A modular metagenomics analysis system for integrated multi-step data exploration.

Motivation: Computational analysis of large-scale metagenomics sequencing datasets has proved to be both incredibly valuable for extracting isolate-level taxonomic and functional insights from complex microbial communities. However, thanks to an ever-expanding ecosystem of metagenomics-specific algorithms and file formats, designing studies, implementing seamless and scalable end-to-end workflows, and exploring the massive amounts of output data have become studies unto themselves. Furthermore, there is little inter-communication between output data of different analytic purposes, such as short-read classification and metagenome assembled genomes (MAG) reconstruction. One-click pipelines have helped to organize these tools into targeted workflows, but they suffer from general compatibility and maintainability issues. Results: To address the gap in easily extensible yet robustly distributable metagenomics workflows, we have developed a module-based metagenomics analysis system written in Snakemake, a popular workflow management system, along with a standardized module and working directory architecture. Each module can be run independently or conjointly with a series of others to produce the target data format (ex. short-read preprocessing alone, or short-read preprocessing followed by de novo assembly), and outputs aggregated summary statistics reports and semi-guided Jupyter notebook-based visualizations, The module system is a bioinformatics-optimzied scaffold designed to be rapidly iterated upon by the research community at large. Availability: The module template as well as the modules described below can be found at https://github.com/MetaSUB-CAMP.

The Paradigm of the Inflammatory Radicular Cyst: Biological Aspects to be Considered.

Inflammatory radicular cysts (IRCs) are chronic lesions that follow the development of periapical granulomas (PGs). IRCs result from multiple inflammatory reactions led initially by several pro-inflammatory interleukins and growth factors that provoke the proliferation of epithelial cells derived from epithelial cell rests of Malassez present in the granulomatous tissue, followed by cyst formation and growth processes. Multiple theories have been proposed to help explain the molecular process involved in the development of the IRC from a PG. However, although multiple studies have demonstrated the presence of epithelial cells in most PGs, it is still not fully understood why not all PGs turn into IRCs, even though both are stages of the same inflammatory phenomenon and receive the same antigenic stimulus. Histopathological examination is currently the diagnostic gold standard for differentiating IRCs from PGs. Although multiple studies have evaluated the accuracy of non-invasive or minimally invasive methods in assessing the histopathological nature of the AP before the intervention, these studies' results are still controversial. This narrative review addresses the biological insights into the complex molecular mechanisms of IRC formation and its histopathological features. In addition, the relevant inflammatory molecular mediators for IRC development and the accuracy of non-invasive or minimally invasive diagnostic approaches are summarised. (EEJ-2022-03-041).

Probióticos: una mirada al mecanismo de acción y aplicaciones clínicas en Pediatría

Introducción: Los probióticos son microorganismos vivos que brindan beneficios al huésped mediante diversos mecanismos de acción. Han sido fuente de estudio en diversas patologías pediátricas, mostrando algunos resultados prometedores. Objetivo: Elaborar una revisión de la literatura sobre los mecanismos de acción y la evidencia actual que tienen los probióticos sobre la salud infantil. Materiales y métodos: Se realizó una revisión narrativa de la literatura con estrategia de búsqueda sistemática de la literatura con términos MESH acerca de los mecanismos de acción de los probióticos y su uso. Se incluyeron metaanálisis, revisiones sistemáticas y ensayos clínicos aleatorizados. Resultados: Los probióticos son una nueva herramienta terapéutica usada para mejorar la salud infantil. Se ha encontrado efecto benéfico en diarrea, en enterocolitis necrosante con una disminución significativa de la mortalidad y se ha mostrado evidencia significativa en las horas de llanto en cólico del lactante. Conclusión: Se requieren más estudios en otro tipo de enfermedades como estreñimiento y en algunos procesos alérgicos e inflamatorios. Los ensayos revisados ofrecen un panorama prometedor, pero la elección de un probiótico debe ser personalizado de acuerdo con la edad, enfermedad, cepa y dosis, dado que cada uno de ellos tiene múltiples mecanismos de acción que impactan de manera diferente en la eficacia clínica.

Introduction: Prebiotics are living microorganisms that provide benefits to the host through various mechanisms of action. They have been a source of study in various pediatric pathologies showing some promising results. Objective: To prepare a review on the mechanisms of action and current evidence that prebiotics have on child health. Materials and methods: A narrative review of the literature was carried out with a systematic literature search strategy with MESH terms about the mechanisms of action of probiotics and their use. Meta-analyzes, systematic reviews, and randomized clinical trials were included. Results: Probiotics are a new therapeutic tool used to improve children's health. A beneficial effect has been found in diarrhea, in necrotizing enterocolitis with a significant decrease in mortality and significant evidence has been shown in the hours of crying in colic in infants. Conclusion: The trials reviewed offer a promising picture, but the choice of a probiotic must be customized according to the age, disease, bacterial strain and dose, since each one has different action mechanisms and clinical effectiveness. More studies are required in some allergic and inflammatory diseases.

Computational Tools for the Analysis of Uncultivated Phage Genomes.

Over a century of bacteriophage research has uncovered a plethora of fundamental aspects of their biology, ecology, and evolution. Furthermore, the introduction of community-level studies through metagenomics has revealed unprecedented insights on the impact that phages have on a range of ecological and physiological processes. It was not until the introduction of viral metagenomics that we began to grasp the astonishing breadth of genetic diversity encompassed by phage genomes. Novel phage genomes have been reported from a diverse range of biomes at an increasing rate, which has prompted the development of computational tools that support the multilevel characterization of these novel phages based solely on their genome sequences. The impact of these technologies has been so large that, together with MAGs (Metagenomic Assembled Genomes), we now have UViGs (Uncultivated Viral Genomes), which are now officially recognized by the International Committee for the Taxonomy of Viruses (ICTV), and new taxonomic groups can now be created based exclusively on genomic sequence information. Even though the available tools have immensely contributed to our knowledge of phage diversity and ecology, the ongoing surge in software programs makes it challenging to keep up with them and the purpose each one is designed for. Therefore, in this review, we describe a comprehensive set of currently available computational tools designed for the characterization of phage genome sequences, focusing on five specific analyses: (i) assembly and identification of phage and prophage sequences, (ii) phage genome annotation, (iii) phage taxonomic classification, (iv) phage-host interaction analysis, and (v) phage microdiversity.

Aneurisma coronario de localización inusual asociado a infarto agudo de miocardio / A coronary aneurysm in an unusual location associated with acute myocardial infarction

Resumen Se presenta un caso clínico de difícil abordaje terapéutico. Paciente masculino joven con obesidad tipo II, quien ingresa por síndrome coronario agudo con elevación del segmento ST, se realiza coronariografía que pone en evidencia un aneurisma ubicado en el tronco coronario con imagen sugestiva de trombo en su interior que se trató con inhibidor de glicoproteína IIb/IIIa. En la evolución presenta falla cardiaca aguda manejada con inotrópicos y vasopresores. En segunda coronariografía se observó desaparición completa del componente trombótico. Como prevención secundaria se deja tratamiento antiagregante plaquetario y antitrombótico. El manejo de estos pacientes a la fecha es un reto ante la posibilidad de presentar un nuevo evento trombótico por la alteración en el flujo laminar intracoronario.

Abstract We present a clinical case with difficult treatment. A young male patient with type II obesity was admitted due to acute coronary syndrome with ST elevation. Coronariography showed an aneurysm on the coronary trunk suggestive of having a thrombus inside. It was treated with a glycoprotein IIb/IIIa antagonist. The patient progressed to acute heart failure managed with inotropes and vasopressors. A second coronariography showed complete disappearance of the thrombotic component. He was prescribed antiplatelet and antithrombotic treatment as secondary prevention. To date, the management of these patients has been a challenge, given the possibility of experiencing a new thrombotic event due to altered intracoronary laminar flow.

Accurate, Efficient and User-Friendly Mutation Calling and Sample Identification for TILLING Experiments.

TILLING (Targeting Induced Local Lesions IN Genomes) is a powerful reverse genetics method in plant functional genomics and breeding to identify mutagenized individuals with improved behavior for a trait of interest. Pooled high throughput sequencing (HTS) of the targeted genes allows efficient identification and sample assignment of variants within genes of interest in hundreds of individuals. Although TILLING has been used successfully in different crops and even applied to natural populations, one of the main issues for a successful TILLING experiment is that most currently available bioinformatics tools for variant detection are not designed to identify mutations with low frequencies in pooled samples or to perform sample identification from variants identified in overlapping pools. Our research group maintains the Next Generation Sequencing Experience Platform (NGSEP), an open source solution for analysis of HTS data. In this manuscript, we present three novel components within NGSEP to facilitate the design and analysis of TILLING experiments: a pooled variants detector, a sample identifier from variants detected in overlapping pools and a simulator of TILLING experiments. A new implementation of the NGSEP calling model for variant detection allows accurate detection of low frequency mutations within pools. The samples identifier implements the process to triangulate the mutations called within overlapping pools in order to assign mutations to single individuals whenever possible. Finally, we developed a complete simulator of TILLING experiments to enable benchmarking of different tools and to facilitate the design of experimental alternatives varying the number of pools and individuals per pool. Simulation experiments based on genes from the common bean genome indicate that NGSEP provides similar accuracy and better efficiency than other tools to perform pooled variants detection. To the best of our knowledge, NGSEP is currently the only tool that generates individual assignments of the mutations discovered from the pooled data. We expect that this development will be of great use for different groups implementing TILLING as an alternative for plant breeding and even to research groups performing pooled sequencing for other applications.

Inestabilidad microsatelital y cáncer gástrico / Microsatellite instability and gastric cancer

La inestabilidad microsatelital es causada por una alteración de los sistemas de reparación de apareamiento incorrecto, que puede afectar los microsatélites dentro de todo el genoma humano, produciendo errores en su replicación. Los estudios publicados, principalmente en la literatura inglesa, han encontrado que algunos tumores, como los gástricos, pueden expresar inestabilidad microsatelital. En la siguiente revisión de tema, se presenta una descripción de los sistemas de reparación de apareamientos incorrectos y su relación con la presencia de inestabilidad microsatelital en los tumores gástricos, así como su posible utilidad clínica, como factor asociado en la respuesta al tratamiento con inmunoterapia en los pacientes con dicha patología

Microsatellite instability is caused by an alteration of the mismatch repair systems, which can affect microsatellites within the entire human genome, causing errors in their replication. Published studies, mainly in the English literature, have found that some tumors, such as gastric ones, can express microsatellite instability. In this review, a description of the mismatch repair systems and their relationship with the presence of microsatellite instability in gastric tumors is presented, as well as its possible clinical utility, as an associated factor in the response to immunotherapy treatment, in patients with gastric cancer

Variations in the anatomical relationship between the common carotid artery and the internal jugular vein:: An ultrasonographic study / Variaciones de la relación anatómica de la arteria carótida común y la vena yugular interna:: Estudio ecográfico

Introduction: The internal jugular vein locates anterior or anterolateral to the common carotid artery in two-thirds of the subjects studied by ultrasound when the head is in a rotated position. Aim:To identify variables associated with the anterior location of the internal jugular vein. Methods: Ultrasound examinations were performed with the patients in the supine position, with the head rotated to the opposite side. The proximal third of the neck was visualized transversely with a 7.5-mHz transducer. The relationship between the vessels was described in accordance with the proportion of the artery overlapped by the vein. Univariate comparisons and a multivariate analysis of potential variables that may affect the anatomic relationships were performed. Results: Seventy-eight patients were included, 44 of whom were men. The patients' ages ranged from 17 to 90 years (median= 64.0, interquartile range 41-73). The right and left sides were studied 75 and 73 times, respectively. The vein was located lateral to the artery in 24.3% (95%CI= 17.4-32.2) of the studies, anterolateral in 33.8% (95%CI= 26.2-41.4) and anterior in 41.9% (95%CI 33.9-49.8). The multivariate analysis identified age group (OR= 3.7, 95%CI= 2.1-6.4) and, less significantly, the left side (OR= 1.7, 95%CI 0.8-3.5) and male gender (OR= 1.2, 95%CI= 0.6-2.7) as variables associated with the anterior position of the vein. Conclusion: The anterior position of the internal jugular vein relative to the common carotid artery increases gradually with age. Additionally, left-sided localization and male sex further increased the probability of an anterior position.

Introducción: La vena yugular interna es anterior o anterolateral a la arteria carótida común en las dos terceras partes de los sujetos estudiados sonográficamente, con la cabeza rotada. Objetivo:Se examinó la asociación de diferentes variables con la ubicación anterior de la vena. Métodos: Las ecografías se realizaron en posición supino, con la cabeza rotada hacia el lado contrario al examinado. Se visualizó transversalmente el tercio proximal del cuello, con un transductor de 7.5 mHz. La relación entre los vasos se describió de acuerdo con la proporción de la arteria cubierta por la vena. Se hicieron comparaciones univariadas con la prueba Chi2 de Pearson y un análisis multivariado de las variables candidatas a afectar las relaciones anatómicas estudiadas Resultados: Se incluyeron 78 individuos, 44 hombres, con edad entre 17-90 años (mediana 64.0, rango= 41-73 años). Se estudió el lado derecho en 75 ocasiones y el izquierdo en 73. La vena se localizó lateral en el 24.3% (IC95%= 17.4-32.2) de los vasos estudiados, anterolateral en el 33.8% (IC95%= 26.2-41.4) y anterior en el 41.9% (IC95%= 33.9-49.8). El análisis multivariado identificó: el grupo etáreo (OR= 3.7, IC95%= 2.1-6.4) y sugiere el lado izquierdo (OR= 1.7, IC95%= 0.8-3.5) y el género masculino (OR= 1.2, IC95%= 0.6-2.7), como variables asociadas con la posición anterior de la vena. Conclusión: La ubicación anterior de la vena yugular interna respecto a la arteria carótida común aumenta gradualmente con la edad. La localización izquierda y el género masculino pueden aumentar adicionalmente esta probabilidad.