Influence of Data Augmentation Strategies on the Segmentation of Oral Histological Images Using Fully Convolutional Neural Networks.

Segmentation of tumor regions in H &E-stained slides is an important task for a pathologist while diagnosing different types of cancer, including oral squamous cell carcinoma (OSCC). Histological image segmentation is often constrained by the availability of labeled training data since labeling histological images is a highly skilled, complex, and time-consuming task. Thus, data augmentation strategies become essential to train convolutional neural networks models to overcome the overfitting problem when only a few training samples are available. This paper proposes a new data augmentation strategy, named Random Composition Augmentation (RCAug), to train fully convolutional networks (FCN) to segment OSCC tumor regions in H &E-stained histological images. Given the input image and their corresponding label, a pipeline with a random composition of geometric, distortion, color transfer, and generative image transformations is executed on the fly. Experimental evaluations were performed using an FCN-based method to segment OSCC regions through a set of different data augmentation transformations. By using RCAug, we improved the FCN-based segmentation method from 0.51 to 0.81 of intersection-over-union (IOU) in a whole slide image dataset and from 0.65 to 0.69 of IOU in a tissue microarray images dataset.

Gene expression noise in spatial patterning: hunchback promoter structure affects noise amplitude and distribution in Drosophila segmentation.

Positional information in developing embryos is specified by spatial gradients of transcriptional regulators. One of the classic systems for studying this is the activation of the hunchback (hb) gene in early fruit fly (Drosophila) segmentation by the maternally-derived gradient of the Bicoid (Bcd) protein. Gene regulation is subject to intrinsic noise which can produce variable expression. This variability must be constrained in the highly reproducible and coordinated events of development. We identify means by which noise is controlled during gene expression by characterizing the dependence of hb mRNA and protein output noise on hb promoter structure and transcriptional dynamics. We use a stochastic model of the hb promoter in which the number and strength of Bcd and Hb (self-regulatory) binding sites can be varied. Model parameters are fit to data from WT embryos, the self-regulation mutant hb(14F), and lacZ reporter constructs using different portions of the hb promoter. We have corroborated model noise predictions experimentally. The results indicate that WT (self-regulatory) Hb output noise is predominantly dependent on the transcription and translation dynamics of its own expression, rather than on Bcd fluctuations. The constructs and mutant, which lack self-regulation, indicate that the multiple Bcd binding sites in the hb promoter (and their strengths) also play a role in buffering noise. The model is robust to the variation in Bcd binding site number across a number of fly species. This study identifies particular ways in which promoter structure and regulatory dynamics reduce hb output noise. Insofar as many of these are common features of genes (e.g. multiple regulatory sites, cooperativity, self-feedback), the current results contribute to the general understanding of the reproducibility and determinacy of spatial patterning in early development.

Regulation of radial glial motility by visual experience.

Radial glia in the developing optic tectum express the key guidance molecules responsible for topographic targeting of retinal axons. However, the extent to which the radial glia are themselves influenced by retinal inputs and visual experience remains unknown. Using multiphoton live imaging of radial glia in the optic tectum of intact Xenopus laevis tadpoles in conjunction with manipulations of neural activity and sensory stimuli, radial glia were observed to exhibit spontaneous calcium transients that were modulated by visual stimulation. Structurally, radial glia extended and retracted many filopodial processes within the tectal neuropil over minutes. These processes interacted with retinotectal synapses and their motility was modulated by nitric oxide (NO) signaling downstream of neuronal NMDA receptor (NMDAR) activation and visual stimulation. These findings provide the first in vivo demonstration that radial glia actively respond both structurally and functionally to neural activity, via NMDAR-dependent NO release during the period of retinal axon ingrowth.

Accuracy of computer-assisted image analysis in the diagnosis of maxillofacial radiolucent lesions: A systematic review and meta-analysis.

OBJECTIVES: This study aimed to search for scientific evidence concerning the accuracy of computer-assisted analysis for diagnosing maxillofacial radiolucent lesions. METHODS: A systematic review was conducted according to the statements of Preferred Reporting Items for Systematic Reviews and Meta-analyses Protocols and considering 10 databases, including the gray literature. Protocol was registered at the International Prospective Register of Systematic Reviews (CRD42018089945). The population, intervention, comparison and outcome strategy was used to define the eligibility criteria and only diagnostic test studies were included. Their risk of bias was assessed by the Joanna Briggs Institute Critical Appraisal tool. Random-effects model meta-analysis was performed and heterogeneity among the included studies was estimated using the I2 statistic. The grade of recommendation, assessment, development, and evaluation (GRADE) tool assessed the quality of evidence and strength of recommendation across included studies. RESULTS: Out of 715 identified citations, four papers, published between 2009 and 2017, fulfilled the criteria and were included in this systematic review. A total of 191 lesions, classified as periapical granuloma and cyst, dentigerous cyst or keratocystic odontogenic tumor, were analyzed. All selected articles scored low risk of bias. The pooled accuracy estimation, regardless of the classification method used, was 88.75% (95% CI = 85.19-92.30). Heterogeneity test reached moderate values (I2 = 57.89%). According to the GRADE tool, the analyzed outcome was classified as having low level of certainty. CONCLUSIONS: The overall evaluation showed all studies presented high accuracy rates of computer-aided diagnosis systems in classifying radiolucent maxillofacial lesions compared to histopathological biopsy. However, due to the moderate heterogeneity found among the studies included in this meta-analysis, a pragmatic recommendation about the use of computer-assisted analysis is not possible.

Studies of aberrant phyllotaxy1 mutants of maize indicate complex interactions between auxin and cytokinin signaling in the shoot apical meristem.

One of the most fascinating aspects of plant morphology is the regular geometric arrangement of leaves and flowers, called phyllotaxy. The shoot apical meristem (SAM) determines these patterns, which vary depending on species and developmental stage. Auxin acts as an instructive signal in leaf initiation, and its transport has been implicated in phyllotaxy regulation in Arabidopsis (Arabidopsis thaliana). Altered phyllotactic patterns are observed in a maize (Zea mays) mutant, aberrant phyllotaxy1 (abph1, also known as abphyl1), and ABPH1 encodes a cytokinin-inducible type A response regulator, suggesting that cytokinin signals are also involved in the mechanism by which phyllotactic patterns are established. Therefore, we investigated the interaction between auxin and cytokinin signaling in phyllotaxy. Treatment of maize shoots with a polar auxin transport inhibitor, 1-naphthylphthalamic acid, strongly reduced ABPH1 expression, suggesting that auxin or its polar transport is required for ABPH1 expression. Immunolocalization of the PINFORMED1 (PIN1) polar auxin transporter revealed that PIN1 expression marks leaf primordia in maize, similarly to Arabidopsis. Interestingly, maize PIN1 expression at the incipient leaf primordium was greatly reduced in abph1 mutants. Consistently, auxin levels were reduced in abph1, and the maize PIN1 homolog was induced not only by auxin but also by cytokinin treatments. Our results indicate distinct roles for ABPH1 as a negative regulator of SAM size and a positive regulator of PIN1 expression. These studies highlight a complex interaction between auxin and cytokinin signaling in the specification of phyllotactic patterns and suggest an alternative model for the generation of altered phyllotactic patterns in abph1 mutants. We propose that reduced auxin levels and PIN1 expression in abph1 mutant SAMs delay leaf initiation, contributing to the enlarged SAM and altered phyllotaxy of these mutants.

A new method for quantifying three-dimensional interactions between biological structures.

In this paper we examine a new distance-based method for identifying and characterizing possible interactions between biological structures and objects, with respect to the initial developmental stages of Echinococcus granulosus. By adopting the surface of the foramen as the distance reference, several interesting results have been identified, including the fact that the cell nuclei tend to be organized with respect to the foramen surface as well as the stability of the spatial distribution of these nuclei along the development stages.