| 1. |
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| 2. |
- Strandberg, B., et al.
(författare)
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Near-threshold π-photoproduction on the deuteron
- 2020
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Ingår i: Physical Review C. - 2469-9985. ; 101:3
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Tidskriftsartikel (refereegranskat)abstract
- The first experimental investigation of the near-threshold cross section for incoherent π-photoproduction on the deuteron γd→π-pp is presented. The experimental technique involved detection of the ≈131 MeV γ ray resulting from the radiative capture of photoproduced π-in the target. The total cross section was measured using an unpolarized tagged-photon beam, a liquid-deuterium target, and three very large NaI(Tl) spectrometers. The data are compared to theoretical models that give insight into the elementary reaction γn→π-p and pion-nucleon and nucleon-nucleon final-state interactions.
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| 3. |
- Wimberger, Sandra, 1987, et al.
(författare)
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Simultaneous inhibition of DNA-PK and Pol ϴ improves integration efficiency and precision of genome editing
- 2023
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Ingår i: Nature Communications. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Genome editing, specifically CRISPR/Cas9 technology, has revolutionized biomedical research and offers potential cures for genetic diseases. Despite rapid progress, low efficiency of targeted DNA integration and generation of unintended mutations represent major limitations for genome editing applications caused by the interplay with DNA double-strand break repair pathways. To address this, we conduct a large-scale compound library screen to identify targets for enhancing targeted genome insertions. Our study reveals DNA-dependent protein kinase (DNA-PK) as the most effective target to improve CRISPR/Cas9-mediated insertions, confirming previous findings. We extensively characterize AZD7648, a selective DNA-PK inhibitor, and find it to significantly enhance precise gene editing. We further improve integration efficiency and precision by inhibiting DNA polymerase theta (Pol ϴ). The combined treatment, named 2iHDR, boosts templated insertions to 80% efficiency with minimal unintended insertions and deletions. Notably, 2iHDR also reduces off-target effects of Cas9, greatly enhancing the fidelity and performance of CRISPR/Cas9 gene editing. Low efficiency of target DNA integration remains a challenge in genome engineering. Here the authors perform large-scale compound library and genetic screens to identify targets that enhance gene editing: they see that combined DNA-PK and Pol ϴ inhibition with potent compounds increases editing efficiency and precision.
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| 4. |
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| 5. |
- Jungebluth, P, et al.
(författare)
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Retraction Statement
- 2023
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Ingår i: Respiration. - : S. Karger AG. - 1423-0356 .- 0025-7931. ; 102:5, s. 402-404
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 6. |
- Kurth, F, et al.
(författare)
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Large-scale analysis of structural brain asymmetries during neurodevelopment : Associations with age and sex in 4265 children and adolescents.
- 2024
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Ingår i: Human Brain Mapping. - 1065-9471 .- 1097-0193. ; 45:11, s. e26754-
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Tidskriftsartikel (refereegranskat)abstract
- Only a small number of studies have assessed structural differences between the two hemispheres during childhood and adolescence. However, the existing findings lack consistency or are restricted to a particular brain region, a specific brain feature, or a relatively narrow age range. Here, we investigated associations between brain asymmetry and age as well as sex in one of the largest pediatric samples to date (n = 4265), aged 1-18 years, scanned at 69 sites participating in the ENIGMA (Enhancing NeuroImaging Genetics through Meta-Analysis) consortium. Our study revealed that significant brain asymmetries already exist in childhood, but their magnitude and direction depend on the brain region examined and the morphometric measurement used (cortical volume or thickness, regional surface area, or subcortical volume). With respect to effects of age, some asymmetries became weaker over time while others became stronger; sometimes they even reversed direction. With respect to sex differences, the total number of regions exhibiting significant asymmetries was larger in females than in males, while the total number of measurements indicating significant asymmetries was larger in males (as we obtained more than one measurement per cortical region). The magnitude of the significant asymmetries was also greater in males. However, effect sizes for both age effects and sex differences were small. Taken together, these findings suggest that cerebral asymmetries are an inherent organizational pattern of the brain that manifests early in life. Overall, brain asymmetry appears to be relatively stable throughout childhood and adolescence, with some differential effects in males and females.
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| 7. |
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| 8. |
- Li, S. Y., et al.
(författare)
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Universal toxin-based selection for precise genome engineering in human cells
- 2021
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Prokaryotic restriction enzymes, recombinases and Cas proteins are powerful DNA engineering and genome editing tools. However, in many primary cell types, the efficiency of genome editing remains low, impeding the development of gene- and cell-based therapeutic applications. A safe strategy for robust and efficient enrichment of precisely genetically engineered cells is urgently required. Here, we screen for mutations in the receptor for Diphtheria Toxin (DT) which protect human cells from DT. Selection for cells with an edited DT receptor variant enriches for simultaneously introduced, precisely targeted gene modifications at a second independent locus, such as nucleotide substitutions and DNA insertions. Our method enables the rapid generation of a homogenous cell population with bi-allelic integration of a DNA cassette at the selection locus, without clonal isolation. Toxin-based selection works in both cancer-transformed and non-transformed cells, including human induced pluripotent stem cells and human primary T-lymphocytes, as well as it is applicable also in vivo, in mice with humanized liver. This work represents a flexible, precise, and efficient selection strategy to engineer cells using CRISPR-Cas and base editing systems. Genome engineering in cell lines or human stem cells often has poor efficiency, limiting the development of research and therapeutic applications. Here, the authors use a toxin-based selection system for precise bi-allelic engineering in cells and in vivo.
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| 9. |
- Abrego, Nerea, et al.
(författare)
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Airborne DNA reveals predictable spatial and seasonal dynamics of fungi
- 2024
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Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 631, s. 835-842
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Tidskriftsartikel (refereegranskat)abstract
- Fungi are among the most diverse and ecologically important kingdoms in life. However, the distributional ranges of fungi remain largely unknown as do the ecological mechanisms that shape their distributions1,2. To provide an integrated view of the spatial and seasonal dynamics of fungi, we implemented a globally distributed standardized aerial sampling of fungal spores3. The vast majority of operational taxonomic units were detected within only one climatic zone, and the spatiotemporal patterns of species richness and community composition were mostly explained by annual mean air temperature. Tropical regions hosted the highest fungal diversity except for lichenized, ericoid mycorrhizal and ectomycorrhizal fungi, which reached their peak diversity in temperate regions. The sensitivity in climatic responses was associated with phylogenetic relatedness, suggesting that large-scale distributions of some fungal groups are partially constrained by their ancestral niche. There was a strong phylogenetic signal in seasonal sensitivity, suggesting that some groups of fungi have retained their ancestral trait of sporulating for only a short period. Overall, our results show that the hyperdiverse kingdom of fungi follows globally highly predictable spatial and temporal dynamics, with seasonality in both species richness and community composition increasing with latitude. Our study reports patterns resembling those described for other major groups of organisms, thus making a major contribution to the long-standing debate on whether organisms with a microbial lifestyle follow the global biodiversity paradigms known for macroorganisms4,5.
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| 10. |
- Ahlström, Aisling, 1976, et al.
(författare)
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A double-blind randomized controlled trial investigating a time-lapse algorithm for selecting Day 5 blastocysts for transfer
- 2022
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Ingår i: Human Reproduction. - : Oxford University Press (OUP). - 0268-1161 .- 1460-2350. ; 37:4, s. 708-717
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Tidskriftsartikel (refereegranskat)abstract
- STUDY QUESTION Can use of a commercially available time-lapse algorithm for Day 5 blastocyst selection improve pregnancy rates compared with morphology alone? SUMMARY ANSWER The use of a time-lapse selection model to choose blastocysts for fresh single embryo transfer on Day 5 did not improve ongoing pregnancy rate compared to morphology alone. WHAT IS KNOWN ALREADY Evidence from time-lapse monitoring suggests correlations between timing of key developmental events and embryo viability. No good quality evidence exists to support improved pregnancy rates following time-lapse selection. STUDY DESIGN, SIZE, DURATION A prospective multicenter randomized controlled trial including 776 randomized patients was performed between 2018 and 2021. Patients with at least two good quality blastocysts on Day 5 were allocated by a computer randomization program in a proportion of 1:1 into either the control group, whereby single blastocysts were selected for transfer by morphology alone, or the intervention group whereby final selection was decided by a commercially available time-lapse model. The embryologists at the time of blastocyst morphological scoring were blinded to which study group the patients would be randomized, and the physician and patients were blind to which group they were allocated until after the primary outcome was known. The primary outcome was number of ongoing pregnancies in the two groups. PARTICIPANTS/MATERIALS, SETTING, METHODS From 10 Nordic IVF clinics, 776 patients with a minimum of two good quality blastocysts on Day 5 (D5) were randomized into one of the two study groups. A commercial time-lapse model decided the final selection of blastocysts for 387 patients in the intervention (time-lapse) group, and blastocysts with the highest morphological score were transferred for 389 patients in the control group. Only single embryo transfers in fresh cycles were performed. MAIN RESULTS AND THE ROLE OF CHANCE In the full analysis set, the ongoing pregnancy rate for the time-lapse group was 47.4% (175/369) and 48.1% (181/376) in the control group. No statistically significant difference was found between the two groups: mean difference -0.7% (95% CI -8.2, 6.7, P = 0.90). Pregnancy rate (60.2% versus 59.0%, mean difference 1.1%, 95% CI -6.2, 8.4, P = 0.81) and early pregnancy loss (21.2% versus 18.5%, mean difference 2.7%, 95% CI -5.2, 10.6, P = 0.55) were the same for the time-lapse and the control group. Subgroup analyses showed that patient and treatment characteristics did not significantly affect the commercial time-lapse model D5 performance. In the time-lapse group, the choice of best blastocyst changed on 42% of occasions (154/369, 95% CI 36.9, 47.2) after the algorithm was applied, and this rate was similar for most treatment clinics. LIMITATIONS, REASONS FOR CAUTION During 2020, the patient recruitment rate slowed down at participating clinics owing to coronavirus disease-19 restrictions, so the target sample size was not achieved as planned and it was decided to stop the trial prematurely. The study only investigated embryo selection at the blastocyst stage on D5 in fresh IVF transfer cycles. In addition, only blastocysts of good morphological quality were considered for transfer, limiting the number of embryos for selection in both groups: also, it could be argued that this manual preselection of blastocysts limits the theoretical selection power of time-lapse, as well as restricting the results mainly to a good prognosis patient group. Most patients were aimed for blastocyst stage transfer when a minimum of five zygotes were available for extended culture. Finally, the primary clinical outcome evaluated was pregnancy to only 6-8 weeks. WIDER IMPLICATIONS OF THE FINDINGS The study suggests that time-lapse selection with a commercially available time-lapse model does not increase chance of ongoing pregnancy after single blastocyst transfer on Day 5 compared to morphology alone. STUDY FUNDING/COMPETING INTEREST(S) The study was financed by a grant from the Swedish state under the ALF-agreement between the Swedish government and the county councils (ALFGBG-723141). Vitrolife supported the study with embryo culture dishes and culture media. During the study period, T.H. changed his employment from Livio AB to Vitrolife AB. All other authors have no conflicts of interests to disclose. DATE OF FIRST PATIENT'S ENROLMENT 11 June 2018.
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| 11. |
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| 12. |
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| 13. |
- Allen-Perkins, Alfonso, et al.
(författare)
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CropPol : a dynamic, open and global database on crop pollination
- 2022
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Ingår i: Ecology. - : Wiley. - 0012-9658 .- 1939-9170. ; 103:3
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Tidskriftsartikel (refereegranskat)abstract
- Seventy five percent of the world's food crops benefit from insect pollination. Hence, there has been increased interest in how global change drivers impact this critical ecosystem service. Because standardized data on crop pollination are rarely available, we are limited in our capacity to understand the variation in pollination benefits to crop yield, as well as to anticipate changes in this service, develop predictions, and inform management actions. Here, we present CropPol, a dynamic, open and global database on crop pollination. It contains measurements recorded from 202 crop studies, covering 3,394 field observations, 2,552 yield measurements (i.e. berry weight, number of fruits and kg per hectare, among others), and 47,752 insect records from 48 commercial crops distributed around the globe. CropPol comprises 32 of the 87 leading global crops and commodities that are pollinator dependent. Malus domestica is the most represented crop (32 studies), followed by Brassica napus (22 studies), Vaccinium corymbosum (13 studies), and Citrullus lanatus (12 studies). The most abundant pollinator guilds recorded are honey bees (34.22% counts), bumblebees (19.19%), flies other than Syrphidae and Bombyliidae (13.18%), other wild bees (13.13%), beetles (10.97%), Syrphidae (4.87%), and Bombyliidae (0.05%). Locations comprise 34 countries distributed among Europe (76 studies), Northern America (60), Latin America and the Caribbean (29), Asia (20), Oceania (10), and Africa (7). Sampling spans three decades and is concentrated on 2001-05 (21 studies), 2006-10 (40), 2011-15 (88), and 2016-20 (50). This is the most comprehensive open global data set on measurements of crop flower visitors, crop pollinators and pollination to date, and we encourage researchers to add more datasets to this database in the future. This data set is released for non-commercial use only. Credits should be given to this paper (i.e., proper citation), and the products generated with this database should be shared under the same license terms (CC BY-NC-SA). This article is protected by copyright. All rights reserved.
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| 14. |
- Alvez, Maria Bueno, et al.
(författare)
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Next generation pan-cancer blood proteome profiling using proximity extension assay
- 2023
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- A comprehensive characterization of blood proteome profiles in cancer patients can contribute to a better understanding of the disease etiology, resulting in earlier diagnosis, risk stratification and better monitoring of the different cancer subtypes. Here, we describe the use of next generation protein profiling to explore the proteome signature in blood across patients representing many of the major cancer types. Plasma profiles of 1463 proteins from more than 1400 cancer patients are measured in minute amounts of blood collected at the time of diagnosis and before treatment. An open access Disease Blood Atlas resource allows the exploration of the individual protein profiles in blood collected from the individual cancer patients. We also present studies in which classification models based on machine learning have been used for the identification of a set of proteins associated with each of the analyzed cancers. The implication for cancer precision medicine of next generation plasma profiling is discussed.
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| 15. |
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| 16. |
- Dankiewicz, Josef, et al.
(författare)
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Hypothermia versus Normothermia after Out-of-Hospital Cardiac Arrest
- 2021
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Ingår i: New England Journal of Medicine. - : MASSACHUSETTS MEDICAL SOC. - 0028-4793 .- 1533-4406. ; 384:24, s. 2283-2294
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Tidskriftsartikel (refereegranskat)abstract
- Hypothermia or Normothermia after Cardiac Arrest This trial randomly assigned patients with coma after out-of-hospital cardiac arrest to undergo targeted hypothermia at 33 degrees C or normothermia with treatment of fever. At 6 months, there were no significant between-group differences regarding death or functional outcomes. Background Targeted temperature management is recommended for patients after cardiac arrest, but the supporting evidence is of low certainty. Methods In an open-label trial with blinded assessment of outcomes, we randomly assigned 1900 adults with coma who had had an out-of-hospital cardiac arrest of presumed cardiac or unknown cause to undergo targeted hypothermia at 33 degrees C, followed by controlled rewarming, or targeted normothermia with early treatment of fever (body temperature, >= 37.8 degrees C). The primary outcome was death from any cause at 6 months. Secondary outcomes included functional outcome at 6 months as assessed with the modified Rankin scale. Prespecified subgroups were defined according to sex, age, initial cardiac rhythm, time to return of spontaneous circulation, and presence or absence of shock on admission. Prespecified adverse events were pneumonia, sepsis, bleeding, arrhythmia resulting in hemodynamic compromise, and skin complications related to the temperature management device. Results A total of 1850 patients were evaluated for the primary outcome. At 6 months, 465 of 925 patients (50%) in the hypothermia group had died, as compared with 446 of 925 (48%) in the normothermia group (relative risk with hypothermia, 1.04; 95% confidence interval [CI], 0.94 to 1.14; P=0.37). Of the 1747 patients in whom the functional outcome was assessed, 488 of 881 (55%) in the hypothermia group had moderately severe disability or worse (modified Rankin scale score >= 4), as compared with 479 of 866 (55%) in the normothermia group (relative risk with hypothermia, 1.00; 95% CI, 0.92 to 1.09). Outcomes were consistent in the prespecified subgroups. Arrhythmia resulting in hemodynamic compromise was more common in the hypothermia group than in the normothermia group (24% vs. 17%, P<0.001). The incidence of other adverse events did not differ significantly between the two groups. Conclusions In patients with coma after out-of-hospital cardiac arrest, targeted hypothermia did not lead to a lower incidence of death by 6 months than targeted normothermia. (Funded by the Swedish Research Council and others; TTM2 ClinicalTrials.gov number, .)
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| 17. |
- Elissa, Kawther, et al.
(författare)
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Self-Perceived Health Status and Sense of Coherence in Children With Type 1 Diabetes in the West Bank, Palestine.
- 2020
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Ingår i: Journal of transcultural nursing : official journal of the Transcultural Nursing Society. - : SAGE Publications. - 1552-7832. ; 31:2
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Tidskriftsartikel (refereegranskat)abstract
- Self-perceived health status and sense of coherence (SOC) are essential constructs for capturing health outcomes in children with type 1 diabetes (T1D). This study measured self-perceived health status and SOC in children with T1D and compared them with a healthy reference group in West Bank, Palestine.One hundred children with T1D aged 8 to 18 years and 300 healthy children completed PedsQL 4.0 Generic Core Scales and SOC-13 in a cross-sectional descriptive study.All children reported acceptable self-perceived health status and low degree of SOC. In the diabetes group, high degree of SOC was associated with better self-perceived health status and more optimal metabolic control. Males in the diabetes group reported higher self-perceived health status than females.The unstable political situation in Palestine may threaten SOC in children in general. Health professionals can monitor self-perceived health status and SOC to evaluate interventions aiming to improve glycemic control.
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| 18. |
- Foster, Rachel A., et al.
(författare)
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Richelia
- 2022
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Ingår i: Bergey's Manual of Systematics of Archaea and Bacteria. - : John Wiley & Sons. - 9781118960608 ; , s. 1-17
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Bokkapitel (refereegranskat)abstract
- Ri.che'li.a. N.L. fem. n. Richelia, named for the Danish admiral Andreas du Plessis de Richelieu (1852–1932).Cyanobacteria / Cyanobacteria / Cyanobacteriales / Nostocaceae / RicheliaFilamentous heterocyst-forming, Gram-stain-negative, aerobic, phototrophic, N2-fixing, and occurring either as free-living or most often associated with several marine diatom genera (Rhizosolenia, Hemiaulus, and Chaetoceros). Filaments (trichomes) contain variable numbers of sheathless vegetative cells and one terminal heterocyst. Filaments lack akinetes and have limited motility via gliding. Gas vesicles are absent. Cyanophycin granules can be present in vegetative cells and heterocysts. Glycogen appears as large deposits, and thylakoids are dispersed randomly. Reproduce by normal cell division and asynchronous with one host diatom Rhizosolenia. DNA G + C content (mol%) from draft genomes varies 33–39%; genome size varies 3.42–6.04 Mb. Reduces atmospheric N2 with nitrogenase. Known habitats are warm (24–27.5°C), marine, and oligotrophic seas with intermediate (32 PSU) to fully marine (36 PSU) salinities. Biogeochemically relevant as N2 fixers and drivers of carbon export. Have been reported in all major ocean basins (Atlantic, Pacific, and Indian) and smaller seas (Mediterranean Sea and Red Sea).DNA G + C content (mol%): 33–39 (genome sequence).Type species: Richelia intracellularis Schmidt in Ostenfeld and Schmidt 1901.
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| 19. |
- Girardi, P., et al.
(författare)
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Anti-Toxin Responses to Natural Enterotoxigenic Escherichia coli (ETEC) Infection in Adults and Children in Bangladesh
- 2023
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Ingår i: Microorganisms. - 2076-2607. ; 11:10
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Tidskriftsartikel (refereegranskat)abstract
- A sero-epidemiology study was conducted in Dhaka, Bangladesh between January 2020 and February 2021 to assess the immune responses to ETEC infection in adults and children. (1) Background: Enterotoxigenic Escherichia coli infection is a main cause of diarrheal disease in endemic countries. The characterization of the immune responses evoked by natural infection can guide vaccine development efforts. (2) Methods: A total of 617 adult and 480 pediatric diarrheal patients were screened, and 43 adults and 46 children (below 5 years of age) with an acute ETEC infection completed the study. The plasma samples were analyzed for antibody responses against the ETEC toxins. (3) Results: Heat-stable toxin (ST)-positive ETEC is the main cause of ETEC infection in adults, unlike in children in an endemic setting. We detected very low levels of anti-ST antibodies, and no ST-neutralizing activity. However, infection with ETEC strains expressing the heat-labile toxin (LT) induced systemic antibody responses in less than 25% of subjects. The antibody levels against LTA and LTB, as well as cholera toxin (CT), correlated well. The anti-LT antibodies were shown to have LT- and CT- neutralizing activity. The antibody reactivity against linear LT epitopes did not correlate with toxin-neutralizing activity. (4) Conclusions: Unlike LT, ST is a poor antigen and even adults have low anti-ST antibody levels that do not allow for the detection of toxin-neutralizing activity.
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| 20. |
- Golub, Malgorzata, et al.
(författare)
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Diel, seasonal, and inter-annual variation in carbon dioxide effluxes from lakes and reservoirs
- 2023
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Ingår i: Environmental Research Letters. - : IOP Publishing. - 1748-9326. ; 18:3
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Tidskriftsartikel (refereegranskat)abstract
- Accounting for temporal changes in carbon dioxide (CO2) effluxes from freshwaters remains a challenge for global and regional carbon budgets. Here, we synthesize 171 site-months of flux measurements of CO2 based on the eddy covariance method from 13 lakes and reservoirs in the Northern Hemisphere, and quantify dynamics at multiple temporal scales. We found pronounced sub-annual variability in CO2 flux at all sites. By accounting for diel variation, only 11% of site-months were net daily sinks of CO2. Annual CO2 emissions had an average of 25% (range 3%-58%) interannual variation. Similar to studies on streams, nighttime emissions regularly exceeded daytime emissions. Biophysical regulations of CO2 flux variability were delineated through mutual information analysis. Sample analysis of CO2 fluxes indicate the importance of continuous measurements. Better characterization of short- and long-term variability is necessary to understand and improve detection of temporal changes of CO2 fluxes in response to natural and anthropogenic drivers. Our results indicate that existing global lake carbon budgets relying primarily on daytime measurements yield underestimates of net emissions.
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| 21. |
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| 22. |
- Gudmundsson, Jon Tomas, 1965-, et al.
(författare)
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Ionization region model of high power impulse magnetron sputtering of copper
- 2022
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Ingår i: Surface & Coatings Technology. - : ELSEVIER SCIENCE SA. - 0257-8972 .- 1879-3347. ; 442
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Tidskriftsartikel (refereegranskat)abstract
- The ionization region model (IRM) is applied to model high power impulse magnetron sputtering (HiPIMS) discharges with a Cu target. We apply the model to three discharges that were experimentally explored in the past, or applied to deposit thin copper films, with the aim to quantify internal plasma process parameters and thereby understand how these discharges differ from each other. The temporal variation of the various neutral and ionic species, the electron density and temperature, as well as internal discharge parameters, such as the ionization probability, back attraction probability, and ionized flux fraction of the sputtered species, are determined. We demonstrate that the Cu+ ions dominate the total ion current to the target surface and that all the discharges are dominated by self-sputter recycling to reach high discharge currents. Furthermore, the ion flux into the diffusion region is dominated by Cu+ ions, which represents roughly 80% of the total ion flux onto the substrate, in agreement with experimental findings. For the discharges operated with peak discharge current densities in the range 0.9 - 1.3 A cm-2, the ion back-attraction probability of the Cu+ ion (beta t) is low compared to previously investigated HiPIMS discharges, or in the range 44 - 50%, while the ionization probability (alpha t) is in the range 61 - 69%, and the ionized flux fraction is in the range 32 - 40%. It is, furthermore, found that operating these Cu HiPIMS discharges at lower working gas pressures (in the present case around 0.5 Pa) is beneficial in terms of optimizing ionization of the sputtered species.
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| 23. |
- Gupta, Dhanu, et al.
(författare)
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Amelioration of systemic inflammation via the display of two different decoy protein receptors on extracellular vesicles
- 2021
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Ingår i: Nature Biomedical Engineering. - Stockholm : Karolinska Institutet, Dept of Laboratory Medicine. - 2157-846X.
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Tidskriftsartikel (refereegranskat)abstract
- Extracellular vesicles (EVs) can be functionalized to display specific protein receptors on their surface. However, surface-display technology typically labels only a small fraction of the EV population. Here, we show that the joint display of two different therapeutically relevant protein receptors on EVs can be optimized by systematically screening EV-loading protein moieties. We used cytokine-binding domains derived from tumour necrosis factor receptor 1 (TNFR1) and interleukin-6 signal transducer (IL-6ST), which can act as decoy receptors for the pro-inflammatory cytokines tumour necrosis factor alpha (TNF-α) and IL-6, respectively. We found that the genetic engineering of EV-producing cells to express oligomerized exosomal sorting domains and the N-terminal fragment of syntenin (a cytosolic adaptor of the single transmembrane domain protein syndecan) increased the display efficiency and inhibitory activity of TNFR1 and IL-6ST and facilitated their joint display on EVs. In mouse models of systemic inflammation, neuroinflammation and intestinal inflammation, EVs displaying the cytokine decoys ameliorated the disease phenotypes with higher efficacy as compared with clinically approved biopharmaceutical agents targeting the TNF-α and IL-6 pathways.
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| 24. |
- Hallgren, M, et al.
(författare)
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Cross-sectional and prospective relationships of passive and mentally active sedentary behaviours and physical activity with depression
- 2020
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Ingår i: The British journal of psychiatry : the journal of mental science. - : Royal College of Psychiatrists. - 1472-1465. ; 217:2, s. 413-419
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Tidskriftsartikel (refereegranskat)abstract
- Sedentary behaviour can be associated with poor mental health, but it remains unclear whether all types of sedentary behaviour have equivalent detrimental effects.AimsTo model the potential impact on depression of replacing passive with mentally active sedentary behaviours and with light and moderate-to-vigorous physical activity. An additional aim was to explore these relationships by self-report data and clinician diagnoses of depression.MethodIn 1997, 43 863 Swedish adults were initially surveyed and their responses linked to patient registers until 2010. The isotemporal substitution method was used to model the potential impact on depression of replacing 30 min of passive sedentary behaviour with equivalent durations of mentally active sedentary behaviour, light physical activity or moderate-to-vigorous physical activity. Outcomes were self-reported depression symptoms (cross-sectional analyses) and clinician-diagnosed incident major depressive disorder (MDD) (prospective analyses).ResultsOf 24 060 participants with complete data (mean age 49.2 years, s.d. 15.8, 66% female), 1526 (6.3%) reported depression symptoms at baseline. There were 416 (1.7%) incident cases of MDD during the 13-year follow-up. Modelled cross-sectionally, replacing 30 min/day of passive sedentary behaviour with 30 min/day of mentally active sedentary behaviour, light physical activity and moderate-to-vigorous activity reduced the odds of depression symptoms by 5% (odds ratio 0.95, 95% CI 0.94–0.97), 13% (odds ratio 0.87, 95% CI 0.76–1.00) and 19% (odds ratio 0.81, 95% CI 0.93–0.90), respectively. Modelled prospectively, substituting 30 min/day of passive with 30 min/day of mentally active sedentary behaviour reduced MDD risk by 5% (hazard ratio 0.95, 95% CI 0.91–0.99); no other prospective associations were statistically significant.ConclusionsSubstituting passive with mentally active sedentary behaviours, light activity or moderate-to-vigorous activity may reduce depression risk in adults.
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| 25. |
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| 26. |
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| 27. |
- Isaksson, Johan, et al.
(författare)
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Nonshared environmental factors in the aetiology of autism and other neurodevelopmental conditions : a monozygotic co-twin control study.
- 2022
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Ingår i: Molecular autism. - : Springer Nature. - 2040-2392. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: A significant proportion of variation in likelihood of neurodevelopmental conditions (NDCs) has been attributed to nonshared environmental (NSE) factors, although it remains unclear which NSE factors pose specific risks for certain NDCs.METHODS: A monozygotic co-twin design was applied in a sample of 224 twins (mean age = 17.70 years, SD = 6.28) controlling for confounders such as genes and shared environment. Generalized estimating equation models were fitted, using perinatal and postnatal indications of NSEs as exposure, operationalized both as separate risk factors and as cumulative risk loads. Categorical and dimensional operationalizations of autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), intellectual disability and other NDCs were used as outcomes.RESULTS: Birth weight discordance was associated with dimensional autism and ADHD for the smaller twin, and medication during infancy was associated with dimensional autism. Among postnatal factors scarlet fever during early childhood was associated with lower IQ. Especially autism was associated with a greater cumulative perinatal or postnatal risk load.LIMITATIONS: When exploring the associations between each condition and specific NSEs the risk of being statistically underpowered increases. Hence, we limit the reported findings on specific indicators of NSEs to trait levels and present descriptive data for categorical NDCs.CONCLUSIONS: The findings support previous research by indicating an association between exposure to perinatal and postnatal risks and subsequent NDCs within twin pairs and suggest that autism may be especially linked to accumulative early environmental risks. The findings are potentially important for developmental outcomes prognoses and may inform targeted prevention and early interventions.
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| 28. |
- Lundin, Erik, 1970-, et al.
(författare)
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Radiotherapy as Elective Treatment of the Node-negative Neck in Oral Squamous Cell Cancer
- 2021
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Ingår i: Anticancer Research. - : International Institute of Anticancer Research. - 0250-7005 .- 1791-7530. ; 41:7, s. 3489-3498
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND/AIM: Previous studies of node-negative oral squamous cell carcinoma have shown a benefit of elective neck dissection compared to observation. Evidence for radiotherapy as single-modality elective treatment of the node-negative neck is so far lacking.PATIENTS AND METHODS: In a retrospective material of 420 early-stage oral cancers from 2000 to 2016, overall survival, disease-free survival, and regional relapse-free survival were calculated with the Kaplan-Meier method.RESULTS: At five years, overall survival was 59.7%, disease-specific survival was 77.2%, and regional relapse-free survival was 83.5%. Among those with adjuvant treatment of the neck after surgery of T1-T2 tumours during 2009-2016, regional relapse-free survival at five years was 85.7% for elective radiotherapy of the neck and 87.4% for elective neck dissection.CONCLUSION: Elective radiotherapy to the neck with a modern technique and adequate dose might be an alternative to neck dissection for patients with early-stage oral squamous cell cancer.
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| 29. |
- Lundin, Linus, 1993, et al.
(författare)
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Powered Two-Wheeler Rider Thoracic Impact Loading in Crashes with the Side of Passenger Cars: Literature Review and Human Body Model Validation
- 2023
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Ingår i: Conference proceedings International Research Council on the Biomechanics of Injury, IRCOBI. - 2235-3151. ; , s. 445-468
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Konferensbidrag (refereegranskat)abstract
- Globally, powered two-wheeler (PTW) riders constitute a vulnerable road user group. This study aims to enhance the understanding of thoracic loading experienced by PTW riders in one of the most common crash configurations, PTW front to passenger car side (PFCS) impacts. A scoping review of the literature identified impact parameters describing common thoracic loading in terms of direction, location, distribution, and magnitude. Four experimental hub and bar post-mortem human subject (PMHS) test series, covering some of the identified variations in thoracic loading, were selected to validate the thorax of the SAFER human body model (HBM). The SAFER HBM demonstrated fair kinetics and kinematics biofidelity for frontal and oblique hub impacts and poor to fair biofidelity for the bar impacts. However, the SAFER HBM can accurately predict the rib fracture risk estimated from the PMHS tests. The findings demonstrate the potential of current HBMs to represent PTW-specific thoracic loading and support development of PTW rider safety systems in upright PFCS impacts. It also highlights a need for novel PMHS tests, in particular ones where the thorax is loaded above mid sternum and preferably including a vertical force component.
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| 30. |
- Lundin, Magnus, et al.
(författare)
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Prognostic utility and characterization of left ventricular hypertrophy using global thickness
- 2023
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Ingår i: Scientific Reports. - 2045-2322. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Cardiovascular magnetic resonance (CMR) can accurately measure left ventricular (LV) mass, and several measures related to LV wall thickness exist. We hypothesized that prognosis can be used to select an optimal measure of wall thickness for characterizing LV hypertrophy. Subjects having undergone CMR were studied (cardiac patients, n = 2543; healthy volunteers, n = 100). A new measure, global wall thickness (GT, GTI if indexed to body surface area) was accurately calculated from LV mass and end-diastolic volume. Among patients with follow-up (n = 1575, median follow-up 5.4 years), the most predictive measure of death or hospitalization for heart failure was LV mass index (LVMI) (hazard ratio (HR)[95% confidence interval] 1.16[1.12-1.20], p < 0.001), followed by GTI (HR 1.14[1.09-1.19], p < 0.001). Among patients with normal findings (n = 326, median follow-up 5.8 years), the most predictive measure was GT (HR 1.62[1.35-1.94], p < 0.001). GT and LVMI could characterize patients as having a normal LV mass and wall thickness, concentric remodeling, concentric hypertrophy, or eccentric hypertrophy, and the three abnormal groups had worse prognosis than the normal group (p < 0.05 for all). LV mass is highly prognostic when mass is elevated, but GT is easily and accurately calculated, and adds value and discrimination amongst those with normal LV mass (early disease).
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| 31. |
- Lundin, Samuel B, 1970, et al.
(författare)
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A novel precision-serology assay for SARS-CoV-2 infection based on linear B-cell epitopes of Spike protein
- 2023
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Ingår i: Frontiers in Immunology. - 1664-3224. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- IntroductionThe COVID-19 pandemic illustrates the need for serology diagnostics with improved accuracy. While conventional serology based on recognition of entire proteins or subunits thereof has made significant contribution to the antibody assessment space, it often suffers from sub-optimal specificity. Epitope-based, high-precision, serology assays hold potential to capture the high specificity and diversity of the immune system, hence circumventing the cross-reactivity with closely related microbial antigens. MethodsWe herein report mapping of linear IgG and IgA antibody epitopes of the SARS-CoV-2 Spike (S) protein in samples from SARS-CoV-2 exposed individuals along with certified SARS-CoV-2 verification plasma samples using peptide arrays. ResultsWe identified 21 distinct linear epitopes. Importantly, we showed that pre-pandemic serum samples contain IgG antibodies reacting to the majority of protein S epitopes, most likely as a result of prior infection with seasonal coronaviruses. Only 4 of the identified SARS-CoV-2 protein S linear epitopes were specific for SARS-CoV-2 infection. These epitopes are located at positions 278-298 and 550-586, just proximal and distal to the RBD, as well as at position 1134-1156 in the HR2 subdomain and at 1248-1271 in the C-terminal subdomain of protein S. To substantiate the applicability of our findings, we tested three of the high-accuracy protein S epitopes in a Luminex assay, using a certified validation plasma sample set from SARS-CoV-2 infected individuals. The Luminex results were well aligned with the peptide array results, and correlated very well with in-house and commercial immune assays for RBD, S1 and S1/S2 domains of protein S. ConclusionWe present a comprehensive mapping of linear B-cell epitopes of SARS-CoV-2 protein S, that identifies peptides suitable for a precision serology assay devoid of cross-reactivity. These results have implications for development of highly specific serology test for exposure to SARS-CoV-2 and other members of the coronaviridae family, as well as for rapid development of serology tests for future emerging pandemic threats.
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| 32. |
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| 33. |
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| 34. |
- Lundin-Ström, Kristina B., et al.
(författare)
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Parental origin of monosomy 7 in acute leukaemia
- 2021
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Ingår i: British Journal of Haematology. - : Wiley-Blackwell Publishing Inc.. - 0007-1048 .- 1365-2141. ; 192:5, s. e132-e135
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
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| 35. |
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| 36. |
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| 37. |
- Ovaskainen, Otso, et al.
(författare)
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Global Spore Sampling Project: A global, standardized dataset of airborne fungal DNA
- 2024
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Ingår i: Scientific Data. - 2052-4463. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Novel methods for sampling and characterizing biodiversity hold great promise for re-evaluating patterns of life across the planet. The sampling of airborne spores with a cyclone sampler, and the sequencing of their DNA, have been suggested as an efficient and well-calibrated tool for surveying fungal diversity across various environments. Here we present data originating from the Global Spore Sampling Project, comprising 2,768 samples collected during two years at 47 outdoor locations across the world. Each sample represents fungal DNA extracted from 24 m3 of air. We applied a conservative bioinformatics pipeline that filtered out sequences that did not show strong evidence of representing a fungal species. The pipeline yielded 27,954 species-level operational taxonomic units (OTUs). Each OTU is accompanied by a probabilistic taxonomic classification, validated through comparison with expert evaluations. To examine the potential of the data for ecological analyses, we partitioned the variation in species distributions into spatial and seasonal components, showing a strong effect of the annual mean temperature on community composition.
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| 38. |
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| 39. |
- Pisanu, Claudia, et al.
(författare)
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Major depression subtypes are differentially associated with migraine subtype, prevalence and severity
- 2020
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Ingår i: Cephalalgia. - : SAGE Publications. - 0333-1024 .- 1468-2982. ; 40:4, s. 347-356
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Migraine and major depressive disorder show a high rate of comorbidity, but little is known about the associations between the subtypes of major depressive disorder and migraine. In this cross-sectional study we aimed at investigating a) the lifetime associations between the atypical, melancholic, combined and unspecified subtype of major depressive disorder and migraine with and without aura and b) the associations between major depressive disorder and its subtypes and the severity of migraine.METHODS: A total of 446 subjects with migraine (migraine without aura: n = 294; migraine with aura: n = 152) and 2511 controls from the population-based CoLaus/PsyCoLaus study, Switzerland, were included. Associations between major depressive disorder subtypes and migraine characteristics were tested using binary logistic or linear regression.RESULTS: Melancholic, combined and unspecified major depressive disorder were associated with increased frequency of migraine with aura, whereas only melancholic major depressive disorder was associated with increased frequency of migraine without aura. Lifetime and unspecified major depressive disorder were associated with severe migraine intensity among subjects with migraine with aura but not migraine without aura, while combined major depressive disorder was associated with higher migraine frequency independently from migraine subtype.CONCLUSION: This study suggests that melancholic but not atypical major depressive disorder is associated with migraine and migraine subtypes. Future studies exploring pathophysiological mechanisms shared between melancholic depression and migraine are warranted.
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| 40. |
- Remberger, Mats, et al.
(författare)
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The CD34+ Cell Dose Matters in Hematopoietic Stem Cell Transplantation with Peripheral Blood Stem Cells from Sibling Donors
- 2020
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Ingår i: Clinical Hematology International. - : Springer Science and Business Media LLC. - 2590-0048. ; 2:2, s. 74-81
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Tidskriftsartikel (refereegranskat)abstract
- The effect of CD34+ cell dose in allogeneic hematopoietic stem cell transplantation (HSCT) on overall survival (OS) and incidence of acute and chronic graft-versus-host disease (GvHD) has not been established and few studies have been performed. Our single center analysis included 189 patients with hematological malignancies who received peripheral blood stem cell (PBSC) grafts from sibling donors. Myeloablative conditioning was used in 88 cases and 101 received reduced intensity conditioning. The median CD34+ cell dose was 5.6 × 106/kg (0.6–17.0). In the multivariate analysis, a CD34 cell dose of 6–7 × 106/kg was associated with better OS and lower transplant-related mortality (TRM), while a dose of <5 × 106/kg led to increased relapse and reduced chronic GVHD (cGVHD). A high CD34 cell-dose (>6.5 × 106/kg) correlated with less acute GVHD (aGVHD) II–IV. We conclude that the CD34 cell dose has an impact on the outcome of HSCT from sibling donor PBSCs.
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| 41. |
- Riggi, Laura, et al.
(författare)
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Early-season mass-flowering crop cover dilutes wild bee abundance and species richness in temperate regions : A quantitative synthesis
- 2024
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Ingår i: Journal of Applied Ecology. - 0021-8901 .- 1365-2664. ; 61:3, s. 452-464
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Tidskriftsartikel (refereegranskat)abstract
- Pollinators benefit from increasing floral resources in agricultural landscapes, which could be an underexplored co-benefit of mass-flowering crop cultivation. However, the impacts of mass-flowering crops on pollinator communities are complex and appear to be context-dependent, mediated by factors such as crop flowering time and the availability of other flower resources in the landscape. A synthesis of research is needed to develop management recommendations for effective pollinator conservation in agroecosystems. By combining 22 datasets from 13 publications conducted in nine temperate countries (20 European, 2 North American), we investigated if mass-flowering crop flowering time (early or late season), bloom state (during or after crop flowering) and extent of non-crop habitat cover in the landscape moderated the effect of mass-flowering crop cover on wild pollinator abundance and species richness in mass-flowering crop and non-crop habitats. During bloom, wild bee abundance and richness are negatively related to mass-flowering crop cover. Dilution effects were predominant in crop habitats and early in the season, except for bumblebees, which declined with mass-flowering crop cover irrespective of habitat or season. Late in the season and in non-crop habitats, several of these negative relationships were either absent or reversed. Late-season mass-flowering crop cover is positively related to honeybee abundance in crop habitats and to other bee abundance in non-crop habitats. These results indicate that crop-adapted species, like honeybees, move to forage and concentrate on late-season mass-flowering crops at a time when flower availability in the landscape is limited, potentially alleviating competition for flower resources in non-crop habitats. We found no evidence of pollinators moving from mass-flowering crop to non-crop habitats after crop bloom. Synthesis and applications: Our results confirm that increasing early-season mass-flowering crop cover dilutes wild pollinators in crop habitats during bloom. We find that dilution effects were absent late in the season. While mass-flowering crop cultivation alone is unlikely to be sufficient for maintaining pollinators, as part of carefully designed diverse crop rotations or mixtures combined with the preservation of permanent non-crop habitats, it might provide valuable supplementary food resources for pollinators in temperate agroecosystems, particularly later in the season when alternative flower resources are scarce.
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| 42. |
- Schiffer, Christian, et al.
(författare)
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Structural inheritance in the North Atlantic
- 2020
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Ingår i: Earth-Science Reviews. - : Elsevier BV. - 0012-8252 .- 1872-6828. ; 206
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Forskningsöversikt (refereegranskat)abstract
- The North Atlantic, extending from the Charlie Gibbs Fracture Zone to the north Norway-Greenland-Svalbard margins, is regarded as both a classic case of structural inheritance and an exemplar for the Wilson-cycle concept. This paper examines different aspects of structural inheritance in the Circum-North Atlantic region: 1) as a function of rejuvenation from lithospheric to crustal scales, and 2) in terms of sequential rifting and opening of the ocean and its margins, including a series of failed rift systems. We summarise and evaluate the role of fundamental lithospheric structures such as mantle fabric and composition, lower crustal inhomogeneities, orogenic belts, and major strike-slip faults during breakup. We relate these to the development and shaping of the NE Atlantic rifted margins, localisation of magmatism, and microcontinent release. We show that, although inheritance is common on multiple scales, the Wilson Cycle is at best an imperfect model for the Circum-North Atlantic region. Observations from the NE Atlantic suggest depth dependency in inheritance (surface, crust, mantle) with selective rejuvenation depending on time-scales, stress field orientations and thermal regime. Specifically, post-Caledonian reactivation to form the North Atlantic rift systems essentially followed pre-existing orogenic crustal structures, while eventual breakup reflected a change in stress field and exploitation of a deeper-seated, lithospheric-scale shear fabrics. We infer that, although collapse of an orogenic belt and eventual transition to a new ocean does occur, it is by no means inevitable.
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| 43. |
- Viloan, Rommel Paulo B., 1988-
(författare)
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Engineered ion-bombardment as a tool in thin film deposition
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Energetic-ion bombardment has become an attractive route to modify the crystal growth and deposit high quality thin films. In high-power impulse magnetron sputtering (HiPIMS) where the discharge is characterized by a significant amount of ions of the sputter-ejected atoms, energetic-ion bombardment effects could not be underestimated. This is due to a combination of ions with better mass match to the growing film and reduced incorporation of the working gas. The ions of the sputtered species in HiPIMS also exhibit a broad ion energy distribution function (IEDF), which increases the average energy of the ion flux. However, the IEDF of a HiPIMS discharge is still dominated by ions with energies corresponding to thermalized species. While it is common to use a substrate bias to increase the energy of the incoming ion flux, some deposition set-up make it challenging or even impossible to apply a substrate bias. Hence, it is important to come up with techniques to address such problem. In this thesis, strategies to increase the energy of the ions in a HiPIMS discharge without any substrate bias were investigated and thin films were deposited to evaluate the effects on the crystal growth and film properties.By varying the power per pulse (Ppulse) in a HiPIMS discharge for the deposition of TiN, it was found that the amount of Ti2+ ions could be effectively tuned. The increase in the amount of Ti2+ correlated well with an increase in the film compressive stress, though an optimum Ppulse could be identified in which the stress is relatively low and hardness is high. The results also indicate a broad IEDF for ions of the sputtered species (Ti+, Ti2+, N+) and narrow IEDF for ions of the working gas (Ar+, Ar2+, N2+). However, using such strategy results to an increase in the average ion energy only within the range of <25 eV.Operating a HiPIMS discharge in bipolar mode, where a positive pulse voltage (Urev) is immediately applied after the main HiPIMS pulse, results to ion acceleration due to an increase in the plasma potential to values close to Urev. A simple model is proposed indicating that ion acceleration occurs at a region in between the target and the grounded substrate. Further IEDF measurements with bipolar HiPIMS with varying length of the main HiPIMS pulse (τneg) and length of the positive pulse (τpos) indicate that most of the acceleration happens at the sheath in front of a grounded substrate. By varying τneg and τpos, it was shown that the fraction of accelerated ions can be optimized such that almost all ions are accelerated when τneg is relatively short and τpos is sufficiently long. The growth of TiN films indicate an increase in the compressive stress, hardness and density with an increase in Urev, typical for films deposited using energetic-ion bombardment. Finally, Cu depositions indicate that, due to the pulsed nature of Urev and since most of the ion acceleration happens at the substrate sheath, bipolar HiPIMS process can be compared to a conventional HiPIMS pulse with a synchronized pulsed bias, which has the same timing as the applied positive pulse.
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| 44. |
- Viloan, Rommel Paulo B., 1988-, et al.
(författare)
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Pulse length selection for optimizing the accelerated ion flux fraction of a bipolar HiPIMS discharge
- 2021
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Ingår i: Plasma sources science & technology. - : Institute of Physics Publishing (IOPP). - 0963-0252 .- 1361-6595. ; 29:12
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Tidskriftsartikel (refereegranskat)abstract
- The effect on the energy distributions of metal and gas ions in a bipolar high-power impulse magnetron sputtering (HiPIMS) discharge as the negative and positive pulse lengths are altered are reported. The results presented demonstrate that the selection of the pulse lengths in a HiPIMS discharge is important in optimizing the amount of accelerated ions. A short enough negative pulse is needed so that ions do not escape to the substrate before being accelerated by the positive pulse that follows the main negative HiPIMS pulse. The length of the positive pulse should also be long enough to accelerate the majority of the ions, but a too long positive pulse depletes the process chamber of electrons so much that it makes it difficult to initiate the next HiPIMS pulse. When pulse lengths of negative and positive pulses are properly selected, the fraction of ions, both metal and gas, accelerated by the positive pulse voltage is close to 100 %.
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| 45. |
- Viloan, Rommel Paulo B., 1988-, et al.
(författare)
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Tuning the stress in TiN films by regulating the doubly charged ion fraction in a reactive HiPIMS discharge
- 2020
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Ingår i: Journal of Applied Physics. - : AIP Publishing. - 0021-8979 .- 1089-7550. ; 127:10
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Tidskriftsartikel (refereegranskat)abstract
- In the present study, we investigate the impact of pulse power (Ppulse) on the ion flux and the properties of TiN films using reactive high-power impulse magnetron sputtering. Ppulse was adjusted in the range of 5–25 kW, while keeping the total average power constant through regulating the pulsing frequency. It is found that the required N2 flow, to produce stoichiometric TiN, decreases as Ppulse is increased, which is due to a decrease in the deposition rate. The plasma conditions when stoichiometric TiN is formed were investigated in detail. In situ ion mass spectrometry measurements of the ion energy distribution functions reveal two distinct ion populations, ions originating from sputtered atoms (Ti+, Ti2+, and N+) and ions originating from the working gas (Ar+, Ar2+, and N2+). The average ion energies (Eave) of the sputtered ions show an increase with increasing Ppulse, while Eave for the gas ions remains almost unaffected. The relative flux intensity Ti2+/Ti+ showed an increasing trend, from 0.28 to 0.47, as Ppulse was increased from 5 to 25 kW. The ion flux changes affect the growth of the TiN film such that 111-textured films are grown for low Ppulse while higher Ppulse results in mixed orientations. In addition, the hardness of the deposited film increases with increasing Ppulse, while the compressive film stress increases significantly at a higher Ppulse. In this way, optimum deposition conditions were identified at Ppulse = 8.3 kW, where a relatively low compressive stress of 0.89 GPa and high hardness of 22.67 GPa were measured.
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| 46. |
- Walsh, Roddy, et al.
(författare)
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Enhancing rare variant interpretation in inherited arrhythmias through quantitative analysis of consortium disease cohorts and population controls
- 2021
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Ingår i: Genetics in Medicine. - : Nature Publishing Group. - 1098-3600 .- 1530-0366. ; 23:1, s. 47-58
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Stringent variant interpretation guidelines can lead to high rates of variants of uncertain significance (VUS) for genetically heterogeneous disease like long QT syndrome (LQTS) and Brugada syndrome (BrS). Quantitative and disease-specific customization of American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) guidelines can address this false negative rate.Methods: We compared rare variant frequencies from 1847 LQTS (KCNQ1/KCNH2/SCN5A) and 3335 BrS (SCN5A) cases from the International LQTS/BrS Genetics Consortia to population-specific gnomAD data and developed disease-specific criteria for ACMG/AMP evidence classes-rarity (PM2/BS1 rules) and case enrichment of individual (PS4) and domain-specific (PM1) variants.Results: Rare SCN5A variant prevalence differed between European (20.8%) and Japanese (8.9%) BrS patients (p = 5.7 x 10(-18)) and diagnosis with spontaneous (28.7%) versus induced (15.8%) Brugada type 1 electrocardiogram (ECG) (p = 1.3 x 10(-13)). Ion channel transmembrane regions and specific N-terminus (KCNH2) and C-terminus (KCNQ1/KCNH2) domains were characterized by high enrichment of case variants and >95% probability of pathogenicity. Applying the customized rules, 17.4% of European BrS and 74.8% of European LQTS cases had (likely) pathogenic variants, compared with estimated diagnostic yields (case excess over gnomAD) of 19.2%/82.1%, reducing VUS prevalence to close to background rare variant frequency.Conclusion: Large case-control data sets enable quantitative implementation of ACMG/AMP guidelines and increased sensitivity for inherited arrhythmia genetic testing.
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| 47. |
- Yammine, Sahar, et al.
(författare)
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Dietary and Circulating Fatty Acids and Ovarian Cancer Risk in the European Prospective Investigation into Cancer and Nutrition
- 2020
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - Philadelphia : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 29:9, s. 1739-1749
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Tidskriftsartikel (refereegranskat)abstract
- Background: Fatty acids impact obesity, estrogens, and inflammation, which are risk factors for ovarian cancer. Few epidemiologic studies have investigated the association of fatty acids with ovarian cancer.Methods: Within the European Prospective Investigation into Cancer and Nutrition (EPIC), 1,486 incident ovarian cancer cases were identified. Cox proportional hazard models with adjustment for ovarian cancer risk factors were used to estimate HRs of ovarian cancer across quintiles of intake of fatty acids. False discovery rate was computed to control for multiple testing. Multivariable conditional logistic regression models were used to estimate ORs of ovarian cancer across tertiles of plasma fatty acids among 633 cases and two matched controls in a nested case-control analysis.Results: Apositive association was found between ovarian cancer and intake of industrial trans elaidic acid [HR comparing fifth with first quintile(Q5-Q1) = 1.29; 95% confidence interval (CI) = 1.03-1.62; P-trend = 0.02, q-value = 0.06]. Dietary intakes of n-6 linoleic acid (HRQ5-Q1 = 1.10; 95% CI = 1.01-1.21; P-trend = 0.03) and n-3 alpha-linolenic acid (HRQ5-Q1 = 1.18; 95% CI = 1.05-1.34; P-trend = 0.007) from deep-frying fats were also positively associated with ovarian cancer. Suggestive associations were reported for circulating elaidic (OR comparing third with first tertile(T3-T1) = 1.39; 95% CI = 0.99-1.94; P-trend = 0.06) anda-linolenic acids (ORT3-T1 = 1.30; 95% CI = 0.98-1.72; P-trend = 0.06).Conclusions: Our results suggest that higher intakes and circulating levels of industrial trans elaidic acid, and higher intakes of linoleic acid and alpha-linolenic acid from deep-frying fat, may be associated with greater risk of ovarian cancer.Impact: If causal, eliminating industrial trans-fatty acids could offer a straightforward public health action for reducing ovarian cancer risk.
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