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Sökning: WFRF:(Brandao J)

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1.
  • Ruilope, LM, et al. (författare)
  • Design and Baseline Characteristics of the Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease Trial
  • 2019
  • Ingår i: American journal of nephrology. - : S. Karger AG. - 1421-9670 .- 0250-8095. ; 50:5, s. 345-356
  • Tidskriftsartikel (refereegranskat)abstract
    • <b><i>Background:</i></b> Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. <b><i>Patients and</i></b> <b><i>Methods:</i></b> The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate ≥25 mL/min/1.73 m<sup>2</sup> and albuminuria (urinary albumin-to-creatinine ratio ≥30 to ≤5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level α = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. <b><i>Conclusions:</i></b> FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049.
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2.
  • Wang, Anqi, et al. (författare)
  • Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants
  • 2023
  • Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 55:12, s. 2065-2074
  • Tidskriftsartikel (refereegranskat)abstract
    • The transferability and clinical value of genetic risk scores (GRSs) across populations remain limited due to an imbalance in genetic studies across ancestrally diverse populations. Here we conducted a multi-ancestry genome-wide association study of 156,319 prostate cancer cases and 788,443 controls of European, African, Asian and Hispanic men, reflecting a 57% increase in the number of non-European cases over previous prostate cancer genome-wide association studies. We identified 187 novel risk variants for prostate cancer, increasing the total number of risk variants to 451. An externally replicated multi-ancestry GRS was associated with risk that ranged from 1.8 (per standard deviation) in African ancestry men to 2.2 in European ancestry men. The GRS was associated with a greater risk of aggressive versus non-aggressive disease in men of African ancestry (P = 0.03). Our study presents novel prostate cancer susceptibility loci and a GRS with effective risk stratification across ancestry groups.
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  • Conti, David, V, et al. (författare)
  • Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction
  • 2021
  • Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 53:1, s. 65-75
  • Tidskriftsartikel (refereegranskat)abstract
    • Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84-5.29) for men of European ancestry to 3.74 (95% CI, 3.36-4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14-2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71-0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction. A meta-analysis of genome-wide association studies across different populations highlights new risk loci and provides a genetic risk score that can stratify prostate cancer risk across ancestries.
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4.
  • Rauer, H., et al. (författare)
  • The PLATO 2.0 mission
  • 2014
  • Ingår i: Experimental astronomy. - : Springer Science and Business Media LLC. - 0922-6435 .- 1572-9508. ; 38:1-2, s. 249-330
  • Tidskriftsartikel (refereegranskat)abstract
    • PLATO 2.0 has recently been selected for ESA's M3 launch opportunity (2022/24). Providing accurate key planet parameters (radius, mass, density and age) in statistical numbers, it addresses fundamental questions such as: How do planetary systems form and evolve? Are there other systems with planets like ours, including potentially habitable planets? The PLATO 2.0 instrument consists of 34 small aperture telescopes (32 with 25 s readout cadence and 2 with 2.5 s cadence) providing a wide field-of-view (2232 deg(2)) and a large photometric magnitude range (4-16 mag). It focuses on bright (4-11 mag) stars in wide fields to detect and characterize planets down to Earth-size by photometric transits, whose masses can then be determined by ground-based radial-velocity follow-up measurements. Asteroseismology will be performed for these bright stars to obtain highly accurate stellar parameters, including masses and ages. The combination of bright targets and asteroseismology results in high accuracy for the bulk planet parameters: 2 %, 4-10 % and 10 % for planet radii, masses and ages, respectively. The planned baseline observing strategy includes two long pointings (2-3 years) to detect and bulk characterize planets reaching into the habitable zone (HZ) of solar-like stars and an additional step-and-stare phase to cover in total about 50 % of the sky. PLATO 2.0 will observe up to 1,000,000 stars and detect and characterize hundreds of small planets, and thousands of planets in the Neptune to gas giant regime out to the HZ. It will therefore provide the first large-scale catalogue of bulk characterized planets with accurate radii, masses, mean densities and ages. This catalogue will include terrestrial planets at intermediate orbital distances, where surface temperatures are moderate. Coverage of this parameter range with statistical numbers of bulk characterized planets is unique to PLATO 2.0. The PLATO 2.0 catalogue allows us to e. g.: - complete our knowledge of planet diversity for low-mass objects, - correlate the planet mean density-orbital distance distribution with predictions from planet formation theories,- constrain the influence of planet migration and scattering on the architecture of multiple systems, and - specify how planet and system parameters change with host star characteristics, such as type, metallicity and age. The catalogue will allow us to study planets and planetary systems at different evolutionary phases. It will further provide a census for small, low-mass planets. This will serve to identify objects which retained their primordial hydrogen atmosphere and in general the typical characteristics of planets in such a low-mass, low-density range. Planets detected by PLATO 2.0 will orbit bright stars and many of them will be targets for future atmosphere spectroscopy exploring their atmospheres. Furthermore, the mission has the potential to detect exomoons, planetary rings, binary and Trojan planets. The planetary science possible with PLATO 2.0 is complemented by its impact on stellar and galactic science via asteroseismology as well as light curves of all kinds of variable stars, together with observations of stellar clusters of different ages. This will allow us to improve stellar models and study stellar activity. A large number of well-known ages from red giant stars will probe the structure and evolution of our Galaxy. Asteroseismic ages of bright stars for different phases of stellar evolution allow calibrating stellar age-rotation relationships. Together with the results of ESA's Gaia mission, the results of PLATO 2.0 will provide a huge legacy to planetary, stellar and galactic science.
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  • Appeltans, W., et al. (författare)
  • The Magnitude of Global Marine Species Diversity
  • 2012
  • Ingår i: Current Biology. - : Elsevier BV. - 0960-9822 .- 1879-0445. ; 22:23, s. 2189-2202
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The question of how many marine species exist is important because it provides a metric for how much we do and do not know about life in the oceans. We have compiled the first register of the marine species of the world and used this baseline to estimate how many more species, partitioned among all major eukaryotic groups, may be discovered. Results: There are similar to 226,000 eukaryotic marine species described. More species were described in the past decade (similar to 20,000) than in any previous one. The number of authors describing new species has been increasing at a faster rate than the number of new species described in the past six decades. We report that there are similar to 170,000 synonyms, that 58,000-72,000 species are collected but not yet described, and that 482,000-741,000 more species have yet to be sampled. Molecular methods may add tens of thousands of cryptic species. Thus, there may be 0.7-1.0 million marine species. Past rates of description of new species indicate there may be 0.5 +/- 0.2 million marine species. On average 37% (median 31%) of species in over 100 recent field studies around the world might be new to science. Conclusions: Currently, between one-third and two-thirds of marine species may be undescribed, and previous estimates of there being well over one million marine species appear highly unlikely. More species than ever before are being described annually by an increasing number of authors. If the current trend continues, most species will be discovered this century.
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7.
  • Bruggmann, P., et al. (författare)
  • Historical epidemiology of hepatitis C virus (HCV) in selected countries
  • 2014
  • Ingår i: Journal of Viral Hepatitis. - Hoboken : Wiley-Blackwell. - 1352-0504 .- 1365-2893. ; 21, s. 5-33
  • Tidskriftsartikel (refereegranskat)abstract
    • Chronic infection with hepatitis C virus (HCV) is a leading indicator for liver disease. New treatment options are becoming available, and there is a need to characterize the epidemiology and disease burden of HCV. Data for prevalence, viremia, genotype, diagnosis and treatment were obtained through literature searches and expert consensus for 16 countries. For some countries, data from centralized registries were used to estimate diagnosis and treatment rates. Data for the number of liver transplants and the proportion attributable to HCV were obtained from centralized databases. Viremic prevalence estimates varied widely between countries, ranging from 0.3% in Austria, England and Germany to 8.5% in Egypt. The largest viremic populations were in Egypt, with 6358000 cases in 2008 and Brazil with 2106000 cases in 2007. The age distribution of cases differed between countries. In most countries, prevalence rates were higher among males, reflecting higher rates of injection drug use. Diagnosis, treatment and transplant levels also differed considerably between countries. Reliable estimates characterizing HCV-infected populations are critical for addressing HCV-related morbidity and mortality. There is a need to quantify the burden of chronic HCV infection at the national level.
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  • Razavi, H., et al. (författare)
  • The present and future disease burden of hepatitis C virus (HCV) infection with today's treatment paradigm
  • 2014
  • Ingår i: Journal of Viral Hepatitis. - Hoboken : Wiley-Blackwell. - 1352-0504 .- 1365-2893. ; 21:Suppl. 1, s. 34-59
  • Tidskriftsartikel (refereegranskat)abstract
    • The disease burden of hepatitis C virus (HCV) is expected to increase as the infected population ages. A modelling approach was used to estimate the total number of viremic infections, diagnosed, treated and new infections in 2013. In addition, the model was used to estimate the change in the total number of HCV infections, the disease progression and mortality in 2013-2030. Finally, expert panel consensus was used to capture current treatment practices in each country. Using today's treatment paradigm, the total number of HCV infections is projected to decline or remain flat in all countries studied. However, in the same time period, the number of individuals with late-stage liver disease is projected to increase. This study concluded that the current treatment rate and efficacy are not sufficient to manage the disease burden of HCV. Thus, alternative strategies are required to keep the number of HCV individuals with advanced liver disease and liver-related deaths from increasing.
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10.
  • Wedemeyer, H., et al. (författare)
  • Strategies to manage hepatitis C virus (HCV) disease burden
  • 2014
  • Ingår i: Journal of Viral Hepatitis. - Hoboken : Wiley-Blackwell. - 1352-0504 .- 1365-2893. ; 21, s. 60-89
  • Tidskriftsartikel (refereegranskat)abstract
    • The number of hepatitis C virus (HCV) infections is projected to decline while those with advanced liver disease will increase. A modeling approach was used to forecast two treatment scenarios: (i) the impact of increased treatment efficacy while keeping the number of treated patients constant and (ii) increasing efficacy and treatment rate. This analysis suggests that successful diagnosis and treatment of a small proportion of patients can contribute significantly to the reduction of disease burden in the countries studied. The largest reduction in HCV-related morbidity and mortality occurs when increased treatment is combined with higher efficacy therapies, generally in combination with increased diagnosis. With a treatment rate of approximately 10%, this analysis suggests it is possible to achieve elimination of HCV (defined as a >90% decline in total infections by 2030). However, for most countries presented, this will require a 3-5 fold increase in diagnosis and/or treatment. Thus, building the public health and clinical provider capacity for improved diagnosis and treatment will be critical.
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  • Cowie, A. L., et al. (författare)
  • Applying a science-based systems perspective to dispel misconceptions about climate effects of forest bioenergy
  • 2021
  • Ingår i: Global Change Biology Bioenergy. - : John Wiley and Sons Inc. - 1757-1693 .- 1757-1707. ; 13:8, s. 1210-1231
  • Tidskriftsartikel (refereegranskat)abstract
    • The scientific literature contains contrasting findings about the climate effects of forest bioenergy, partly due to the wide diversity of bioenergy systems and associated contexts, but also due to differences in assessment methods. The climate effects of bioenergy must be accurately assessed to inform policy-making, but the complexity of bioenergy systems and associated land, industry and energy systems raises challenges for assessment. We examine misconceptions about climate effects of forest bioenergy and discuss important considerations in assessing these effects and devising measures to incentivize sustainable bioenergy as a component of climate policy. The temporal and spatial system boundary and the reference (counterfactual) scenarios are key methodology choices that strongly influence results. Focussing on carbon balances of individual forest stands and comparing emissions at the point of combustion neglect system-level interactions that influence the climate effects of forest bioenergy. We highlight the need for a systems approach, in assessing options and developing policy for forest bioenergy that: (1) considers the whole life cycle of bioenergy systems, including effects of the associated forest management and harvesting on landscape carbon balances; (2) identifies how forest bioenergy can best be deployed to support energy system transformation required to achieve climate goals; and (3) incentivizes those forest bioenergy systems that augment the mitigation value of the forest sector as a whole. Emphasis on short-term emissions reduction targets can lead to decisions that make medium- to long-term climate goals more difficult to achieve. The most important climate change mitigation measure is the transformation of energy, industry and transport systems so that fossil carbon remains underground. Narrow perspectives obscure the significant role that bioenergy can play by displacing fossil fuels now, and supporting energy system transition. Greater transparency and consistency is needed in greenhouse gas reporting and accounting related to bioenergy. 
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18.
  • Shen, Ruidan, et al. (författare)
  • Insights into the importance of WPD-loop sequence for activity and structure in protein tyrosine phosphatases
  • 2022
  • Ingår i: Chemical Science. - : Royal Society of Chemistry. - 2041-6520 .- 2041-6539. ; 13:45, s. 13524-13540
  • Tidskriftsartikel (refereegranskat)abstract
    • Protein tyrosine phosphatases (PTPs) possess a conserved mobile catalytic loop, the WPD-loop, which brings an aspartic acid into the active site where it acts as an acid/base catalyst. Prior experimental and computational studies, focused on the human enzyme PTP1B and the PTP from Yersinia pestis, YopH, suggested that loop conformational dynamics are important in regulating both catalysis and evolvability. We have generated a chimeric protein in which the WPD-loop of YopH is transposed into PTP1B, and eight chimeras that systematically restored the loop sequence back to native PTP1B. Of these, four chimeras were soluble and were subjected to detailed biochemical and structural characterization, and a computational analysis of their WPD-loop dynamics. The chimeras maintain backbone structural integrity, with somewhat slower rates than either wild-type parent, and show differences in the pH dependency of catalysis, and changes in the effect of Mg2+. The chimeric proteins' WPD-loops differ significantly in their relative stability and rigidity. The time required for interconversion, coupled with electrostatic effects revealed by simulations, likely accounts for the activity differences between chimeras, and relative to the native enzymes. Our results further the understanding of connections between enzyme activity and the dynamics of catalytically important groups, particularly the effects of non-catalytic residues on key conformational equilibria.
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19.
  • Brandao, A, et al. (författare)
  • The CHEK2 Variant C.349A>G Is Associated with Prostate Cancer Risk and Carriers Share a Common Ancestor
  • 2020
  • Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 12:11
  • Tidskriftsartikel (refereegranskat)abstract
    • The identification of recurrent founder variants in cancer predisposing genes may have important implications for implementing cost-effective targeted genetic screening strategies. In this study, we evaluated the prevalence and relative risk of the CHEK2 recurrent variant c.349A>G in a series of 462 Portuguese patients with early-onset and/or familial/hereditary prostate cancer (PrCa), as well as in the large multicentre PRACTICAL case–control study comprising 55,162 prostate cancer cases and 36,147 controls. Additionally, we investigated the potential shared ancestry of the carriers by performing identity-by-descent, haplotype and age estimation analyses using high-density SNP data from 70 variant carriers belonging to 11 different populations included in the PRACTICAL consortium. The CHEK2 missense variant c.349A>G was found significantly associated with an increased risk for PrCa (OR 1.9; 95% CI: 1.1–3.2). A shared haplotype flanking the variant in all carriers was identified, strongly suggesting a common founder of European origin. Additionally, using two independent statistical algorithms, implemented by DMLE+2.3 and ESTIAGE, we were able to estimate the age of the variant between 2300 and 3125 years. By extending the haplotype analysis to 14 additional carrier families, a shared core haplotype was revealed among all carriers matching the conserved region previously identified in the high-density SNP analysis. These findings are consistent with CHEK2 c.349A>G being a founder variant associated with increased PrCa risk, suggesting its potential usefulness for cost-effective targeted genetic screening in PrCa families.
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  • Guimaraes, K. S. D., et al. (författare)
  • Lactiplantibacillus plantarum WJL administration during pregnancy and lactation improves lipid profile, insulin sensitivity and gut microbiota diversity in dyslipidemic dams and protects male offspring against cardiovascular dysfunction in later life
  • 2020
  • Ingår i: Food & Function. - : Royal Society of Chemistry (RSC). - 2042-6496 .- 2042-650X. ; 11:10, s. 8939-8950
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and aim: Maternal dyslipidemia is recognized as a risk factor for the development of arterial hypertension (AH) and cardiovascular dysfunction in offspring. Here we evaluated the effects of probiotic administration of a specific strain of Lactiplantibacillus plantarum(WJL) during pregnancy and lactation on gut microbiota and metabolic profile in dams fed with a high-fat and high-cholesterol (HFHC) diet and its long-term effects on the cardiovascular function in male rat offspring.Methods and results: Pregnant Wistar rats were allocated into three groups: dams fed a control diet (CTL = 5), dams fed a HFHC diet (DLP = 5) and dams fed a HFHC diet and receivingL. plantarum WJL during pregnancy and lactation (DLP-Lp(WJL)).L. plantarum WJL (1 x 10(9)CFU) or vehicle (NaCl, 0.9%) was administered daily by oral gavage for 6 weeks, covering the pregnancy and lactation periods. After weaning, male offspring received a standard diet up to 90 days of life. Biochemical measurements and gut microbiota were evaluated in dams. In male offspring, blood pressure (BP), heart rate (HR) and vascular reactivity were evaluated at 90 days of age. Dams fed with a HFHC diet during pregnancy and lactation had increased lipid profile and insulin resistance and showed dysbiotic gut microbiota. Administration of L. plantarum WJL to dams having maternal dyslipidemia improved gut microbiota composition, lipid profile and insulin resistance in them. Blood pressure was augmented and vascular reactivity was impaired with a higher contractile response and a lower response to endothelium-dependent vasorelaxation in DLP male offspring. In contrast, male offspring of DLP-Lp(WJL) dams had reduced blood pressure and recovered vascular function in later life.Conclusion: Administration ofL. plantarum WJL during pregnancy and lactation in dams improved gut microbiota diversity, reduced maternal dyslipidemia and prevented cardiovascular dysfunction in male rat offspring.
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  • Pontarollo, G., et al. (författare)
  • Commensal bacteria weaken the intestinal barrier by suppressing epithelial neuropilin-1 and Hedgehog signaling
  • 2023
  • Ingår i: Nature Metabolism. - 2522-5812. ; 5:7, s. 1174-87
  • Tidskriftsartikel (refereegranskat)abstract
    • The gut microbiota influences intestinal barrier integrity through mechanisms that are incompletely understood. Here we show that the commensal microbiota weakens the intestinal barrier by suppressing epithelial neuropilin-1 (NRP1) and Hedgehog (Hh) signaling. Microbial colonization of germ-free mice dampens signaling of the intestinal Hh pathway through epithelial Toll-like receptor (TLR)-2, resulting in decreased epithelial NRP1 protein levels. Following activation via TLR2/TLR6, epithelial NRP1, a positive-feedback regulator of Hh signaling, is lysosomally degraded. Conversely, elevated epithelial NRP1 levels in germ-free mice are associated with a strengthened gut barrier. Functionally, intestinal epithelial cell-specific Nrp1 deficiency (Nrp1(& UDelta;IEC)) results in decreased Hh pathway activity and a weakened gut barrier. In addition, Nrp1(& UDelta;IEC) mice have a reduced density of capillary networks in their small intestinal villus structures. Collectively, our results reveal a role for the commensal microbiota and epithelial NRP1 signaling in the regulation of intestinal barrier function through postnatal control of Hh signaling. A molecular mechanism is revealed through which commensal bacteria modulate intestinal epithelial barrier function.
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25.
  • Razavi, Homie A., et al. (författare)
  • Hepatitis D double reflex testing of all hepatitis B carriers in low-HBV- and high-HBV/HDV-prevalence countries
  • 2023
  • Ingår i: JOURNAL OF HEPATOLOGY. - : Elsevier. - 0168-8278 .- 1600-0641. ; 79:2, s. 576-580
  • Tidskriftsartikel (refereegranskat)abstract
    • Hepatitis D virus (HDV) infection occurs as a coinfection with hepatitis B and increases the risk of hepatocellular carcinoma, decompensated cirrhosis, and mortality compared to hepatitis B virus (HBV) monoinfection. Reliable estimates of the prevalence of HDV infection and disease burden are essential to formulate strategies to find coinfected individuals more effectively and efficiently. The global prevalence of HBV infections was estimated to be 262,240,000 in 2021. Only 1,994,000 of the HBV in-fections were newly diagnosed in 2021, with more than half of the new diagnoses made in China. Our initial estimates indicated a much lower prevalence of HDV antibody (anti-HDV) and HDV RNA positivity than previously reported in published studies. Ac-curate estimates of HDV prevalence are needed. The most effective method to generate estimates of the prevalence of anti-HDV and HDV RNA positivity and to find undiagnosed individuals at the national level is to implement double reflex testing. This re-quires anti-HDV testing of all hepatitis B surface antigen-positive individuals and HDV RNA testing of all anti-HDV-positive in-dividuals. This strategy is manageable for healthcare systems since the number of newly diagnosed HBV cases is low. At the global level, a comprehensive HDV screening strategy would require only 1,994,000 HDV antibody tests and less than 89,000 HDV PCR tests. Double reflex testing is the preferred strategy in countries with a low prevalence of HBV and those with a high prevalence of both HBV and HDV. For example, in the European Union and North America only 35,000 and 22,000 cases, respectively, will require anti-HDV testing annually.
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  • Razavi-Shearer, Devin M., et al. (författare)
  • Adjusted estimate of the prevalence of hepatitis delta virus in 25 countries and territories
  • 2024
  • Ingår i: JOURNAL OF HEPATOLOGY. - 0168-8278 .- 1600-0641. ; 80:2, s. 232-242
  • Tidskriftsartikel (refereegranskat)abstract
    • Background & Aims: Hepatitis delta virus (HDV) is a satellite RNA virus that requires the hepatitis B virus (HBV) for assembly and propagation. Individuals infected with HDV progress to advanced liver disease faster than HBV-monoinfected individuals. Recent studies have estimated the global prevalence of anti-HDV antibodies among the HBV-infected population to be 5-15%. This study aimed to better understand HDV prevalence at the population level in 25 countries/territories. Methods: We conducted a literature review to determine the prevalence of anti-HDV and HDV RNA in hepatitis B surface antigen (HBsAg)-positive individuals in 25 countries/territories. Virtual meetings were held with experts from each setting to discuss the findings and collect unpublished data. Data were weighted for patient segments and regional heterogeneity to estimate the prevalence in the HBV-infected population. The findings were then combined with The Polaris Observatory HBV data to estimate the anti-HDV and HDV RNA prevalence in each country/territory at the population level. Results: After adjusting for geographical distribution, disease stage and special populations, the anti-HDV prevalence among the HBsAg+ population changed from the literature estimate in 19 countries. The highest anti-HDV prevalence was 60.1% in Mongolia. Once adjusted for the size of the HBsAg+ population and HDV RNA positivity rate, China had the highest absolute number of HDV RNA+ cases. Conclusions: We found substantially lower HDV prevalence than previously reported, as prior meta-analyses primarily focused on studies conducted in groups/regions that have a higher probability of HBV infection: tertiary care centers, specific risk groups or geographical regions. There is large uncertainty in HDV prevalence estimates. The implementation of reflex testing would improve estimates, while also allowing earlier linkage to care for HDV RNA+ individuals. The logistical and economic burden of reflex testing on the health system would be limited, as only HBsAg+ cases would be screened.
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  • Agner, Tove, et al. (författare)
  • Contact sensitisation in hand eczema patients-relation to subdiagnosis, severity and quality of life: a multi-centre study
  • 2009
  • Ingår i: Contact Dermatitis. - 0105-1873. ; 61:5, s. 291-296
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Contact sensitisation has been identified as a factor associated with poor prognosis for patients with hand eczema. Objectives To study implications of contact sensitisation with respect to severity, quality of life (QoL) and subdiagnosis of hand eczema. Methods The study was performed as a multi-centre, cross-sectional study from 10 European clinics. All patients were patch tested, and severity of hand eczema assessed by Hand Eczema Severity Index. A multi-variate analysis was performed to explore which factors influenced severity, QoL and sick leave. Results A total 416 patients were included, and 63% had contact sensitisation to one or more of the tested allergens. More women (66%) than men (51%) were sensitized. No significant association was found between sensitisation to specific allergens, disease severity, QoL or diagnostic subgroups. High age, male sex, atopic eczema and presence of contact sensitisation were independent risk factors for increased severity as measured by Hand Eczema Severity Index. Furthermore, the severity of hand eczema increased by the number of contact sensitisations detected (P = 0.023). High age and personal history of atopic eczema were independent risk factors for low QoL, as measured by Dermatology Life Quality Index, and atopic eczema as well as allergic contact dermatitis as subdiagnosis was associated with increased sick leave. Conclusion Diagnostic subgroups were not found to be related to specific allergens. Contact sensitisation was found to be a risk factor for increased severity of hand eczema, as did high age, male sex and atopic eczema.
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28.
  • Agner, Tove, et al. (författare)
  • Hand eczema severity and quality of life: a cross-sectional, multicentre study of hand eczema patients
  • 2008
  • Ingår i: Contact Dermatitis. - : Wiley. - 0105-1873 .- 1600-0536. ; 59:1, s. 43-47
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and Objectives: Hand eczema is a chronic disease with negative impact on quality of life (QoL). In this study, QoL in hand eczema patients is assessed and related to age, sex, severity, and diagnostic subgroups. Methods: A total of 416 patients with hand eczema from 10 European patch test clinics participated in the study. Data on QoL were obtained from a self-administered questionnaire using the Dermatology Life Quality Index (DLQI). Severity was assessed by a scoring system (Hand Eczema Severity Index, HECSI) as well as frequency of eruptions and sick leave due to hand eczema. Results: No significant difference was found between males and females with respect to QoL [DLQI median values and 25/75 percentiles for males and females being 7.0 (3-14) and 8.0 (3-13), respectively], although males were more severely affected than females (P < 0.025). A significant positive correlation was found for hand eczema severity and age (P < 0.001), while no significant correlation was found for QoL and age. QoL was found increasingly reduced when sick leave was getting higher (P < 0.001). A statistically significant correlation between QoL (as measured by DLQI) and hand eczema severity as measured by HECSI was found (P < 0.001). No significant difference in QoL was found between diagnostic subgroups. Conclusions: QoL was found markedly negatively affected in hand eczema patients and was significantly correlated to disease severity. No significant difference in QoL was found between males and females, in spite of significantly more severe eczema in males, indicating that QoL in female patients is more easily affected.
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29.
  • Barbosa, E.A., et al. (författare)
  • Quality improvement and geographical indication of cachaça (Brazilian spirit) by using locally selected yeast strains
  • 2016
  • Ingår i: Journal of Applied Microbiology. - : Oxford University Press (OUP). - 1365-2672 .- 1364-5072. ; 121:4, s. 1038-1051
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims In order to improve the quality and to create a biological basis for obtainment of the protected denomination of origin (PDO), indigenous yeast were isolated and characterized for use in Salinas city (the Brazilian region of quality cachaça production). Material and methods Seven thousand and two hundred yeast colonies from 15 Salinas city distilleries were screened based on their fermentative behaviour and the physicochemical composition of cachaça. Molecular polymorphic analyses were performed to characterize these isolates. Results Two Saccharomyces cerevisiae strains (nos. 678 and 680) showed appropriate characteristics to use in the cachaça production: low levels of acetaldehyde and methanol, and high ethyl lactate/ethyl acetate ratio respectively. They also presented polymorphic characteristics more closely related between themselves even when compared to other strains from Salinas. Conclusions The application of selected yeast to cachaça production can contribute for the improvement of the quality product as well as be used as a natural marker for PDO. Significance and Impact of the Study This study suggests that the use of selected yeast strains could contribute to obtain a cachaça similar to those produced traditionally, while getting wide acceptation in the market, yet presenting more homogeneous organoleptic characteristics, and thus contributing to the PDO implementation.
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30.
  • Brandao, Luiz Eduardo M., et al. (författare)
  • Social Jetlag Changes During the COVID-19 Pandemic as a Predictor of Insomnia - A Multi-National Survey Study
  • 2021
  • Ingår i: Nature and Science of Sleep. - : Dove Medical Press. - 1179-1608. ; 13, s. 1711-1722
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: Lifestyle and work habits have been drastically altered by restrictions due to the COVID-19 pandemic. Whether the associated changes in sleep timing modulate the risk of suffering from symptoms of insomnia, the most prevalent sleep disorder, is however incompletely understood. Here, we evaluate the association between the early pandemic-associated change in 1) the magnitude of social jetlag (SJL) - ie, the difference between sleep timing on working vs free days - and 2) symptoms of insomnia.Patients and Methods: A total of 14,968 anonymous participants (mean age: 40 years; 64% females) responded to a standardized internet-based survey distributed across 14 countries. Using logistic multivariate regression, we examined the association between the degree of social jetlag and symptoms of insomnia, controlling for important confounders like social restriction extension, country specific COVID-19 severity and psychological distress, for example.Results: In response to the pandemic, participants reported later sleep timing, especially during workdays. Most participants (46%) exhibited a reduction in their SJL, whereas 20% increased it; and 34% reported no change in SJL. Notably, we found that both increased and decreased SJL, as a result of the COVID-19 pandemic, were associated with later sleep midpoint (indicating a later chronotype) as well as more recurrent and moderate-to-severe symptoms of insomnia (about 23-54% higher odds ratio than subjects with unchanged SJL). Primarily those with reduced SJL shifted their bedtimes to a later timepoint, compared with those without changes in SJL.Conclusion: Our findings offer important insights into how self-reported changes to the stability of sleep/wake timing, as reflected by changes in SJL, can be a critical marker of the risk of experiencing insomnia-related symptoms - even when individuals manage to reduce their social jetlag. These findings emphasize the clinical importance of analyzing sleep-wake regularity.
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31.
  • Brandão, Rita D., et al. (författare)
  • Targeted RNA-seq successfully identifies normal and pathogenic splicing events in breast/ovarian cancer susceptibility and Lynch syndrome genes
  • 2019
  • Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 145:2, s. 401-414
  • Tidskriftsartikel (refereegranskat)abstract
    • A subset of genetic variants found through screening of patients with hereditary breast and ovarian cancer syndrome (HBOC) and Lynch syndrome impact RNA splicing. Through target enrichment of the transcriptome, it is possible to perform deep-sequencing and to identify the different and even rare mRNA isoforms. A targeted RNA-seq approach was used to analyse the naturally-occurring splicing events for a panel of 8 breast and/or ovarian cancer susceptibility genes (BRCA1, BRCA2, RAD51C, RAD51D, PTEN, STK11, CDH1, TP53), 3 Lynch syndrome genes (MLH1, MSH2, MSH6) and the fanconi anaemia SLX4 gene, in which monoallelic mutations were found in non-BRCA families. For BRCA1, BRCA2, RAD51C and RAD51D the results were validated by capillary electrophoresis and were compared to a non-targeted RNA-seq approach. We also compared splicing events from lymphoblastoid cell-lines with those from breast and ovarian fimbriae tissues. The potential of targeted RNA-seq to detect pathogenic changes in RNA-splicing was validated by the inclusion of samples with previously well characterized BRCA1/2 genetic variants. In our study, we update the catalogue of normal splicing events for BRCA1/2, provide an extensive catalogue of normal RAD51C and RAD51D alternative splicing, and list splicing events found for eight other genes. Additionally, we show that our approach allowed the identification of aberrant splicing events due to the presence of BRCA1/2 genetic variants and distinguished between complete and partial splicing events. In conclusion, targeted-RNA-seq can be very useful to classify variants based on their putative pathogenic impact on splicing.
  •  
32.
  • Chazot, Nicolas, et al. (författare)
  • Conserved ancestral tropical niche but different continental histories explain the latitudinal diversity gradient in brush-footed butterflies
  • 2021
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
  • Tidskriftsartikel (refereegranskat)abstract
    • The global increase in species richness toward the tropics across continents and taxonomic groups, referred to as the latitudinal diversity gradient, stimulated the formulation of many hypotheses to explain the underlying mechanisms of this pattern. We evaluate several of these hypotheses to explain spatial diversity patterns in a butterfly family, the Nymphalidae, by assessing the contributions of speciation, extinction, and dispersal, and also the extent to which these processes differ among regions at the same latitude. We generate a time-calibrated phylogeny containing 2,866 nymphalid species (~45% of extant diversity). Neither speciation nor extinction rate variations consistently explain the latitudinal diversity gradient among regions because temporal diversification dynamics differ greatly across longitude. The Neotropical diversity results from low extinction rates, not high speciation rates, and biotic interchanges with other regions are rare. Southeast Asia is also characterized by a low speciation rate but, unlike the Neotropics, is the main source of dispersal events through time. Our results suggest that global climate change throughout the Cenozoic, combined with tropical niche conservatism, played a major role in generating the modern latitudinal diversity gradient of nymphalid butterflies.
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33.
  • Diepgen, T. L., et al. (författare)
  • Hand eczema classification: a cross-sectional, multicentre study of the aetiology and morphology of hand eczema
  • 2009
  • Ingår i: British Journal of Dermatology. - : Oxford University Press (OUP). - 1365-2133 .- 0007-0963. ; 160:2, s. 353-358
  • Tidskriftsartikel (refereegranskat)abstract
    • Hand eczema is a long-lasting disease with a high prevalence in the background population. The disease has severe, negative effects on quality of life and sometimes on social status. Epidemiological studies have identified risk factors for onset and prognosis, but treatment of the disease is rarely evidence based, and a classification system for different subdiagnoses of hand eczema is not agreed upon. Randomized controlled trials investigating the treatment of hand eczema are called for. For this, as well as for clinical purposes, a generally accepted classification system for hand eczema is needed. The present study attempts to characterize subdiagnoses of hand eczema with respect to basic demographics, medical history and morphology. Clinical data from 416 patients with hand eczema from 10 European patch test clinics were assessed. A classification system for hand eczema is proposed. It is suggested that this classification be used in clinical work and in clinical trials.
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34.
  • Fiuza, Felipe P., et al. (författare)
  • Aging Alters Daily and Regional Calretinin Neuronal Expression in the Rat Non-image Forming Visual Thalamus
  • 2021
  • Ingår i: Frontiers in Aging Neuroscience. - : Frontiers Media S.A.. - 1663-4365. ; 13
  • Tidskriftsartikel (refereegranskat)abstract
    • Aging affects the overall physiology, including the image-forming and non-image forming visual systems. Among the components of the latter, the thalamic retinorecipient inter-geniculate leaflet (IGL) and ventral lateral geniculate (vLGN) nucleus conveys light information to subcortical regions, adjusting visuomotor, and circadian functions. It is noteworthy that several visual related cells, such as neuronal subpopulations in the IGL and vLGN are neurochemically characterized by the presence of calcium binding proteins. Calretinin (CR), a representative of such proteins, denotes region-specificity in a temporal manner by variable day-night expression. In parallel, age-related brain dysfunction and neurodegeneration are associated with abnormal intracellular concentrations of calcium. Here, we investigated whether daily changes in the number of CR neurons are a feature of the aged IGL and vLGN in rats. To this end, we perfused rats, ranging from 3 to 24 months of age, within distinct phases of the day, namely zeitgeber times (ZTs). Then, we evaluated CR immunolabeling through design-based stereological cell estimation. We observed distinct daily rhythms of CR expression in the IGL and in both the retinorecipient (vLGNe) and non-retinorecipient (vLGNi) portions of the vLGN. In the ZT 6, the middle of the light phase, the CR cells are reduced with aging in the IGL and vLGNe. In the ZT 12, the transition between light to dark, an age-related CR loss was found in all nuclei. While CR expression predominates in specific spatial domains of vLGN, age-related changes appear not to be restricted at particular portions. No alterations were found in the dark/light transition or in the middle of the dark phase, ZTs 0, and 18, respectively. These results are relevant in the understanding of how aging shifts the phenotype of visual related cells at topographically organized channels of visuomotor and circadian processing.
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35.
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36.
  • Garcia, R., et al. (författare)
  • A meta-analysis of the life cycle greenhouse gas balances of microalgae biodiesel
  • 2020
  • Ingår i: The International Journal of Life Cycle Assessment. - : Springer. - 0948-3349 .- 1614-7502. ; 25:9, s. 1737-1748
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: Microalgae biodiesel has attracted considerable attention as a potential substitute for fossil fuels and biodiesel from food crops. Nevertheless, its reported climate impacts in the scientific literature vary significantly. This article describes and synthesizes the range of results found in the life cycle assessment (LCA) literature regarding microalgae biodiesel studies to investigate whether particular parameters, e.g. technologies, were associated with higher or lower greenhouse gas (GHG) emissions so that a best practice can be inferred from currently available LCA data and thereby recommended. Methods: A systematic literature review and meta-regression analysis (MRA) of 36 LCA studies that report on the GHG emissions of microalgae biodiesel was conducted. An assessment of key aspects, including modelling choices and technologies, was performed. Furthermore, MRA models were formulated considering several variables of interest describing both technical and modelling choices to identify the main causes for the variability in GHG emissions per MJ of biodiesel. Variables chosen include: microalgae species; culture medium; cultivation system; source of CO2; extraction technology; conversion technology; system boundary; geographical scope; inclusion or exclusion of capital goods; and how multifunctionality was handled. Results and discussion: The reviewed studies altogether reported 308 results ranging from -0.7 to 3.8 kg CO2 eq. MJ-1biodiesel, portraying 19 different system configurations. Despite the comprehensive range of variables assessed, the models generated could not plausibly explain that the variability in GHG emissions depends either on the technologies considered or on the methodological choices adopted. However, the following relationships could be observed: location in Europe and high oil productivity were associated with lower emissions, whilst dry extraction should be avoided for leading to higher GHG emissions, on average. Conclusions: There is a large degree of variability within the technologies considered, as well as the methodological choices adopted, so that no robust conclusions could be drawn from the MRA. Notwithstanding, average GHG emissions reported were more than twice as high as fossil diesel and, while there are some studies showing large benefits, none of the various algae technologies performed consistently better than fossil diesel, questioning the climate-mitigation potential of microalgae biodiesel. 
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37.
  • Garzón-Orduña, Ivonne J., et al. (författare)
  • Wing pattern diversity in Eunica butterflies (Nymphalidae: Biblidinae) : phylogenetic analysis implies decoupled adaptive trends in dorsal sexual dimorphism and ventral eyespot evolution
  • 2024
  • Ingår i: Cladistics. - 0748-3007. ; 40:1, s. 1-20
  • Tidskriftsartikel (refereegranskat)abstract
    • Butterfly eyespots are wing patterns reminiscent of vertebrate eyes, formed by concentric rings of contrastingly coloured scales. Eyespots are usually located close to the wing margin and often regarded as the single most conspicuous pattern element of butterfly wing colour displays. Recent efforts to understand the processes involved in the formation of eyespots have been driven mainly by evo-devo approaches focused on model species. However, patterns of change implied by phylogenetic relationships can also inform hypotheses about the underlying developmental mechanisms associated with the formation or disappearance of eyespots, and the limits of phenotypic diversity occurring in nature. Here we present a combined evidence phylogenetic hypothesis for the genus Eunica, a prominent member of diverse Neotropical butterfly communities, that features notable variation among species in eyespot patterns on the ventral hind wing surface. The data matrix consists of one mitochondrial gene region (COI), four nuclear gene regions (GAPDH, RPS5, EF1a and Wingless) and 68 morphological characters. A combined cladistic analysis with all the characters concatenated produced a single most parsimonious tree that, although fully resolved, includes many nodes with modest branch support. The phylogenetic hypothesis presented corroborates a previously proposed morphological trend leading to the loss of eyespots, together with an increase in the size of the conserved eyespots, relative to outgroup taxa. Furthermore, wing colour pattern dimorphism and the presence of androconia suggest that the most remarkable instances of sexual dimorphism are present in the species of Eunica with the most derived eyespot patterns, and are in most cases accompanied by autapomorphic combinations of scent scales and “hair pencils”. We discuss natural and sexual selection as potential adaptive explanations for dorsal and ventral wing patterns.
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38.
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39.
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40.
  • Linhares, Sarah Sophia G., et al. (författare)
  • Prenatal exposure to fluoxetine modulates emotionality and aversive memory in male and female rat offspring
  • 2022
  • Ingår i: Behavioural Pharmacology. - : Lippincott Williams & Wilkins. - 0955-8810 .- 1473-5849. ; 33:8, s. 575-588
  • Tidskriftsartikel (refereegranskat)abstract
    • During pregnancy, women are prone to depression, for which selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine. are usually the first-line treatment. However, fluoxetine can cross the placental barrier and affect fetuses, causing changes in serotonin levels early in life. Long-term effects in the brain circuits that control cognitive and emotional behavior are related to early fluoxetine exposure during development. In this study, we aimed to investigate whether fluoxetine exposure (10 mg/kg/day) from the 13th gestational day (GD13) to GD21 may lead to behavioral emotional-cognitive changes in male and female rat offspring approximately 90 days postnatally (similar to PN90). We have analyzed the performance of individuals in the open field and in the plus-maze discriminative avoidance task, which assesses anxiety and learning/memory processing behaviors. We have found that prenatal (GD13-GD21) exposure to fluoxetine strengthened aversive memory and induced higher anxiety levels in males, and quick extinction of aversive memory in females. Taken together, these results suggest that early exposure to fluoxetine impairs the basal state of anxiety and the cognitive functions of rats during adulthood, which may be in a sex-specific manner because males appear more susceptible than females.
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41.
  • Moraes, Simeão de Souza, et al. (författare)
  • A double-edged sword : Unrecognized cryptic diversity and taxonomic impediment in Eois (Lepidoptera, Geometridae)
  • 2021
  • Ingår i: Zoologica Scripta. - : Wiley. - 0300-3256 .- 1463-6409. ; 50:5, s. 633-646
  • Tidskriftsartikel (refereegranskat)abstract
    • The genus Eois Hübner (Geometridae: Larentiinae) comprises 254 valid species. Being a hyperdiverse genus, Eois potentially includes many undescribed cryptic species and embodies a problematic taxonomic scenario. The actual diversity of Eois is greatly underestimated and the Neotropical fauna needs to be well known since it figures as one of the most threatened terrestrial ecosystem. In the present study, we compare three species delimitation methods to highlight the hidden diversity within a subset of Eois species: Automatic Barcode Gap Discovery, Bayesian Poisson Tree Processes and Multi-Rate Poisson Tree Processes. Our results point to an increase up to 176% in the currently valid species number. The hypothesis of cryptic diversity is corroborated by morphological characters within some species complexes. For complexes comprising species of Brazilian fauna, we provide a preliminary taxonomic assessment. Additionally, we found no congruence among the three delimitation methods for some species complexes, which indicates the importance of species and locality sampling as well as the previous alpha taxonomic knowledge in avoiding result bias. In this sense, we tried to standardize the identification provided for the Genbank sequences used in most relevant publications for Eois, in order to minimize biases and maximize the replicability of analyses in future studies. Moreover, we stress the importance of an integrative taxonomic approach for cryptic species discovery approach by employing both morphological attributes and life history to corroborate molecular analysis.
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42.
  • Moritz, J., et al. (författare)
  • Functional integration approaches via laser powder bed processing
  • 2019
  • Ingår i: Journal of laser applications. - : Laser Institute of America. - 1042-346X .- 1938-1387. ; 31:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Additive manufacturing design rules are different from those of conventional fabrication techniques. These allow geometries that would not be possible to achieve otherwise. One example of application is the integration of functional parts as part of the manufacturing process. Conceivable applications range from mechanical functions like integration of moving parts or thermodynamic functions, for example, cooling channels or incorporation of electric circuits for electrical functionalization [J. Glasschroeder, E. Prager, and M. F. Zaeh, Rapid Prototyping J. 21, 207–215 (2015)]. Nevertheless, the potential of functional integration using powder-bed processes is far from being exhausted. The present approach addresses the generation of inner cavities and internal structures of titanium-based parts or components by the use of selective laser melting. This paper focusses on the investigation of voids and cavities regarding their capabilities to add new functions to the material. To this end, comprehensive characterization is performed using destructive as well as nondestructive testing methods. These include 3D scanning, computed tomography, and surface roughness measurements as well as microscopic analysis. Voids and cavities were filled with different thermoplastic materials, followed by the qualitative assessment of the mold filling and resulting material properties. Finally, applications are derived and evaluated with respect to the field of lightweight design or damping structures.
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43.
  • Novaes, Renan M. L., et al. (författare)
  • Estimating 20-year land-use change and derived CO2 emissions associated with crops, pasture and forestry in Brazil and each of its 27 states
  • 2017
  • Ingår i: Global Change Biology. - : WILEY. - 1354-1013 .- 1365-2486. ; 23:9, s. 3716-3728
  • Tidskriftsartikel (refereegranskat)abstract
    • Land-use change (LUC) in Brazil has important implications on global climate change, ecosystem services and biodiversity, and agricultural expansion plays a critical role in this process. Concerns over these issues have led to the need for estimating the magnitude and impacts associated with that, which are increasingly reported in the environmental assessment of products. Currently, there is an extensive debate on which methods are more appropriate for estimating LUC and related emissions and regionalized estimates are lacking for Brazil, which is a world leader in agricultural production (e.g. food, fibres and bioenergy). We developed a method for estimating scenarios of past 20-year LUC and derived CO2 emission rates associated with 64 crops, pasture and forestry in Brazil as whole and in each of its 27 states, based on time-series statistics and in accordance with most used carbon-footprinting standards. The scenarios adopted provide a range between minimum and maximum rates of CO2 emissions from LUC according to different possibilities of land-use transitions, which can have large impacts in the results. Specificities of Brazil, like multiple cropping and highly heterogeneous carbon stocks, are also addressed. The highest CO2 emission rates are observed in the Amazon biome states and crops with the highest rates are those that have undergone expansion in this region. Some states and crops showing large agricultural areas have low emissions associated, especially in southern and eastern Brazil. Native carbon stocks and time of agricultural expansion are the most decisive factors to the patterns of emissions. Some implications on LUC estimation methods and standards and on agri-environmental policies are discussed.
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44.
  • Palmieri, M., et al. (författare)
  • Frequency and Evolution of Acute Oral Complications in Patients Undergoing Radiochemotherapy Treatment for Head and Neck Squamous Cell Carcinoma
  • 2021
  • Ingår i: Ear, Nose and Throat Journal. - : SAGE Publications. - 0145-5613 .- 1942-7522. ; 100:5 suppl.
  • Tidskriftsartikel (refereegranskat)abstract
    • Despite its effectiveness, radiochemotherapy treatment in the head and neck region is accompanied by acute oral complications such as oral mucositis, dysphagia, xerostomia, and dysgeusia. The aim of this study was to analyze and prospectively assess the frequency and evolution of acute oral complications during radiochemotherapy in patients diagnosed with squamous cell carcinoma in the head and neck region. We have analyzed oral complications of 20 patients during 6 weeks of radiochemotherapy treatment for squamous cell carcinoma. Oral mucositis was evaluated according to the World Health Organization criteria, dysphagia, and dysgeusia according to the National Cancer Institute Common Toxicity Criteria, and xerostomia according to parameters set by the Seminars in Radiation Oncology. Mucositis was first observed in the second week and all patients presented some degree of mucositis in the fourth week of radiotherapy. Xerostomia and dysphagia were initially reported already in the first week of radiotherapy. All patients presented xerostomia in the fourth week; however, dysphagia was observed in all patients, only in the sixth week. Dysgeusia was first observed in the second week, becoming more severe in the third week. Acute oral complications can be observed throughout the treatment, but the third week of radiotherapy seems to represent a critical week, regardless of the grade of the complication. The sixth week presents the worst grades of these complications. Knowledge about the natural course of oral complications during radiotherapy is important to develop better strategies for treatment and improve the patients’ quality of life. © The Author(s) 2019.
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45.
  • Puerta, Adrián, et al. (författare)
  • Early pharmacological profiling of isatin derivatives as potent and selective cytotoxic agents
  • 2024
  • Ingår i: Biochemical Pharmacology. - : Elsevier. - 0006-2952 .- 1356-1839. ; 222
  • Tidskriftsartikel (refereegranskat)abstract
    • Isatin derivatives have attracted a lot of interest for their potential in the development of new anticancer drugs. A library of 38 isatin derivatives, created through an Ugi four-component reaction, underwent an initial screening in a panel of six human solid tumor cell lines. The four most active derivatives were then selected for further testing. These compounds showed selectivity towards the non-small cell lung cancer (NSCLC) cell line SW1573, whilst NSCLC A549 cells were barely affected. The combination of phenotypic assays, including wound healing, clonogenic and continuous live cell imaging provided a deeper understanding of the compounds’ mode of action. In particular, the latter demonstrated that isatin derivatives were able to induce necroptosis in SW1573 cells. The kinetics of cell death showed that necroptosis appeared after 2.5 h of exposure, which could be delayed to 7 h when co-treated with necrostatin-1. Interaction between the isatin derivatives and the KRAS G12C protein variant was discarded after in silico studies. Further studies are warranted to identify the cellular target responsible for the observed selectivity among cell lines. 
  •  
46.
  • Schinke, Robert J., et al. (författare)
  • International society of sport psychology position stand : elite athlete mental health revisited
  • 2024
  • Ingår i: International Journal of Sport and Exercise Psychology. - Abingdon : Routledge. - 1612-197X .- 1557-251X. ; 22:4, s. 775-801
  • Tidskriftsartikel (refereegranskat)abstract
    • Athlete mental health, though long present within research and practice, has recently become a central topic area within the sport and exercise psychology field. The International Society of Sport Psychology has been at the forefront of these discussions, evidenced by a foundational position stand in 2018 and subsequent consensus statements derived from international think tanks. Within this position stand, contributors from the international community spanning five continents collaborated to present key, updated ideas and emerging concepts relating to clinical understandings of athlete mental health, trends in athlete mental health status, the role of the sport environment, mental health in relation to athlete careers, the global treatment of athlete mental health, cultural considerations in relation to understanding this topic, and nine synthesising postulates. © 2024 International Society of Sport Psychology.
  •  
47.
  • Schinke, Robert J., et al. (författare)
  • International society of sport psychology position stand: elite athlete mental health revisited
  • 2024
  • Ingår i: International Journal of Sport and Exercise Psychology. - : Taylor & Francis. - 1612-197X .- 1557-251X. ; , s. 1-27
  • Tidskriftsartikel (refereegranskat)abstract
    • Athlete mental health, though long present within research and practice, has recently become a central topic area within the sport and exercise psychology field. The International Society of Sport Psychology has been at the forefront of these discussions, evidenced by a foundational position stand in 2018 and subsequent consensus statements derived from international think tanks. Within this position stand, contributors from the international community spanning five continents collaborated to present key, updated ideas and emerging concepts relating to clinical understandings of athlete mental health, trends in athlete mental health status, the role of the sport environment, mental health in relation to athlete careers, the global treatment of athlete mental health, cultural considerations in relation to understanding this topic, and nine synthesising postulates.
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48.
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