Publications by authors named "Carlos Castilla"

Introduction: Learning laparoscopy (LAP) is challenging and requires different skills to conventional open surgery. There is a recognized need for a standardized laparoscopic training framework within urology to overcome these difficulties and to shift learning curve from patient to skills laboratory. Simulation-based training has been widely commented, but implementation in real day practice is lacking.

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Alternative splicing (AS) plays a key role in cancer: all its hallmarks have been associated with different mechanisms of abnormal AS. The improvement of the human transcriptome annotation and the availability of fast and accurate software to estimate isoform concentrations has boosted the analysis of transcriptome profiling from RNA-seq. The statistical analysis of AS is a challenging problem not yet fully solved.

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The development of predictive biomarkers of response to targeted therapies is an unmet clinical need for many antitumoral agents. Recent genome-wide loss-of-function screens, such as RNA interference (RNAi) and CRISPR-Cas9 libraries, are an unprecedented resource to identify novel drug targets, reposition drugs and associate predictive biomarkers in the context of precision oncology. In this work, we have developed and validated a large-scale bioinformatics tool named DrugSniper, which exploits loss-of-function experiments to model the sensitivity of 6237 inhibitors and predict their corresponding biomarkers of sensitivity in 30 tumor types.

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The advent of RNA-seq technologies has switched the paradigm of genetic analysis from a genome to a transcriptome-based perspective. Alternative splicing generates functional diversity in genes, but the precise functions of many individual isoforms are yet to be elucidated. Gene Ontology was developed to annotate gene products according to their biological processes, molecular functions and cellular components.

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The migration of cancer cells is highly regulated by the biomechanical properties of their local microenvironment. Using 3D scaffolds of simple composition, several aspects of cancer cell mechanosensing (signal transduction, EMC remodeling, traction forces) have been separately analyzed in the context of cell migration. However, a combined study of these factors in 3D scaffolds that more closely resemble the complex microenvironment of the cancer ECM is still missing.

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We present a 3D bioimage analysis workflow to quantitatively analyze single, actin-stained cells with filopodial protrusions of diverse structural and temporal attributes, such as number, length, thickness, level of branching, and lifetime, in time-lapse confocal microscopy image data. Our workflow makes use of convolutional neural networks trained using real as well as synthetic image data, to segment the cell volumes with highly heterogeneous fluorescence intensity levels and to detect individual filopodial protrusions, followed by a constrained nearest-neighbor tracking algorithm to obtain valuable information about the spatio-temporal evolution of individual filopodia. We validated the workflow using real and synthetic 3-D time-lapse sequences of lung adenocarcinoma cells of three morphologically distinct filopodial phenotypes and show that it achieves reliable segmentation and tracking performance, providing a robust, reproducible and less time-consuming alternative to manual analysis of the 3D+t image data.

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Article Synopsis
  • Microfluidic devices help scientists study how lung cancer cells move in different environments, like how they behave in small tubes filled with special jelly-like materials.
  • The study shows that the way cancer cells move changes depending on the type of jelly they are in; sometimes they move faster, and sometimes slower, depending on how thick the jelly is.
  • This research can help create better ways to test treatments for cancer by using smart tools that can control the environment for the cells, making it easier to understand how to fight the disease.
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The geometry of 3D collagen networks is a key factor that influences the behavior of live cells within extra-cellular matrices. This paper presents a method for automatic quantification of the 3D collagen network geometry with fiber resolution in confocal reflection microscopy images. The proposed method is based on a smoothing filter and binarization of the collagen network followed by a fiber reconstruction algorithm.

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Background: The management of hydatid liver disease (HLD) includes various nonsurgical and surgical treatment options.

Methods: The purpose of the present longitudinal study was to report the changes in surgical management and the consequent outcome of HLD patients in 10 referral surgical centres in Argentina from 1975 to 2007. The study result analysis was divided into two study periods (1975-1990 and 1991-2007).

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Parkinson's disease (PD) is a common neurodegenerative disorder that produces progressive disability despite symptomatic treatment. Several strategies, including stereotaxic brain lesions, deep brain stimulation, transplants of dopamine cells and administration of neurotrophic factors, have been proposed to improve efficacy and to counteract the progression of the disease. We here report the effects of repetitive intracerebral infusion of basic fibroblast growth factor (bFGF) and glial-derived neurotrophic factor, up to 1 year, in Cynomolgus monkeys with long standing asymmetric parkinsonism produced by unilateral intracarotid injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).

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