Terabyte-scale supervised 3D training and benchmarking dataset of the mouse kidney

The performance of machine learning algorithms, when used for segmenting 3D biomedical images, does not reach the level expected based on results achieved with 2D photos. This may be explained by the comparative lack of high-volume, high-quality training datasets, which require state-of-the-art imaging facilities, domain experts for annotation and large computational and personal resources. The HR-Kidney dataset presented in this work bridges this gap by providing 1.7 TB of artefact-corrected synchrotron radiation-based X-ray phase-contrast microtomography images of whole mouse kidneys and validated segmentations of 33 729 glomeruli, which corresponds to a one to two orders of magnitude increase over currently available biomedical datasets. The image sets also contain the underlying raw data, threshold- and morphology-based semi-automatic segmentations of renal vasculature and uriniferous tubules, as well as true 3D manual annotations. We therewith provide a broad basis for the scientific community to build upon and expand in the fields of image processing, data augmentation and machine learning, in particular unsupervised and semi-supervised learning investigations, as well as transfer learning and generative adversarial networks

Terabyte-scale supervised 3D training and benchmarking dataset of the mouse kidney

The performance of machine learning algorithms, when used for segmenting 3D biomedical images, does not reach the level expected based on results achieved with 2D photos. This may be explained by the comparative lack of high-volume, high-quality training datasets, which require state-of-the-art imaging facilities, domain experts for annotation and large computational and personal resources. The HR-Kidney dataset presented in this work bridges this gap by providing 1.7 TB of artefact-corrected synchrotron radiation-based X-ray phase-contrast microtomography images of whole mouse kidneys and validated segmentations of 33 729 glomeruli, which corresponds to a one to two orders of magnitude increase over currently available biomedical datasets. The image sets also contain the underlying raw data, threshold- and morphology-based semi-automatic segmentations of renal vasculature and uriniferous tubules, as well as true 3D manual annotations. We therewith provide a broad basis for the scientific community to build upon and expand in the fields of image processing, data augmentation and machine learning, in particular unsupervised and semi-supervised learning investigations, as well as transfer learning and generative adversarial networks

Metamorphic testing for cybersecurity

Metamorphic testing (MT) can enhance security testing by providing an alternative to using a testing oracle, which is often unavailable or impractical. The authors report how MT detected previously unknown bugs in real-world critical applications such as code obfuscators, giving evidence that software testing requires diverse perspectives to achieve greater cybersecurity

Evolution of hypoxia and hypoxia-inducible factor asparaginyl hydroxylase regulation in chronic kidney disease

Background The roles of hypoxia and hypoxia inducible factor (HIF) during chronic kidney disease (CKD) are much debated. Interventional studies with HIF-α activation in rodents have yielded contradictory results. The HIF pathway is regulated by prolyl and asparaginyl hydroxylases. While prolyl hydroxylase inhibition is a well-known method to stabilize HIF-α, little is known about the effect asparaginyl hydroxylase factor inhibiting HIF (FIH). Methods We used a model of progressive proteinuric CKD and a model of obstructive nephropathy with unilateral fibrosis. In these models we assessed hypoxia with pimonidazole and vascularization with three-dimensional micro-computed tomography imaging. We analysed a database of 217 CKD biopsies from stage 1 to 5 and we randomly collected 15 CKD biopsies of various severity degrees to assess FIH expression. Finally, we modulated FIH activity in vitro and in vivo using a pharmacologic approach to assess its relevance in CKD. Results In our model of proteinuric CKD, we show that early CKD stages are not characterized by hypoxia or HIF activation. At late CKD stages, some areas of hypoxia are observed, but these are not colocalizing with fibrosis. In mice and in humans, we observed a downregulation of the HIF pathway, together with an increased FIH expression in CKD, according to its severity. Modulating FIH in vitro affects cellular metabolism, as described previously. In vivo, pharmacologic FIH inhibition increases the glomerular filtration rate of control and CKD animals and is associated with decreased development of fibrosis. Conclusions The causative role of hypoxia and HIF activation in CKD progression is questioned. A pharmacological approach of FIH downregulation seems promising in proteinuric kidney disease

Operational Research: Methods and Applications

Throughout its history, Operational Research has evolved to include a variety of methods, models and algorithms that have been applied to a diverse and wide range of contexts. This encyclopedic article consists of two main sections: methods and applications. The first aims to summarise the up-to-date knowledge and provide an overview of the state-of-the-art methods and key developments in the various subdomains of the field. The second offers a wide-ranging list of areas where Operational Research has been applied. The article is meant to be read in a nonlinear fashion. It should be used as a point of reference or first-port-of-call for a diverse pool of readers: academics, researchers, students, and practitioners. The entries within the methods and applications sections are presented in alphabetical order

High resolution 3D functional anatomy database of the kidney

The kidney is the organ responsible for blood filtration and is supplied with blood independently of its oxygen demand. This project was embedded in an overarching research initiative to investigate the properties and behavior of oxygen distribution of the kidney and its effects on oxygen-dependent mechanisms. Computational modeling of oxygen transport and distribution in the murine kidney requires detailed three-dimensional (3D) structural data of blood vessels, the main oxygen suppliers, and tubules, the main oxygen consumers. In order to provide these data on the whole kidney level, vascular casting protocols for X-ray microcomputed tomography imaging were developed. Mouse kidneys were subsequently imaged at synchrotron radiation facilities to acquire vascular and tubular structure datasets with full capillary resolution. Image processing and segmentation was performed on the resulting terabyte-scale dataset using high performance computing clusters, building the first 3D atlas of the vascular and tubular structure of a whole mouse kidney. To make the process more widely accessible, a cross-linkable, polymeric X-ray contrast agent was developed and used for combined vascular and tubular imaging with widely available laboratory X ray source micro-CT equipment, which was previously reserved to synchrotron radiation facilities. Vascular and tubular structures were segmented in a simplified workflow based on free software and workstation-grade hardware