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Protocol and quality assurance for carotid imaging in 100,000 participants of UK Biobank: development and assessment.

Biobank publications - 2 hours 14 min ago

Protocol and quality assurance for carotid imaging in 100,000 participants of UK Biobank: development and assessment.

Eur J Prev Cardiol. 2017 Jan 01;:2047487317732273

Authors: Coffey S, Lewandowski AJ, Garratt S, Meijer R, Lynum S, Bedi R, Paterson J, Yaqub M, Noble JA, Neubauer S, Petersen SE, Allen N, Sudlow C, Collins R, Matthews PM, Leeson P

Abstract
Background Ultrasound imaging is able to quantify carotid arterial wall structure for the assessment of cerebral and cardiovascular disease risks. We describe a protocol and quality assurance process to enable carotid imaging at large scale that has been developed for the UK Biobank Imaging Enhancement Study of 100,000 individuals. Design An imaging protocol was developed to allow measurement of carotid intima-media thickness from the far wall of both common carotid arteries. Six quality assurance criteria were defined and a web-based interface (Intelligent Ultrasound) was developed to facilitate rapid assessment of images against each criterion. Results and conclusions Excellent inter and intra-observer agreements were obtained for image quality evaluations on a test dataset from 100 individuals. The image quality criteria then were applied in the UK Biobank Imaging Enhancement Study. Data from 2560 participants were evaluated. Feedback of results to the imaging team led to improvement in quality assurance, with quality assurance failures falling from 16.2% in the first two-month period examined to 6.4% in the last. Eighty per cent had all carotid intima-media thickness images graded as of acceptable quality, with at least one image acceptable for 98% of participants. Carotid intima-media thickness measures showed expected associations with increasing age and gender. Carotid imaging can be performed consistently, with semi-automated quality assurance of all scans, in a limited timeframe within a large scale multimodality imaging assessment. Routine feedback of quality control metrics to operators can improve the quality of the data collection.

PMID: 28925747 [PubMed - as supplied by publisher]

The common variants implicated in microstructural abnormality of first episode and drug-naïve patients with schizophrenia.

Biobank publications - 2 hours 14 min ago
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The common variants implicated in microstructural abnormality of first episode and drug-naïve patients with schizophrenia.

Sci Rep. 2017 Sep 18;7(1):11750

Authors: Ren HY, Wang Q, Lei W, Zhang CC, Li YF, Li XJ, Li ML, Deng W, Huang CH, Du F, Zhao LS, Wang YC, Ma XH, Hu X, Li T

Abstract
Both post-mortem and neuroimaging studies have identified abnormal white matter (WM) microstructure in patients with schizophrenia. However, its genetic underpinnings and relevant biological pathways remain unclear. In order to unravel the genes and the pathways associated with abnormal WM microstructure in schizophrenia, we recruited 100 first-episode, drug-naïve patients with schizophrenia and 140 matched healthy controls to conduct genome-wide association analysis of fractional anisotropy (FA) value measured using diffusing tensor imaging (DTI), followed by multivariate association study and pathway enrichment analysis. The results showed that one intergenic SNP (rs11901793), which is 20 kb upstream of CXCR7 gene on chromosome 2, was associated with the total mean FA values with genome-wide significance (p = 4.37 × 10(-8)), and multivariate association analysis identified a strong association between one region-specific SNP (rs10509852), 400 kb upstream of SORCS1 gene on chromosome 10, and the global trait of abnormal WM microstructure (p = 1.89 × 10(-7)). Furthermore, one pathway that is involved in cell cycle regulation, REACTOME_CHROMOSOME _MAINTENANCE, was significantly enriched by the genes that were identified in our study (p = 1.54 × 10(-17)). In summary, our study provides suggestive evidence that abnormal WM microstructure in schizophrenia is associated with genes that are likely involved in diverse biological signals and cell-cycle regulation although further replication in a larger independent sample is needed.

PMID: 28924203 [PubMed - in process]

The iPSYCH2012 case-cohort sample: new directions for unravelling genetic and environmental architectures of severe mental disorders.

Biobank publications - 2 hours 14 min ago
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The iPSYCH2012 case-cohort sample: new directions for unravelling genetic and environmental architectures of severe mental disorders.

Mol Psychiatry. 2017 Sep 19;:

Authors: Pedersen CB, Bybjerg-Grauholm J, Pedersen MG, Grove J, Agerbo E, Bækvad-Hansen M, Poulsen JB, Hansen CS, McGrath JJ, Als TD, Goldstein JI, Neale BM, Daly MJ, Hougaard DM, Mors O, Nordentoft M, Børglum AD, Werge T, Mortensen PB

Abstract
The Integrative Psychiatric Research (iPSYCH) consortium has established a large Danish population-based Case-Cohort sample (iPSYCH2012) aimed at unravelling the genetic and environmental architecture of severe mental disorders. The iPSYCH2012 sample is nested within the entire Danish population born between 1981 and 2005, including 1 472 762 persons. This paper introduces the iPSYCH2012 sample and outlines key future research directions. Cases were identified as persons with schizophrenia (N=3540), autism (N=16 146), attention-deficit/hyperactivity disorder (N=18 726) and affective disorder (N=26 380), of which 1928 had bipolar affective disorder. Controls were randomly sampled individuals (N=30 000). Within the sample of 86 189 individuals, a total of 57 377 individuals had at least one major mental disorder. DNA was extracted from the neonatal dried blood spot samples obtained from the Danish Neonatal Screening Biobank and genotyped using the Illumina PsychChip. Genotyping was successful for 90% of the sample. The assessments of exome sequencing, methylation profiling, metabolome profiling, vitamin-D, inflammatory and neurotrophic factors are in progress. For each individual, the iPSYCH2012 sample also includes longitudinal information on health, prescribed medicine, social and socioeconomic information, and analogous information among relatives. To the best of our knowledge, the iPSYCH2012 sample is the largest and most comprehensive data source for the combined study of genetic and environmental aetiologies of severe mental disorders.Molecular Psychiatry advance online publication, 19 September 2017; doi:10.1038/mp.2017.196.

PMID: 28924187 [PubMed - as supplied by publisher]

Genetic contributions to Trail Making Test performance in UK Biobank.

Biobank publications - 2 hours 14 min ago
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Genetic contributions to Trail Making Test performance in UK Biobank.

Mol Psychiatry. 2017 Sep 19;:

Authors: Hagenaars SP, Cox SR, Hill WD, Davies G, Liewald DCM, CHARGE consortium Cognitive Working Group, Harris SE, McIntosh AM, Gale CR, Deary IJ

Abstract
The Trail Making Test (TMT) is a widely used test of executive function and has been thought to be strongly associated with general cognitive function. We examined the genetic architecture of the TMT and its shared genetic aetiology with other tests of cognitive function in 23 821 participants from UK Biobank. The single-nucleotide polymorphism-based heritability estimates for trail-making measures were 7.9% (part A), 22.4% (part B) and 17.6% (part B-part A). Significant genetic correlations were identified between trail-making measures and verbal-numerical reasoning (rg>0.6), general cognitive function (rg>0.6), processing speed (rg>0.7) and memory (rg>0.3). Polygenic profile analysis indicated considerable shared genetic aetiology between trail making, general cognitive function, processing speed and memory (standardized β between 0.03 and 0.08). These results suggest that trail making is both phenotypically and genetically strongly associated with general cognitive function and processing speed.Molecular Psychiatry advance online publication, 19 September 2017; doi:10.1038/mp.2017.189.

PMID: 28924184 [PubMed - as supplied by publisher]

ß-1,3-galactosyl-O-glycosyl-glycoprotein ß-1,6-N-acetylglucosaminyltransferase 3 Increases MCAM Stability, Which Enhances S100A8/A9-Mediated Cancer Motility.

Biobank publications - 2 hours 14 min ago
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ß-1,3-galactosyl-O-glycosyl-glycoprotein ß-1,6-N-acetylglucosaminyltransferase 3 Increases MCAM Stability, Which Enhances S100A8/A9-Mediated Cancer Motility.

Oncol Res. 2017 Sep 18;:

Authors: Sumardika IW, Youyi C, Kondo E, Inoue Y, Ruma IMW, Murata H, Kinoshita R, Yamamoto KI, Tomida S, Shien K, Satoh H, Yamauchi A, Futami J, Putranto EW, Hibino T, Toyooka S, Nishibori M, Sakaguchi M

Abstract
We previously identified novel S100A8/A9 receptors, Extracellular Matrix Metalloproteinase Inducer (EMMPRIN), MelanomaCell Adhesion Molecule (MCAM), Activated Leukocyte Cell Adhesion Molecule (ALCAM) and Neuroplastin (NPTN) ß, that are critically involved in S100A8/A9-mediated cancer metastasis and inflammation when expressed at high levels. However, little is known about the presence of any cancerspecific mechanism(s) that modifies these receptors, further inducing upregulation at protein levels without any transcriptional regulation. Expression levels of glycosyltransferase-encoding genes were examined by a PCR-based profiling array followed by confirmation with quantitative real time PCR. Cell migration and invasion were assessed by a using Boyden chamber. Western blotting was used to examine the protein level, and the RNA level was examined by Northern blotting. Immunohistochemistry was used to examine the expression pattern of GCNT3 and MCAM in melanoma tissue. We found that ß-1,3-galactosyl-O-glycosyl-glycoprotein ß-1,6-N-acetylglucosaminyltransferase 3 (GCNT3) is overexpressed in highly metastatic melanomas. Silencing and functional inhibition of GCNT3 greatly suppressed migration and invasion of melanoma cells, resulting in the loss of S100A8/A9 responsiveness. Among the novel S100A8/A9 receptors, GCNT3 favorably glycosylates the MCAM receptor, extending its half-life and leading to further elevation of S100A8/A9-mediated cellular motility in melanoma cells. GCNT3 expression is positively correlated to MCAM expression in patients with high-grade melanomas. Collectively, our results showed that GCNT3 is an upstream regulator of MCAM protein and indicate the possibility of a potential molecular target in melanoma therapeutics through abrogation of the S100A8/A9-MCAM axis.

PMID: 28923134 [PubMed - as supplied by publisher]

Training the Next Generation of Biobankers: A Two-Year Master's Course in the Management of Biobanks.

Biobank publications - Tue, 09/19/2017 - 14:30
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Training the Next Generation of Biobankers: A Two-Year Master's Course in the Management of Biobanks.

Biopreserv Biobank. 2017 Sep 18;

Authors: Gormally E, Hardy I, Caboux E, di Donato JH, Hainaut P, Hofman P

Abstract
The growing complexity of biobanking requires dedicated professional staff who are trained in multiple aspects of the biobanking process, including technical, managerial, regulatory, and ethical aspects, and who have a good understanding of the challenges of biospecimen research, but also of the challenges related to the sustainability of future biobanks. Up to the present, biobanking staff have been trained in an ad-hoc manner, usually through specific short duration courses, for example, summer schools. In this article, we describe the development/establishment of a systematic 2-year training program at the Master level intended for students with a background in life sciences and providing them with a professional qualification as a "Biobank Manager." This course was developed in 2010 as a joint initiative of the Catholic University of Lyon and the University of Nice-Sophia-Antipolis (France). The multidisciplinary training offers courses on biobank design and infrastructure, on pre- and postanalytical processing of different types of biospecimens, on protocol development, on ethical and regulatory aspects, as well as an introduction to epidemiology and translational research. In parallel, students also receive generic training in management, budget planning, data analysis, and statistics, as well as 11 months of hands-on training in various biobanks handling human, animal, plant, or microbial biospecimens. Four groups of students have graduated since 2012, for a total of 44 students, who all found jobs in biobanking within 6 months of graduation.

PMID: 28922617 [PubMed - as supplied by publisher]

The Effects of Cryopreservation on Different Passages of Fibroblast Cell Culture in Brown Brocket Deer (Mazama gouazoubira).

Biobank publications - Tue, 09/19/2017 - 14:30
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The Effects of Cryopreservation on Different Passages of Fibroblast Cell Culture in Brown Brocket Deer (Mazama gouazoubira).

Biopreserv Biobank. 2017 Sep 18;

Authors: Magalhães LC, Bhat MH, Freitas JLS, Melo LM, Teixeira DIA, Pinto LCA, Câmara LMC, Duarte JMB, Freitas VJF

Abstract
The brown brocket deer Mazama gouazoubira is 1 of the 10 recognized brocket deer of the Neotropical region. Recently, this species has suffered a population decline due to current threats, mainly poaching and habitat loss. Several studies have shown that some endangered species can benefit from interspecies somatic cell nuclear transfer technology through the use of their somatic cells, such as the fibroblasts. Thus, the aim of this study was to verify the viability and the effect of cryopreservation on fibroblasts after several passages. For this purpose, fibroblast cells were cultured until passages 4, 7, and 10 (cultured control groups) and cryopreserved in cryotubes (frozen/warmed groups). The cellular viability, functionality, and percentage of cells undergoing necrosis and apoptosis were evaluated. The survival rates were always higher than 80% irrespective of the tested group, except for passage 10 in the frozen/warmed group. Population doubling time of cultured cells from passage 10 was significantly higher than that of passages 4 and 7, exhibiting low metabolic activity and a higher percentage of cells in initial apoptosis. In conclusion, the M. gouazoubira fibroblast-derived cell line provides an essential resource for further studies regarding reproductive biotechniques and is likely to be useful as an ex situ conservation strategy.

PMID: 28922611 [PubMed - as supplied by publisher]

C-reactive protein upregulates the whole blood expression of CD59 - an integrative analysis.

Biobank publications - Tue, 09/19/2017 - 14:30
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C-reactive protein upregulates the whole blood expression of CD59 - an integrative analysis.

PLoS Comput Biol. 2017 Sep 18;13(9):e1005766

Authors: Lepik K, Annilo T, Kukuškina V, Kisand K, Kutalik Z, Peterson P, Peterson H, eQTLGen Consortium

Abstract
Elevated C-reactive protein (CRP) concentrations in the blood are associated with acute and chronic infections and inflammation. Nevertheless, the functional role of increased CRP in multiple bacterial and viral infections as well as in chronic inflammatory diseases remains unclear. Here, we studied the relationship between CRP and gene expression levels in the blood in 491 individuals from the Estonian Biobank cohort, to elucidate the role of CRP in these inflammatory mechanisms. As a result, we identified a set of 1,614 genes associated with changes in CRP levels with a high proportion of interferon-stimulated genes. Further, we performed likelihood-based causality model selection and Mendelian randomization analysis to discover causal links between CRP and the expression of CRP-associated genes. Strikingly, our computational analysis and cell culture stimulation assays revealed increased CRP levels to drive the expression of complement regulatory protein CD59, suggesting CRP to have a critical role in protecting blood cells from the adverse effects of the immune defence system. Our results show the benefit of integrative analysis approaches in hypothesis-free uncovering of causal relationships between traits.

PMID: 28922377 [PubMed - as supplied by publisher]

Automated arteriole and venule classification using deep learning for retinal images from the UK Biobank cohort.

Biobank publications - Sun, 09/17/2017 - 14:44
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Automated arteriole and venule classification using deep learning for retinal images from the UK Biobank cohort.

Comput Biol Med. 2017 Sep 08;90:23-32

Authors: Welikala RA, Foster PJ, Whincup PH, Rudnicka AR, Owen CG, Strachan DP, Barman SA, UK Biobank Eye and Vision Consortium

Abstract
The morphometric characteristics of the retinal vasculature are associated with future risk of many systemic and vascular diseases. However, analysis of data from large population based studies is needed to help resolve uncertainties in some of these associations. This requires automated systems that extract quantitative measures of vessel morphology from large numbers of retinal images. Associations between retinal vessel morphology and disease precursors/outcomes may be similar or opposing for arterioles and venules. Therefore, the accurate detection of the vessel type is an important element in such automated systems. This paper presents a deep learning approach for the automatic classification of arterioles and venules across the entire retinal image, including vessels located at the optic disc. This comprises of a convolutional neural network whose architecture contains six learned layers: three convolutional and three fully-connected. Complex patterns are automatically learnt from the data, which avoids the use of hand crafted features. The method is developed and evaluated using 835,914 centreline pixels derived from 100 retinal images selected from the 135,867 retinal images obtained at the UK Biobank (large population-based cohort study of middle aged and older adults) baseline examination. This is a challenging dataset in respect to image quality and hence arteriole/venule classification is required to be highly robust. The method achieves a significant increase in accuracy of 8.1% when compared to the baseline method, resulting in an arteriole/venule classification accuracy of 86.97% (per pixel basis) over the entire retinal image.

PMID: 28917120 [PubMed - as supplied by publisher]

LSD1-Mediated Epigenetic Reprogramming Drives CENPE Expression and Prostate Cancer Progression.

Biobank publications - Sun, 09/17/2017 - 14:44
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LSD1-Mediated Epigenetic Reprogramming Drives CENPE Expression and Prostate Cancer Progression.

Cancer Res. 2017 Sep 15;:

Authors: Liang Y, Ahmed M, Guo H, Soares F, Hua JT, Gao S, Lu C, Poon C, Han W, Langstein J, Ekram MB, Li B, Davicioni E, Takhar M, Erho N, Karnes RJ, Chadwick D, van der Kwast T, Boutros PC, Arrowsmith CH, Feng FY, Joshua AM, Zoubeidi A, Cai C, He HH

Abstract
Androgen receptor (AR) signaling is a key driver of prostate cancer (PCa), and androgen-deprivation therapy (ADT) is a standard treatment for patients with advanced and metastatic disease. However, patients receiving ADT eventually develop incurable castration-resistant PCa (CRPC). Here we report that the chromatin modifier LSD1, an important regulator of AR transcriptional activity, undergoes epigenetic reprogramming in CRPC. LSD1 reprogramming in this setting activated a subset of cell cycle genes including CENPE, a centromere binding protein and mitotic kinesin. CENPE was regulated by the co-binding of LSD1 and AR to its promoter, which was associated with loss of RB1 in CRPC. Notably, genetic deletion or pharmacological inhibition of CENPE significantly decrease tumor growth. Our findings show how LSD1-mediated epigenetic reprogramming drives CRPC, and they offer a mechanistic rationale for its therapeutic targeting in this disease.

PMID: 28916652 [PubMed - as supplied by publisher]

Serologic Evidence of Gut-driven Systemic Inflammation in Juvenile Idiopathic Arthritis.

Biobank publications - Sun, 09/17/2017 - 14:44
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Serologic Evidence of Gut-driven Systemic Inflammation in Juvenile Idiopathic Arthritis.

J Rheumatol. 2017 Sep 15;:

Authors: Fotis L, Shaikh N, Baszis KW, Samson CM, Lev-Tzion R, French AR, Tarr PI

Abstract
OBJECTIVE: Accumulating evidence links juvenile idiopathic arthritis (JIA) to nonhost factors such as gut microbes. We hypothesize that children with new-onset JIA have increased intestinal bacterial translocation and circulating lipopolysaccharide (LPS).
METHODS: We studied systemic treatment-naive patients with JIA [polyarticular JIA, n = 22, oligoarticular JIA, n = 31, and spondyloarthropathies (SpA), n = 16], patients with established inflammatory bowel disease-related arthritis (IBD-RA, n = 11), and 34 healthy controls. We determined circulating IgG reactivity against LPS, LPS-binding protein (LBP), α-1-acid glycoprotein (α-1AGP), and C-reactive protein (CRP) in plasma or serum from these patients and controls. Juvenile Arthritis Disease Activity Score (JADAS-27) was calculated for patients with JIA.
RESULTS: Circulating anticore LPS antibody concentrations in patients with polyarticular JIA (p = 0.001), oligoarticular JIA (p = 0.024), and SpA (p = 0.001) were significantly greater than in controls, but there were no significant intergroup differences. Circulating LBP concentrations were also significantly greater in patients with polyarticular JIA (p = 0.001), oligoarticular JIA (p = 0.002), and SpA (p = 0.006) than controls, as were α-1AGP concentrations (p = 0.001, 0.001, and 0.003, respectively). No differences were observed between controls and patients with IBD-RA in any of the assays. Circulating concentrations of LBP and α-1AGP correlated strongly with CRP concentrations (r = 0.78 and r = 0.66, respectively). Anticore LPS antibody levels and CRP (r = 0.26), LBP (r = 0.24), and α-AGP (r = 0.22) concentrations had weaker correlations. JADAS-27 scores correlated with LBP (r = 0.66) and α-1AGP concentrations (r = 0.58).
CONCLUSION: Children with polyarticular JIA, oligoarticular JIA, and SpA have evidence of increased exposure to gut bacterial products. These data reinforce the concept that the intestine is a source of immune stimulation in JIA.

PMID: 28916545 [PubMed - as supplied by publisher]

MiR-223-3p inhibits angiogenesis and promotes resistance to cetuximab in head and neck squamous cell carcinoma.

Biobank publications - Sun, 09/17/2017 - 14:44
Related Articles

MiR-223-3p inhibits angiogenesis and promotes resistance to cetuximab in head and neck squamous cell carcinoma.

Oncotarget. 2017 Aug 22;8(34):57174-57186

Authors: Bozec A, Zangari J, Butori-Pepino M, Ilie M, Lalvee S, Juhel T, Butori C, Brest P, Hofman P, Vouret-Craviari V

Abstract
MicroRNAs (miRs) participate in tumor growth and dissemination by regulating expression of various target genes. MiR-223-3p is suspected of being involved in head and neck squamous cell carcinoma (HNSCC) growth although its precise role has not been elucidated. In this study, we showed that miR-223-3p is present in biopsies of HNSCC patients and that its presence is correlated with high neutrophil infiltrate. We found that overexpression of miR-223-3p slightly increased proliferation of the CAL27 squamous carcinoma cell line both in vitro and in vivo. Moreover, miR-223-3p induced CAL27 apoptosis in an orthotopic xenograft mouse model, counteracting the proliferative effect and resulting in no impact on overall tumor growth. We analyzed the effect of miR-223-3p overexpression on signaling pathways and showed that it induced pERK2, pAKT and AKT, consistent with an increase in cell proliferation. In addition, we found that miR-223-3p reduced the STAT3 level correlating with increased cell apoptosis and inhibited vasculature formation. In HNSCC tissues, miR-223-3p expression was inversely correlated to CD31, highlighting the relationship between miR-223 and vessel formation. Finally, we studied the effect of miR-223-3p on response to selected anticancer agents and showed that cells expressing miR-223-3p are more resistant to drugs, notably cetuximab. In conclusion, our study is the first to show the antiangiogenic properties of miR-223-3p in HNSCC patients and to question whether expression levels of miR-223-3p can be evaluated as an indicator of eligibility for non-treatment of HNSCC patients with cetuximab.

PMID: 28915663 [PubMed - in process]

Marsdenia tenacissima extract overcomes Axl- and Met-mediated erlotinib and gefitinib cross-resistance in non-small cell lung cancer cells.

Biobank publications - Sun, 09/17/2017 - 14:44
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Marsdenia tenacissima extract overcomes Axl- and Met-mediated erlotinib and gefitinib cross-resistance in non-small cell lung cancer cells.

Oncotarget. 2017 Aug 22;8(34):56893-56905

Authors: Han SY, Zhao W, Han HB, Sun H, Xue D, Jiao YN, He XR, Jiang ST, Li PP

Abstract
Tyrosine kinase inhibitors (TKIs) are an effective treatment strategy for non-small cell lung cancer (NSCLC) patients harboring mutations that result in constitutive activation of the epidermal growth factor receptor (EGFR). However, most patients eventually develop resistance to TKIs. This occurs due to additional EGFR mutations or the activation of bypass signaling pathways. In our previous work, we demonstrated that Marsdenia tenacissima extract (MTE) restored gefitinib sensitivity in resistant NSCLC cells with EGFR T790M or K-ras mutations. However, the potential efficacy of MTE in NSCLC cells with resistance mediated by Axl and c-Met, and the related molecular mechanisms need to be elucidated. In this study we evaluated the ability of MTE to restore erlotinib/gefitinib sensitivity in TKI resistant HCC827/ER cells and xenograft mice models. Our results demonstrate that MTE overcomes erlotinib and gefitinib resistance driven by Axl and c-Met in vitro and in vivo. Combination therapy significantly suppressed EGFR downstream molecules and the c-Met and Axl activated bypass signaling pathways. Moreover, we observed that MTE is more efficient at restoring resistance to erlotinib than gefitinib. As the Axl and c-Met mediated bypass pathways share the same downstream signaling cascade as EGFR, simultaneous targeting of these pathways is a promising strategy to overcome acquired resistance of TKIs. Our results demonstrate that MTE treatment attenuates Axl phosphorylation and the associated epithelial-mesenchymal transition, suggesting MTE treatment may be a potential therapeutic strategy for overcoming erlotinib and gefitinib cross-resistance in NSCLC, especially for erlotinib resistance.

PMID: 28915640 [PubMed - in process]

Sample Identification Capacity of 20 Single Nucleotide Polymorphisms in Blood-Derived Genomic DNA Samples of Korean Individuals.

Biobank publications - Sat, 09/16/2017 - 13:25

Sample Identification Capacity of 20 Single Nucleotide Polymorphisms in Blood-Derived Genomic DNA Samples of Korean Individuals.

Biopreserv Biobank. 2017 Sep 15;

Authors: Lee JE, Kwon D, Lee M, Kim YY

PMID: 28915363 [PubMed - as supplied by publisher]

[China Hainan Centenarian Cohort Study: study design and preliminary results].

Biobank publications - Sat, 09/16/2017 - 13:25
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[China Hainan Centenarian Cohort Study: study design and preliminary results].

Zhonghua Liu Xing Bing Xue Za Zhi. 2017 Sep 10;38(9):1292-1298

Authors: He Y, Luan FX, Yao Y, Yang SS, Xie HG, Li J, Liu M, Wang JH, Wu L, Zhu Q, Chen XP, Ning CX, Wang LN, Li XY, Zhang SB, Zhang F, Zhao YL

Abstract
Objective: To investigate the health status, functional ability, mental psychology, health care and other longevity-related characteristics of individuals aged ≥100 years as well as risk factors in Hainan province, China. Methods: China Hainan Centenarian Cohort Study (CHCCS) is a community-based, prospective cohort study to establish multi-dimensional database consisting of questionnaire findings, anthropometric parameters and biological specimens as well as imaging features. With the household registration information provided by the Department of Civil Affairs of Hainan province, a baseline survey was conducted in centenarians in 18 counties in Hainan with the oldest old in 5 counties as controls between 2014 and 2017. The survey included face to face interview, physical examination and biological specimen collection. After the baseline survey, the participants of CHCCS were followed up at an interval of 2 years to collect the information about their living status, disease status or major death causes. Results: According to the information provided by the Department of Civil Affairs of Hainan province in 2014, the survey found that 1 473 centenarians were still living. By December 2016, 1 002 of them had agreed to be surveyed. The average age of 722 centenarians with complete information in the baseline survey was (102.7±2.7) years, the majority of them were females (83.0%), widows (88.8%), in Han ethnic group (84.5%), lived with family members (87.8%), illiterates (89.7%) and farmers (81.0%). Conclusion: CHCCS has provided longevity-related information of the large longevity population and collected the valuable and rare biological specimens with great urgency to establish an interdisciplinary platform and base for longevity, senility and healthy aging research.

PMID: 28910949 [PubMed - in process]

MicroRNA-382-5p aggravates breast cancer progression by regulating the RERG/Ras/ERK signaling axis.

Biobank publications - Sat, 09/16/2017 - 13:25
Related Articles

MicroRNA-382-5p aggravates breast cancer progression by regulating the RERG/Ras/ERK signaling axis.

Oncotarget. 2017 Apr 04;8(14):22443-22459

Authors: Ho JY, Hsu RJ, Liu JM, Chen SC, Liao GS, Gao HW, Yu CP

Abstract
Aberrant activation of the Ras/ERK pathway mediates breast cancer initiation and aggressiveness. Therefore, it is important to identify miRNAs that modulate the Ras/ERK pathway during breast carcinogenesis and progression. The Ras GTPase superfamily member RERG (Ras-related and estrogen-regulated growth inhibitor) acts as a tumor suppressor to reduce breast cancer cell proliferation and tumor formation and has been suggested to have a regulatory role in the Ras/ERK pathway. In this study, we found that RERG exerted its tumor suppressor role by attenuating the activation of Ras/ERK signaling effectors. Furthermore, we found that miR-382-5p directly targets and represses RERG to attenuate the inhibitory effects of RERG on the oncogenic Ras/ERK pathway. Thereby, miR-382-5p promoted breast cancer cell viability, clonogenicity, survival, migration, invasion and in vivo tumorigenesis/metastasis. In clinical interpretation, miR-382-5p expression was negatively correlated with RERG expression, and it also significantly functioned as an independent oncomiR for the higher incidence and poorer prognosis of breast cancer. This novel connection highlights new diagnostic and prognostic roles for miR-382-5p and RERG in breast cancer.

PMID: 27705918 [PubMed - indexed for MEDLINE]

Prospective investigation of risk factors for prostate cancer in the UK Biobank cohort study.

Biobank publications - Fri, 09/15/2017 - 14:18
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Prospective investigation of risk factors for prostate cancer in the UK Biobank cohort study.

Br J Cancer. 2017 Sep 14;:

Authors: Perez-Cornago A, Key TJ, Allen NE, Fensom GK, Bradbury KE, Martin RM, Travis RC

Abstract
BACKGROUND: Prostate cancer is the most common cancer in British men but its aetiology is not well understood. We aimed to identify risk factors for prostate cancer in British males.
METHODS: We studied 219 335 men from the UK Biobank study who were free from cancer at baseline. Exposure data were collected at recruitment. Prostate cancer risk by the different exposures was estimated using multivariable-adjusted Cox proportional hazards models.
RESULTS: In all, 4575 incident cases of prostate cancer occurred during 5.6 years of follow-up. Prostate cancer risk was positively associated with the following: black ethnicity (hazard ratio black vs white=2.61, 95% confidence interval=2.10-3.24); having ever had a prostate-specific antigen test (1.31, 1.23-1.40); being diagnosed with an enlarged prostate (1.54, 1.38-1.71); and having a family history of prostate cancer (1.94, 1.77-2.13). Conversely, Asian ethnicity (Asian vs white hazard ratio=0.62, 0.47-0.83), excess adiposity (body mass index (⩾35 vs <25 kg m(-2)=0.75, 0.64-0.88) and body fat (⩾30.1 vs <20.5%=0.81, 0.73-0.89)), cigarette smoking (current vs never smokers=0.85, 0.77-0.95), having diabetes (0.70, 0.62-0.80), and never having had children (0.89, 0.81-0.97) or sexual intercourse (0.53, 0.33-0.84) were related to a lower risk.
CONCLUSIONS: In this new large British prospective study, we identified associations with already-established, putative and possible novel risk factors for being diagnosed with prostate cancer. Future research will examine associations by tumour characteristics.British Journal of Cancer advance online publication 14 September 2017; doi:10.1038/bjc.2017.312 www.bjcancer.com.

PMID: 28910820 [PubMed - as supplied by publisher]

Effects of Cold Ischemia on RNA Stability and Quality of Lung Tissues Based on Standard PREanalytical Code Categorization.

Biobank publications - Fri, 09/15/2017 - 14:18
Related Articles

Effects of Cold Ischemia on RNA Stability and Quality of Lung Tissues Based on Standard PREanalytical Code Categorization.

Biopreserv Biobank. 2017 Sep 14;

Authors: Matsubara T, Tomida S, Soh J, Uwabo T, Mori Y, Morita M, Nasu Y, Kanazawa S, Toyooka S

PMID: 28910147 [PubMed - as supplied by publisher]

Efficacy evaluation of low-dose aspirin in IVF/ICSI patients evidence from 13 RCTs: A systematic review and meta-analysis.

Biobank publications - Fri, 09/15/2017 - 14:18
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Efficacy evaluation of low-dose aspirin in IVF/ICSI patients evidence from 13 RCTs: A systematic review and meta-analysis.

Medicine (Baltimore). 2017 Sep;96(37):e7720

Authors: Wang L, Huang X, Li X, Lv F, He X, Pan Y, Wang L, Zhang X

Abstract
BACKGROUND: We conducted a systematic review and meta-analysis of existing literature to evaluate the different outcomes of low-dose aspirin on patients undergoing in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI), including clinical pregnancy rate, implantation rate, live birth rate, miscarriage rate, fertilization rate, number of oocytes retrieved, and so forth.
METHODS: Electronic databases including PubMed, MEDLINE, and Embase were searched between 1997 and March 2016 to identity eligible studies. The following comparisons between treatment groups were included: aspirin versus placebo; aspirin versus control group; aspirin versus aspirin + prednisolone + control.
RESULTS: Thirteen randomized controlled trials which included 3104 participants were selected. There were no significant differences in implantation rate (RR = 1.15; 95% CI = 0.78-1.70), live birth rate (RR = 1.06; 95% CI = 0.93-1.21), miscarriage rate (RR = 1.28; 95% CI = 0.93-1.77), fertilization rate (RR = 0.91; 95% CI = 0.75-1.11), and endometrial thickness (WMD = 0.15; 95% CI = -0.38-0.67). But the research showed that aspirin treatment may improve the clinical pregnancy rate (RR = 1.16; 95% CI = 1.04-1.28) compared to placebo or no treatment, and reduce the number of oocytes retrieved (WMD = -0.68; 95% CI = -0.91-0.46).
CONCLUSIONS: Our findings suggest that low-dose aspirin may improve the pregnancy rate in IVF/ICSI, with the recommended clinical use dose of 100 mg/day. Considering the limitation of included studies, further well-designed large-scaled RCTs are necessary to clarify whether aspirin may improve assisted reproduction outcomes in IVF/ICSI patients.

PMID: 28906358 [PubMed - in process]

Evolving DNA methylation and gene expression markers of B-cell chronic lymphocytic leukemia are present in pre-diagnostic blood samples more than 10 years prior to diagnosis.

Biobank publications - Fri, 09/15/2017 - 14:18
Related Articles

Evolving DNA methylation and gene expression markers of B-cell chronic lymphocytic leukemia are present in pre-diagnostic blood samples more than 10 years prior to diagnosis.

BMC Genomics. 2017 Sep 13;18(1):728

Authors: Georgiadis P, Liampa I, Hebels DG, Krauskopf J, Chatziioannou A, Valavanis I, de Kok TMCM, Kleinjans JCS, Bergdahl IA, Melin B, Spaeth F, Palli D, Vermeulen RCH, Vlaanderen J, Chadeau-Hyam M, Vineis P, Kyrtopoulos SA, EnviroGenomarkers consortium

Abstract
BACKGROUND: B-cell chronic lymphocytic leukemia (CLL) is a common type of adult leukemia. It often follows an indolent course and is preceded by monoclonal B-cell lymphocytosis, an asymptomatic condition, however it is not known what causes subjects with this condition to progress to CLL. Hence the discovery of prediagnostic markers has the potential to improve the identification of subjects likely to develop CLL and may also provide insights into the pathogenesis of the disease of potential clinical relevance.
RESULTS: We employed peripheral blood buffy coats of 347 apparently healthy subjects, of whom 28 were diagnosed with CLL 2.0-15.7 years after enrollment, to derive for the first time genome-wide DNA methylation, as well as gene and miRNA expression, profiles associated with the risk of future disease. After adjustment for white blood cell composition, we identified 722 differentially methylated CpG sites and 15 differentially expressed genes (Bonferroni-corrected p < 0.05) as well as 2 miRNAs (FDR < 0.05) which were associated with the risk of future CLL. The majority of these signals have also been observed in clinical CLL, suggesting the presence in prediagnostic blood of CLL-like cells. Future CLL cases who, at enrollment, had a relatively low B-cell fraction (<10%), and were therefore less likely to have been suffering from undiagnosed CLL or a precursor condition, showed profiles involving smaller numbers of the same differential signals with intensities, after adjusting for B-cell content, generally smaller than those observed in the full set of cases. A similar picture was obtained when the differential profiles of cases with time-to-diagnosis above the overall median period of 7.4 years were compared with those with shorted time-to-disease. Differentially methylated genes of major functional significance include numerous genes that encode for transcription factors, especially members of the homeobox family, while differentially expressed genes include, among others, multiple genes related to WNT signaling as well as the miRNAs miR-150-5p and miR-155-5p.
CONCLUSIONS: Our findings demonstrate the presence in prediagnostic blood of future CLL patients, more than 10 years before diagnosis, of CLL-like cells which evolve as preclinical disease progresses, and point to early molecular alterations with a pathogenetic potential.

PMID: 28903739 [PubMed - in process]