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Sökning: WFRF:(Nyström T.)

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  • Thompson, B.A., et al. (författare)
  • Application of a 5-tiered scheme for standardized classification of 2,360 unique mismatch repair gene variants in the InSiGHT locus-specific database
  • 2014
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 46:2, s. 107-115
  • Tidskriftsartikel (refereegranskat)abstract
    • The clinical classification of hereditary sequence variants identified in disease-related genes directly affects clinical management of patients and their relatives. The International Society for Gastrointestinal Hereditary Tumours (InSiGHT) undertook a collaborative effort to develop, test and apply a standardized classification scheme to constitutional variants in the Lynch syndrome-associated genes MLH1, MSH2, MSH6 and PMS2. Unpublished data submission was encouraged to assist in variant classification and was recognized through microattribution. The scheme was refined by multidisciplinary expert committee review of the clinical and functional data available for variants, applied to 2,360 sequence alterations, and disseminated online. Assessment using validated criteria altered classifications for 66% of 12,006 database entries. Clinical recommendations based on transparent evaluation are now possible for 1,370 variants that were not obviously protein truncating from nomenclature. This large-scale endeavor will facilitate the consistent management of families suspected to have Lynch syndrome and demonstrates the value of multidisciplinary collaboration in the curation and classification of variants in public locus-specific databases. © 2014 Nature America, Inc.
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  • Carmona-Gutierrez, D., et al. (författare)
  • Guidelines and recommendations on yeast cell death nomenclature
  • 2018
  • Ingår i: Microbial Cell. - : Shared Science Publishers OG. - 2311-2638. ; 5:1, s. 4-31
  • Forskningsöversikt (refereegranskat)abstract
    • Elucidating the biology of yeast in its full complexity has major implications for science, medicine and industry. One of the most critical processes determining yeast life and physiology is cellular demise. However, the investigation of yeast cell death is a relatively young field, and a widely accepted set of concepts and terms is still missing. Here, we propose unified criteria for the definition of accidental, regulated, and programmed forms of cell death in yeast based on a series of morphological and biochemical criteria. Specifically, we provide consensus guidelines on the differential definition of terms including apoptosis, regulated necrosis, and autophagic cell death, as we refer to additional cell death routines that are relevant for the biology of (at least some species of) yeast. As this area of investigation advances rapidly, changes and extensions to this set of recommendations will be implemented in the years to come. Nonetheless, we strongly encourage the authors, reviewers and editors of scientific articles to adopt these collective standards in order to establish an accurate framework for yeast cell death research and, ultimately, to accelerate the progress of this vibrant field of research.
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  • Gomez Real, F., et al. (författare)
  • Hormone replacement therapy, body mass index and asthma in perimenopausal women: a cross sectional survey
  • 2006
  • Ingår i: Thorax.. ; 61:1
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Hormone replacement therapy (HRT) and obesity both appear to increase the risk of asthma. A study was undertaken to investigate the association of HRT with asthma and hay fever in a population of perimenopausal women, focusing on a possible interaction with body mass index (BMI). METHODS: A postal questionnaire was sent to population based samples in Denmark, Estonia, Iceland, Norway, and Sweden in 1999-2001, and 8588 women aged 25-54 years responded (77%). Pregnant women, women using oral contraceptives, and women <46 years were excluded. Analyses included 2206 women aged 46-54 years of which 884 were menopausal and 540 used HRT. Stratified analyses by BMI in tertiles were performed. RESULTS: HRT was associated with an increased risk for asthma (OR 1.57 (95% CI 1.07 to 2.30)), wheeze (OR 1.60 (95% CI 1.22 to 2.10)), and hay fever (OR 1.48 (95% CI 1.15 to 1.90)). The associations with asthma and wheeze were significantly stronger among women with BMI in the lower tertile (asthma OR 2.41 (95% CI 1.21 to 4.77); wheeze OR 2.04 (95% CI 1.23 to 3.36)) than in heavier women (asthma: p(interaction) = 0.030; wheeze: p(interaction) = 0.042). Increasing BMI was associated with more asthma (OR 1.08 (95% CI 1.05 to 1.12) per kg/m(2)). This effect was only found in women not taking HRT (OR 1.10 (95% CI 1.05 to 1.14) per kg/m(2)); no such association was detected in HRT users (OR 1.00 (95% CI 0.92 to 1.08) per kg/m(2)) (p(interaction) = 0.046). Menopause was not significantly associated with asthma, wheeze, or hay fever. CONCLUSIONS: In perimenopausal women there is an interaction between HRT and BMI in the effects on asthma. Lean women who were HRT users had as high a risk for asthma as overweight women not taking HRT. It is suggested that HRT and overweight increase the risk of asthma through partly common pathways.
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  • Guimond, S. E., et al. (författare)
  • Synthetic Heparan Sulfate Mimetic Pixatimod (PG545) Potently Inhibits SARS-CoV-2 by Disrupting the Spike-ACE2 Interaction
  • 2022
  • Ingår i: ACS Central Science. - : American Chemical Society (ACS). - 2374-7943 .- 2374-7951. ; 8:5, s. 527-545
  • Tidskriftsartikel (refereegranskat)abstract
    • Heparan sulfate (HS) is a cell surface polysaccharide recently identified as a coreceptor with the ACE2 protein for the S1 spike protein on SARS-CoV-2 virus, providing a tractable new therapeutic target. Clinically used heparins demonstrate an inhibitory activity but have an anticoagulant activity and are supply-limited, necessitating alternative solutions. Here, we show that synthetic HS mimetic pixatimod (PG545), a cancer drug candidate, binds and destabilizes the SARS-CoV-2 spike protein receptor binding domain and directly inhibits its binding to ACE2, consistent with molecular modeling identification of multiple molecular contacts and overlapping pixatimod and ACE2 binding sites. Assays with multiple clinical isolates of SARS-CoV-2 virus show that pixatimod potently inhibits the infection of monkey Vero E6 cells and physiologically relevant human bronchial epithelial cells at safe therapeutic concentrations. Pixatimod also retained broad potency against variants of concern (VOC) including B.1.1.7 (Alpha), B.1.351 (Beta), B.1.617.2 (Delta), and B.1.1.529 (Omicron). Furthermore, in a K18-hACE2 mouse model, pixatimod significantly reduced SARS-CoV-2 viral titers in the upper respiratory tract and virus-induced weight loss. This demonstration of potent anti-SARS-CoV-2 activity tolerant to emerging mutations establishes proof-of-concept for targeting the HS-Spike protein-ACE2 axis with synthetic HS mimetics and provides a strong rationale for clinical investigation of pixatimod as a potential multimodal therapeutic for COVID-19.
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  • Murphy, M. P., et al. (författare)
  • Guidelines for measuring reactive oxygen species and oxidative damage in cells and in vivo
  • 2022
  • Ingår i: Nature Metabolism. - : Springer Science and Business Media LLC. - 2522-5812. ; 4:6, s. 651-662
  • Tidskriftsartikel (refereegranskat)abstract
    • Multiple roles of reactive oxygen species (ROS) and their consequences for health and disease are emerging throughout biological sciences. This development has led researchers unfamiliar with the complexities of ROS and their reactions to employ commercial kits and probes to measure ROS and oxidative damage inappropriately, treating ROS (a generic abbreviation) as if it were a discrete molecular entity. Unfortunately, the application and interpretation of these measurements are fraught with challenges and limitations. This can lead to misleading claims entering the literature and impeding progress, despite a well-established body of knowledge on how best to assess individual ROS, their reactions, role as signalling molecules and the oxidative damage that they can cause. In this consensus statement we illuminate problems that can arise with many commonly used approaches for measurement of ROS and oxidative damage, and propose guidelines for best practice. We hope that these strategies will be useful to those who find their research requiring assessment of ROS, oxidative damage and redox signalling in cells and in vivo. Reactive oxygen species (ROS) have important roles in health and disease, but are chemically complex and difficult to measure accurately. This consensus statement proposes guidelines and best practices on the nomenclature and assessment of ROS, oxidative reactions and oxidative damage in cells, tissues and in vivo.
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  • Brokopp, T, et al. (författare)
  • KAMEDO Report No. 91: 2004 tsunami disaster in Asia--home transport and emergency care in Sweden
  • 2008
  • Ingår i: Prehospital and disaster medicine. - : Cambridge University Press (CUP). - 1049-023X .- 1945-1938. ; 23:5, s. 472-5
  • Tidskriftsartikel (refereegranskat)abstract
    • This is a descriptive report of the Swedish authorities' responses to the tsunami that affected Southeast Asia in December 2004. The main focus is the care of survivors and the injured during their transportation from Thailand and their return to Sweden. The psychological and physical after-effects also are presented based on a poll conducted one year after the tsunami.
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  • Damm, S., et al. (författare)
  • Wall motion abnormalities in male elite orienteers are aggravated by exercise
  • 1999
  • Ingår i: Clinical Physiology. - : Wiley. - 0144-5979 .- 1365-2281. ; 19:2, s. 121-126
  • Tidskriftsartikel (refereegranskat)abstract
    • During the period 1979-92, 16 (15 men and one woman) sudden unexpected cardiac deaths occurred among young Swedish orienteers. This finding indicated a sharp increase in the death rate of orienteers, and necropsy demonstrated that myocarditis was a common histopathological finding. Therefore, an extensive non-invasive cardiac investigation was performed. A total of 59 male élite orienteers (mean age 23 years) and 36 cross-country skiers and middle-distance runners (mean age 22 years), serving as controls, were examined by both echocardiography at rest and radionuclide ventriculography at rest and during exercise. Wall motion abnormalities were found in eight orienteers using echocardiography. The purpose of this study was to examine whether the group of orienteers with wall motion abnormalities found using echocardiography had a smaller increase in ejection fraction from rest to exercise using radionuclide ventriculography than the rest of the orienteers and the controls, indicating an aggravation of the wall motion abnormalities during exercise. There were no significant differences in the ejection fraction at rest between the groups. In the orienteers with wall motion abnormalities (group 1), 62% (five out of eight) had less than a 0.05 unit increase in left ventricular ejection fraction compared with 27% (14 out of 51) of the remaining orienteers (group 2) and 19% (7 out of 36) of the controls (group 3). A comparison of athletes in group 1 with those in groups 2 and 3 combined revealed a statistically significant difference (P < 0.05). The divergent response in left ventricular ejection fraction during exercise suggests an aggravation of the wall motion abnormalities with exercise. Both the echocardiographic and the radionuclide ventriculographic findings indicate that the orienteers in group 1 had concealed left ventricular damage.
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  • Dunn, Matt J, et al. (författare)
  • Minimal reporting guideline for research involving eye tracking (2023 edition)
  • Ingår i: Behavior Research Methods. - 1554-3528.
  • Tidskriftsartikel (refereegranskat)abstract
    • A guideline is proposed that comprises the minimum items to be reported in research studies involving an eye tracker and human or non-human primate participant(s). This guideline was developed over a 3-year period using a consensus-based process via an open invitation to the international eye tracking community. This guideline will be reviewed at maximum intervals of 4 years.
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  • Gullström, Charlie (författare)
  • High-fidelity Mock-up Report : Public deliverable D.2.4 from COMPEIT, EU FP7 project
  • 2015
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • COMPEIT is a 3-year EU 7th framework project and focuses on a web-based system for highly interactive, personalised, shared media experiences by developing technologies that A) enrich social connections, B) improve the feeling of being together in one shared space and C) enhance collaboration whilst being separated in time or space. COMPEIT takes the view that Internet-based distribution will transform traditional broadcasting towards higher levels of interactivity and integration with virtual and augmented reality, enabled by advanced web technologies and the proliferation of tangible devices. The project addresses Quality of Experience as a key variable in the experience of media production and consumption systems.A first mock-up of the COMPEIT system has been put together. It illustrates technical components from WP 4 (Mediated Presence Components); services from WP 5 (New Media Services); and D3.2 Initial System Specification. It informs further research towards D3.4 First Prototype.
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  • Gyllenberg, A, et al. (författare)
  • Variability in the CIITA gene interacts with HLA in multiple sclerosis.
  • 2014
  • Ingår i: Genes and immunity. - Stockholm : Springer Science and Business Media LLC. - 1476-5470 .- 1466-4879. ; 15, s. 162-167
  • Tidskriftsartikel (refereegranskat)abstract
    • The human leukocyte antigen (HLA) is the main genetic determinant of multiple sclerosis (MS) risk. Within the HLA, the class II HLA-DRB1*15:01 allele exerts a disease-promoting effect, whereas the class I HLA-A*02 allele is protective. The CIITA gene is crucial for expression of class II HLA molecules and has previously been found to associate with several autoimmune diseases, including MS and type 1 diabetes. We here performed association analyses with CIITA in 2000 MS cases and up to 6900 controls as well as interaction analysis with HLA. We find that the previously investigated single-nucleotide polymorphism rs4774 is associated with MS risk in cases carrying the HLA-DRB1*15 allele (P=0.01, odds ratio (OR): 1.21, 95% confidence interval (CI): 1.04-1.40) or the HLA-A*02 allele (P=0.01, OR: 1.33, 95% CI: 1.07-1.64) and that these associations are independent of the adjacent confirmed MS susceptibility gene CLEC16A. We also confirm interaction between rs4774 and HLA-DRB1*15:01 such that individuals carrying the risk allele for rs4774 and HLA-DRB1*15:01 have a higher than expected risk for MS. In conclusion, our findings support previous data that variability in the CIITA gene affects MS risk, but also that the effect is modulated by MS-associated HLA haplotypes. These findings further underscore the biological importance of HLA for MS risk.Genes and Immunity advance online publication, 16 January 2014; doi:10.1038/gene.2013.71.
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  • Ittermann, T., et al. (författare)
  • Standardized Map of Iodine Status in Europe
  • 2020
  • Ingår i: Thyroid. - : Mary Ann Liebert Inc. - 1050-7256 .- 1557-9077. ; 30:9
  • Tidskriftsartikel (refereegranskat)abstract
    • Background:Knowledge about the population's iodine status is important, because it allows adjustment of iodine supply and prevention of iodine deficiency. The validity and comparability of iodine-related population studies can be improved by standardization, which was one of the goals of the EUthyroid project. The aim of this study was to establish the first standardized map of iodine status in Europe by using standardized urinary iodine concentration (UIC) data. Materials and Methods:We established a gold-standard laboratory in Helsinki measuring UIC by inductively coupled plasma mass spectrometry. A total of 40 studies from 23 European countries provided 75 urine samples covering the whole range of concentrations. Conversion formulas for UIC derived from the gold-standard values were established by linear regression models and were used to postharmonize the studies by standardizing the UIC data of the individual studies. Results:In comparison with the EUthyroid gold-standard, mean UIC measurements were higher in 11 laboratories and lower in 10 laboratories. The mean differences ranged from -36.6% to 49.5%. Of the 40 postharmonized studies providing data for the standardization, 16 were conducted in schoolchildren, 13 in adults, and 11 in pregnant women. Median standardized UIC was <100 mu g/L in 1 out of 16 (6.3%) studies in schoolchildren, while in adults 7 out of 13 (53.8%) studies had a median standardized UIC <100 mu g/L. Seven out of 11 (63.6%) studies in pregnant women revealed a median UIC Conclusions:We demonstrate that iodine deficiency is still present in Europe, using standardized data from a large number of studies. Adults and pregnant women, particularly, are at risk for iodine deficiency, which calls for action. For instance, a more uniform European legislation on iodine fortification is warranted to ensure that noniodized salt is replaced by iodized salt more often. In addition, further efforts should be put on harmonizing iodine-related studies and iodine measurements to improve the validity and comparability of results.
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  • Janson, C., et al. (författare)
  • Insomnia is more common among subjects living in damp buildings
  • 2005
  • Ingår i: Occup Environ Med. ; 62:2
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Insomnia is a condition with a high prevalence and a great impact on quality of life. Little is known about the relation between and sleep disturbances and the home environment. AIM: To analyse the association between insomnia and building dampness. METHODS: In a cross-sectional, multicentre, population study, 16 190 subjects (mean age 40 years, 53% women) were studied from Reykjavik in Iceland, Bergen in Norway, Umea, Uppsala, and Goteborg in Sweden, Aarhus in Denmark, and Tartu in Estonia. Symptoms related to insomnia were assessed by questionnaire. RESULTS: Subjects living in houses with reported signs of building dampness (n = 2873) had a higher prevalence of insomnia (29.4 v 23.6%; crude odds ratio 1.35, 95% CI 1.23 to 1.48). The association between insomnia and different indicators of building dampness was strongest for floor dampness: "bubbles or discoloration on plastic floor covering or discoloration of parquet floor" (crude odds ratio 1.96, 95% CI 1.66 to 2.32). The associations remained significant after adjusting for possible confounders such as sex, age, smoking history, housing, body mass index, and respiratory diseases. There was no significant difference between the centres in the association between insomnia and building dampness. CONCLUSION: Insomnia is more common in subjects living in damp buildings. This indicates that avoiding dampness in building constructions and improving ventilation in homes may possibly have a positive effect on the quality of sleep.
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  • Landin-Olsson, Mona, et al. (författare)
  • Immunoreactive trypsin(Ogen) in the sera of children with recent-onset insulin-dependent diabetes and matched controls
  • 1990
  • Ingår i: Pancreas. - : Ovid Technologies (Wolters Kluwer Health). - 0885-3177. ; 5:3, s. 241-247
  • Tidskriftsartikel (refereegranskat)abstract
    • To evaluate the exocrine pancreatic function at the time of diagnosis of insulin-dependent diabetes mellitus, we determined immunoreactive an-odal and cathodal trypsin(ogen) levels in sera from almost all children (n = 375) 0-14 years of age in Sweden in whom diabetes developed during 1 year, and in sex-, age-, and geographically matched control subjects (n = 312). The median level of anodal trypsin(ogen) was 5 (quartile range, 3-7) µg/L in children with newly diagnosed diabetes, compared with a median level of 7 (quartile range, 4-8) µg/L in control subjects (p < 0.0001). Similarly, the median level of cathodal trypsin(ogen) was 8 (quartile range, 4-10) µg/L in children with diabetes, compared with a median level of 11 (quartile range, 7-15) µg/L in control subjects (p < 0.0001). The median of the individual ratios between cathodal and anodal trypsin(ogen) was 1.4 in the diabetic patients and 1.7 in the control children (p < 0.001). In a multivariate test, however, only the decrease in cathodal trypsin(ogen) concentration was associated with diabetes. The levels of trypsin(ogen)s did not correlate with levels of islet cell antibodies, present in 81% of the diabetic children. Several mechanisms may explain our findings, for example, similar pathogenetic factors may affect both the endocrine and exocrine pancreas simultaneously, a failing local trophic stimulation by insulin on the exocrine cells may decrease the trypsinogen production, and there may be an increased elimination of trypsin(ogen) because of higher filtration through the kidneys in the hyperglycemic state.
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  • Mollehave, L. T., et al. (författare)
  • Register-based information on thyroid diseases in Europe: lessons and results from the EUthyroid collaboration
  • 2022
  • Ingår i: Endocrine Connections. - : Bioscientifica. - 2049-3614. ; 11:3
  • Tidskriftsartikel (refereegranskat)abstract
    • ObjectiveRegisters of diagnoses and treatments exist in different forms in the European countries and are potential sources to answer important research questions. Prevalence and incidence of thyroid diseases are highly dependent on iodine intake and, thus, iodine deficiency disease prevention programs. We aimed to collect European register data on thyroid outcomes to compare the rates between countries/regions with different iodine status and prevention programs. DesignRegister-based cross-sectional study. MethodsNational register data on thyroid diagnoses and treatments were requested from 23 European countries/regions. The provided data were critically assessed for suitability for comparison between countries/regions. Sex- and age-standardized rates were calculated. ResultsRegister data on >= 1 thyroid diagnoses or treatments were available from 22 countries/regions. After critical assessment, data on medication, surgery, and cancer were found suitable for comparison between 9, 10, and 13 countries/regions, respectively. Higher rates of antithyroid medication and thyroid surgery for benign disease and lower rates of thyroid hormone therapy were found for countries with iodine insufficiency before approx. 2001, and no relationship was observed with recent iodine intake or prevention programs. ConclusionsThe collation of register data on thyroid outcomes from European countries is impeded by a high degree of heterogeneity in the availability and quality of data between countries. Nevertheless, a relationship between historic iodine intake and rates of treatments for hyper- and hypothyroid disorders is indicated. This study illustrates both the challenges and the potential for the application of register data of thyroid outcomes across Europe.
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  • Sandén, Anna Maria, et al. (författare)
  • Limiting factors in Escherichia coli fed-batch production of recombinant proteins
  • 2003
  • Ingår i: Biotechnology and Bioengineering. - : Wiley. - 0006-3592 .- 1097-0290. ; 81:2, s. 158-166
  • Tidskriftsartikel (refereegranskat)abstract
    • Fed-batch production of recombinant beta-galactosidase in E. coli was studied with respect to the specific growth rate at induction. The cultivations were designed to induce protein production by IPTG at a glucose feed rate corresponding to high (mu = 0.5 h(-1)) or low (mu = 0.1 h(-1)) specific growth rate. Protein production rate was approximately 100% higher at the higher specific growth rate, resulting in the accumulation of beta-galactosidase up to 30% of the total cell protein. Transcription analysis showed that beta-galactosidase-specific messenger RNA was immediately formed after induction (<5 min), but the amount was the same in both cases and was thus not the initial limiting factor. The content of ribosomes, as represented by rRNA, rapidly decreased with specific growth rate from a relative level of 100%, at the high specific growth rate, to 20% at the low specific growth rate. At high specific growth rate, ribosomes were additionally degraded upon induction due to the high production level. Translation therefore seemed to be the initial limiting factor of the protein synthesis capacity. The alarmone guanosine tetraphosphate increased at both high and low feed level inductions, indicating an induction-forced starvation of charged tRNA and/or glucose. The altered physiological status was also detected by the formation of acetic acid. However, the higher production rate resulted in high-level accumulation of acetic acid, which was absent at low feed rate production. Acetic acid production is thus coupled to the high product formation rate and is proposed to be due either to a precursor drain of Krebs cycle intermediates and a time lag before induction of the glyoxalate shunt, or to single amino acid overflow, since the model product is relatively poor in glycin and alanin. In conclusion, it is proposed that production at high specific growth rate becomes precursor-limited, while production at low specific growth rate is carbon- and/or energy-limited.
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  • Toft, N, et al. (författare)
  • Results of NOPHO ALL2008 treatment for patients aged 1-45 years with acute lymphoblastic leukemia.
  • 2018
  • Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 1476-5551 .- 0887-6924. ; 32, s. 606-615
  • Tidskriftsartikel (refereegranskat)abstract
    • Adults with acute lymphoblastic leukemia (ALL) do worse than children. From 7/2008 to 12/2014, Nordic and Baltic centers treated 1509 consecutive patients aged 1-45 years with Philadelphia chromosome-negative ALL according to the NOPHO ALL2008 without cranial irradiation. Overall, 1022 patients were of age 1-9 years (A), 266 were 10-17 years (B) and 221 were 18-45 years (C). Sixteen patients (three adults) died during induction. All others achieved remission after induction or 1-3 intensive blocks. Subsequently, 45 patients (12 adults) died, 122 patients relapsed (32 adults) with a median time to relapse of 1.6 years and 13 (no adult) developed a second malignancy. Median follow-up time was 4.6 years. Among the three age groups, older patients more often had higher risk ALL due to T-ALL (32%/25%/9%, P<0.001), KMT2A rearrangements (6%/5%/3%, P<0.001) and higher day 29 residual leukemia for B-lineage (P<0.001), but not T-ALL (P=0.53). Event-free survival rates (pEFS5y) were 89±1% (A), 80±3% (B) and 74±4% (C) with significant differences only for non-high risk groups. Except for thrombosis, pancreatitis and osteonecrosis, the risk of 19 specified toxicities was not enhanced by age above 10 years. In conclusion, a pediatric-based protocol is tolerable and effective for young adults, despite their increased frequency of higher risk features.Leukemia advance online publication, 22 September 2017; doi:10.1038/leu.2017.265.
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  • Al-Khalili, Lubna, et al. (författare)
  • Profiling of human myotubes reveals an intrinsic proteomic signature associated with type 2 diabetes
  • 2014
  • Ingår i: Translational Proteomics. - : Elsevier BV. - 2212-9634 .- 2212-9626. ; 2:1, s. 25-38
  • Tidskriftsartikel (refereegranskat)abstract
    • The development of insulin resistance and type 2 diabetes (T2D) involves a complex array of metabolic defects in skeletal muscle. An in vitro cell culture system excludes the acute effects of external systemic factors existing in vivo. Thus, we aimed to determine whether intrinsic differences in the protein profile exist in cultured myotubes derived from T2D versus normal glucose tolerant (NGT) healthy people. Applying two dimensional difference gel electrophoresis technology (2-D DIGE), the abundance of 47 proteins differed in myotubes derived from T2D patients versus NGT donors. Proteins involved in fatty acid and amino acid metabolism, TCA cycle, mitochondrial function, mRNA processing, DNA repair and cell survival showed higher abundance, while proteins associated with redox signaling (PARK7; Parkinson disease 7), glutathione metabolism (glutathione S-transferase, GST, isoforms T1, P1 and M2), and protein dynamics (heat shock protein, HSP, isoform B1 and 90A) showed reduced abundance in myotubes derived from T2D versus NGT donors. Consistent with our proteome analysis results, the level of total glutathione was reduced in myotubes obtained from T2D versus NGT donors. Taken together, our data provide evidence for intrinsic differences in the profile of proteins involved in energy metabolism, cellular oxidative stress, protein dynamics and gene regulation in myotubes derived from T2D patients. These differences thereby suggest a genetic or epigenetic influence on protein content level, which can be further investigated to understand the molecular underpinnings of T2D progression and lead to new therapeutic approaches.
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35.
  • Ammar, Yosr, et al. (författare)
  • Exploring future ecosystem novelty and resilience using the adaptive cycle
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • Marine ecosystems worldwide are under unprecedented pressure from the impacts of climate change and human activities. Such pressure increased novelty in species assemblages, i.e., assemblages increasingly outside their historical range of variation. It may further rise in the future, and whether it will unfold and influence resilience remains unclear. Using the adaptive cycle, we explore the relationship between resilience and novelty under the compound effect of climate, nutrient load, and fishing management scenarios in the Finnish Archipelago Sea (FAS) future food web model. Novelty was measured as the minimum dissimilarity over time relative to a specific baseline. Ecological Network Analysis indices associated to the model: ascendancy, capacity, and overhead flow, were used as indicators of connectedness, potential, and resilience axes of the adaptive cycle. A model-based clustering method distinguished four regimes determined by the impact of the nutrient load and climate on the bottom-up dynamic of the FAS food web. Resilience decreased in regimes where higher and faster novelty emerged in response to warmer climate pathways. The number of reorganization phases of the adaptive cycle, characterized by the generation of novelty, was greater in regimes under low nutrient load management scenarios. We highlight the importance of understanding ecosystem reorganization and resilience in a growing Anthropogenic novelty to inform future management. 
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36.
  • Andersson, Lars-Göran, et al. (författare)
  • Thallium-201 Myocardial Imaging at Rest in Male Orienteers and Other Endurance Athletes
  • 2001
  • Ingår i: Upsala Journal of Medical Sciences. - : Uppsala Medical Society. - 0300-9734 .- 2000-1967. ; 106:1, s. 59-66
  • Tidskriftsartikel (refereegranskat)abstract
    • During the period 1979 to 1992, 16 sudden unexpected cardiac deaths were known to have occurred in young Swedish orienteers. Autopsy indicated myocarditis to be the most frequent finding, most often combined with extensive myocardial fibrosis. The aim of the present investigation was to explore whether young male orienteers show a higher frequency than other young elite endurance athletes (controls) in the occurrence of Thallium-201 myocardial perfusion defects at rest, suggestive of fibrosis evoked by myocarditis. Thallium-201 perfusion abnormalities at rest were more frequently found in the controls than in the orienteers (26% vs. 12%, p=0.03). Uneven Tl-201 perfusion was associated with left ventricular mass (r=0.32, r=0.24, p<0.01, p=0.02) and body weight (r=0.30, r=0.31, p<0.01, p=0.03) in orienteers and controls, respectively. Echocardiographic left ventricular wall motion abnormalities were found in 11 athletes (9 orienteers and 2 controls) but only two displayed an abnormal Thallium-201 perfusion scan at rest. Perfusion abnormalities at rest did not occur more frequently in the orienteers but were commonly found in both groups of apparently healthy athletes making it futile to discern abnormals from normals. Thallium-201 perfusion aberrations were not associated with left ventricular wall motion abnormalities obtained by echocardiography.
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  • Anthony, Kenneth R. N., et al. (författare)
  • Operationalizing resilience for adaptive coral reef management under global environmental change
  • 2015
  • Ingår i: Global Change Biology. - : Wiley. - 1354-1013 .- 1365-2486. ; 21:1, s. 48-61
  • Forskningsöversikt (refereegranskat)abstract
    • Cumulative pressures from global climate and ocean change combined with multiple regional and local-scale stressors pose fundamental challenges to coral reef managers worldwide. Understanding how cumulative stressors affect coral reef vulnerability is critical for successful reef conservation now and in the future. In this review, we present the case that strategically managing for increased ecological resilience (capacity for stress resistance and recovery) can reduce coral reef vulnerability (risk of net decline) up to a point. Specifically, we propose an operational framework for identifying effective management levers to enhance resilience and support management decisions that reduce reef vulnerability. Building on a system understanding of biological and ecological processes that drive resilience of coral reefs in different environmental and socio-economic settings, we present an Adaptive Resilience-Based management (ARBM) framework and suggest a set of guidelines for how and where resilience can be enhanced via management interventions. We argue that press-type stressors (pollution, sedimentation, overfishing, ocean warming and acidification) are key threats to coral reef resilience by affecting processes underpinning resistance and recovery, while pulse-type (acute) stressors (e.g. storms, bleaching events, crown-of-thorns starfish outbreaks) increase the demand for resilience. We apply the framework to a set of example problems for Caribbean and Indo-Pacific reefs. A combined strategy of active risk reduction and resilience support is needed, informed by key management objectives, knowledge of reef ecosystem processes and consideration of environmental and social drivers. As climate change and ocean acidification erode the resilience and increase the vulnerability of coral reefs globally, successful adaptive management of coral reefs will become increasingly difficult. Given limited resources, on-the-ground solutions are likely to focus increasingly on actions that support resilience at finer spatial scales, and that are tightly linked to ecosystem goods and services.
  •  
39.
  • Arnesen, H., et al. (författare)
  • Microbial experience through housing in a farmyard-type environment alters intestinal barrier properties in mouse colons
  • 2023
  • Ingår i: Scientific Reports. - 2045-2322. ; 13:1
  • Tidskriftsartikel (refereegranskat)abstract
    • To close the gap between ultra-hygienic research mouse models and the much more environmentally exposed conditions of humans, we have established a system where laboratory mice are raised under a full set of environmental factors present in a naturalistic, farmyard-type habitat-a process we have called feralization. In previous studies we have shown that feralized (Fer) mice were protected against colorectal cancer when compared to conventionally reared laboratory mice (Lab). However, the protective mechanisms remain to be elucidated. Disruption of the protective intestinal barrier is an acknowledged player in colorectal carcinogenesis, and in the current study we assessed colonic mucosal barrier properties in healthy, feralized C57BL/6JRj male mice. While we found no effect of feralization on mucus layer properties, higher expression of genes encoding the mucus components Fcgbp and Clca1 still suggested mucus enforcement due to feralization. Genes encoding other proteins known to be involved in bacterial defense (Itln1, Ang1, Retnlb) and inflammatory mechanisms (Zbp1, Gsdmc2) were also higher expressed in feralized mice, further suggesting that the Fer mice have an altered intestinal mucosal barrier. These findings demonstrate that microbial experience conferred by housing in a farmyard-type environment alters the intestinal barrier properties in mice possibly leading to a more robust protection against disease. Future studies to unravel regulatory roles of feralization on intestinal barrier should aim to conduct proteomic analyses and in vivo performance of the feralized mice intestinal barrier.
  •  
40.
  • Axelsson, Susanne, et al. (författare)
  • Psychotherapy students' experiences of supervisee-centred supervision based on deliberate practice, feedback-informed treatment and self-compassion
  • 2024
  • Ingår i: Counselling and Psychotherapy Research. - : John Wiley & Sons. - 1473-3145 .- 1746-1405. ; 24:2, s. 719-733
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: There are few methods that focus on therapists' experiences of supervision. To facilitate the development of psychologist students, a supervisee-centred supervision, based on deliberate practice, feedback informed treatment and self-compassion, was introduced.Methods: This study examines six supervisees’ experiences of a supervisee-centred supervision. A semi- structured interview was used for the collection of the data, which identified two main themes: Learning and Development and five associated sub-themes: structure and purposesfulness, prerequisites, experience-based learning, therapeutic skills and personal development.Conclusion: The experience- and feedback-based approach was perceived as efficient, structured and goal oriented. This created high-focused activity and participation, a strong group dynamic and a good alliance with the supervisors, providing a good climate for learning and development. Focusing on performance and feedback was perceived as a potential obstacle that could create stress and anxiety.
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41.
  •  
42.
  •  
43.
  • Boman, G, et al. (författare)
  • Fatal asthma in sweden is decreasing
  • 2002
  • Ingår i: European Respiratory Journal. ; 20 Supplement 38, s. 199-
  • Recension (populärvet., debatt m.m.)
  •  
44.
  •  
45.
  •  
46.
  • Bylund, Johan, 1975, et al. (författare)
  • Proinflammatory activity of a cecropin-like antibacterial peptide from Helicobacter pylori
  • 2001
  • Ingår i: Antimicrob Agents Chemother. ; 45:6, s. 1700-4
  • Tidskriftsartikel (refereegranskat)abstract
    • Helicobacter pylori, the bacterial pathogen associated with gastritis and peptic ulcers, is highly successful in establishing infection in the human gastric mucosa, a process typically associated with massive infiltration of inflammatory cells. Colonization of the mucosa is suggested to be facilitated by H. pylori-produced cecropin-like peptides with antibacterial properties, giving the microbe a competitive advantage over other bacteria. We show that a cecropin-like antibacterial peptide from H. pylori, Hp(2-20), not only has a potent bactericidal effect but also induces proinflammatory activities in human neutrophils, e.g., upregulation of integrins (Mac-1), induction of chemotaxis, and activation of the oxygen radical producing NADPH-oxidase. Furthermore, we show that these effects are mediated through binding of Hp(2-20) to the promiscuous, G-protein-linked lipoxin A(4) receptor-formyl peptide-like receptor 1.
  •  
47.
  • Bäcklund, Christian, et al. (författare)
  • Exploring the relationship between personality and gaming disorder symptoms in a sample of Dota 2 players
  • 2024
  • Ingår i: Current Psychology. - : Springer. - 1046-1310 .- 1936-4733.
  • Tidskriftsartikel (refereegranskat)abstract
    • This study explored the relationship between the big five personality traits and gaming disorder symptoms (GDS) in a sample of Dota 2 players. Recent research has indicated that the relationship between personality traits and GDS may depend on the video game genre investigated. However, the association between GDS and personality has yet to be investigated within a specific game, which may be even more relevant to explore as each game offers unique gameplay mechanics that can influence player behavior differently. Thus, the present study investigated the relationship between the big five personality traits and GDS in a sample of video game players from a specific game, DOTA 2 (n = 321, M = 23.25 years, SD = 4.51). Multiple linear regression was used to analyze GDS formatted as a composite score, and multinomial logistic regressions were further conducted for analyses in which gamers were classified into normal gamers (i.e., less than three criteria endorsed), moderate-risk gamers (i.e., four criteria endorsed), and high-risk gamers (i.e., all criteria endorsed). The analysis of the composite score showed a significant relationship between neuroticism, conscientiousness, agreeableness, and GDS. Analyses of the gaming classifications revealed that neuroticism was the most crucial factor concerning differentiating moderate-risk and high-risk from normal gamers. The findings and their practical implications are further discussed.
  •  
48.
  • Collingwood, T N, et al. (författare)
  • A natural transactivation mutation in the thyroid hormone beta receptor: impaired interaction with putative transcriptional mediators.
  • 1997
  • Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - 0027-8424. ; 94:1, s. 248-53
  • Tidskriftsartikel (refereegranskat)abstract
    • The syndrome of resistance to thyroid hormone is characterized by elevated serum free thyroid hormones, failure to suppress pituitary thyrotropin secretion, and variable peripheral refractoriness to hormone action. Here we describe a novel leucine to valine mutation in codon 454 (L454V) of the thyroid hormone beta receptor (TR beta) in this disorder, resulting in a mutant receptor with unusual functional properties. Although the mutant protein binds ligand comparably to wild-type receptor and forms homo- and heterodimers on direct repeat, everted repeat, or palindromic thyroid response elements, its ability to activate transcription via these elements is markedly impaired. The hydrophobic leucine residue lies within an amphipathic alpha-helix at the carboxyl terminus of TR beta and the position of the homologous residue in the crystal structure of TR alpha indicates that its side chain is solvent-exposed and might interact with other proteins. We find that two putative transcriptional mediators (RIP140 and SRC-1) exhibit hormone-dependent association with wild-type TR. In comparison, the interaction of this natural mutant (L454V) and artificial mutants (L454A, E457A) with RIP140 and SRC-1 is markedly reduced. Furthermore, coexpression of SRC-1 is able to restore the transcriptional activity of the L454V mutant receptor, indicating that the interaction of this residue with accessory proteins is critical for transcriptional activation. Finally, the occurrence of the L454V mutation in resistance to thyroid hormone, together with impaired negative regulation of the thyroid-stimulating hormone alpha promoter by this mutant, suggests that the amphipathic alpha-helix also mediates hormone-dependent transcriptional inhibition, perhaps via interaction with these or other accessory factors.
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49.
  • Colombo, Simone, et al. (författare)
  • Mining players’ experience in computer games: Immersion affects flow but not presence
  • 2023
  • Ingår i: Computers in Human Behavior Reports. - : Elsevier. - 2451-9588. ; 12
  • Tidskriftsartikel (refereegranskat)abstract
    • Understanding how different levels of immersion influence the experiences of flow and presence can shed light on the intricate interplay between these constructs and provide valuable insights into the factors that contribute to engaging and immersive gameplay. The independent variable, immersion, was manipulated in three conditions (high, moderate, and low) in a between-subject design within the video game Minecraft. Participants were asked to complete 15 min of gameplay and then fill out the questionnaires concerning flow and presence. The experiment was conducted remotely on a video-sharing platform. Bayesian analysis revealed an effect of immersion level on flow, while no evidence of an effect was found for the experience of presence. This study provides evidence in favor of a relation between flow and immersion while supporting a presumed double dissociation of immersion from presence. Future research using a Bayesian approach is encouraged to build further knowledge on this research topic.
  •  
50.
  • Corman, ML, et al. (författare)
  • Consensus conference on the stapled transanal rectal resection (STARR) for disordered defaecation
  • 2006
  • Ingår i: Colorectal Disease. - : Wiley. - 1462-8910 .- 1463-1318. ; 8:2, s. 98-101
  • Tidskriftsartikel (refereegranskat)abstract
    • An international working party was convened in Rome, Italy on 16–17 June, 2005, with the purpose of developing a consensus on the application of the circular stapling instrument to the treatment of certain rectal conditions, the so-called Stapled Transanal Rectal Resection (STARR). Since the procedure has been submitted to only limited objective analysis it was felt prudent to hold a meeting of interested individuals for the purpose of evaluating the current status and to make conclusions and recommendations concerning the applicability of this new approach.
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