| 1. |
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| 2. |
- Clark, Andrew G., et al.
(författare)
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Evolution of genes and genomes on the Drosophila phylogeny
- 2007
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 450:7167, s. 203-218
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Tidskriftsartikel (refereegranskat)abstract
- Comparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ten of which are presented here for the first time (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi), illustrate how rates and patterns of sequence divergence across taxa can illuminate evolutionary processes on a genomic scale. These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution. Despite remarkable similarities among these Drosophila species, we identified many putatively non-neutral changes in protein-coding genes, non-coding RNA genes, and cis-regulatory regions. These may prove to underlie differences in the ecology and behaviour of these diverse species.
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| 3. |
- Avetisyan, A., et al.
(författare)
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Preface
- 2019
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Ingår i: APSSE 2019 Actual Problems of System and Software Engineering. - : CEUR-WS. ; , s. 1-2
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Konferensbidrag (refereegranskat)
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| 4. |
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| 5. |
- Krys, K, et al.
(författare)
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Happiness Maximization Is a WEIRD Way of Living
- 2024
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Ingår i: Perspectives on psychological science : a journal of the Association for Psychological Science. - 1745-6924. ; , s. 17456916231208367-
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Tidskriftsartikel (refereegranskat)
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| 6. |
- Bernal, Ximena E., et al.
(författare)
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Empowering Latina scientists
- 2019
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 363:6429, s. 825-826
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 7. |
- Sartelli, Massimo, et al.
(författare)
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Ten golden rules for optimal antibiotic use in hospital settings: the WARNING call to action
- 2023
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Ingår i: WORLD JOURNAL OF EMERGENCY SURGERY. - 1749-7922. ; 18:1
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Forskningsöversikt (refereegranskat)abstract
- Antibiotics are recognized widely for their benefits when used appropriately. However, they are often used inappropriately despite the importance of responsible use within good clinical practice. Effective antibiotic treatment is an essential component of universal healthcare, and it is a global responsibility to ensure appropriate use. Currently, pharmaceutical companies have little incentive to develop new antibiotics due to scientific, regulatory, and financial barriers, further emphasizing the importance of appropriate antibiotic use. To address this issue, the Global Alliance for Infections in Surgery established an international multidisciplinary task force of 295 experts from 115 countries with different backgrounds. The task force developed a position statement called WARNING (Worldwide Antimicrobial Resistance National/International Network Group) aimed at raising awareness of antimicrobial resistance and improving antibiotic prescribing practices worldwide. The statement outlined is 10 axioms, or "golden rules," for the appropriate use of antibiotics that all healthcare workers should consistently adhere in clinical practice.
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| 8. |
- Zewinger, Stephen, et al.
(författare)
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Relations between lipoprotein(a) concentrations, LPA genetic variants, and the risk of mortality in patients with established coronary heart disease : a molecular and genetic association study
- 2017
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Ingår i: The Lancet Diabetes and Endocrinology. - : ELSEVIER SCIENCE INC. - 2213-8587 .- 2213-8595. ; 5:7, s. 534-543
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Tidskriftsartikel (refereegranskat)abstract
- Background: Lipoprotein(a) concentrations in plasma are associated with cardiovascular risk in the general population. Whether lipoprotein(a) concentrations or LPA genetic variants predict long-term mortality in patients with established coronary heart disease remains less clear.Methods: We obtained data from 3313 patients with established coronary heart disease in the Ludwigshafen Risk and Cardiovascular Health (LURIC) study. We tested associations of tertiles of lipoprotein(a) concentration in plasma and two LPA single-nucleotide polymorphisms ([SNPs] rs10455872 and rs3798220) with all-cause mortality and cardiovascular mortality by Cox regression analysis and with severity of disease by generalised linear modelling, with and without adjustment for age, sex, diabetes diagnosis, systolic blood pressure, BMI, smoking status, estimated glomerular filtration rate, LDL-cholesterol concentration, and use of lipid-lowering therapy. Results for plasma lipoprotein(a) concentrations were validated in five independent studies involving 10 195 patients with established coronary heart disease. Results for genetic associations were replicated through large-scale collaborative analysis in the GENIUS-CHD consortium, comprising 106 353 patients with established coronary heart disease and 19 332 deaths in 22 studies or cohorts.Findings: The median follow-up was 9.9 years. Increased severity of coronary heart disease was associated with lipoprotein(a) concentrations in plasma in the highest tertile (adjusted hazard radio [HR] 1.44, 95% CI 1.14-1.83) and the presence of either LPA SNP (1.88, 1.40-2.53). No associations were found in LURIC with all-cause mortality (highest tertile of lipoprotein(a) concentration in plasma 0.95, 0.81-1.11 and either LPA SNP 1.10, 0.92-1.31) or cardiovascular mortality (0.99, 0.81-1.2 and 1.13, 0.90-1.40, respectively) or in the validation studies.Interpretation: In patients with prevalent coronary heart disease, lipoprotein(a) concentrations and genetic variants showed no associations with mortality. We conclude that these variables are not useful risk factors to measure to predict progression to death after coronary heart disease is established.
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| 9. |
- Wang, Xin, et al.
(författare)
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Global burden of respiratory infections associated with seasonal influenza in children under 5 years in 2018 : a systematic review and modelling study
- 2020
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Ingår i: The Lancet Global Health. - : Elsevier. - 2214-109X. ; 8:4, s. E497-E510
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Forskningsöversikt (refereegranskat)abstract
- Background: Seasonal influenza virus is a common cause of acute lower respiratory infection (ALRI) in ung children. In 2008, we estimated that 20 million influenza-virus-associated ALRI and 1 million fluenza-virus-associated severe ALRI occurred in children under 5 years globally. Despite this bstantial burden, only a few low-income and middle-income countries have adopted routine influenza ccination policies for children and, where present, these have achieved only low or unknown levels of ccine uptake. Moreover, the influenza burden might have changed due to the emergence and rculation of influenza A/H1N1pdm09. We aimed to incorporate new data to update estimates of the obal number of cases, hospital admissions, and mortality from influenza-virus-associated respiratory fections in children under 5 years in 2018.Methods: We estimated the regional and global burden of influenza-associated respiratory infections in ildren under 5 years from a systematic review of 100 studies published between Jan 1, 1995, and Dec , 2018, and a further 57 high-quality unpublished studies. We adapted the Newcastle-Ottawa Scale to sess the risk of bias. We estimated incidence and hospitalisation rates of influenza-virus-associated spiratory infections by severity, case ascertainment, region, and age. We estimated in-hospital deaths om influenza virus ALRI by combining hospital admissions and in-hospital case-fatality ratios of fluenza virus ALRI. We estimated the upper bound of influenza virus-associated ALRI deaths based on e number of in-hospital deaths, US paediatric influenza-associated death data, and population-based ildhood all-cause pneumonia mortality data in six sites in low-income and lower-middle-income untries.Findings: In 2018, among children under 5 years globally, there were an estimated 109.5 million fluenza virus episodes (uncertainty range [UR] 63.1-190.6), 10.1 million influenza-virus-associated ALRI ses (6.8-15.1); 870 000 influenza-virus-associated ALRI hospital admissions (543 000-1 415 000), 15 300 -hospital deaths (5800-43 800), and up to 34 800 (13 200-97 200) overall influenza-virus-associated ALRI deaths. Influenza virus accounted for 7% of ALRI cases, 5% of ALRI hospital admissions, and 4% of ALRI deaths in children under 5 years. About 23% of the hospital admissions and 36% of the in-hospital deaths were in infants under 6 months. About 82% of the in-hospital deaths occurred in low-income and lower-middle-income countries.Interpretation: A large proportion of the influenza-associated burden occurs among young infants and in low-income and lower middle-income countries. Our findings provide new and important evidence for maternal and paediatric influenza immunisation, and should inform future immunisation policy particularly in low-income and middle-income countries.
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| 10. |
- Jansen, Willemijn J, et al.
(författare)
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Prevalence Estimates of Amyloid Abnormality Across the Alzheimer Disease Clinical Spectrum.
- 2022
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Ingår i: JAMA neurology. - : American Medical Association (AMA). - 2168-6157 .- 2168-6149. ; 79:3, s. 228-243
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Tidskriftsartikel (refereegranskat)abstract
- One characteristic histopathological event in Alzheimer disease (AD) is cerebral amyloid aggregation, which can be detected by biomarkers in cerebrospinal fluid (CSF) and on positron emission tomography (PET) scans. Prevalence estimates of amyloid pathology are important for health care planning and clinical trial design.To estimate the prevalence of amyloid abnormality in persons with normal cognition, subjective cognitive decline, mild cognitive impairment, or clinical AD dementia and to examine the potential implications of cutoff methods, biomarker modality (CSF or PET), age, sex, APOE genotype, educational level, geographical region, and dementia severity for these estimates.This cross-sectional, individual-participant pooled study included participants from 85 Amyloid Biomarker Study cohorts. Data collection was performed from January 1, 2013, to December 31, 2020. Participants had normal cognition, subjective cognitive decline, mild cognitive impairment, or clinical AD dementia. Normal cognition and subjective cognitive decline were defined by normal scores on cognitive tests, with the presence of cognitive complaints defining subjective cognitive decline. Mild cognitive impairment and clinical AD dementia were diagnosed according to published criteria.Alzheimer disease biomarkers detected on PET or in CSF.Amyloid measurements were dichotomized as normal or abnormal using cohort-provided cutoffs for CSF or PET or by visual reading for PET. Adjusted data-driven cutoffs for abnormal amyloid were calculated using gaussian mixture modeling. Prevalence of amyloid abnormality was estimated according to age, sex, cognitive status, biomarker modality, APOE carrier status, educational level, geographical location, and dementia severity using generalized estimating equations.Among the 19097 participants (mean [SD] age, 69.1 [9.8] years; 10148 women [53.1%]) included, 10139 (53.1%) underwent an amyloid PET scan and 8958 (46.9%) had an amyloid CSF measurement. Using cohort-provided cutoffs, amyloid abnormality prevalences were similar to 2015 estimates for individuals without dementia and were similar across PET- and CSF-based estimates (24%; 95% CI, 21%-28%) in participants with normal cognition, 27% (95% CI, 21%-33%) in participants with subjective cognitive decline, and 51% (95% CI, 46%-56%) in participants with mild cognitive impairment, whereas for clinical AD dementia the estimates were higher for PET than CSF (87% vs 79%; mean difference, 8%; 95% CI, 0%-16%; P=.04). Gaussian mixture modeling-based cutoffs for amyloid measures on PET scans were similar to cohort-provided cutoffs and were not adjusted. Adjusted CSF cutoffs resulted in a 10% higher amyloid abnormality prevalence than PET-based estimates in persons with normal cognition (mean difference, 9%; 95% CI, 3%-15%; P=.004), subjective cognitive decline (9%; 95% CI, 3%-15%; P=.005), and mild cognitive impairment (10%; 95% CI, 3%-17%; P=.004), whereas the estimates were comparable in persons with clinical AD dementia (mean difference, 4%; 95% CI, -2% to 9%; P=.18).This study found that CSF-based estimates using adjusted data-driven cutoffs were up to 10% higher than PET-based estimates in people without dementia, whereas the results were similar among people with dementia. This finding suggests that preclinical and prodromal AD may be more prevalent than previously estimated, which has important implications for clinical trial recruitment strategies and health care planning policies.
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| 11. |
- Gei, Maga, et al.
(författare)
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Legume abundance along successional and rainfall gradients in Neotropical forests
- 2018
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Ingår i: Nature Ecology & Evolution. - : Springer Science and Business Media LLC. - 2397-334X. ; 2:7
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Tidskriftsartikel (refereegranskat)abstract
- The nutrient demands of regrowing tropical forests are partly satisfied by nitrogen-fixing legume trees, but our understanding of the abundance of those species is biased towards wet tropical regions. Here we show how the abundance of Leguminosae is affected by both recovery from disturbance and large-scale rainfall gradients through a synthesis of forest inventory plots from a network of 42 Neotropical forest chronosequences. During the first three decades of natural forest regeneration, legume basal area is twice as high in dry compared with wet secondary forests. The tremendous ecological success of legumes in recently disturbed, water-limited forests is likely to be related to both their reduced leaflet size and ability to fix N2, which together enhance legume drought tolerance and water-use efficiency. Earth system models should incorporate these large-scale successional and climatic patterns of legume dominance to provide more accurate estimates of the maximum potential for natural nitrogen fixation across tropical forests.
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| 12. |
- Jung, Christian, et al.
(författare)
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A comparison of very old patients admitted to intensive care unit after acute versus elective surgery or intervention
- 2019
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Ingår i: Journal of critical care. - : W B SAUNDERS CO-ELSEVIER INC. - 0883-9441 .- 1557-8615. ; 52, s. 141-148
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Tidskriftsartikel (refereegranskat)abstract
- Background: We aimed to evaluate differences in outcome between patients admitted to intensive care unit (ICU) after elective versus acute surgery in a multinational cohort of very old patients (80 years; VIP). Predictors of mortality, with special emphasis on frailty, were assessed.Methods: In total, 5063 VIPs were induded in this analysis, 922 were admitted after elective surgery or intervention, 4141 acutely, with 402 after acute surgery. Differences were calculated using Mann-Whitney-U test and Wilcoxon test. Univariate and multivariable logistic regression were used to assess associations with mortality.Results: Compared patients admitted after acute surgery, patients admitted after elective surgery suffered less often from frailty as defined as CFS (28% vs 46%; p < 0.001), evidenced lower SOFA scores (4 +/- 5 vs 7 +/- 7; p < 0.001). Presence of frailty (CFS >4) was associated with significantly increased mortality both in elective surgery patients (7% vs 12%; p = 0.01), in acute surgery (7% vs 12%; p = 0.02).Conclusions: VIPs admitted to ICU after elective surgery evidenced favorable outcome over patients after acute surgery even after correction for relevant confounders. Frailty might be used to guide clinicians in risk stratification in both patients admitted after elective and acute surgery.
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| 13. |
- Fernandez, A. I., et al.
(författare)
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The impact of Mediterranean diet on coronary plaque vulnerability, microvascular function, inflammation and microbiome after an acute coronary syndrome: study protocol for the MEDIMACS randomized, controlled, mechanistic clinical trial
- 2021
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Ingår i: Trials. - : Springer Science and Business Media LLC. - 1745-6215. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Primary prevention trials have demonstrated that the traditional Mediterranean diet is associated with a reduction in cardiovascular mortality and morbidity. However, this benefit has not been proven for secondary prevention after an acute coronary syndrome (ACS). We hypothesized that a high-intensity Mediterranean diet intervention after an ACS decreases the vulnerability of atherosclerotic plaques by complex interactions between anti-inflammatory effects, microbiota changes and modulation of gene expression. Methods: The MEDIMACS project is an academically funded, prospective, randomized, controlled and mechanistic clinical trial designed to address the effects of an active randomized intervention with the Mediterranean diet on atherosclerotic plaque vulnerability, coronary endothelial dysfunction and other mechanistic endpoints. One hundred patients with ACS are randomized 1:1 to a monitored high-intensity Mediterranean diet intervention or to a standard-of-care arm. Adherence to diet is assessed in both arms using food frequency questionnaires and biomarkers of compliance. The primary endpoint is the change (from baseline to 12 months) in the thickness of the fibrous cap of a non-significant atherosclerotic plaque in a non-culprit vessel, as assessed by repeated optical coherence tomography intracoronary imaging. Indices of coronary vascular physiology and changes in gastrointestinal microbiota, immunological status and protein and metabolite profiles will be evaluated as secondary endpoints. Discussion: The results of this trial will address the key effects of dietary habits on atherosclerotic risk and will provide initial data on the complex interplay of immunological, microbiome-, proteome- and metabolome-related mechanisms by which non-pharmacological factors may impact the progression of coronary atherosclerosis after an ACS.
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| 14. |
- Artaxo, Paulo, et al.
(författare)
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Tropical and Boreal Forest – Atmosphere Interactions : A Review
- 2022
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Ingår i: Tellus. Series B, Chemical and physical meteorology. - : Stockholm University Press. - 0280-6509 .- 1600-0889. ; 74:1, s. 24-163
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Forskningsöversikt (refereegranskat)abstract
- This review presents how the boreal and the tropical forests affect the atmosphere, its chemical composition, its function, and further how that affects the climate and, in return, the ecosystems through feedback processes. Observations from key tower sites standing out due to their long-term comprehensive observations: The Amazon Tall Tower Observatory in Central Amazonia, the Zotino Tall Tower Observatory in Siberia, and the Station to Measure Ecosystem-Atmosphere Relations at Hyytiäla in Finland. The review is complemented by short-term observations from networks and large experiments.The review discusses atmospheric chemistry observations, aerosol formation and processing, physiochemical aerosol, and cloud condensation nuclei properties and finds surprising similarities and important differences in the two ecosystems. The aerosol concentrations and chemistry are similar, particularly concerning the main chemical components, both dominated by an organic fraction, while the boreal ecosystem has generally higher concentrations of inorganics, due to higher influence of long-range transported air pollution. The emissions of biogenic volatile organic compounds are dominated by isoprene and monoterpene in the tropical and boreal regions, respectively, being the main precursors of the organic aerosol fraction.Observations and modeling studies show that climate change and deforestation affect the ecosystems such that the carbon and hydrological cycles in Amazonia are changing to carbon neutrality and affect precipitation downwind. In Africa, the tropical forests are so far maintaining their carbon sink.It is urgent to better understand the interaction between these major ecosystems, the atmosphere, and climate, which calls for more observation sites, providing long-term data on water, carbon, and other biogeochemical cycles. This is essential in finding a sustainable balance between forest preservation and reforestation versus a potential increase in food production and biofuels, which are critical in maintaining ecosystem services and global climate stability. Reducing global warming and deforestation is vital for tropical forests.
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| 15. |
- Auffret, Alistair G., et al.
(författare)
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HistMapR : Rapid digitization of historical land-use maps in R
- 2017
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Ingår i: Methods in Ecology and Evolution. - 2041-210X. ; 8:11, s. 1453-1457
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Tidskriftsartikel (refereegranskat)abstract
- Habitat destruction and degradation represent serious threats to biodiversity, and quantification of land-use change over time is important for understanding the consequences of these changes to organisms and ecosystem service provision. Comparing land use between maps from different time periods allows estimation of the magnitude of habitat change in an area. However, digitizing historical maps manually is time-consuming and analyses of change are usually carried out at small spatial extents or at low resolutions. HistMapR contains a number of functions that can be used to semi-automatically digitize historical land use according to a map's colours, as defined by the RGB bands of the raster image. We test the method on different historical land-use map series and compare results to manual digitizations. Digitization is fast, and agreement with manually digitized maps of around 80-90% meets common targets for image classification. We hope that the ability to quickly classify large areas of historical land use will promote the inclusion of land-use change into analyses of biodiversity, species distributions and ecosystem services.
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| 16. |
- Bricarello, Daniel A, et al.
(författare)
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Inhibiting host-pathogen interactions using membrane-based nanostructures
- 2012
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Ingår i: Trends in Biotechnology. - : Elsevier. - 0167-7799 .- 1879-3096. ; 30:6, s. 323-330
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Forskningsöversikt (refereegranskat)abstract
- Virulent strains of bacteria and viruses recognize host cells by their plasma membrane receptors and often exploit the native translocation machinery to invade the cell. A promising therapeutic concept for early interruption of pathogen infection is to subvert this pathogenic trickery using exogenously introduced decoys that present high-affinity mimics of cellular receptors. This review highlights emerging applications of molecularly engineered lipid-bilayer-based nanostructures, namely (i) functionalized liposomes, (ii) supported colloidal bilayers or protocells and (Hi) reconstituted lipoproteins, which display functional cellular receptors in optimized conformational and aggregative states. These decoys outcompete host cell receptors by preferentially binding to and neutralizing virulence factors of both bacteria and viruses, thereby promising a new approach to antipathogenic therapy.
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| 17. |
- Dzidic, Majda, et al.
(författare)
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Oral microbiota maturation during the first 7 years of life in relation to allergy development
- 2018
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Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - : WILEY. - 0105-4538 .- 1398-9995. ; 73:10, s. 2000-2011
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Tidskriftsartikel (refereegranskat)abstract
- Background Allergic diseases have become a major public health problem in affluent societies. Microbial colonization early in life seems to be critical for instructing regulation on immune system maturation and allergy development in children. Even though the oral cavity is the first site of encounter between a majority of foreign antigens and the immune system, the influence of oral bacteria on allergy development has not yet been reported. Objective Methods We sought to determine the bacterial composition in longitudinally collected saliva samples during childhood in relation to allergy development. Illumina sequencing of the 16S rDNA gene was used to characterize the oral bacterial composition in saliva samples collected at 3, 6, 12, 24 months, and 7 years of age from children developing allergic symptoms and sensitization (n = 47) and children staying healthy (n = 33) up to 7 years of age. Results Conclusion Children developing allergic disease, particularly asthma, had lower diversity of salivary bacteria together with highly divergent bacterial composition at 7 years of age, showing a clearly altered oral microbiota in these individuals, likely as a consequence of an impaired immune system during infancy. Moreover, the relative amounts of several bacterial species, including increased abundance of Gemella haemolysans in children developing allergies and Lactobacillus gasseri and L. crispatus in healthy children, were distinctive during early infancy, likely influencing early immune maturation. Early changes in oral microbial composition seem to influence immune maturation and allergy development. Future experiments should test the probiotic potential of L. gasseri and L. crispatus isolates.
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| 18. |
- Joseph, S., et al.
(författare)
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The Murine Oral Metatranscriptome Reveals Microbial and Host Signatures of Periodontal Disease
- 2023
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Ingår i: Journal of Dental Research. - : Sage Publications. - 0022-0345 .- 1544-0591. ; 102:5, s. 565-573
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Tidskriftsartikel (refereegranskat)abstract
- Periodontal disease is accompanied by alterations to cellular profiles and biological activities of both the subgingival microbiome and host tissues. Although significant progress has been made in describing the molecular basis of the homeostatic balance of host–commensal microbe interactions in health compared to the destructive imbalance in disease, particularly with respect to immune and inflammatory systems, few studies have attempted a comprehensive analysis in diverse host models. Here, we describe the development and application of a metatranscriptomic approach to analysis of host–microbe gene transcription in a murine periodontal disease model, based on oral gavage infection using Porphyromonas gingivalis in C57BL6/J mice. We generated 24 metatranscriptomic libraries from individual mouse oral swabs, representing health and disease. On average, 76% ± 11.7% reads in each sample belonged to the murine host genome and the remainder to the microbes. We found 3,468 (2.4% of the total) murine host transcripts differentially expressed between health and disease, of which 76% were overexpressed in periodontitis. Predictably, there were prominent alterations to genes and pathways linked with the host immune compartment in disease—the CD40 signaling pathway being the top enriched biological process in this data set. However, in addition, we observed significant alterations to other biological processes in disease, particularly cellular/metabolic processes and biological regulation. The number of differentially expressed microbial genes particularly indicated shifts in carbon metabolism pathways in disease with potential consequences for metabolic end-product formation. Together, these metatranscriptome data reveal marked changes between the gene expression patterns in both the murine host and microbiota, which may represent signatures of health and disease, providing the basis for future functional studies of prokaryotic and eukaryotic cellular responses in periodontal disease. In addition, the noninvasive protocol developed in this study will enable further longitudinal and interventionist studies of host–microbe gene expression networks.
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| 19. |
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| 20. |
- Pistocchi, Alberto, et al.
(författare)
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European scale assessment of the potential of ozonation and activated carbon treatment to reduce micropollutant emissions with wastewater
- 2022
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Ingår i: Science of the Total Environment. - : Elsevier BV. - 0048-9697 .- 1879-1026. ; 848
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Tidskriftsartikel (refereegranskat)abstract
- Micropollutants (MPs) in wastewater pose a growing concern for their potential adverse effects on the receiving aquatic environment, and some countries have started requiring that wastewater treatment plants remove them to a certain extent. Broad spectrum advanced treatment processes, such as ozonation, activated carbon or their combination, are expected to yield a significant reduction in the toxicity of effluents. Here we quantify the reduction of effluent toxicity potentially achieved by implementing these advanced treatment solutions in a selection of European wastewater treatment plants. To this end, we refer to a list of “total pollution proxy substances” (TPPS) composed of 1337 chemicals commonly found in wastewater effluents according to a compilation of datasets of measured concentrations. We consider these substances as an approximation of the “chemical universe” impinging on the European wastewater system. We evaluate the fate of the TPPS in conventional and advanced treatment plants using a compilation of experimental physicochemical properties that describe their sorption, volatilization and biodegradation during activated sludge treatment, as well as known removal efficiency in ozonation and activated carbon treatment, while filling the gaps through in silico prediction models.We estimate that the discharge of micropollutants with wastewater effluents in the European Union has a cumulative MP toxicity to the environment equal to the discharge of untreated wastewater of ca. 160 million population equivalents (PE), i.e. about 30 % of the generated wastewater in the EU. If all plants above a capacity of 100,000 PE were equipped with advanced treatment, we show that this load would be reduced to about 95 million PE. In addition, implementing advanced treatment in wastewater plants above 10,000 PE discharging to water bodies with an average dilution ratio smaller than 10 would yield a widespread improvement in terms of exposure of freshwater ecosystems to micropollutants, almost halving the part of the stream network exposed to the highest toxic risks.Our analysis provides background for a cost-effectiveness appraisal of advanced treatment “at the end of the pipe”, which could lead to optimized interventions. This should not be regarded as a stand-alone solution, but as a complement to policies for the control of emissions at the source for the most problematic MPs.
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| 21. |
- Repsilber, Dirk, 1971-, et al.
(författare)
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Reducing false positive rates by rotating microarray-based genomotyping data
- 2004
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Ingår i: Biometrical Journal. - : Wiley. - 0323-3847 .- 1521-4036. ; 46, s. 57-
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Tidskriftsartikel (refereegranskat)abstract
- Microarray-based comparative genomic hybridization is leading to an increased understanding of bacterial evolution and patho-genesis by efficiently comparing whole genomes. Here, a sample genome is compared to a reference genome via comparative hybridization using two different fluorescent dyes. The logratio of the fluorescence intensities for sample and reference genome for each gene on the array is then usually compared to a cutoff classifying the belonging gene as absent or present with respect to the sample genome. The resulting list of candidate absent genes then undergoes confirmational analyses, i.e. PCR or sequencing, which are decisive with respect to both time and costs of the experiment. Thus, there is vital interest to reduce the rate of false positives in the list of candidate absent genes from the comparative genomic hybridization step. Our approach to accomplish this task uses the expected relationship between the logratio and the mean log intensities for absent genes to linear transform the inten-sity data before comparing to a cutoff. For validated data from a series of comparative genomic hybridizations for two Bartonella species we assessed significance and efficacy of the new approach. We show that we are able to halve the rate of false positives in the list of candidate absent genes for a typical comparative genomic hybridization experiment, thus significantly reducing time and costs of necessary confirmational analyses.
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| 22. |
- Swami, Viren, et al.
(författare)
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The Attractive Female Body Weight and Female Body Dissatisfaction in 26 Countries Across 10 World Regions : Results of the International Body Project I
- 2010
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Ingår i: Personality and Social Psychology Bulletin. - : Sage Publications. - 0146-1672 .- 1552-7433. ; 36:3, s. 309-325
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Tidskriftsartikel (refereegranskat)abstract
- This study reports results from the first International Body Project (IBP-I), which surveyed 7,434 individuals in 10 major world regions about body weight ideals and body dissatisfaction. Participants completed the female Contour Drawing Figure Rating Scale (CDFRS) and self-reported their exposure to Western and local media. Results indicated there were significant cross-regional differences in the ideal female figure and body dissatisfaction, but effect sizes were small across high-socioeconomic-status (SES) sites. Within cultures, heavier bodies were preferred in low-SES sites compared to high-SES sites in Malaysia and South Africa (ds = 1.94-2.49) but not in Austria. Participant age, body mass index (BMI), and Western media exposure predicted body weight ideals. BMI and Western media exposure predicted body dissatisfaction among women. Our results show that body dissatisfaction and desire for thinness is commonplace in high-SES settings across world regions, highlighting the need for international attention to this problem.
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| 23. |
- Wang, Jian, et al.
(författare)
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Amazon boundary layer aerosol concentration sustained by vertical transport during rainfall
- 2016
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 539:7629, s. 416-419
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Tidskriftsartikel (refereegranskat)abstract
- The nucleation of atmospheric vapours is an important source of new aerosol particles that can subsequently grow to form cloud condensation nuclei in the atmosphere(1). Most field studies of atmospheric aerosols over continents are influenced by atmospheric vapours of anthropogenic origin (for example, ref. 2) and, in consequence, aerosol processes in pristine, terrestrial environments remain poorly understood. The Amazon rainforest is one of the few continental regions where aerosol particles and their precursors can be studied under near-natural conditions(3-5), but the origin of small aerosol particles that grow into cloud condensation nuclei in the Amazon boundary layer remains unclear(6-8). Here we present aircraft- and ground-based measurements under clean conditions during the wet season in the central Amazon basin. We find that high concentrations of small aerosol particles (with diameters of less than 50 nanometres) in the lower free troposphere are transported from the free troposphere into the boundary layer during precipitation events by strong convective downdrafts and weaker downward motions in the trailing stratiform region. This rapid vertical transport can help to maintain the population of particles in the pristine Amazon boundary layer, and may therefore influence cloud properties and climate under natural conditions.
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| 24. |
- Andersson, C, et al.
(författare)
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Preparation and incorporation of microcapsules in functional coatings for self-healing of packaging board
- 2009
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Ingår i: Packaging technology & science. - 0894-3214 .- 1099-1522. ; 22:5, s. 275-291
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Tidskriftsartikel (refereegranskat)abstract
- The replacement of flexible polyolefin barrier layers with novel, thin, functional polymer coatings in the production of paperboard packaging involves the risk of deteriorated barrier and mechanical properties during the converting process. Local defects or cracks in the protective barrier layer can arise because of the stress induced in creasing and folding operations. In this study, the incorporation of microencapsulated self-healing agents in coating formulations applied both by spot- and uniform-coating techniques was studied. The preparation process of microcapsules with a hydrophobic core surrounded by a hydrophobically modified polysaccharide membrane in aqueous suspension was developed to obtain capsules fulfilling both the criteria of small capsule size and reasonably high solids content to match the requirements set on surface treatment of paperboard for enhancement of packaging functionality. The survival of the microcapsules during application and their effectiveness as self-healing agents were investigated. The results showed a reduced tendency for deteriorated barrier properties and local termination of cracks formed upon creasing. The self-healing mechanism involves the rupture of microcapsules local to the applied stress, with subsequent release of the core material. Crack propagation is hindered by plasticization of the underlying coating layer, while the increased hydrophobicity helps to maintain the barrier properties.
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| 25. |
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| 26. |
- Bankvall, M., et al.
(författare)
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Metataxonomic and metaproteomic profiling of the oral microbiome in oral lichen planus - a pilot study
- 2023
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Ingår i: Journal of Oral Microbiology. - : Informa UK Limited. - 2000-2297. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: A growing body of evidence demonstrates a different bacterial composition in the oral cavity of patients with oral lichen planus (OLP). Patients and methods: Buccal swab samples were collected from affected and non-affected sites of six patients with reticular OLP and the healthy oral mucosa of six control subjects. 16S rRNA gene MiSeq sequencing and mass spectrometry-based proteomics were utilised to identify the metataxonomic and metaproteomic profiles of the oral microbiome in both groups. Results: From the metataxonomic analysis, the most abundant species in the three subgroups were Streptococcus oralis and Pseudomonas aeruginosa, accounting for up to 70% of the total population. Principal Coordinates Analysis showed differential clustering of samples from the healthy and OLP groups. ANCOM-BC compositional analysis revealed multiple species (including P. aeruginosa and several species of Veillonella, Prevotella, Streptococcus and Neisseria) significantly over-represented in the control group and several (including Granulicatella elegans, Gemella haemolysans and G. parahaemolysans) in patients with OLP. The metaproteomic data were generally congruent and revealed that several Gemella haemolysans-belonging peptidases and other proteins with inflammatory and virulence potential were present in OLP lesions. Conclusion: Our data suggest that several bacterial species are associated with OLP. Future studies with larger cohorts should be conducted to determine their role in the aetiology of OLP and evaluate their potential as disease biomarkers.
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| 27. |
- Benedet, Andréa L., et al.
(författare)
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Plasma neurofilament light associates with Alzheimer's disease metabolic decline in amyloid-positive individuals
- 2019
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Ingår i: Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring. - : Wiley. - 2352-8729. ; 11, s. 679-689
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: Neurofilament light chain (NfL) is a promising blood biomarker to detect neurodegeneration in Alzheimer's disease (AD) and other brain disorders. However, there are limited reports of how longitudinal NfL relates to imaging biomarkers. We herein investigated the relationship between blood NfL and brain metabolism in AD. Methods: Voxelwise regression models tested the cross-sectional association between [18F]fluorodeoxyglucose ([18F]FDG) and both plasma and cerebrospinal fluid NfL in cognitively impaired and unimpaired subjects. Linear mixed models were also used to test the longitudinal association between NfL and [18F]FDG in amyloid positive (Aβ+) and negative (Aβ−) subjects. Results: Higher concentrations of plasma and cerebrospinal fluid NfL were associated with reduced [18F]FDG uptake in correspondent brain regions. In Aβ+ participants, NfL associates with hypometabolism in AD-vulnerable regions. Longitudinal changes in the association [18F]FDG-NfL were confined to cognitively impaired Aβ+ individuals. Discussion: These findings indicate that plasma NfL is a proxy for neurodegeneration in AD-related regions in Aβ+ subjects.
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| 28. |
- de Vries, Franciska T., et al.
(författare)
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Soil food web properties explain ecosystem services across European land use systems
- 2013
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Ingår i: Proceedings of the National Academy of Sciences. - Washington, DC : Proceedings of the National Academy of Sciences. - 1091-6490 .- 0027-8424. ; 110:35, s. 14296-14301
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Tidskriftsartikel (refereegranskat)abstract
- Intensive land use reduces the diversity and abundance of many soil biota, with consequences for the processes that they govern and the ecosystem services that these processes underpin. Relationships between soil biota and ecosystem processes have mostly been found in laboratory experiments and rarely are found in the field. Here, we quantified, across four countries of contrasting climatic and soil conditions in Europe, how differences in soil food web composition resulting from land use systems (intensive wheat rotation, extensive rotation, and permanent grassland) influence the functioning of soils and the ecosystem services that they deliver. Intensive wheat rotation consistently reduced the biomass of all components of the soil food web across all countries. Soil food web properties strongly and consistently predicted processes of C and N cycling across land use systems and geographic locations, and they were a better predictor of these processes than land use. Processes of carbon loss increased with soil food web properties that correlated with soil C content, such as earthworm biomass and fungal/bacterial energy channel ratio, and were greatest in permanent grassland. In contrast, processes of N cycling were explained by soil food web properties independent of land use, such as arbuscular mycorrhizal fungi and bacterial channel biomass. Our quantification of the contribution of soil organisms to processes of C and N cycling across land use systems and geographic locations shows that soil biota need to be included in C and N cycling models and highlights the need to map and conserve soil biodiversity across the world.
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| 29. |
- Dini, P., et al.
(författare)
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Proceedings - 5th International Conference on Software Engineering Advances, ICSEA 2010 : Preface
- 2010
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Ingår i: International Conference on Software Engineering Advances (ICSEA). - : Institute of Electrical and Electronics Engineers (IEEE). ; , s. xii-xiii
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Konferensbidrag (populärvet., debatt m.m.)abstract
- Presents the introductory welcome message from the conference proceedings. May include the conference officers' congratulations to all involved with the conference event and publication of the proceedings record.
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| 30. |
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| 31. |
- El Sayed, Mira, et al.
(författare)
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Insights into Dissolution and Solution Chemistry of Multidrug Formulations of Antihypertensive Drugs
- 2020
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Ingår i: Molecular Pharmaceutics. - : American Chemical Society (ACS). - 1543-8384 .- 1543-8392. ; 17:10, s. 4018-4028
-
Tidskriftsartikel (refereegranskat)abstract
- Using fixed dose combinations of drugs instead of administering drugs separately can be beneficial for both patients and the health care system, but the current understanding of how multidrug formulations work at the molecular level is still in its infancy. Here, we explore dissolution, solubility, and supersaturation of various drug combinations in amorphous formulations. The effect of chemical structural similarity on combination behavior was investigated by using structurally related compounds of both drugs. The effect of polymer type on solution behavior was also evaluated using chemically diverse polymers. Indapamide (IPM) concentration decreased when combined with felodipine (FDN) or its analogues, which occurred even when the IPM solution was undersaturated. The extent of solubility decrease of FDN was less than that of IPM from the dissolution of an equimolar formulation of the drugs. No significant solubility decrease was observed for FDN at low contents of IPM which was also observed for other dihydropyridines, whereas FDN decreases at high contents of IPM. This was explained by the complex nature of the colloidal precipitates of the combinations which impacts the chemical potential of the drugs in solution at different levels. The maximum achievable concentration of FDN and IPM during dissolution of the polyvinylpyrrolidone-based amorphous solid dispersion was higher than the value measured with the hydroxypropyl methylcellulose acetate succinate-based formulation. This emphasizes the significance of molecular properties and chemical diversity of drugs and polymers on solution chemistry and solubility profiles. These findings may apply to drugs administered as a single dosage form or in separate dosage forms and hence need to be well controlled to assure effective treatments and patient safety.
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| 32. |
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| 33. |
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| 34. |
- Gil-Lespinard, Mercedes, et al.
(författare)
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Plasma concentration of 36 (poly)phenols and prospective body weight change in participants from the EPIC cohort
- 2024
-
Ingår i: Annals of Nutrition and Metabolism. - : S. Karger. - 0250-6807 .- 1421-9697. ; 80:2, s. 87-100
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Dietary intake of (poly)phenols has been linked to reduced adiposity and body weight (BW) in several epidemiological studies. However, epidemiological evidence on (poly)phenol biomarkers, particularly plasma concentrations, is scarce. We aimed to investigate the associations between plasma (poly)phenols and prospective BW change in participants from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.Methods: This study included 761 participants with data on BW at baseline and after 5 years of follow-up. Plasma concentrations of 36 (poly)phenols were measured at baseline using liquid chromatography-tandem mass spectrometry. Associations were assessed through general linear mixed models and multinomial logistic regression models, using change in BW as a continuous or as a categorical variable (BW loss, maintenance, gain), respectively. Plasma (poly)phenols were assessed as log2-transformed continuous variables. The false discovery rate (FDR) was used to control for multiple comparisons.Results: Doubling plasma (poly)phenol concentrations showed a borderline trend towards a positive association with BW loss. Plasma vanillic acid showed the strongest association (−0.53 kg/5 years; 95% confidence interval [CI]: −0.99, −0.07). Similar results were observed for plasma naringenin comparing BW loss versus BW maintenance (odds ratio: 1.1; 95% CI: 1.0, 1.2). These results did not remain significant after FDR correction.Conclusion: Higher concentrations of plasma (poly)phenols suggested a tendency towards 5-year BW maintenance or loss. While certain associations seemed promising, they did not withstand FDR correction, indicating the need for caution in interpreting these results. Further studies using (poly) phenol biomarkers are needed to confirm these suggestive protective trends.
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| 35. |
- Gobom, Johan, et al.
(författare)
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Validation of the LUMIPULSE automated immunoassay for the measurement of core AD biomarkers in cerebrospinal fluid.
- 2022
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Ingår i: Clinical chemistry and laboratory medicine. - : Walter de Gruyter GmbH. - 1437-4331 .- 1434-6621. ; 60:2, s. 207-219
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Tidskriftsartikel (refereegranskat)abstract
- The core cerebrospinal fluid (CSF) biomarkers; total tau (tTau), phospho-tau (pTau), amyloid β1-42(Aβ 1-42), and the Aβ 1-42/Aβ 1-40 ratio have transformed Alzheimer's disease (AD) research and are today increasingly used in clinical routine laboratories as diagnostic tools. Fully automated immunoassay instruments with ready-to-use assay kits and calibrators has simplified their analysis and improved reproducibility of measurements. We evaluated the analytical performance of the fully automated immunoassay instrument LUMIPULSE G (Fujirebio) for measurement of the four core AD CSF biomarkers and determined cutpoints for AD diagnosis.Comparison of the LUMIPULSE G assays was performed with the established INNOTEST ELISAs (Fujirebio) for hTau Ag, pTau 181, β-amyloid 1-42, and with V-PLEX Plus Aβ Peptide Panel 1 (6E10) (Meso Scale Discovery) for Aβ 1-42/Aβ 1-40, as well as with a LC-MS reference method for Aβ 1-42. Intra- and inter-laboratory reproducibility was evaluated for all assays. Clinical cutpoints for Aβ 1-42, tTau, and pTau was determined by analysis of three cohorts of clinically diagnosed patients, comprising 651 CSF samples. For the Aβ 1-42/Aβ 1-40 ratio, the cutpoint was determined by mixture model analysis of 2,782 CSF samples.The LUMIPULSE G assays showed strong correlation to all other immunoassays (r>0.93 for all assays). The repeatability (intra-laboratory) CVs ranged between 2.0 and 5.6%, with the highest variation observed for β-amyloid 1-40. The reproducibility (inter-laboratory) CVs ranged between 2.1 and 6.5%, with the highest variation observed for β-amyloid 1-42. The clinical cutpoints for AD were determined to be 409ng/L for total tau, 50.2ng/L for pTau 181, 526ng/L for β-amyloid 1-42, and 0.072 for the Aβ 1-42/Aβ 1-40 ratio.Our results suggest that the LUMIPULSE G assays for the CSF AD biomarkers are fit for purpose in clinical laboratory practice. Further, they corroborate earlier presented reference limits for the biomarkers.
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| 36. |
- Jose Farre, Maria, et al.
(författare)
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Orbitrap molecular fingerprint of dissolved organic matter in natural waters and its relationship with NDMA formation potential
- 2019
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Ingår i: Science of the Total Environment. - : ELSEVIER SCIENCE BV. - 0048-9697 .- 1879-1026. ; 670, s. 1019-1027
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Tidskriftsartikel (refereegranskat)abstract
- N-nitrosodimethylamine (NDMA) is a disinfection byproduct that has been classified as probable human carcinogen by the US Environmental Protection Agency. According to the published literature, natural dissolved organic matter (DOM) can be a source of NDMA precursors in drinking water. New advances in chemical characterization of DOM with high resolution mass spectrometry (HRMS) are allowing researchers to understand these ultra-complex mixtures. The objective of this study is to investigate analytical methodologies based on HRMS to explore NDMA formation from natural waters. To this aim, different waters from drinking water reservoirs in Spain containing NDMA precursors (quantified by means of NDMA formation potential) in concentrations between 17 and 60 ng/L have been studied. The workflow includes DOM solid-phase extraction and Orbitrap analysis with and without chromatographic separation. Here, we show that the molecular composition of DOM across the studied drinking water reservoirs is correlated with the NDMA formation potential. In particular, we found that NDMA formation potential is associated with compounds with high hydrogen saturation (H/C >= 1.5), corresponding also to reservoirs with higher background nutrient concentrations and wastewater indicators. Further chromatographic fractionation did not allow better definition of these possible precursors as they were present in different fractions of the chromatogram, suggesting that they were isomerically complex.
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| 37. |
- Kajko-Mattsson, Mira, et al.
(författare)
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A framework for roles for development, evolution and maintenance of SOA-based systems
- 2007
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Ingår i: Proceedings - ICSE 2007 Workshops. - 0769529607 - 9780769529608 ; , s. 4273295-
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Konferensbidrag (refereegranskat)abstract
- Development, evolution and maintenance of SOAbased systems demands rethinking of the traditional roles for performing these activities. The key objective of this paper is to present preliminary ideas on the roles required for developing, evolving and maintaining SOA-based systems and to suggest a framework for areas of needed research.
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| 38. |
- Kajko-Mattsson, Mira, et al.
(författare)
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An outline of CM(3) : Emergency problem management
- 2005
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Ingår i: EUROMICRO-SEAA 2005: 31ST EUROMICRO CONFERENCE ON SOFTWARE ENGINEERING AND ADVANCED APPLICATIONS, PROCEEDINGS. - 0769524311 ; , s. 292-300
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Konferensbidrag (refereegranskat)abstract
- Despite its importance, the process for emergency corrective maintenance has received very little attention. Today, we do not have any standard process models for handling emergency situations. The only models that have been defined can be found within the industry. In this paper, we outline an emergency corrective maintenance process model and evaluate its applicability to manage the new technology systems, the Web service systems. Our model has been elicited at Scandinavian Airline Systems (SAS). It provides a basis for developing a more detailed model of emergency corrective maintenance process - CM(3): Emergency Problem Management.
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| 39. |
- Kajko-Mattsson, Mira, et al.
(författare)
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Evolution and maintenance of SOA-based systems at SAS
- 2008
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Ingår i: Proc. Annu. Hawaii Int. Conf. Syst. Sci.. - 0769530753 - 9780769530758
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Konferensbidrag (refereegranskat)abstract
- As SOA-based systems are becoming more common, there is a need to consider how traditional IT roles and responsibilities need to change. This paper proposes a framework for roles that are required for evolving and maintaining SOA-based systems. It builds on work on traditional IT roles, as well as insights emerging from current research on SOA. The paper also presents a questionnaire for collecting data from organizations on roles that they use for SOA-based systems maintenance and evolution. Results from a pilot use of the questionnaire with Scandinavian Airline Systems (SAS) are presented.
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| 40. |
- Kajko-Mattsson, Mira, et al.
(författare)
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International workshop on processes for software evolution and maintenance (WoPSEM 2010)
- 2010
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Ingår i: 2010 17th Working Conference on Reverse Engineering (WCRE). - 9780769541235 ; , s. 281-282
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Konferensbidrag (refereegranskat)abstract
- Software evolution and maintenance processes have been and continue to be an unexplored domain. Current process models and standards do not cover the whole evolution and maintenance domain. As a result, the software community still possesses a blurred understanding of its scope, an unclear picture of how various processes are interrelated, how they impact each other and the product. The software community is also insecure about how to adapt evolution and maintenance processes to new methods and technologies. This workshop aims at discussing the challenges, problems and evolution and maintenance process models according to the latest findings.
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| 41. |
- Kajko-Mattsson, Mira Miroslawa, et al.
(författare)
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Eliciting a model of emergency corrective maintenance at SAS
- 2005
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Ingår i: SERP '05: PROCEEDINGS OF THE 2005 INTERNATIONAL CONFERENCE ON SOFTWARE ENGINEERING RESEARCH AND PRACTICE, VOLS 1 AND 2. - 1932415513 ; , s. 694-700
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Konferensbidrag (refereegranskat)abstract
- Disciplined corrective maintenance requires good insight into all of its inherent activities, both within planned and unplanned maintenance. In this paper, we outline an emergency corrective maintenance process model. The model has been elicited at Scandinavian Airline Systems (SAS). This paper provides a foundation for developing a more detailed model of emergency corrective maintenance process.
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| 42. |
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| 43. |
- Kajko-Mattsson, Mira, et al.
(författare)
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Refounding software engineering : The Semat initiative (Invited presentation)
- 2012
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Ingår i: Software Engineering (ICSE), 2012 34th International Conference on. - : IEEE Computer Society. - 9781467310673 ; , s. 1649-1650
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Konferensbidrag (refereegranskat)abstract
- The new software engineering initiative, Semat, is in the process of developing a kernel for software engineering that stands on a solid theoretical basis. So far, it has suggested a set of kernel elements for software engineering and basic language constructs for defining the elements and their usage. This paper describes a session during which Semat results and status will be presented. The presentation will be followed by a discussion panel.
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| 44. |
- Kallionpaa, Roope A., et al.
(författare)
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Characterization of Immune Cell Populations of Cutaneous Neurofibromas in Neurofibromatosis 1
- 2024
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Ingår i: LABORATORY INVESTIGATION. - 0023-6837 .- 1530-0307. ; 104:1
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Tidskriftsartikel (refereegranskat)abstract
- Cutaneous neurofibromas (cNFs) are characteristic of neurofibromatosis 1 (NF1), yet their immune microenvironment is incompletely known. A total of 61 cNFs from 10 patients with NF1 were immunolabeled for different types of T cells and macrophages, and the cell densities were correlated with clinical characteristics. Eight cNFs and their overlying skin were analyzed for T cell receptor CDR domain sequences, and mass spectrometry of 15 cNFs and the overlying skin was performed to study immune-related processes. Intratumoral T cells were detected in all cNFs. Tumors from individuals younger than the median age of the study participants (33 years), growing tumors, and tumors smaller than the data set median showed increased T cell density. Most samples displayed intratumoral or peritumoral aggregations of CD3-positive cells. T cell receptor sequencing demonstrated that the skin and cNFs host distinct T cell populations, whereas no dominant cNF-specific T cell clones were detected. Unique T cell clones were fewer in cNFs than in skin, and mass spectrometry suggested lower expression of proteins related to T cell-mediated immunity in cNFs than in skin. CD163-positive cells, suggestive of M2 macrophages, were abundant in cNFs. Human cNFs have substantial T cell and macrophage populations that may be tumorspecific.
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| 45. |
- Karikari, Thomas, et al.
(författare)
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Blood phosphorylated tau 181 as a biomarker for Alzheimer's disease: a diagnostic performance and prediction modelling study using data from four prospective cohorts.
- 2020
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Ingår i: The Lancet. Neurology. - 1474-4465 .- 1474-4422. ; 19:5, s. 422-433
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Tidskriftsartikel (refereegranskat)abstract
- CSF and PET biomarkers of amyloid β and tau accurately detect Alzheimer's disease pathology, but the invasiveness, high cost, and poor availability of these detection methods restrict their widespread use as clinical diagnostic tools. CSF tau phosphorylated at threonine 181 (p-tau181) is a highly specific biomarker for Alzheimer's disease pathology. We aimed to assess whether blood p-tau181 could be used as a biomarker for Alzheimer's disease and for prediction of cognitive decline and hippocampal atrophy.We developed and validated an ultrasensitive blood immunoassay for p-tau181. Assay performance was evaluated in four clinic-based prospective cohorts. The discovery cohort comprised patients with Alzheimer's disease and age-matched controls. Two validation cohorts (TRIAD and BioFINDER-2) included cognitively unimpaired older adults (mean age 63-69 years), participants with mild cognitive impairment (MCI), Alzheimer's disease, and frontotemporal dementia. In addition, TRIAD included healthy young adults (mean age 23 years) and BioFINDER-2 included patients with other neurodegenerative disorders. The primary care cohort, which recruited participants in Montreal, Canada, comprised control participants from the community without a diagnosis of a neurological condition and patients referred from primary care physicians of the Canadian National Health Service for specialist care. Concentrations of plasma p-tau181 were compared with established CSF and PET biomarkers and longitudinal measurements using Spearman correlation, area under the curve (AUC), and linear regression analyses.We studied 37 individuals in the discovery cohort, 226 in the first validation cohort (TRIAD), 763 in the second validation cohort (BioFINDER-2), and 105 in the primary care cohort (n=1131 individuals). In all cohorts, plasma p-tau181 showed gradual increases along the Alzheimer's disease continuum, from the lowest concentrations in amyloid β-negative young adults and cognitively unimpaired older adults, through higher concentrations in the amyloid β-positive cognitively unimpaired older adults and MCI groups, to the highest concentrations in the amyloid β-positive MCI and Alzheimer's disease groups (p<0·001, Alzheimer's disease vs all other groups). Plasma p-tau181 distinguished Alzheimer's disease dementia from amyloid β-negative young adults (AUC=99·40%) and cognitively unimpaired older adults (AUC=90·21-98·24% across cohorts), as well as other neurodegenerative disorders, including frontotemporal dementia (AUC=82·76-100% across cohorts), vascular dementia (AUC=92·13%), progressive supranuclear palsy or corticobasal syndrome (AUC=88·47%), and Parkinson's disease or multiple systems atrophy (AUC=81·90%). Plasma p-tau181 was associated with PET-measured cerebral tau (AUC=83·08-93·11% across cohorts) and amyloid β (AUC=76·14-88·09% across cohorts) pathologies, and 1-year cognitive decline (p=0·0015) and hippocampal atrophy (p=0·015). In the primary care cohort, plasma p-tau181 discriminated Alzheimer's disease from young adults (AUC=100%) and cognitively unimpaired older adults (AUC=84·44%), but not from MCI (AUC=55·00%).Blood p-tau181 can predict tau and amyloid β pathologies, differentiate Alzheimer's disease from other neurodegenerative disorders, and identify Alzheimer's disease across the clinical continuum. Blood p-tau181 could be used as a simple, accessible, and scalable test for screening and diagnosis of Alzheimer's disease.Alzheimer Drug Discovery Foundation, European Research Council, Swedish Research Council, Swedish Alzheimer Foundation, Swedish Dementia Foundation, Alzheimer Society Research Program.
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| 46. |
- Karyotaki, Eirini, et al.
(författare)
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Internet-Based Cognitive Behavioral Therapy for Depression : A Systematic Review and Individual Patient Data Network Meta-analysis
- 2021
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Ingår i: JAMA psychiatry. - : American Medical Association. - 2168-6238 .- 2168-622X. ; 78:4, s. 361-371
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Forskningsöversikt (refereegranskat)abstract
- IMPORTANCE: Personalized treatment choices would increase the effectiveness of internet-based cognitive behavioral therapy (iCBT) for depression to the extent that patients differ in interventions that better suit them.OBJECTIVE: To provide personalized estimates of short-term and long-term relative efficacy of guided and unguided iCBT for depression using patient-level information.DATA SOURCES: We searched PubMed, Embase, PsycInfo, and Cochrane Library to identify randomized clinical trials (RCTs) published up to January 1, 2019.STUDY SELECTION: Eligible RCTs were those comparing guided or unguided iCBT against each other or against any control intervention in individuals with depression. Available individual patient data (IPD) was collected from all eligible studies. Depression symptom severity was assessed after treatment, 6 months, and 12 months after randomization.DATA EXTRACTION AND SYNTHESIS: We conducted a systematic review and IPD network meta-analysis and estimated relative treatment effect sizes across different patient characteristics through IPD network meta-regression.MAIN OUTCOMES AND MEASURES: Patient Health Questionnaire-9 (PHQ-9) scores.RESULTS: Of 42 eligible RCTs, 39 studies comprising 9751 participants with depression contributed IPD to the IPD network meta-analysis, of which 8107 IPD were synthesized. Overall, both guided and unguided iCBT were associated with more effectiveness as measured by PHQ-9 scores than control treatments over the short term and the long term. Guided iCBT was associated with more effectiveness than unguided iCBT (mean difference [MD] in posttreatment PHQ-9 scores, -0.8; 95% CI, -1.4 to -0.2), but we found no evidence of a difference at 6 or 12 months following randomization. Baseline depression was found to be the most important modifier of the relative association for efficacy of guided vs unguided iCBT. Differences between unguided and guided iCBT in people with baseline symptoms of subthreshold depression (PHQ-9 scores 5-9) were small, while guided iCBT was associated with overall better outcomes in patients with baseline PHQ-9 greater than 9.CONCLUSIONS AND RELEVANCE: In this network meta-analysis with IPD, guided iCBT was associated with more effectiveness than unguided iCBT for individuals with depression, benefits were more substantial in individuals with moderate to severe depression. Unguided iCBT was associated with similar effectiveness among individuals with symptoms of mild/subthreshold depression. Personalized treatment selection is entirely possible and necessary to ensure the best allocation of treatment resources for depression.
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| 47. |
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| 48. |
- Lenz, Tobias L., et al.
(författare)
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Widespread non-additive and interaction effects within HLA loci modulate the risk of autoimmune diseases
- 2015
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Ingår i: Nature Genetics. - : Macmillan Publishers Ltd.. - 1061-4036 .- 1546-1718. ; 47:9, s. 1085-1090
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Tidskriftsartikel (refereegranskat)abstract
- Human leukocyte antigen (HLA) genes confer substantial risk for autoimmune diseases on a log-additive scale. Here we speculated that differences in autoantigen-binding repertoires between a heterozygote's two expressed HLA variants might result in additional non-additive risk effects. We tested the non-additive disease contributions of classical HLA alleles in patients and matched controls for five common autoimmune diseases: rheumatoid arthritis (n(cases) = 5,337), type 1 diabetes (T1D; n(cases) = 5,567), psoriasis vulgaris (n(cases) = 3,089), idiopathic achalasia (n(cases) = 727) and celiac disease (ncases = 11,115). In four of the five diseases, we observed highly significant, non-additive dominance effects (rheumatoid arthritis, P = 2.5 x 10(-12); T1D, P = 2.4 x 10(-10); psoriasis, P = 5.9 x 10(-6); celiac disease, P = 1.2 x 10(-87)). In three of these diseases, the non-additive dominance effects were explained by interactions between specific classical HLA alleles (rheumatoid arthritis, P = 1.8 x 10(-3); T1D, P = 8.6 x 10(-27); celiac disease, P = 6.0 x 10(-100)). These interactions generally increased disease risk and explained moderate but significant fractions of phenotypic variance (rheumatoid arthritis, 1.4%; T1D, 4.0%; celiac disease, 4.1%) beyond a simple additive model.
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| 49. |
- Lessa Benedet, Andréa, et al.
(författare)
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Stage-specific links between plasma neurofilament light and imaging biomarkers of Alzheimer's disease
- 2020
-
Ingår i: Brain. - : Oxford University Press (OUP). - 0006-8950 .- 1460-2156. ; 143:12, s. 3793-3804
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Tidskriftsartikel (refereegranskat)abstract
- Neurofilament light (NfL) is a marker of neuroaxonal injury, a prominent feature of Alzheimer's disease. It remains uncertain, however, how it relates to amyloid and tau pathology or neurodegeneration across the Alzheimer's disease continuum. The aim of this study was to investigate how plasma NfL relates to amyloid and tau PET and MRI measures of brain atrophy in participants with and without cognitive impairment. We retrospectively examined the association between plasma NfL and MRI measures of grey/white matter volumes in the Alzheimer's Disease Neuroimaging Initiative [ADNI: n = 1149; 382 cognitively unimpaired control subjects and 767 cognitively impaired participants (mild cognitive impairment n = 420, Alzheimer's disease dementia n = 347)]. Longitudinal plasma NfL was measured using single molecule array (Simoa) technology. Cross-sectional associations between plasma NfL and PET amyloid and tau measures were independently assessed in two cohorts: ADNI [n = 198; 110 cognitively unimpaired, 88 cognitively impaired (MCI n = 67, Alzheimer's disease dementia n = 21), data accessed October 2018]; and Translational Biomarkers in Aging and Dementia [TRIAD, n = 116; 74 cognitively unimpaired, 42 cognitively impaired (MCI n = 16, Alzheimer's disease dementia n = 26), data obtained November 2017 to January 2019]. Associations between plasma NfL and imaging-derived measures were examined voxel-wise using linear regression (cross-sectional) and linear mixed effect models (longitudinal). Cross-sectional analyses in both cohorts showed that plasma NfL was associated with PET findings in brain regions typically affected by Alzheimer's disease; associations were specific to amyloid PET in cognitively unimpaired and tau PET in cognitively impaired (P < 0.05). Longitudinal analyses showed that NfL levels were associated with grey/white matter volume loss; grey matter atrophy in cognitively unimpaired was specific to APOE ϵ4 carriers (P < 0.05). These findings suggest that plasma NfL increases in response to amyloid-related neuronal injury in preclinical stages of Alzheimer's disease, but is related to tau-mediated neurodegeneration in symptomatic patients. As such, plasma NfL may a useful measure to monitor effects in disease-modifying drug trials.
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- Lund, Peter A., et al.
(författare)
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Understanding How Microorganisms Respond to Acid pH Is Central to Their Control and Successful Exploitation
- 2020
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Ingår i: Frontiers in Microbiology. - : Frontiers Media SA. - 1664-302X. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Microbes from the three domains of life,Bacteria,Archaea, andEukarya, share the need to sense and respond to changes in the external and internal concentrations of protons. When the proton concentration is high, acidic conditions prevail and cells must respond appropriately to ensure that macromolecules and metabolic processes are sufficiently protected to sustain life. While, we have learned much in recent decades about the mechanisms that microbes use to cope with acid, including the unique challenges presented by organic acids, there is still much to be gained from developing a deeper understanding of the effects and responses to acid in microbes. In this perspective article, we survey the key molecular mechanisms known to be important for microbial survival during acid stress and discuss how this knowledge might be relevant to microbe-based applications and processes that are consequential for humans. We discuss the research approaches that have been taken to investigate the problem and highlight promising new avenues. We discuss the influence of acid on pathogens during the course of infections and highlight the potential of using organic acids in treatments for some types of infection. We explore the influence of acid stress on photosynthetic microbes, and on biotechnological and industrial processes, including those needed to produce organic acids. We highlight the importance of understanding acid stress in controlling spoilage and pathogenic microbes in the food chain. Finally, we invite colleagues with an interest in microbial responses to low pH to participate in the EU-funded COST Action network called EuroMicropH and contribute to a comprehensive database of literature on this topic that we are making publicly available.
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