Genome-wide DNA methylation analysis for diabetic nephropathy in type 1 diabetes mellitus

BACKGROUND: Diabetic nephropathy is a serious complication of diabetes mellitus and is associated with considerable morbidity and high mortality. There is increasing evidence to suggest that dysregulation of the epigenome is involved in diabetic nephropathy. We assessed whether epigenetic modification of DNA methylation is associated with diabetic nephropathy in a case-control study of 192 Irish patients with type 1 diabetes mellitus (T1D). Cases had T1D and nephropathy whereas controls had T1D but no evidence of renal disease. METHODS: We performed DNA methylation profiling in bisulphite converted DNA from cases and controls using the recently developed Illumina Infinium(R) HumanMethylation27 BeadChip, that enables the direct investigation of 27,578 individual cytosines at CpG loci throughout the genome, which are focused on the promoter regions of 14,495 genes. RESULTS: Singular Value Decomposition (SVD) analysis indicated that significant components of DNA methylation variation correlated with patient age, time to onset of diabetic nephropathy, and sex. Adjusting for confounding factors using multivariate Cox-regression analyses, and with a false discovery rate (FDR) of 0.05, we observed 19 CpG sites that demonstrated correlations with time to development of diabetic nephropathy. Of note, this included one CpG site located 18 bp upstream of the transcription start site of UNC13B, a gene in which the first intronic SNP rs13293564 has recently been reported to be associated with diabetic nephropathy. CONCLUSION: This high throughput platform was able to successfully interrogate the methylation state of individual cytosines and identified 19 prospective CpG sites associated with risk of diabetic nephropathy. These differences in DNA methylation are worthy of further follow-up in replication studies using larger cohorts of diabetic patients with and without nephropathy

W2S: Microscopy Data with Joint Denoising and Super-Resolution for Widefield to SIM Mapping

In fluorescence microscopy live-cell imaging, there is a critical trade-off between the signal-to-noise ratio and spatial resolution on one side, and the integrity of the biological sample on the other side. To obtain clean high-resolution (HR) images, one can either use microscopy techniques, such as structured-illumination microscopy (SIM), or apply denoising and super-resolution (SR) algorithms. However, the former option requires multiple shots that can damage the samples, and although efficient deep learning based algorithms exist for the latter option, no benchmark exists to evaluate these algorithms on the joint denoising and SR (JDSR) tasks. To study JDSR on microscopy data, we propose such a novel JDSR dataset, Widefield2SIM (W2S), acquired using a conventional fluorescence widefield and SIM imaging. W2S includes 144,000 real fluorescence microscopy images, resulting in a total of 360 sets of images. A set is comprised of noisy low-resolution (LR) widefield images with different noise levels, a noise-free LR image, and a corresponding high-quality HR SIM image. W2S allows us to benchmark the combinations of 6 denoising methods and 6 SR methods. We show that state-of-the-art SR networks perform very poorly on noisy inputs. Our evaluation also reveals that applying the best denoiser in terms of reconstruction error followed by the best SR method does not necessarily yield the best final result. Both quantitative and qualitative results show that SR networks are sensitive to noise and the sequential application of denoising and SR algorithms is sub-optimal. Lastly, we demonstrate that SR networks retrained end-to-end for JDSR outperform any combination of state-of-the-art deep denoising and SR networksComment: ECCVW 2020. Project page: \<https://github.com/ivrl/w2s

Blockage of angiotensin II type I receptor decreases the synthesis of growth factors and induces apoptosis in C6 cultured cells and C6 rat glioma

Angiotensin II (Ang II) is a main effector peptide in the renin–angiotensin system and participates in the regulation of vascular tone. It also has a role in the expression of growth factors that induce neovascularisation which is closely associated to the growth of malignant gliomas. We have shown that the selective blockage of the AT1 receptor of angiotensin inhibites tumour growth, cell proliferation and angiogenesis of C6 rat glioma. The aim of this study was to study the effects of the blockage of AT1 receptor on the synthesis of growth factors, and in the genesis of apoptosis in cultured C6 glioma cells and in rats with C6 glioma. Administration of losartan at doses of 40 or 80 mg kg−1 to rats with C6 glioma significantly decreased tumoral volume and production of platelet-derived growth factor, vascular endothelial growth factor and basic fibroblast growth factor. It also induced apoptosis in a dose-dependent manner. Administration of Ang II increased cell proliferation of cultured C6 cells which decreased by the administration of losartan. Our results suggest that the selective blockage of AT1 diminishes tumoral growth through inhibition of growth factors and promotion of apoptosis

Addition of ultrasound to mammography in the case of dense breast tissue: systematic review and meta-analysis.

BACKGROUND: Mammography is less effective in detecting cancer in dense than in fatty breasts. METHODS: We undertook a systematic search in PubMed to identify studies on women with dense breasts who underwent screening with mammography supplemented with ultrasound. A meta-analysis was undertaken on the proportion of cancers detected only by ultrasound, out of all screen-detected cancers, and the proportion of women with negative mammography who were referred for assessment following ultrasound screening. RESULTS: Twenty-nine studies satisfied our inclusion criteria. The proportion of total cancers detected only by ultrasound was 0.29 (95% CI: 0.27-0.31), consistent with an approximately 40% increase in the detection of cancers compared to mammography. In the studied populations, this translated into an additional 3.8 (95% CI: 3.4-4.2) screen-detected cases per 1000 mammography-negative women. About 13% (32/248) of cancers were in situ from 17 studies with information on this subgroup. Ultrasound approximately doubled the referral for assessment in three studies with these data. CONCLUSIONS: Studies have consistently shown an increased detection of breast cancer by supplementary ultrasound screening. An inclusion of supplementary ultrasound into routine screening will need to consider the availability of ultrasound and diagnostic assessment capacities.Department of Health Policy Research Programme (106/0001). Cancer Research UK (grants C8162/A16892 and C569/A16891)