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In the context of Artificial Intelligence, Generative Adversarial Nets (GANs) allow the creation and reproduction of artificial data from real datasets. The aims of this work are to seek to verify the equivalence of synthetic data with real data and to verify the possibilities of GAN in educational research. The research methodology begins with the creation of a survey that collects data related to the self-perceptions of university teachers regarding their digital competence and technological-pedagogical knowledge of the content (TPACK model). Once the original dataset is generated, twenty-nine different synthetic samples are created (with an increasing N) using the COPULA-GAN procedure. Finally, a two-stage cluster analysis is applied to verify the interchangeability of the synthetic samples with the original, in addition to extracting descriptive data of the distribution characteristics, thereby checking the similarity of the qualitative results. In the results, qualitatively very similar cluster structures have been obtained in the 150 tests carried out, with a clear tendency to identify three types of teaching profiles, based on their level of technical-pedagogical knowledge of the content. It is concluded that the use of synthetic samples is an interesting way of improving data quality, both for security and anonymization and for increasing sample sizes.

Introduction Determining aetiology of severe illness can be difficult, especially in settings with limited diagnostic resources, yet critical for providing life-saving care. Our objective was to describe the accuracy of antemortem clinical diagnoses in young children in high-mortality settings, compared with results of specific postmortem diagnoses obtained from Child Health and Mortality Prevention Surveillance (CHAMPS).Methods We analysed data collected during 2016–2022 from seven sites in Africa and South Asia. We compared antemortem clinical diagnoses from clinical records to a reference standard of postmortem diagnoses determined by expert panels at each site who reviewed the results of histopathological and microbiological testing of tissue, blood, and cerebrospinal fluid. We calculated test characteristics and 95% CIs of antemortem clinical diagnostic accuracy for the 10 most common causes of death. We classified diagnostic discrepancies as major and minor, per Goldman criteria later modified by Battle.Results CHAMPS enrolled 1454 deceased young children aged 1–59 months during the study period; 881 had available clinical records and were analysed. The median age at death was 11 months (IQR 4–21 months) and 47.3% (n=417) were female. We identified a clinicopathological discrepancy in 39.5% (n=348) of deaths; 82.3% of diagnostic errors were major. The sensitivity of clinician antemortem diagnosis ranged from 26% (95% CI 14.6% to 40.3%) for non-infectious respiratory diseases (eg, aspiration pneumonia, interstitial lung disease, etc) to 82.2% (95% CI 72.7% to 89.5%) for diarrhoeal diseases. Antemortem clinical diagnostic specificity ranged from 75.2% (95% CI 72.1% to 78.2%) for diarrhoeal diseases to 99.0% (95% CI 98.1% to 99.6%) for HIV.Conclusions Antemortem clinical diagnostic errors were common for young children who died in areas with high childhood mortality rates. To further reduce childhood mortality in resource-limited settings, there is an urgent need to improve antemortem diagnostic capability through advances in the availability of diagnostic testing and clinical skills.

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

Summary: Palaeoproteomic analysis of skeletal proteomes is used to provide taxonomic identifications for an increasing number of archaeological specimens. The success rate depends on a range of taphonomic factors and differences in the extraction protocols employed. By analyzing 12 archaeological bone specimens from two archaeological sites, we demonstrate that reducing digestion duration from 18 to 3 hours has no measurable impact on the obtained taxonomic identifications. Peptide marker recovery, COL1 sequence coverage, or proteome complexity are also not significantly impacted. Although we observe minor differences in sequence coverage and glutamine deamidation, these are not consistent across our dataset. A 6-fold reduction in digestion time reduces electricity consumption, and therefore CO2 emission intensities. We furthermore demonstrate that working in 96-well plates further reduces electricity consumption by 60%, in comparison to individual microtubes. Reducing digestion time therefore has no impact on the taxonomic identifications, while reducing the environmental impact of palaeoproteomic projects.

Leishmaniasis and Chagas disease are parasitic infections that affect millions of people worldwide, producing thousands of deaths per year. The current treatments against these pathologies are not totally effective and produce some side effects in the patients. Acrylonitrile derivatives are a group of compounds that have shown activity against these two diseases. In this work, four novels synthetic acrylonitriles were evaluated against the intracellular form and extracellular forms of L. amazonensis and T. cruzi. The compounds 2 and 3 demonstrate to have good selectivity indexes against both parasites, specifically the compound 3 against the amastigote form (SI = 6 against L. amazonensis and SI = 7.4 against T. cruzi). In addition, the parasites treated with these two compounds demonstrate to produce a programmed cell death, since they were positive for the events studied related to this type of death, including chromatin condensation, accumulation of reactive oxygen species and alteration of the mitochondrial membrane potential. In conclusion, this work confirms that acrylonitriles is a source of possible new compounds against kinetoplastids, however, more studies are needed to corroborate this activity.

Chagas disease is caused by a protozoan parasite called Trypanosoma cruzi. The infection produces a first clinical phase, commonly asymptomatic or showing non-specific symptoms, and a second chronic phase characterized by cardiac and digestive dysfunctions in some individuals with the disease. This disease affects 7 million people and has been categorized by the World Health Organisation as a neglected tropical disease. In addition, the drugs used to combat it were developed in the 1970s and present major toxicity problems and limited efficacy in the chronicity of the disease. This has led to research into new active compounds that are effective against the disease, with studies on cyanoderivatives showing promising activity. In this work, eight active E-cyanoacrylamides/5-imino pyrrolones were studied. Compounds B and F showed excellent activity, while compounds C and G stood out for their lower cytotoxicity. After correlating the activity and cytotoxicity of the compounds, it was observed that compounds B, C, and G obtained the most favourable results. Various cell death studies were carried out with these compounds, and it was determined that all of them produced programmed cell death, with compound B standing out as being at a late stage in the process.

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

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

Thin films of transition metal oxides and oxynitrides have proven highly effective in protecting stainless steels against corrosion in both chemically aggressive environments and biological fluids. In the present work, cerium zirconium oxynitride thin films were deposited to enhance the corrosion resistance of surgical-grade stainless steel to be used in osteosynthesis processes. Two techniques were employed: co-sputtering and radiofrequency (RF) sputtering, and the morphology and corrosion efficiency of the coatings deposited by each technique were evaluated. X-ray diffraction, X-ray photoelectron spectroscopy and field emission transmission electron microscopy were used to characterize the morphological and chemical structure, respectively. Additionally, the corrosion resistance of the oxynitride-coated surgical grade stainless steel system (ZrCeOxNy-AISI 316L) was assessed using Hank’s solution as the corrosive electrolyte, to determine its resistance to corrosion in biological media. The results show that ZrCeOxNy coatings increase the corrosion resistance of surgical grade stainless steel by two orders of magnitude and that the Ce(III)/Ce(IV) equilibrium decreases the corrosion rate, thereby increasing the durability of the steel in a biological environment. The results show that Ce coatings increase the corrosion resistance of surgical grade stainless steel by two orders of magnitude and that the Ce(III)/Ce(IV) equilibrium decreases the corrosion rate, thereby increasing the durability of the steel in a biological environment.

Although time use is one of people’s most important resources, there are social forces and inequalities that shape how time is used. The aim of this research is to examine gender differences in time use from adolescence to old age and to analyze the association of such use with sociodemographic characteristics and with women’s and men’s health and well-being. A cross-sectional study was conducted with a sample of 5700 women (54.2%) and men (45.8%) from the Spanish general population, aged 14 to 85 years. Participants were assessed using five self-reported measures of time use, health, mental symptoms, psychological well-being, life satisfaction, social support, and masculine/instrumental and feminine/expressive traits. The results showed that although there were important differences in life cycle stage and occupation, women spent more time than men on housework, childcare, and caring for sick relatives, while men spent more time than women on enjoying activities and exercise. More time spent on housework was associated with worse health and well-being for women and more exercise with better health and well-being for both genders. It is concluded that gender is relevant to time use and the impact of different uses of time on health and well-being.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has had an unprecedented impact on health care and cardiac surgery. We report cardiac surgeons concerns, perceptions, and responses during the COVID-19 pandemic. METHODS: A detailed survey was sent to recruit participating adult cardiac surgery centers in North America. Data regarding cardiac surgeons perceptions and changes in practice were analyzed. RESULTS: Our study comprises 67 institutions with diverse geographic distribution across North America. Nurses were most likely to be redeployed (88%), followed by advanced care practitioners (69%), trainees (28%), and surgeons (25%). Examining surgeon concerns in regard to COVID-19, they were most worried with exposing their family to COVID-19 (81%), followed by contracting COVID-19 (68%), running out of personal protective equipment (PPE) (28%), and hospital resources (28%). In terms of PPE conservation strategies among users of N95 respirators, nearly half were recycling via decontamination with ultraviolet light (49%), followed by sterilization with heat (13%) and at home or with other modalities (13%). Reuse of N95 respirators for 1 day (22%), 1 week (21%) or 1 month (6%) was reported. There were differences in adoption of methods to conserve N95 respirators based on institutional pandemic phase and COVID-19 burden, with higher COVID-19 burden institutions more likely to resort to PPE conservation strategies. CONCLUSIONS: The present study demonstrates the impact of COVID-19 on North American cardiac surgeons. Our study should stimulate further discussions to identify optimal solutions to improve workforce preparedness for subsequent surges, as well as facilitate the navigation of future healthcare crises.

Chagas disease causes a problematic pathology that can lead to megacolon and heart disease, and can even cause the death of the patient. Current therapies for this disease are the same as they were 50 years ago, are not fully effective and have strong side effects. The lack of a safe and effective therapy makes it necessary to search for new, less toxic and totally effective compounds against this parasite. In this work, the antichagasic activity of 46 novel cyanomethyl vinyl ether derivatives was studied. In addition, to elucidate the type of cell death that these compounds produce in parasites, several events related to programmed cell death were studied. The results highlight four more selective compounds, E63, E64, E74 and E83, which also appear to trigger programmed cell death, and are therefore postulated as good candidates to use in future therapeutics for Chagas disease.

Robert Rowland (São Paulo, 1945 - Lisboa, 2023). Farei um pequeno resumo da sua carreira universitária, em parte conhecida, seguido das circunstâncias do contacto e do trabalho que desenvolvi com ele. O impacto do Robert na academia portuguesa e a influência das suas ideias e dos seus métodos serão abordados ao longo deste percurso. Trata-se de um testemunho pessoal, com tudo o que implica de subjetividade.

Este artículo presenta la co-ocurrencia entre el uso de los materiales didácticos digitales (MDD) y la valoración de los recursos digitales, a partir de tres grupos de discusión en el que participaron un total de 16 personas con hijos e hijas en el 2º ciclo de educación infantil en la Comunidad Autónoma Canaria. Los códigos pertinentes a las categorías se obtuvieron de manera inductiva, para posteriormente ser observados por cuatro investigadoras de forma simultánea y finalmente fusionados, con el objetivo de obtener fiabilidad en el análisis de contenido realizado con el software Atlas.ti. Los resultados muestran una alta co-ocurrencia entre los códigos de estas categorías como los obtenidos entre los beneficios del uso de las TIC y la aceptación de la tecnología (1.57), los beneficios del uso de las TIC con la tecnología y juegos tradicionales (0.96), así como el uso didáctico de los recursos TIC educativos con la selección de estos materiales (0.68). Las conclusiones apuntan a una relación bidireccional en el tipo de uso que se hacen de los recursos digitales en los diferentes contextos, influenciando estrechamente la forma en la que se introducen estas tecnologías en los procesos educativos.

Abstract Activation of nucleic acid sensors in endothelial cells (ECs) has been shown to drive inflammation across pathologies including cancer, atherosclerosis and obesity. We previously showed that enhancing cytosolic DNA sensing by inhibiting three prime exonuclease 1 (TREX1) in ECs led to EC dysfunction and impaired angiogenesis. Here we show that activation of a cytosolic RNA sensor, Retinoic acid Induced Gene 1 (RIG-I) diminishes EC survival, angiogenesis and triggers tissue specific gene expression programs. We discovered a RIG-I dependent 7 gene signature that affects angiogenesis, inflammation and coagulation. Among these, we identified the thymidine phosphorylase TYMP as a key mediator of RIG-I induced EC dysfunction via its regulation of a subset of interferon stimulated genes. Our RIG-I induced gene signature was also conserved in the context of human diseases – in lung cancer vasculature and herpesvirus infection of lung endothelial cells. Pharmacological or genetic inhibition of TYMP rescues RIG-I induced EC death, migration arrest and restores sprouting angiogenesis. Interestingly, using RNAseq we identified a gene expression program that was RIG-I induced but TYMP dependent. Analysis of this dataset indicated that IRF1 and IRF8 dependent transcription is diminished in RIG-I activated cells when TYMP is inhibited. Functional RNAi screen of our TYMP dependent EC genes, we found that a group of 5 genes - Flot1, Ccl5, Vars2, Samd9l and Ube2l6 are critical for endothelial cell death mediated by RIG-I activation. Our observations identify mechanisms by which RIG-I drives EC dysfunction and define pathways that can be pharmacologically targeted to ameliorate RIG-I induced vascular inflammation.

Leishmaniasis, produced by Leishmania spp., and Chagas disease, produced by Trypanosoma cruzi, affect millions of people around the world. The treatments for these pathologies are not entirely effective and produce some side effects. For these reasons, it is necessary to develop new therapies that are more active and less toxic for patients. Some initiatives, such as the one carried out by the Medicines for Malaria Venture, allow for the screening of a large number of compounds of different origins to find alternatives to the lack of trypanocide treatments. In this work, 240 compounds were tested from the Global Health Priority Box (80 compounds with confirmed activity against drug-resistant malaria, 80 compounds for screening against neglected and zoonotic diseases and diseases at risk of drug resistance, and 80 compounds with activity against various vector species) against Trypanosoma cruzi and Leishmania amazonensis. Flucofuron, a compound with activity against vectors and with previous activity reported against Staphylococcus spp. and Schistosoma spp., demonstrates activity against L. amazonensis and T. cruzi and produces programmed cell death in the parasites. Flucofuron seems to be a good candidate for continuing study and proving its use as a trypanocidal agent.

In less developed countries (LDC), health tourism can be seen as a way of specializing in tourism. Covid19 makes even more imperative the need to promote health tourism and also to link it to a greater extent to wellness tourism, thus responding to the current market requirements. The main objective of this study is to assess whether the current tourism offer in Senegal (LDC) could allow health tourism to be implemented. An ad-hoc study has been performed in Senegal’s Coastal Region, where interviews directed at the socioeconomic agents and structured questionnaires have been developed, collecting information from the two populations: one sample of 21 private clinics and another of 31 hotels. The data obtained were analyzed following a descriptive analysis. The results indicate that it is possible the developing of wellness tourism, but not medical tourism. Even in the case of a labor intensive product, offering health tourism as a new tourist product requires more modern and sophisticated technological equipment.

In the context of Artificial Intelligence, Generative Adversarial Nets (GANs) allow the creation and reproduction of artificial data from real datasets. The aims of this work are to seek to verify the equivalence of synthetic data with real data and to verify the possibilities of GAN in educational research. The research methodology begins with the creation of a survey that collects data related to the self-perceptions of university teachers regarding their digital competence and technological-pedagogical knowledge of the content (TPACK model). Once the original dataset is generated, twenty-nine different synthetic samples are created (with an increasing N) using the COPULA-GAN procedure. Finally, a two-stage cluster analysis is applied to verify the interchangeability of the synthetic samples with the original, in addition to extracting descriptive data of the distribution characteristics, thereby checking the similarity of the qualitative results. In the results, qualitatively very similar cluster structures have been obtained in the 150 tests carried out, with a clear tendency to identify three types of teaching profiles, based on their level of technical-pedagogical knowledge of the content. It is concluded that the use of synthetic samples is an interesting way of improving data quality, both for security and anonymization and for increasing sample sizes.

Leishmaniasis and Chagas disease, two of the most prevalent neglected tropical diseases, are a world health problem. The harsh reality of these infective diseases is the absence of effective and safe therapies. In this framework, natural products play an important role in overcoming the current need to development new antiparasitic agents. The present study reports the synthesis, antikinetoplastid screening, mechanism study of fourteen withaferin A derivatives (2-15). Nine of them (2-6, 8-10 and 12) showed a potent dose-dependent inhibitory effect on the proliferation of Leishmania amazonensis and L. donovani promastigotes and Trypanosoma cruzi epimastigotes with IC50 values ranging from 0.19 to 24.01 µM. Outstandingly, the fully acetylated derivative 10 (4,27-diacetylwithaferin A) was the most potent compound showing IC50 values of 0.36, 2.82 and 0.19 µM against L. amazonensis, L. donovani and T. cruzi, respectively. Furthermore, analogue 10 exhibited approximately 18 and 36-fold greater antikinetoplastid activity, on L. amazonensis and T. cruzi, than the reference drugs. The activity was accompanied by significantly lower cytotoxicity on the murine macrophage cell line. Moreover, compounds 2, 3, 5-7, 9 and 10 showed more potent activity than the reference drug against the intracellular amastigotes forms of L. amazonensis and T.cruzi, with a good selectivity index on a mammalian cell line. In addition, withaferin A analogues 3, 5-7, 9 and 10 induce programmed cell death through a process of apoptosis-like and autophagy. These results strengthen the anti-parasitic potential of withaferin A-related steroids against neglected tropical diseases caused by Leishmania spp. and T. cruzi parasites.

The deep-sea Caribbean lobster (Metanephrops binghami) and the Norway lobster (Nephrops norvegicus) are Nephropidae species of high commercial interest. Although the first one still remains unexploited, the second is overexploited in the Mediterranean Sea. For effective fisheries management, size at sexual maturity is an essential indicator to protect immature individuals from exploitation. The estimation of this indicator can, however, be biased due to the difficulty of differentiating juveniles from adults by their size structure due to the natural process of molting. This study aims to estimate the size at sexual maturity of M. binghami and N. norvegicus females by comparing the effectiveness of the morphometric method versus the macroscopic evaluation of gonad maturity. Samples of M. binghami were collected from the Colombian Caribbean Sea in August and December 2009, March and May 2010, and August 2020 to May 2021. Samples of N. norvegicus were collected from the northwestern Mediterranean Sea from 2019 to 2022. Similar sizes at sexual maturity were found for M. binghami between the morphometric approach (ranging from 28.6 to 33.9 mm cephalothorax length, CL) and the gonadal staging approach (31.4 mm CL). Conversely, for N. norvegicus, the morphometric approach yielded higher measurements (between 27.2 and 30.4 mm CL) than the gonadal approach (26.0 mm CL). This discrepancy might stem from the intense fishing overexploitation conditions of N. norvergicus, leading to a physiological adaptation that enables earlier gonadal maturation at faster rates than morphometric adaptation. Further research is required to elucidate these discrepancies and the effect of overexploitation on physiological (i.e., mature gonads) and functional maturity (i.e., capacity to brood eggs at a larger size).