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| 2. |
- Lawrenson, Kate, et al.
(författare)
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Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10-20), ER-negative BC (P=1.1 × 10-13), BRCA1-associated BC (P=7.7 × 10-16) and triple negative BC (P-diff=2 × 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10-3) and ABHD8 (P<2 × 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk.
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| 3. |
- Aimo, Alberto, et al.
(författare)
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Cardiac remodelling - Part 2: Clinical, imaging and laboratory findings. A review from the Study Group on Biomarkers of the Heart Failure Association of the European Society of Cardiology
- 2022
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Ingår i: European Journal of Heart Failure. - : WILEY. - 1388-9842 .- 1879-0844. ; 24:6, s. 944-958
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Forskningsöversikt (refereegranskat)abstract
- In patients with heart failure, the beneficial effects of drug and device therapies counteract to some extent ongoing cardiac damage. According to the net balance between these two factors, cardiac geometry and function may improve (reverse remodelling, RR) and even completely normalize (remission), or vice versa progressively deteriorate (adverse remodelling, AR). RR or remission predict a better prognosis, while AR has been associated with worsening clinical status and outcomes. The remodelling process ultimately involves all cardiac chambers, but has been traditionally evaluated in terms of left ventricular volumes and ejection fraction. This is the second part of a review paper by the Study Group on Biomarkers of the Heart Failure Association of the European Society of Cardiology dedicated to ventricular remodelling. This document examines the proposed criteria to diagnose RR and AR, their prevalence and prognostic value, and the variables predicting remodelling in patients managed according to current guidelines. Much attention will be devoted to RR in patients with heart failure with reduced ejection fraction because most studies on cardiac remodelling focused on this setting.
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| 4. |
- Gonzalez, Arantxa, et al.
(författare)
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Cardiac remodelling - Part 1: From cells and tissues to circulating biomarkers. A review from the Study Group on Biomarkers of the Heart Failure Association of the European Society of Cardiology
- 2022
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Ingår i: European Journal of Heart Failure. - : WILEY. - 1388-9842 .- 1879-0844. ; 24:6, s. 927-943
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Forskningsöversikt (refereegranskat)abstract
- Cardiac remodelling refers to changes in left ventricular structure and function over time, with a progressive deterioration that may lead to heart failure (HF) development (adverse remodelling) or vice versa a recovery (reverse remodelling) in response to HF treatment. Adverse remodelling predicts a worse outcome, whilst reverse remodelling predicts a better prognosis. The geometry, systolic and diastolic function and electric activity of the left ventricle are affected, as well as the left atrium and on the long term even right heart chambers. At a cellular and molecular level, remodelling involves all components of cardiac tissue: cardiomyocytes, fibroblasts, endothelial cells and leucocytes. The molecular, cellular and histological signatures of remodelling may differ according to the cause and severity of cardiac damage, and clearly to the global trend toward worsening or recovery. These processes cannot be routinely evaluated through endomyocardial biopsies, but may be reflected by circulating levels of several biomarkers. Different classes of biomarkers (e.g. proteins, non-coding RNAs, metabolites and/or epigenetic modifications) and several biomarkers of each class might inform on some aspects on HF development, progression and long-term outcomes, but most have failed to enter clinical practice. This may be due to the biological complexity of remodelling, so that no single biomarker could provide great insight on remodelling when assessed alone. Another possible reason is a still incomplete understanding of the role of biomarkers in the pathophysiology of cardiac remodelling. Such role will be investigated in the first part of this review paper on biomarkers of cardiac remodelling.
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| 5. |
- Ng, Theam Foo, et al.
(författare)
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Automated feature weighting in fuzzy declustering-based vector quantization
- 2010
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Konferensbidrag (refereegranskat)abstract
- Feature weighting plays an important role in improving the performance of clustering technique. We propose an automated feature weighting in fuzzy declustering-based vector quantization (FDVQ), namely AFDVQ algorithm, for enhancing effectiveness and efficiency in classification. The proposed AFDVQ imposes weights on the modified fuzzy c-means (FCM) so that it can automatically calculate feature weights based on their degrees of importance rather than treating them equally. Moreover, the extension of FDVQ and AFDVQ algorithms based on generalized improved fuzzy partitions (GIFP), known as GIFP-FDVQ and GIFP-AFDVQ respectively, are proposed. The experimental results on real data (original and noisy data) and modified data (biased and noisy-biased data) have demonstrated that the proposed algorithms outperformed standard algorithms in classifying clusters especially for biased data.
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| 6. |
- Ng, Theam Foo, et al.
(författare)
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Feature interaction in subspace clustering using the Choquet integral
- 2012
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Ingår i: Pattern Recognition. - : Elsevier. - 0031-3203 .- 1873-5142. ; 45:7, s. 2645-2660
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Tidskriftsartikel (refereegranskat)abstract
- Subspace clustering has recently emerged as a popular approach to removing irrelevant and redundant features during the clustering process. However, most subspace clustering methods do not consider the interaction between the features. This unawareness limits the analysis performance in many pattern recognition problems. In this paper, we propose a novel subspace clustering technique by introducing the feature interaction using the concepts of fuzzy measures and the Choquet integral. This new framework of subspace clustering can provide optimal subsets of interacted features chosen for each cluster, and hence can improve clustering-based pattern recognition tasks. Various experimental results illustrate the effective performance of the proposed method.
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| 7. |
- Ng, Theam Foo, et al.
(författare)
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Fuzzy Knowledge-Based Subspace Clustering for Life Science Data Analysis
- 2013
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Ingår i: Knowledge-Based Systems in Biomedicine and Computational Life Science. - Berlin, Heidelberg : Springer Berlin/Heidelberg. - 9783642330148 - 9783642330155 ; , s. 177-213
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Features or attributes play an important role when handling multi-dimensional datasets. Generally, not all the features are needed to find several groups of similar objects in traditional clustering methods because some of the features may not be relevant and also redundant. Hence, the concept of identifying subsets of the features that are relevant to clusters is introduced, instead of using the full set of features. This chapter discusses the use of the prior knowledge of the importance of features and their interaction in constructing both fuzzy measures and signed fuzzy measures for subspace clustering. The Choquet integral, which is known as a useful aggregation operator with respect to fuzzy measure, is used to aggregate the importance and interaction of the features. The concept of fuzzy knowledge-based subspace clustering is applied especially to the analysis of life science data in this chapter.
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| 8. |
- Ng, Theam Foo, et al.
(författare)
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Justification of Fuzzy Declustering Vector Quantization Modeling in Classification of Genotype-Image Phenotypes
- 2010
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Konferensbidrag (refereegranskat)abstract
- With the fast development of multi‐dimensional data compression and pattern classification techniques, vector quantization (VQ) has become a system that allows large reduction of data storage and computational effort. One of the most recent VQ techniques that handle the poor estimation of vector centroids due to biased data from undersampling is to use fuzzy declustering‐based vector quantization (FDVQ) technique. Therefore, in this paper, we are motivated to propose a justification of FDVQ based hidden Markov model (HMM) for investigating its effectiveness and efficiency in classification of genotype‐image phenotypes. The performance evaluation and comparison of the recognition accuracy between a proposed FDVQ based HMM (FDVQ‐HMM) and a well‐known LBG (Linde, Buzo, Gray) vector quantization based HMM (LBG‐HMM) will be carried out. The experimental results show that the performances of both FDVQ‐HMM and LBG‐HMM are almost similar. Finally, we have justified the competitiveness of FDVQ‐HMM in classification of cellular phenotype image database by using hypotheses t‐test. As a result, we have validated that the FDVQ algorithm is a robust and an efficient classification technique in the application of RNAi genome‐wide screening image data.
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| 9. |
- Poch, Christine M, et al.
(författare)
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Migratory and anti-fibrotic programmes define the regenerative potential of human cardiac progenitors
- 2022
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Ingår i: Nature Cell Biology. - Stockholm : Karolinska Institutet, Dept of Cell and Molecular Biology. - 1465-7392 .- 1476-4679.
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Tidskriftsartikel (refereegranskat)abstract
- Heart regeneration is an unmet clinical need, hampered by limited renewal of adult cardiomyocytes and fibrotic scarring. Pluripotent stem cell-based strategies are emerging, but unravelling cellular dynamics of host–graft crosstalk remains elusive. Here, by combining lineage tracing and single-cell transcriptomics in injured non-human primate heart biomimics, we uncover the coordinated action modes of human progenitor-mediated muscle repair. Chemoattraction via CXCL12/CXCR4 directs cellular migration to injury sites. Activated fibroblast repulsion targets fibrosis by SLIT2/ROBO1 guidance in organizing cytoskeletal dynamics. Ultimately, differentiation and electromechanical integration lead to functional restoration of damaged heart muscle. In vivo transplantation into acutely and chronically injured porcine hearts illustrated CXCR4-dependent homing, de novo formation of heart muscle, scar-volume reduction and prevention of heart failure progression. Concurrent endothelial differentiation contributed to graft neovascularization. Our study demonstrates that inherent developmental programmes within cardiac progenitors are sequentially activated in disease, enabling the cells to sense and counteract acute and chronic injury.
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