| 1. |
- Abelev, Betty, et al.
(författare)
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Long-range angular correlations on the near and away side in p-Pb collisions at root S-NN=5.02 TeV
- 2013
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Ingår i: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 719:1-3, s. 29-41
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Tidskriftsartikel (refereegranskat)abstract
- Angular correlations between charged trigger and associated particles are measured by the ALICE detector in p-Pb collisions at a nucleon-nucleon centre-of-mass energy of 5.02 TeV for transverse momentum ranges within 0.5 < P-T,P-assoc < P-T,P-trig < 4 GeV/c. The correlations are measured over two units of pseudorapidity and full azimuthal angle in different intervals of event multiplicity, and expressed as associated yield per trigger particle. Two long-range ridge-like structures, one on the near side and one on the away side, are observed when the per-trigger yield obtained in low-multiplicity events is subtracted from the one in high-multiplicity events. The excess on the near-side is qualitatively similar to that recently reported by the CMS Collaboration, while the excess on the away-side is reported for the first time. The two-ridge structure projected onto azimuthal angle is quantified with the second and third Fourier coefficients as well as by near-side and away-side yields and widths. The yields on the near side and on the away side are equal within the uncertainties for all studied event multiplicity and p(T) bins, and the widths show no significant evolution with event multiplicity or p(T). These findings suggest that the near-side ridge is accompanied by an essentially identical away-side ridge. (c) 2013 CERN. Published by Elsevier B.V. All rights reserved.
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| 2. |
- Abelev, Betty, et al.
(författare)
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Measurement of prompt J/psi and beauty hadron production cross sections at mid-rapidity in pp collisions at root s=7 TeV
- 2012
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Ingår i: Journal of High Energy Physics. - 1029-8479. ; :11
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Tidskriftsartikel (refereegranskat)abstract
- The ALICE experiment at the LHC has studied J/psi production at mid-rapidity in pp collisions at root s = 7 TeV through its electron pair decay on a data sample corresponding to an integrated luminosity L-int = 5.6 nb(-1). The fraction of J/psi from the decay of long-lived beauty hadrons was determined for J/psi candidates with transverse momentum p(t) > 1,3 GeV/c and rapidity vertical bar y vertical bar < 0.9. The cross section for prompt J/psi mesons, i.e. directly produced J/psi and prompt decays of heavier charmonium states such as the psi(2S) and chi(c) resonances, is sigma(prompt J/psi) (p(t) > 1.3 GeV/c, vertical bar y vertical bar < 0.9) = 8.3 +/- 0.8(stat.) +/- 1.1 (syst.)(-1.4)(+1.5) (syst. pol.) mu b. The cross section for the production of b-hadrons decaying to J/psi with p(t) > 1.3 GeV/c and vertical bar y vertical bar < 0.9 is a sigma(J/psi <- hB) (p(t) > 1.3 GeV/c, vertical bar y vertical bar < 0.9) = 1.46 +/- 0.38 (stat.)(-0.32)(+0.26) (syst.) mu b. The results are compared to QCD model predictions. The shape of the p(t) and y distributions of b-quarks predicted by perturbative QCD model calculations are used to extrapolate the measured cross section to derive the b (b) over bar pair total cross section and d sigma/dy at mid-rapidity.
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| 3. |
- Abelev, Betty, et al.
(författare)
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Underlying Event measurements in pp collisions at root s=0.9 and 7 TeV with the ALICE experiment at the LHC
- 2012
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Ingår i: Journal of High Energy Physics. - 1029-8479. ; :7
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Tidskriftsartikel (refereegranskat)abstract
- We present measurements of Underlying Event observables in pp collisions at root s = 0 : 9 and 7 TeV. The analysis is performed as a function of the highest charged-particle transverse momentum p(T),L-T in the event. Different regions are defined with respect to the azimuthal direction of the leading (highest transverse momentum) track: Toward, Transverse and Away. The Toward and Away regions collect the fragmentation products of the hardest partonic interaction. The Transverse region is expected to be most sensitive to the Underlying Event activity. The study is performed with charged particles above three different p(T) thresholds: 0.15, 0.5 and 1.0 GeV/c. In the Transverse region we observe an increase in the multiplicity of a factor 2-3 between the lower and higher collision energies, depending on the track p(T) threshold considered. Data are compared to PYTHIA 6.4, PYTHIA 8.1 and PHOJET. On average, all models considered underestimate the multiplicity and summed p(T) in the Transverse region by about 10-30%.
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| 4. |
- Thompson, Paul M., et al.
(författare)
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The ENIGMA Consortium : large-scale collaborative analyses of neuroimaging and genetic data
- 2014
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Ingår i: BRAIN IMAGING BEHAV. - : Springer Science and Business Media LLC. - 1931-7557 .- 1931-7565. ; 8:2, s. 153-182
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Tidskriftsartikel (refereegranskat)abstract
- The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium is a collaborative network of researchers working together on a range of large-scale studies that integrate data from 70 institutions worldwide. Organized into Working Groups that tackle questions in neuroscience, genetics, and medicine, ENIGMA studies have analyzed neuroimaging data from over 12,826 subjects. In addition, data from 12,171 individuals were provided by the CHARGE consortium for replication of findings, in a total of 24,997 subjects. By meta-analyzing results from many sites, ENIGMA has detected factors that affect the brain that no individual site could detect on its own, and that require larger numbers of subjects than any individual neuroimaging study has currently collected. ENIGMA's first project was a genome-wide association study identifying common variants in the genome associated with hippocampal volume or intracranial volume. Continuing work is exploring genetic associations with subcortical volumes (ENIGMA2) and white matter microstructure (ENIGMA-DTI). Working groups also focus on understanding how schizophrenia, bipolar illness, major depression and attention deficit/hyperactivity disorder (ADHD) affect the brain. We review the current progress of the ENIGMA Consortium, along with challenges and unexpected discoveries made on the way.
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| 5. |
- Oddsson, Asmundur, et al.
(författare)
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Deficit of homozygosity among 1.52 million individuals and genetic causes of recessive lethality
- 2023
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Genotypes causing pregnancy loss and perinatal mortality are depleted among living individuals and are therefore difficult to find. To explore genetic causes of recessive lethality, we searched for sequence variants with deficit of homozygosity among 1.52 million individuals from six European populations. In this study, we identified 25 genes harboring protein-altering sequence variants with a strong deficit of homozygosity (10% or less of predicted homozygotes). Sequence variants in 12 of the genes cause Mendelian disease under a recessive mode of inheritance, two under a dominant mode, but variants in the remaining 11 have not been reported to cause disease. Sequence variants with a strong deficit of homozygosity are over-represented among genes essential for growth of human cell lines and genes orthologous to mouse genes known to affect viability. The function of these genes gives insight into the genetics of intrauterine lethality. We also identified 1077 genes with homozygous predicted loss-of-function genotypes not previously described, bringing the total set of genes completely knocked out in humans to 4785.
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| 6. |
- Bott, Lukas Thomas, et al.
(författare)
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Coulomb dissociation of O-16 into He-4 and C-12
- 2023
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Ingår i: NUCLEAR PHYSICS IN ASTROPHYSICS - X, NPA-X 2022. - : EDP Sciences. - 2100-014X. ; 279
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Konferensbidrag (refereegranskat)abstract
- We measured the Coulomb dissociation of O-16 into He-4 and C-12 within the FAIR Phase-0 program at GSI Helmholtzzentrum fur Schwerionenforschung Darmstadt, Germany. From this we will extract the photon dissociation cross section O-16(alpha,gamma)C-12, which is the time reversed reaction to C-12(alpha,gamma)O-16. With this indirect method, we aim to improve on the accuracy of the experimental data at lower energies than measured so far. The expected low cross section for the Coulomb dissociation reaction and close magnetic rigidity of beam and fragments demand a high precision measurement. Hence, new detector systems were built and radical changes to the (RB)-B-3 setup were necessary to cope with the high-intensity O-16 beam. All tracking detectors were designed to let the unreacted O-16 ions pass, while detecting the C-12 and He-4.
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| 7. |
- Edvinsson, Lars, et al.
(författare)
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Effect of the calcitonin gene-related peptide (CGRP) receptor antagonist telcagepant in human cranial arteries.
- 2010
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Ingår i: Cephalalgia. - : SAGE Publications. - 0333-1024 .- 1468-2982. ; 30:10, s. 1233-1240
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Calcitonin gene-related peptide (CGRP) is a neuronal messenger in intracranial sensory nerves and is considered to play a significant role in migraine pathophysiology. MATERIALS AND METHODS: We investigated the effect of the CGRP receptor antagonist, telcagepant, on CGRP-induced cranial vasodilatation in human isolated cerebral and middle meningeal arteries. We also studied the expression of the CGRP receptor components in cranial arteries with immunocytochemistry. Concentration response curves to αCGRP were performed in human isolated cerebral and middle meningeal arteries in the absence or presence of telcagepant. Arterial slices were stained for RAMP1, CLR and actin in a double immunofluorescence staining. RESULTS: In both arteries, we found that: (i) telcagepant was devoid of any contractile or relaxant effects per se; (ii) pretreatment with telcagepant antagonised the αCGRP-induced relaxation in a competitive manner; and (iii) immunohistochemistry revealed expression and co-localisation of CLR and RAMP1 in the smooth muscle cells in the media layer of both arteries. CONCLUSIONS: Our findings provide morphological and functional data on the presence of CGRP receptors in cerebral and meningeal arteries, which illustrates a possible site of action of telcagepant in the treatment of migraine.
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| 8. |
- Edwards, Robert A., et al.
(författare)
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Global phylogeography and ancient evolution of the widespread human gut virus crAssphage
- 2019
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Ingår i: Nature Microbiology. - : Springer Science and Business Media LLC. - 2058-5276. ; 4:10, s. 1727-1736
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Tidskriftsartikel (refereegranskat)abstract
- Microbiomes are vast communities of microorganisms and viruses that populate all natural ecosystems. Viruses have been considered to be the most variable component of microbiomes, as supported by virome surveys and examples of high genomic mosaicism. However, recent evidence suggests that the human gut virome is remarkably stable compared with that of other environments. Here, we investigate the origin, evolution and epidemiology of crAssphage, a widespread human gut virus. Through a global collaboration, we obtained DNA sequences of crAssphage from more than one-third of the world's countries and showed that the phylogeography of crAssphage is locally clustered within countries, cities and individuals. We also found fully colinear crAssphage-like genomes in both Old-World and New-World primates, suggesting that the association of crAssphage with primates may be millions of years old. Finally, by exploiting a large cohort of more than 1,000 individuals, we tested whether crAssphage is associated with bacterial taxonomic groups of the gut microbiome, diverse human health parameters and a wide range of dietary factors. We identified strong correlations with different clades of bacteria that are related to Bacteroidetes and weak associations with several diet categories, but no significant association with health or disease. We conclude that crAssphage is a benign cosmopolitan virus that may have coevolved with the human lineage and is an integral part of the normal human gut virome.
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| 9. |
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Encyclopedia of Slavic Languages and Linguistics Online : Editor-in-Chief: Marc L. Greenberg, University of Kansas; Lenore A. Grenoble, General Editor, University of Chicago; Associate Editors: Stephen M. Dickey, University of Kansas; Masako Ueda Fidler, Brown University; René Genis, University of Amsterdam; Marek Łaziński, University of Warsaw; Anita Peti-Stantić, University of Zagreb; Björn Wiemer, University of Mainz; Nadežda V. Zorixina-Nilsson, Stockholm University
- 2020
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Samlingsverk (redaktörskap) (refereegranskat)abstract
- The most comprehensive reference work on Slavic languages ever published. It provides authoritative treatment of all important aspects of the Slavic language family from its Indo-European origins to the present day, as well as consideration of the interaction of Slavic with other languages.
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| 10. |
- Flach, Carl-Fredrik, 1977, et al.
(författare)
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Pro-inflammatory cytokine gene expression in the stomach correlates with vaccine-induced protection against Helicobacter pylori infection in mice: an important role for interleukin-17 during the effector phase. : Immune correlates to H. pylori protection
- 2011
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Ingår i: Infection and immunity. - 1098-5522. ; 79:2, s. 879-886
-
Tidskriftsartikel (refereegranskat)abstract
- CD4(+) T cells have been shown to be essential for vaccine-induced protection against Helicobacter pylori infection in mice. Less is known about relative contributions of individual cell subpopulations, such as TH1 and TH17 cells, and their associated cytokines. The aim of the present study was to find immune correlates to vaccine-induced protection and further study their role in protection against H. pylori infection. Immunized and unimmunized mice were challenged with H. pylori and immune responses were compared. Vaccine-induced protection was assessed by measuring H. pylori colonization in the stomach. Gastric gene expression of TH1- and/or TH17-associated cytokines was analyzed by quantitative PCR and contributions of individual cytokines to protection were evaluated by antibody-mediated in vivo neutralization. By analyzing immunized and unimmunized mice a significant inverse correlation could be demonstrated between levels of interleukin (IL)-12p40, tumor necrosis factor α (TNF), interferon γ (IFNγ) and IL-17 gene expression and number of H. pylori in the stomach of individual animals after challenge. In a kinetic study, up-regulation of TNF, IFNγ and IL-17 coincided with vaccine-induced protection 7 days after H. pylori challenge and was sustained for at least 21 days. In vivo neutralization of these cytokines during the effector phase of the immune response revealed a significant role for IL-17, but not for IFNγ or TNF, in vaccine-induced protection. In conclusion, although both TH1- and TH17-associated gene expression in the stomach correlate with vaccine-induced protection against H. pylori infection, our study indicates that mainly TH17 effector mechanisms are of critical importance to protection.
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| 11. |
- Ge, Changrong, et al.
(författare)
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Structural Basis of Cross-Reactivity of Anti-Citrullinated Protein Antibodies
- 2019
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Ingår i: Arthritis & Rheumatology. - : WILEY. - 2326-5191 .- 2326-5205. ; 71:2, s. 210-221
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Tidskriftsartikel (refereegranskat)abstract
- Objective Anti-citrullinated protein antibodies (ACPAs) develop many years before the clinical onset of rheumatoid arthritis (RA). This study was undertaken to address the molecular basis of the specificity and cross-reactivity of ACPAs from patients with RA. Methods Antibodies isolated from RA patients were expressed as monoclonal chimeric antibodies with mouse Fc. These antibodies were characterized for glycosylation using mass spectrometry, and their cross-reactivity was assessed using Biacore and Luminex immunoassays. The crystal structures of the antigen-binding fragment (Fab) of the monoclonal ACPA E4 in complex with 3 different citrullinated peptides were determined using x-ray crystallography. The prevalence of autoantibodies reactive against 3 of the citrullinated peptides that also interacted with E4 was investigated by Luminex immunoassay in 2 Swedish cohorts of RA patients. Results Analysis of the crystal structures of a monoclonal ACPA from human RA serum in complex with citrullinated peptides revealed key residues of several complementarity-determining regions that recognized the citrulline as well as the neighboring peptide backbone, but with limited contact with the side chains of the peptides. The same citrullinated peptides were recognized by high titers of serum autoantibodies in 2 large cohorts of RA patients. Conclusion These data show, for the first time, how ACPAs derived from human RA serum recognize citrulline. The specific citrulline recognition and backbone-mediated interactions provide a structural explanation for the promiscuous recognition of citrullinated peptides by RA-specific ACPAs.
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| 12. |
- Gunnlaugsson, Adalsteinn, et al.
(författare)
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PSA decay during salvage radiotherapy for prostate cancer as a predictor of disease outcome – 5 year follow-up of a prospective observational study
- 2020
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Ingår i: Clinical and Translational Radiation Oncology. - : Elsevier BV. - 2405-6308. ; 24, s. 23-28
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: Biochemical recurrence after prostatectomy is commonly treated with salvage radiotherapy (SRT). In this prospective observational study we investigated the PSA decay rate, determined by predefined serial PSA measurements during SRT, as a predictor for treatment outcome.Materials and methods: Between 2013 and 2016, 214 patients were included in the study. The prescribed dose to the prostate bed was 70 Gy in 35 fractions (7 weeks) without hormonal treatment. PSA was measured weekly during SRT. Assuming first order kinetics, a PSA decay-rate constant (k) was calculated for 196 eligible patients. The ability of k to predict disease progression was compared with known clinical prediction parameters using Cox regression, logistic regression and ROC analyses. Disease progression was defined as continuously rising PSA after SRT, PSA increase by ≥0.2 ng/ml above nadir after SRT, hormonal treatment or clinical progression.Results: After a median follow up of 4.7 years the estimated failure-free survival at 5 years was 56%. The PSA decay-rate constant (k) was found to be the strongest predictor of disease progression in both uni-and multivariable analyses.Conclusion: The addition of k to established clinical variables significantly improves the possibility to predict treatment outcome after SRT and could be used to personalize future therapies.
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| 13. |
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| 14. |
- Hess, Timo, et al.
(författare)
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Dissecting the genetic heterogeneity of gastric cancer
- 2023
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Ingår i: EBioMedicine. - : Elsevier. - 2352-3964. ; 92
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Tidskriftsartikel (refereegranskat)abstract
- Background: Gastric cancer (GC) is clinically heterogenous according to location (cardia/non-cardia) and histopathology (diffuse/intestinal). We aimed to characterize the genetic risk architecture of GC according to its subtypes. Another aim was to examine whether cardia GC and oesophageal adenocarcinoma (OAC) and its precursor lesion Barrett's oesophagus (BO), which are all located at the gastro-oesophageal junction (GOJ), share polygenic risk architecture.Methods: We did a meta-analysis of ten European genome-wide association studies (GWAS) of GC and its subtypes. All patients had a histopathologically confirmed diagnosis of gastric adenocarcinoma. For the identification of risk genes among GWAS loci we did a transcriptome-wide association study (TWAS) and expression quantitative trait locus (eQTL) study from gastric corpus and antrum mucosa. To test whether cardia GC and OAC/BO share genetic aetiology we also used a European GWAS sample with OAC/BO.Findings: Our GWAS consisting of 5816 patients and 10,999 controls highlights the genetic heterogeneity of GC according to its subtypes. We newly identified two and replicated five GC risk loci, all of them with subtype-specific association. The gastric transcriptome data consisting of 361 corpus and 342 antrum mucosa samples revealed that an upregulated expression of MUC1, ANKRD50, PTGER4, and PSCA are plausible GC-pathomechanisms at four GWAS loci. At another risk locus, we found that the blood-group 0 exerts protective effects for non-cardia and diffuse GC, while blood-group A increases risk for both GC subtypes. Furthermore, our GWAS on cardia GC and OAC/BO (10,279 patients, 16,527 controls) showed that both cancer entities share genetic aetiology at the polygenic level and identified two new risk loci on the single-marker level.Interpretation: Our findings show that the pathophysiology of GC is genetically heterogenous according to location and histopathology. Moreover, our findings point to common molecular mechanisms underlying cardia GC and OAC/BO.
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| 15. |
- Hudson, Lawrence N, et al.
(författare)
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The database of the PREDICTS (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems) project
- 2017
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Ingår i: Ecology and Evolution. - : John Wiley & Sons. - 2045-7758. ; 7:1, s. 145-188
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Tidskriftsartikel (refereegranskat)abstract
- The PREDICTS project-Projecting Responses of Ecological Diversity In Changing Terrestrial Systems (www.predicts.org.uk)-has collated from published studies a large, reasonably representative database of comparable samples of biodiversity from multiple sites that differ in the nature or intensity of human impacts relating to land use. We have used this evidence base to develop global and regional statistical models of how local biodiversity responds to these measures. We describe and make freely available this 2016 release of the database, containing more than 3.2 million records sampled at over 26,000 locations and representing over 47,000 species. We outline how the database can help in answering a range of questions in ecology and conservation biology. To our knowledge, this is the largest and most geographically and taxonomically representative database of spatial comparisons of biodiversity that has been collated to date; it will be useful to researchers and international efforts wishing to model and understand the global status of biodiversity.
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| 16. |
- In ’t Veld, Sjors G.J.G., et al.
(författare)
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Detection and localization of early- and late-stage cancers using platelet RNA
- 2022
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Ingår i: Cancer Cell. - : Elsevier. - 1535-6108 .- 1878-3686. ; 40:9, s. 999-1009.e6
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Tidskriftsartikel (refereegranskat)abstract
- Cancer patients benefit from early tumor detection since treatment outcomes are more favorable for less advanced cancers. Platelets are involved in cancer progression and are considered a promising biosource for cancer detection, as they alter their RNA content upon local and systemic cues. We show that tumor-educated platelet (TEP) RNA-based blood tests enable the detection of 18 cancer types. With 99% specificity in asymptomatic controls, thromboSeq correctly detected the presence of cancer in two-thirds of 1,096 blood samples from stage I–IV cancer patients and in half of 352 stage I–III tumors. Symptomatic controls, including inflammatory and cardiovascular diseases, and benign tumors had increased false-positive test results with an average specificity of 78%. Moreover, thromboSeq determined the tumor site of origin in five different tumor types correctly in over 80% of the cancer patients. These results highlight the potential properties of TEP-derived RNA panels to supplement current approaches for blood-based cancer screening.
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| 17. |
- Johansson, Cecilia, et al.
(författare)
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Campylobacter coli clade 3 isolates induce rapid cell death in vitro
- 2019
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Ingår i: Applied and Environmental Microbiology. - 0099-2240 .- 1098-5336. ; 85:5
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Tidskriftsartikel (refereegranskat)abstract
- Campylobacter are major human enteropathogens. C. coli show less genetic diversity than C. jejuni and cluster into three clades, of which clade 1 includes most human and farm animal isolates while environmental C. coli mainly belong to clades 2 and 3. Recently, we whole genome-sequenced eight C. coli clade 2 and 3 isolates cultivated from water, and here we studied their interaction with human HT-29 colon cancer cells compared to clinical clade 1 isolates. All C. coli clade 3 isolates caused cell necrosis already 1-2 hours after inoculation, whereas none of the clade 1 and 2 isolates analyzed induced cell death. Isolates from clades 2 and 3 adhered better than clade 1 isolates to epithelial cells but all isolates induced similar levels of IL-8. Alignment and phylogenetic analysis of translated putative virulence genes cadF, flpA, iamA, ciaB and ceuE revealed clade-specific protein sequence variations with clade 1 and 2 sequences more closely related and clade 3 sequences further apart in general.Moreover, when RNA levels were measured, clade 3 isolates showed a significantly lower expression of cadF, iamA and ceuE than clade 2 isolates, while flpA levels were higher in clade 3 isolates. The cytolethal distending toxin genes were also expressed in clades 2 and 3 although there was no difference between clades. Our findings demonstrate differences between effects of C. coli clade 1, 2 and 3 isolates on human cells and suggest that C. coli clade 3 might be more virulent than clade 2 due to the observed cytotoxicity.IMPORTANCECampylobacter coli is a common zoonotic cause of gastroenteritis in humans worldwide. The majority of infections are caused by C. coli clade 1 isolates, whereas infections due to clade 2 and 3 isolates are rare. Whether this depends on a low prevalence of clade 2 and 3 isolates in reservoirs important for human infections or their lower ability to cause human disease is unknown. Here, we studied the effects of C. coli clade 2 and 3 isolates on a human cell line. These isolates adhered to human cells to a higher degree than clinical clade 1 isolates. Furthermore, we could show that C. coli clade 3 isolates rapidly induced cell death suggesting differences in the virulence of C. coli The exact mechanism of cell death remains to be revealed but selected genes showed interesting clade-specific expression patterns.
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| 18. |
- Johansson, Cecilia, et al.
(författare)
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Differences in virulence gene expression between human blood and stool Campylobacter coli clade 1 ST828CC isolates
- 2019
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Ingår i: Gut Pathogens. - : BioMed Central. - 1757-4749. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Campylobacter colonise the gastrointestinal tract of warm-blooded animals and are major enteropathogens in humans. C. coli is less common than C. jejuni and accounts for about 10% of the total number of Campylobacter infections although the two species seem to share many virulence determinants. Campylobacter bacteraemia is rare, estimated to occur in less than 1% of the infections, and the exact mechanisms regulating the progression of the infection from the gastrointestinal tract to the blood stream are unclear. Here, we looked at the contribution of C. coli to Campylobacter infections and further compared various virulence traits in C. coli clade 1 blood and stool isolates. Results: We assessed the numbers of C. jejuni and C. coli among typed isolates in the PubMLST database and found that C. coli accounted for 25.9% of blood isolates, but only 8.9% of the stool isolates. Phylogenetic analysis of 128 C. coli clade 1 whole genome sequences deposited to NCBI revealed no specific clustering of the human blood, stool or animal isolates. Of the six C. coli isolates chosen for phenotypic analyses, stool isolates adhered significantly better to human HT-29 colon cancer cells than the blood isolates, while there was no difference in induced IL-8 levels between the isolates. Furthermore, the stool isolates had two-to fourfold higher RNA expression levels of the flpA, ciaB, iamA and cdt virulence genes than the blood isolates. Finally, we looked at the gene structure of the cdtA, B and C toxin genes and found numerous nucleotide additions and deletions disrupting the open reading frames. In contrast to 58% isolates of animal origin, only 38% and 32% of human blood and stool isolates, respectively, had all three cdt genes intact, a prerequisite to produce functional toxins. Conclusions: This study reveals interesting differences between C. coli clade 1 isolates of human and animal origin on one hand, and also between human blood and stool isolates, on the other. The results suggest that C. coli might downregulate and/or inactivate various virulence determinants as the isolates pass from the animal host to the human gastrointestinal tract and enter the human blood stream.
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| 19. |
- Jonsson, Kenneth, et al.
(författare)
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Traffic compensated luminance estimation
- 2015
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Active control of street light sources based on sensor data is desired to meet requirements on traffic safety and environmental protection. In this report, we summarise the results of a research study focusing on some of the fundamental problems occurring when performing real-world sensor measurements for lighting control. In particular, we present results on the impact of traffic and the relationship between sensor angle and measured road surface luminance. Moreover, we present a comparison between different approaches to estimating the veiling luminance in tunnel lighting applications.
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| 20. |
- 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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| 21. |
- Jönsson, Mari, et al.
(författare)
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Inequality persists in a large citizen science programme despite increased participation through ICT innovations
- 2024
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Ingår i: Ambio: A Journal of Environment and Society. - 0044-7447 .- 1654-7209. ; 53:1, s. 126-137
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Tidskriftsartikel (refereegranskat)abstract
- Biological recording is a prominent and widely practised form of citizen science, but few studies explore long-term demographic trends in participation and knowledge production. We studied long-term demographic trends of age and gender of participants reporting to a large online citizen science multi-taxon biodiversity platform (www.artportalen.se). Adoption by user communities and continually developing Information and Communications Technologies (ICTs) greatly increased the number of par- ticipants reporting data, but profound long-term imbalances in gender contribution across species groups persisted over time. Reporters identifying as male dominated in numbers, spent more days in the field reporting and reported more species on each field day. Moreover, an age imbalance towards older participants amplified over time. As the first long-term study of citizen participation by age and gender, our results show that it is important for citizen science project developers to account for cultural and social developments that might exclude participants, and to engage with under- represented and younger participants. This could facilitate the breadth of engagement and learning across a larger societal landscape, ensure project longevity and biodiversity data representation (e.g. mitigate gender bias influence on the number of reports of different species groups).
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| 22. |
- Kompus, Kristiina, et al.
(författare)
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Deficits in inhibitory executive functions in Klinefelter (47, XXY) syndrome
- 2011
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Ingår i: Psychiatry Research. - : Elsevier BV. - 0165-1781 .- 1872-7123. ; 189:1, s. 135-140
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Tidskriftsartikel (refereegranskat)abstract
- Klinefelter syndrome (47, XXY) is a sex chromosome aneuploidy associated with mild deficits in cognitive and language functions. Dysfunctions have also been reported in performance of tasks which examine executive functions. However, it is unclear whether the impaired performance is caused or accentuated by problems with semantic processing and information processing speed. In the present study we used an experimental task which is relatively insensitive to these confounding factors. We examined inhibitory executive functions in a group of XXY males compared with male (XY) and female (XX) controls, using a dichotic listening speech sound task with instructions to focus attention on either the right or the left ear stimulus. With this task, inhibitory executive functions can be assessed separately from language, processing speed, and attention orientation abilities. We found that XXY males showed a selective deficit in inhibitory executive functions compared to both control groups, whereas attentional orientation was not impaired. The present findings suggest that executive dysfunctions associated to Klinefelter syndrome can be selectively identified, and are particularly accentuated in the inhibitory sub-component. Such improved understanding of the nature of executive dysfunctions in XXY males may aid the development of specific neuropsychological rehabilitation strategies.
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| 23. |
- Lechman, Eric R, et al.
(författare)
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miR-126 Regulates Distinct Self-Renewal Outcomes in Normal and Malignant Hematopoietic Stem Cells.
- 2016
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Ingår i: Cancer Cell. - : Elsevier BV. - 1878-3686 .- 1535-6108. ; 29:2, s. 214-228
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Tidskriftsartikel (refereegranskat)abstract
- To investigate miRNA function in human acute myeloid leukemia (AML) stem cells (LSC), we generated a prognostic LSC-associated miRNA signature derived from functionally validated subpopulations of AML samples. For one signature miRNA, miR-126, high bioactivity aggregated all in vivo patient sample LSC activity into a single sorted population, tightly coupling miR-126 expression to LSC function. Through functional studies, miR-126 was found to restrain cell cycle progression, prevent differentiation, and increase self-renewal of primary LSC in vivo. Compared with prior results showing miR-126 regulation of normal hematopoietic stem cell (HSC) cycling, these functional stem effects are opposite between LSC and HSC. Combined transcriptome and proteome analysis demonstrates that miR-126 targets the PI3K/AKT/MTOR signaling pathway, preserving LSC quiescence and promoting chemotherapy resistance.
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| 24. |
- Lindgren, Johan, et al.
(författare)
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Fossil insect eyes shed light on trilobite optics and the arthropod pigment screen
- 2019
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Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 573:7772, s. 122-125
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Tidskriftsartikel (refereegranskat)abstract
- Fossilized eyes permit inferences of the visual capacity of extinct arthropods1–3. However, structural and/or chemical modifications as a result of taphonomic and diagenetic processes can alter the original features, thereby necessitating comparisons with modern species. Here we report the detailed molecular composition and microanatomy of the eyes of 54-million-year-old crane-flies, which together provide a proxy for the interpretation of optical systems in some other ancient arthropods. These well-preserved visual organs comprise calcified corneal lenses that are separated by intervening spaces containing eumelanin pigment. We also show that eumelanin is present in the facet walls of living crane-flies, in which it forms the outermost ommatidial pigment shield in compound eyes incorporating a chitinous cornea. To our knowledge, this is the first record of melanic screening pigments in arthropods, and reveals a fossilization mode in insect eyes that involves a decay-resistant biochrome coupled with early diagenetic mineralization of the ommatidial lenses. The demonstrable secondary calcification of lens cuticle that was initially chitinous has implications for the proposed calcitic corneas of trilobites, which we posit are artefacts of preservation rather than a product of in vivo biomineralization4–7. Although trilobite eyes might have been partly mineralized for mechanical strength, a (more likely) organic composition would have enhanced function via gradient-index optics and increased control of lens shape.
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| 25. |
- Lindgren, Mikael, 1963, et al.
(författare)
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Traffic compensated luminance estimation
- 2015
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Ingår i: 28th CIE Session, 28 jun - 4 jul 2015 Manchester UK.
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)
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| 26. |
- Liseau, Rene, et al.
(författare)
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q1 Eridani : a solar-type star with a planet and a dust belt
- 2008
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 480:3, s. L47-L50
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Tidskriftsartikel (refereegranskat)abstract
- Context. Far-infrared excess emission from main-sequence stars is due to dust produced by orbiting minor bodies. In these disks, larger bodies, such as planets, may also be present and the understanding of their incidence and influence currently presents a challenge. Aims. Only very few solar-type stars exhibiting an infrared excess and harbouring planets are known to date. Indeed, merely a single case of a star-planet-disk system has previously been detected at submillimeter (submm) wavelengths. Consequently, one of our aims is to understand the reasons for these poor statistics, i.e., whether these results reflected the composition and/or the physics of the planetary disks or were simply due to observational bias and selection effects. Finding more examples would be very significant. Methods. The selected target, q(1) Eri, is a solar-type star, which was known to possess a planet, q(1) Eri b, and to exhibit excess emission at IRAS wavelengths, but had remained undetected in the millimeter regime. Therefore, submm flux densities would be needed to better constrain the physical characteristics of the planetary disk. Consequently, we performed submm imaging observations of q(1) Eri. Results. The detected dust toward q(1) Eri at 870 mu m exhibits the remarkable fact that the entire SED, from the IR to mm-wavelengths, is fit by a single-temperature blackbody function (60 K). This would imply that the emitting regions are confined to a narrow region (ring) at radial distances much larger than the orbital distance of q(1) Eri b, and that the emitting particles are considerably larger than some hundred micron. However, the 870 mu m source is extended, with a full-width-half-maximum of roughly 600AU. Therefore, a physically more compelling model also invokes a belt of cold dust (17 K), located at 300AU from the star and about 60AU wide. Conclusions. The minimum mass of 0.04 M-circle plus (3 M-Moon) of 1 mm-size icy ring-particles is considerable, given the stellar age of >= 1Gyr. These big grains form an inner edge at about 25 AU, which may suggest the presence of an unseen outer planet (q(1) Eri c).
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| 27. |
- Liseau, René, 1949, et al.
(författare)
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q1 Eridani: a solar-type star with a planet and a dust belt
- 2008
-
Ingår i: Astronomy & Astrophysics. ; 480, s. L47-L50
-
Tidskriftsartikel (refereegranskat)abstract
- Context: Far-infrared excess emission from main-sequence stars is due to dust produced by orbiting minor bodies. In these disks, larger bodies, such as planets, may also be present and the understanding of their incidence and influence currently presents a challenge. Aims: Only very few solar-type stars exhibiting an infrared excess and harbouring planets are known to date. Indeed, merely a single case of a star-planet-disk system has previously been detected at submillimeter (submm) wavelengths. Consequently, one of our aims is to understand the reasons for these poor statistics, i.e., whether these results reflected the composition and/or the physics of the planetary disks or were simply due to observational bias and selection effects. Finding more examples would be very significant. Methods: The selected target, q1 Eri, is a solar-type star, which was known to possess a planet, q1 Eri b, and to exhibit excess emission at IRAS wavelengths, but had remained undetected in the millimeter regime. Therefore, submm flux densities would be needed to better constrain the physical characteristics of the planetary disk. Consequently, we performed submm imaging observations of q1 Eri. Results: The detected dust toward q1 Eri at 870 μm exhibits the remarkable fact that the entire SED, from the IR to mm-wavelengths, is fit by a single-temperature blackbody function (60 K). This would imply that the emitting regions are confined to a narrow region (ring) at radial distances much larger than the orbital distance of q1 Eri b, and that the emitting particles are considerably larger than some hundred micron. However, the 870 μm source is extended, with a full-width-half-maximum of roughly 600 AU. Therefore, a physically more compelling model also invokes a belt of cold dust (17 K), located at 300 AU from the star and about 60 AU wide. Conclusions: The minimum mass of 0.04 M⊕ (3 M_Moon) of 1 mm-size icy ring-particles is considerable, given the stellar age of ⪆ 1 Gyr. These big grains form an inner edge at about 25 AU, which may suggest the presence of an unseen outer planet (q1 Eri c).Based on observations with APEX, Llano Chajnantor, Chile.
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| 28. |
- Liu, Ilon, et al.
(författare)
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The landscape of tumor cell states and spatial organization in H3-K27M mutant diffuse midline glioma across age and location
- 2022
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 54:12, s. 1881-1894
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Tidskriftsartikel (refereegranskat)abstract
- Histone 3 lysine27-to-methionine (H3-K27M) mutations most frequently occur in diffuse midline gliomas (DMGs) of the childhood pons but are also increasingly recognized in adults. Their potential heterogeneity at different ages and midline locations is vastly understudied. Here, through dissecting the single-cell transcriptomic, epigenomic and spatial architectures of a comprehensive cohort of patient H3-K27M DMGs, we delineate how age and anatomical location shape glioma cell-intrinsic and -extrinsic features in light of the shared driver mutation. We show that stem-like oligodendroglial precursor-like cells, present across all clinico-anatomical groups, display varying levels of maturation dependent on location. We reveal a previously underappreciated relationship between mesenchymal cancer cell states and age, linked to age-dependent differences in the immune microenvironment. Further, we resolve the spatial organization of H3-K27M DMG cell populations and identify a mitotic oligodendroglial-lineage niche. Collectively, our study provides a powerful framework for rational modeling and therapeutic interventions.
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| 29. |
- Loza, M. J., et al.
(författare)
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Validated and longitudinally stable asthma phenotypes based on cluster analysis of the ADEPT study
- 2016
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Ingår i: Respiratory Research. - : Springer Nature. - 1465-9921 .- 1465-993X. ; 17:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Asthma is a disease of varying severity and differing disease mechanisms. To date, studies aimed at stratifying asthma into clinically useful phenotypes have produced a number of phenotypes that have yet to be assessed for stability and to be validated in independent cohorts. The aim of this study was to define and validate, for the first time ever, clinically driven asthma phenotypes using two independent, severe asthma cohorts: ADEPT and U-BIOPRED. Methods: Fuzzy partition-around-medoid clustering was performed on pre-specified data from the ADEPT participants (n = 156) and independently on data from a subset of U-BIOPRED asthma participants (n = 82) for whom the same variables were available. Models for cluster classification probabilities were derived and applied to the 12-month longitudinal ADEPT data and to a larger subset of the U-BIOPRED asthma dataset (n = 397). High and low type-2 inflammation phenotypes were defined as high or low Th2 activity, indicated by endobronchial biopsies gene expression changes downstream of IL-4 or IL-13. Results: Four phenotypes were identified in the ADEPT (training) cohort, with distinct clinical and biomarker profiles. Phenotype 1 was "mild, good lung function, early onset", with a low-inflammatory, predominantly Type-2, phenotype. Phenotype 2 had a "moderate, hyper-responsive, eosinophilic" phenotype, with moderate asthma control, mild airflow obstruction and predominant Type-2 inflammation. Phenotype 3 had a "mixed severity, predominantly fixed obstructive, non-eosinophilic and neutrophilic" phenotype, with moderate asthma control and low Type-2 inflammation. Phenotype 4 had a "severe uncontrolled, severe reversible obstruction, mixed granulocytic" phenotype, with moderate Type-2 inflammation. These phenotypes had good longitudinal stability in the ADEPT cohort. They were reproduced and demonstrated high classification probability in two subsets of the U-BIOPRED asthma cohort. Conclusions: Focusing on the biology of the four clinical independently-validated easy-to-assess ADEPT asthma phenotypes will help understanding the unmet need and will aid in developing tailored therapies. Trial registration:NCT01274507(ADEPT), registered October 28, 2010 and NCT01982162(U-BIOPRED), registered October 30, 2013.
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| 30. |
- Nilsson, Anna, et al.
(författare)
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Characterization of Swedish Campylobacter coli clade 2 and clade 3 water isolates
- 2018
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Ingår i: MicrobiologyOpen. - : Wiley. - 2045-8827. ; 7:4
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Tidskriftsartikel (refereegranskat)abstract
- Campylobacter jejuni and Campylobacter coli are important bacterial enteropathogens. Poultry is the best-known reservoir for Campylobacter infection but natural bodies of water have also been shown to be important pathways for transmission. Campylobacter can survive in cold water but most of the studies have focused on C. jejuni only. In this paper, we take a closer look at the biology and water survival strategies of C. coil. Eight C. coil isolates cultivated from raw (incoming) surface water at water plants in Sweden were characterized using whole-genome sequencing and phenotypical assays. Phylogenetic analysis assigned the Swedish water isolates to clades 2 and 3, known to include C. coil of environmental origin. In addition, 53 earlier published sequences of C. coil clade 2 and 3 from environmental waters were included for in silico analyses. Generally, clade 2 isolates had larger genomes, which included a functional tricarballylate utilization locus, while clade 3 isolates contained different genes involved in oxidative stress as well as putative virulence factors. The Swedish water isolates of clade 2 formed large, blurry bacterial colonies on agar, whereas clade 3 colonies were smaller. All Swedish isolates were motile, but clade 3 isolates formed larger motility zones on soft agar, and none of these isolates produced biofilm. Although water survival varied between the analyzed isolates, there were hardly any clade-specific significant differences. Our results highlight the diversity of C. coil in general, and show differences in metabolic capabilities and ways to handle oxidative stress between clade 2 and 3 water isolates.
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| 31. |
- Nilsson, Anna, et al.
(författare)
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Genomic and phenotypic characteristics of Swedish C. jejuni water isolates
- 2017
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 12:12
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Tidskriftsartikel (refereegranskat)abstract
- Campylobacter jejuni is the most common cause of bacterial gastroenteritis. Major reservoirs are warm-blooded animals, poultry in particular, but Campylobacter can also be transmitted via water. In this paper, we have taken a closer look at the biology and potential virulence of C. jejuni water isolates. Seven C. jejuni isolates from incoming surface water at water plants in Sweden were characterized with whole genome sequencing and phenotypical testing. Multi locus sequence typing analysis revealed that these isolates belonged to groups known to include both common (ST48CC) and uncommon (ST1275CC, ST683, ST793 and ST8853) human pathogens. Further genomic characterization revealed that these isolates had potential for arsenic resistance (due to presence of arsB gene in all isolates), an anaerobic dimethyl sulfoxide oxidoreductase (in three isolates) and lacked the MarR-type transcriptional regulator gene rrpB (in all but one isolate) earlier shown to be involved in better survival under oxidative and aerobic stress. As putative virulence factors were concerned, there were differences between the water isolates in the presence of genes coding for cytolethal distending toxin (cdtABC), Type VI secretion system and sialylated LOS, as well as in biofilm formation. However, all isolates were motile and could adhere to and invade the human HT-29 colon cancer cell line in vitro and induce IL-8 secretion suggesting potential to infect humans. This is, to the best of our knowledge, the first study where C. jejuni water isolates have been characterized using whole genome sequencing and phenotypical assays. We found differences and shared traits among the isolates but also potential to infect humans.
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| 32. |
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| 33. |
- Nilsson, Anna, et al.
(författare)
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Survival of Campylobacter jejuni and C. coli water isolates in lake and well water
- 2018
-
Ingår i: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS). - : Wiley. - 0903-4641 .- 1600-0463. ; 126:9, s. 762-770
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Tidskriftsartikel (refereegranskat)abstract
- The role of water for transmission of Campylobacter jejuni and C. coli to humans might be underestimated, as factors important for bacterial viability in water are largely unknown. We have studied water survival of seven C. jejuni and eight C. coli isolates originally isolated from Swedish waters, together with selected reference strains, over eight days at 4 °C in the dark in untreated water collected from a local lake and a private well. To study seasonality, lake water samples were collected during spring and autumn. Samples for culturable bacterial counts were taken on days 2, 4, 6, and 8 and compared to the start inoculum. For C. jejuni, a significantly better survival was observed in autumn than in spring lake water. Furthermore, C. jejuni had a significantly better survival than C. coli in autumn lake and well water samples; the rate of culturability loss was almost double for C. coli in autumn lake water. These findings contribute to a better understanding on the seasonality of waterborne Campylobacter infections and the general predominance of C. jejuni.
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| 34. |
- Nilsson, Ricky, 1979-, et al.
(författare)
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A submillimetre search for cold extended debris disks in the β Pictoris moving group
- 2009
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 508:2, s. 1057-1065
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Tidskriftsartikel (refereegranskat)abstract
- Context. Previous observations with the Infrared Astronomical Satellite and the Infrared Space Observatory, and ongoing observations with Spitzer and AKARI, have led to the discovery of over 200 debris disks, based on detected mid-and far infrared excess emission, indicating warm circumstellar dust. To constrain the properties of these systems, e.g., to more accurately determine the dust mass, temperature and radial extent, follow-up observations in the submillimetre wavelength region are needed. Aims. The beta Pictoris moving group is a nearby stellar association of young (similar to 12 Myr) co-moving stars including the classical debris disk star beta Pictoris. Due to their proximity and youth, they are excellent targets when searching for submillimetre emission from cold, extended, dust components produced by collisions in Kuiper-Belt-like disks. They also allow an age independent study of debris disk properties as a function of other stellar parameters. Methods. We observed 7 infrared-excess stars in the beta Pictoris moving group with the LABOCA bolometer array, operating at a central wavelength of 870 mu m at the 12-m submillimetre telescope APEX. The main emission at these wavelengths comes from large, cold dust grains, which constitute the main part of the total dust mass, and hence, for an optically thin case, make better estimates on the total dust mass than earlier infrared observations. Fitting the spectral energy distribution with combined optical and infrared photometry gives information on the temperature and radial extent of the disk. Results. From our sample, beta Pic, HD181327, and HD172555 were detected with at least 3 sigma certainty, while all others are below 2 sigma and considered non-detections. The image of beta Pic shows an offset flux density peak located near the south-west extension of the disk, similar to the one previously found by SCUBA at the JCMT. We present SED fits for detected sources and give an upper limit on the dust mass for undetected ones. Conclusions. We find a mean fractional dust luminosity (f) over bar (dust) = 1.1 x 10(-3) at t approximate to 12 Myr, which together with recent data at 100 Myr suggests an f(dust) proportional to t(-alpha) a decline of the emitting dust, with alpha > 0.8.
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| 35. |
- Nilsson, Ricky, 1979-, et al.
(författare)
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Kuiper belts around nearby stars
- 2010
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 518, s. A40-
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Tidskriftsartikel (refereegranskat)abstract
- Context. The existence of dusty debris disks around a large fraction of solar type main-sequence stars, inferred from excess far-IR and submillimetre emission compared to that expected from stellar photospheres, suggests that leftover planetesimal belts analogous to the asteroid-and comet reservoirs of the solar system are common. Aims. Sensitive submillimetre observations are essential to detect and characterise cold extended dust originating from collisions of small bodies in disks, belts, or rings at Kuiper-belt distances (30-50 AU or beyond). Measurements of the flux densities at these wavelengths will extend existing IR photometry and permit more detailed modelling of the Rayleigh-Jeans tail of the disks spectral energy distribution (SED), effectively constraining dust properties and disk extensions. By observing stars spanning from a few up to several hundred Myr, the evolution of debris disks during crucial phases of planet formation can be studied. Methods. We observed 22 exo-Kuiper-belt candidates at 870 mu m, as part of a large programme with the LABOCA bolometer at the APEX telescope. Dust masses (or upper limits) were calculated from integrated 870 mu m fluxes, and fits to the SED of detected sources revealed the fractional dust luminosities f(dust), dust temperatures T(dust), and power-law exponents beta of the opacity law. Results. A total of 10 detections with at least 3 sigma significance were made, out of which five (HD95086, HD131835, HD161868, HD170773, and HD207129) have previously never been detected at submillimetre wavelengths. Three additional sources are marginally detected with > 2.5 sigma significance. The best-fit beta parameters all lie between 0.1 and 0.8, in agreement with previous results indicating the presence of significantly larger grains than those in the ISM. From our relatively small sample we estimate f(dust) proportional to t(-alpha), with a similar to 0.8-2.0, and identify an evolution of the characteristic radial dust distance R(dust) that is consistent with the t(1/3) increase predicted from models of self-stirred collisions in debris disks.
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| 36. |
- Nilsson, R., et al.
(författare)
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VLT imaging of the beta Pictoris gas disk
- 2012
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 544
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Tidskriftsartikel (refereegranskat)abstract
- Context. Circumstellar debris disks older than a few Myr should be largely devoid of primordial gas remaining from the protoplanetary disk phase. Tracing the origin of observed atomic gas in Keplerian rotation in the edge-on debris disk surrounding the similar to 12 Myr old star beta Pictoris requires more detailed information about its spatial distribution than has previously been acquired by limited slit spectroscopy. Especially indications of asymmetries and presence of Ca II gas at high disk latitudes call for additional investigation to exclude or confirm its connection to observed dust structures or suggested cometary bodies on inclined eccentric orbits. Aims. We set out to recover a complete image of the Fe I and Ca II gas emission around beta Pic by spatially resolved, high-resolution spectroscopic observations to better understand the morphology and origin of the gaseous disk component. Methods. The multiple fiber facility FLAMES/GIRAFFE at the Very Large Telescope (VLT), with the large integral-field-unit ARGUS, was used to obtain spatially resolved optical spectra (from 385.9 to 404.8 nm) in four regions covering the northeast and southwest side of the disk. Emission lines from Fe I (at 386.0 nm) and Ca II (at 393.4 and 396.8 nm) were mapped and could be used to fit a parametric function for the disk gas distribution, using a gas-ionisation code for gas-poor debris disks. Results. Both Fe I and Ca II emission are clearly detected, with the former dominating along the disk midplane, and the latter revealing vertically more extended gas. The surface intensity of the Fe I emission is lower but more extended in the northeast (reaching the 210 AU limit of our observations) than in the southwest, while Ca II shows the opposite asymmetry. The modelled Fe gas disk profile shows a linear increase in scale height with radius, and a vertical profile that suggests dynamical interaction with the dust. We also qualitatively demonstrate that the Ca II emission profile can be explained by optical thickness in the disk midplane, and does not require Ca to be spatially separated from Fe.
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| 37. |
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| 38. |
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| 39. |
- Nilsson, Sten, et al.
(författare)
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Two-Year Survival Follow-Up of the Randomized, Double-Blind, Placebo-Controlled Phase II Study of Radium-223 Chloride in Patients With Castration-Resistant Prostate Cancer and Bone Metastases
- 2013
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Ingår i: Clinical Genitourinary Cancer. - : Elsevier. - 1558-7673 .- 1938-0682. ; 11:1, s. 20-26
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Tidskriftsartikel (refereegranskat)abstract
- In this 24-month follow-up of a phase II study in patients with castration-resistant prostate cancer (CRPC) and bone metastases, radium-223 (4 injections of 50 kBq/kg every 4 weeks [n = 33]) improved median overall survival vs. matching placebo (n = 31) (65.3 vs. 46.4 weeks, respectively; log-rank P = .056), with no long-term safety concerns. Data suggest that treatment of bone disease with radium-223 has survival benefits. less thanbrgreater than less thanbrgreater thanBackground: This phase II randomized, placebo-controlled study was conducted to evaluate efficacy and safety of radium-223 in patients with castration-resistant prostate cancer (CRPC) and painful bone metastases. Twelve-and 18-month survival results were reported previously. Here we report 24-month overall survival (OS) and safety data from the period 12 to 24 months after the first injection of study medication. Methods: Patients with CRPC and bone pain were randomized 1: 1 to receive 4 injections of radium-223 (50 kBq/kg [n = 33]) or placebo (n = 31) after external-beam radiotherapy; each injection was given every 4 weeks. Endpoints for this report were 24-month OS, long-term safety, and treatment-related adverse events (AEs) occurring in the 12- to 24-month period. Results: After 24 months, 10 (30%) patients were alive in the radium-223 group compared with 4 patients (13%) in the placebo group. Patients who received at least 1 dose of study medication had a median OS of 65 weeks in the radium-223 group vs. 46 weeks in the placebo group (log-rank P = .056). The hazard ratio (HR) for OS, adjusted for baseline covariates, was 0.476 (95% confidence interval [CI], 0.258-0.877; Cox regression P = .017). The most frequent cause of death for both arms was disease progression. There were no reports of treatment-related AEs or long-term hematologic toxicity during the 12- to 24-month follow-up. Conclusion: Radium-223 had a highly favorable safety profile, with no evidence of second malignancies at 24-month follow-up. The significant improvement in OS observed in patients receiving radium-223 vs. placebo suggests that treatment of bone disease with radium-223 has survival benefits. Clinical Genitourinary Cancer, Vol. 11, No. 1, 20-6
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| 40. |
- Pett, Christian, et al.
(författare)
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Effective Assignment of α2,3/α2,6-Sialic Acid Isomers by LC-MS/MS-Based Glycoproteomics
- 2018
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Ingår i: Angewandte Chemie International Edition. - : Wiley-VCH Verlagsgesellschaft. - 1433-7851 .- 1521-3773. ; 57:30, s. 9320-9324
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Tidskriftsartikel (refereegranskat)abstract
- Distinct structural changes of the α2,3/α2,6-sialic acid glycosidic linkages on glycoproteins are of importance in cancer biology, inflammatory diseases, and virus tropism. Current glycoproteomic methodologies are, however, not amenable toward high-throughput characterization of sialic acid isomers. To enable such assignments, a mass spectrometry method utilizing synthetic model glycopeptides for the analysis of oxonium ion intensity ratios was developed. This method was successfully applied in large-scale glycoproteomics, thus allowing the site-specific structural characterization of sialic acid isomers.
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| 41. |
- Rasmusson, Elisabeth, et al.
(författare)
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Low-dose rate brachytherapy with I-125 seeds has an excellent 5-year outcome with few side effects in patients with low-risk prostate cancer
- 2016
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Ingår i: Acta Oncologica. - Oxon : Taylor & Francis. - 0284-186X .- 1651-226X. ; 55:8, s. 1016-1021
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Tidskriftsartikel (refereegranskat)abstract
- Background: Low-dose rate brachytherapy (LDR-BT) has been used in Sweden for more than a decade for treatment of low-risk prostate cancer. This study presents the outcome for patients treated with LDR-BT at a single institution with focus on the association between dose and biochemical failure-free survival (BFFS).Methods: In total 195 patients were treated with LDR-BT between 2004 and 2008. The patients were followed systematically for side effects for at least one year. PSA levels were followed regularly from three months and for at least five years. Outcome was analyzed in relation to clinical variables at baseline and to radiotherapy data.Results: Kaplan-Meier estimated BFFS at five years was 95.7%. Dose to the prostate in terms of D-90% was significantly associated with BFFS [HR 0.90 (95%CI 0.83-0.96), p=0.002].Conclusion: Out data confirmed that absorbed dose is a predictive factor for BFFS for low-risk patients without androgen deprivation therapy. With our treatment routines and dosimetry, a D-90% in the range of 170-180Gy gives excellent outcomes with acceptable toxicity for patients with low-risk prostate cancer.
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| 42. |
- Rasmusson, Elisabeth, et al.
(författare)
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Low rate of lymphedema after extended pelvic lymphadenectomy followed by pelvic irradiation of node-positive prostate cancer
- 2013
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Ingår i: Radiation Oncology. - 1748-717X. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Background: The aim of the present study was to evaluate the prevalence and severity of lower limb lymphedema after pelvic lymphadenectomy and radiotherapy to the pelvic lymph nodes in patients with prostate cancer. Methods: Twenty-six patients underwent combined treatment for high-risk node-positive prostate cancer at Skane University Hospital between April 2008 and March 2011. The treatment consisted of extended pelvic lymphadenectomy followed by androgen deprivation therapy and radiotherapy. The pelvic lymphnodes, prostate and seminal vesicles were treated with external beam radiotherapy (EBRT) to an absorbed dose of 50 Gy followed by a brachytherapy (BT) boost of 2x10 Gy to the prostate only. Twenty-two patients accepted an invitation to a clinical examination with focus on lower limb swelling. The median time between the end of radiotherapy and examination was 2.2 years (range 1.2-4.1). Results: Six patients (27%) experienced grade 1 lymphedema and two patients (9%) grade 2 while none had grade 3 or 4 according to the CTC Common Toxicity Criteria scale 4.0. Three patients required treatment with compression stockings. Conclusion: Brachytherapy and pelvic EBRT have a low incidence of lymphedema (at median 2.2 y after treatment) in patients with high-risk node-positive prostate cancer that have undergone pelvic lymph node dissection.
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| 43. |
- Ringerike, Tove, et al.
(författare)
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Detection of immunotoxicity using T-cell based cytokine reporter cell lines ("Cell Chip").
- 2005
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Ingår i: Toxicology. - : Elsevier BV. - 0300-483X .- 1879-3185. ; 206:2, s. 257-72
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Tidskriftsartikel (refereegranskat)abstract
- Safety assessment of chemicals and drugs is an important regulatory issue. The evaluation of potential adverse effects of compounds on the immune system depends today on animal experiments. An increasing demand, however, exists for in vitro alternatives. Cytokine measurement is a promising tool to evaluate chemical exposure effects on the immune system. Fortunately, this type of measurement can be performed in conjunction with in vitro exposure models. We have taken these considerations as the starting point to develop an in vitro method to efficiently screen compounds for potential immunotoxicity. The T-cell lymphoma cell line EL-4 was transfected with the regulatory sequences of interleukin (IL)-2, IL-4, IL-10, interferon (IFN)-gamma or actin fused to the gene for enhanced green fluorescent protein (EGFP) in either a stabile or a destabilised form. Consequently, changes in fluorescence intensity represent changes in cytokine expression with one cell line per cytokine. We used this prototype "Cell Chip" to test, by means of flow cytometry, the immunomodulatory potential of 13 substances and were able to detect changes in cytokine expression in 12 cases (successful for cyclosporine, rapamycin, pentamidine, thalidomide, bis(tri-n-butyltin)oxide, house dust mite allergen (Der p I), 1-chloro-2,4-dinitrobenzene, benzocaine, tolylene 2,4-diisocyanate, potassium tetrachloroplatinate, sodium dodecyl sulphate and mercuric chloride; unsuccessful for penicillin G). In conclusion, this approach seems promising for in vitro screening for potential immunotoxicity, especially when additional cell lines besides T-cells are included.
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| 44. |
- Sydow, Saskia, et al.
(författare)
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MDM2 amplification in rod-shaped chromosomes provides clues to early stages of circularized gene amplification in liposarcoma
- 2024
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Ingår i: Communications Biology. - : Springer Nature. - 2399-3642. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Well-differentiated liposarcoma (WDLS) displays amplification of genes on chromosome 12 (Chr12) in supernumerary ring or giant marker chromosomes. These structures have been suggested to develop through chromothripsis, followed by circularization and breakage-fusion-bridge (BFB) cycles. To test this hypothesis, we compared WDLSs with Chr12 amplification in rod-shaped chromosomes with WDLSs with rings. Both types of amplicons share the same spectrum of structural variants (SVs), show higher SV frequencies in Chr12 than in co-amplified segments, have SVs that fuse the telomeric ends of co-amplified chromosomes, and lack interspersed deletions. Combined with the finding of cells with transient rod-shaped structures in tumors with ring chromosomes, this suggests a stepwise process starting with the gain of Chr12 material that, after remodeling which does not fit with classical chromothripsis, forms a dicentric structure with other chromosomes. Depending on if and when telomeres from other chromosomes are captured, circularized or linear gain of 12q sequences will predominate.
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| 45. |
- Thellenberg-Karlsson, Camilla, 1972-, et al.
(författare)
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Bone-targeted Novel Cytotoxic Polybisphosphonate Conjugate in Castration-resistant Prostate Cancer : A Multicenter Phase 1 Study
- 2016
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Ingår i: Anticancer Research. - : International Institute of Anticancer Research. - 0250-7005 .- 1791-7530. ; 36:12, s. 6499-6504
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Osteodex (ODX) is a cytotoxic bone-targeting polybisphosphonate, intended for treatment of bone metastasis from castration-resistant prostate cancer (CRPC). The primary objective of this study was to describe the tolerability and toxicity of such treatment by defining its maximum tolerated dose (MTD) and dose-limiting toxicity (DLT).PATIENTS AND METHODS: Twenty-eight patients with castration-resistant prostate cancer and confirmed bone metastasis were assigned to seven infusions of ODX every third week, divided in seven ascending dose cohorts.RESULTS: No DLT's were observed and as pre-specified, the highest dose administered was defined as MTD. In total, 206 adverse events (AE) were recorded and 13,6% were classified as treatment-related, while none were serious or severe (SAE). No cumulative toxicity and no renal toxicity were recorded.CONCLUSION: ODX was well tolerated, with few and mild side-effects and with apparent treatment efficacy in the highest dose cohort. Further clinical development is currently in progress.
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| 46. |
- Wibroe, Morten, et al.
(författare)
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Cerebellar mutism syndrome in children with brain tumours of the posterior fossa
- 2017
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Ingår i: BMC Cancer. - : BIOMED CENTRAL LTD. - 1471-2407. ; 17
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Tidskriftsartikel (refereegranskat)abstract
- Background: Central nervous system tumours constitute 25% of all childhood cancers; more than half are located in the posterior fossa and surgery is usually part of therapy. One of the most disabling late effects of posterior fossa tumour surgery is the cerebellar mutism syndrome (CMS) which has been reported in up to 39% of the patients but the exact incidence is uncertain since milder cases may be unrecognized. Recovery is usually incomplete. Reported risk factors are tumour type, midline location and brainstem involvement, but the exact aetiology, surgical and other risk factors, the clinical course and strategies for prevention and treatment are yet to be determined.Methods: This observational, prospective, multicentre study will include 500 children with posterior fossa tumours. It opened late 2014 with participation from 20 Nordic and Baltic centres. From 2016, five British centres and four Dutch centres will join with a total annual accrual of 130 patients. Three other major European centres are invited to join from 2016/17. Follow-up will run for 12 months after inclusion of the last patient. All patients are treated according to local practice. Clinical data are collected through standardized online registration at pre-determined time points pre- and postoperatively. Neurological status and speech functions are examined pre- operatively and postoperatively at 1-4 weeks, 2 and 12 months. Pre- and postoperative speech samples are recorded and analysed. Imaging will be reviewed centrally. Pathology is classified according to the 2007 WHO system. Germline DNA will be collected from all patients for associations between CMS characteristics and host genome variants including pathway profiles.Discussion: Through prospective and detailed collection of information on 1) differences in incidence and clinical course of CMS for different patient and tumour characteristics, 2) standardized surgical data and their association with CMS, 3) diversities and results of other therapeutic interventions, and 4) the role of host genome variants, we aim to achieve a better understanding of risk factors for and the clinical course of CMS - with the ultimate goal of defining strategies for prevention and treatment of this severely disabling condition.
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