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The proliferation of child sexual abuse material (CSAM) online is a global epidemic. Recently, programs to prevent child sexual abuse perpetration are being developed, and mounting evidence suggests that these measures can mitigate the risk of abuse. This study investigates the factors associated with help-seeking among CSAM offenders to inform efforts to increase uptake and strengthen effectiveness of such interventions. We analyze survey responses from 4,493 individuals who self-report to use CSAM. 55.0% of respondents report that they would like to stop using CSAM; however, only 13.8% have sought help, and only 3.2% have accessed help. The respondents most likely to want to stop using CSAM are those who report difficulties with mental health, in daily life, and related to use of CSAM. The respondents most likely to have sought treatment include those who report that they have sought contact with children, have experienced self-harm or suicidal thoughts, are in contact with other offenders, experience difficulties related to CSAM and in daily life, and view CSAM depicting toddlers and infants. We complement the findings with insights from a survey of 255 help-seeking individuals participating in an online self-help program to stop CSAM use. [ABSTRACT FROM AUTHOR]

Acanthamoeba is a ubiquitous genus of amoebae that can trigger a severe and progressive ocular disease known as Acanthamoeba Keratitis (AK). Furthermore, current treatment protocols are based on the combination of different compounds that are not fully effective. Therefore, an urgent need to find new compounds to treat Acanthamoeba infections is clear. In the present study, we evaluated staurosporine as a potential treatment for Acanthamoeba keratitis using mouse cornea as an ex vivo model, and a comparative proteomic analysis was conducted to elucidate a mechanism of action. The obtained results indicate that staurosporine altered the conformation of actin and tubulin in treated trophozoites of A. castellanii. In addition, proteomic analysis of treated trophozoites revealed that this molecule induced overexpression and a downregulation of proteins related to key functions for Acanthamoeba infection pathways. Additionally, the ex vivo assay used validated this model for the study of the pathogenesis and therapies of AK. Finally, staurosporine eliminated the entire amoebic population and prevented the adhesion and infection of amoebae to the epithelium of treated mouse corneas. [ABSTRACT FROM AUTHOR]

El objetivo de este trabajo es presentar la metodología de documentación y análisis llevada a cabo sobre un cepo de plomo de época antigua perteneciente a la colección de cepos del Museo de Cádiz (Andalucía, España). La eliminación de los diferentes estratos de alteración que cubría la superficie durante los tratamientos de conservación y restauración dejó al descubierto un conjunto iconográfico y epigráfico inédito, así como posibles huellas de fabricación y uso. Sin embargo, el estado de conservación deficiente de la superficie original no permitía visualizar los detalles en su conjunto mediante técnicas convencionales, por lo que se decidió el empleo de la documentación fotogramétrica y posterior tratamiento de los modelos mediante diferentes herramientas de análisis en Sistemas de Información Geográfica (SIG) como QGIS y procesamiento de nubes de puntos (CloudCompare). El análisis tridimensional (3D) viene siendo empleado con éxito en la documentación de detalles superficiales sobre objetos arqueológicos. La combinación de los métodos tradicionales con las ventajas de la fotogrametría ha demostrado una mejora sustancial del método. Los resultados obtenidos gracias a la metodología empleada sobre la pieza objeto de esta investigación han revelado detalles microsuperficiales del conjunto iconográfico y epigráfico imposibles de apreciar mediante técnicas de documentación convencionales. El bajo coste y la facilidad de aplicación, así como las posibilidades de procesamiento posterior de los datos obtenido con diferentes programas, hacen de esta metodología una herramienta muy útil frente a otras técnicas. Los datos microsuperficiales obtenidos, junto con los obtenidos mediante la reconstrucción 3D aportan una valiosa información para la interpretación del objeto. Las tareas llevadas a cabo también plantean una metodología de estudio eficaz para el análisis de otros cepos de plomo, una tipología de material muy abundante en colecciones de museos a lo largo de todo el Mediterráneo y parte del Atlántico y cuyo estudio permitirá conocer más sobre las anclas de época antigua, sus características morfológicas, procesos de fabricación, elementos epigráficos e iconográficos, mecanismos de alteración, etc. Lo más destacado: • Se presenta la metodología de documentación 3D llevada a cabo para estudiar y analizar un cepo de plomo de época antigua y su conjunto iconográfico y epigráfico inédito. • La aplicación de programas SIG y de procesamiento de nubes de puntos ha permitido documentar detalles microsuperficiales de la superficie del cepo no apreciables a simple vista. • El análisis volumétrico y el modelado 3D presenta una ventaja a la hora de conocer más detalles sobre las anclas con cepos de plomo de época antigua.

We present a framework for a federated, virtual biorepository system (VBS) with locally collected and managed specimens, as a 'global public good' model based on principles of equitable access and benefit sharing. The VBS is intended to facilitate timely access to biological specimens and associated data for outbreak-prone infectious diseases to accelerate the development and evaluation of diagnostics, assess vaccine efficacy, and to support surveillance and research needs. The VBS is aimed to be aligned with the WHO BioHub and other specimen sharing efforts as a force multiplier to meet the needs of strengthening global tools for countering epidemics. The purpose of our initial research is to lay the basis of the collaboration, management and principles of equitable sharing focused on low- and middle-income country partners. Here we report on surveys and interviews undertaken with biorepository-interested parties to better understand needs and barriers for specimen access and share examples from the ZIKAlliance partnership on the governance and operations of locally organized biorepositories.

Current therapies of leishmaniasis and Chagas disease, two of the most widespread neglected tropical diseases, have limited efficacy and toxic side effects. In this regard, natural products play an important role in overcoming the current need for new antiparasitic agents. The present study reports the leishmanicidal and trypanocidal activities of twenty-four known silyl-ether derivatives of withaferin A. Eleven compounds from this series (4, 7, 8, 10, 12, 15, 17, 18, 20, 22 and 25) showed a potent dose-dependent inhibitory effect on the proliferation of Leishmania amazonensis promastigotes and Trypanosoma cruzi epimastigotes respectively, even higher than the references drugs, miltefosine and benznidazole. Among them, the most promising compound, derivative 10, exhibited approximately 34-fold higher leishmanicidal activity and 49-fold higher trypanocidal activity compared to the reference drugs, as well as lower cytotoxicity. Moreover, compounds 4, 7, 10, 12 and 15 were more active than the reference drugs against the amastigote forms of L. amazonensis, presenting a high selectivity index. Assays performed to study the ATP levels, mitochondrial membrane potential, plasma membrane permeability, chromatin condensation, reactive oxygen species and autophagy indicated that these withaferin A-silyl analogs appear to induce events characteristic of apoptosis-like and also autophagy leading to programmed cell death. These findings support the therapeutic potential of withaferin A-related steroids as anti-Leishmania and Trypanosoma agents.

Abstract We investigate different final state features in Mueller–Navelet jets events at hadron colliders. The focus lies on the average rapidity ratio between subsequent minijet emissions which has been investigated in previous works but now is modified to also incorporate the transverse momenta together with the rapidities of the emitted jets. We study the dependence of this observable on a lower transverse momentum veto which does affect the typical minijet multiplicity of the events under scrutiny. We find that this observable is stable when including higher order quantum corrections, also when collinear terms are resummed to all orders.

Coastal areas are characterized by high energetic conditions associated to the wave transformation process and by numerous underwater cultural heritage (UCH) sites whose preservation is crucial given their cultural and economic value. UCH management requires a decision support system to prioritize UCH interventions and actions for long-term preservation. This paper presents a novel UCH risk assessment methodology to quantitatively assess the impact of wave-induced hazards on UCH in coastal environments at a local level and the screening of UCH sites at risk. The UCH risk is calculated as a function of vulnerability (depending on archaeological materials, slope, and seabed type), hazard (decontextualization, scouring, and erosive wear), and exposure computed for the UCH sites registered in an archaeological database. The procedure was validated at two shipwreck sites, Bucentaure and Fougueux, in the Bay of Cadiz. An agreement between the risk index value and the in situ measurements of the rates of scouring and corrosion (used as a proxy of erosive wear) was observed. The methodology was tested in the Bay of Cadiz using an archaeological database containing 56 UCH sites. It allowed identifying the UCH sites at high risk: six are at risk of decontextualization, four are in peril of scouring erosion, and two are at risk of erosive wear. Two UCH sites at high risk of at least two hazards were also identified. This UCH risk assessment methodology is a stepping stone towards a decision support system that will give priority to research, prospection, management, and protection measures in the UCH sites analyzed to ensure their preservation in a context of climate change in the era of a sustainable blue economy.

Protein supplements (PS) are trendy foods, especially those made from whey. In addition to providing protein, these products are a source of metals, providing essential elements (Na, K, Mg, Ca, Mo, Mn, Fe, Co, Cu, and Zn) and other potentially toxic elements (Al, B, Sr, V Ba, and Ni). In this study, 47 whey PS samples were analyzed for mineral elements by ICP-OES, and their dietary exposures were assessed for three consumption scenarios. Elements found in higher concentrations were K (4689.10 mg/kg) and Ca (3811.27 mg/kg). The intake of 30 g PS (average recommended amount/day) provides about 20% of the established reference value (NRI) for Cr (18.30% for men and 25.63% for women) and Mo (26.99%). In a high daily consumption scenario (100 g PS/day) and when the maximum concentrations are considered, Cr, Zn, Fe, Mo, and Mg dietary intakes of these metals exceed the daily recommended intakes and could pose a risk. The daily intake of 30, 60, and 100 g of whey PS for 25 years does not pose a health risk since the hazard index (HI) is less than one in these consumption scenarios, and the essential elements contributing most to HI are Co, followed by Mo and Cr. It is recommended to improve the information to the consumers of these new products. Furthermore, to help in the management and prevention of these potential health risks, it would be advisable to improve the regulation of these dietary supplements and their labeling.

Over the last few years, due to various climatic, anthropogenic, and environmental factors, a large amount of submerged heritage has been unearthed and exposed to deterioration processes in the Bay of Algeciras. These impacts can be more severe in shallow waters, where the cultural heritage is more vulnerable to natural and human-induced impacts. This makes it urgent to document cultural heritage at risk of disappearing using different techniques whose efficiencies in the archaeological record need to be determined and compared. For this purpose, we have documented a shipwreck in the Bay of Algeciras using two techniques: photogrammetry and a multibeam echosounder. The photogrammetric method consists of obtaining a 3D model from numerous photographs taken of an object or a site. The processing software creates three-dimensional points from two-dimensional points found in the photographs that are equivalent to each other. Multibeam echosounders are capable of providing side scan imagery information in addition to generating contour maps and 3D perspectives of the surveyed area and can be installed in an unmanned surface vehicle. As a result, we have obtained two 3D visualisations of the shipwreck, i.e., digital copies, that are being used both for the analysis of its naval architecture and for its dissemination. Through the comparison of the two techniques, we have concluded that while a multibeam echosounder provides a detailed digital terrain model of the seabed, photogrammetry performed by divers gives the highest resolution data on objects and structures. In conclusion, our results demonstrate the benefits of this combined approach for accurately documenting and monitoring shipwrecks in shallow waters, providing valuable information for conservation and management efforts.

Sports nutrition supplementation is a widespread practice. Whey protein supplements contribute not only to protein intake but also to dietary exposure to minerals. The labelling present provides the percentage of protein and rarely refers to other components, such as potentially toxic elements such as B, Cu, Mo, Zn, and V that present tolerable upper intake levels set by the European Food Safety Authority. The percentage of protein declared on supplement labelling was checked using the Kjeldahl method, and the levels of Ca, Mg, K, Na, Ba, B, Co, Cu, Cr, Sr, Fe, Li, Mn, Mo, Ni, V, Zn, and Al were analyzed by ICP-OES with the aim of characterizing the protein and mineral contents of isolate and concentrate whey protein supplements representative of the European market. The protein content was 70.9% (18–92.3%) and statistically significant differences were observed between the declared and real protein percentages. Among the minerals, K (4689.10 mg/kg) and Ca (3811.27 mg/kg) presented the highest levels, whereas Co (0.07 mg/kg) and V (0.04 mg/kg) showed the lowest levels. It was concluded that the quality and safety of these products needs to be monitored and regulated. A high degree of non-compliance with labelling claims was detected. Furthermore, the contributions to the recommended and tolerable intakes among regular consumers need to be assessed.

La presente investigación es desarrollada en un taller de reparaciones de transportes ferroviarios. El objetivo general es realizar la valoración socioeconómica del programa de intervención de los principales riesgos laborales presentes en el taller de reparaciones. El método aplicado se desglosa en tres pasos fundamentales como: la identificación de riesgos laborales, elaboración del plan de medidas y de actividades preventivas para la eliminación o reducción y control de los diferentes riesgos laborales encontrados, por último, la evaluación del impacto de las medidas propuestas a través del Índice socioeconómico. Como resultado se obtiene la identificación de los riesgos laborales en las áreas de Corte y conformado, Frenos o Neumáticos, Maquinado y Subconjunto. A partir de la aplicación del Índice socioeconómico se obtuvo el orden de prioridad para la ejecución de las medidas propuestas para reducir o eliminar los riesgos laborales identificados.

Antecedentes: Una de las razones para estudiar las enfermedades infecciosas es el incremento del control y erradicación de las mismas. Los modelos matemáticos pueden ser una herramienta poderosa para este fin, permitiendo optimizar los recursos limitados y dirigir medidas más efectivas; se utilizan para la predicción y comprensión del fenómeno en estudio. Objetivo. Realizar simulaciones con el modelo estocástico Susceptible, Infectado, Recuperado (SIR) para introducirlos en la docencia, en los análisis epizootiológicos y en la toma de decisiones. Métodos: Se simuló de manera virtual con un modelo estocástico la entrada de diez aves migratorias enfermas de procesos respiratorios en fincas de criadores, donde hay como promedio un total de 5000 aves de corral de diferentes tipos. Se determinó R0 (número reproductivo básico) de acuerdo a la incidencia. Resultados: La simulación se corrió con un índice de transmisibilidad bajo (1,8 %) y cada ave contacta un promedio de cinco aves de manera aleatoria durante 10 días. De no hacer ninguna intervención habría a los 20 días un pico de enfermos que sobrepasaría los 3000. Se encontró un número reproductivo básico mayor que la unidad (R0=1,14) por lo que califica como brote epidémico. Conclusiones: Se realizaron simulaciones con el modelo estocástico con una herramienta analítica sustentable basada en el programa libre R. Se constató la necesidad de integrar la epizootiología, la epidemiologia y la matemática; por lo que deben entrenarse en estos aspectos a los estudiantes relacionados con la salud animal y la salud pública.

Fundamento: En Cuba, durante el período inicial de la pandemia, el comportamiento de la COVID-19 presentó un incremento diario de casos similar a la situación mundial. La provincia Camagüey no escapó a esta realidad; sin embargo, los resultados del enfrentamiento a la pandemia mostraron un comportamiento favorable en este territorio. El objetivo del presente trabajo está dirigido a valorar aspectos del enfrentamiento social y clínico-epidemiológico a la COVID-19 en la provincia Camagüey durante el periodo comprendido entre los meses de marzo y mayo de 2020. Método: Se realizó un estudio observacional descriptivo y transversal en la provincia Camagüey. El universo estuvo compuesto por los 48 pacientes confirmados al virus SARS-CoV-2 en este territorio en el período mencionado. Resultados: La enfermedad se registró en ambos sexos de forma similar, mientras que predominaron los pacientes con edades comprendidas entre 40 y 59 años. Discusión: La mayoría de los individuos no presentó complicaciones. Con el cumplimiento de las indicaciones establecidas por las autoridades sanitarias se limitó el tiempo posible de la transmisión de la enfermedad en la provincia.

Among neglected tropical diseases, leishmaniasis is one of the leading causes, not only of deaths but also of disability-adjusted life years. This disease, caused by protozoan parasites of the genus Leishmania, triggers different clinical manifestations, with cutaneous, mucocutaneous, and visceral forms. As existing treatments for this parasitosis are not sufficiently effective or safe for the patient, in this work, different sesquiterpenes isolated from the red alga Laurencia johnstonii have been studied for this purpose. The different compounds were tested in vitro against the promastigote and amastigote forms of Leishmania amazonensis. Different assays were also performed, including the measurement of mitochondrial potential, determination of ROS accumulation, and chromatin condensation, among others, focused on the detection of the cell death process known in this type of organism as apoptosis-like. Five compounds were identified that displayed leishmanicidal activity: laurequinone, laurinterol, debromolaurinterol, isolaurinterol, and aplysin, showing IC50 values against promastigotes of 1.87, 34.45, 12.48, 10.09, and 54.13 µM, respectively. Laurequinone was the most potent compound tested and was shown to be more effective than the reference drug miltefosine against promastigotes. Different death mechanism studies carried out showed that laurequinone appears to induce programmed cell death or apoptosis in the parasite studied. The obtained results underline the potential of this sesquiterpene as a novel anti-kinetoplastid therapeutic agent.

Leishmaniasis and Chagas disease affect millions of people worldwide. The available treatments against these parasitic diseases are limited and display multiple undesired effects. The brown alga belonging to the genus Gongolaria has been previously reported as a source of compounds with different biological activities. In a recent study from our group, Gongolaria abies-marine was proven to present antiamebic activity. Hence, this brown alga could be a promising source of interesting molecules for the development of new antiprotozoal drugs. In this study, four meroterpenoids were isolated and purified from a dichloromethane/ethyl acetate crude extract through a bioguided fractionation process targeting kinetoplastids. Moreover, the in vitro activity and toxicity were evaluated, and the induction of programmed cell death was checked in the most active and less toxic compounds, namely gongolarone B (2), 6Z-1′-methoxyamentadione (3) and 1′-methoxyamentadione (4). These meroterpenoids triggered mitochondrial malfunction, oxidative stress, chromatin condensation and alterations of the tubulin network. Furthermore, a transmission electron microscopy (TEM) image analysis showed that meroterpenoids (2–4) induced the formation of autophagy vacuoles and ER and Golgi complex disorganization. The obtained results demonstrated that the mechanisms of action at the cellular level of these compounds were able to induce autophagy as well as an apoptosis-like process in the treated parasites.

Cutaneous leishmaniasis (CL) poses a significant public health concern in endemic regions due to its increasing prevalence and substantial impact on affected individuals. This disease is primarily caused by the Leishmania protozoa, which are transmitted through insect bites, and it manifests as a range of symptoms, from self-healing lesions to severe disfigurement. Current treatments, which often involve the parenteral administration of antimonials, face challenges such as poor compliance and adverse effects. This study investigates the efficacy of topical formulations containing meglumine antimoniate (MA) and amphotericin B (AmB), using Sepigel as an excipient, for treating CL. In the in vivo study, BALB/c mice infected with L. amazonensis developed lesions at the injection site five weeks post-infection. Subsequently, the mice were divided into eight groups: untreated mice, mice treated orally with miltefosine, mice treated intraperitoneally with MA, and mice treated topically with 15%, 22.5%, and 30% MA-Sepigel, as well as those treated with AmB-Sepigel. Treatments were applied daily for two weeks, and the results revealed a significant reduction in lesion size and parasite burden following topical application, particularly with the AmB-Sepigel formulations and 30% MA-Sepigel. Additionally, Sepigel-based treatments demonstrated improved patient compliance and reduced toxicity compared to systemic therapies. These findings underscore the potential of Sepigel-based formulations as a promising alternative for CL treatment. They offer enhanced efficacy and tolerability, while reducing the systemic toxicity associated with conventional therapies. [ABSTRACT FROM AUTHOR]

The rapid advancement of technology necessitates the continual development of versatile materials that can adapt to new electronic devices. Rare earth elements, which are scarce in nature, possess the set of properties required for use as semiconductors. Consequently, this research aims to achieve similar properties using materials that are abundant in nature and have a low commercial cost. To this end, nickel and copper were utilized to synthesize thin films of nickel–copper binary oxynitride via reactive RF sputtering. The influence of nitrogen flow on the structure, morphology, chemical composition, and optical properties of the films was investigated using various characterization techniques, including X-ray diffraction (XRD), scanning electron microscopy (SEM), atomic force microscopy (AFM), and X-ray photoelectron spectroscopy (XPS), as well as transmittance and absorbance measurements. The crystalline structure of the films shows that they can have preferential growth or be polycrystalline according to the nitrogen flow used during deposition and that both the oxides and oxynitrides of metals are formed. We identified unknown phases specific to this material, termed "NiCuOxNy". The morphology revealed that the grain size of the coatings was dependent on the nitrogen flow rate, with grain size decreasing as the nitrogen flow rate increased. Notably, the coatings demonstrated transparency for wavelengths exceeding 1000 nm, with an optical band gap ranging from 1.21 to 1.86 eV. [ABSTRACT FROM AUTHOR]

Adolescents' mental health and well-being is a public health concern. We examined gender differences in stress, psychological distress and well-being and predictors of distress and well-being in adolescent boys and girls. A cross-sectional study with a sample of 954 Spanish adolescents aged between 13 and 17 years was conducted. All participants were assessed through questionnaires that measure psychological distress, eudaimonic well-being, life satisfaction, stress, coping styles, masculine/instrumental and feminine/expressive traits, self-esteem and social support. We find that girls scored higher than boys in psychological distress, chronic stress, minor daily hassles, social support, eudaimonic well-being and in feminine-expressive trait whereas boys scored higher than girls in detachment coping style and in masculine-instrumental trait. Hierarchical multiple regression analysis revealed that the most relevant variable in the psychological distress of both girls and boys was higher emotional coping style, followed by higher number of life events during the previous year. The most relevant variables in boys' and girls' psychological well-being were higher self-esteem and social support. Higher scores in rational coping style and in masculine/instrumental trait were also important predictors of eudaimonic well-being in adolescent boys and girls. Furthermore, in boys, older age was associated with greater distress and lower well-being and life satisfaction, while, as for the girls, a smaller number of life events and greater emotional coping style were associated with lower eudaimonic well-being and life satisfaction. Results are relevant for the design of policies and programs aimed at promoting mental health and well-being in adolescence. [ABSTRACT FROM AUTHOR]

This article describes the preparation of a clinical study on a connected medical device dedicated to facilitate the prevention of lymphedema for patients treated for breast cancer after axillary lymph node dissection (ALND), and to alert them of any manifestation or resurgence in order to prevent its aggravation. A simulator of the entire physical process called digital twin has been developed for this purpose, in a hardware-in-the-loop framework. Statistical calibration of its input parameters, by stochastic inversion and using sensitivity studies, led to establish one or more measurement protocols allowing to capture the signal on a mobile device (phone or tablet) and to detect signal breaks that are physically significant. The measured signal makes it possible to report quickly on the worsening of the patient’s condition and to warn the therapists within a very reasonable period of time. The general methodology of this work seems to us to be easily reproducible in the preparation of clinical studies of other types for connected devices, which aim to develop measurement protocols limiting the often significant cost of such studies. One of the immediate prospects of this work is the initiation of a clinical study on different patients who have been treated by surgery for breast cancer, after improving the robustness of the design of the prototype to take into account the uncertainties affecting the measurements.

It is usual to associate the word “demagogue” with bad political leadership. At worst, it is also usual to think about a leader that uses deception and feeds on the more primal emotions of the people to get what he wants. But, in reality, answering the question of what a demagogue was is far from easy. Thus, this paper hypothesizes that there is no substantial difference between a demagogue and a rhetor in Athenian democracy. As its method, the paper analyses the context of use of the term by the different actors as to shed some light on their intentions. First, the paper examines the concept of “demagogue” and how the term appears in the democratic tradition, by focusing on its usage in the works of authors such as Aristophanes, Lysias and Thucydides. Next, it refers to the way in which adversaries of Athenian democracy, especially deriving from philosophy, used the term. As this paper will show, there is a significant difference between the two usages, the former being descriptive and the latter pejorative. Finally, the paper concludes that both in the descriptive and pejorative sense, being a demagogue meant to be a rhetor, a leader of the demos.

Background: a third of the total deaths that occur in the world, due to non-transmissible diseases, are due to cardiovascular diseases. They constitute the first cause of death worldwide and in Cuba. Objective: to characterize the mortality from cardiovascular diseases in Cuba that occurred in the period 2009-2018. Methods: an ecological study was carried out. Statistical yearbooks published by the Cuban Ministry of Public Health and the International Classification of Diseases (ICD-10) were used. Mortality rates from heart diseases and their behavior by provinces were considered, as well as mortality rates from diseases of the circulatory system and their distribution by age group. The rates used were gross. Results: in Cuba, diseases of the circulatory system provide a mortality rate between 299.4 and 360.0 per 100 000 inhabitants with a tendency to increase. Mortality rates for diseases of the heart and arteries, arterioles, and capillaries, from 2009 to 2018, were higher in men. Regarding stroke diseases, they exceeded in women, except in the years 2014, 2016-2018. In 2013 and 2015 they were very similar for both sexes. Within cardiovascular diseases, heart diseases contributed more potentially lost years of life, supported by stroke diseases and to a lesser extent those of arteries, arterioles and capillaries. Conclusions: cardiovascular diseases continue to be a serious health problem, which is why it is necessary to act on the causes that cause them, gaining in the perception of cardiovascular risk and in the responsibility, of each person, in the self-care of the health. DeCS: CARDIOVASCULAR DISEASES/epidemiology; CARDIOVASCULAR DISEASES/mortality; NONCOMMUNICABLE DISEASES /prevention&control; HEART DISEASES; EARLY MEDICAL INTERVENTION.

Abstract The role of the Androgen Receptor (AR) expression and its activity in the prognosis of hepatocellular carcinoma (HCC) remains inconclusive. The aim of this study is to analyze the role of the AR expression and its activity as prognostic biomarkers in HCC. Three-hundred and thirty-seven patients from The Cancer Genome Atlas (TCGA) (107 females; 59.42 years [SD = 13.0]) were included. To infer AR activity, the expression-profile of previously validated androgen responsive genes (ARGs) was included. AR activity was shown by the AR-Score-21 (21 ARGs) and AR-Score-13 (13 ARGs) that were computed based on the expression of the selected ARGs. Those ARGs whose expression was significantly different between histological grades were used for computing two new AR-Scores. HCC patients with higher AR expression showed a higher median overall survival (OS). AR-Score 21 and AR-Score-13 did not show any association with prognosis. Six of the 21 ARGs of the AR-Score-21 and 7 of the 13 ARGs of the AR-Score-13 showed a significant different expression profile among histological grades. Based on these differences, another two AR-Scores were computed (AR-Score-6 and AR-Score-7). They showed the relative increase of upregulated to downregulated ARGs in high-grade HCC. Higher AR activity inferred by these AR-Scores was associated with worse outcomes. The expression of AR is associated with a better prognosis in HCC. However, the activity of the AR seems to be qualitatively different among histological grades. The AR activity inferred by the shifted ARGs is associated with a worse prognosis in HCC patients.