In recent decades, particularly intense changes have occurred in Spanish urban areas. This is the result of demographic and urbanizing transformations that have led to a change in the city model. The predominance of compact forms has been replaced by the growing prominence of urban sprawl. Structures are now more extensive, characterized, in turn, by fragmentation and notable consumption of land in the peripheries. In medium-sized cities, the municipalities bordering the central cities have concentrated the processes of suburbanization and periurbanization. This paper addresses the process of change for 34 cities and their urban areas located in inland Spain. A proposal is made for the delimitation and characterization of urban areas, taking the municipality as the unit of analysis. At the methodological level, six variables are used, analyzed by means of multicriteria statistical techniques combined with the use of GIS tools. An Urban Transformation Index (ITU) has been developed that synthesizes urbanizing, demographic and socioeconomic dynamics. In the territorial area, the 20-minute isochrone is used as a reference. In the temporal domain, the period of analysis addresses the events of the first two decades of the twenty-first century.

The railway infrastructure has played a crucial role in urban development since its inception in the 19th century. This article aims to show how the transformations resulting from the implementa-tion of this transport system have had a particular impact on the city of Istanbul, considering a technical, an engineering and the heritage perspective. To achieve this, an exhaustive review of collected drawings, articles and reports has been carried out since 2012, while starting to work on the architectural coordination of the project. These documents reflect how the Marmaray project covers different aspects, such as materials, signage, civil protection and landscaping. The results obtained demonstrate how a railway infrastructure project not only improves the technical and operational efficiency of traffic in the city, but also protects the natural and historical heritage. As a main conclusion of this investigation, it highlights the necessity for proper coordination between technical interventions in the infrastructure and a comprehensive and integrated strategy that encompasses both the heritage and the urban landscape of Istanbul.

Objective: To carry out a bibliometric analysis study of systematic reviews and meta-analyses in dentistry, divided into different thematic areas. Material and method: A search was conducted in the Science Citation Index-Expanded on the core collection of Web of Science, they were selected from the area of Dentistry and Oral Surgery and Medicine categories, the data was downloaded on April 20, 2022 and The 100 most cited articles from each of the thematic areas were selected. Results: An increase in this type of articles was observed in the last decade in the areas of pediatric and medical dentistry and oral pathology. The thematic area that received the most citations was periodontics. The two authors with the most citations are Zwahlen, Marcel and Pjetursson, Bjarni Eluar. The countries that receive the most citations are European, along with the USA and China. The topics that are most published in this type of article deal with Cancer with 50 publications, caries treatment with 25 and fluoridation with 1. The entities that finance this type of articles the most are private companies (26.76%). Conclusions: Together with an exponential increase in the number of publications in dentistry, there has been an increase in the number of publications in systematic reviews. The areas publishing the most articles and having the most citations are Periodontics and Implantology, despite the fact that the most studied topic is cancer.

One of the hallmarks of the Alternative Lengthening of Telomeres (ALT) is the association with Promyelocytic Leukemia (PML) Nuclear Bodies, known as APBs. In the last years, APBs have been described as the main place where telomeric extension occurs in ALT positive cancer cell lines. A different set of proteins have been associated with APBs function, however, the molecular mechanisms behind their assembly, colocalization, and clustering of telomeres, among others, remain unclear. To improve the understanding of APBs in the ALT pathway, we integrated multi-omics analyses to evaluate genomic, transcriptomic and proteomic alterations, and functional interactions of 71 APBs-related genes/proteins in 32 PanCancer Atlas studies from The Cancer Genome Atlas Consortium (TCGA). As a result, we identified 13 key proteins which showed distinctive mutations, interactions, and functional enrichment patterns across all the cancer types and proposed this set of proteins as candidates for future ex vivo and in vivo analyses that will validate these proteins to improve the understanding of the ALT pathway, fill the current research gap about APBs function and their role in ALT, and be considered as potential therapeutic targets for the diagnosis and treatment of ALT positive cancers in the future.

Osteosarcoma is the most common subtype of primary bone cancers, affecting mostly adolescents. In recent years, several studies have focused on elucidating the molecular mechanisms of this sarcoma; however, its molecular etiology has still not been determined with precision. Therefore, we applied a consensus strategy with the use of several bioinformatics tools to prioritize genes involved in its pathogenesis. Subsequently, we assessed the physical interactions of the previously selected genes and applied a communality analysis to this protein-protein interaction network. The consensus strategy prioritized a total list of 553 genes. Our enrichment analysis validates several studies that describe the signaling pathways PI3K/AKT and MAPK/ERK as pathogenic. The gene ontology described TP53 as a principal signal transducer that chiefly mediates processes associated with cell cycle and DNA damage response It is interesting to note that the communality analysis clusters several members involved in metastasis events such as MMP2 and MMP9 and genes associated with DNA repair complexes, like ATM, ATR, CHEK1, and RAD51. In this study, we could identify well-known pathogenic genes for osteosarcoma and prioritized genes that need to be further explored.

The protein TRPM8, a non-selective, calcium (Ca2+) permeable ion channel is implicated in several pathological conditions, including neuropathic pain states. In our previous research endeavors, we have identified β–lactam derivatives with high hydrophobic character that exhibit potent and selective TRPM8 antagonist activity. This work describes the synthesis of novel derivatives featuring C-terminal amides and diversely substituted N’-terminal monobenzyl groups, in an attempt to increase the total polar surface area (TPSA) in this family of compounds. The primary goal was to assess the influence of these substituents on the inhibition of menthol-induced cellular Ca2+ entry, thereby establishing critical structure-activity relationships. While the substitution of the tert-butyl ester by isobutyl amide moieties improved the antagonist activity, none of the N’-monobencyl derivatives, regardless of the substituent on the phenyl ring, achieved the activity of the model dibenzyl compound. The antagonist potency of the most effective compounds was subsequently verified using Patch-Clamp electrophysiology experiments. Furthermore, we evaluated the selectivity of one of these compounds against other members of the TRP ion channel family and some receptors connected to peripheral pain pathways. This compound demonstrated specificity for TRPM8 channels. To better comprehend the potential mode of interaction, we conducted docking experiments to uncover plausible binding sites on the functionally active tetrameric protein, which come upon four main poses by the pore zone, differents from those described for other known antagonists. Finally, in vivo experiments, involving a couple of selected compounds, revealed significant antinociceptive activity within a mice model of cold allodynia induced by oxaliplatin.

Introduction: The exponential growth of the SARS-CoV-2 virus transmission during the first months of 2020 has placed substantial pressure on health systems worldwide. The complications derived from the novel coronavirus disease (COVID-19) vary in due to comorbidities, sex and age, with more than 50% of the patients who require some level of intensive care developing acute respiratory distress syndrome (ARDS). Areas covered: Various complications caused by SARS-CoV-2 infection have been identified, the most lethal being the acute respiratory distress syndrome, caused most likely by the presence of severe immune cell response and the concomitant alveolus inflammation. The authors carried out an extensive and comprehensive literature review on SARS-CoV-2 infection, the clinical, pathological and radiological presentation as well as the current treatment strategies. Expert Opinion Elevation of inflammatory biomarkers is a common trend among seriously ill patients. The information available strongly suggests that in COVID-19 patients, their altered immune response, including a massive cytokine storm, is responsible for the further damage evidenced among ARDS patients. The increasingly high number of scientific articles and evidence available can only suggest that the individualization of each case is the norm, not all patients with acute respiratory failure due to COVID-19 meet the Berlin definition and therefore ARDS should be considered as a heterogeneous disease, with a wide range in the expression of its severity and clinical manifestations.

Coronaviruses are an extensive family of viruses that can cause disease in both animals and humans. The current classification of coronaviruses recognizes 39 species in 27 subgenera that belong to the family Coronaviridae. From those, at least seven coronaviruses are known to cause respiratory infections in humans. Four of these viruses can cause common cold-like symptoms, while others that infect animals can evolve and become infectious to humans. Three recent examples of this viral jumps include SARS CoV, MERS-CoV and SARS CoV-2 virus. They are responsible for causing severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS) and the most recently discovered coronavirus disease during 2019 (COVID-19).COVID-19, a respiratory disease caused by the SARS-CoV-2 virus, was declared a pandemic by the World Health Organization (WHO) on 11 March 2020. The rapid spread of the disease has taken the scientific and medical community by surprise. Latest figures from 14 April 2020 show more than 2 million people had been infected with the virus, causing more than 120,000 deaths in over 210 countries worldwide. The large amount of information we receive every day concerning this new disease is so abundant and dynamic that medical staff, health authorities, academics and the media are not able to keep up with this new pandemic. In order to offer a clear insight of the extensive literature available, we have conducted a comprehensive literature review of the SARS CoV-2 Virus and the Coronavirus Diseases 2019 (COVID-19).