| 1. |
- Hollestelle, Antoinette, et al.
(författare)
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No clinical utility of KRAS variant rs61764370 for ovarian or breast cancer
- 2016
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Ingår i: Gynecologic Oncology. - : Elsevier BV. - 0090-8258 .- 1095-6859. ; 141:2, s. 386-401
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Tidskriftsartikel (refereegranskat)abstract
- Objective Clinical genetic testing is commercially available for rs61764370, an inherited variant residing in a KRAS 3′ UTR microRNA binding site, based on suggested associations with increased ovarian and breast cancer risk as well as with survival time. However, prior studies, emphasizing particular subgroups, were relatively small. Therefore, we comprehensively evaluated ovarian and breast cancer risks as well as clinical outcome associated with rs61764370. Methods Centralized genotyping and analysis were performed for 140,012 women enrolled in the Ovarian Cancer Association Consortium (15,357 ovarian cancer patients; 30,816 controls), the Breast Cancer Association Consortium (33,530 breast cancer patients; 37,640 controls), and the Consortium of Modifiers of BRCA1 and BRCA2 (14,765 BRCA1 and 7904 BRCA2 mutation carriers). Results We found no association with risk of ovarian cancer (OR = 0.99, 95% CI 0.94-1.04, p = 0.74) or breast cancer (OR = 0.98, 95% CI 0.94-1.01, p = 0.19) and results were consistent among mutation carriers (BRCA1, ovarian cancer HR = 1.09, 95% CI 0.97-1.23, p = 0.14, breast cancer HR = 1.04, 95% CI 0.97-1.12, p = 0.27; BRCA2, ovarian cancer HR = 0.89, 95% CI 0.71-1.13, p = 0.34, breast cancer HR = 1.06, 95% CI 0.94-1.19, p = 0.35). Null results were also obtained for associations with overall survival following ovarian cancer (HR = 0.94, 95% CI 0.83-1.07, p = 0.38), breast cancer (HR = 0.96, 95% CI 0.87-1.06, p = 0.38), and all other previously-reported associations. Conclusions rs61764370 is not associated with risk of ovarian or breast cancer nor with clinical outcome for patients with these cancers. Therefore, genotyping this variant has no clinical utility related to the prediction or management of these cancers.
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| 4. |
- Berger, Thomas, et al.
(författare)
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Internet-based treatment of depression : a randomized controlled trial comparing guided with unguided self-help
- 2011
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Ingår i: Cognitive behaviour therapy. - : Routledge. - 1651-2316 .- 1650-6073. ; 40:4, s. 251-266
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Tidskriftsartikel (refereegranskat)abstract
- Internet-delivered self-help for depression with therapist guidance has shown efficacy in several trials. Results from meta-analyses suggest that guidance is important and that self-help programs without support are less effective. However, there are no direct experimental comparisons between guided and unguided internet-based treatments for depression. The present study compared the benefits of a 10-week web-based unguided self-help treatment with the same intervention complemented with weekly therapist support via e-mail. A waiting-list control group was also included. Seventy-six individuals meeting the diagnostic criteria of major depression or dysthymia were randomly assigned to one of the three conditions. The Beck Depression Inventory (BDI-II) was used as the primary outcome measure. Secondary outcomes included general psychopathology, interpersonal problems, and quality of life. Sixty-nine participants (91%) completed the assessment at posttreatment and 59 (78%) at 6-month follow-up. Results showed significant symptom reductions in both treatment groups compared to the waiting-list control group. At posttreatment, between-group effect sizes on the BDI-II were d = .66 for unguided self-help versus waiting-list and d = 1.14 for guided self-help versus waiting-list controls. In the comparison of the two active treatments, small-to-moderate, but not statistically significant effects in favor of the guided condition were found on all measured dimensions. In both groups, treatment gains were maintained at 6-month follow-up. The findings provide evidence that internet-delivered treatments for depression can be effective whether support is added or not. However, all participants were interviewed in a structured diagnostic telephone interview before inclusion, which prohibits conclusions regarding unguided treatments that are without any human contact.
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| 5. |
- Boehme, Katja, et al.
(författare)
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Concerted Actions of a Thermo-labile Regulator and a Unique Intergenic RNA Thermosensor Control Yersinia Virulence
- 2012
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Ingår i: PLOS PATHOGENS. - : Public Library of Science (PLoS). - 1553-7366 .- 1553-7374. ; 8:2, s. e1002518-
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Tidskriftsartikel (refereegranskat)abstract
- Expression of all Yersinia pathogenicity factors encoded on the virulence plasmid, including the yop effector and the ysc type III secretion genes, is controlled by the transcriptional activator LcrF in response to temperature. Here, we show that a protein-and RNA-dependent hierarchy of thermosensors induce LcrF synthesis at body temperature. Thermally regulated transcription of lcrF is modest and mediated by the thermo-sensitive modulator YmoA, which represses transcription from a single promoter located far upstream of the yscW-lcrF operon at moderate temperatures. The transcriptional response is complemented by a second layer of temperature-control induced by a unique cis-acting RNA element located within the intergenic region of the yscW-lcrF transcript. Structure probing demonstrated that this region forms a secondary structure composed of two stemloops at 25 degrees C. The second hairpin sequesters the lcrF ribosomal binding site by a stretch of four uracils. Opening of this structure was favored at 37 degrees C and permitted ribosome binding at host body temperature. Our study further provides experimental evidence for the biological relevance of an RNA thermometer in an animal model. Following oral infections in mice, we found that two different Y. pseudotuberculosis patient isolates expressing a stabilized thermometer variant were strongly reduced in their ability to disseminate into the Peyer's patches, liver and spleen and have fully lost their lethality. Intriguingly, Yersinia strains with a destabilized version of the thermosensor were attenuated or exhibited a similar, but not a higher mortality. This illustrates that the RNA thermometer is the decisive control element providing just the appropriate amounts of LcrF protein for optimal infection efficiency.
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| 6. |
- Frazier-Wood, Alexis C., et al.
(författare)
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Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses
- 2016
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Ingår i: Nature Genetics. - : Nature Research (part of Springer Nature). - 1061-4036 .- 1546-1718. ; 48, s. 624-
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Tidskriftsartikel (refereegranskat)abstract
- Very few genetic variants have been associated with depression and neuroticism, likely because of limitations on sample size in previous studies. Subjective well-being, a phenotype that is genetically correlated with both of these traits, has not yet been studied with genome-wide data. We conducted genome-wide association studies of three phenotypes: subjective well-being (n = 298,420), depressive symptoms (n = 161,460), and neuroticism (n = 170,911). We identify 3 variants associated with subjective well-being, 2 variants associated with depressive symptoms, and 11 variants associated with neuroticism, including 2 inversion polymorphisms. The two loci associated with depressive symptoms replicate in an independent depression sample. Joint analyses that exploit the high genetic correlations between the phenotypes (vertical bar(p) over cap vertical bar approximate to 0.8) strengthen the overall credibility of the findings and allow us to identify additional variants. Across our phenotypes, loci regulating expression in central nervous system and adrenal or pancreas tissues are strongly enriched for association.
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| 7. |
- Ganeva, Dessislava, et al.
(författare)
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In-situ start and end of growing season dates of major European crop types from France and Bulgaria at a field level
- 2023
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Ingår i: Data in Brief. - 2352-3409. ; 51
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Tidskriftsartikel (refereegranskat)abstract
- Crop phenology data offer crucial information for crop yield estimation, agricultural management, and assessment of agroecosystems. Such information becomes more important in the context of increasing year-to-year climatic variability. The dataset provides in-situ crop phenology data (first leaves emergence and harvest date) of major European crops (wheat, corn, sunflower, rapeseed) from seventeen field study sites in Bulgaria and two in France. Additional information such as the sowing date, area of each site, coordinates, method and equipment used for phenophase data estimation, and photos of the France sites are also provided. The georeferenced ground-truth dataset provides a solid base for a better understanding of crop growth and can be used to validate the retrieval of phenological stages from remote sensing data.
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| 8. |
- Kooistra, Lammert, et al.
(författare)
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Reviews and syntheses : Remotely sensed optical time series for monitoring vegetation productivity
- 2024
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Ingår i: Biogeosciences. - 1726-4170. ; 21:2, s. 473-511
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Forskningsöversikt (refereegranskat)abstract
- Vegetation productivity is a critical indicator of global ecosystem health and is impacted by human activities and climate change. A wide range of optical sensing platforms, from ground-based to airborne and satellite, provide spatially continuous information on terrestrial vegetation status and functioning. As optical Earth observation (EO) data are usually routinely acquired, vegetation can be monitored repeatedly over time, reflecting seasonal vegetation patterns and trends in vegetation productivity metrics. Such metrics include gross primary productivity, net primary productivity, biomass, or yield. To summarize current knowledge, in this paper we systematically reviewed time series (TS) literature for assessing state-of-the-art vegetation productivity monitoring approaches for different ecosystems based on optical remote sensing (RS) data. As the integration of solar-induced fluorescence (SIF) data in vegetation productivity processing chains has emerged as a promising source, we also include this relatively recent sensor modality. We define three methodological categories to derive productivity metrics from remotely sensed TS of vegetation indices or quantitative traits: (i) trend analysis and anomaly detection, (ii) land surface phenology, and (iii) integration and assimilation of TS-derived metrics into statistical and process-based dynamic vegetation models (DVMs). Although the majority of used TS data streams originate from data acquired from satellite platforms, TS data from aircraft and unoccupied aerial vehicles have found their way into productivity monitoring studies. To facilitate processing, we provide a list of common toolboxes for inferring productivity metrics and information from TS data. We further discuss validation strategies of the RS data derived productivity metrics: (1) using in situ measured data, such as yield; (2) sensor networks of distinct sensors, including spectroradiometers, flux towers, or phenological cameras; and (3) inter-comparison of different productivity metrics. Finally, we address current challenges and propose a conceptual framework for productivity metrics derivation, including fully integrated DVMs and radiative transfer models here labelled as "Digital Twin". This novel framework meets the requirements of multiple ecosystems and enables both an improved understanding of vegetation temporal dynamics in response to climate and environmental drivers and enhances the accuracy of vegetation productivity monitoring.
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| 9. |
- 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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| 10. |
- Smith, Jennifer A, et al.
(författare)
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Genome-wide association study identifies 74 loci associated with educational attainment
- 2016
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Ingår i: Nature (London). - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 533:7604, s. 539-542
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Tidskriftsartikel (refereegranskat)abstract
- Educational attainment is strongly influenced by social and other environmental factors, but genetic factors are estimated to account for at least 20% of the variation across individuals. Here we report the results of a genome-wide association study (GWAS) for educational attainment that extends our earlier discovery sample of 101,069 individuals to 293,723 individuals, and a replication study in an independent sample of 111,349 individuals from the UK Biobank. We identify 74 genome-wide significant loci associated with the number of years of schooling completed. Single-nucleotide polymorphisms associated with educational attainment are disproportionately found in genomic regions regulating gene expression in the fetal brain. Candidate genes are preferentially expressed in neural tissue, especially during the prenatal period, and enriched for biological pathways involved in neural development. Our findings demonstrate that, even for a behavioural phenotype that is mostly environmentally determined, a well-powered GWAS identifies replicable associated genetic variants that suggest biologically relevant pathways. Because educational attainment is measured in large numbers of individuals, it will continue to be useful as a proxy phenotype in efforts to characterize the genetic influences of related phenotypes, including cognition and neuropsychiatric diseases.
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