A novel endoimaging system for endoscopic 3D reconstruction in bladder cancer patients.

INTRODUCTION: The methods employed to document cystoscopic findings in bladder cancer patients lack accuracy and are subject to observer variability. We propose a novel endoimaging system and an online documentation platform to provide post-procedural 3D bladder reconstructions for improved diagnosis, management and follow-up. MATERIAL AND METHODS: The RaVeNNA4pi consortium is comprised of five industrial partners, two university hospitals and two technical institutes. These are grouped into hardware, software and clinical partners according to their professional expertise. The envisaged endoimaging system consists of an innovative cystoscope that generates 3D bladder reconstructions allowing users to remotely access a cloud-based centralized database to visualize individualized 3D bladder models from previous cystoscopies archived in DICOM format. RESULTS: Preliminary investigations successfully tracked the endoscope's rotational and translational movements. The structure-from-motion pipeline was tested in a bladder phantom and satisfactorily demonstrated 3D reconstructions of the processing sequence. AI-based semantic image segmentation achieved a 0.67 dice-score-coefficient over all classes. An online-platform allows physicians and patients to digitally visualize endoscopic findings by navigating a 3D bladder model. CONCLUSIONS: Our work demonstrates the current developments of a novel endoimaging system equipped with the potential to generate 3D bladder reconstructions from cystoscopy videos and AI-assisted automated detection of bladder tumors.

Single-cell mRNA profiling reveals changes in solute carrier expression and suggests a metabolic switch during zebrafish pronephros development.

Developing organisms need to adapt to environmental variations as well as to rapid changes in substrate availability and energy demands imposed by fast-growing tissues and organs. Little is known about the adjustments that kidneys undergo in response to these challenges. We performed single-cell RNA sequencing of zebrafish pronephric duct cells to understand how the developing kidney responds to changes in filtered substrates and intrinsic energy requirements. We found high levels of glucose transporters early in development and increased expression of monocarboxylate transporters at later times. This indicates that the zebrafish embryonic kidney displays a high glucose transporting capacity during early development, which is replaced by the ability to absorb monocarboxylates and amino acids at later stages. This change in transport capacity was accompanied by the upregulation of mitochondrial carriers, indicating a switch to increased oxidative phosphorylation to meet the increasing energy demand of a developing kidney.NEW & NOTEWORTHY The zebrafish embryonic kidney has high levels of glucose transporters during early development, which are replaced by monocarboxylate and amino acid transporters later on. Inhibition of Na+-glucose cotransporter-dependent glucose transport by sotagliflozin also increased slc2a1a expression, supporting the idea that the glucose transport capacity is dynamically adjusted during zebrafish pronephros development. Concurrent upregulation of mitochondrial SCL25 transporters at later stages supports the idea that the pronephros adjusts to changing substrate supplies and/or energy demands during embryonic development.

Nephrocystin-4 is required for pronephric duct-dependent cloaca formation in zebrafish.

NPHP4 mutations cause nephronophthisis, an autosomal recessive cystic kidney disease associated with renal fibrosis and kidney failure. The NPHP4 gene product nephrocystin-4 interacts with other nephrocystins, cytoskeletal and ciliary proteins; however, the molecular and cellular functions of nephrocystin-4 have remained elusive. Here we demonstrate that nephrocystin-4 is required for normal cloaca formation during zebrafish embryogenesis. Time-lapse imaging of the developing zebrafish pronephros revealed that tubular epithelial cells at the distal pronephros actively migrate between the yolk sac extension and the blood island towards the ventral fin fold to join the proctodeum and to form the cloaca. Nphp4-deficient pronephric duct cells failed to connect with their ectodermal counterparts, and instead formed a vesicle at the obstructed end of the pronephric duct. Nephrocystin-4 interacts with nephrocystin-1 and Par6. Depletion of zebrafish NPHP1 (nphp1) increased the incidence of cyst formation and randomization of the normal body axis, but did not augment cloaca malformation in nphp4-deficient zebrafish embryos. However, simultaneous depletion of zebrafish Par6 (pard6) aggravated cloaca formation defects in nphp4-depleted embryos, suggesting that nphp4 orchestrates directed cell migration and cloaca formation through interaction with the Par protein complex.