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1.	Bernal, Ximena E., et al. (författare) Empowering Latina scientists 2019 Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 363:6429, s. 825-826 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
2.	Bossini-Castillo, Lara, et al. (författare) Confirmation of association of the macrophage migration inhibitory factor gene with systemic sclerosis in a large European population. 2011 Ingår i: Rheumatology (Oxford, England). - : Oxford University Press (OUP). - 1462-0332 .- 1462-0324. ; 50, s. 1976-1981 Tidskriftsartikel (refereegranskat)abstract Objectives. The aim of this study was to confirm the implication of macrophage migration inhibitory factor (MIF) gene in SSc susceptibility or clinical phenotypes in a large European population.Methods. A total of 3800 SSc patients and 4282 healthy controls of white Caucasian ancestry from eight different European countries were included in the study. The MIF -173 single nucleotide polymorphism (SNP) was selected as genetic marker and genotyped using Taqman 5' allelic discrimination assay.Results. The MIF -173 SNP showed association with SSc [P = 0.04, odds ratio (OR) = 1.10, 95% CI 1.00, 1.19]. Analysis of the MIF -173 polymorphism according to SSc clinical phenotype revealed that the frequency of the -173C allele was significantly higher in the dcSSc group compared with controls (P = 5.30E-03, OR = 1.21, 95% CI 1.07, 1.38). Conversely, the frequency of the MIF -173C allele was significantly underrepresented in the lcSSc group compared with dcSSc patients, supporting previous findings [(P = 0.04, OR = 0.86, 95% CI 0.75, 0.99); meta-analysis including previous results (P = 0.005, OR = 0.83, 95% CI 0.73, 0.94)].Conclusion. Our results confirm the role of MIF -173 promoter polymorphism in SSc, and provide evidence of a strong association with the dcSSc subgroup of patients. Hence, the MIF -173 variant is confirmed as a promising clinical phenotype genetic marker.
3.	Kehoe, Laura, et al. (författare) Make EU trade with Brazil sustainable 2019 Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6438, s. 341- Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
4.	Klionsky, Daniel J, et al. (författare) Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition). 2016 Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 12:1, s. 1-222 Tidskriftsartikel (refereegranskat)
5.	López-Isac, Elena, et al. (författare) Brief Report : IRF4 Newly Identified as a Common Susceptibility Locus for Systemic Sclerosis and Rheumatoid Arthritis in a Cross-Disease Meta-Analysis of Genome-Wide Association Studies 2016 Ingår i: Arthritis & Rheumatology. - : Wiley. - 2326-5191 .- 2326-5205. ; 68:9, s. 2338-2344 Tidskriftsartikel (refereegranskat)abstract Objective: Systemic sclerosis (SSc) and rheumatoid arthritis (RA) are autoimmune diseases that have similar clinical and immunologic characteristics. To date, several shared SSc–RA genetic loci have been identified independently. The aim of the current study was to systematically search for new common SSc–RA loci through an interdisease meta–genome-wide association (meta-GWAS) strategy. Methods: The study was designed as a meta-analysis combining GWAS data sets of patients with SSc and patients with RA, using a strategy that allowed identification of loci with both same-direction and opposite-direction allelic effects. The top single-nucleotide polymorphisms were followed up in independent SSc and RA case–control cohorts. This allowed an increase in the sample size to a total of 8,830 patients with SSc, 16,870 patients with RA, and 43,393 healthy controls. Results: This cross-disease meta-analysis of the GWAS data sets identified several loci with nominal association signals (P < 5 × 10−6) that also showed evidence of association in the disease-specific GWAS scans. These loci included several genomic regions not previously reported as shared loci, as well as several risk factors that were previously found to be associated with both diseases. Follow-up analyses of the putatively new SSc–RA loci identified IRF4 as a shared risk factor for these 2 diseases (Pcombined = 3.29 × 10−12). Analysis of the biologic relevance of the known SSc–RA shared loci identified the type I interferon and interleukin-12 signaling pathways as the main common etiologic factors. Conclusion: This study identified a novel shared locus, IRF4, for the risk of SSc and RA, and highlighted the usefulness of a cross-disease GWAS meta-analysis strategy in the identification of common risk loci.
6.	Forouzanfar, Mohammad H, et al. (författare) Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks in 188 countries, 1990-2013 : a systematic analysis for the Global Burden of Disease Study 2013. 2015 Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 386:10010, s. 2287-2323 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: The Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) is the first of a series of annual updates of the GBD. Risk factor quantification, particularly of modifiable risk factors, can help to identify emerging threats to population health and opportunities for prevention. The GBD 2013 provides a timely opportunity to update the comparative risk assessment with new data for exposure, relative risks, and evidence on the appropriate counterfactual risk distribution.METHODS: Attributable deaths, years of life lost, years lived with disability, and disability-adjusted life-years (DALYs) have been estimated for 79 risks or clusters of risks using the GBD 2010 methods. Risk-outcome pairs meeting explicit evidence criteria were assessed for 188 countries for the period 1990-2013 by age and sex using three inputs: risk exposure, relative risks, and the theoretical minimum risk exposure level (TMREL). Risks are organised into a hierarchy with blocks of behavioural, environmental and occupational, and metabolic risks at the first level of the hierarchy. The next level in the hierarchy includes nine clusters of related risks and two individual risks, with more detail provided at levels 3 and 4 of the hierarchy. Compared with GBD 2010, six new risk factors have been added: handwashing practices, occupational exposure to trichloroethylene, childhood wasting, childhood stunting, unsafe sex, and low glomerular filtration rate. For most risks, data for exposure were synthesised with a Bayesian meta-regression method, DisMod-MR 2.0, or spatial-temporal Gaussian process regression. Relative risks were based on meta-regressions of published cohort and intervention studies. Attributable burden for clusters of risks and all risks combined took into account evidence on the mediation of some risks such as high body-mass index (BMI) through other risks such as high systolic blood pressure and high cholesterol.FINDINGS: All risks combined account for 57·2% (95% uncertainty interval [UI] 55·8-58·5) of deaths and 41·6% (40·1-43·0) of DALYs. Risks quantified account for 87·9% (86·5-89·3) of cardiovascular disease DALYs, ranging to a low of 0% for neonatal disorders and neglected tropical diseases and malaria. In terms of global DALYs in 2013, six risks or clusters of risks each caused more than 5% of DALYs: dietary risks accounting for 11·3 million deaths and 241·4 million DALYs, high systolic blood pressure for 10·4 million deaths and 208·1 million DALYs, child and maternal malnutrition for 1·7 million deaths and 176·9 million DALYs, tobacco smoke for 6·1 million deaths and 143·5 million DALYs, air pollution for 5·5 million deaths and 141·5 million DALYs, and high BMI for 4·4 million deaths and 134·0 million DALYs. Risk factor patterns vary across regions and countries and with time. In sub-Saharan Africa, the leading risk factors are child and maternal malnutrition, unsafe sex, and unsafe water, sanitation, and handwashing. In women, in nearly all countries in the Americas, north Africa, and the Middle East, and in many other high-income countries, high BMI is the leading risk factor, with high systolic blood pressure as the leading risk in most of Central and Eastern Europe and south and east Asia. For men, high systolic blood pressure or tobacco use are the leading risks in nearly all high-income countries, in north Africa and the Middle East, Europe, and Asia. For men and women, unsafe sex is the leading risk in a corridor from Kenya to South Africa.INTERPRETATION: Behavioural, environmental and occupational, and metabolic risks can explain half of global mortality and more than one-third of global DALYs providing many opportunities for prevention. Of the larger risks, the attributable burden of high BMI has increased in the past 23 years. In view of the prominence of behavioural risk factors, behavioural and social science research on interventions for these risks should be strengthened. Many prevention and primary care policy options are available now to act on key risks.FUNDING: Bill & Melinda Gates Foundation.
7.	Naghavi, Mohsen, et al. (författare) Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013 2015 Ingår i: The Lancet. - 1474-547X .- 0140-6736. ; 385:9963, s. 117-171 Tidskriftsartikel (refereegranskat)abstract Background Up-to-date evidence on levels and trends for age-sex-specifi c all-cause and cause-specifi c mortality is essential for the formation of global, regional, and national health policies. In the Global Burden of Disease Study 2013 (GBD 2013) we estimated yearly deaths for 188 countries between 1990, and 2013. We used the results to assess whether there is epidemiological convergence across countries. Methods We estimated age-sex-specifi c all-cause mortality using the GBD 2010 methods with some refinements to improve accuracy applied to an updated database of vital registration, survey, and census data. We generally estimated cause of death as in the GBD 2010. Key improvements included the addition of more recent vital registration data for 72 countries, an updated verbal autopsy literature review, two new and detailed data systems for China, and more detail for Mexico, UK, Turkey, and Russia. We improved statistical models for garbage code redistribution. We used six different modelling strategies across the 240 causes; cause of death ensemble modelling (CODEm) was the dominant strategy for causes with sufficient information. Trends for Alzheimer's disease and other dementias were informed by meta-regression of prevalence studies. For pathogen-specifi c causes of diarrhoea and lower respiratory infections we used a counterfactual approach. We computed two measures of convergence (inequality) across countries: the average relative difference across all pairs of countries (Gini coefficient) and the average absolute difference across countries. To summarise broad findings, we used multiple decrement life-tables to decompose probabilities of death from birth to exact age 15 years, from exact age 15 years to exact age 50 years, and from exact age 50 years to exact age 75 years, and life expectancy at birth into major causes. For all quantities reported, we computed 95% uncertainty intervals (UIs). We constrained cause-specific fractions within each age-sex-country-year group to sum to all-cause mortality based on draws from the uncertainty distributions. Findings Global life expectancy for both sexes increased from 65.3 years (UI 65.0-65.6) in 1990, to 71.5 years (UI 71.0-71.9) in 2013, while the number of deaths increased from 47.5 million (UI 46.8-48.2) to 54.9 million (UI 53.6-56.3) over the same interval. Global progress masked variation by age and sex: for children, average absolute diff erences between countries decreased but relative diff erences increased. For women aged 25-39 years and older than 75 years and for men aged 20-49 years and 65 years and older, both absolute and relative diff erences increased. Decomposition of global and regional life expectancy showed the prominent role of reductions in age-standardised death rates for cardiovascular diseases and cancers in high-income regions, and reductions in child deaths from diarrhoea, lower respiratory infections, and neonatal causes in low-income regions. HIV/AIDS reduced life expectancy in southern sub-Saharan Africa. For most communicable causes of death both numbers of deaths and age-standardised death rates fell whereas for most non-communicable causes, demographic shifts have increased numbers of deaths but decreased age-standardised death rates. Global deaths from injury increased by 10.7%, from 4.3 million deaths in 1990 to 4.8 million in 2013; but age-standardised rates declined over the same period by 21%. For some causes of more than 100 000 deaths per year in 2013, age-standardised death rates increased between 1990 and 2013, including HIV/AIDS, pancreatic cancer, atrial fibrillation and flutter, drug use disorders, diabetes, chronic kidney disease, and sickle-cell anaemias. Diarrhoeal diseases, lower respiratory infections, neonatal causes, and malaria are still in the top five causes of death in children younger than 5 years. The most important pathogens are rotavirus for diarrhoea and pneumococcus for lower respiratory infections. Country-specific probabilities of death over three phases of life were substantially varied between and within regions. Interpretation For most countries, the general pattern of reductions in age-sex specifi c mortality has been associated with a progressive shift towards a larger share of the remaining deaths caused by non-communicable disease and injuries. Assessing epidemiological convergence across countries depends on whether an absolute or relative measure of inequality is used. Nevertheless, age-standardised death rates for seven substantial causes are increasing, suggesting the potential for reversals in some countries. Important gaps exist in the empirical data for cause of death estimates for some countries; for example, no national data for India are available for the past decade.
8.	Zamora, Juan Carlos, et al. (författare) Considerations and consequences of allowing DNA sequence data as types of fungal taxa 2018 Ingår i: IMA Fungus. - : INT MYCOLOGICAL ASSOC. - 2210-6340 .- 2210-6359. ; 9:1, s. 167-185 Tidskriftsartikel (refereegranskat)abstract Nomenclatural type definitions are one of the most important concepts in biological nomenclature. Being physical objects that can be re-studied by other researchers, types permanently link taxonomy (an artificial agreement to classify biological diversity) with nomenclature (an artificial agreement to name biological diversity). Two proposals to amend the International Code of Nomenclature for algae, fungi, and plants (ICN), allowing DNA sequences alone (of any region and extent) to serve as types of taxon names for voucherless fungi (mainly putative taxa from environmental DNA sequences), have been submitted to be voted on at the 11th International Mycological Congress (Puerto Rico, July 2018). We consider various genetic processes affecting the distribution of alleles among taxa and find that alleles may not consistently and uniquely represent the species within which they are contained. Should the proposals be accepted, the meaning of nomenclatural types would change in a fundamental way from physical objects as sources of data to the data themselves. Such changes are conducive to irreproducible science, the potential typification on artefactual data, and massive creation of names with low information content, ultimately causing nomenclatural instability and unnecessary work for future researchers that would stall future explorations of fungal diversity. We conclude that the acceptance of DNA sequences alone as types of names of taxa, under the terms used in the current proposals, is unnecessary and would not solve the problem of naming putative taxa known only from DNA sequences in a scientifically defensible way. As an alternative, we highlight the use of formulas for naming putative taxa (candidate taxa) that do not require any modification of the ICN.
9.	Agache, Ioana, et al. (författare) Prioritizing research challenges and funding for allergy and asthma and the need for translational research—The European Strategic Forum on Allergic Diseases 2019 Ingår i: Allergy: European Journal of Allergy and Clinical Immunology. - : Wiley. - 0105-4538. ; 74:11, s. 2064-2076 Tidskriftsartikel (refereegranskat)abstract The European Academy of Allergy and Clinical Immunology (EAACI) organized the first European Strategic Forum on Allergic Diseases and Asthma. The main aim was to bring together all relevant stakeholders and decision-makers in the field of allergy, asthma and clinical Immunology around an open debate on contemporary challenges and potential solutions for the next decade. The Strategic Forum was an upscaling of the EAACI White Paper aiming to integrate the Academy's output with the perspective offered by EAACI's partners. This collaboration is fundamental for adapting and integrating allergy and asthma care into the context of real-world problems. The Strategic Forum on Allergic Diseases brought together all partners who have the drive and the influence to make positive change: national and international societies, patients’ organizations, regulatory bodies and industry representatives. An open debate with a special focus on drug development and biomedical engineering, big data and information technology and allergic diseases and asthma in the context of environmental health concluded that connecting science with the transformation of care and a joint agreement between all partners on priorities and needs are essential to ensure a better management of allergic diseases and asthma in the advent of precision medicine together with global access to innovative and affordable diagnostics and therapeutics.
10.	Al-Rudainy, Basel, et al. (författare) Impact of lignin content on the properties of hemicellulose hydrogels 2019 Ingår i: Polymers. - : MDPI AG. - 2073-4360. ; 11:1 Tidskriftsartikel (refereegranskat)abstract Hemicellulose is a promising renewable raw material for the production of hydrogels. This polysaccharide exists in large amounts in various waste streams, in which they are usually impure and heavily diluted. Several downstream processing methods can be combined to concentrate and purify the hemicellulose. However, such an approach can be costly; hence, the effect of impurities on the formation and properties of hydrogels must be determined. Lignin usually exists in these waste streams as a major impurity that is also difficult to separate. This compound can darken hydrogels and decrease their swellability and reactivity, as shown in many studies. Other properties and effects of lignin impurities are equally important for the end application of hydrogels and the overall process economy. In this work, we examined the feasibility of producing hydrogels from hemicelluloses that originated from sodium-based spent sulfite liquor. A combination of membrane filtration and anti-solvent precipitation was used to extract and purify various components. The influence of the purity of hemicellulose and the addition of lignosulfonates (emulated impurities in the downstream processing) to the crosslinking reaction mixture on the mechanical, thermal, and chemical properties of hydrogels was determined.
11.	Arcos-Hernandez, Monica, et al. (författare) Thermoresponsive Glycopolymers Based on Enzymatically Synthesized Oligo-β-Mannosyl Ethyl Methacrylates and N-Isopropylacrylamide 2021 Ingår i: Biomacromolecules. - : American Chemical Society (ACS). - 1526-4602 .- 1525-7797. ; 22:6, s. 2338-2351 Tidskriftsartikel (refereegranskat)abstract We here present a series of thermoresponsive glycopolymers in the form of poly(N-isopropylacrylamide)-co-(2-[β-manno[oligo]syloxy] ethyl methacrylate)s. These copolymers were prepared from oligo-β-mannosyl ethyl methacrylates that were synthesized through enzymatic catalysis, and were subsequently investigated with respect to their aggregation and phase behavior in aqueous solution using a combination of 1H NMR spectroscopy, dynamic light scattering, cryogenic transmission electron microscopy (TEM) and small angle X-ray scattering (SAXS). The thermoresponsive glycopolymers were prepared by conventional free radical copolymerizations of different mixtures of 2-(β-manno[oligo]syloxy)ethyl methacrylates (with either one or two saccharide units) and N-isopropyl acrylamide (NIPAm). The results showed that below the lower critical solution temperature (LCST) of poly(NIPAm), the glycopolymers readily aggregate into nanoscale structures, partly due to the presence of the saccharide moieties. Above the LCST of poly(NIPAm), the glycopolymers rearrange into a heterogeneous mixture of fractal and disc/globular aggregates. Cryo-TEM and SAXS data demonstrated that the presence of the pendant β-mannosyl moieties in the glycopolymers induces a gradual conformational change over a wide temperature range. Even though the onset of this transition is not different from the LCST of poly(NIPAm), this gradual conformational change offers a variation of the temperature-dependent properties in comparison to poly(NIPAm), which displays a sharp coil-to-globule transition. Importantly, the compacted form of the glycopolymers show a larger colloidal stability compared to the unmodified poly(NIPAm). In addition, the thermoresponsiveness can be conveniently tuned by varying the sugar unit-length and the oligo-β-mannosyl ethyl methacrylate content.
12.	Benatar, Michael, et al. (författare) Safety and efficacy of arimoclomol in patients with early amyotrophic lateral sclerosis (ORARIALS-01) : a randomised, double-blind, placebo-controlled, multicentre, phase 3 trial 2024 Ingår i: Lancet Neurology. - : Elsevier. - 1474-4422 .- 1474-4465. ; 23:7, s. 687-699 Tidskriftsartikel (refereegranskat)abstract Background: Amyotrophic lateral sclerosis is a progressive neurodegenerative disorder leading to muscle weakness and respiratory failure. Arimoclomol, a heat-shock protein-70 (HSP70) co-inducer, is neuroprotective in animal models of amyotrophic lateral sclerosis, with multiple mechanisms of action, including clearance of protein aggregates, a pathological hallmark of sporadic and familial amyotrophic lateral sclerosis. We aimed to evaluate the safety and efficacy of arimoclomol in patients with amyotrophic lateral sclerosis.Methods: ORARIALS-01 was a multinational, randomised, double-blind, placebo-controlled, parallel-group trial done at 29 centres in 12 countries in Europe and North America. Patients were eligible if they were aged 18 years or older and met El Escorial criteria for clinically possible, probable, probable laboratory-supported, definite, or familial amyotrophic lateral sclerosis; had an ALS Functional Rating Scale-Revised score of 35 or more; and had slow vital capacity at 70% or more of the value predicted on the basis of the participant's age, height, and sex. Patients were randomly assigned (2:1) in blocks of 6, stratified by use of a stable dose of riluzole or no riluzole use, to receive oral arimoclomol citrate 1200 mg/day (400 mg three times per day) or placebo. The Randomisation sequence was computer generated centrally. Investigators, study personnel, and study participants were masked to treatment allocation. The primary outcome was the Combined Assessment of Function and Survival (CAFS) rank score over 76 weeks of treatment. The primary outcome and safety were analysed in the modified intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT03491462, and is completed.Findings: Between July 31, 2018, and July 17, 2019, 287 patients were screened, 245 of whom were enrolled in the trial and randomly assigned. The modified intention-to-treat population comprised 239 patients (160 in the arimoclomol group and 79 in the placebo group): 151 (63%) were male and 88 (37%) were female; mean age was 57·6 years (SD 10·9). CAFS score over 76 weeks did not differ between groups (mean 0·51 [SD 0·29] in the arimoclomol group vs 0·49 [0·28] in the placebo group; p=0·62). Cliff's delta comparing the two groups was 0·039 (95% CI –0·116 to 0·194). Proportions of participants who died were similar between the treatment groups: 29 (18%) of 160 patients in the arimoclomol group and 18 (23%) of 79 patients in the placebo group. Most deaths were due to disease progression. The most common adverse events were gastrointestinal. Adverse events were more often deemed treatment-related in the arimoclomol group (104 [65%]) than in the placebo group (41 [52%]) and more often led to treatment discontinuation in the arimoclomol group (26 [16%]) than in the placebo group (four [5%]).Interpretation: Arimoclomol did not improve efficacy outcomes compared with placebo. Although available biomarker data are insufficient to preclude future strategies that target the HSP response, safety data suggest that a higher dose of arimoclomol would not have been tolerated.Funding: Orphazyme.
13.	Bonjour, Olivier, et al. (författare) Lignin-Inspired Polymers with High Glass Transition Temperature and Solvent Resistance from 4-Hydroxybenzonitrile, Vanillonitrile, and Syringonitrile Methacrylates 2021 Ingår i: ACS Sustainable Chemistry & Engineering. - : American Chemical Society (ACS). - 2168-0485. ; 9:50, s. 16874-16880 Tidskriftsartikel (refereegranskat)abstract We here report on the synthesis and polymerization of nitrile-containing methacrylate monomers, prepared via straightforward nitrilation of the corresponding lignin-inspired aldehyde. The polymethacrylates reached exceptionally high glass transition temperatures (Tg values), i.e., 150, 164, and 238 °C for the 4-hydroxybenzonitrile, vanillonitrile, and syringonitrile derivatives, respectively, and were thermally stable up to above 300 °C. Copolymerizations of the nitrile monomers with styrene and methyl methacrylate, respectively, gave potentially melt processable materials with tunable Tg values and enhanced solvent resistance. The use of lignin-derived nitrile-containing monomers represents an efficient strategy toward well-defined biobased high Tg polymer materials.
14.	Bossini-Castillo, Lara, et al. (författare) A GWAS follow-up study reveals the association of the IL12RB2 gene with systemic sclerosis in Caucasian populations 2012 Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 21:4, s. 926-933 Tidskriftsartikel (refereegranskat)abstract A single-nucleotide polymorphism (SNP) at the IL12RB2 locus showed a suggestive association signal in a previously published genome-wide association study (GWAS) in systemic sclerosis (SSc). Aiming to reveal the possible implication of the IL12RB2 gene in SSc, we conducted a follow-up study of this locus in different Caucasian cohorts. We analyzed 10 GWAS-genotyped SNPs in the IL12RB2 region (2309 SSc patients and 5161 controls). We then selected three SNPs (rs3790567, rs3790566 and rs924080) based on their significance level in the GWAS, for follow-up in an independent European cohort comprising 3344 SSc and 3848 controls. The most-associated SNP (rs3790567) was further tested in an independent cohort comprising 597 SSc patients and 1139 controls from the USA. After conditional logistic regression analysis of the GWAS data, we selected rs3790567 [P-MH = 1.92 x 10(-5) odds ratio (OR) = 1.19] as the genetic variant with the firmest independent association observed in the analyzed GWAS peak of association. After the first follow-up phase, only the association of rs3790567 was consistent (P-MH = 4.84 x 10(-3) OR = 1.12). The second follow-up phase confirmed this finding (P-chi 2 = 2.82 x 10(-4) OR = 1.34). After performing overall pooled-analysis of all the cohorts included in the present study, the association found for the rs3790567 SNP in the IL12RB2 gene region reached GWAS-level significant association (P-MH = 2.82 x 10(-9) OR = 1.17). Our data clearly support the IL12RB2 genetic association with SSc, and suggest a relevant role of the interleukin 12 signaling pathway in SSc pathogenesis.
15.	Butler, Samuel J., et al. (författare) Transglycosylation by β-mannanase TrMan5A variants and enzyme synergy for synthesis of allyl glycosides from galactomannan 2022 Ingår i: Process Biochemistry. - : Elsevier BV. - 1359-5113. ; 112, s. 154-166 Tidskriftsartikel (refereegranskat)abstract Retaining β-mannanases are glycoside hydrolases (GHs) that can potentially be applied for synthesis of glycosides by catalysis of transglycosylation reactions. A novel active-site double mutant (R171K/E205D) of the catalytic module (CM) of the family GH5 Trichoderma reesei β-mannanase (TrMan5A) was expressed in Pichia pastoris and purified. TrMan5A, CM and CM-variants R171K and R171K/E205D had pH optima between pH 4.0–5.3 and showed >80 % remaining activity after incubation at 40 °C for 48 h. The enzymes were screened for transglycosylation capacity toward oligomeric and polymeric donor substrates and alcohol acceptors using mass-spectrometry. Hydrolysis and transglycosylation products were analysed by a novel HPLC procedure using an NH2 column. R171K/E205D was superior in reactions with mannotetraose and the acceptor allyl alcohol, it had twice as high propensity for transglycosylation as wild-type TrMan5A. Wild-type TrMan5A produced the highest amounts of allyl β-mannosides (with 1–3 mannosyls) from locust bean galactomannan. Applying enzyme synergy, adding the GH27 guar α-galactosidase to the reaction (to cleave off galactomannan side-groups), gave a 2.1-fold increase of allyl mannosides and simultaneously a significant production of allyl galactopyranoside, increasing overall yield of allyl glycosides 4.4-fold, from 2.2% to 9.8%. The enzymatic synthesis of reactive allyl glycosides opens up for production of novel biomaterials and glycopolymers.
16.	Clothier, Richard, et al. (författare) A database of IC50 values and principal component analysis of results from six basal cytotoxicity assays, for use in the modelling of the in vivo and in vitro data of the EU ACuteTox project. 2008 Ingår i: Altern Lab Anim. - 0261-1929. ; 36:5, s. 503-19 Tidskriftsartikel (refereegranskat)abstract The main aim of the ACuteTox project (part of the EU 6th Framework programme) is to demonstrate that animal tests for acute systemic toxicity can be replaced by alternative in vitro assays. In this project, data for 97 reference chemicals were collected in the AcuBase database, designed to handle deposited in vitro and in vivo (human and animal) data. To demonstrate the applicability of in vitro basal cytotoxicity tests and in vitro-in vivo modelling, it was deemed necessary to obtain data that were generated via defined standard operating procedures. The molar basal cytotoxicity IC50 values (the 50% inhibitory concentrations for the endpoint measured) for a mouse fibroblast cell line (3T3), a human hepatic cell line (HepG2), a rat hepatic cell line (Fa32), and a human neutrophil cell line (HL-60), were compared, and gave an R(2) correlation of 0.83. To identify chemicals that showed differential cytotoxicity to the various cell types involved, principal component analysis (PCA) was undertaken independently, once all the results had been returned. This showed that colchicine, cycloheximide, digoxin, 5-fluorouracil and hexachlorobenzene gave the lowest correlations with the first score vector of the PCA. The results presented are to be used to identify outliers that need to be further studied via the use of tissue-specific in vitro assays.
17.	David Carmona, F., et al. (författare) Association of a non-synonymous functional variant of the ITGAM gene with systemic sclerosis 2011 Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 70:11, s. 203-2050 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
18.	Dicks, Lynn, et al. (författare) Knowledge synthesis for environmental decisions : an evaluation of existing methods, and guidance for their selection, use and development : a report from the EKLIPSE project 2017 Rapport (övrigt vetenskapligt/konstnärligt)
19.	Fathi, Kambiz, et al. (författare) Evolution of structure in late-type spiral galaxies. I : Ionized gas kinematics in NGC 628 2007 Ingår i: Astronomy and Astrophysics. ; 466:905 Tidskriftsartikel (refereegranskat)abstract Aims.We study two dimensional Fabry-Perot interferometric observations of the nearby face-on late-type spiral galaxy, NGC 628, in order to analyse the ionized gas component of the interstellar medium. Covering the galaxy out to a radius larger than 12 kpc, and with a spatial sampling of 1.6'', we aim to investigate the large-scale dynamics as well as feedback from individual H ii regions into their surrounding medium. Methods: The observed Hα emission distribution and kinematics are compared with auxiliary data from molecular and atomic gas observations, which display many similarities. We decompose the observed line-of-sight velocities into rotational and higher-order harmonic components, and study the role of gravitational perturbations along with that of external triggers which can disturb the kinematics and morphology of NGC 628. We calculate radial profiles of the emission-line velocity dispersion which we use to study the role of feedback from individual H ii regions. Results: We verify the presence of an inner rapidly rotating disc-like component in NGC 628, which we interpret as caused by slow secular evolution of the large-scale spiral arms and oval structure. In combination with auxiliary data, we find indication for that gas is falling in from the outer parts towards the central regions, where a nuclear ring has formed at the location of the inner Lindblad resonance radius of an an m=2 perturbation. Complementary continuum subtracted narrow band images in Hα have been used to identify 376 H ii regions with calibrated luminosities. The mean velocity dispersion for the ionized gas (even when excluding pixels belonging to H ii regions) is almost constant out to 12 kpc, although it varies from 14 to 20 km s-1, with a steady decline in the outer parts. Conclusions: We have found kinematic signatures of radial motions caused by an m=2 perturbation. Such a perturbation may well be responsible for the inflow of material forming the nuclear ring and the inner rapidly rotating disc-like structure. The latter, in turn, could help build a pseudo-bulge in NGC 628. The current paper demonstrates a number of tools that we have developed for building a solid frame work for studying the evolution of structure in spiral galaxies using two dimensional kinematic observations.
20.	Ferro, Ana, et al. (författare) Fruits and vegetables intake and gastric cancer risk : A pooled analysis within the Stomach cancer Pooling Project. 2020 Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 147:11, s. 3090-3101 Tidskriftsartikel (refereegranskat)abstract A low intake of fruits and vegetables is a risk factor for gastric cancer, although there is uncertainty regarding the magnitude of the associations. In our study, the relationship between fruits and vegetables intake and gastric cancer was assessed, complementing a previous work on the association betweenconsumption of citrus fruits and gastric cancer. Data from 25 studies (8456 cases and 21 133 controls) with information on fruits and/or vegetables intake were used. A two-stage approach based on random-effects models was used to pool study-specific adjusted (sex, age and the main known risk factors for gastric cancer) odds ratios (ORs) and the corresponding 95% confidence intervals (CIs). Exposure-response relations, including linear and nonlinear associations, were modeled using one- and two-order fractional polynomials. Gastric cancer risk was lower for a higher intake of fruits (OR: 0.76, 95% CI: 0.64-0.90), noncitrus fruits (OR: 0.86, 95% CI: 0.73-1.02), vegetables (OR: 0.68, 95% CI: 0.56-0.84), and fruits and vegetables (OR: 0.61, 95% CI: 0.49-0.75); results were consistent across sociodemographic and lifestyles categories, as well as study characteristics. Exposure-response analyses showed an increasingly protective effect of portions/day of fruits (OR: 0.64, 95% CI: 0.57-0.73 for six portions), noncitrus fruits (OR: 0.71, 95% CI: 0.61-0.83 for six portions) and vegetables (OR: 0.51, 95% CI: 0.43-0.60 for 10 portions). A protective effect of all fruits, noncitrus fruits and vegetables was confirmed, supporting further dietary recommendations to decrease the burden of gastric cancer.
21.	Font, Joan, et al. (författare) DETECTION OF INFALLING HYDROGEN IN TRANSFER BETWEEN THE INTERACTING GALAXIES NGC 5426 AND NGC 5427 2011 Ingår i: The Astrophysical Journal. Letters. - 2041-8205. ; 740:1, s. L1- Tidskriftsartikel (refereegranskat)abstract Using velocity tagging we have detected hydrogen from NGC 5426 falling onto its interacting partner NGC 5427. Our observations, with the GHaFaS Fabry-Perot spectrometer, produced maps of the two galaxies in H alpha surface brightness and radial velocity. We found emission with the range of velocities associated with NGC 5426 along lines of sight apparently emanating from NGC 5427, superposed on the velocity map of the latter. After excluding instrumental effects we assign the anomalous emission to gas pulled from NGC 5426 during its passage close to NGC 5427. Its distribution, more intense between the arms and just outside the disk of NGC 5427, and weak, or absent, in the arms, suggests that the infalling gas is behind the disk, ionized by Lyman continuum photons escaping from NGC 5427. Modeling this, we estimate the distances of these gas clouds behind the plane: a few hundred parsecs to a few kiloparsecs. We also estimate the mass of the infalling (ionized plus neutral) gas, finding an infall rate of 10 M(circle dot) per year, consistent with the high measured star formation rate across the disk of NGC 5427 and with the detected circumnuclear galactic wind.
22.	Fullman, Nancy, et al. (författare) Measuring performance on the Healthcare Access and Quality Index for 195 countries and territories and selected subnational locations: A systematic analysis from the Global Burden of Disease Study 2016 2018 Ingår i: The Lancet. - : Lancet Publishing Group. - 1474-547X .- 0140-6736. ; 391:10136, s. 2236-2271 Tidskriftsartikel (refereegranskat)
23.	Galárraga-Espinosa, Daniela, et al. (författare) Evolution of cosmic filaments in the MTNG simulation? 2024 Ingår i: Astronomy and Astrophysics. - 0004-6361. ; 684 Tidskriftsartikel (refereegranskat)abstract We present a study of the evolution of cosmic filaments across redshift with an emphasis on some important properties: filament lengths, growth rates, and radial profiles of galaxy densities. Following an observation-driven approach, we built cosmic filament catalogues at z = 0, 1, 2, 3, and 4 from the galaxy distributions of the large hydro-dynamical run of the MilleniumTNG project. We employed the extensively used DisPerSE cosmic web finder code, for which we provide a user-friendly guide, including the details of a physics-driven calibration procedure, with the hope of helping future users. We performed the first statistical measurements of the evolution of connectivity in a large-scale simulation, finding that the connectivity of cosmic nodes (defined as the number of filaments attached) globally decreases from early to late times. The study of cosmic filaments in proper coordinates reveals that filaments grow in length and radial extent, as expected from large-scale structures in an expanding Universe. But the most interesting results arise once the Hubble flow is factored out. We find remarkably stable comoving filament length functions and over-density profiles, showing only little evolution of the total population of filaments in the past ∼12.25 Gyr. However, by tracking the spatial evolution of individual structures, we demonstrate that filaments of different lengths actually follow different evolutionary paths. While short filaments preferentially contract, long filaments expand along their longitudinal direction with growth rates that are the highest in the early, matter-dominated Universe. Filament diversity at a fixed redshift is also shown by the different (∼5σ) density values between the shortest and longest filaments. Our results hint that cosmic filaments can be used as additional probes for dark energy, but further theoretical work is still needed.
24.	Garcia, Adriana Alvarado, et al. (författare) Fostering HCI Research in, by, and for Latin America 2020 Ingår i: Extended Abstracts of the 2020 CHI Conference on Human Factors in Computing Systems, CHI 2020. - New York, NY, USA : Association for Computing Machinery (ACM). Konferensbidrag (refereegranskat)abstract Over the last 20 years, the Latin American Human-Computer Interaction (HCI) community has been working to shed light on how the diverse populations in the region are adopting, using, and making sense of computational technologies. Latin America's tense socio-political context, plurality of languages, collectivist culture, and historical relationship with the Global North make it a unique and rich space for HCI research. Considering the growing number of studies about Latin American communities and the emergent efforts to contribute to the HCI literature, we propose to host a SIG meeting at the 2020 ACM CHI conference. Our goal is to consolidate these efforts to better promote HCI research in, by, and for Latin America, by (1) bringing together researchers, practitioners, and students who are interested in engaging with Latin America through their research and practice, (2) envisioning a shared research agenda, and (3) identifying strategies for making its contributions more visible and impactful in the international community.
25.	Guevara-Cruz, Martha, et al. (författare) Intermittent fasting, calorie restriction, and a ketogenic diet improve mitochondrial function by reducing lipopolysaccharide signaling in monocytes during obesity: A randomized clinical trial 2024 Ingår i: Clinical Nutrition. - 1532-1983 .- 0261-5614. ; 43:8, s. 1914-1928 Tidskriftsartikel (refereegranskat)abstract Background : Mitochondrial dysfunction occurs in monocytes during obesity and contributes to a low-grade inflammatory state; therefore, maintaining good mitochondrial conditions is a key aspect of maintaining health. Dietary interventions are primary strategies for treating obesity, but little is known about their impact on monocyte bioenergetics. Thus, the aim of this study was to evaluate the effects of calorie restriction (CR), intermittent fasting (IF), a ketogenic diet (KD), and an ad libitum habitual diet (AL) on mitochondrial function in monocytes and its modulation by the gut microbiota. Methods and findings : A randomized controlled clinical trial was conducted in which individuals with obesity were assigned to one of the 4 groups for 1 month. Subsequently, the subjects received rifaximin and continued with the assigned diet for another month. The oxygen consumption rate (OCR) was evaluated in isolated monocytes, as was the gut microbiota composition in feces and anthropometric and biochemical parameters. Forty-four subjects completed the study, and those who underwent CR, IF and KD interventions had an increase in the maximal respiration OCR (p = 0.025, n2p = 0.159 [0.05, 0.27] 95% confidence interval) in monocytes compared to that in the AL group. The improvement in mitochondrial function was associated with a decrease in monocyte dependence on glycolysis after the IF and KD interventions. Together, diet and rifaximin increased the gut microbiota diversity in the IF and KD groups (p = 0.0001), enriched the abundance of Phascolarctobacterium faecium (p = 0.019) in the CR group and Ruminococcus bromii (p = 0.020) in the CR and KD groups, and reduced the abundance of lipopolysaccharide (LPS)-producing bacteria after CR, IF and KD interventions compared to the AL group at the end of the study according to ANCOVA with covariate adjustment. Spearman's correlation between the variables measured highlighted LPS as a potential modulator of the observed effects. In line with this findings, serum LPS and intracellular signaling in monocytes decreased with the three interventions (CR, p = 0.002; IF, p = 0.001; and KD, p = 0.001) compared to those in the AL group at the end of the study. Conclusions : We conclude that these dietary interventions positively regulate mitochondrial bioenergetic health and improve the metabolic profile of monocytes in individuals with obesity via modulation of the gut microbiota. Moreover, the evaluation of mitochondrial function in monocytes could be used as an indicator of metabolic and inflammatory status, with potential applications in future clinical trials. Trial registration: This trial was registered with ClinicalTrials.gov (NCT05200468).
26.	Hardisty, Alex R., et al. (författare) BioVeL: A virtual laboratory for data analysis and modelling in biodiversity science and ecology 2016 Ingår i: BMC Ecology. - : Springer Science and Business Media LLC. - 1472-6785. ; 16 Tidskriftsartikel (refereegranskat)abstract © 2016 The Author(s).Background: Making forecasts about biodiversity and giving support to policy relies increasingly on large collections of data held electronically, and on substantial computational capability and capacity to analyse, model, simulate and predict using such data. However, the physically distributed nature of data resources and of expertise in advanced analytical tools creates many challenges for the modern scientist. Across the wider biological sciences, presenting such capabilities on the Internet (as "Web services") and using scientific workflow systems to compose them for particular tasks is a practical way to carry out robust "in silico" science. However, use of this approach in biodiversity science and ecology has thus far been quite limited. Results: BioVeL is a virtual laboratory for data analysis and modelling in biodiversity science and ecology, freely accessible via the Internet. BioVeL includes functions for accessing and analysing data through curated Web services; for performing complex in silico analysis through exposure of R programs, workflows, and batch processing functions; for on-line collaboration through sharing of workflows and workflow runs; for experiment documentation through reproducibility and repeatability; and for computational support via seamless connections to supporting computing infrastructures. We developed and improved more than 60 Web services with significant potential in many different kinds of data analysis and modelling tasks. We composed reusable workflows using these Web services, also incorporating R programs. Deploying these tools into an easy-to-use and accessible 'virtual laboratory', free via the Internet, we applied the workflows in several diverse case studies. We opened the virtual laboratory for public use and through a programme of external engagement we actively encouraged scientists and third party application and tool developers to try out the services and contribute to the activity. Conclusions: Our work shows we can deliver an operational, scalable and flexible Internet-based virtual laboratory to meet new demands for data processing and analysis in biodiversity science and ecology. In particular, we have successfully integrated existing and popular tools and practices from different scientific disciplines to be used in biodiversity and ecological research.
27.	Hernandez Alava, Monica, et al. (författare) Measuring quality of life of patients with axial spondyloarthritis for economic evaluation 2022 Ingår i: RMD Open. - : BMJ. - 2056-5933. ; 8:1 Tidskriftsartikel (refereegranskat)abstract Objectives To estimate the relationship between EQ5D (three levels, UK version) and the Ankylosing Spondylitis Disease Activity Score (ASDAS) for use in the economic evaluation of health technologies for people with axial spondyloarthritis (axSpA). To compare against the relationship with the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Methods An electronic, prospective, Portuguese, nationwide, rheumatic disease register (Reuma.pt) provided data on 1140 patients (5483 observations) with a confirmed diagnosis of axSpA. We estimated models of EQ5D as a function of ASDAS, alone or in combination with measures of functional impairment, using bespoke mixture models which reflect the complex distributional features of EQ5D. The SPondyloArthritis Caught Early cohort provided data from 344 patients (1405 observations) in four European countries and was used for validation. A previously published model of BASDAI/Bath Ankylosing Spondylitis Functional Index (BASFI) was also used to generate predicted EQ5D scores and model performance compared. Results A non-linear relationship exists between EQ5D from ASDAS. The final model included ASDAS, ASDAS squared, age and age squared and demonstrated close fit in both datasets except where data were sparse for patients with very high levels of disease activity (ASDAS >4). This finding held in the validation dataset. Models that included BASFI improved model fit. The ASDAS based models fit the data marginally less well than models using BASDAI. Conclusions Mapping models linking ASDAS to EQ5D allow results from clinical studies to be used in economic evaluation of health technologies with confidence. There is some loss of information compared with BASDAI but this has only a marginal impact.
28.	Hernández-González, Juan S., et al. (författare) Petrology and geochemistry of high-Al chromitites from the Medellín Metaharzburgitic Unit (MMU), Colombia 2020 Ingår i: Boletín de la Sociedad Geológica Mexicana. - : Universidad Nacional Autónoma de México. - 1405-3322 .- 1405-3322. ; 72:3 Tidskriftsartikel (refereegranskat)abstract The Medellin Metaharzburgitic Unit (MMU), emplaced onto the western continental margin of Pangea during Triassic time, is located in the Central Cordillera of Colombia and consists of metaharzburgites, minor metadunites and chromitite bodies (Patio Bonito and San Pedro ore deposits). The ultramafic rocks contain relicts of mantle-derived olivine, chromian spinel and minor orthopyroxene, and a later metamorphic mineral assemblage composed by tremolite, chlorite, talc, fine-grained recrystallized olivine, serpentine-group minerals, magnetite, and secondary chromian spinel, formed during the thermal evolution of the unit. The Cr# [Cr/(Cr+Al) atomic ratio] of the accessory primary chromian spinel in the metaperidotites ranges from 0.58 to 0.62 and overlaps those of supra-subduction peridotites from ophiolites. According to textural and compositional variations, the accessory chromian spinel in the metaperidotites can be classified into three groups: i) partially altered chromian spinel with an Al-rich core, ii) porous, Cr-Fe2+-enriched and Al-Mg-depleted chromian spinel, and iii) homogeneous Fe3+-rich chromian spinel. These variations can be related to superimposed medium-T metamorphism that reached amphibolite facies (ca. 600 ºC). Chromitite bodies associated with the metaperidotites have massive and semi-massive textures, and mainly consist of chromian spinel crystals, which show large unaltered cores surrounded by thin alteration rims of ferrian chromian spinel and chlorite. Chromitites are Al-rich (#Cr <0.6) and strongly depleted in platinum group elements (ΣPGE <41 ppb). The primary petrological and geochemical characteristics preserved in the metaperidotites and chromitites indicate that the MMU formed at shallow levels of a suboceanic lithospheric mantle related to a supra-subduction zone (back-arc basin/incipient arc scenario), and that the chromitites crystallized from a tholeiitic magma (back-arc basin basalt type).
29.	Jin, Shoko, et al. (författare) The wide-field, multiplexed, spectroscopic facility WEAVE : Survey design, overview, and simulated implementation 2024 Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press. - 0035-8711 .- 1365-2966. ; 530:3, s. 2688-2730 Tidskriftsartikel (refereegranskat)abstract WEAVE, the new wide-field, massively multiplexed spectroscopic survey facility for the William Herschel Telescope, saw first light in late 2022. WEAVE comprises a new 2-deg field-of-view prime-focus corrector system, a nearly 1000-multiplex fibre positioner, 20 individually deployable 'mini' integral field units (IFUs), and a single large IFU. These fibre systems feed a dual-beam spectrograph covering the wavelength range 366-959nm at R similar to 5000, or two shorter ranges at . After summarizing the design and implementation of WEAVE and its data systems, we present the organization, science drivers, and design of a five- to seven-year programme of eight individual surveys to: (i) study our Galaxy's origins by completing Gaia's phase-space information, providing metallicities to its limiting magnitude for similar to 3 million stars and detailed abundances for similar to 1.5 million brighter field and open-cluster stars; (ii) survey similar to 0.4 million Galactic-plane OBA stars, young stellar objects, and nearby gas to understand the evolution of young stars and their environments; (iii) perform an extensive spectral survey of white dwarfs; (iv) survey similar to 400 neutral-hydrogen-selected galaxies with the IFUs; (v) study properties and kinematics of stellar populations and ionized gas in z < 0.5 cluster galaxies; (vi) survey stellar populations and kinematics in field galaxies at 0.3 less than or similar to z less than or similar to 0.7; (vii) study the cosmic evolution of accretion and star formation using >1 million spectra of LOFAR-selected radio sources; and (viii) trace structures using intergalactic/circumgalactic gas at z > 2. Finally, we describe the WEAVE Operational Rehearsals using the WEAVE Simulator.
30.	Kassebaum, Nicholas J., et al. (författare) Global, regional, and national disability-adjusted life-years (DALYs) for 315 diseases and injuries and healthy life expectancy (HALE), 1990-2015 : a systematic analysis for the Global Burden of Disease Study 2015 2016 Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 388:10053, s. 1603-1658 Tidskriftsartikel (refereegranskat)abstract Background Healthy life expectancy (HALE) and disability-adjusted life-years (DALYs) provide summary measures of health across geographies and time that can inform assessments of epidemiological patterns and health system performance, help to prioritise investments in research and development, and monitor progress toward the Sustainable Development Goals (SDGs). We aimed to provide updated HALE and DALYs for geographies worldwide and evaluate how disease burden changes with development. Methods We used results from the Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015) for all-cause mortality, cause-specific mortality, and non-fatal disease burden to derive HALE and DALYs by sex for 195 countries and territories from 1990 to 2015. We calculated DALYs by summing years of life lost (YLLs) and years of life lived with disability (YLDs) for each geography, age group, sex, and year. We estimated HALE using the Sullivan method, which draws from age-specific death rates and YLDs per capita. We then assessed how observed levels of DALYs and HALE differed from expected trends calculated with the Socio-demographic Index (SDI), a composite indicator constructed from measures of income per capita, average years of schooling, and total fertility rate. Findings Total global DALYs remained largely unchanged from 1990 to 2015, with decreases in communicable, neonatal, maternal, and nutritional (Group 1) disease DALYs off set by increased DALYs due to non-communicable diseases (NCDs). Much of this epidemiological transition was caused by changes in population growth and ageing, but it was accelerated by widespread improvements in SDI that also correlated strongly with the increasing importance of NCDs. Both total DALYs and age-standardised DALY rates due to most Group 1 causes significantly decreased by 2015, and although total burden climbed for the majority of NCDs, age-standardised DALY rates due to NCDs declined. Nonetheless, age-standardised DALY rates due to several high-burden NCDs (including osteoarthritis, drug use disorders, depression, diabetes, congenital birth defects, and skin, oral, and sense organ diseases) either increased or remained unchanged, leading to increases in their relative ranking in many geographies. From 2005 to 2015, HALE at birth increased by an average of 2.9 years (95% uncertainty interval 2.9-3.0) for men and 3.5 years (3.4-3.7) for women, while HALE at age 65 years improved by 0.85 years (0.78-0.92) and 1.2 years (1.1-1.3), respectively. Rising SDI was associated with consistently higher HALE and a somewhat smaller proportion of life spent with functional health loss; however, rising SDI was related to increases in total disability. Many countries and territories in central America and eastern sub-Saharan Africa had increasingly lower rates of disease burden than expected given their SDI. At the same time, a subset of geographies recorded a growing gap between observed and expected levels of DALYs, a trend driven mainly by rising burden due to war, interpersonal violence, and various NCDs. Interpretation Health is improving globally, but this means more populations are spending more time with functional health loss, an absolute expansion of morbidity. The proportion of life spent in ill health decreases somewhat with increasing SDI, a relative compression of morbidity, which supports continued efforts to elevate personal income, improve education, and limit fertility. Our analysis of DALYs and HALE and their relationship to SDI represents a robust framework on which to benchmark geography-specific health performance and SDG progress. Country-specific drivers of disease burden, particularly for causes with higher-than-expected DALYs, should inform financial and research investments, prevention efforts, health policies, and health system improvement initiatives for all countries along the development continuum.
31.	Kiadaliri, Ali, et al. (författare) Mapping EQ-5D-3L from the Knee Injury and Osteoarthritis Outcome Score (KOOS) 2020 Ingår i: Quality of Life Research. - : Springer Science and Business Media LLC. - 1573-2649 .- 0962-9343. ; 29:1, s. 265-274 Tidskriftsartikel (refereegranskat)abstract PURPOSE: To develop a mapping model to estimate EQ-5D-3L from the Knee Injury and Osteoarthritis Outcome Score (KOOS).METHODS: The responses to EQ-5D-3L and KOOS questionnaires (n = 40,459 observations) were obtained from the Swedish National anterior cruciate ligament (ACL) Register for patients ≥ 18 years with the knee ACL injury. We used linear regression (LR) and beta-mixture (BM) for direct mapping and the generalized ordered probit model for response mapping (RM). We compared the distribution of the original data to the distributions of the data generated using the estimated models.RESULTS: Models with individual KOOS subscales performed better than those with the average of KOOS subscale scores (KOOS5, KOOS4). LR had the poorest performance overall and across the range of disease severity particularly at the extremes of the distribution of severity. Compared with the RM, the BM performed better across the entire range of disease severity except the most severe range (KOOS5 < 25). Moving from the most to the least disease severity was associated with 0.785 gain in the observed EQ-5D-3L. The corresponding value was 0.743, 0.772 and 0.782 for LR, BM and RM, respectively. LR generated simulated EQ-5D-3L values outside the feasible range. The distribution of simulated data generated from the BM model was almost identical to the original data.CONCLUSIONS: We developed mapping models to estimate EQ-5D-3L from KOOS facilitating application of KOOS in cost-utility analyses. The BM showed superior performance for estimating EQ-5D-3L from KOOS. Further validation of the estimated models in different independent samples is warranted.
32.	Kun-Rodrigues, Celia, et al. (författare) A comprehensive screening of copy number variability in dementia with Lewy bodies. 2019 Ingår i: Neurobiology of aging. - : Elsevier BV. - 1558-1497 .- 0197-4580. ; 75 Tidskriftsartikel (refereegranskat)abstract The role of genetic variability in dementia with Lewy bodies (DLB) is now indisputable; however, data regarding copy number variation (CNV) in this disease has been lacking. Here, we used whole-genome genotyping of 1454 DLB cases and 1525 controls to assess copy number variability. We used 2 algorithms to confidently detect CNVs, performed a case-control association analysis, screened for candidate CNVs previously associated with DLB-related diseases, and performed a candidate gene approach to fully explore the data. We identified 5 CNV regions with a significant genome-wide association to DLB; 2 of these were only present in cases and absent from publicly available databases: one of the regions overlapped LAPTM4B, a known lysosomal protein, whereas the other overlapped the NME1 locus and SPAG9. We also identified DLB cases presenting rare CNVs in genes previously associated with DLB or related neurodegenerative diseases, such as SNCA, APP, and MAPT. To our knowledge, this is the first study reporting genome-wide CNVs in a large DLB cohort. These results provide preliminary evidence for the contribution of CNVs in DLB risk.
33.	Kun-Rodrigues, Celia, et al. (författare) Analysis of C9orf72 repeat expansions in a large international cohort of dementia with Lewy bodies 2017 Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 49 Tidskriftsartikel (refereegranskat)abstract . C9orf72 repeat expansions are a common cause of amyotrophic lateral sclerosis and frontotemporal dementia. To date, no large-scale study of dementia with Lewy bodies (DLB) has been undertaken to assess the role of . C9orf72 repeat expansions in the disease. Here, we investigated the prevalence of . C9orf72 repeat expansions in a large cohort of DLB cases and identified no pathogenic repeat expansions in neuropathologically or clinically defined cases, showing that . C9orf72 repeat expansions are not causally associated with DLB.
34.	Laurie, Steven, et al. (författare) The RD-Connect Genome-Phenome Analysis Platform : Accelerating diagnosis, research, and gene discovery for rare diseases 2022 Ingår i: Human Mutation. - : John Wiley & Sons. - 1059-7794 .- 1098-1004. ; 43:6, s. 717-733 Tidskriftsartikel (refereegranskat)abstract Rare disease patients are more likely to receive a rapid molecular diagnosis nowadays thanks to the wide adoption of next-generation sequencing. However, many cases remain undiagnosed even after exome or genome analysis, because the methods used missed the molecular cause in a known gene, or a novel causative gene could not be identified and/or confirmed. To address these challenges, the RD-Connect Genome-Phenome Analysis Platform (GPAP) facilitates the collation, discovery, sharing, and analysis of standardized genome-phenome data within a collaborative environment. Authorized clinicians and researchers submit pseudonymised phenotypic profiles encoded using the Human Phenotype Ontology, and raw genomic data which is processed through a standardized pipeline. After an optional embargo period, the data are shared with other platform users, with the objective that similar cases in the system and queries from peers may help diagnose the case. Additionally, the platform enables bidirectional discovery of similar cases in other databases from the Matchmaker Exchange network. To facilitate genome-phenome analysis and interpretation by clinical researchers, the RD-Connect GPAP provides a powerful user-friendly interface and leverages tens of information sources. As a result, the resource has already helped diagnose hundreds of rare disease patients and discover new disease causing genes.
35.	Lind, Marianne, et al. (författare) Cross-linguistic adaptations of The Comprehensive Aphasia Test: Challenges and solutions 2016 Konferensbidrag (refereegranskat)
36.	Martrat, Griselda, et al. (författare) Exploring the link between MORF4L1 and risk of breast cancer 2011 Ingår i: Breast Cancer Research. - : Springer Science and Business Media LLC. - 1465-5411 .- 1465-542X. ; 13:2 Tidskriftsartikel (refereegranskat)abstract Introduction: Proteins encoded by Fanconi anemia (FA) and/or breast cancer (BrCa) susceptibility genes cooperate in a common DNA damage repair signaling pathway. To gain deeper insight into this pathway and its influence on cancer risk, we searched for novel components through protein physical interaction screens. Methods: Protein physical interactions were screened using the yeast two-hybrid system. Co-affinity purifications and endogenous co-immunoprecipitation assays were performed to corroborate interactions. Biochemical and functional assays in human, mouse and Caenorhabditis elegans models were carried out to characterize pathway components. Thirteen FANCD2-monoubiquitinylation-positive FA cell lines excluded for genetic defects in the downstream pathway components and 300 familial BrCa patients negative for BRCA1/2 mutations were analyzed for genetic mutations. Common genetic variants were genotyped in 9,573 BRCA1/2 mutation carriers for associations with BrCa risk. Results: A previously identified co-purifying protein with PALB2 was identified, MRG15 (MORF4L1 gene). Results in human, mouse and C. elegans models delineate molecular and functional relationships with BRCA2, PALB2, RAD51 and RPA1 that suggest a role for MRG15 in the repair of DNA double-strand breaks. Mrg15-deficient murine embryonic fibroblasts showed moderate sensitivity to g-irradiation relative to controls and reduced formation of Rad51 nuclear foci. Examination of mutants of MRG15 and BRCA2 C. elegans orthologs revealed phenocopy by accumulation of RPA-1 (human RPA1) nuclear foci and aberrant chromosomal compactions in meiotic cells. However, no alterations or mutations were identified for MRG15/MORF4L1 in unclassified FA patients and BrCa familial cases. Finally, no significant associations between common MORF4L1 variants and BrCa risk for BRCA1 or BRCA2 mutation carriers were identified: rs7164529, P-trend = 0.45 and 0.05, P-2df = 0.51 and 0.14, respectively; and rs10519219, P-trend = 0.92 and 0.72, P-2df = 0.76 and 0.07, respectively. Conclusions: While the present study expands on the role of MRG15 in the control of genomic stability, weak associations cannot be ruled out for potential low-penetrance variants at MORF4L1 and BrCa risk among BRCA2 mutation carriers.
37.	Mont, Lluís, et al. (författare) Pre-participation cardiovascular evaluation for athletic participants to prevent sudden death : Position paper from the EHRA and the EACPR, branches of the ESC. Endorsed by APHRS, HRS, and SOLAECE 2017 Ingår i: European Journal of Preventive Cardiology. - : Oxford University Press (OUP). - 2047-4873 .- 2047-4881. ; 24:1, s. 41-69 Tidskriftsartikel (refereegranskat)
38.	Mont, Lluís, et al. (författare) Pre-participation cardiovascular evaluation for athletic participants to prevent sudden death: Position paper from the EHRA and the EACPR, branches of the ESC. Endorsed by APHRS, HRS, and SOLAECE. 2017 Ingår i: Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology. - : Oxford University Press (OUP). - 1532-2092 .- 1099-5129. ; 19:1, s. 139-163 Tidskriftsartikel (refereegranskat)
39.	Naidjonoka, Polina, et al. (författare) On the interaction of softwood hemicellulose with cellulose surfaces in relation to molecular structure and physicochemical properties of hemicellulose 2020 Ingår i: Soft Matter. - : Royal Society of Chemistry (RSC). - 1744-683X .- 1744-6848. ; 16:30, s. 7063-7076 Tidskriftsartikel (refereegranskat)abstract The substantial part of the water-soluble hemicellulose fraction, obtained when processing cellulose to produce paper and other products, has so far been discarded. The aim of this work is to reveal the interfacial properties of softwood hemicellulose (galactoglucomannan, GGM) in relation to their molecular and solution structure. In this study the sugar composition of GGM was characterised by chemical analysis as well as 1D and 2D NMR spectroscopy. Previously it has been demonstrated that hemicellulose has high affinity towards cellulose and has the ability to alter the properties of cellulose based products. This study is focused on the interactions between hemicellulose and the cellulose surface. Therefore, adsorption to hydrophobized silica and cellulose surfaces of two softwood hemicellulose samples and structurally similar seed hemicelluloses (galactomannans, GMs) was studied with ellipsometry, QCM-D and neutron reflectometry. Aqueous solutions of all samples were characterized with light scattering to determine how the degree of side-group substitution and molecular weight affect the conformation and aggregation of these polymers in the bulk. In addition, hemicellulose samples were studied with SAXS to investigate backbone flexibility. Light scattering results indicated that GM polymers form globular particles while GGMs were found to form rod-like aggregates in the solution. The polysaccharides exhibit higher adsorption to cellulose than on hydrophobic surfaces. A clear correlation between the increase in molecular weight of polysaccharides and increasing adsorbed amount on cellulose was observed, while the adsorbed amount on the hydrophobic surface was fairly independent of the molecular weight. The obtained layer thickness was compared with bulk scattering data and the results indicated flat conformation of the polysaccharides on the surface.
40.	Phillips, Helen R. P., et al. (författare) Global distribution of earthworm diversity 2019 Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 366:6464, s. 480- Tidskriftsartikel (refereegranskat)abstract Soil organisms, including earthworms, are a key component of terrestrial ecosystems. However, little is known about their diversity, their distribution, and the threats affecting them. We compiled a global dataset of sampled earthworm communities from 6928 sites in 57 countries as a basis for predicting patterns in earthworm diversity, abundance, and biomass. We found that local species richness and abundance typically peaked at higher latitudes, displaying patterns opposite to those observed in aboveground organisms. However, high species dissimilarity across tropical locations may cause diversity across the entirety of the tropics to be higher than elsewhere. Climate variables were found to be more important in shaping earthworm communities than soil properties or habitat cover. These findings suggest that climate change may have serious implications for earthworm communities and for the functions they provide.
41.	Primmer, Eeva, et al. (författare) Mapping Europe's institutional landscape for forest ecosystem service provision, innovations and governance 2021 Ingår i: Ecosystem Services. - : Elsevier BV. - 2212-0416. ; 47 Tidskriftsartikel (refereegranskat)abstract There has been a strong quest for mapping and assessing ecosystem services (ES) to support governance. Yet, the institutional landscape that governs ES provision across multiple contexts has received less attention. We fill this research gap by developing and operationalising a framework for the analysis of policy documents that address European forest ES provision. By coding and analysing references to forest ES as well as innovations and governance mechanisms addressing these ES in national strategies on forest, biodiversity and bioeconomy, we map the institutional landscape of forest ES provision in Europe. We further analyse how biophysical supply of forest ES is connected to policies paying attention to ES and identifying innovations and governance for their provision. Innovations identified in policies centre around value chains of wood and bioenergy or biodiversity conservation, while non-wood forest products, cultural heritage, and recreation receive little attention. Biophysical supply of provisioning ES is connected to policies emphasising many innovations, while little supply of regulating ES could trigger service innovations and several new governance mechanisms. As forest ecosystems have received much attention in global, European and national sustainability policies, our institutional mapping illustrates that there is room for more use of innovations in promoting ES provision.
42.	Reynolds-Cuellar, Pedro, et al. (författare) Para Cima y Pa' Abajo : Building Bridges Between HCI Research in Latin America and in the Global North 2023 Ingår i: PROCEEDINGS OF THE 2023 CHI CONFERENCE ON HUMAN FACTORS IN COMPUTING SYSTEMS (CHI 2023). - : Association for Computing Machinery (ACM). Konferensbidrag (refereegranskat)abstract The Human-computer Interaction (HCI) community has the opportunity to foster the integration of research practices across the Global South and North to begin overcoming colonial relationships. In this paper, we focus on the case of Latin America (LATAM), where initiatives to increase the representation of HCI practitioners lack a consolidated understanding of the practices they employ, the factors that infuence them, and the challenges that practitioners face. To address this knowledge gap, we employ a mixed-methods approach, comprising a survey (66 respondents) and in-depth interviews (19 interviewees). Our analyses characterize a set of research perspectives on how HCI is practiced in/about LATAM; a set of driving forces and tensions with a heavy reliance on diasporic dynamics; and a set of professional demands and associated structural limitations. We also ofer a roadmap towards building connections across HCI communities, in an attempt to rebuild HCI as a pluriverse.
43.	Rofes, Adrìa, et al. (författare) Imageability ratings across languages 2018 Ingår i: Behavior Research Methods. - : Springer Science and Business Media LLC. - 1554-351X .- 1554-3528. ; 50:3, s. 1187-1197 Tidskriftsartikel (refereegranskat)abstract Imageability is a psycholinguistic variable that indicates how well a word gives rise to a mental image or sensory experience. Imageability ratings are used extensively in psycholinguistic, neuropsychological, and aphasiological studies. However, little formal knowledge exists about whether and how these ratings are associated between and within languages. Fifteen imageability databases were cross-correlated using nonparametric statistics. Some of these corresponded to unpublished data collected within a European research network—the Collaboration of Aphasia Trialists (COST IS1208). All but four of the correlations were significant. The average strength of the correlations (rho = .68) and the variance explained (R2 = 46%) were moderate. This implies that factors other than imageability may explain 54% of the results. Imageability ratings often correlate across languages. Different possibly interacting factors may explain the moderate strength and variance explained in the correlations: (1) linguistic and cultural factors; (2) intrinsic differences between the databases; (3) range effects; (4) small numbers of words in each database, equivalent words, and participants; and (5) mean age of the participants. The results suggest that imageability ratings may be used cross-linguistically. However, further understanding of the factors explaining the variance in the correlations will be needed before research and practical recommendations can be made.
44.	Rofes, Adrìa, et al. (författare) Word imageability from a cross-linguistic perspective 2016 Konferensbidrag (refereegranskat)
45.	Rosengren, Anna, et al. (författare) Enzymatic synthesis and polymerisation of β-mannosyl acrylates produced from renewable hemicellulosic glycans 2019 Ingår i: Green Chemistry. - : Royal Society of Chemistry (RSC). - 1463-9270 .- 1463-9262. ; 21:8, s. 2104-2118 Tidskriftsartikel (refereegranskat)abstract We show that glycoside hydrolases can catalyse the synthesis of glycosyl acrylate monomers using renewable hemicellulose as glycosyl donor, and we also demonstrate the preparation of novel glycopolymers by radical polymerisation of these monomers. For this, two family 5 β-mannanases (TrMan5A from Trichoderma reesei and AnMan5B from Aspergillus niger) were evaluated for transglycosylation capacity using 2-hydroxyethyl methacrylate (HEMA) as glycosyl acceptor. Both enzymes catalysed conjugation between manno-oligosaccharides and HEMA, as analysed with MALDI-ToF mass spectrometry (MS) as initial product screening method. The two enzymes gave different product profiles (glycosyl donor length) with HEMA, as well as with allyl alcohol as acceptor molecules. AnMan5A appeared to prefer saccharide acceptors with lower intensity MS peaks detected for the desired allyl and HEMA conjugations. Contrary to AnMan5A, TrMan5A gave pronounced MS peaks for HEMA-saccharide conjugation products.TrMan5A was shown to catalyse the synthesis of β-mannosyl acrylates using locust bean gum galactomannan or softwood hemicellulose (acetyl-galactoglucomannan) as donor substrate. Evaluation of reaction conditions using galactomannan as donor, HEMA as acceptor and TrMan5A as enzyme catalyst was followed by the enzymatic production and preparative liquid chromatography purification of 2-(β-manno(oligo)syloxy) ethyl methacrylates (Mannosyl-EMA and Mannobiosyl-EMA). The chemical structures and radical polymerisations of these novel monomers were concluded using 1H and 13C NMR spectroscopy and size-exclusion chromatography. The two new water soluble polymers have a polyacrylate backbone with one or two pendant mannosyl groups per monomeric EMA unit, respectively. These novel glycopolymers may show properties suitable for various technical and biomedical applications responding to the current demand for functional greener materials to replace fossil based ones.
46.	Rota, Matteo, et al. (författare) Education and gastric cancer risk-An individual participant data meta-analysis in the StoP project consortium 2020 Ingår i: International Journal of Cancer. - : WILEY. - 0020-7136 .- 1097-0215. ; 146:3, s. 671-681 Tidskriftsartikel (refereegranskat)abstract Low socioeconomic position (SEP) is a strong risk factor for incidence and premature mortality from several cancers. Our study aimed at quantifying the association between SEP and gastric cancer (GC) risk through an individual participant data meta-analysis within the "Stomach cancer Pooling (StoP) Project". Educational level and household income were used as proxies for the SEP. We estimated pooled odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) across levels of education and household income by pooling study-specific ORs through random-effects meta-analytic models. The relative index of inequality (RII) was also computed. A total of 9,773 GC cases and 24,373 controls from 25 studies from Europe, Asia and America were included. The pooled OR for the highest compared to the lowest level of education was 0.60 (95% CI, 0.44-0.84), while the pooled RII was 0.45 (95% CI, 0.29-0.69). A strong inverse association was observed both for noncardia (OR 0.39, 95% CI, 0.22-0.70) and cardia GC (OR 0.47, 95% CI, 0.22-0.99). The relation was stronger among H. pylori negative subjects (RII 0.14, 95% CI, 0.04-0.48) as compared to H. pylori positive ones (RII 0.29, 95% CI, 0.10-0.84), in the absence of a significant interaction (p = 0.28). The highest household income category showed a pooled OR of 0.65 (95% CI, 0.48-0.89), while the corresponding RII was 0.40 (95% CI, 0.22-0.72). Our collaborative pooled-analysis showed a strong inverse relationship between SEP indicators and GC risk. Our data call for public health interventions to reduce GC risk among the more vulnerable groups of the population. What's new? Gastric cancer is associated with low socioeconomic position but the precise impact of education on gastric cancer risk needs to be quantified. Here the authors provide an updated quantification through the analysis of the Stomach cancer Pooling (StoP) Project, a large international consortium of case-control studies. They observe a similar to 40% decreased risk of gastric cancer among individuals with intermediate/high education status as compared to less educated study subjects. The association was evident regardless of Helicobacter pylori infection, underscoring the need for public health interventions to reduce gastric cancer risk.
47.	Sánchez Van Kammen, Mayte, et al. (författare) Characteristics and Outcomes of Patients with Cerebral Venous Sinus Thrombosis in SARS-CoV-2 Vaccine-Induced Immune Thrombotic Thrombocytopenia 2021 Ingår i: JAMA Neurology. - : American Medical Association. - 2168-6149 .- 2168-6157. ; 78:11, s. 1314-1323 Tidskriftsartikel (refereegranskat)abstract Importance: Thrombosis with thrombocytopenia syndrome (TTS) has been reported after vaccination with the SARS-CoV-2 vaccines ChAdOx1 nCov-19 (Oxford-AstraZeneca) and Ad26.COV2.S (Janssen/Johnson & Johnson).Objective: To describe the clinical characteristics and outcome of patients with cerebral venous sinus thrombosis (CVST) after SARS-CoV-2 vaccination with and without TTS.Design, Setting, and Participants: This cohort study used data from an international registry of consecutive patients with CVST within 28 days of SARS-CoV-2 vaccination included between March 29 and June 18, 2021, from 81 hospitals in 19 countries. For reference, data from patients with CVST between 2015 and 2018 were derived from an existing international registry. Clinical characteristics and mortality rate were described for adults with (1) CVST in the setting of SARS-CoV-2 vaccine-induced immune thrombotic thrombocytopenia, (2) CVST after SARS-CoV-2 vaccination not fulling criteria for TTS, and (3) CVST unrelated to SARS-CoV-2 vaccination.Exposures: Patients were classified as having TTS if they had new-onset thrombocytopenia without recent exposure to heparin, in accordance with the Brighton Collaboration interim criteria.Main Outcomes and Measures: Clinical characteristics and mortality rate.Results: Of 116 patients with postvaccination CVST, 78 (67.2%) had TTS, of whom 76 had been vaccinated with ChAdOx1 nCov-19; 38 (32.8%) had no indication of TTS. The control group included 207 patients with CVST before the COVID-19 pandemic. A total of 63 of 78 (81%), 30 of 38 (79%), and 145 of 207 (70.0%) patients, respectively, were female, and the mean (SD) age was 45 (14), 55 (20), and 42 (16) years, respectively. Concomitant thromboembolism occurred in 25 of 70 patients (36%) in the TTS group, 2 of 35 (6%) in the no TTS group, and 10 of 206 (4.9%) in the control group, and in-hospital mortality rates were 47% (36 of 76; 95% CI, 37-58), 5% (2 of 37; 95% CI, 1-18), and 3.9% (8 of 207; 95% CI, 2.0-7.4), respectively. The mortality rate was 61% (14 of 23) among patients in the TTS group diagnosed before the condition garnered attention in the scientific community and 42% (22 of 53) among patients diagnosed later.Conclusions and Relevance: In this cohort study of patients with CVST, a distinct clinical profile and high mortality rate was observed in patients meeting criteria for TTS after SARS-CoV-2 vaccination..
48.	Teresita Martin-Marquez, Beatriz, et al. (författare) The DNA co-vaccination using Sm antigen and IL-10 as prophylactic experimental therapy ameliorates nephritis in a model of lupus induced by pristane 2021 Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 16:10 Tidskriftsartikel (refereegranskat)abstract Introduction: Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the production of autoantibodies such as anti-Sm. Studies in patients with SLE and murine models of lupus reveal that the most critical anti-Sm autoantibodies are predominantly direct against D1((83-119),) D2, and B/B epitopes.Objectives: The present study aimed to analyze the induction of antigen-specific tolerance after prophylactic immunization with a DNA vaccine encoding the epitopes: D1(83-119), D2, B/B, and B/B-COOH in co-vaccination with IFN-gamma or IL-10 in a murine model of lupus induced by pristane.Material and methods: To obtain endotoxin-free DNA vaccines, direct cloning techniques using pcDNA were performed: D1(83-119), D2, B'/B, B'/B-COOH, IFN-gamma, or IL-10. Lupus was induced by 0.5 mL of pristane via intraperitoneal in BALB/c female mice. Immunoprecipitation with K562 cells was metabolically labeled with S-35 and ELISA to detect serum antibodies or mice IgG1, IgG2a isotypes. ELISA determined IL-10 and IFN-gamma from splenocytes supernatants. Proteinuria was assessed monthly, and lupus nephritis was evaluated by immunofluorescence, and electron microscopy.Results: The prophylactic co-vaccination with D2/IL-10 reduced the expression of kidney damage observed by electron microscopy, direct immunofluorescence, and H & E, along with reduced level of anti-nRNP/Sm antibodies (P = 0.048).Conclusion: The prophylactic co-vaccination of IL-10 with D2 in pristane-induced lupus ameliorates the renal damage maybe by acting as prophylactic DNA tolerizing therapy.
49.	van der Lee, Sven J, et al. (författare) Correction to: A nonsynonymous mutation in PLCG2 reduces the risk of Alzheimer's disease, dementia with Lewy bodies and frontotemporal dementia, and increases the likelihood of longevity. 2020 Ingår i: Acta neuropathologica. - : Springer Science and Business Media LLC. - 1432-0533 .- 0001-6322. Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract The IPDGC (The International Parkinson Disease Genomics Consortium) and EADB (Alzheimer Disease European DNA biobank) are listed correctly as an author to the article, however, they were incorrectly listed more than once.
50.	Villar, Jesus, et al. (författare) A Quantile Analysis of Plateau and Driving Pressures : Effects on Mortality in Patients With Acute Respiratory Distress Syndrome Receiving Lung-Protective Ventilation 2017 Ingår i: Critical Care Medicine. - 0090-3493 .- 1530-0293. ; 45:5, s. 843-850 Tidskriftsartikel (refereegranskat)abstract Objectives: The driving pressure (plateau pressure minus positive end-expiratory pressure) has been suggested as the major determinant for the beneficial effects of lung-protective ventilation. We tested whether driving pressure was superior to the variables that define it in predicting outcome in patients with acute respiratory distress syndrome.Design: A secondary analysis of existing data from previously reported observational studies.Setting: A network of ICUs.Patients: We studied 778 patients with moderate to severe acute respiratory distress syndrome.Interventions: None.Measurements and Main Results: We assessed the risk of hospital death based on quantiles of tidal volume, positive end-expiratory pressure, plateau pressure, and driving pressure evaluated at 24 hours after acute respiratory distress syndrome diagnosis while ventilated with standardized lung-protective ventilation. We derived our model using individual data from 478 acute respiratory distress syndrome patients and assessed its replicability in a separate cohort of 300 acute respiratory distress syndrome patients. Tidal volume and positive end-expiratory pressure had no impact on mortality. We identified a plateau pressure cut-off value of 29 cm H2O, above which an ordinal increment was accompanied by an increment of risk of death. We identified a driving pressure cut-off value of 19 cm H2O where an ordinal increment was accompanied by an increment of risk of death. When we cross tabulated patients with plateau pressure less than 30 and plateau pressure greater than or equal to 30 with those with driving pressure less than 19 and driving pressure greater than or equal to 19, plateau pressure provided a slightly better prediction of outcome than driving pressure in both the derivation and validation cohorts (p < 0.0000001).Conclusions: Plateau pressure was slightly better than driving pressure in predicting hospital death in patients managed with lung-protective ventilation evaluated on standardized ventilator settings 24 hours after acute respiratory distress syndrome onset.

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