Early Diagnosis of Oral Cancer: A Complex Polyhedral Problem with a Difficult Solution

Oral and oropharyngeal cancers are a growing problem, accounting for 377,713 and 98,412 new cases per year all over the world and 177,757 and 48,143 deaths annually, respectively. Despite the substantial improvement in diagnostic procedures and treatment techniques in recent years, the mortality rate has not decreased substantially in the last 40 years, which is still close to 50% of cases. The major cause responsible for this high mortality is associated with the high percentage of oral cancers diagnosed in advanced stages (stages III and IV) where the treatment harbors poor efficacy, resulting in challenges, mutilations, or disability. The main reason for cancer to be diagnosed at an advanced stage is a diagnostic delay, so it is critical to reduce this delay in order to improve the prognosis of patients suffering from oral cancer. The causes of oral cancer diagnostic delay are complex and concern patients, healthcare professionals, and healthcare services. In this manuscript, oral cancer diagnostic delay is critically reviewed based on current evidence, as well as their major causes, main problems, and potential improvement strategiesResearch group CTS-392 (Plan Andaluz de Investigación, Junta de Andalucía, Spain

Prognostic and Clinicopathological Significance of CCND1/Cyclin D1 Upregulation in Melanomas: A Systematic Review and Comprehensive Meta-Analysis

We would like to thank the research group CTS-392 (Plan Andaluz de Investigación, Junta de Andalucía, Spain).Simple Summary The incidence of cutaneous melanoma is increasing worldwide, currently responsible for 287,723 new cases and 60,712 deaths per year (GLOBOCAN, IARC, WHO). It should be also highlighted that some less frequent subtypes of melanomas-i.e., acral, uveal, and mucous melanoma-are responsible for significant morbidity associated with metastasis, responding typically worse to newer therapies. Therefore, new biomarkers are needed to improve the prognosis in individual patients. In this sense, the present study showed that CCND1/cyclin D1 upregulation is a common molecular oncogenic alteration in melanomas that probably favors the growth and expansion on cutaneous primary melanomas. Furthermore, immunohistochemical cyclin D1 overexpression strongly predicted a higher Breslow thickness, currently considered the most relevant prognostic factor in individual patients with melanomas. Finally, special attention should be paid to the CCND1/cyclin D1 complex in mucosal melanomas, whose upregulation was strikingly altered. Our objective was to evaluate the prognostic and clinicopathological significance of cyclin D1 (CD1) overexpression/CCND1 amplification in melanomas. We searched studies published before September 2019 (PubMed, Embase, Web of Science, Scopus). We evaluated the quality of the studies included (QUIPS tool). The impact of CD1 overexpression/CCND1 amplification on overall survival and relevant clinicopathological characteristic were meta-analyzed. We performed heterogeneity, sensitivity, small-study effects, and subgroup analyses. Forty-one studies and 3451 patients met inclusion criteria. Qualitative evaluation demonstrated that not all studies were performed with the same rigor, finding the greatest risk of bias in the study confounding domain. Quantitative evaluation showed that immunohistochemical CD1 overexpression had a statistical association with Breslow thickness (p = 0.007; OR = 2.09,95% CI = 1.23-3.57), significantly higher frequency of CCND1/cyclin D1 abnormalities has been observed in the primary tumor compared to distant metastases (p = 0.004), revealed also by immunohistochemical overexpression of the protein (p < 0.001; OR = 0.53,95% CI = 0.40-0.71), while the CCND1 gene amplification does not show association (p = 0.43); while gene amplification, on the contrary, appeared more frequently in distant metastases (p = 0.04; OR = 1.70,95% CI = 1.01-2.85) and not in the primary tumor. In conclusion, CCND1/cyclin D1 upregulation is a common molecular oncogenic alteration in melanomas that probably favors the growth and expansion of the primary tumor. This upregulation is mainly consequence to the overexpression of the cyclin D1 protein, and not to gene amplification

Sound absorption in glasses

The paper presents a description of the sound wave absorption in glasses, from the lowest temperatures up to the glass transition, in terms of three compatible phenomenological models. Resonant tunneling, the rise of the relaxational tunneling to the tunneling plateau and the crossover to classical relaxation are universal features of glasses and are well described by the tunneling model and its extension to include soft vibrations and low barrier relaxations, the soft potential model. Its further extension to non-universal features at higher temperatures is the very flexible Gilroy–Phillips model, which allows to determine the barrier density of the energy landscape of the specific glass from the frequency and temperature dependence of the sound wave absorption in the classical relaxation domain. To apply it properly at elevated temperatures, one needs its formulation in terms of the shear compliance. As one approaches the glass transition, universality sets in again with an exponential rise of the barrier density reflecting the frozen fast Kohlrausch tβ-tail (in time t, with β close to 1/2) of the viscous flow at the glass temperature. The validity of the scheme is checked for literature data of several glasses and polymers with and without secondary relaxation peaks. The frozen Kohlrausch tail of the mechanical relaxation shows no indication of the strongly temperature-dependent barrier density observed in dielectric data of molecular glasses with hydrogen bonds. Instead, the mechanical relaxation data indicate an energy landscape describable with a frozen temperature-independent barrier density for any glassM.A.R. acknowledges financial support from the Spanish Ministry of Science and Innovation through the ‘‘María de Maeztu’’ Programme for Units of Excellence in R&D (CEX2018-000805-M), as well as from the Autonomous Community of Madrid through program S2018/NMT-4321 (NANOMAGCOST-CM). X. L. acknowledges support from the Office of Naval Researc

Diseño y construcción de un prototipo autosustentable de tratamiento de agua para consumo humano

El presente proyecto técnico tuvo por objetivo diseñar y construir un prototipo autosustentable para tratamiento de agua para consumo humano. La revisión bibliográfica permitió establecer los parámetros de diseño fundamentales en el prototipo. Se empleó la metodología del diseño concurrente que permitió la generación de posibles alternativas de selección de componentes mediante la aplicación del QFD. Mediante la interpretación de un análisis fisicoquímico de agua realizado a una muestra tomada en la comunidad de Rumicruz se encontró presencia de coliformes, por lo cual se determinó que el tratamiento adecuado de desinfección de agua es el método de radiación ultravioleta, sin embargo, el uso de este sistema implicó la generación de 65 W que han sido proporcionados a través de energía solar y mediante el uso de una batería que permitió el funcionamiento continuo del prototipo. Además, para facilitar el mantenimiento del sistema de desinfección se implementó el uso de una electroválvula alimentada por medio de la micro hidro generación de una microturbina que aprovecha el potencial hidro cinético presente en las tuberías de agua de la comunidad. Los componentes mecánicos de la microturbina fueron calculados y diseñados teóricamente para después ser verificados mediante la modelación en el software SolidWorks para luego llevar a cabo un análisis dinámico del fluido y un análisis de elementos finitos en el software ANSYS, donde se verificó el comportamiento tanto del fluido como del mecanismo sometido a cargas máximas para su posterior construcción. Se realizaron pruebas de funcionamiento del prototipo que comprobaron su auto sustentabilidad para un funcionamiento continuo, además el sistema de desinfección obtuvo resultados favorables ya que se redujo la presencia de coliformes de 300 UFC/100ml a ausencia de estas, eliminando la presencia de microorganismos en el agua, proporcionando datos de análisis encontrados dentro del rango de referencia de la norma INEN 1108.The objective of this technical project was to design and build a self-sustaining prototype for water treatment for human consumption. The bibliographical review allowed to establish the fundamental design parameters in the protype. The concurrent design methodology was used, which allowed the generation of possible component selection alternatives through the application of the QFD. Through the interpretation of a physicochemical analysis of water carried out on a sample taken in the Rumicruz community, the presence of coliforms was found, for which it was determined that the adequate treatment of water disinfection is the ultraviolet radiation method, however, the use of this system implied the generation of 65 W that have been provided through solar energy and through the use of a battery that allowed the continuous operation of the prototype. In addition, to facilitate the maintenance of the disinfection system, the use of a solenoid valve powered by the micro hydro generation of a micro turbine that takes advantage of the hydro kinetic potential present in the community water pipes was implemented. The mechanical components of the microturbine were calculated and theoretically designed to later be verified by means of modeling in the SolidWorks software to later carry out a dynamic analysis of the fluid and a finite element analysis in the ANSYS software, where the behavior of both the fluid as well as the mechanism subjected to maximum loads for its subsequent construction. Functional tests of the prototype were carried out, which verified its self-sustainability for continuous operation, in addition, the disinfection system obtained favorable results since the presence of coliforms of 300 CFU/100ml was reduced in the absence of these, eliminating the presence of microorganisms in the water, providing analysis data found within the reference range of the INEN 1108 standard

Dysplasia in oral lichen planus: relevance, controversies and challenges. A position paper

Background: Patients with oral lichen planus (OLP) have an increased risk of oral cancer. For this reason, OLP is classified as an oral potentially malignant disorder. However, the precise personal (or individual) risk is unknown. Recent meta-analytical studies have reported that dysplastic OLP may transform to cancer in around 6% of cases, while the rate of transformation is lower (<1.5%) in non-dysplastic cases. The presence of epithelial dysplasia has emerged as the most powerful indicator for assessing cancer risk in oral potentially malignant disorders in routine practice. However, the general acceptance of epithelial dysplasia as an accompanying histologic feature in OLP is subject to great controversy. Many pathologists consider the presence of dysplasia as a criterion to exclude OLP when routinely reporting on this disease. This practice, widespread among oral pathology professionals, has resulted in the underestimation of the potential for malignancy of OLP. Material and Methods: A review of the literature was carried out in order to critically analyze the relevance, controversies and challenges encountered across the diagnosis of epithelial dysplasia in OLP. Results: 12 studies have been published examining dysplastic changes in OLP, reporting figures ranging from 0.54% to 25% of cases with dysplasia in the first diagnostic biopsy. The diagnosis of dysplasia in the OLP poses an additional difficulty due to the fact that the affected oral epithelium per se develops changes related to autoimmune aggression. Among the most frequent histological features of OLP that develops dysplasia are basal cell hyperplasia with basaloid appearance, loss of basal cells polarity, cellular and nuclear pleomorphism and irregular stratification. Conclusions: Epithelial dysplasia should not be considered an exclusion criterion for OLP; its evaluation requires experienced pathologists in this field

A Discrete-Event Simulation Metamodel for Obtaining Simulation Models from Business Process Models

Organizations need to be agile and fl exible to meet the continuous changes. Business Process Management (BPM) is harnessing the continuous changes suffered by organizations in the value chain and, therefore, in their processes. Simulation models offer the ability to experience different decisions and analyze their results in systems where the cost or risk of actual experimentation are prohibitive. BPMN models are not directly executable nor is it possible to simulate their behavior in various input parameters. This paper proposes the application of model-driven engineering (MDE) to integrate the defi nition of business processes with Discrete- Event Simulation (DES) as a tool to support decision-making. We propose a platform independent DES metamodel and a set of rules, to automatically generate the simulation model from BPMN 2.0 based business process in accordance with previous metamodel.Ministerio de Economía y competitividad TIN2010- 20057- C03-02Ministerio de Economía y Competitividad TIN2010-20057-C03-03Junta de Andalucía TIC-5789Junta de Andalucía TIC-19

Thermal characterization and diffusivity of two mono-component epoxies for transformer insulation

The main aim of this study is the thermal characterization of an organic insulation. This insulation is a compound of two mono-component epoxy resins: Epoxylite® primer and Elmotherm® varnish. A mono-component epoxy resin usually needs a high temperature to cure; through differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA), non-isothermal curves are obtained, allowing the estimation of activation energies of curing and decomposition processes respectively. If Model Free Kinetic (MFK) is used from DSC curves, it is possible to simulate isothermal curves at different temperatures and times, plotting activation energy as a function of the conversion degree. The simulation from TGA curves can be used to estimate lifetime of the resins and compare them following the Toop method. DSC also allows measurement of thermal conductivity, the melting peak of metallic gallium being used for this measurement. Finally, water diffusion in resins is studied. Currently, the Materials Performance research group of UC3M is working on the European project named "Essial", where this organic insulation is used to protect the windings and the whole transformer from the environment. The results obtained will be used to determinate the optimal operating range for this insulator, demonstrating that both epoxies are required to achieve the insulating performance of the transformer and long curing times are required for full curing of Epoxylite®.This research was funded by European Union's Horizon 2020 research and innovation programme under grant agreement No 766437 (ESSIAL project)

Capacitive platform for real-time wireless monitoring of liquid wicking in a paper strip

Understanding the phenomenon of liquid wicking in porous media is crucial for various applications, including the transportation of fluids in soils, the absorption of liquids in textiles and paper, and the development of new and efficient microfluidic paper-based analytical devices (μPADs). Hence, accurate and real-time monitoring of the liquid wicking process is essential to enable precise flow transport and control in microfluidic devices, thus enhancing their performance and usefulness. However, most existing flow monitoring strategies require external instrumentation, are generally bulky and unsuitable for portable systems. In this work, we present a portable, compact, and cost-effective electronic platform for real-time and wireless flow monitoring of liquid wicking in paper strips. The developed microcontroller-based system enables flow and flow rate monitoring based on the capacitance measurement of a pair of electrodes patterned beneath the paper strip along the liquid path, with an accuracy of 4 fF and a full-scale range of 8 pF. Additionally to the wired transmission of the monitored data to a computer via USB, the liquid wicking process can be followed in real-time via Bluetooth using a custom-developed smartphone application. The performance of the capacitive monitoring platform was evaluated for different aqueous solutions (purified water and 1 M NaCl solution), various paper strip geometries, and several custom-made chemical valves for flow retention (chitosan-, wax-, and sucrose-based barriers). The experimental validation delivered a full-scale relative error of 0.25%, resulting in an absolute capacitance error of ±10 fF. In terms of reproducibility, the maximum uncertainty was below 10 nl s−1 for flow rate determination in this study. Furthermore, the experimental data was compared and validated with numerical analysis through electrical and flow dynamics simulations in porous media, providing crucial information on the wicking process, its physical parameters, and liquid flow dynamics

Difusión del software libre en la universidad : la experiencia piloto Moodle en la Universidad del País Vasco

La experiencia piloto Moodle UPV/EHU que aquí se presenta, comenzó en 2003 impulsada por un pequeño grupo de profesores apoyados por el centro informático de la universidad (CIDIR). Este grupo ha colaborado de manera desinteresada con los profesores investigadores de la Universidad que han solicitado su ayuda en el uso de Moodle, ofreciéndoles soporte técnico y formación. A partir del curso 2004-2005, este colectivo de profesores ha conformado el Grupo iKide. En este artículo se muestra cómo la filosofía del software libre puede ayudar a impulsar la innovación docente.The UPV-EHU Moodle pilot experience presented in this paper was set up in 2003, driven by a small group of lecturers with the help of the Computer Centre of the UPV/EHU (CIDIR). This group has voluntarily collaborated with those university teachers who were interested in working with Moodle and offered them technical support and training. From the course 2004-2005 onwards, the foremencioned group of lecturers became the iKide Group. This paper shows how Open Source philosophy can help to foster teaching innovation

Correction to: Dimensions of leisure-time physical activity and risk of depression in the “Seguimiento Universidad de Navarra” (SUN) prospective cohort

After publication of our article [1] we have been notified that Table 2 was incorrectly formatte