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- Obon-Santacana, M, et al.
(författare)
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Meta-Analysis and Validation of a Colorectal Cancer Risk Prediction Model Using Deep Sequenced Fecal Metagenomes
- 2022
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 14:17
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Tidskriftsartikel (refereegranskat)abstract
- The gut microbiome is a potential modifiable risk factor for colorectal cancer (CRC). We re-analyzed all eight previously published stool sequencing data and conducted an MWAS meta-analysis. We used cross-validated LASSO predictive models to identify a microbiome signature for predicting the risk of CRC and precancerous lesions. These models were validated in a new study, Colorectal Cancer Screening (COLSCREEN), including 156 participants that were recruited in a CRC screening context. The MWAS meta-analysis identified 95 bacterial species that were statistically significantly associated with CRC (FDR < 0.05). The LASSO CRC predictive model obtained an area under the receiver operating characteristic curve (aROC) of 0.81 (95%CI: 0.78–0.83) and the validation in the COLSCREEN dataset was 0.75 (95%CI: 0.66–0.84). This model selected a total of 32 species. The aROC of this CRC-trained model to predict precancerous lesions was 0.52 (95%CI: 0.41–0.63). We have identified a signature of 32 bacterial species that have a good predictive accuracy to identify CRC but not precancerous lesions, suggesting that the identified microbes that were enriched or depleted in CRC are merely a consequence of the tumor. Further studies should focus on CRC as well as precancerous lesions with the intent to implement a microbiome signature in CRC screening programs.
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- Eberhardt, F., et al.
(författare)
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A Uniform and Isotropic Cytoskeletal Tiling Fills Dendritic Spines
- 2022
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Ingår i: eNeuro. - : Society for Neuroscience. - 2373-2822. ; 9:5
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Tidskriftsartikel (refereegranskat)abstract
- Dendritic spines are submicron, subcellular compartments whose shape is defined by actin filaments and associated proteins. Accurately mapping the cytoskeleton is a challenge, given the small size of its components. It remains unclear whether the actin-associated structures analyzed in dendritic spines of neurons in vitro apply to dendritic spines of intact, mature neurons in situ. Here, we combined advanced preparative methods with multitilt serial section electron microscopy (EM) tomography and computational analysis to reveal the full three-dimensional (3D) internal architecture of spines in the intact brains of male mice at nanometer resolution. We compared hippocampal (CA1) pyramidal cells and cerebellar Purkinje cells in terms of the length distribution and connectivity of filaments, their branching-angles and absolute orientations, and the elementary loops formed by the network. Despite differences in shape and size across spines and between spine heads and necks, the internal organization was remarkably similar in both neuron types and largely homogeneous throughout the spine volume. In the tortuous mesh of highly branched and interconnected filaments, branches exhibited no preferred orientation except in the immediate vicinity of the cell membrane. We found that new filaments preferentially split off from the convex side of a bending filament, consistent with the behavior of Arp2/3-mediated branching of actin under mechanical deformation. Based on the quantitative analysis, the spine cytoskeleton is likely subject to considerable mechanical force in situ.
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- Partridge, EA, et al.
(författare)
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An extra-uterine system to physiologically support the extreme premature lamb
- 2017
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8, s. 15112-
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Tidskriftsartikel (refereegranskat)abstract
- In the developed world, extreme prematurity is the leading cause of neonatal mortality and morbidity due to a combination of organ immaturity and iatrogenic injury. Until now, efforts to extend gestation using extracorporeal systems have achieved limited success. Here we report the development of a system that incorporates a pumpless oxygenator circuit connected to the fetus of a lamb via an umbilical cord interface that is maintained within a closed ‘amniotic fluid’ circuit that closely reproduces the environment of the womb. We show that fetal lambs that are developmentally equivalent to the extreme premature human infant can be physiologically supported in this extra-uterine device for up to 4 weeks. Lambs on support maintain stable haemodynamics, have normal blood gas and oxygenation parameters and maintain patency of the fetal circulation. With appropriate nutritional support, lambs on the system demonstrate normal somatic growth, lung maturation and brain growth and myelination.
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- Partridge, EA, et al.
(författare)
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Corrigendum: An extra-uterine system to physiologically support the extreme premature lamb
- 2017
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8, s. 15794-
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Tidskriftsartikel (refereegranskat)abstract
- Nature Communications 8: Article number: 15112 (2017); Published 25 April 2017; Updated 23 May 2017 A patent based on the work reported in this Article was inadvertently omitted from the Competing interests section of this article. The Competing interests statement should read: E.M., A.F. and M.D. are co-authors on a patent entitled ‘Extracorporeal life support system and methods of use thereof’ (Patent no.
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