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Semantic Web technologies have been applied in educational settings for different purposes in recent years, with the type of application being mainly defined by the way in which knowledge is represented and exploited. The basic technology for knowledge representation in Semantic Web settings is the ontology, which represents a common, shareable and reusable view of a particular application domain. Ontologies can support different activities in educational settings such as organizing course contents, classifying learning objects or assessing learning levels. Consequently, ontologies can become a very useful tool from a pedagogical perspective. This paper focuses on two different experiences where Semantic Web technologies are used in educational settings, the difference between them lying in how knowledge is obtained and represented. On the one hand, the OeLE platform uses ontologies as a support for assessment processes. Such ontologies have to be designed and implemented in semantic languages apt to be used by OeLE. On the other hand, the ENSEMBLE project pursues the development of semantic web applications by creating specific knowledge representations drawn from user needs. Our paper is consequently going to offer an in-depth analysis of the role played by ontologies, showing how they can be used in different ways drawing a comparison between model patterns and examining the ways in which they can complement each other as well as their practical implications.

Abstract Background The mitral annular plane systolic excursion (MAPSE) is used to analyze the left ventricle longitudinal function. However, the accuracy of MAPSE in diagnosing oncological populations is unclear. In this study, we aimed to assess the accuracy of MAPSE in diagnosing subclinical cardiotoxicity in women with breast cancer undergoing anthracycline treatment. Methods This retrospective cohort study included echocardiographic assessments of patients with breast cancer who underwent anthracycline treatment as part of their therapeutic regimen. Assessments were performed before treatment, after administering the first dose of anthracycline, after completing anthracycline treatment, and 6 and 12 months after treatment. Left ventricular ejection fraction was calculated using the modified biplane Simpson method. The performances of MAPSE and global longitudinal strain (GLS) were analyzed using receiver operating characteristic (ROC) curves. Their accuracies were measured using the area under the ROC curves. Results Sixty-one patients were included in this study. Of them, 8.2% presented cardiotoxicity 6 months after treatment completion. Patients with cardiotoxicity had lower LVEF (47% vs. 63%; p

Abstract Background The use of antiretrovirals has increased the survival of People Living with HIV/AIDS (PLWHA), resulting in an aging population and a rise in the incidence of sarcopenia. The lack of uniformity among the prevalences found in studies may be associated with the use of different diagnostic criteria, highlighting the need for local studies to determine the prevalence of sarcopenia. Methods Cross-sectional study to estimate the prevalence and associated factors of sarcopenia using the revised criteria of the European Working Group on Sarcopenia in Older People (EWGSOP2). This study included PLWHA of both sexes, aged 40 years or older, who were treated at the infectious disease outpatient clinic of a tertiary hospital from 2019 to 2021. Muscle mass was quantified through electrical bioimpedance, using resistance and reactance to calculate appendicular lean mass (ALM) in kg/m². Muscle strength, measured in kg, was assessed using a manual dynamometer, and muscle function was evaluated using the gait speed test (m/s). Numerical variables were analyzed using measures of central tendency and dispersion. The chi-square test was used to assess associations in categorical variables. Odds ratios (OR) and 95% Confidence Intervals (CI) were calculated to evaluate the strength of associations. Results Among the 218 PLWHA, the prevalence of sarcopenia was 8.7% (95% CI: 5.6 to 13.3). The mean age of the study population was 51.8 ± 8.3 years; 53.7% were male, 72.9% were brown/Black, 97.7% reported not using illicit drugs, and 24.8% were classified as obese. Multivariate analysis showed that the time since HIV diagnosis (P = 0.022) and the use of illicit drugs were associated with the diagnosis of sarcopenia. Conclusion The prevalence of sarcopenia using the EWGSOP2 criteria was low. People with a longer duration of HIV infection and those using illicit drugs were more likely to develop sarcopenia.

Abstract Background Common bean (Phaseolus vulgaris) is one of the main nutritional resources in the world, and a low environmental impact source of protein. However, the majority of its cultivation areas are affected by drought and this scenario is only expected to worsen with climate change. Stomatal closure is one of the most important plant responses to drought and the MYB60 transcription factor is among the key elements regulating stomatal aperture. If targeting and mutating the MYB60 gene of common bean would be a valuable strategy to establish more drought-tolerant beans was therefore investigated. Results The MYB60 gene of common bean, with orthology to the Arabidopsis AtMYB60 gene, was found to have conserved regions with MYB60 typical motifs and architecture. Stomata-specific expression of PvMYB60 was further confirmed by q-RT PCR on organs containing stomata, and stomata-enriched leaf fractions. Further, function of PvMYB60 in promoting stomata aperture was confirmed by complementing the defective phenotype of a previously described Arabidopsis myb60-1 mutant. Conclusions Our study finally points PvMYB60 as a potential target for obtaining more drought-tolerant common beans in the present context of climate change which would further greatly contribute to food security particularly in drought-prone countries.

Abstract Introduction This study aimed to assess the effects of a monoclonal antibody (mAb) combination on symptoms, daily function, and overall health-related quality of life. Methods We analyzed patient-reported outcomes data from symptomatic outpatients in a phase 1/2/3 trial. Patients with confirmed SARS-CoV-2 infection and ≥ 1 risk factor for severe COVID-19 received mAb treatment (casirivimab plus imdevimab 1200 mg) or placebo. Prespecified exploratory assessments included time to sustained symptoms resolution, usual health, and return to usual activities (assessed daily for 29 days). The trial was conducted from September 2020 to February 2021, prior to widespread COVID-19 vaccination programs and Omicron-lineage variants against which casirivimab + imdevimab is not active. Results In this analysis 736 outpatients received mAb and 1341 received placebo. Median time to sustained symptoms resolution was consistently shorter with mAb versus placebo (≥ 2 consecutive days: 14 vs 17 days, [nominal p = 0.0017]; ≥ 3 consecutive days: 17 vs 21 days, [nominal p = 0.0046]). Median time to sustained return to usual health and usual activities were both consistently shorter with mAb versus placebo (≥ 2 consecutive days: 12 vs 15 days [nominal p = 0.0001] and 9 vs 11 days [nominal p = 0.0001], respectively; ≥ 3 consecutive days: 14 vs 18 days [nominal p = 0.0003] and 10 vs 13 days [nominal p = 0.0041], respectively). Conclusions mAb treatment against susceptible SARS-CoV-2 strains improved how patients feel and function, as evidenced by shortened time to sustained symptoms resolution and return to usual health and activities. Future studies are warranted to assess the patient experience with next generation mAbs. ClinicalTrials.gov Registration number, NCT04425629; Submission date June 11, 2020.

Aim. The aim of this study was to evaluate adherence to spironolactone in a group of unselected patients with arterial hypertension by analysis of measured serum spironolactone and canrenone concentrations according to a proposed two-step decision scheme based on pharmacokinetic considerations. Materials and Methods. Simulation of serum concentration-time profiles of spironolactone and canrenone based on population pharmacokinetic parameters described in literature and a body weight-normalized spironolactone dose / canrenone level nomogram derived from a group of adherent patients with conservatively treated primary hyperaldosteronism, were used to create a two-step decision scheme. 71 outpatients treated with spironolactone for resistant hypertension with spironolactone and canrenone serum concentrations measured between 2018 and 2021 were analyzed according to the proposed scheme. We compared our proposed methodology to the standard approach for adherence testing. Results. With the most sensitive traditional approach to adherence assessment through detectable serum concentrations of spironolactone and/or canrenone, 9 (12.7%) non-adherent patients were identified. With our two-step assessment of adherence, we were able to identify 18 (25.4%) non-adherent patients. Conclusion. Consideration of the pharmacokinetic properties of parental drug and its metabolite led to improved sensitivity in non-adherence detection in patients with arterial hypertension. This approach enables better interpretation of measured spironolactone and canrenone serum concentrations and should be used in clinical practice.

We use supervised machine learning to predict Hodge numbers for Calabi-Yau threefolds encoded by reflexive polyhedra. The Hodge number is invariant to the order of the vertices and the swapping of axes. Incorporating these properties, i.e. the invariance of column and row permutations for a matrix containing the polyhedron's vertices, promises better performance for Hodge number prediction. On a medium-sized subset of the Kreuzer-Skarke dataset, we train and evaluate approaches with different degrees of invariance. Our comparison shows that machine learning models incorporating symmetries actually outperform models that do not, with our best model achieving almost 97% accuracy.

Abstract Background Infection with porcine reproductive and respiratory syndrome virus (PRRSV) leads to significant economic losses worldwide. One of the initial measures following an outbreak is to stabilise the herd and to prevent vertical transmission of PRRSV. The objective of this study was to detect PRRSV in different sampling material, both in an experimental model and on a commercial piglet producing farm, with a focus on evaluating the suitability of tongue fluid samples. Results In the experimental model, PRRSV negative pregnant gilts were infected with PRRSV-1 AUT15-33 on gestation day 85 and necropsy of gilts and foetuses was performed three weeks later. 38.3% of individual foetal serum and 39.4% of individual foetal thymus samples were considered PRRSV RT-qPCR positive. Tongue fluids from individual foetuses showed a 33.0% positivity rate. PRRSV RNA was detected in all but one sample of litter-wise pooled processing fluids and tongue fluids. In the field study, the investigated farm remained PRRSV positive and unstable for five consecutive farrowing groups after the start of the sampling process. Tongue fluid samples pooled by litter in the first investigated farrowing group had a 54.5% positivity rate, with the overall highest viral load obtained in the field study. In this farrowing group, 33.3% of investigated litter-wise pooled processing fluid samples and all investigated serum samples (pools of 4–6 individuals, two piglets per litter) were considered positive. Across all investigated farrowing groups, tongue fluid samples consistently showed the highest viral load. Moreover, tongue fluid samples contained the virus in moderate amounts for the longest time compared to the other investigated sampling material. Conclusion It can be concluded that the viral load in individual foetuses is higher in serum or thymus compared to tongue fluid samples. However, litter-wise pooled tongue fluid samples are well-suited for detecting vertical transmission within the herd, even when the suspected prevalence of vertical transmission events is low.

We investigated molecular evolution and spatiotemporal dynamics of atypical Legionella pneumophila serogroup 1 sequence type 1905 and determined its long-term persistence and linkage to human disease in dispersed locations, far beyond the large 2014 outbreak epicenter in Portugal. Our finding highlights the need for public health interventions to prevent further disease spread.

Abstract HROB promotes the MCM8-9 helicase in DNA damage response. To understand how HROB activates MCM8-9, we defined their interaction interface. We showed that HROB makes important yet transient contacts with both MCM8 and MCM9, and binds the MCM8-9 heterodimer with the highest affinity. MCM8-9-HROB prefer branched DNA structures, and display low DNA unwinding processivity. MCM8-9 unwinds DNA as a hexamer that assembles from dimers on DNA in the presence of ATP. The hexamer involves two repeating protein-protein interfaces between the alternating MCM8 and MCM9 subunits. One of these interfaces is quite stable and forms an obligate heterodimer across which HROB binds. The other interface is labile and mediates hexamer assembly, independently of HROB. The ATPase site formed at the labile interface contributes disproportionally more to DNA unwinding than that at the stable interface. Here, we show that HROB promotes DNA unwinding downstream of MCM8-9 loading and ring formation on ssDNA.

Nickel nanoparticles have wide-ranging applications in diverse fields, including electronics, catalysis, and biomedicine. The unique properties of these nanoparticles depend on their physical and chemical attributes. Consequently, there is a growing interest in understanding the performance relationships through a nuanced comprehension of their controlled synthesis. This review explores the advancements related to precisely defined nickel nanoparticles, with a specific focus on unraveling the connections between performance and their physical/chemical characteristics. The emphasis is on elucidating how manipulating synthetic parameters, such as precursor concentration, reductant agent properties, temperature, time, and the presence of stabilizing agents, can provide additional avenues for refining the performance in terms of size and morphology. Through the analysis of each variable, we illustrate the methodology for synthesizing well-controlled nickel nanoparticles, showcasing the ability to exert precision over their composition, size, and surface morphology.

Abstract Meyer’s minority stress model posits that sexual minority communities can act as protective factors for individuals within the sexual minority. Given that existing evidence on this proposition is inconclusive, a social network approach was employed to capture diversity in the social environment of individuals involved in chemsex that might account for variations in social resources and sexual health. This study examined the social networks of men who have sex with men (MSM) involved in sexualised drug use, using data from a cross-sectional online survey. Utilising cluster analysis, four distinct social network types were identified based on network composition: MSM-diverse, partner-focused, family-diverse, and chemsex-restricted. In terms of social resources, the four network types did not exhibit significant differences in social support. However, individuals with a chemsex-restricted social network reported stronger social influence related to chemsex and less social engagement outside of chemsex. Contrary to initial expectations, the four network types did not differ in chemsex-related consequences or sexual satisfaction. MSM engaged in chemsex for over 5 years reported more chemsex-related consequences and lower sexual satisfaction, particularly those with a family-diverse social network. Additionally, indicators of network quality, such as perceived emotional closeness, reciprocity with network members, and overall satisfaction with the network, were more influential in predicting sexual health outcomes than social resources. The findings of the study suggest that the social environment of MSM engaged in chemsex plays a role in shaping their experiences. Insufficient inclusion in a sexual minority community is potentially associated with an elevated risk of poor sexual health. These findings underscore the importance of tailoring interventions to address the diverse needs of individuals exposed to different social environments.

Background: Carbapenemase-producing Enterobacterales (CPE) is an increasing problem in healthcare settings. This study aimed to identify the source of a CPE outbreak that occurred in 2022, in a tertiary hospital in the North of Portugal, to identify exposed patients, and to assess the risk of becoming CPE-positive following hospital admission. Methods: A multi-disciplinary investigation was conducted including descriptive, analytical, and molecular epidemiology, environmental screening, and assessment of infection control measures. Clinical and environmental isolates were analyzed using whole-genome sequencing and phylogenetic analysis. Additionally, a prospective observational cohort study was conducted to further investigate the risk factors associated with the emergence of new cases in cohorts of CPE-negative admitted patients. Results: We observed the presence of multispecies KPC-, IMP-, and/or NDM-producing isolates. Genetically indistinguishable clinical and environmental isolates were found on the same room/ward. The ST45 KPC-3-producing Klebsiella pneumoniae clone was the responsible for the outbreak. During patients’ treatment, we detected the emergence of resistance to ceftazidime-avibactam, associated with mutations in the blaKPC-3 gene (blaKPC-46, blaKPC-66 and blaKPC-124, the last variant never previously reported), suggesting a vertical evolutionary trajectory. Patients aged ≥ 75 years, hygiene/feeding-care dependent, and/or subjected to secretion aspiration were risk factors for CPE colonization after hospital admission. Additionally, cases with previous admission to the emergency department suggest that CPE dissemination may occur not only during hospitalization but also in the emergency department. Conclusion: Overall, the study highlights that selection pressure with antibiotics, like ceftazidime-avibactam, is a contributing factor to the emergence of new β-lactamase variants and antibiotic resistance. It also shows that the hospital environment can be a significant source of CPE transmission, and that routine use of infection control measures and real-time molecular epidemiology investigations are essential to ensure the long-term termination of CPE outbreaks and prevent future resurgences.

Moringa stenopetala is often consumed as food and used in folkloric medicine for the management of several diseases including neurodegenerative diseases. This study investigated the protective effect and antioxidant efficacy of aqueous extract of Moringa stenopetala in BV-2 microglial cells. Aqueous extracts of M. stenopetala were prepared, lyophilized and reconstituted in 0.5% dimethylsulphoxide (DMSO). Cells were treated with M. stenopetala extracts (0.1–100 µg/ml) for cell viability assay and nitric oxide (NO) production tests. However, M. stenopetala extract (50 µg/ml) was used in the treatment of cells for the determination of protein carbonyl content and reactive oxygen species (ROS) level. Incubation of BV-2 microglia cell with M. stenopetala extract maintained cell viability, diminished NO and ROS levels, and reduced protein carbonyl contents. Chlorogenic acid, rutin, kaempferol and quercetin derivatives were the main phenolic compounds identified in M. stenopetala leaf extract. In conclusion, this study suggests that M. stenopetala extract is rich in antioxidant and contains bioactive neuroprotective agents.

O artigo discute as relações entre público e privado na educação mobilizando categorias do pensamento materialista histórico-dialético que situam o debate como parte da totalidade da sociedade capitalista. Em torno de uma perspectiva solucionista, analisam-se as formas de atuação do privado que historicamente se propõe a salvar a educação pública. Desde as tradicionais formas analógicas de privatização até o atual processo de transformação digital da educação protagonizado por sujeitos privados, verifica-se a vinculação do conteúdo das propostas privadas ao projeto mais amplo do capital. Palavras-chave: Público-privado; Soluções educacionais; Capitalismo na era digital.

Abstract Temperature is projected to continue increasing in the upcoming years. The effects of temperature warming in deforested stream populations have not been addressed yet and are a promising area to understand the consequences of increased temperature on fish physiology. Therefore, the aims of this study were to determine the manner in which Bryconops giacopinii from deforested habitat modulates the LDH kinetics in response to warming and whether the antioxidant system is able to withstand thermal stress. We collected individuals from two roadside streams (deforested) and one forested stream and measured the LDH kinetics parameters (Vmax and Km) for pyruvate and lactate, measured the total ROS production, and measured the activity of antioxidant enzymes and the oxidative stress biomarker. Our results showed lower affinity and higher LDH activity for lactate oxidation in road-side populations, suggesting that populations living in high temperatures use lactate as aerobic fuel. Besides, there was an increase in ROS production, and CAT and GSH levels in road-side populations, but not LPO levels, suggesting that B. giacopinni is able to neutralize the ROS production with the antioxidant systems. Our results bring important findings in the adaptation of this specie to a warm environment.

The present paper deals with the process analysis of a biomass-to-electricity industrial plant. Starting from the process simulation by means of Aspen Plus software, this work discusses the technical, environmental, and economic performance of a biomass integrated gasification combined cycle (BIGCC) power plant. To enable a safe integration, a mid-to-high temperature cleaning system has been implemented to target reference inorganic contaminants that hinder the use of syngas in commercial applications, namely hydrochloric acid, and hydrogen sulphide. The actual effectiveness of the overall system has been evaluated by performing a holistic assessment of a 7 MWe BIGCC using hazelnut shells as biomass and equipped with sorbent reactors to remove the target contaminants before entering the power generation section of the plant.

Doxorubicin (DOX) is an anthracycline used to treat a wide range of tumours. Despite its effectiveness, it is associated with a long range of adverse effects, of which cognitive deficits stand out. The present study aimed to assess the neurologic adverse outcome pathways of two clinically relevant cumulative doses of DOX. Adult male CD-1 mice received biweekly intraperitoneal administrations for 3 weeks until reaching cumulative doses of 9 mg/kg (DOX9) or 18 mg/kg (DOX18). Animals were euthanized one week after the last administration, and biomarkers of oxidative stress and brain metabolism were evaluated in the whole brain. Coronal sections of fixed brains were used for specific determinations of the prefrontal cortex (PFC) and hippocampal formation (HF). In the whole brain, DOX18 tended to disrupt the antioxidant defences, affecting glutathione levels and manganese superoxide dismutase expression. Considering the regional analysis, DOX18 increased the volume of all brain areas evaluated, while GFAP-immunoreactive astrocytes decreased in the dentate gyrus (DG) and increased in the CA3 region of HF, both in a dose-dependent manner. Concerning the apoptosis pathway, whereas Bax increased in the DOX9 group, it decreased in the DOX18 group. Only in the latter group did Bcl-2 levels also decrease. While p53 only increased in the CA3 region of the DOX9 group, AIF increased in the PFC and DG of DOX18. Finally, phosphorylation of Tau decreased with the highest DOX dose in DG and CA3, while TNF-α levels increased in CA1 of DOX18. Our results indicate new pathways not yet described that could be responsible for the cognitive impairments observed in treated patients.

The cytoprotective transcription factor NRF2 regulates the expression of several hundred genes in mammalian cells and is a promising therapeutic target in a number of diseases associated with oxidative stress and inflammation. Hence, an ability to monitor basal and inducible NRF2 signalling is vital for mechanistic understanding in translational studies. Due to some caveats related to the direct measurement of NRF2 levels, the modulation of NRF2 activity is typically determined by measuring changes in the expression of one or more of its target genes and/or the associated protein products. However, there is a lack of consensus regarding the most relevant set of these genes/proteins that best represents NRF2 activity across cell types and species. We present the findings of a comprehensive literature search that according to stringent criteria identifies GCLC, GCLM, HMOX1, NQO1, SRXN1 and TXNRD1 as a robust panel of markers that are directly regulated by NRF2 in multiple cell and tissue types. We assess the relevance of these markers in clinically accessible biofluids and highlight future challenges in the development and use of NRF2 biomarkers in humans.

ABSTRACT Introduction and objectives: Transcatheter aortic valve implantation (TAVI) is an established treatment option for patients with symptomatic severe aortic stenosis often performed via transfemoral access route (TF-TAVI). Therefore, successful closure of large-bore access sites is essential. This study aims to investigate the safety and effectiveness of the MANTA (Teleflex/Essential Medical, United States) vascular closure device (VCD) in patients undergoing TF-TAVI in an unselected and consecutive cohort of patients. Methods: We conducted a single-center, observational study of 245 consecutive patients undergoing TF-TAVI in whom the arterial large-bore femoral access was closed with a MANTA device from March 2020 through February 2022. The primary efficacy outcome measure was the rate of VCD failure according to the VARC-3 definition. Results: Successful closure of the large-bore access site occurred in 92.2% of the patients (n = 226). According to the VARC-3 definition, no major vascular or bleeding complications related to the plug-based VCD were reported. Patients with failed VCDs (7.8%) had significantly smaller minimal femoral artery diameters (6.6 ± 1.1 mm vs 7.6 ± 1.4 mm; P = .005) and consequently, significant higher sheath-to-femoral artery diameter ratios (0.78 ± 0.16 vs 0.69 ± 0.15; P = .019). No other inter-group differences were found. Conclusions: In this single-center, real-world, unselected large cohort of consecutive patients treated with TF-TAVI, a plug-based VCD for large-bore arteriotomy closure turned out effective and safe, and enabled arterial access-site management with a low rate of complications.

RESUMEN Introducción y objetivos: El implante percutáneo de válvula aórtica (TAVI) es una opción de tratamiento establecida para pacientes con estenosis aórtica grave sintomática, generalmente realizado por acceso transfemoral (TAVI-TF). Por lo tanto, el cierre exitoso de los sitios de acceso de gran calibre es esencial. Este estudio tiene como objetivo investigar la seguridad y la eficacia del dispositivo de cierre vascular (DCV) MANTA (Teleflex/Essential Medical, Estados Unidos) en pacientes tratados con TAVI-TF en una cohorte consecutiva y no seleccionada. Métodos: Se realizó un estudio observacional de un solo centro, con 245 pacientes consecutivos tratados con TAVI-TF en quienes el acceso femoral arterial de gran calibre se cerró con MANTA, entre marzo de 2020 y febrero de 2022. La medida de resultado de eficacia primaria fue la incidencia de fallo del DCV usando la definición VARC-3. Resultados: En el 92,2% (n = 226) de los pacientes se logró el cierre exitoso del sitio de acceso de gran calibre. De acuerdo con la definición VARC-3, no se informaron complicaciones vasculares ni hemorrágicas importantes relacionadas con el DCV basado en tapón. Los pacientes con fallo del DCV (7,8%) tenían un diámetro mínimo de la arteria femoral significativamente más pequeño (6,6 ± 1,1 frente a 7,6 ± 1,4 mm; p = 0,005) y, en consecuencia, una relación significativamente mayor entre el diámetro de la vaina y la arteria femoral (0,78 ± 0,16 frente a 0,69 ± 0,15; p = 0,019). No se encontraron otras diferencias entre los grupos. Conclusiones: En esta gran cohorte no seleccionada de un solo centro, del mundo real, de pacientes con TAVI-TF consecutivos, un DCV basado en tapón para el cierre de la arteriotomía de gran calibre fue eficaz y seguro, lo que permitió el manejo del sitio de acceso arterial con una baja tasa de complicaciones.

O presente artigo objetiva refletir sobre concepções da pesquisa educacional em perspectivas multiculturais, interculturais e decoloniais, problematizadoras de formas eurocentradas e homogeneizadas pelas quais questões educacionais como avaliação, currículo, planejamento educacional, formação de professores, políticas públicas, entre outras, têm sido tratadas. Nesse sentido, busca, também, articular tais considerações à análise de pesquisas institucionais, teses e dissertações, produzidas em grupos de pesquisa que têm buscado concretizar tais perspectivas no contexto das questões educativas, discutindo seus desafios e suas potencialidades.

Abstract Background In January 2021, a female 1-year-old Kunekune was presented at the University Clinic for Swine with severe reduction of the field of vision resulting in prolonged reaction time when targeting barriers, due to moderate to severe thickening of the skin around both orbits also affecting the eyelids. Methods Clinical examination revealed skin hyperplasia, nodular enlargement of the skin pores of the axillar and inguinal region. Ophthalmologists decided to remove parts of the thickened periocular skin, followed by histopathological examination. Results Once large amounts of demodectic mites were detected by histopathology, demodicosis could be diagnosed and treatment of the pig was started using sarolaner. Morphological and molecular analyses were performed. Histopathological and parasitological exams led to the aetiological diagnosis of demodicosis in the affected Kunekune pig. Severe skin lesions were revealed to be the consequence of an infestation with Demodex sp. Morphological analyses confirmed the involvement of D. phylloides. Molecular characterization indicated a Demodex species closely related to mites documented in wild boar - most probably D. phylloides for which no explicit sequences are available in GenBank yet. Treatment with sarolaner (2.6 mg/kg) resulted in a substantial regression of skin lesions, already detectable 1 month after first treatment. Conclusions Demodicosis is a very rare disease in pigs that is most probably related to an impaired immune response to the mites. Demodectic mange should be included in the list of differential diagnoses in cases of periocular alterations of the skin of pigs. Graphical Abstract

Abstract The escalating antimicrobial resistance crisis urges the development of new antibacterial treatments with innovative mechanisms of action, particularly against the critical priority carbapenem-resistant Acinetobacter baumannii (CRAB), Pseudomonas aeruginosa (CRPA) and Enterobacteriaceae (CRE). Membrane-disrupting dodecyl deoxyglycosides have been reported for their interesting phosphatidylethanolamine-associated bactericidal activity against Gram-positive strains; however, their inability to penetrate the Gram-negative outer membrane (OM) renders them useless against the most challenging pathogens. Aiming to repurpose alkyl deoxyglycosides against Gram-negative bacteria, this study investigates the antimicrobial effects of five reference compounds with different deoxygenation patterns or anomeric configurations in combination with polymyxins as adjuvants for enhanced OM permeability. The generation of the lead 4,6-dideoxy scaffold was optimized through a simultaneous dideoxygenation step and applied to the synthesis of a novel alkyl 4,6-dideoxy C-glycoside 5, herein reported for the first time. When combined with subtherapeutic colistin concentrations, most glycosides demonstrated potent antimicrobial activity against several multidrug-resistant clinical isolates of CRAB, CRE and CRPA exhibiting distinct carbapenem resistance mechanisms, together with acceptable cytotoxicity against human HEK-293T and Caco-2 cells. The novel 4,6-dideoxy C-glycoside 5 emerged as the most promising prototype structure for further development (MIC 3.1 μg/mL when combined with colistin 0.5 μg/mL against CRPA or 0.25 μg/mL against several CRE and CRAB strains), highlighting the potential of C-glycosylation for an improved bioactive profile. This study is the first to show the potential of IM-targeting carbohydrate-based compounds for the treatment of infections caused by MDR Gram-negative pathogens of clinical importance.

Background/Objectives: Alcohol can directly damage the liver, causing steatosis, steatohepatitis, cirrhosis, and hepatocellular cancer. The aim of this study was to examine 28-day survival in hospitalized patients with alcohol-related liver disease (ALD) cirrhosis, as well as to develop and validate a new survival prediction model. Methods: A total of 145 patients with ALD cirrhosis were included; 107 were diagnosed with acute decompensation (AD) and 38 with acute-on-chronic liver failure (ACLF). The new liver mortality inpatients (LIV-IN) score was calculated using the following variables: hepatic encephalopathy (HE), hepatorenal syndrome (HRS), ascites, systemic inflammatory response syndrome (SIRS), community-acquired infection (CAI), and fibrinogen. The diagnostic accuracy of the LIV-IN score was tested, along with the model for end-stage liver disease (MELD), model for end-stage liver disease-sodium (MELD-Na), albumin-bilirubin (ALBI), neutrophil-to-lymphocyte ratio (NLR), chronic liver failure consortium-C acute decompensation (CLIF-C AD), and chronic liver failure consortium-acute-on-chronic liver failure (CLIF-C ACLF). Results: Lethal outcome occurred in 46 (31.7%) patients. The mortality rate was higher in the ACLF group (n = 22, 57.9%) compared to the AD group (n = 24, 22.4%) (p < 0.01). The highest predictive power for short-term mortality was observed for the LIV-IN score (AUC 73.4%, p < 0.01). In patients with AD, the diagnostic accuracy of the CLIF-C AD score was better than for the LIV-IN score (AUC 0.699; p = 0.004, AUC 0.686; p = 0.007, respectively). In patients with ACLF, only the LIV-IN score had statistically significant discriminative power in predicting 28-day survival. Conclusions: The liver mortality inpatients prognostic score is a new, reliable prognostic model in predicting 28-day mortality.

The integration of highly transparent and highly conductive layers plays a crucial role in the advancement of various next-generation optoelectronic technologies. Here, we demonstrate a comparison of optical, electrical and wettability properties of Aluminum-doped Zinc Oxide (AZO) deposited by Atomic Layer Deposition Technique (ALD) with commercially available Fluorine-doped Tin Oxide (FTO) and Indium-doped Tin Oxide (ITO) Transparent Conductive Oxide (TCO) layers. Their impact on the electro-optical modulation behavior when applied in Liquid Crystal (LC) device assemblies are compared and discussed. The AZO layers performance prove that are fully competitive to the commercial FTO and ITO layers and verify the high demand for the next generation indium tin oxide (ITO)-free technology.

A key goal of teaching math is for students to develop a deep understanding of concepts. This understanding is the foundation for all future learning in math. The purpose of this study was to improve students' conceptual understanding and problem-solving skills in GeoGebra-assisted mathematics learning with Model Eliciting Activities (MEAs). The quantitative method with a nonequivalent (pre-test and post-test) group design was used to answer the hypothesis. The instruments used were pre-test and post-test in the form of descriptions consisting of 5 questions. The participants in this study were 26 junior high school students. Data analysis used Paired Sample T-tests (t-test) to determine the level of conceptual understanding and problem-solving ability of students. The results of data analysis obtained that the application of Model Eliciting Activities (MEAs) assisted by GeoGebra is effective in increasing student’ understanding of mathematical concepts and student problem-solving skills. So, it is concluded that learning with the Eliciting Activities Model (MEAs) assisted by GeoGebra can improve students' conceptual understanding and problem-solving skills. In the future teachers are recommended to use Model Eliciting Activities (MEAs) assisted by GeoGebra in learning mathematics.

O papel da agricultura familiar vem ganhando força, impulsionado através de debates embasados no desenvolvimento rural sustentável, na geração de trabalho e renda, contribuindo para a segurança alimentar. A piscicultura orgânica é uma atividade que pode ser desenvolvida por estes agricultores na promoção da sustentabilidade. Nesta perspectiva, o objetivo deste trabalho é analisar a viabilidade econômica/financeira, ambiental e social da produção de peixe em sistema orgânico em viveiros escavados com base em um estudo de caso. A metodologia adotada para alcançar os objetivos tem caráter exploratório e descritivo combinando pesquisa bibliográfica sobre estudos de análises da produção orgânica em geral e na piscicultura com estudo de caso. Em um período de dezesseis meses foi acompanhada a produção em sistema de policultivo de peixes, orgânico, utilizando alimentos naturais e provenientes da propriedade. Nas análises foram utilizadas técnicas de análise de viabilidade econômica: Valor Presente Líquido (VPL); Payback descontado (PB); Taxa Interna de Retorno (TIR); e Índice de Lucratividade (IL). O valor investido nos viveiros foi de R$ 3.220,60. O valor estimado para a comercialização dos peixes foi de R$ 2.477,50. Na análise de viabilidade econômico/financeira os resultados indicam retorno a partir do segundo ciclo produtivo. Na dimensão social se destaca a mão de obra familiar ocupada e cuja maior demanda é no período de implementação, enquanto na manutenção é baixa esta necessidade. Na análise ambiental os resultados indicaram a preservação de recursos naturais, com reaproveitamento de resíduos de alimentos produzidos na propriedade e cuidados com a água e geração de efluentes.

Summary: The integrated stress response (ISR) is a key cellular signaling pathway activated by environmental alterations that represses protein synthesis to restore homeostasis. To prevent sustained damage, the ISR is counteracted by the upregulation of growth arrest and DNA damage-inducible 34 (GADD34), a stress-induced regulatory subunit of protein phosphatase 1 that mediates translation reactivation and stress recovery. Here, we uncover a novel ISR regulatory mechanism that post-transcriptionally controls the stability of PPP1R15A mRNA encoding GADD34. We establish that the 3′ untranslated region of PPP1R15A mRNA contains an active AU-rich element (ARE) recognized by proteins of the ZFP36 family, promoting its rapid decay under normal conditions and stabilization for efficient expression of GADD34 in response to stress. We identify the tight temporal control of PPP1R15A mRNA turnover as a component of the transient ISR memory, which sets the threshold for cellular responsiveness and mediates adaptation to repeated stress conditions.

A small tile panel created by the Italian ceramic painter Francisco Niculoso (active 1498-1529) from the private collection of Ferdinand Saxe-Coburg-Gotha (1816-1885), king consort to Queen Maria II of Portugal (1819-1853), was in 1902 acquired by the Rijksmuseum. Although the ownership history of this Visitation panel is not fully documented, this essay provides a more comprehensive understanding of its historical narrative, by exploring the various contexts of acquisition and collecting. The panel’s journey from Lisbon to Amsterdam vividly illustrates the remarkable fluidity and permeability that defined the boundaries of art markets and museums around the turn of the twentieth century.

ABSTRACT: The Amazonian manatee (Trichechusinunguis) is an aquatic mammal threatened with extinction. However, few studies have investigated the pathogens in this species, which may affect both animal and human health. This study aimed to evaluate the frequency, distribution, and patterns of antimicrobial susceptibility of Staphylococcus spp. and Escherichiacoli colonizing the nasal and rectal cavities of Amazonian manatees kept in captivity at the National Institute for Amazonian Research (INPA) in the state of Amazonas, Brazil. Rectal and nasal swabs from 44 manatees of different ages were used in this study. The genus Staphylococcus was isolated from the nasal swabs of 32 (72.7%) animals, with two individuals harboring more than one species of Staphylococcus. S. sciuri was the most commonly isolated species. Resistance to penicillin was observed in 13 (40.6%) isolates, more frequent than the other antimicrobials tested (P = 0.01). E. coli was isolated from the rectal swabs of all animals, with phylogroup B1 being the most frequent among the strains obtained (P = 0.0008). Four isolates (6.8%) were positive for virulence factors, three of which were classified as enterotoxigenicE. coli (ETEC) and one as enteropathogenicE. coli (EPEC). To our knowledge, this is the first study to evaluate Staphylococcus spp. and E. coli in Amazonian manatee samples. This study revealed nasal colonization by Staphylococcus spp., mainly S. sciuri, and diarrheagenicE. coli isolates, including antimicrobial-resistant strains.