Autism Spectrum disorder (ASD) and intellectual disability (ID) are the most frequent develop-mental disorders with a prevalence between 3% and 5% of the population. In addition, both ASD and ID can be found in the same patient. Mutations in several genes involved in the epigenetic regulation of gene expression have been linked to different ID associated with ASD features including alterations of the ly-sine-acetyltransferase 6A (KAT6A) gene in KAT6A syndrome. KAT6A enzyme participates in a wide range of critical cellular functions such as chromatin remodeling, gene expression, protein synthesis, cell metabolism, and replication. In this manuscript, we examined the pathophysiolog-ical alterations in fibroblasts derived from three patients harboring KAT6A mutations. We ad-dressed survival in stress medium, histone acetylation, protein expression patterns and tran-scriptome analysis as well as cell bioenergetics. In addition, we evaluated the therapeutic effec-tiveness of epigenetic modulators and mitochondrial boosting agents such as pantothenate and L-carnitine in correcting the mutant phenotype. Pantothenate and L-carnitine treatment increased histone acetylation and corrected protein and transcriptomic expression patterns in mutant KAT6A cells. Furthermore, cell bioenergetics of mutant cells was significantly improved. Our results suggest that pantothenate and L-carnitine can significantly correct the mutant phe-notype in cellular models of KAT6A syndrome.

Nemaline myopathy (NM) is one of the most common forms of congenital myopathy and it is identified by the presence of "nemaline bodies" (rods) in muscle fibers by histopathological exam-ination. The most common forms of NM are caused by mutations in the ACTA1 (Actin Alpha 1) and NEB (Nebulin) genes. Clinical features include hypotonia and muscle weakness. Unfortunate-ly, there is no curative treatment and the pathogenetic mechanisms remains unclear. In this man-uscript, we examined the pathophysiological alterations in NM using dermal fibroblasts derived from patients with mutations in ACTA1 and NEB genes. Patients’ fibroblasts were stained with rhodamine phalloidin to analyze the polymerization of actin filaments by fluorescence microsco-py. We found that patients' fibroblasts showed incorrect actin filament polymerization compared to control fibroblasts. Actin filament polymerization defects was associated with mitochondrial dysfunction. Furthermore, we identified two mitochondrial boosting compounds, linoleic acid (LA) and L-carnitine (LCAR), that improved the formation of actin filaments in mutant fibro-blasts and corrected mitochondrial bioenergetics. Our results indicate that cellular models can be useful to study the pathophysiological mechanisms involved in NM and to find new potential therapies. Furthermore, targeting mitochondrial dysfunction with LA and LCAR can revert the pathological alterations in NM cellular models.

The term neurodegeneration with brain iron accumulation (NBIA) brings together a broad set of progressive and disabling neurological genetic disorders in which iron is deposited preferentially in certain areas of the brain. Among NBIA disorders, the most frequent subtype is pantothenate kinase-associated neurodegeneration (PKAN) caused by pathologic variants in the PANK2 gene codifying the enzyme pantothenate kinase 2 (PANK2). Nowadays, there are no effective treatments to stop the progression of these diseases. This review discusses the utility of patient-derived cell models as a valuable tool for the identification of commercial pharmacological or natural compounds for implementing polytarget precision medicine in PKAN. In the last years, several studies have described that PKAN patient-derived fibroblasts manifest the main pathological changes associated with the disease including intracellular iron overload. Interestingly, treatment of mutant cell cultures with various supplements such as pantothenate, pantethine, thiamine, L-carnitine, vitamin E, omega 3, and -lipoic acid improved all pathophysiological alterations in PKAN fibroblasts with residual expression of the PANK2 enzyme. The information provided by pharmacological screenings in patient-derived cellular models can help to optimize therapeutic strategies in individual PKAN patients.

Neurodegeneration with brain iron accumulation (NBIA) is a group of rare neurogenetic dis-orders frequently associated with iron accumulation in the basal nuclei of the brain. Among NBIA subtypes, β -propeller protein-associated neurodegeneration (BPAN) is associated with mutations in the autophagy gene WDR45. The aim of this study was to demonstrate autophagic defects and secondary pathological con-sequences in cellular models derived from two patient harboring WDR45 mutations. Both protein and mRNA expression levels of WDR45 were decreased in patient-derived fibro-blasts. In addition, the increase of LC3B upon treatments with autophagy inducers or inhibitors was lower in mutant cells compared to control cells, suggesting decreased autophagosome formation and impaired autophagic flux. Transmission electron microscopy (TEM) analysis showed mitochondrial vacuolization associated with accumulation of lipofuscin-like aggregates containing undegraded material. Autophagy dysregulation was also associated with iron ac-cumulation and lipid peroxidation. In addition, mutant fibroblasts showed altered mitochon-drial bioenergetics. Antioxidants such as pantothenate, vitamin E and α-lipoic prevented lipid peroxidation and iron accumulation. However, antioxidants were not able to correct the ex-pression levels of WDR45 neither the autophagy defect nor cell bioenergetics. Our study demonstrated that WDR45 mutations in BPAN cellular models impaired autophagy, iron metabolism and cell bioenergetics. Antioxidant partially improved cell physiopathology, however autophagy and cell bioenergetics remained affected.

Climate change is predicted to alter the geographic distribution of a wide variety of taxa, including butterfly species. Research has focused primarily on high latitude species in North America, with no known studies examining responses of taxa in the southeastern US. The Diana fritillary (Speyeria diana) has experienced a recent range retraction in that region, disappearing from lowland sites and now persisting in two, phylogenetically disjunct mountainous regions. These findings are consistent with the predicted effects of a warming climate on numerous taxa, including other butterfly species in North America and Europe. We used ecological niche modeling to predict future changes to the distribution of S. diana under several climate models. To evaluate how climate change might influence the geographic distribution of this butterfly, we developed ecological niche models using Maxent. We used two global circulation models, CCSM and MIROC, under low and high emissions scenarios to predict the future distribution of S. diana. Models were evaluated using the Receiver Operating Characteristics Area Under Curve test and the True Skill Statistics (mean AUC = 0.91± 0.0028 SE, TSS = 0.87 ± 0.0032 SE for RCP = 4.5, and mean AUC = 0.87± 0.0031SE, TSS = 0.84 ± 0.0032 SE for RCP = 8.5), which both indicate that the models we produced were significantly better than random (0.5). The four modeled climate scenarios resulted in an average loss of 91% of suitable habitat for S. diana by 2050. Populations in the Southern Appalachian Mountains were predicted to suffer the most severe fragmentation and reduction in suitable habitat, threatening an important source of genetic diversity for the species. The geographic and genetic isolation of populations in the west suggest that those populations are equally as vulnerable to decline in the future, warranting ongoing conservation of those populations as well. Our results suggest that the Diana fritillary is under threat of decline by 2050 across its entire distribution from climate change, and is likely to be negatively affected by other human-induced factors as well.

Frosty pod rot, caused by Moniliophthora roreri, is the most damaging disease of cacao in Latin America. However, to better comprehend its epidemiology, we must understand its dissemination and proliferation. Still, we ignore how loads of M. roreri spores fluctuate across growing seasons since we lack a reliable technique to quantify M. roreri spores in the fields. Therefore, we developed a method that uses a spore trap to capture M. roreri spores and qPCR to quantify them. This study demonstrated that this technique could quantify 3.9 x104 M. roreri spores with a 95 % confidence level. However, it could not differentiate between M. roreri and its close relative, M. perniciosa. Despite this limitation, we could detect and quantify Moniliophthora spores from environmental samples taken from a cacao field. This technique can help the phytopathologist address studies more accurately in disseminating cacao pathogens.

This study presents a detailed assessment on the impact of the Brazilian legal framework related to the access and benefit sharing provisions of the UN Convention on Biological Diversity. The research is based on a comprehensive dataset that was systematically collected over several years, directly from the official government bodies responsible for its implementation. The aim of the study is to contribute to a fact-based discussion on the effectiveness of national ABS laws, focusing on the Brazilian legal framework, first established in the year 2000 and revised in 2015, as a case example. This study balances the costs and benefits of the Brazilian ABS system and assesses the regulatory challenges it poses to individuals, companies, and institutions that perform research, share knowledge, develop, manufacture or market products derived from Brazilian biodiversity. The study indicates that, after over 22 years of operation, the regulatory challenges are still real and relevant, and that the significant volume of data collected from users on access, prior commercialization and shipment of genetic materials abroad was never systematically assessed by the agencies in charge. Besides, it shows that the costs incurred by the government in managing the policy itself have been higher than the economic benefits it has made possible, and that the institutional mechanisms in place since 2015 have not been able to allocate the monetary benefits contributed by users to the National Benefit Sharing Fund to any projects aimed at developing sustainable uses or preserving Brazilian biodiversity.

Background: The mental state is important in the health/illness process. Including stress, depression and anxiety. Nature immersion therapies have been implemented as a valid method for reducing these disorders. The aim will evaluate the effect of forest intervention therapies on levels of stress, depression, and anxiety. Methods: We searched for randomized clinical trials related to stress, anxiety and depression levels. Risk of bias was assessed according to the guidelines of the Cochrane Handbook for International Systematic Reviews. Results: We identified and synthesized eight publications. Two studies for cortisol showed significant differences between the pre-test and post-test levels in the intervention groups. One study including Natural killer cells, that reported a significant decrease in the intervention group compared to the control group. Two studies used the Stress Response Inventory, indicated a significant reduction in stress levels in the intervention group compared to the control group. Regarding Restorative Out-come Scale, no significant differences were found. Three studies were selected for the evaluation of anxiety and depression levels according to the Positive and Negative Affect Schedule. Four studies used The Profile of Mood States scale; no significant difference was observed. Conclusions: There is limited evidence to recommend forest bathing for reducing these disorders.

Adequate public spaces and urban green areas are key criteria for urban development and infrastructure implementation of healthy cities. Latterly, there has been an increasing number of research methods using artificial intelligence (AI) to monitor, quantify, and control the state of these spaces with an aim towards pioneering research in Urban Studies. However, in informal areas, open-data access tends to lack adequate and updated information, making it difficult to use AI methods. Hence, we propose a methodology for restricted open data collection and preparation for future use in machine learning or spatial data science models for similar areas. To that extent, we examine two peripheral and low-income neighborhoods in Quito, Ecuador, La Bota and Toctiuco, to analyze their public spaces, urban green areas, points of interest, and road networks, and how they address healthy cities criteria. We develop an original methodological approach that combines an index of proximity, accessibility, quantity, and quality of these spaces with geospatial and network analysis techniques. Results indicate that the connectivity and structure of these spaces are centralized and nodal, representing exclusion and segregation. This work provides insights on potential healthy spaces, and information to urban planners and policymakers in decision-making for healthy urban infrastructure.

This research analyzes the Physical Education students’ degree of academic performance with the incorporation of active methodologies, specifically the flipped classroom mixed learning, restricted to evaluation periods in the months of June and September. The study focuses on whether there are significant differences in this variable through the scores obtained. Through a simple random sampling, 131 students participated in this empiric-analytic research, using an ex-post-facto study with a retrospective design with quasi control group. A robust test of averages comparison, multiple linear regressions and an evaluation of the relative importance of predictors is conducted. The results show how flipped classroom methodology linearly and positively influences academic performance and correlationally motivation and support. As main conclusion, in a hybrid and digitalized learning context, the value of the consideration of active methodologies (flipped classroom) based on emerging pedagogies, allows improving students’ achievement and competence development, providing critical, significant, ubiquitous, transformational and especially motivating experiences.

Mucormycoses are rare but serious opportunistic fungal infections caused by filamentous organisms of the order Mucorales. Here we report the first molecular identification of Rhizopus oryzae (heterotypic synonym Rhizopus arrhizus), R. delemar, and Apophysomyces ossiformis as the etiological agents of three cases of severe mucormycosis in Honduras. Conventional microbiological cultures were carried out, and DNA was extracted from both clinical samples and axenic cultures. The ITS ribosomal region was amplified and sequenced. Molecular tools are suitable strategies for diagnosing and identifying Mucorales in tissues and cultures, especially in middle-income countries lacking routine diagnostic strategies.

Human Rhinovirus (HRV) is the most common cause of upper respiratory infections and exacerbations of asthma. In this work, we selected 14 peptides (6 from HRV A and 8 from HRV C) encompassing potential CD4 T cell epitopes. Peptides were selected for being highly conserved in HRV A and C serotypes and predicted to bind to multiple HLA II molecules. We found positive T cell recall responses by IFNγ-ELISPOT assays to 8 peptides, validating 7 of them (3 from HRV A and 4 from HRV C) as CD4 T cell epitopes through intracellular cytokine staining assays. Additionally, we verified their promiscuous binding to multiple HLA II molecules by quantitative binding assays. According to their experimental HLA II binding profile, the combination of all these 7 epitopes could be presented and recognized by > 95 % of the world population. We actually determined IFNγ responses to a pool encompassing these CD4 T cell epitopes by intracellular cytokine staining, finding positive responses in 29 out of 30 donors. The CD4 T cell epitopes identified in this study could be key to monitor HRV infections and to develop peptide-based vaccines against most HRV A and C serotypes.

Objectives: COVID-19 pandemic interrupted the Spanish professional football competition until May 2020, when it was restarted following a surveillance protocol established by LaLiga. The aims were to describe the infective and serological status of professional football players (PLY) and staff (STF) between May 5th 2020 until April 22nd 2021, to analyze the spatial-temporal distribution of the COVID-19 disease in this cohort and its comparison to the Spanish population. Methods: a prospective observational cohort study was carried out. Differences between PLY and STF were assessed by Chi-squared test and test of equality of proportions. Pearson correlation test was used to measure the presence of an association between the percentages of positivity in population and LaLiga cohort. Results: 137,420 RT-PCR and 20,376 IgG serology tests were performed in 7,112 professionals. Positive baseline serology was detected in 10.57% of PLY and 6.38% of STF. Among those who started the follow-up as not infected and before STF vaccination, 11.87% of PLY and 5.03% of STF became positive. Before summer 2020 the prevalence of infection was similar than the observed at national level. The percentage of positivity in the Spanish population was higher than in LaLiga cohort, but both series showed a similar decreasing trend.

The present paper offers a reading of three selected novels by two Anglophone Arab writers Diana Abujaber and Fadia Faqir. Our reading is fundamentally based on a philosophical post-humanist perception of other ethnic minorities as being inferior and un-human. In interpreting the three novels, Arabian Jazz (2003), My Name is Salma (2007) and Willow Trees Don’t Weep (2014), a main concern is to bring to light how Arabs –and Muslims –have been zombified and de-humanized in Western mainstream media and culture based on a biased stigmatization and stereotyping of a large heterogeneous ethnic group wherein religions, traditions, languages and cultures are diverse. Also, a pivotal preoccupation is going to be the exiling journey of the protagonists from their homelands to Western countries, and how these journeys contribute to the post-humanization of the self, the identity and the culture of Arab displaced immigrants.

Background: Historically, in the United States and globally, women have supported other women before, during, and after childbirth. Birth doulas are considered an important component to eliminating racial disparities in maternal morbidity and mortality. To address disparities in birth outcomes, Healthy Women Healthy Futures (HWHF) provides free birth and postpartum doula services to low-income women and communities of color in New York City. Methods: Secondary analysis of program data (n=364) collected between 2020 and 2021 was conducted. Univariate and multivariable analyses focused on: method of delivery, preterm birth, low-birthweight birth, breastfeeding, maternal-infant skin contact. The key exposure variable was total doula hours. Results: Clients who received prenatal doula support had low rates of preterm birth (8.8%) and low birthweight (7.1%), and high rates of vaginal delivery (69.1%), breastfeeding in the hospital (90.9%), and maternal-infant skin contact (78.2%). Multivariable analysis did not identify an association between number of doula hours and any of the five outcomes examined. Conclusion: While descriptive results point to positive birth outcomes, these effects did not persist in multivariable analyses. Data quality concerns from this intervention likely hindered the ability to detect a program impact, emphasizing the importance of funding to support data collection and management activities.

Anemonia viridis is an abundant and widely-distributed temperate sea anemone that can form dense congregations of individuals. Despite the potential severity of its sting, few detailed cases have been reported. We report a case of a severe toxic reaction following an A. viridis sting in a 35-year-old oceanographer. She developed severe pain, itching, redness and burning sensation, which worsened one week after treatment with anti-inflammatories, antihistamines and corticosteroids. Prompted by this event, and due to the insufficient risk prevention, lack of training for marine-environment users and lack of research into sting-specific first-aid protocols, we evaluated the cnidocyst response to five different compounds commonly recommended as rinse solutions in first-aid protocols (seawater, vinegar, ammonia, baking soda and freshwater) by means of the Tentacle Solution Assay. Vinegar and ammonia triggered an immediate and massive cnidocyst discharge after their application and were classified as activator solutions. Baking soda and freshwater were also classified as activator solutions, although with a lower intensity of discharge. Only seawater was classified as a neutral solution and therefore recommended as a rinse solution after A. viridis sting, at least until an inhibitory solution is discovered.

The current study compared the goodness of fit and estimation precision of Bayes and maximum likelihood (ML) structural equation modeling across sample sizes. Data consisted of Markov Chain Monte Carlo generated samples of 50, 75, 100, 125, 150, 200, 250, 500, 750, 1000, and 1500 observations. The Bayes and ML methods were used to estimate a structural equation model with 40 parameters, including 12 continuous observed indicators, four latent variables, and three structural paths. Analyses were conducted with the Mplus 8.0 statistical software and were replicated 500 times with each of the 22 conditions (11 sample sizes x 2 estimation methods). Indices of model fit were the Bayes information criterion, the Tucker-Lewis index, the comparative fit index, the root mean square error of approximation, the posterior predictive p-value (for Bayes models), and the ꭓ2 test (for ML models). Results showed that as the sample size increased, both estimation methods exhibited improved model fit and enhanced estimation precision, and both methods performed well with samples of 200 or larger; however, ML demonstrated a marginally superior fit with smaller samples. These findings were not consistent with previous research and suggest that ML remains a better choice with continuous data and small samples.

Consumers are attracted by the increasing number of available SVOD platforms, but subscribing to all of them would be too expensive. To reduce costs, consumers could combine the use of proprietary subscriptions, non-proprietary subscriptions, and illegal streaming sites. In turn, platforms could enforce access control, a decision that could produce the desired reduction in non-proprietary subscriptions but also an undesired reduction in proprietary subscriptions. The effects of this decision and the determinants of SVOD content demand remain largely unexplored. We propose a baseline model where the SVOD content demand is driven by variety seeking, household financial situation, ethical evaluation, and social norms, as well as a change model where the subscription variation is driven by users’ trait reactance and perceived fairness of the decision. We conducted a survey on the current ways of SVOD content consumption and the responses to a hypothetical access control enforcement, with four randomized versions of the authentication mode. Results confirmed many of the proposed determinants and showed a noteworthy reduction in proprietary subscriptions due to the control enforcement but no effect due to the authentication modes. All these findings may help improve future models on SVOD content consumption and better address the difficult challenge of converting unauthorized users into authorized ones.

Potato is a starchy, tuberous crop from the perennial Solanum tuberosum having high nutritional values. This paper is the first analytical approach to quantify Pt and Rh in vegetal food. In this study a total of 38 different potatoes samples produced in Europe and one in Australia were investigated. Determinations of Pt and Rh in potatoes samples were carried out by Differential Pulse Voltammetry (DPV/a) for platinum and by Adsorptive Stripping Voltammetry (AdSV) for Rh using standard addition procedure. Because no certified reference potatoes containing platinum and rhodium are available, we used addition standard method. The quantification limits for Pt and Rh are 0.007 and 0.0008 μg Kg−1 respectively. Considering all the potatoes samples, concentrations of Pt and Rh vary in the ranges from 0.007 to 109 μg Kg−1 (sample n° 6 potatoes grown in Sicily) and from 0.0008 to 0.030 μg Kg−1 (sample n°23 of potatoes grown in Emilia Romagna) respectively. For both metals, in many cases the concentrations fall near the quantification limit. In all the samples, platinum is always more abundant than rhodium and their ratio meanly is 14500, which is much greater than that of the earth's crust (about 100).

Non-standard Lagrangians do not display any discernible energy-like terms, yet they give the same equations of motion as standard Lagrangians, which have easily identifiable energy-like terms. A new method to derive non-standard Lagrangians for second-order nonlinear differential equations with damping is developed and the limitations of this method are explored. It is shown that the limitations do not exist only for those nonlinear dynamical systems that can be converted into linear ones. The obtained results are applied to selected population dynamics models for which non-standard Lagrangians and their corresponding null Lagrangians and gauge functions are derived, and their roles in the population dynamics are discussed.

The task of determining the distance from one object to another is one of the important tasks solved in robotics systems. Conventional algorithms rely on an iterative process of predicting distance estimates, which results in an increased computational burden. Algorithms used in robotic systems should require minimal time costs, as well as be resistant to the presence of noise. To solve these problems, the paper proposes an algorithm for Kalman combination filtering with a Goldschmidt divisor and a median filter. Software simulation showed an increase in the accuracy of predicting the estimate of the developed algorithm in comparison with the traditional filtering algorithm, as well as an increase in the speed of the algorithm. The results obtained can be effectively applied in various computer vision systems.

Periodontal disease is that condition resulting in the destruction of periodontal tissues, bone re-sorption and tooth loss, the etiology of which is linked to immunological and microbiological factors. The aim of the study is to evaluate the potential trigger of periodontal disease in a rat model using the bacterial species incriminated in the pathology of human periodontitis and to establish their optimal concentration capable of reproducing the disease, with the idea of subsequently devel-oping innovative treatments for the condition. We included in the study 15 male Wistar rats, aged 20 weeks, which we divided into three groups. In each group, we applied ligatures with gingival retraction wire, on the maxillary incisors. 4 days/week, 4 weeks, the ligature and the gingival sac were contaminated with fresh cultures of Aggregatibacter actinomycetemcomitans, Fusobacterium nucleatum and Streptococcus oralis in concentrations of 108, 109 and 1010CFU/ml. The clinical monitoring period was 28 days, during which we followed the expression of clinical signs specific to periodontitis, the evolution of body weight and we took weekly samples from the oral cavity for the microbiological identification of the tested bacteria and blood samples for the hematological examination. At the end of the study, the animals were euthanized and the ligated incisors were taken for histopathological analysis. The characteristic symptomatology of periodontal disease was expressed from the first week of the study and was maintained until the end, the bacteria being able to be identified at each examina-tion. Hematologically, the number of neutrophils decreased dramatically (P<0.0001) in the case of group 109, unlike the other groups, as did the number of lymphocytes. Histopathologically, we identified neutrophilic infiltrate in all groups. The presence of coccobacilli, periodontal tissue hyperplasia and periodontal lysis, but in group 109 we also observed pulpal tissue with necrotic bone fragments and pyogranulomatous inflammatory reaction. By corroborating the data, we can conclude that for the development of periodontal disease using A.a, F.n and S.o, a concentration of 109 or 1010CFU/ml is required, which must necessarily con-taminate a ligature thread applied to the level of the rat's dental pack.

High-resolution GPS/GSM dataloggers provide spatial information of the highest quality, which outperform previous tracking methods, such as Argos telemetry or conventional VHF ground-tracking. As a result, this has improved our knowledge of home-range behavior and spatial ecology of many species, including large raptors. In this paper, we use high-resolution GPS/GSM dataloggers to assess the home-range size and the role of sex, season (breeding or non-breeding season), and breeding status (reproductive or non-reproductive individuals) on the space use of Bonelli’s eagle (Aquila fasciata). To this end, 51 territorial individuals (25 females and 26 males) were equipped with GPS/GSM transmitters and were tracked over 7 years (2015–2021) in eastern Spain. Overall, we recorded 4,791,080 fixes that were analyzed through kernel density methods (50%, 75%, and 95% fixed kernels). The average individual home-range size according to the 95%, 75%, and 50% kernels was 54.84 ± 20.78 km², 24.30 ± 10.18 km², and 11.17 ± 4.90 km², respectively. Overall, the home-range size of individuals occupying the same territory was similar, mainly due to the cooperative hunting behavior exhibited by the species. We did not find interannual differences in the home-range size (95% fixed kernel) of the majority of individuals, showing a strong territorial fidelity of the breeding pairs. In general, females’ home-range size was slightly smaller than males’ size due to the decrease in activity in the breeding season as a result of laying, incubation, and chick attendance at nests. No seasonal variation in the 95% kernel was found, but it was found in the 75% and 50% kernels. In regard to the breeding status, higher home-range size was recorded in the non-reproductive individuals. Moreover, we found a low neighbor overlap among the territories (4.18% ± 3.06%), which evidences a high level of intraspecific competition in the Bonelli’s eagle. Finally, this study highlights the advantages of the use of accurate telemetry information to improve our understanding of the spatial ecology of the endangered Bonelli’s eagle, which ultimately will serve to better inform management actions for its conservation.

Band structure calculations using the spin-polarized relativistic Korringa-Kohn-Rostoker (SPRKKR) band structure method have been performed to determine the intrinsic magnetic properties (magnetic moments, magneto-crystalline anisotropy -MAE and Curie temperatures) of the Fe5-x-yCoxMySiB2 (M = Re, W) alloys. The general gradient approximation for ex-change-correlation potential and the atomic sphere approximation (GGA ASA) have been em-ployed. Previous studies showed that the Co doping is turning the in-plane into axial anisotropy for a certain doping range, whilst the 5d doping enables a strong spin-orbit coupling of Fe-3d and M-5d states which is needed to enhance the MAE. The theoretical calculations aim to find the dependence of the anisotropy constant K1 for combined Co and M doping, building a two-dimensional (2D) map of K1 for 0 ≤ x ≤ 2 and 0 ≤ y ≤ 1. Similar theoretical 2D maps for magnetization and Curie temperature vs. Co and M content (M = W and Re) have been built, allowing to select alloy compositions with enhanced values of uniaxial anisotropy, magnetization and Curie temperature. Magnetic properties of Fe4.1W0.9SiB2 alloy that meets the selection criteria for axial anisotropy K1 > 0.2 meV/f.u., Curie temperature Tc > 800 K determined by mean field approach and magnetization µ0Ms > 1 T are discussed.

In this work we discuss the insights from activity landscape, docking and molecular dynamics towards the understanding of the structure-activity relationships of dual inhibitors of major epigenetic targets: lysine metiltransferase (G9a) and DNA metiltranferase 1 (DNMT1). The study was based on a novel data set of 50 published compounds with reported experimental activity for both targets. The activity landscape analysis revealed the presence of activity cliffs, e.g., pairs of compounds with high structure similarity but large activity difference. Activity cliffs were further rationalized at the molecular level by means of molecular docking and dynamics simulations that led to the identification of interactions with key residues involved in the dual activity or selectivity with the epigenetic targets.

Self-consciousness can be considered as the internal disposition to direct attention to oneself. This dispositional tendency can be focused on private aspects of the self, but also on public characteristics of the individual. We examine self-consciousness in online consumer behavior. This concept has been poorly investigated in consumer research. The main objective of this paper is to analyze the influence of the dimensions of self-consciousness in consumer adoption of online shopping. This study is based on a sample of 725 Spanish undergraduates. Results indicated that public self-consciousness is a significant predictor of the adoption of online shopping.

The Lagrangian formalism is developed for the population dynamics of interacting species that are described by several well-known models. The formalism is based on standard Lagrangians, which represent differences between the physical kinetic and potential energy-like terms. A method to derive these Lagrangians is presented and applied to selected theoretical models of the population dynamics. The role of the derived Lagrangians and the energy-like terms in the population dynamics is investigated, and it is shown that the obtained standard Lagrangians can be used to study oscillatory behavior of the models and the period of their oscillations, which may have ecological and environmental implications. These and other physical and biological insights gained from the derived standard Lagrangians are discussed.

The emergence of prosumers, who actively participate in designing and producing goods, has generated interest in domestically manufactured products. Factors such as innovation, design methods, component reuse, prototyping, and digital fabrication empower prosumer designers to realize their ideas and enhance products to meet their specific design requirements. This article presents a case that combines bioinspired design methods with prosumer characteristics from the perspective of a designer who uses biological research results acting as a prosumer. By analyzing prosumer needs, bioinspired design, and domestic fabrication requirements, designers define the methods that best suit their possibilities. As a result of using biological information, the geometry of Samara seeds, propeller sizing, wind tunnel tests, and subsequent improvements, the custom design of a bioinspired microgenerator has been refined to the final design of a bicycle flashlight. The aim is to popularize a working approach that facilitates the interaction of design methods and reinforces domestic manufacturing processes. Implementing bioinspired design methods within the prosumer context offers a methodological alternative to transform the current economic model, promoting systemic sustainability and the development of proprietary technologies.

The general purpose of the Design Thinking approach (concept taken over in Romanian without its translation and which involves conception-oriented thinking) is to support the conception and design of products, services, processes, strategies, spaces, architecture and experiences ideal for use optimal. Applying the approach leads to the development of practical and innovative solutions to the problems identified in the product and / or technology design departments of companies. As described in the article Design Thinking is a process springing from the user-centered conception-design paradigm. The objective of the article is to highlight the need to combine urban study within Design Thinking, in the case of all areas of conception-design of solutions.

As consequence of COVID-19, millions of households suffered mobility restrictions and changes in their lifestyle during several months. The aim of this study was to evaluate the effects of COVID-19 home confinement in food habits, lifestyle and emotional balance of the Spanish population. This cross-sectional study used data collected via an anonymous online questionnaire during the last month before lockdown finished in Spain in a total of 675 participants. 38.8% of the respondents experienced weight gain while 31.1% lost weight during confinement. The increase in body weight was positively correlated with the age (Rs = 0.14, p &lt;0.05) and BMI (Rs = 0.20, p &lt;0.05). We also identified that 39.7% reported poorer quality sleep, it was positively correlated with BMI (Rs = -0.18, p &lt;0.05) and with age (Rs = -0.21, p &lt;0.05). 44.7% of the participants had not performed physical exercise during confinement with differences by sex (p &lt;0.05), by age (p &lt;0.05), by BMI (p &lt;0.05) and sleep quality (p &lt;0.05). According to emotional-eater questionnaire, 21.8% and 11% were classified as emotional eater and very emotional eater, respectively. We emphasize the importance of adopting a healthy lifestyle, as the COVID-19 pandemic nowadays is ongoing.

Pinus patula is one of the most planted wood conifer species worldwide; however, no foliar nutrient standards exist for this species up to date. The objective of the present study was to generate and verify two sets of foliar nutrient standards for nearly ten-year-old P. patula trees: critical nutrient concentrations and DRIS norms. Nutrients studied were N, P, K, Ca, Mg, Fe, Cu, Zn, Mn, and B. The reference standards were verified experimentally by installing two fertilization trials; one of them located in Huayacocotla, state of Veracruz and the other one in Aquixtla, state of Puebla, Mexico. Nutrient status of each fertilization trial was correctly predicted by critical nutrient values and DRIS as well. Both standards were able to detect the secondary growth-limiting nutrient deficiency in the Huayacocotla trial, where the primary limitation for growth was scarcity of solar radiation within tree crowns. The limiting nutrient in both experimental trials was K.

In recent years, the widespread introduction of bike-sharing systems in China has had a profound impact on the daily lives of Chinese citizens and the development of the urban transport system. This article attempts to analyse the impact of this phenomenon on sustainability. The gradual improvement of related monitoring measures has facilitated the maturation of the bike-sharing industry from the initial stage of uncontrolled growth to the current stage of standardised management. By tracing the global development of bike-sharing systems with a special focus on China, this study sheds light on the platformisation of bicycles and its multiple impacts on technical, environmental, cultural, economic and social sustainability. Furthermore, the study provides a comprehensive analysis of the transformation of bicycles in China and highlights the diverse impacts of platform-based bike sharing on various facets of Chinese society. The development of different bike-sharing systems in China is a unique and crucial case to interpret the current situation of bike-sharing and imagine future scenarios. In contrast to the prevailing and uniform approach derived from the experiences of Northern European countries, the massive and widespread experimentation with different bike-sharing schemes in China reveals not only potentials and aspects of sustainability, innovation and urban and social regeneration, but also some hidden shadows similar to those in small-scale contexts such as Northern Europe. Furthermore, the study emphasises the crucial role of sustainable development principles in addressing urban challenges specific to China.

There is an urgent need to develop new therapies for cancer treatment due to high rates of resistance and tumor relapse. Moreover, chemotherapy and radiation weaken the immune system and leave patients susceptible to sudden death from infections and organ failure since antineoplastic drugs lack specificity. Hence, scientists worldwide continue the search for natural alternatives with anticancer activities and fewer side effects. In this regard, traditional medicine offers strategies for preventing and treating numerous diseases and nowadays scientific studies worldwide highlight some of the mechanisms underlying their potential as an effective alternative for the management of cancer. In Mexico, Mayan healers have been prescribed mainly medicinal plants for more than 2,000 years. Furthermore, their ethnomedical knowledge has led to drug discovery or the development of herbal remedies. Medicinal plants from the genus of Cissus remain an important element of all indigenous medical systems in Mexico including the Mayan tribes in Yucatan, particularly for the management of gastrointestinal illnesses, sores, cutaneous diseases, and tumors. In this review, we present the reported bioactivities against cancer cells of the extract and compounds from the species of Cissus with a particular focus on recent studies on the phytochemistry of C. trifoliata which is widely distributed in Mexican territory and used for tumor management in traditional medicine.

Background: It is well known the adverse effect of mercury exposure on pregnant women and newborns. Interactions between environmental factors and individual genetic susceptibility have been identified, particularly polymorphisms of codifying genes for the Glutathione S-transferase family (GSTs). Herein, we report a case series of patients with high Hg levels in biosamples. Case Series: Fourteen cases with high Hg levels were identified. Non-occupational or home exposure risk factors were identified. All mothers reported fish consumption during pregnancy. Almost 60% of the individuals were null for either one GSTs gene. To date, in the subsequent mother-child pairs toxicology controls no signs or symptoms of poisoning were identified and most of the mercury levels decreased and are below the accepted limit. Discussion: In this case series we found some similarities with the literature; among them, the relation of Hg ratio in maternal blood and umbilical cord, a possible exposure factor is the consumption of fish during pregnancy and, the high levels of Hg may be related with susceptibility biomarkers such as GSTs gene polymorphisms. This case series highlights the need to develop studies that evaluate the interactions between environmental factors and individual genetic susceptibility. Additionally, the importance of evaluating which Colombian fish species present the highest levels of Hg.

BACKGROUND Detecting total cholesterol in dried blood spots could aid in identifying individuals with a high likelihood of familial hypercholesterolemia and could be used as a screening measure. This study aims to assess the diagnostic accuracy of dried blood spots on Whatman 903 paper cards using a manual enzymatic technique. METHODS A total of 394 samples collected as serum and dried blood spots were compared. Cholesterol was determined in serum using the automated reference method, while cholesterol on paper was measured using a manual enzymatic method. Within- and between-day diagnostic variability were analyzed. The correlation between both methods was assessed using Passing-Bablok regression and Bland-Altman plot. Internal validation of our correlation formula was performed on 149 samples, along with external validation of the formula proposed by Corso et al. RESULTS The within- and between-day coefficient of variation was found to be lower than 10.14% and 14.09%, respectively. Method comparison yielded an area under the curve of 0.976, with a standard error of 0.009. Passing-Bablok regression indicated a precision of 0.803 and an accuracy of 0.96. Internal validation precision was measured at 0.716. Regarding internal validation, calculated cholesterol with our regression line did not differ from serum cholesterol analysis, while significant differences were observed in calculated cholesterol levels using the external formula. CONCLUSIONS Total cholesterol analysis in dot blood spots demonstrates high precision and reproducibility. This method reliably enables the incorporation of this biological marker into neonatal screening for familial hypercholesterolemia detection.

The changes in consumer preferences and the increasingly competitive global market have demanded that food entrepreneurs engage in innovative value-added activities. The date is a delicatessen fruit known by its content of active compounds (e.g., dietary fiber and antioxidants) and its biological activity which has a vast potential in the design of new products such as bioactive ingredients, sugar substitutes, dietary supplements, functional foods, among others. In the current paper, innovative approaches to the value addition to date fruits and their processing by-products have been reviewed from recent high-quality scientific works. New processes such as ultrafiltration and hydrothermal treatments are shown as a useful alternative to obtain differentiated date-based ingredients (e.g., fiber concentrates, sap syrups, and date powders). Moreover, the use of date fruits and their byproducts as natural sources of value-added active compounds in the preparation of dairy, meat, and bakery and cereal products is also presented.

Initially, renal resistive index (RRI) was investigated to improve diagnosis in kidney diseases, but failed to meet this goal. Recently many papers highlighted the prognostic significance of RRI in chronic kidney disease, in the estimation of revascularization success of renal artery stenoses or the evolution of the graft and recipients in renal transplantation. Moreover, RRI gained importance in prediction of acute kidney injury in critically ill patients. Along with RRI study in renal pathology have been revealed correlations of this index with parameters of systemic circulation. The theoretical and experimental premises of this connection were reconsidered, and studies for analyzing the link between RRI and arterial stiffness, central and peripheral pressure or left ventricular flow were conducted with this purpose. A high amount of data is currently indicating that RRI is influenced more by pulse pressure and vascular compliance than by renal vascular resistance – assuming that RRI reflects the complex interplay between systemic circulation and renal microcirculation and should be considered as a marker of systemic cardiovascular risk beyond its prognostic relevance for kidney disease. In this review we will go through clinical research that revealed the implications of RRI in renal and cardiovascular disease.

The tourism sector in general and the hotelier in particular face the challenge of managing appropriate measures to deal with the covid-19 pandemic. In this sense it is useful to know what the measures are most demanded by the clientele. This research, by analyzing the variance (ANOVA) of a factor concluded that women are more demanding than men in terms of the level of demand in relation to the measures to be taken in hotels. This, as a practical application, allows to know more accurately the expectations, demands and demands of the client segmented by sex, in order to satisfy and improve the tourist experiences.

We consider an $N$ fermion system at low temperature $T$ in which we encounter special particle number values $N_m$ exhibiting special traits. These values arise in focusing attention upon the degree of mixture (DM) of the pertinent quantum states. Given the coupling constant of the Hamiltonian, the DMs stay constant for all $N$-values, but experience sudden jumps at the $N_m$. For a quantum state described by the matrix $\rho$, its purity is expressed by $Tr \rho^2$ and then the degree of mixture is given by $1 - Tr \rho^2$, a quantity that coincides with the entropy $S_q$ for $q=2$. Thus, Tsallis entropy of index two faithfully represents the degree of mixing of a state, that is, it measures the extent to which the state departs from maximal purity . Macroscopic manifestations of the degree of mixing can be observed through various physical quantities. Our present study is closely related to properties of many-fermion systemsn that are usually manipulated at zero temperature. Here we wish to study the subject at finite temperature. Gibbs' ensemble is appealed to. Some interesting insights are thereby gained.

The tourism sector in general and the hotelier in particular face the challenge of managing appropriate measures to deal with the covid-19 pandemic. In this sense it is useful to know what the measures are most demanded by the clientele. This research, by analyzing the variance (ANOVA) of a factor concluded that women are more demanding than men in terms of the level of demand in relation to the measures to be taken in hotels. This, as a practical application, allows to know more accurately the expectations, demands and demands of the client segmented by sex, in order to satisfy and improve the tourist experiences.

The tourism sector in general and the hotelier in particular face the challenge of managing appropriate measures to deal with the covid-19 pandemic. In this sense it is useful to know what the measures are most demanded by the clientele. This research, by analyzing the variance (ANOVA) of a factor concluded that women are more demanding than men in terms of the level of demand in relation to the measures to be taken in hotels. This, as a practical application, allows to know more accurately the expectations, demands and demands of the client segmented by sex, in order to satisfy and improve the tourist experiences.

Water is a fundamental resource for ecosystems, humans, and the development of all economic sectors; it is necessary to identify and evaluate its environmental pressures or impacts. The water footprint (WF) is an appropriate indicator for the consumption of water used to produce a product. The present study uses this tool to evaluate the green and blue water requirements and the sustainability of irrigation water use for agroindustrial avocado production in Ziracuaretiro, Michoacán (2012-2021). Our analysis was based on aggregating weather and soil data at the municipal level and official government databases of avocado cultivated surface, fruit production, and water rights concessions. The analysis considers the homogeneity of information throughout the study area. We estimated that rainfed plantations require 839.03 m³/ton and irrigated plantations require 2355.80 m³/ton, with an average of 1597.47 m³/ton. In addition, we determined that avocado cultivation can demand up to 124.3% of agricultural water concessions in this municipality. In addition to the WF estimates, the analysis indicates that such studies are fundamental for decision-makers to develop and implement water use-efficiency strategies and shows the need for further research related to water consumption of avocado as a crop at more detailed scales to reduce uncertainty.

The main objective of this paper is to assess pro-environmental behavior, climate change perception, anxiety, hope and despair in different political orientations. Specific aims included to validate all the instruments; to assess whether the factor structure of the scales were valid across political orientations; to evaluate their reliability; to assess differences concerning age, gender and political orientation; to know the variables that explain pro-environment behavior; and to evaluate the moderating role of climate change perception, despair and hope in the relationship between climate change anxiety and pro-environmental behavior. Confirmatory factor analysis (CFAs), multi-group CFAs (to measurement invariance), multiple linear regressions and moderations were performed. Results showed that pro-environment behavior and climate change hope achieved the four levels of invariance across different political orientations; climate change anxiety achieved the three first levels of invariance; climate change perception and climate change despair achieved configural invariance. Climate change anxiety personal experience, climate change perception total, reality and consequences present higher values in left political orientation that in right or center. Climate change anxiety variables contribute most to explaining pro-environmental behaviors. Hope, despair and climate change perception consequences moderate de relationship between climate change anxiety and pro-environment behavior. These results open up new avenues of investigation, namely, to understand why high levels of anxiety lead to more pro-environment al behaviors.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the loss of dopamin-ergic neurons responsible for unintended or uncontrollable movements. Mutations in leu-cine-rich repeat kinase 2 locus, contributes to genetic forms of PD. The fruit fly Drosophila mela-nogaster carrying this mutation (LRRK2-Dm), is an in vivo model of PD that develops motor impairment and stands for an eligible non mammalian paradigm to test novel therapeutic ap-proaches. Dehydrozingerone (DHZ) is a natural phenolic compound isolated from ginger. Pre-sents anti-inflammatory, antioxidant and neuroprotective properties making it a potential therapeutic target for PD. We administered DHZ and its C2-symmetric dimer (DHZ-DIM) at 0.5 and 1mM, for 14 and 21 days, in the LRRK2-Dm, with the aim to assess changes for rescuing motor behavior, brain dopaminergic neurons, mitochondria and synapses (T-Bars). The shorter treat-ment with both molecules revealed efficacy at the higher dose improving climbing behavior with a prevention of dopaminergic neuronal demise. After 21 days, a recovery of the motor disability, dopaminergic neuron loss, mitochondrial damage and T-Bars failure was observed with the DHZ-DIM. Our data indicates that the DHZ-DIM exerts a more potent neuroprotective effect respect to the monomer in LRRK2-Dm, prompting further investigation of these compounds in rodent models of PD.

Non steady applied magnetic field impact on a liquid metals has good prospects for industry. For a better understanding of heat and mass transfer processes under these circumstances, numerical simulations are needed. A combination of finite elements and volumes methods was used to calculate the flow and solidification of liquid metal under electromagnetic influence. Validation of numerical results was carried out by means of measuring with ultrasound Doppler velocimetry technique, as well as with neutron radiography snapshots of the position and shape of the solid/liquid interface. As a result of the first part of the work, a numerical model of electromagnetic stirring and solidification was developed and validated. This model could be an effective tool for analyzing the electromagnetic stirring during the solidification process. In the second part, the dependences of the velocity pulsation amplitude and the melt velocity maximum value on the magnetic field pulsation frequency are obtained. It was found numerically the ability of the pulsating force action to develop higher values of the liquid metal velocity at a frequency close to the MHD resonance. Obtained characteristics give a more detailed description of the electrically conductive liquid behaviour under action of pulsating traveling magnetic field.

Background and Objectives: Knee osteoarthritis (KOA) is a degenerative disease that is targeting continuously people of different ages, but especially the elderly population, the number of which tends to increase continuously at the global level. Apart from age, excess weight can influence the evolution of the disease, with obesity being associated with a weak inflammation stage, and an imbalance between pro-inflammatory and anti-inflammatory cytokines. The present work aimed to identify specific biomarkers alike ACRP-30, IL-10, TNF-α, and IL-6 in synovial fluid and correlate them with patients’ clinical data. Materials and Methods: 24 subjects with KOA and over 50 years of age are involved in the present study. All patients performed a supine X-ray at the target knee. Ultrasound was performed using an ESAOTE MyLab Omega (ESAOTE Spa, Italy) ultrasound device and a 6-19 MHz linear array transducer. Results: The obtained results highlighted a significant correlation between age and adiponectin level (p=0.0451, r=-0.412). Also, the IL-10 values are lower in cases where the intensity of the pain is more pronounced (p=0.0405, r=-0.421). In addition, analyzing the data by gender, it was observed that in the case of males, stiffness is more related to age (p=0.0079, r=0.7993), compared to women (p=0.0203, r=0.6223). In the case of women, the progression of the disease tends to increase more intensively total WOMAC score’s values (p=0.00031, r=0.8342), compared with men (p=0.0289, r=7013). Regarding interleukins and BMI, significant correlations were observed only in the case of men. Conclusions: A significant correlation between age and adiponectin, and adiponectin and IL-6, suggests that advanced age may contribute to adiponectin reduction. Comparing men with women, it was observed that men's age is more related to rigidity, and IL-6 and IL-10 are directly correlated to BMI and women seem to be more sensitive to pain and stiffness.

We investigated the dynamics of a simple master equation describing the evolution of a probability distribution between two states, \( p_1 \) and \( p_2 \) (with \( p_1 + p_2 = 1 \)). Our focus is on the behavior of the entropy \( S \), the distance \( D \) from the uniform distribution (\( p_1 = p_2 = 1/2 \)), and the free energy \( F \). We define two ratios, \( \eta_S = \frac{dS/dt}{dF/dt} \) and \( \eta_D = \frac{dD/dt}{dF/dt} \), and find that both diverge to plus-minus infinity as the system evolves towards the uniform distribution. This divergence marks a critical transition point where the master equation temporarily loses physical meaning. However, after this divergence, the system settles into a new, well-behaved regime where the solutions stabilize at finite values, representing a new equilibrium or steady state. This two-regime behavior underscores the intricate dynamics of simple probabilistic systems as they approach and surpass equilibrium, providing insights into the complex interplay of entropy, distance, and free energy in statistical mechanics.

Pericytes are increasingly recognized as being important in the control of blood-brain barrier permeability and vascular flow. Research on this important cell type has been hindered by widespread confusion regarding the phenotypic identity and nomenclature of pericytes and other perivascular cell types. In addition, pericyte heterogeneity and mouse-human species differences have contributed to confusion. Herein we summarize our present knowledge on the identification of pericytes and pericyte subsets in humans, primarily focusing on recent findings in humans and nonhuman primates. Precise identification and definition of pericytes and pericyte subsets in humans may help us to better understand pericyte biology and develop new therapeutic approaches specifically targeting disease-associated pericyte subsets.

Scaffolds are widely used in tissue engineering because their manufacture is based on natural and synthetic polymers, which allows them to have properties such as biocompatibility and biodegradability, creating an ideal environment for cell growth on their surface. In this context, among the polymers studied in Tissue Engineering are Chitosan (CH) and Polyvinyl Alcohol (PVA). CH is a versatile polymer obtained from de-acetylation of chitin, which is used for its high biodegradability and biocompatibility, although its mechanical properties must be improved. It has been found that one of the ways to improve the mechanical properties of CH is to mix it with other synthetic polymers such as PVA. PVA is known for its biocompatibility, biodegradability, zero toxicity and ease of preparation due to its solubility in water and excellent mechanical properties, such as tensile strength and ease in the formation of films and barriers. In this study we evaluated the capacity of scaffolds made with CH and PVA in different concentrations (2: 1, 1: 1, 1: 2, respectively) as a possible application in bone regeneration. This was made through different characterization tests such as Infrared Spectroscopy, AFM, Swelling test and Porosity test, where we obtained information about its structural and physicochemical properties. Additionally, a cellular quality control was performed on the material through the MTT assay. The Fourier transform infrared spectroscopy (FTIR) study showed that there are strong intermolecular hydrogen bonds between the chitosan and polyvinyl alcohol molecules. The Swelling and Porosity tests showed favorable results, obtaining maximum values ​​of 5519% and 72.17% respectively. MTT tests determined that the prepared materials are not cytotoxic. These findings suggest that scaffolds possess properties suitable for use in Tissue Engineering.

The purpose of this study is to analyse the feasibility of using waste from granite gang saws (GCW-GS) to manufacture ultra-high performance, steel-fibre reinforced concrete (UHPFRC). These machines cut granite blocks by abrasion using a steel blade and slurry containing fine steel grit. The waste generated by gang saws (GCW-GS) contains up to 15% Fe2O3 and up to 5% CaO. This is the main difference from the waste produced by diamond saws (GCW-D). Consequently, the second objective of this study is to compare the results of the waste obtained with gang saws with that from diamond saws, in order to determine the influence of iron and calcium oxides. The waste from cutting granite with gang saws was used in different percentages to replace micronized quartz powder of natural origin in the manufacture of UHPRFC. All the test specimens were analysed to determine their compressive strength, elasticity modulus, flexural strength and indirect tensile strength. The final conclusion is that wastes from both gang saws and diamond saws can be used to manufacture UHPFRC with an improvement in the mechanical properties up to a 35% replacement. The results for GCW-GS are better, mainly due to the pozzolanic effect of the iron dioxide. For higher percentage replacements the mechanical properties are close to the control concrete with small decreases.

Mutations in the lipoyltransferase 1 (LIPT1) gene are rare inborn errors of metabolism leading to a fatal condition characterized by lipoylation defects of the 2-ketoacid dehydrogenase complexes causing early-onset seizures, psychomotor retardation, abnormal muscle tone, severe lactic aci-dosis and increased urine lactate, ketoglutarate, and 2-oxoacids levels. In this article, we characterized the disease pathophysiology using fibroblasts and induced neurons derived from a patient bearing a compound heterozygous mutation in LIPT1. Western blot analysis revealed reduced expression of LIPT1 and absent expression of lipoylated pyruvate dehydrogenase E2 (PDH E2) and alpha-ketoglutarate dehydrogenase E2 (α-KGDH E2) subunits. Accordingly, activities of PDH and α-KGDH were markedly reduced, associated with cell bioenergetics failure, iron accumulation and lipid peroxidation. In addition, using a pharmacological screening, we identified a cocktail of antioxidants and mitochondrial boosting agents consisting of pantothenate, nicotinamide, vitamin E, thiamine, biotin, and alpha-lipoic acid, which is capable of rescuing LIPT1 patho-physiology, increasing LIPT1 expression and lipoylation of mitochondrial proteins, improving cell bioenergetics, and eliminating iron overload and lipid peroxidation. Furthermore, our data suggest that the beneficial effect of the treatment is mainly mediated by SIRT3 activation. In conclusion, we have identified a promising therapeutic approach for correcting LIPT1 mutations.

Biopolymers based on plant and animal proteins are interesting alternatives in the development of films with future prospects as food packaging. Considering that in recent years there has been an increasing interest in the valorization of agro-industrial residues and by-products and that the blending of polymers can lead to materials with improved properties, in this work, keratin-rich feather fibers and gliadins were blended at different ratios in order to develop sustainable and biodegradable films. Control gliadin G100, feather F100 films and their blends at 3:1 (G75F25) , 2:2 (G50F50) and 1:3 (G25F75) ratios were successfully developed through thermoprocessing. The physical properties were differentiated as a function of the concentration of both polymeric matrices. Although gliadins showed higher hydrophilicity confirmed by its highest swelling degree, films with high gliadin ratios exhibited lower water permeability values at low and medium relative humidities. On the other hand, the feathers displayed the highest Young´s modulus values and provided oxygen barrier to the blends, principally at the highest relative humidity. In conclusion, the blend of these protein-based polymers at different ratio resulted on interesting composites whose physical properties could be adjusted.

Consuming fish sustainably means consuming less and better, considering environmental, social, and economic impacts. This demands more knowledge to make informed decisions. In this study, the main goal was to understand how sustainability education can be used as a tool to raise awareness and promote new habits regarding the sustainable consumption of fish in 4th-grade students at primary school. During the COVID-19 pandemic, face-to-face and online learning methodologies were used in two different groups of students to understand whether the teaching method impacted learning. A sequential explanatory mixed methodology was applied, with a pre-test/post-test design, combined with focus group sessions. Between the pre and post-tests three learning modules were performed. The results showed that the students were unaware of many aspects related to fish sustainable consumption, but the developed activities significantly increased their knowledge of the subject and impacted students to change their consumption behaviours. It was also found that the construction of knowledge by the students after the activities was achieved either by face-to-face or online learning. Interviews from focus group sessions showed that students got to know new fish species, learned about the concept of minimum landing size and closure season and that fish are labelled like other types of food.

We study different aspects of an exactly solvable master equation (ME). Its simplicity allows one direct access to the details of its workings, highlighting significant features and peculiarities. The existence of phase transitions is unveiled.

Access and Benefit Sharing (ABS) is a framework which refers to a relatively recent type of legal requirements for access to and/or use of “genetic resources”. They are based on diverse national and regional laws and regulations, which mostly result from the implementation of the United Nations’ Convention on Biological Diversity (CBD) and its supplementary agreement, the Nagoya Protocol. Their ambition is to achieve fair and equitable sharing of benefits arising out of the use of genetic resources as an incentive to conserve and sustainably use them. This paper describes the experiences, practical constraints and complexities encountered by users of genetic resources when dealing with ABS legislation, with a focus on users from the private sector. We provide insights on how ABS laws have fundamentally changed the way of working with genetic resources in the hope that it inspires re-thinking of the ABS framework, to better support the overall objectives of the CBD.

The diagnosis and treatment of autoimmune diseases are major challenges. Their signs, symptoms, and their clinical severity change throughout the course of the disease. The available treatments for these conditions do not result in complete remission, and their long-term use generates several side effects. The main challenges in this field are the development of more sensitive diagnostic tools, and effective treatments. Studies in patients and animal models reported alterations in monocyte phenotype, activation, and function. These cells play an essential role in the pathogenesis of chronic inflammatory states and have become a target for extracorporeal monitoring and specific intervention. Nanoparticles (NPs) are ultrafine particles that can be used as contrast agents in diagnostic imaging techniques to detect specific cells in inflammatory infiltrates in tissues that are not easily accessible by biopsy. In addition, NPs can be designed to deliver drugs to a cell population or tissue. This review describes several experimental pieces of evidence demonstrating that monocytes and macrophages can specifically uptake various types of NPs, thus becoming detectable in vivo by magnetic resonance imaging and susceptible to be modulated by therapeutic agents. Hence, nanoparticles targeting mononuclear phagocytes represent promising tools for diagnosing and treatment.

The use of probiotics in reproductive-related dysbiosis is an area of continuous progress due to the growing interest from clinicians and patients suffering recurrent reproductive microbiota disorders. An imbalance in the natural colonization sites related to reproductive health: vaginal, cervicovaginal, endometrial and also pregnancy-related altered microbiota could play decisive role in reproductive outcomes. Oral and vaginal administrations are in continuous discussion regarding the clinical effect pursued, but probiotics as oral supplement therapy is the route administration better studied. To complement and summarise with qualitative and quantitative information of vaginal probiotics clinical studies, the main objective of this work was to retrieve the standardised protocols commonly used and their microbiota modulation capacities. The studies selected were related to treat bacterial vaginosis (BV) as the most commonly disorder, few studies on vulvovaginal candidiasis (VVC) and also administration to stabilise microbiota before in vitro fertilisation (IVF). Probiotic doses administered were similar to oral probiotics protocols, ranging from ≥ 107 CFU/day to 2.5 x 1010 CFU/day, and variable regarding posology duration from 1 day to 12 weeks, being 1 week commonly applied. Moderate modulation was achieved regarding the relative abundance decrease of abnormal microbiota, coinciding with parallel increase in Lactobacillus species.

Large datasets play a crucial role in the progression of surgical robotics, facilitating advancements in the fields of surgical task recognition and automation. Moreover, public datasets enable the comparative analysis of various algorithms and methodologies, thereby assessing their effectiveness and performance. The ROSMA (Robotics Surgical Maneuvers) dataset provides 206 trials of common surgical training tasks performed with the da Vinci Research Kit (dVRK). In this work, we extend ROSMA dataset with two annotated subsets: ROSMAT24, which contains bounding box annotations for instrument detection, and ROSMAG40, which contains high and low level gesture annotations. We propose an annotation method that provides independent labels for the right-handed tool and the left-handed tool. For instrument identification, we validate our proposal with a YOLOv4 model in two experimental scenarios. We demonstrate the generalization capabilities of the network to detect instruments in unseen scenarios. For gesture segmentation, we propose two label categories: high-level annotations that describe gestures at a maneuvers level, and low-level annotations that describe gestures at a fine-grain level. To validate this proposal, we have designed a recurrent neural network based on a bidirectional long-short term memory layer. We present results for four cross-validation experimental setups, reaching up to a 77.35% mAP.

Artificial Intelligence (AI) has emerged as a disruptive technology in various areas, and medicine is no exception. In the last decade, there has been rapid progress in the application of AI in healthcare, from diagnosing and prognosticating diseases to improving operational efficiency in hospitals. This literature review explores the advances of artificial intelligence in the field of medicine, discusses its benefits, and discusses the ethical and regulatory challenges that need to be addressed to maximize its potential.

A project-based module on Sustainable Development Goal number 5, Gender Equality, was im-plemented on 5 different groups of Business English students consisting of a total number of 62 students in higher education. The main purpose of this project was to raise awareness of this goal by means of a flipped method in which students were required to carry out some research on specific areas of the aforementioned goal and work in teams to elaborate oral presentations. Once their findings were shared in class, students were expected to answer a written questionnaire of open-ended questions which were part of a qualitative analysis. Results of this survey showed that not only 90% of the students gained in depth knowledge of this goal, but also 85% had built a positive attitude to take initiative and 80% were optimistic about future gender equality. Finally, 70% of students suggested further social action to curb the problem of gender discrimination. On the whole, the flipped classroom method of learning combined with project-based group work have proven to be an effective way to raise awareness of this goal, create a more positive attitude, in-crease their willingness to take action as well as widening their English lexical resources.

Keywords: contamination; bioaccumulation; fish and mollusks tissue; ecosystem components; heavy metals; organochlorine pesticides; polychlorinated biphenyls; polycyclic aromatic hydrocarbons.

The modern supply chain (SC) is growing in terms of data, devices, users, and stakeholders, which introduced new security challenges and threats, especially with the reliance on centralized servers or cloud platforms. In addition, increased trust among system participants exposes the SC to a higher risk of vulnerabilities which require strong security measures. This article proposes a hybrid security framework for SC systems, BC-DRLzSC, that integrates Blockchain (BC) and Deep Reinforcement Learning (DRL) designed to operate in a zero trust (ZT) environment. In particular, we propose a decentralized BC-based approach integrated with smart contracts to manage system participant registration and authentication and to control access to system resources. BC-DRLzSC adopts a ZT architecture to reinforce SC security, which can be achieved with an advocate to verify each entity’s trustworthiness before granting or retaining access to system resources. Incorporating the ZT architecture, with BC and DRL, can potentially and significantly bolster SC system security. DRL is employed to develop a proactive attack detection model that continuously monitors the incoming traffic from authenticated nodes within the network and predicts any malicious actions. Finally, we evaluate the performance of our proposed DRL solution using the NSL-KDD dataset.

As a service business models have been ranked by management consultants the management innovation of 2020, and yet are scarcely theorized. Therein, value stipulations in customer contracts lead to the shift from product to service. However, there is no available research about the nature, formula and decisional process about these value stipulations. The motive for this research is to fill in this gap. The goal is to provide first insight about value stipulations in as a service business models: their formula and decisional methodology. The article is a multiple theory building case study on leading platform as a service providers, which aims to contruct the paradigm of the value decision methodology to invest in this technology by purchasing it from dedicated vendors. The methodology works to identify the management instruments involved in the decisional activities to invest in digital technology, where each management instrument is assumed to match an activity at seller and buyer; the sequence of the activities using the Critical Path Method gives the decisional process. Dependent variables are the elements of the as a service business contracts: the customer offering (product-service solution) and the value created, captured and delivered by the solution. Independent variables are given by empirical data analysis. Findings show a relationship between dependent variable value in the as a service business model contracts and independent variables governance objective, strategy, as a service business model type, activity management techniques (roadmap, program, project, operations, lean start-up), capital allocation techniques (equity, debt, options, venture capital typology). If innovation is exploitative, then the customer offering is known and value is determinable via roadmap – project management techniques (program, project, an operations) and capital allocation techniques for precictable environment, If innovation is radical, then the customer offering is not known and value is a target used to architect the solution via lean start-up innovation techniques funded by venture capital. The contribution is a new theoretical construct and deep insight into the practice of digital transformation considering all inherent issues.

Modern computational biology makes widespread use of mathematical models of biological systems, in particular systems of ordinary differential equations, as well as models of dynamic systems described in other formalisms, such as agent-based models. Parameters are numerical values of quantities reflecting certain properties of a modeled system and affecting model solu-tions. At the same time, depending on parameter values, different dynamic regimes - stationary, oscillatory, established as a result of transient modes of various types - can be implemented in the system. Predicting changes in the solution dynamics type depending on changes of model parameters is an important scientific task. Nevertheless, this problem does not have an analytical solution for all formalisms in a general case. The routinely used method of performing a series of computa-tional experiments, i.e. solving a series of direct problems with various sets of parameters fol-lowed by expert analysis of solution plots is labor-intensive with a large number of parameters and a decreasing step of the parametric grid. In this regard, the development of methods allow-ing to obtain and analyze information on a set of computational experiments in an aggregate form is relevant. This work is devoted to developing a method for visualization and classification of various dy-namic regimes of a model using a composition of the dynamic time warping (DTW-algorithm) and principal coordinates analysis (PCoA) methods. This method allows to obtain a qualitative visualisation of the results of the set of solutions of a mathematical model and to carry out the correspondence between the values of the model parameters and the type of dynamic regimes of its solutions. This method has been tested on the Lotka-Volterra model and artificial sets of var-ious dynamics

By analyzing the urban landscape, this investigation focuses on commercial typologies in historical urban areas and its relationship with the urban landscape and its heritage values. Trade plays an essential role in historical urban areas, both in the past and in the present, since it is part of the urban landscape—creating it and modifying it, but also preserving it. Historical protected urban areas contain diverse elements reflecting the impacts of commercial activities that have existed in cities throughout history. At present, the urban landscape of commercial activity is made up of a multiplicity of typologies and formats which interact with the historical landscape and its values, using them to strengthen its strategies of attraction, differentiation, and sales. Shop owners contribute to the preservation of historic urban areas by maintaining the commercial functions within them. Therefore, we affirm that the role of commercial activity in the preservation of urban protected areas is essential. However, further research is needed because this aspect has not been addressed in depth by the scientific community specializing in the management of cultural heritage.

It is documented that maternal diseases or treatments influence a newborn’s clinical status at birth; autoimmune diseases with circulating antibodies are often clinically expressed transiently in newborns due to the crossover of the specific IgG through the placenta during pregnancy. The offspring can inherit maternal genetic anomalies, but clinical expression usually becomes patent later in life. If prenatal medical history is not available or if signs or symptoms of a mother’s disease are revealed for the first time during pregnancy or postpartum, their effects on the newborn may be misattributed. In this article, we present three cases of pregnant women, without any known pathology before or during pregnancy, who gave birth to very sick preterm newborns that required admission to the Neonatal Intensive Care Unit (NICU). The neonates’ complications were considered initially as consequences of prematurity or infection, but later investigations revealed transient autoimmune disease in two of the cases (myasthenia gravis and hyperthyroidism) and a severe form of thrombophilia in the third case. In all cases, mothers were asymptomatic and unaware of their subclinical disease. Preemies’ diagnosis has contributed to the identification of their mothers’ pathology and adequate treatment was prescribed with favourable short- and long-term outcomes. In one of the cases (myasthenia gravis) both mother and child had associated infectious diseases in the perinatal period that complicated the clinical picture and created problems of diagnosis. This article intends to emphasize the paramount importance of prenatal care, for both mother and newborn. Repeated medical visits and investigations throughout the pregnancy are a good opportunity to detect subclinical diseases or predispositions. As newborns usually develop non-specific signs, one should have experience and pay attention to differentiate among etiologies. Our paper takes a reversed approach to the usual medical diagnosis pathway: from infant to mother instead of mother towards the infant, proving that inter-speciality collaboration can work bi-directionally.

The aim of the study was to determine the possibility of suppression of the prostaglandin synthesis by new derivatives of N-phenylanthranilic acids; they inhibit the activity of the microsomal prostaglandin E synthase-1 (mPGES-1) enzyme using the method of a flexible molecular docking. For the docking studies the crystallographic structural models with high resolution from Protein Data Bank were used: mPGES-1 in the complex with glutathione (pdb code 4AL0). A flexible molecular docking was carried out using the Molecular Operating Environment (MOE) software package. According to the results of the docking studies four scoring functions were calculated (Affinity dG Scoring, Alpha HB Scoring, London dG Scoring, GBVI/WSA dG Scoring). The values of the scoring functions calculated indicate the thermodynamic probability and energy favorability of forming complexes between molecules of the substances under research and the specified receptor, in which arrangement of ligands in the active site of the receptor and residues of amino acids of side chains are of similar geometry and types of binding of the known inhibitors of mPGES-1 determined on the basis of the crystallographic studies.

The energy sector plays an important role in Mexico’s development trajectory. Mexico makes an interesting case study, because it shows how difficult it is to reduce fossil energy dependence despite geographic and climatic conditions that favour renewable energy deployment and use. Resolving path dependencies and the related carbon lock-in are key to Mexico’s sustainable energy transition. This case study aims to identify and discuss how carbon lock-in affects Mexico’s sustainable energy transition. Mexico’s carbon lock-in involves oil and oil-run power plants that are costly to build but relatively inexpensive to operate. This case study identifies potential entry points for transitioning towards sustainable energy in Mexico – resources that can promote the use of clean energy despite carbon lock-in. For example, focusing on electrification – particularly of the carbon-intensive sectors – can help Mexico transit towards sustainable energy despite institutional constraints. Complementing this case study is a teaching guide with recommendations for using Mexico’s energy transition in courses on sustainability. It introduces a “learning activation framework” to identify emerging opportunities that can advance sustainable energy transitions in different cases of carbon lock-in. Finally, the framework also gives students a chance to help dismantle or cope with carbon lock-ins.

The lipid fraction of margarines and fast-food French-fries, two types of foods traditionally high in trans fatty acids (TFA), is assessed. TFA data reported worldwide during the last 20 years have been gathered, and show that some countries still report high TFA amounts in these products. The content of TFA was analysed in margarines (2 store and 4 premium brands) and French-fries from fast-food restaurants (5 chains). Margarines showed mean values of 0.68% and 0.43% (gTFA/100g fat) for store and premium brands, respectively. French-fries values ranged from 0.49% to 0.89%. All samples were lower than the 2% set by some European countries as the maximum legal content of TFA in fats, and contained less than 0.5g/serving, so they could also be considered “trans free products”. This work confirmed that the presence of TFA is not significant in the two analysed products and contributes to update food composition tables, key tools for epidemiological and nutrition studies.

Anonymous communications networks were born to protect the privacy of our communications, preventing censorship and traffic analysis. The most famous anonymous communication network is Tor. This anonymous communication network provides some interesting features, among them, we can mention user’s IP location or Tor Hidden Services (THS) as a mechanism to conceal the location of servers, mainly, web servers. THS is an important research field in Tor. However, there is a lack of reviews that sump up main findings and research challenges. In this article we present a systematic literature review that aims to offer a comprehensive view on the research made on Tor Hidden services presenting the state of the art and the different research challenges to be addressed. This review has been developed from a selection of 57 articles and present main findings and advances regarding Tor Hidden Services, limitations found, and future issues to be investigated.

This paper presents a novel improvement of MuSIASEM (Multiscale Integrated Analysis of the Societal and Ecological Metabolism) by incorporating a new regional analysis of the electricity metabolism across levels. An analysis of Mexico illustrates this toolkit and shows that the industry sector had Economic Energy Intensity (EEI) with 40.3 MWh/MMXN reached a higher value than the commerce and services sector with 0.84 MWh/MMXN. Regarding the Economic Labor Productivity (ELP) indicator (AV/h), the industrial sector with 208.5 TMXN/Kh reached a higher value than the Commercial and services sector with 114.3 TMXN/Kh. With reference to the Exosomatic Metabolic Rate (EMR), the Household sector obtained 59.3 KWh/Kh whereas the paid sector reached 2,486.4 KWh/Kh. Disaggregation of the EMR indicator into economic sectors shows that the Industrial sector obtained 8.4 KWh/Kh and the commercial and services sector reached 0.10 KWh/Kh. The lack of complete data for the agricultural sector does not allow us to calculate EEI, ELP, and EMR indicators accurately. Considering the analysis of indicators by regions, regarding the EEI rate, the Central region had the lowest value with 12.7 MWh/MMXN, followed by the Northeast with 21.4 MWh/MMXN and Western with 29.4 MWh/ MMXN, which means that they require less electricity to produce more added value. In terms of the ELP indicator, it was found regions with higher values were Northeast with 182.3 MMXN/Mh, Central with 177.5 MMXN/Mh, and North with 127 MMXN/Mh, which means that these regions produce more added value per hour of work. About the EMR, it is observed that regions in the northern part of the country had higher values: Northwest with 337 KWh/Kh, Baja California Sur with 334 KWh/Kh, Baja California with 328 KWh/Kh, North with 313 KWh/Kh and Northeast with 274 KWh/Kh, which means that these regions consume more electricity per hour. This innovative approach is useful for governance because it helps to understand and reduce asymmetries across regions, resulting in more social equality and a better economic equilibrium across sectors and regions.

Cellular senescence is a permanent condition of cell cycle arrest caused by a progressive shorten-ing of telomeres defined as replicative senescence. Stem cells may also undergo an accelerated se-nescence response, distinct from telomere shortening, known as premature senescence as a re-sponse to different stress agents. Various treatment protocols have been developed based on epi-genetic changes in cells throughout senescence, using different drugs and antioxidants, senolytic vaccines, or reprogramming of somatic senescent cells using Yamanaka factors. Even with all the recent advancements, it is still unknown how different epigenetic modifications interact with ge-netic profile and how other factors such as microbiota physiological conditions, psychological states and diet influence the interaction between genetic and epigenetic pathways. The aim of this review is to highlight the new epigenetic modifications that are involved in stem cell senescence. Here, we review recent senescence-related epigenetic alterations such as DNA methylation, chro-matin remodeling, histone modification, RNA modification, and non-coding RNA regulation outlining new possible targets for therapy of aging-related diseases. The advantages and disad-vantages of the animal models used in the study of cellular senescence are also briefly presented.

Currently, large cell neuroendocrine carcinoma of the lung (LCNEC) is classified as a rare lung cancer subtype, but given the high incidence of lung cancer, the overall number of cases is considerable. The pathologic diagnosis is based on the microscopic appearance of the tumor cells, the amount of intra-tumoral necrosis, the mitotic rate, and the presence of positive neuroendocrine markers identified by immunohistochemistry. Recently, a subdivision into two main categories was proposed based on mutation signatures involving the RB1, TP53, KRAS, and STK11/LKB1 genes, into SCLC-like (small cell lung cancer-like) and NSCLC-like (non-small cell lung cancer-like) LCNEC. In terms of treatment, surgery remains the best option for resectable, stage I–IIIA cases. Chemotherapy and radiotherapy have conflicting evidence. Etoposide/platinum remains the standard chemotherapy regimen. However, based on the newly proposed LCNEC subtypes, some retrospective series report better outcomes using a pathology-driven chemotherapy approach. Encouraging outcomes have also been reported for immunotherapy and targeted therapy, but the real impact of these strategies is still being determined in the absence of adequate prospective clinical trials. The current paper scrutinizes the epidemiology, reviews the reliability of pathologic diagnosis, discusses the need for molecular subtyping, and reviews the heterogeneity of treatment algorithms in LCNEC.

Breast cancer (BC) is the most common cancer diagnosed in women worldwide. Approximately 70% of BC patients have the luminal subtype, which expresses hormone receptors (HR+). Adjuvant endocrine treatments are the standard of care for HR+/HER2- BC patients. Over time, approximately 30% of those patients develop endocrine resistance and metastatic disease. Cyclin-dependent kinase inhibitors (CDKi) in combination with an aromatase inhibitor or fulvestrant have demonstrated superior efficacies in increasing progression-free survival, with a safe toxicity profile, in HR+/HER2- metastatic BC patients. CDKi blocks kinases 4/6, preventing G1/S cell cycle transition. However, not all patients respond to CDKi, and those who do respond ultimately develop resistance to the combined therapy. Studies in tumour tissues and cell lines have tried to elucidate the mechanisms underlying this progression, but there are still no conclusive data. Over the last few years, liquid biopsy has contributed relevant information. Circulating tumour materials are potential prognostic markers for determining patient prognosis in metastatic luminal BC, for monitoring disease and for treatment selection. This review outlines the different studies performed using liquid biopsy in patients with HR+ metastatic BC treated with CDKi plus endocrine therapy. We focus mainly on those studies that describe possible resistance mechanisms in circulating tumour-derived material.

Breast cancer is the most commonly diagnosed cancer in women worldwide. Approximately, 70 % of breast cancer patients express hormone receptors (HR) (Luminal subtype). Adjuvant endocrine treatments are the standard of care in HR+/HER2- breast cancer. Over time, about 50% of those patients develop endocrine resistance and metastatic breast cancer. Cyclin-dependent kinase inhibitors (CDKi) in combination with an aromatase inhibitor or fulvestrant have demonstrated superior efficacy increasing progression-free survival, with a safe toxicity profile, in HR+/HER2- metastatic breast cancer patients. CDKi blocks kinases 4/6 ATP-binding domain preventing G1/S cell cycle transition. Despite this, not all patients respond to CDKi and those who respond, finally develop resistance to combination therapy. Different studies, in tumour tissue or cell lines, have tried to elucidate the mechanisms underlying this progression, but there are still no conclusive data. In the last few years, liquid biopsy has contributed relevant information to this knowledge. Liquid biopsy can be performed in real-time, non-invasively and be repeated whenever needed. Circulating tumour material are potential prognostic markers in metastatic luminal breast cancer to determine patient prognosis, monitor disease and treatment selection. The objective of this review is to outline the different studies carried out in HR+ metastatic breast cancer patients treated with CDKi plus endocrine therapy using liquid biopsy approaches looking for possible resistance mechanisms.

Enophthalmos is a severe complication of primary reconstruction following orbital floor frac-tures, oncological resections or maxillo-facial syndromes. The goal of secondary reconstruction is to re-store symmetrical globe positions to recover function and aesthetics. In this article we pre-sent a method of computer-assisted orbital floor reconstruction using a mirroring technique and a customized titanium or high-density polyethylene mesh, printed using computer aided manufac-turing techniques. This reconstructive protocol involves 4 steps: mirroring of the healthy orbit at the affected site, vir-tual design of a patient specific orbital floor mesh, computer-assisted manufacturing (CAD) of the implant, and surgical insertion of the device. Using a computed tomography data set, the un-injured side of the craniofacial skeleton was reflected onto the contralateral injured side, and a reconstructive orbital floor prosthesis was virtually designed on the mirrored orbital bone sur-face. The solid-to-layer (.STL) files of the prosthesis were then manufactured using Direct Metal Laser Sintering (DMLS) or Computer Numerical Control (CNC) methods, leading to the produc-tion of 10 titanium meshes and 2 high density polyethylene (HDPE) implants. Clinical outcomes were assessed using 3dMD photogrammetry and computed tomography measures in 14 treated patients. The technique described here appears to be a viable method to correct complex orbital floor de-fects needing delayed reconstruction. This article represents the prosecution of a previous study, which is part of a wider experimental protocol for orbital floor reconstruction using comput-er-assisted design-computer-assisted manufacturing (CAD-CAM) technology

Background and aims: Only one cohort study exists on the incidence of the risk of malnutrition (RM) in older adults, though numerous cross-sectional –and that cohort research– have reported several risk factors associated with the prevalence and incidence of this condition. However, alterations of body composition and impaired physical performance as exposition variables of RM have not been explored. This study assessed the incidence of RM and determined its association with excess fat mass, low total lean tissue, gait speed, and handgrip strength as exposition variables for RM in community-dwelling older adults. Methods: This is a secondary analysis in older adults (≥60 years old) derived from the study “Frailty, dynapenia, and sarcopenia in Mexican adults (FraDySMex)” a prospective cohort project conducted from 2014 to 2019 in Mexico City. At baseline, volunteers underwent body composition analysis and physical performance tests. Several covariates were identified through comprehensive geriatric assessment. At baseline and follow-up, RM was assessed using the long form of the mini nutritional assessment (MNA-LF) scale. Associations between the exposition variables and RM were assessed by multiple logistic regression. Results: The cohort included 241 subjects. Average age was 75.6±7.8 years; 83.4% were women. The mean follow-up period was 4.1 years, during which 28.6% of subjects developed RM. This condition was less likely to occur in subjects with excess fat mass index, even after adjusting for several covariates. RM was also more likely to occur in subjects with low total lean tissue index, according to both an unadjusted model and after adjusting for the corresponding variables. Regarding the association between RM and gait speed, RM was also more likely to occur in subjects with low gait speed according to both the unadjusted and adjusted models. Similar results were found for RM in relation to low handgrip strength; however, after adjusting for the associated covariates, models 1 and 2 no longer reached the level of significance. Conclusion: The risk of malnutrition diagnosed by MNA-LF was significantly less likely to occur among subjects with excess fat mass, but possibility was significantly higher in those with low total lean tissue and low gait speed after 4.1 years of follow-up in community-dwelling older adults. These results highlight that excess fat mass, low total lean tissue, and low gait speed are first than risk of malnutrition and not vice versa.

The goal of this study is both to determine the opinion that professors and students at the University of (details removed for peer review) have of active methodologies and to describe the perception and opinion of the modes of organization, methodological focuses, and evaluation systems that define the teaching-learning process. On surveying the professors and the students in their classes, we found significant differences in 32 of the 92 variables in common. The content of these results shows that professors and students are believe they are making progress toward a learning-centered model, that implementation of active methodologies implies new functions in their teaching practice.

Mandibular third molar is the most frequently impacted tooth. Mandibular third molar impaction bears consequences on the adjacent mandibular second molar (MSM) like bone loss. It can be identified initially using orthopantomography (OPG). The objective is to compare the changes in the bone level distal to MSM between patients with extracted and non-extracted impacted man-dibular third molars (IMTM) using OPG. In this retrospective case-control study, 160 archived (OPGs) of 80 patients visiting the Dental Hospital of the University of Barcelona (HOUB) were randomly selected. The participants were stratified into two groups. The study group involved measuring the bone level distal to the mandibular second molar before and after the extraction of the IMTM. The control group, on the other hand, had bone levels measured twice within 3–6-month period without the extraction of the IMTM. The mean ages of patients in study and control groups were 35.5 ± 15.45 and 33 ± 16.49, respectively. Study group demonstrated signifi-cant (p < 0.05) bone gain after extraction, whereas control group demonstrated significant bone loss (p < 0.0001) after follow-up. Bone improvements were observed distal to the mandibular second molar after the extraction of the IMTM compared to those in control group.

Parental stresses are normal responses to raising children. They are affected by stresses parents and children accumulate and bring to their interrelations. Background factors like economic difficulties or the relations between the parents may affect parental stresses as well as demographic and environmental factors like noise and access to urban parks. Most studies on parental stress are based on a verified psychological questionnaire. We suggest using frequency domain heart rate variability index (HRV) to measure parental stress enabling, by thus, the measurement of physiological aspects of stress and risk to health. Parental stress is measured as the difference between HRV accumulated at home while staying with the children and without the husband and HRV measured in the neighborhood while staying without the children and the husband. We use the index to compare differences among Muslim and Jewish mothers in exposure to maternal stress at their homes and to expose the factors that predict differences in maternal stress. We found that Muslim mothers suffer from home-related maternal stress while Jewish mother do not. Number of children and ethnically related environmental aspects predict differences in maternal stress between Muslim and Jewish mothers. Muslims' lower access to parks stems from lack of home garden and parks in their neighborhoods in the Arab towns but mainly by restrictions on Muslim women's' freedom of movement to parks. Despite differences in levels of noise at home and in the status of the mother in the household, these factors did not predict differences in parental stress. Instead, the study highlights the crucial role of greenery and freedom of movement to parks in moderating home-related maternal stress.

The analysis of curated genomic, metagenomic, and proteomic data are of paramount importance in the fields of biology, medicine, education, and bioinformatics. Although this type of data is usually hosted in raw form in free international repositories, its access requires plenty of computing, storage, and processing capacities for the domestic user. The purpose of the study is to offer a comprehensive set of genomic and proteomic reference data, in an accessible and easy-to-use form to the scientific community. A representative type material set of genomes, proteomes and metagenomes were directly downloaded from the site: https://www.ncbi.nlm.nih.gov/assembly/ and from Genome Taxonomy Database, associated with the major groups of Bacteria, Archaea, Virus, and Fungi. Sketched databases were subsequently created and stored on handy raw reduced representations, by using Mash software. Our dataset contains near to 100 GB of space disk reduced to 585.78 MB and represents 87,476 genomics/proteomic records from eight informative contexts, which have been prefiltered to make them accessible, usable, and user-friendly with computational resources. Potential uses of this dataset include but are not limited to, microbial species delimitation, estimation of genomic distances, genomic novelties, paired comparisons between proteomes, genomes, and metagenomes.

An economic and business history approach is used to show the rise and relative failure of the Spanish wind industry during the period between 2004-2015, when Spain became the fourth country after China, the US and Germany in installed capacity of renewable energies and, in relative terms, the second country after Denmark. This study is unique in that it provides an integrated vision of the reasons for the relative fall of Spain in the world ranking of wind energy producers. The methodology of the economic analysis of industrial policies makes it possible to explain the fall in the relative importance of Spain in the international panorama of wind farms. There were no reasons related to technological obsolescence or inability of the CECRE managing renewable energies to explain the fall.

This review aims to explore the intricate relationship between epigenetic mechanisms, stress, and affective disorders, focusing on how early life experiences and coping mechanisms contribute to susceptibility to mood disorders. Epigenetic factors play a crucial role in regulating gene expression without altering the DNA (deoxyribonucleic acid) sequence, and recent research has revealed associations between epigenetic changes and maladaptive responses to stress or psychiatric disorders. A scoping review of 33 studies employing the PRISMA-S (Preferred Reporting Items for Systematic Reviews and Meta-Analyses – Statement) guidelines investigates the role of stress-induced epigenetic mechanisms and coping strategies in affective disorders' occurrence, development, and progression. The analysis encompasses various stress factors, including childhood trauma, work-related stress, and dietary deficiencies, alongside epigenetic changes such as DNA methylation and altered gene expression. Findings indicate that specific stress-related genes frequently exhibit epigenetic changes associated with affective disorders. Moreover, the review examines coping mechanisms in patients with bipolar disorder and major depressive disorder, revealing mixed associations between coping strategies and symptom severity. While active coping is correlated with better outcomes, emotion-focused coping may exacerbate depressive or manic episodes. Overall, this review underscores the complex interplay between genetic predisposition, environmental stressors, coping mechanisms, and affective disorders. Understanding these interactions is essential for developing targeted interventions and personalized treatment strategies for individuals with mood disorders. However, further research is needed to elucidate specific genomic loci involved in affective disorders and the clinical implications of coping strategies in therapeutic settings.

The aim of this study was to evaluate the biomechanical changes of the cornea after wearing soft contact lenses (CLs) in healthy myopic patients measured with the Corvis ST® analyzer. This prospective, cross-sectional, single-center study was performed in twenty-two Caucasian patients aged between 19 and 24 years (20.64 ± 1.21 years) range). Five device-specific biomechanical parameters, central corneal thickness and intraocular pressure were measured prior to fitting and one month after CLs wear. Differences between the means of the DA Ratio and the standard deviation of the DA Ratio pre- and post-CLs wear were found to be significant (p value=0.002 in both cases). Significant differences were found between pre- and post-CLs wear values in CCT (p value=0.013). For all other biomechanical measures, no significant differences were observed before and after treatment. A significant association was found between changes in bIOP and classification according to changes in Int. Radius (p value = 0.047) and SSI (p value = 0.026) standard deviations. The corneal biomechanical indices provided by CST demonstrate that fitting of soft CLs is a safe optical compensation method for the stability of corneal stiffness. No significant differences were found pre- and post-CLs wear in the assessment of bIOP.

We show that loophole-free Bell-type no-go theorems cannot be derived in theories involving local hidden fields. At the time of measurement, a contextuality loophole appears because each particle’s electromagnetic field interacts with the field of its respective apparatus, preventing the expression of the probability density as a function independent of the orientation of the measuring devices. Then, we use the dynamical evolution of the probability distribution to show that the spin-correlation integral can neither be expressed in terms of initial Cauchy data restricted to the particles. A correlation loophole ensues, which prevents the usage of the non-contextual correlation integrals required to demonstrate the CHSH-Bell inequality. We obtain a new inequality not violated by quantum correlation functions of entangled spin pairs, and propose that Maxwell’s electrodynamic field is the missing hidden variable triggering the coupled nonlinear oscillations of the particles, which bring about the synchronicities observed in the Einstein-Podolsky-Rosen-Bohm (EPRB) experiment.

The present is a study of the CFD simulations intended to simulate the emissions of pollutants that are generated after the combustion of proposed alternative aircraft fuels (Hydrogen, Ethanol and Methane) to compare with the emissions generated after the combustion of Kerosene and Benzene in a 2D cylindrical combustion chamber. Given that air traffic is a main contributor to not only 3% of man-made greenhouse effects but also of the generation of smog over heavy air traffic urban areas generating an impact on the air quality and the population of those areas.

This essay studies Afro-Asian sociocultural interactions in cultural production by or about Asian Latin Americans, with an emphasis on Cuba and Brazil. Among the recurrent characters are the black slave, the china mulata, or the black ally who expresses sympathy or even marries the Asian character. This reflects a common history of bondage shared by black slaves, Chinese coolies, and Japanese indentured workers, as well as a common history of marronage. These conflicts and alliances between Asians and blacks contest the official discourse of mestizaje (Spanish-indigenous dichotomies in Mexico and Andean countries, for example, or black and white binaries in Brazil and the Caribbean), which, under the guise of incorporating the Other, favored whiteness, all the while attempting to silence, ignore, or ultimately erase their worldviews and cultures.

This article aims to approach the Mudejar architecture developed in Mexico during the 16th and 17th centuries. The subject has been little studied although both general and specific contributions have been made by the author’s research group. At the methodological level, this study is based on the existing bibliography as well as archive and field research which allow an accurate scientific approach and results. The article analyses the social and productive conditions in Mexico during the Viceregal period along with the systematization carried by the Viceroy Antonio de Mendoza, the guild ordinances and the architectural typologies. The perception of territory and the use of constructive models by the Viceregal authorities would justify the use of the Mudejar style as cultural and unity criteria

All cancer registries constantly show striking differences in cancer incidence by age and among tissues. For example, lung cancer is diagnosed hundreds of times more often at age 70 than at age 20, and this cancer in nonsmokers occurs thousands of times more frequently than heart cancer in smokers. An analysis of these differences using basic concepts in cell biology indicates that cancer is the end-result of the accumulation of cell divisions in stem cells. In other words, the main determinant of carcinogenesis is the number of cell divisions that the DNA of a stem cell has accumulated in any type of cell from the zygote. Cell division, process by which a cell copies and separates its cellular components to finally split into two cells, is necessary to produce the large number of cells required for living. However, cell division can lead to a variety of cancer-promoting errors, such as mutations occurring during DNA replication, chromosome aberrations arising during mitosis, errors in the distribution of cell-fate determinants between the daughter cells, and failures to restore physical interactions with other tissue components. Some of these errors are spontaneous, others are promoted by endogenous DNA damage occurring during quiescence, and others are influenced by pathological and environmental factors. The cell divisions required for carcinogenesis are primarily caused by multiple local and systemic physiological signals rather than by errors in the DNA of the cells. As carcinogenesis progresses, the accumulation of DNA errors promotes cell division and eventually triggers cell division under permissive extracellular environments. The accumulation of cell divisions in stem cells drives not only the accumulation of the DNA alterations required for carcinogenesis, but also the formation and growth of the abnormal cell populations that characterize the disease. This model of carcinogenesis provides a new framework for understanding the disease and has important implications for cancer prevention and therapy.

Synthesis of nickel oxide nanoparticles (NiO NPs) is a low cost and ecofriendly route that brings great benefits over chemical and physical methods of synthesis. Our approach consisted of using aqueous extracts from treated waste of Manihot Esculenta (Cassava) as reducing, stabilizing and capping agents for the synthesis of NiO NPs. The results proved this approach might be a viable alternative. Extracts were mixed during 30 minutes with Ni(NO3)2.6H2O leading to NPs formation. NiO NPs were characterized through FTIR, XRD, TEM and Raman spectroscopy. NiO NPs showed different shapes and sizes around 5-10 nm in agreement with the particle size calculated by XRD Scherrer equation.

The behaviour of the pseudo-protic ionic liquids TOAH+Cl- and TODAH+Cl- in the facilitated transport of indium(III) from HCl solutions is described. Metal transport is investigated as a function of different variables: hydrodynamic conditions, HCl concentration in the feed phase and indium and carrier concentrations. The experimental data are used to model both transport systems and to estimate diffusional parameters associated to them.

This study delves into the complex interplay among attachment styles, hypersexuality, and sexual and couple satisfaction in emerging adults within the Mexican population. Despite established correlations between anxious and avoidant attachment styles and emotion dysregulation and hypersexuality, the roles of sexual and couple satisfaction in this context have remained relatively unexplored. This study aims to fill this gap by examining how these variables interact and contribute to psychological distress and sexual risk behaviors. Data analysis on 214 emerging adults, utilizing the Experiences in Close Relationships scale, Couple Satisfaction Index, Sexual Satisfaction Scale, SCL-90, and SAST-R, revealed a significant association between risky sexual behaviors—such as a higher number of sexual partners, drug and alcohol use during sexual activity, and lack of sexual protection—and heightened levels of hypersexuality. Notably, individuals with hypersexual tendencies reported diminished levels of sexual satisfaction but elevated levels of couple satisfaction. Avoidant attachment emerged as the attachment style most strongly correlated with early sexual experiences. Moreover, the abbreviated versions of the Couple Satisfaction Index (CSI-4) and the Experiences in Close Relationships scale (ECR-8) exhibited commendable psychometric properties, enhancing their applicability for research and clinical purposes. This research furnishes valuable insights into the complex dynamics among attachment styles, hypersexuality, and couple and sexual satisfaction, emphasizing the need for targeted interventions to foster healthier sexual and relationship behaviors among emerging adults.

Glioblastoma is a central nervous system cancer type with a poor prognosis. One of its main features is the constant change of metabolism phenotype to support its development and progression. Mitochondria play a critical role in cellular metabolism. Acetylation on lysine residues of mitochondrial enzymes is a mechanism for regulating protein function. This modification negatively affects the mitochondrial proteome function and is counteracted by the enzyme sirtuin 3 (SIRT3). To better understand how SIRT3 regulates mitochondrial metabolism, we inhibited SIRT3 and examined by high-resolution mass spectrometry analysis the proteome and acetylome of two glioblastoma cell lines with different metabolic preferences. Our results indicate that protein synthesis machinery is regulated by lysine acetylation and plays a role in the metabolic phenotype. We also identified new SIRT3 targets not previously associated with specific functions, highlighting their potential as future targets for further study. This study shed light on the role of SIRT3 in mitochondria and its implication for cellular metabolism. We have generated knowledge at the proteome and acetylome levels on the dynamics between two glioblastoma cell lines with opposing metabolic phenotypes. Our results might guide in searching for biomarkers at both proteome and acetylome levels in glioblastoma.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has become an effective and widely used tool in the treatment of Parkinson’s disease (PD). STN-DBS has varied effects on speech. Clinical speech ratings suggest worsening following STN-DBS, but quantitative intelligibility, perceptual, and acoustic studies have produced mixed and inconsistent results. Improvements in phonation and declines in articulation have frequently been reported during different speech tasks under different stimulation conditions. Questions remain about preferred STN-DBS stimulation settings. Seven right-handed, native speakers of English with PD treated with bilateral STN-DBS were studied off medication at three stimulation conditions: stimulators off, 60 Hz (low frequency stimulation - LFS), and the typical clinical setting of 185 Hz (High frequency - HFS). Spontaneous speech was recorded in each condition and excerpts were prepared for transcription (intelligibility) and difficulty judgements. Separate excerpts were prepared for listeners to rate abnormalities in voice, articulation, fluency, and rate. Intelligibility for spontaneous speech was reduced at both HFS and LFS when compared to STN-DBS off. Speech produced at HFS was more intelligible than that produced at LFS, but HFS made the intelligibility task (transcription) subjectively more difficult. Both voice quality and articulation were judged to be more abnormal with STN-DBS on. STN-DBS reduced the intelligibility of spontaneous speech at both LFS and HFS but lowering the frequency did not improve intelligibility. Voice quality ratings with STN-DBS were correlated with the ratings made without stimulation. This was not true for articulation ratings. STN-DBS exacerbated an existing voice disorder and may have introduced new articulatory abnormalities.

Autoimmune blistering diseases represent a group of chronic severe, disabling, potentially fatal disorders of the skin and/or mucous membranes primarily mediated by pathogenic auto-antibodies. Despite their rarity, these diseases are associated with significant morbidity and mortality, a profound negative impact on the patient’s quality of life and impose a considerable economic burden. Rituximab, an anti CD-20 monoclonal antibody represents the first line of therapy for pemphigus, regardless of its severity as it ensures high rates of rapid, long-lasting complete remission. Nevertheless, disease recurrence is the rule, all patients requiring maintenance therapy with rituximab sooner or later. While innate resistance to rituximab in pemphigus patients is exceptional, acquired resistance is frequent and may develop even in patients with initial complete response to rituximab, representing a real challenge for physicians. We discuss the various resistance mechanisms and their complex interplay, as well as the numerous therapeutic alternatives that may be used to circumvent rituximab resistance. As no therapeutic measure is universally efficient, individualization of rituximab treatment regimen and tailored adjuvant therapies in refractory pemphigus cases are mandatory.

A large diversity of epigenetic factors, such as microRNAs and histones modifications, are known to be capable of regulating gene expression without altering DNA sequence itself. In particular, miR-1 is considered the first essential microRNA in cardiac development. In this study, miR-1 potential role in early cardiac chamber differentiation is analyzed through specific signaling pathways. For this, we performed in chick embryos functional experiments by means of miR-1 microinjections into the posterior cardiac precursors -of both primitive endocardial tubes- committed to sinoatrial region fates. Subsequently, embryos were subjected to whole mount in situ hybridization, immunohistochemistry and RT-qPCR analysis. As a relevant nov-elty, our results revealed that miR-1 increases Tbx5, Gata4 and AMHC1, while this microRNA diminishes Mef2c expression, during early differentiation of cardiac sinoatrial region. Further-more, we observed in this developmental context that miR-1 upregulates CRABPII and RARß, and downregulates CRABPI, which are three crucial factors in retinoic acid signaling pathway. Interestingly, we also noticed that miR-1 directly interacts with HDAC4 and Calmodulin, as well as with Erk2/MAPK1, which are three key factors actively involved in Mef2c regulation. Our study shows, for the first time, a key role of miR-1 as an epigenetic regulator in early differenti-ation of cardiac sinoatrial region through orchestrating opposite actions between retinoic acid and Mef2c, fundamental to properly assign cardiac cells to their respective heart chambers. A better understanding of those molecular mechanisms modulated by miR-1 will definitely help in fields applied to therapy and cardiac regeneration and repair.

The origin of cancer remains one of the most important enigmas in modern biology. This paper presents a hypothesis for the origin of carcinomas in which cellular aging and inflammation enable the recovery of cellular plasticity that may ultimately result in cancer. The process is described as the result of dedifferentiation undergone by epithelial cells in hyperplasia due to replicative senescence towards a mesenchymal cell state with potential cancerous behavior. In support of the hypothesis, the molecular, cellular, and histopathological evidence was critically reviewed and reinterpreted when necessary to postulate a plausible generic model for the origin and progression of carcinomas. In addition, the implications of this theoretical framework for the current strategies of cancer treatment are discussed against recent evidence of the molecular events underlying the epigenetic switches involved in the resistance of breast carcinomas. Subsequently, is proposed an epigenetic landscape for their progression and a potential mechanism to restrain the degree of dedifferentiation and malignant behavior. Finally, is suggested a novel understanding of the involution and carcinogenesis of tissues associated with aging as a perspective that might inspire integrative approaches in the study and management of chronic diseases.

Veganism and the interest towards a plant-based diet are experiencing exponential growth worldwide, and in Italy more and more individuals and families are adopting this lifestyle and diet, too.Such a change in eating habits also imperatively implies the support and expertise of medical and health care professionals, who to date are still often unprepared and skeptical about this dietary pattern, despite scientific evidence.

Currently, skin cancer is the most commonly diagnosed form of cancer in humans and is one of the leading causes of death in patients with cancer. Biopsy methods are an invasive research method and are not always available for primary diagnosis. Imaging methods have low accuracy and depend on the experience of the dermatologist. Artificial intelligence technologies can match and surpass visual analysis methods in accuracy, but they have the risk of a false negative response when a malignant pigmented lesion can be recognized as benign. One possible way to improve accuracy and reduce the risk of false negatives is to analyze heterogeneous data, combine different preprocessing methods, and use modified loss functions to eliminate the negative impact of unbalanced dermatological data. The paper proposes a multimodal neural network system with a modified cross-entropy loss function that is sensitive to unbalanced heterogeneous dermatological data. The accuracy of recognition in 10 diagnostically significant categories for the proposed system was 85.19%. The novelty of the proposed system lies in the use of cross-entropy loss when training the modified function with the help of weight coefficients. The introduction of weighting factors has reduced the number of false negative forecasts, as well as improved accuracy by 1.02-4.03 percentage points compared to the original multimodal systems. The introduction of the proposed multimodal system as an auxiliary diagnostic tool can reduce the consumption of financial and labor resources involved in the medical industry, as well as increase the chance of early detection of skin cancer.

The Medi-test system we developed was motivated by the large number of resources available for the medical domain, as well as the number of tests needed in this field (during and after the medical school) for evaluation, promotion, certification, etc. Generating questions to support learning and user interactivity has been an interesting and dynamic topic in NLP since the availability of e-book curricula and e-learning platforms. Current e-learning platforms offer increased support for student evaluation, with an emphasis in exploiting automation in both test generation and evaluation. In this context, our system is able to evaluate a student’s academic performance for the medical domain. Using as input medical reference texts and supported by a specially designed medical ontology, Medi-test generates different types of questionnaires for Romanian language. The evaluation includes 4 types of questions (multiple-choice, fill in the blanks, true/false and match), can have customizable length and difficulty and can be automatically graded. A recent extension of our system also allows for the generation of tests which include images. We evaluated our system with a local testing team, but also with a set of medicine students, and user satisfaction questionnaires showed that the system can be used to enhance learning.