher A., et al.
(författare)
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Interplay between BRCA1 and RHAMM Regulates Epithelial Apicobasal Polarization and May Influence Risk of Breast Cancer
- 2011
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Ingår i: PLoS Biology. - : Public Library of Science (PLoS). - 1545-7885 .- 1544-9173. ; 9:11
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Tidskriftsartikel (refereegranskat)abstract
- Differentiated mammary epithelium shows apicobasal polarity, and loss of tissue organization is an early hallmark of breast carcinogenesis. In BRCA1 mutation carriers, accumulation of stem and progenitor cells in normal breast tissue and increased risk of developing tumors of basal-like type suggest that BRCA1 regulates stem/progenitor cell proliferation and differentiation. However, the function of BRCA1 in this process and its link to carcinogenesis remain unknown. Here we depict a molecular mechanism involving BRCA1 and RHAMM that regulates apicobasal polarity and, when perturbed, may increase risk of breast cancer. Starting from complementary genetic analyses across families and populations, we identified common genetic variation at the low-penetrance susceptibility HMMR locus (encoding for RHAMM) that modifies breast cancer risk among BRCA1, but probably not BRCA2, mutation carriers: n = 7,584, weighted hazard ratio ((w)HR) = 1.09 (95% CI 1.02-1.16), p(trend) = 0.017; and n = 3,965, (w)HR = 1.04 (95% CI 0.94-1.16), p(trend) = 0.43; respectively. Subsequently, studies of MCF10A apicobasal polarization revealed a central role for BRCA1 and RHAMM, together with AURKA and TPX2, in essential reorganization of microtubules. Mechanistically, reorganization is facilitated by BRCA1 and impaired by AURKA, which is regulated by negative feedback involving RHAMM and TPX2. Taken together, our data provide fundamental insight into apicobasal polarization through BRCA1 function, which may explain the expanded cell subsets and characteristic tumor type accompanying BRCA1 mutation, while also linking this process to sporadic breast cancer through perturbation of HMMR/RHAMM.
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| 34. |
- Medina-Dols, Aina, et al.
(författare)
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Role of PATJ in stroke prognosis by modulating endothelial to mesenchymal transition through the Hippo/Notch/PI3K axis
- 2024
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Ingår i: Cell Death Discovery. - : Springer Nature. - 2058-7716. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Through GWAS studies we identified PATJ associated with functional outcome after ischemic stroke (IS). The aim of this study was to determine PATJ role in brain endothelial cells (ECs) in the context of stroke outcome. PATJ expression analyses in patient's blood revealed that: (i) the risk allele of rs76221407 induces higher expression of PATJ, (ii) PATJ is downregulated 24 h after IS, and (iii) its expression is significantly lower in those patients with functional independence, measured at 3 months with the modified Rankin scale ((mRS) <= 2), compared to those patients with marked disability (mRS = 4-5). In mice brains, PATJ was also downregulated in the injured hemisphere at 48 h after ischemia. Oxygen-glucose deprivation and hypoxia-dependent of Hypoxia Inducible Factor-1 alpha also caused PATJ depletion in ECs. To study the effects of PATJ downregulation, we generated PATJ-knockdown human microvascular ECs. Their transcriptomic profile evidenced a complex cell reprogramming involving Notch, TGF-ss, PI3K/Akt, and Hippo signaling that translates in morphological and functional changes compatible with endothelial to mesenchymal transition (EndMT). PATJ depletion caused loss of cell-cell adhesion, upregulation of metalloproteases, actin cytoskeleton remodeling, cytoplasmic accumulation of the signal transducer C-terminal transmembrane Mucin 1 (MUC1-C) and downregulation of Notch and Hippo signaling. The EndMT phenotype of PATJ-depleted cells was associated with the nuclear recruitment of MUC1-C, YAP/TAZ, beta-catenin, and ZEB1. Our results suggest that PATJ downregulation 24 h after IS promotes EndMT, an initial step prior to secondary activation of a pro-angiogenic program. This effect is associated with functional independence suggesting that activation of EndMT shortly after stroke onset is beneficial for stroke recovery.
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| 35. |
- Nerpin, Elisabet, 1962-, et al.
(författare)
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Bronchodilator response and lung function decline : Associations with exhaled nitric oxide with regard to sex and smoking status
- 2021
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Ingår i: World Allergy Organization Journal. - : Elsevier. - 1939-4551. ; 14:5
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Tidskriftsartikel (refereegranskat)abstract
- Background: Fractional exhaled nitric oxide (FeNO) is a marker of type-2 inflammation used both to support diagnosis of asthma and follow up asthma patients. The associations of FeNO with lung function decline and bronchodilator (BD) response have been studied only scarcely in large populations.Objectives: To study the association between FeNO and a) retrospective lung function decline over 20 years, and b) lung function response to BD among asthmatic subjects compared with non-asthmatic subjects and with regards to current smoking and sex.Methods: Longitudinal analyses of previous lung function decline and FeNO level at follow-up and cross-sectional analyses of BD response and FeNO levels in 4257 participants (651 asthmatics) from the European Community Respiratory Health Survey.Results: Among asthmatic subjects, higher percentage declines of FEV1 and FEV1/FVC were associated with higher FeNO levels (p = 0.001 for both) at follow-up. These correlations were found mainly among non-smoking individuals (p = 0.001) and females (p = 0.001) in stratified analyses.Percentage increase in FEV1 after BD was positively associated with FeNO levels in non-asthmatic subjects. Further, after stratified for sex and smoking separately, a positive association was seen between FEV1 and FeNO levels in non-smokers and women, regardless of asthma status.Conclusions: We found a relationship between elevated FeNO and larger FEV1 decline over 20 years among subjects with asthma who were non-smokers or women. The association between elevated FeNO levels and larger BD response was found in both non-asthmatic and asthmatic subjects, mainly in women and non-smoking subjects.
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| 36. |
- Pavlides, Michael, et al.
(författare)
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Liver investigation: Testing marker utility in steatohepatitis (LITMUS): Assessment & validation of imaging modality performance across the NAFLD spectrum in a prospectively recruited cohort study (the LITMUS imaging study): Study protocol
- 2023
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Ingår i: Contemporary Clinical Trials. - : ELSEVIER SCIENCE INC. - 1551-7144 .- 1559-2030. ; 134
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Tidskriftsartikel (refereegranskat)abstract
- Non-alcoholic fatty liver disease (NAFLD) is the liver manifestation of the metabolic syndrome with global prevalence reaching epidemic levels. Despite the high disease burden in the population only a small proportion of those with NAFLD will develop progressive liver disease, for which there is currently no approved pharmacotherapy. Identifying those who are at risk of progressive NAFLD currently requires a liver biopsy which is problematic. Firstly, liver biopsy is invasive and therefore not appropriate for use in a condition like NAFLD that affects a large proportion of the population. Secondly, biopsy is limited by sampling and observer dependent variability which can lead to misclassification of disease severity. Non-invasive biomarkers are therefore needed to replace liver biopsy in the assessment of NAFLD. Our study addresses this unmet need. The LITMUS Imaging Study is a prospectively recruited multi-centre cohort study evaluating magnetic resonance imaging and elastography, and ultrasound elastography against liver histology as the reference standard. Imaging biomarkers and biopsy are acquired within a 100-day window. The study employs standardised processes for imaging data collection and analysis as well as a real time central monitoring and quality control process for all the data submitted for analysis. It is anticipated that the high-quality data generated from this study will underpin changes in clinical practice for the benefit of people with NAFLD. Study Registration: clinicaltrials.gov: NCT05479721
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| 37. |
- Pulgarín-R, Paulo C., et al.
(författare)
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Migratory birds as vehicles for parasite dispersal? Infection by avian haemosporidians over the year and throughout the range of a long-distance migrant
- 2019
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Ingår i: Journal of Biogeography. - : Wiley. - 0305-0270 .- 1365-2699. ; 46:1, s. 83-96
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Tidskriftsartikel (refereegranskat)abstract
- Aim: The role of migratory birds in the spread of parasites is poorly known, in part because migratory strategies and behaviours potentially affecting transmission are not easy to study. We investigated the dynamics of infection by blood parasites through the annual cycle of a long-distance Nearctic–Neotropical migratory songbird to examine the role of this species in dispersing parasites between continents. Location: The Americas. Taxon: Grey-cheeked Thrush (Catharus minimus, Aves, Passeriformes, Turdidae), Birds. Methods: We used molecular and microscopy screening of haemosporidian parasites (Plasmodium, Haemoproteus, and Leucocytozoon) to examine the prevalence, distribution, and diversity of lineages through the annual cycle (breeding, migration, and wintering) of the grey-cheeked thrush in North and Central America, Santa Marta mountains, the Andes, and the Amazon. We aimed to identify transmission areas, to examine the degree of sharing of haemosporidian lineages with resident birds in various areas and to assess the potential role of immunologically naïve juvenile individuals in parasite transmission. Results: Prevalence and lineage diversity of haemosporidians varied significantly over time, being higher during breeding and fall and spring migration, and declining during wintering. Grey-cheeked thrush shared few parasite lineages with tropical resident birds and slightly more lineages with other migratory and resident boreal species. We detected gametocytes in blood during spring migration stopover, but these were of lineages not found in resident tropical birds, indicating relapses of parasites transmitted elsewhere. Transmission likely occurs mostly on the breeding grounds, where juveniles and adults carried lineages restricted to closely related species of thrushes and other species of boreal birds. Main conclusions: Long-distance migratory songbirds are likely not important dispersers of blood parasites because there are ecological and evolutionary barriers to the interchange of parasites across vastly separated areas. Further work with thorough spatial and temporal sampling across other species, and considering the role of vectors, is necessary to understand the ecological and evolutionary factors explaining the distribution of parasites over broad scales.
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| 38. |
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| 39. |
- Sattui, Sebastian E., et al.
(författare)
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Outcomes of COVID-19 in patients with primary systemic vasculitis or polymyalgia rheumatica from the COVID-19 Global Rheumatology Alliance physician registry : a retrospective cohort study
- 2021
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Ingår i: The Lancet Rheumatology. - : Elsevier. - 2665-9913. ; 3:12, s. E855-E864
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Tidskriftsartikel (refereegranskat)abstract
- Background Patients with primary systemic vasculitis or polymyalgia rheumatica might be at a high risk for poor COVID-19 outcomes due to the treatments used, the potential organ damage cause by primary systemic vasculitis, and the demographic factors associated with these conditions. We therefore aimed to investigate factors associated with COVID-19 outcomes in patients with primary systemic vasculitis or polymyalgia rheumatica. Methods In this retrospective cohort study, adult patients (aged >= 18 years) diagnosed with COVID-19 between March 12, 2020, and April 12, 2021, who had a history of primary systemic vasculitis (antineutrophil cytoplasmic antibody [ANCA]-associated vasculitis, giant cell arteritis, Behcet's syndrome, or other vasculitis) or polymyalgia rheumatica, and were reported to the COVID-19 Global Rheumatology Alliance registry were included. To assess COVID-19 outcomes in patients, we used an ordinal COVID-19 severity scale, defined as: (1) no hospitalisation; (2) hospitalisation without supplemental oxygen; (3) hospitalisation with any supplemental oxygen or ventilation; or (4) death. Multivariable ordinal logistic regression analyses were used to estimate odds ratios (ORs), adjusting for age, sex, time period, number of comorbidities, smoking status, obesity, glucocorticoid use, disease activity, region, and medication category. Analyses were also stratified by type of rheumatic disease. Findings Of 1202 eligible patients identified in the registry, 733 (61.0%) were women arid 469 (39.0%) were men, and their mean age was 63.8 years (SD 17.1). A total of 374 (31.1%) patients had polymyalgia rheumatica, 353 (29.4%) had ANCA-associated vasculitis, 183 (15.2%) had giant cell arteritis, 112 (9.3%) had Behcet's syndrome, and 180 (15.0%) had other vasculitis. Of 1020 (84. 9%) patients with outcome data, 512 (S0.2%) were not hospitalised, 114 (11.2%) were hospitalised and did not receive supplemental oxygen, 239 (23 - 4%) were hospitalised and received ventilation or supplemental oxygen, and 155 (15.2%) died. A higher odds of poor COVID-19 outcomes were observed in patients who were older (per each additional decade of life OR 1.44 [95% CI 1. 31-1- 571), were male compared with female (1.38 [1.05-1.801), had more comorbidities (per each additional comorbidity 1.39 [1- 23-1- 581), were taking 10 mg/day or more of prednisolone compared with none (2.14 [1.50-3.04J), or had moderate, or high or severe disease activity compared with those who had disease remission or low disease activity (2.12 [1.49-3.021). Risk factors varied among different disease subtypes. Interpretation Among patients with primary systemic vasculitis and polymyalgia rheumatica, severe COVID-19 outcomes were associated with variable and largely unmodifiable risk factors, such as age, sex, and number of comorbidities, as well as treatments, including high-dose glucocorticoids. Our results could be used to info rm mitigation strategies for patients with these diseases.
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| 40. |
- Seiz, Emma G., et al.
(författare)
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Human midbrain precursors activate the expected developmental genetic program and differentiate long-term to functional A9 dopamine neurons in vitro. Enhancement by Bcl-X-L
- 2012
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Ingår i: Experimental Cell Research. - : Elsevier BV. - 1090-2422 .- 0014-4827. ; 318:19, s. 2446-2459
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Tidskriftsartikel (refereegranskat)abstract
- Understanding the molecular programs of the generation of human dopaminergic neurons (DAn) from their ventral mesencephalic (VM) precursors is of key importance for basic studies, progress in cell therapy, drug screening and pharmacology in the context of Parkinson's disease. The nature of human DAn precursors in vitro is poorly understood, their properties unstable, and their availability highly limited. Here we present positive evidence that human VM precursors retaining their genuine properties and long-term capacity to generate A9 type Substantia nigra human DAn (hVM1 model cell line) can be propagated in culture. During a one month differentiation, these cells activate all key genes needed to progress from pro-neural and pro-dopaminergic precursors to mature and functional DAn. For the first time, we demonstrate that gene cascades are correctly activated during differentiation, resulting in the generation of mature DAn. These DAn have morphological and functional properties undistinguishable from those generated by VM primary neuronal cultures. In addition, we have found that the forced expression of Bcl-X-L induces an increase in the expression of key developmental genes (MSX1, NGN2), maintenance of PITX3 expression temporal profile, and also enhances genes involved in DAn long-term function, maintenance and survival (EN1, LMX1B, NURR1 and PITX3). As a result, Bcl-X-L anticipates and enhances DAn generation. (C) 2012 Elsevier Inc. All rights reserved.
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| 42. |
- Terenius, Olle, et al.
(författare)
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RNA interference in Lepidoptera : An overview of successful and unsuccessful studies and implications for experimental design
- 2011
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Ingår i: Journal of insect physiology. - : Elsevier BV. - 0022-1910 .- 1879-1611. ; 57:2, s. 231-245
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Tidskriftsartikel (refereegranskat)abstract
- Gene silencing through RNA interference (RNAi) has revolutionized the study of gene function, particularly in non-model insects. However, in Lepidoptera (moths and butterflies) RNAi has many times proven to be difficult to achieve. Most of the negative results have been anecdotal and the positive experiments have not been collected in such a way that they are possible to analyze. In this review, we have collected detailed data from more than 150 experiments including all to date published and many unpublished experiments. Despite a large variation in the data, trends that are found are that RNAi is particularly successful in the family Saturniidae and in genes involved in immunity. On the contrary, gene expression in epidermal tissues seems to be most difficult to silence. In addition, gene silencing by feeding dsRNA requires high concentrations for success. Possible causes for the variability of success in RNAi experiments in Lepidoptera are discussed. The review also points to a need to further investigate the mechanism of RNAi in lepidopteran insects and its possible connection to the innate immune response. Our general understanding of RNAi in Lepidoptera will be further aided in the future as our public database at http://insectacentral.org/RNAi will continue to gather information on RNAi experiments.
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| 43. |
- Tinetti, G., et al.
(författare)
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A chemical survey of exoplanets with ARIEL
- 2018
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Ingår i: Experimental Astronomy. - : Springer Science and Business Media LLC. - 0922-6435 .- 1572-9508. ; 46:1, s. 135-209
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Tidskriftsartikel (refereegranskat)abstract
- Thousands of exoplanets have now been discovered with a huge range of masses, sizes and orbits: from rocky Earth-like planets to large gas giants grazing the surface of their host star. However, the essential nature of these exoplanets remains largely mysterious: there is no known, discernible pattern linking the presence, size, or orbital parameters of a planet to the nature of its parent star. We have little idea whether the chemistry of a planet is linked to its formation environment, or whether the type of host star drives the physics and chemistry of the planet’s birth, and evolution. ARIEL was conceived to observe a large number (~1000) of transiting planets for statistical understanding, including gas giants, Neptunes, super-Earths and Earth-size planets around a range of host star types using transit spectroscopy in the 1.25–7.8 μm spectral range and multiple narrow-band photometry in the optical. ARIEL will focus on warm and hot planets to take advantage of their well-mixed atmospheres which should show minimal condensation and sequestration of high-Z materials compared to their colder Solar System siblings. Said warm and hot atmospheres are expected to be more representative of the planetary bulk composition. Observations of these warm/hot exoplanets, and in particular of their elemental composition (especially C, O, N, S, Si), will allow the understanding of the early stages of planetary and atmospheric formation during the nebular phase and the following few million years. ARIEL will thus provide a representative picture of the chemical nature of the exoplanets and relate this directly to the type and chemical environment of the host star. ARIEL is designed as a dedicated survey mission for combined-light spectroscopy, capable of observing a large and well-defined planet sample within its 4-year mission lifetime. Transit, eclipse and phase-curve spectroscopy methods, whereby the signal from the star and planet are differentiated using knowledge of the planetary ephemerides, allow us to measure atmospheric signals from the planet at levels of 10–100 part per million (ppm) relative to the star and, given the bright nature of targets, also allows more sophisticated techniques, such as eclipse mapping, to give a deeper insight into the nature of the atmosphere. These types of observations require a stable payload and satellite platform with broad, instantaneous wavelength coverage to detect many molecular species, probe the thermal structure, identify clouds and monitor the stellar activity. The wavelength range proposed covers all the expected major atmospheric gases from e.g. H2O, CO2, CH4 NH3, HCN, H2S through to the more exotic metallic compounds, such as TiO, VO, and condensed species. Simulations of ARIEL performance in conducting exoplanet surveys have been performed – using conservative estimates of mission performance and a full model of all significant noise sources in the measurement – using a list of potential ARIEL targets that incorporates the latest available exoplanet statistics. The conclusion at the end of the Phase A study, is that ARIEL – in line with the stated mission objectives – will be able to observe about 1000 exoplanets depending on the details of the adopted survey strategy, thus confirming the feasibility of the main science objectives.
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| 44. |
- Zaina, Silvio, et al.
(författare)
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A DNA Methylation Map of Human Atherosclerosis.
- 2014
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Ingår i: Circulation: Cardiovascular Genetics. - 1942-325X. ; 7:5, s. 692-700
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Tidskriftsartikel (refereegranskat)abstract
- -Epigenetic alterations may contribute to the development of atherosclerosis. In particular, DNA methylation, a reversible and highly regulated DNA modification, could influence disease onset and progression since it functions as an effector for environmental influences, including diet and lifestyle, both of which are risk factors for cardiovascular diseases.
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