Impact of Image Preprocessing Methods and Deep Learning Models for Classifying Histopathological Breast Cancer Images

Early diagnosis of cancer is very important as it significantly increases the chances of appropriate treatment and survival. To this end, Deep Learning models are increasingly used in the classification and segmentation of histopathological images, as they obtain high accuracy index and can help specialists. In most cases, images need to be preprocessed for these models to work correctly. In this paper, a comparative study of different preprocessing methods and deep learning models for a set of breast cancer images is presented. For this purpose, the statistical test ANOVA with data obtained from the performance of five different deep learning models is analyzed. An important conclusion from this test can be obtained; from the point of view of the accuracy of the system, the main repercussion is the deep learning models used, however, the filter used for the preprocessing of the image, has no statistical significance for the behavior of the system.Spanish Government PID2021-128317OB-I00Government of Andalusia P20-0016

Interaction of Nanoparticles with Blood Components and Associated Pathophysiological Effects

Nanotechnology currently plays a pivotal role in several fields and has enabled substantial advances in a relatively short time. In biomedicine, nanomaterials can be potentially employed as a tool for early diagnosis and an innovative mode of drug delivery. Novel nanomaterials are currently widely manipulated without a full assessment of their potential health risks. It is commonly thought that nanomaterials’ first contact with the organism is through the different components of the immune system. However, if the entry route is intravenous, the first contact will be with the blood’s components (erythrocytes, platelets, white cells, plasma and complement proteins). The presence of nanomaterials within a dynamic environment such as the bloodstream can produce potential harmful effects following interaction with several blood components. The design of innovative strategies leading to the development of more hemocompatible nanomaterials is also necessary

Leukemia multiclass assessment and classification from Microarray and RNA-seq technologies integration at gene expression level

In more recent years, a significant increase in the number of available biological experiments has taken place due to the widespread use of massive sequencing data. Furthermore, the continuous developments in the machine learning and in the high performance computing areas, are allowing a faster and more efficient analysis and processing of this type of data. However, biological information about a certain disease is normally widespread due to the use of different sequencing technologies and different manufacturers, in different experiments along the years around the world. Thus, nowadays it is of paramount importance to attain a correct integration of biologically-related data in order to achieve genuine benefits from them. For this purpose, this work presents an integration of multiple Microarray and RNA-seq platforms, which has led to the design of a multiclass study by collecting samples from the main four types of leukemia, quantified at gene expression. Subsequently, in order to find a set of differentially expressed genes with the highest discernment capability among different types of leukemia, an innovative parameter referred to as coverage is presented here. This parameter allows assessing the number of different pathologies that a certain gen is able to discern. It has been evaluated together with other widely known parameters under assessment of an ANOVA statistical test which corroborated its filtering power when the identified genes are subjected to a machine learning process at multiclass level. The optimal tuning of gene extraction evaluated parameters by means of this statistical test led to the selection of 42 highly relevant expressed genes. By the use of minimum- Redundancy Maximum-Relevance (mRMR) feature selection algorithm, these genes were reordered and assessed under the operation of four different classification techniques. Outstanding results were achieved by taking exclusively the first ten genes of the ranking into consideration. Finally, specific literature was consulted on this last subset of genes, revealing the occurrence of practically all of them with biological processes related to leukemia. At sight of these results, this study underlines the relevance of considering a new parameter which facilitates the identification of highly valid expressed genes for simultaneously discerning multiple types of leukemia.This work was supported by Project TIN2015-71873-R (Spanish Ministry of Economy and Competitiveness -MINECO- and the European Regional Development Fund -ERDF) and Junta de Andalucı´a (P12–TIC–2082)

Phagocytic clearance of presynaptic dystrophies by reactive astrocytes in Alzheimer's disease

Reactive astrogliosis, a complex process characterized by cell hypertrophy and upregulation ofcomponents of intermediate filaments, is a common feature in brains of Alzheimer’s patients. Reac-tive astrocytes are found in close association with neuritic plaques; however, the precise role ofthese glial cells in disease pathogenesis is unknown. In this study, using immunohistochemical tech-niques and light and electron microscopy, we report that plaque-associated reactive astrocytesenwrap, engulf and may digest presynaptic dystrophies in the hippocampus of amyloid precursorprotein/presenilin-1 (APP/PS1) mice. Microglia, the brain phagocytic population, was apparentlynot engaged in this clearance. Phagocytic reactive astrocytes were present in 35% and 67% ofamyloid plaques at 6 and 12 months of age, respectively. The proportion of engulfed dystrophicneurites was low, around 7% of total dystrophies around plaques at both ages. This fact, alongwith the accumulation of dystrophic neurites during disease course, suggests that the efficiency ofthe astrocyte phagocytic process might be limited or impaired. Reactive astrocytes surroundingand engulfing dystrophic neurites were also detected in the hippocampus of Alzheimer’spatientsby confocal and ultrastructural analysis. We posit that the phagocytic activity of reactive astrocytesmight contribute to clear dysfunctional synapses or synaptic debris, thereby restoring impairedneural circuits and reducing the inflammatory impact of damaged neuronal parts and/or limitingthe amyloid pathology. Therefore, potentiation of the phagocytic properties of reactive astrocytesmay represent a potential therapy in Alzheimer s disease.Fondo de Investigación Sanitaria (FIS). Instituto de Salud Carlos III (ISCiii) de España y fondos FEDER de la Unión Europea. PI15/00796 y PI15/00957Fundación La Marató-TV3 de Cataluña, España. 20141432, 20141431, 20141433, y 20141430Centro de investigación en red de enfermedades neurodegenerativas (CIBERNED) de España. PI2015-2/02Junta de Andalucía. Proyecto de Excelencia CTS-203

A nonsynonymous FCER1B SNP is associated with risk of developing allergic rhinitis and with IgE levels

Allergic rhinitis is associated with elevated serum IgE levels. IgE response is mediated by the highaffinity IgE receptor (FcεRI), which is polymorphic. Studies analyzing the association between allergic rhinitis and FcεRI variants have been conducted with controversial results. The objective of this study is to analyze, in 1,041 individuals, the putative clinical association of allergic rhinitis with common polymorphisms in FcεRI subunits genes. These SNPs included FECR1A rs2494262, rs2427837 and rs2251746; FECR1B rs1441586, rs569108 and rs512555; FCER1G rs11587213, rs2070901 and rs11421. Statistically significant differences were observed for the FCER1B rs569108 and rs512555 polymorphisms frequencies when comparing patients with allergic rhinitis without asthma and controls. The OR (95% CI) value for the 237Gly allele (rs569108) is equal to 0.26 (0.08–0.86, P = 0.017) and for the G allele (rs512555) it is equal to 0.27 (0.08–0.88, P = 0.020). These two SNPs are linked (D’ = 1.0, LOD = 56.05). Also observed was a statistically significant trend towards lower IgE values among allergic rhinitis patients with variant alleles for both SNPs. In conclusion, in patients with allergic rhinitis without asthma, the FCER1B rs569108 and rs512555 polymorphisms are associated with increased risk of developing allergic rhinitis and with lower IgE levels.Trabajo financiado por: Instituto de Salud Carlos III. Fondo de Investigación Sanitaria. Becas PI12/00241, PI12/00324 y RETICS RD12/0013/0002 Junta de Extremadura y Fondos FEDER. Ayuda GR15026peerReviewe

Expression of Gls and Gls2 glutaminase isoforms in astrocytes

The expression of glutaminase in glial cells has been a controversial issue and matter of debate for many years. Actually, glutaminase is essentially considered as a neuronal marker in brain. Astrocytes are endowed with efficient and high capacity transport systems to recapture synaptic glutamate which seems to be consistent with the absence of glutaminase in these glial cells. In this work, a comprehensive study was devised to elucidate expression of glutaminase in neuroglia and, more concretely, in astrocytes. Immunocytochemistry in rat and human brain tissues employing isoform-specific antibodies revealed expression of both Gls and Gls2 glutaminase isozymes in glutamatergic and GABAergic neuronal populations as well as in astrocytes. Nevertheless, there was a different subcellular distribution: Gls isoform was always present in mitochondria while Gls2 appeared in two different locations, mitochondria and nucleus. Confocal microscopy and double immunofluorescence labeling in cultured astrocytes confirmed the same pattern previously seen in brain tissue samples. Astrocytic glutaminase expression was also assessed at the mRNA level, real-time quantitative RT-PCR detected transcripts of four glutaminase isozymes but with marked differences on their absolute copy number: the predominance of Gls isoforms over Gls2 transcripts was remarkable (ratio of 144:1). Finally, we proved that astrocytic glutaminase proteins possess enzymatic activity by in situ activity staining: concrete populations of astrocytes were labeled in the cortex, cerebellum and hippocampus of rat brain demonstrating functional catalytic activity. These results are relevant for the stoichiometry of the Glu/Gln cycle at the tripartite synapse and suggest novel functions for these classical metabolic enzymes

Consecuencias del estrés calórico sobre la reproducción del ganado vacuno

Heat stress represents one of the major environmental factors that adversely affect the reproductive performance of cattle. In this paper the behavioral adjustments, physical mechanisms and physiological responses to heat loss are described; bos indicus adaptive advantages with respect to bos Taurus, pathophysiology of heat stress and heat stress effects in animal reproduction, both the male and the female.El estrés calórico representa unos de los principales factores del medio ambiente que repercuten negativamente en el desempeño reproductivo del ganado vacuno. En este trabajo se describen los ajustes conductuales, mecanismos físicos y respuestas fisiológicas para la pérdida calórica; ventajas adaptativas del bos indicus con respecto al bos Taurus, fisiopatología del estrés calórico y repercusiones del estrés calórico en la reproducción animal, tanto en el macho como en la hembra